5.1 cm x 3.4 cm erythematous plaque with scale and a 3 cm x 1.5 cm central ulceration on left lateral neck

Case authors Danny Zakria, MD, MBA, Ryan Rivera-Oyola, MD, and Darrell Rigel, MD, MS, present a case of a 58-year-old male with a history of sun exposure and a skin lesion showing signs of malignancy. 

Accurately Assessing Prognosis for High-Risk Squamous Cell Carcinoma

Aaron Farberg, MD 
Bare Dermatology
Baylor Scott & White Health System
Dallas, TX

Discuss the role of gene expression profiling for the management of skin cancers 

Describe how to integrate gene expression profiling for cutaneous melanoma and SCC to inform risk- and appropriate management decisions 

Optimizing The Patient Skin Cancer Journey With Gene Expression Profiling

We're going to be talking about optimizing the patient's skin cancer journey with gene expression profiling. So this is who we are, and our learning objectives are to discuss the role of gene expression profiling, which I'll call GEP for the management of skin cancers, and then to talk about how we integrate GEP into our treatment and workup for, ah, for melanoma and SCC. Okay. And this is accredited for 0.5 CME credits. Okay, so I'm going to now turn it over to Dr. Regal, who's going to start with the first case. Well, thank you so much. We have five cases. We're going to present it very quickly. This is the first case of 47 year old, the Fitzpatrick skin type. Two male with settle for a skin check, had a history of significant sun exposure, works indoors. He'd had moles removed before, but none for cancer. So the issue here is, here's the path, and as you can see, there's inflammation, but it's really indeterminate, really is not helping you with this. So how can a diagnosis be obtained with this if you're not sure the path is equivocal? Yeah, I think that this is a tough case. So these are the cases where you show them to ten different dermatopathologists and you're not going to have consensus on the answer. So a lot of times we'll start with sending these out in consult, but if we want more information, this is a place where we can use gene expression profiling to say not just what does this look like clinically or histologically, but genetically, does this look more like melanoma, like a benign lesion? So this is really an example of where you can use it. And this is just to show you, this is the test, the 23 GP test. And the data is kind of interesting because really, it's a higher number than I would have thought from this data, where the diagnosis is ambiguous for pigmented lesions. But the bottom line is that using the 23 genes in the model here for this, it classifies the patients in lesions, amlignant, indeterminate or benign, and most of them get classified in one way or the other. Basically, the one limitation with this that's important is you have to get at least 10% of the lesion in to be analyzed for this. But the bottom line, it can be performed only for non pediatric cases greater than 18 years of age. That's one of those. And it doesn't work for metastatic lesions. But bottom line, it can make a difference for this a number of clinical validation studies. And again, this is in your handout, so you can pull these, but also clinical utility. In other words, if you have the test, does it make a difference in management? That's what the utility tests do. And what it showed with this is an interesting study. They had 25 patients who were found to be benign, and they followed them, and you can see 88% of them did not have a reexcision, 12% did decide to excise anyway. But of the 25 cases, there were no recurrences or metastases reported. Any patient. These were all patients that were said they were benign from the study. And again, the whole concept of a personalized medicine, the conclusion, this is one study that came out showing that it influences the treatment of diagnostically challenging lesions, makes a difference. Okay, let's go to case two. This is a 68 year old white male with history of extensive sun exposure that presented with this lesion on the back. It was a 1.2 millimeter melanoma. How aggressively would you manage this patient? Yeah, so these are tough. So when we have a four millimeter melanoma, we know we have to be aggressive. When we look at this and we say it's probably a superficial spreading melanoma. I'm going to talk with the patient about what is the risk that this has spread? What are your next options? And so again, we can use things like nomograms, we can use things like the NCCN guidelines, but sometimes patients will really push me know, well, how likely is it that that sentinel node is going to be positive, or how likely is it that this is going to metastasize? And so that's when people want kind of a more personalized answer, that it can be helpful to have things like GEP. So basically, this is a perfect case for GP. And I think this is a 31 GP test that was developed to assess risk of recurrence for this. And there's basically, I think most of you use this at this point, but there's four different possibilities. One a, one b, two a, two b. This is actually the distribution that occurs for this. So about 10% of the cases that are tested, obviously a skewed view, but tested are actually in that highest risk group. So what's nice about this, if you compare the prediction of this versus just using the traditional AJCC eight alone, here's the value for AJCC eight. But look at how you dichotomize each of those, stage one, stage two, and stage three, into much more predictive outcomes based on having the additional data from the GEP, there have been a number of studies that have shown basically the efficacy of their test for relapse free survival and distant metastasis free survival. And again, this is a study. It was alluded to earlier today, but we'll hear about it a little more tomorrow. About a cohort of this was done at the NCI with data from the NCI, where there was GP testing data available. In other words, an independent data set that really looks at the validity of this test in a variety of ways. What was also interested in the multivariate analysis on this, you can see that the information from the GP test class was more significant, had a better ODS ratio than did the other factors we typically think of as being important. Okay, this is case three. Yeah, I thought that data was really interesting. And also, Daryl, I know when we had talked about it before that having the GEP result actually resulted in higher survival for the patients who had had the test done. So I think it's going to be neat to see how that all matures. I think it's going to be interesting. Obviously, the test is not therapeutic, so I think they're probably managed more efficiently is what happened. Right, yeah, more effective. So this is an example of a management challenge. So this is a patient who came in to see me. He's 85 years old. This was his first time ever coming to a dermatologist, because his PCP sent him, actually, for the lesion that you can see in front of his ear, which was ulcerated. And when I just sort of walked around and started looking at his skin and looked behind his ear, he had no idea that he had this very large, broad pigmented lesion. So he couldn't really give me any history, but I figured he'd probably been there a long time. And so I did biopsy it. And this was a superficial spreading melanoma. The Breslow thickness was 0.7 least. So I had a resident with me. I said, the key thing here is you really want to make sure you biopsy at least to a millimeter. You're not going to remove this entire thing. And then, of course, I did the biopsy, and I'm the one who got the positive deep margin, so it was not ulcerated, which was good. Other than that thickness, it really had lower risk features, 0 /mm squared, and the lateral and deep margins were positive. It, of course, also had an adjacent basal cell carcinoma that I couldn't even see, but that I found as part of this biopsy. So now what would you do next? Well, I think this is a perfect case where you want to look at the GP test for it, because if you don't know the thickness, that's the key here. And unfortunately, I've shaved through them, too. I think everybody in this room has shaved through a melanoma at some point and not realizing, you get that report, it's 0.7 to the base. You don't know what the real thickness is. And if you re excise it, you can't add it, you can't say, oh, it's 1.2 plus the 0.7 because there's regrowth and the tissue is growing back. So you're stuck. But with having that information, it can help you much better assess the risk for this patient in management. Yeah. So we actually brought him back in to the office and I saw him together with my mo surgeon, and I said, I can't believe I did this. But now we got to really make sure that we've accurately staged him. And how extensive is this? So we actually went and did. I'm not a fan of scouting biopsies in a primary melanoma, but it can be helpful if there's areas that were missed when you know that the diagnosis is definitely melanoma. We also wanted to see how extensive it was. And interestingly, every area that we biopsied came back as a melanoma and cyto. So now, the other challenge with this is not just does he need a sentinel node or not, but if he does, this is going to be a really tough lesion to clear. I mean, this is big. It's going behind the ear. The margins are very indistinct. So if we send him off for a sentinel node to surgical oncology, we don't have the ability to do sort of MOS or slow mos. So we said, well, let's see how high risk this really is. So we ordered a GEP test. So we ordered this, and we have now IgEP, which is an integrated result. So it's not just, is it class one a, which we did get that result. It was a class one a, so lowest risk. Interestingly, you also get a numeric score. So class one a can go from zero to zero point 41. He was 00:27 so sort of in the middle range. I could now also give him more information, like, what is your distant metastasis? Free survival, for example, was over 95%. But also, what was really key here was, what's the likelihood of this being having sent a positive sentinel node, and it was 2.9%. So when we talk about where did NCCN guidelines come from, they came from looking at the probability of a node being positive. And so the only thing you could correlate with was thickness. But in this case, we were able to say, normally, if the thickness would tell us that the likelihood of a positive node is less than 5%, we would recommend against it. Now, given the patient's age and other in the genetic features, as well as the thickness and other prognostic features, we could say his risk was below 5%. And we decided that the low possibility of missing a positive sentinel node was definitely outweighed by the great benefit of being able to have, under local anesthesia, slow mos. So he has now undergone slow mos and we've cleared this tumor, and now we get to move on to the other ten that were on his face. So I move on to my next case. So this is a 36 year old woman who came to see us eleven weeks pregnant. So, interestingly, we have a lot of access issues, so we have a pretty robust edrmatology storm forward platform that we use. And so she sent in the top photo, and she was then triaged. She came in to see us on dermascopy. This was clearly going to be a melanoma. So in this case, we were smarter. We did a narrow margin excision. So we said in that minute, we need to get this off. But this was a long discussion with the patient, because not only was she eleven weeks pregnant, she was being followed by maternal fetal medicine because she had had a previous late term pregnancy loss. So she was extremely anxious. So we biopsied this lesion and we had found that it had a Breslow thickness of 0.9 mm. So this is a t one b lesion. It is, because it's not ulcerated. The mitotic count was low. It was 1 /mm squared. So I really still consider that as a very low mitotic rate free margin. So we know we've identified this entire lesion. So now the discussion was, what do we do next? So we actually presented her at tumor board. We actually had a really robust discussion. Some people said, you know what? You should go ahead and do this. Pregnant women may have a higher risk. It clearly meets criteria. Do a sentinel node. The patient said, I don't want to do anything to risk this pregnancy. I've been through so much. So we said, why don't we discuss some other options, too? So we talked about the guidelines of care for melanoma. So this was published in the jad in 2019. In pregnant women, it is recommended that you avoid sentinel node biopsy, if possible, in the first trimester. Now, she could have waited a week or two. Our surgical oncologists can actually do this under local, apparently. So that is an option, but there is still going to be the radiation exposure. So this generated a lot of conversation. So we did get her score. So she was a class one a. And again, looking at the numerical score was helpful, because, again, that goes zero to 00:41 hers was zero point 13. We knew that her recurrence free survival was 95% distant. Metastasis free survival was over 96%. Now, her likelihood of a sentinel node being positive was 7%. So that's really a product of her age. We know that younger people are more likely to have a positive sentinel node that is probably not due to the risk of their tumor, but due to the makeup of their lymphatics. So, taking this all into consideration, we talked to her, and she elected to undergo reexcision under local and not to have the sentinel node biopsy done. So if we look at the data on this, this was a large study out of Oregon. And so this was looking at patients who had t one to t tumor, to t one t two tumors who had been referred for a sentinel node, and then looking at their class one a one b class status and their age, and looking at the probability using that to find their probability of a positive node. So we can see here that if you have patients who are older than 55, that if they have a class one a tumor, the probability of having a positive node is actually under 5%. Thinking back to those NCCN guidelines, that gives us some comfort. And then patients who have a one b or higher do have a higher probability. So we also know, again, if that patient had a two b tumor, I would be having a pretty serious discussion with her about getting that sentinel node. So how do we use these results? Class one a probability of a positive node less than 5%. We talk about potentially avoiding it. If we're in between that five to 10%, the guidelines would say discuss and consider, and if it's greater than 10%, I will nudge them in the direction. And again, with the IGEP, we get even more granular results. So in her case, it was a big benefit to be able to avoid that sentinel node. Okay, this is our last case assessing squamous cell prognosis. This was a 58 year old Fitzpatrick typesuit male, presented for a skin check. He grew up in Florida, had a lot of sun. He worked at construction with outdoors. He'd had a lot of spots frozen over the years, but never been diagnosed with a skin cancer. But he presented with this lesion and he first noticed it two years ago, but let it go. He said it itched. Occasionally it got bigger. He tried to treat it with 1% of hydrocortisone. Not pretty effective for that. I don't think so. Biopsy was showing invasive squamous cell for this comet. Yeah, I'm even more afraid of bad squamous cells sometimes than I am of melanoma, particularly intermediate thickness melanoma. So this is kind of a scary tumor. It's large, it's 5.1 cm. It looks like it's ulcerated. I'd be interested to see what kind of histologic features you have. And then again, this isn't a tough area. If you think about, do you just dive right into adjuvant therapy, like radiation? The neck is a tough area to get radiation, so I'd want to have a really informed discussion with that patient. Well, that's the challenge. And obviously, one way to use this and really cone in on what the risk is going to be is using the 40 gp test, which has been validated to predict metastatic risk for squamous cell patients. This again shows you the three different outcomes here. Class one for low biologic risk, class two a is moderate, and class three is a high biologic risk for metastatic disease. So again, the two b's have a 50% plus chance of metastatic risk to do this, putting this in a distribution, and this is not for squamous cell carcinoma site use or little ditzels or things that are kind of called aks, maybe early squamous cell. This is really for tumors with risk factors for squamous cell. But you can see in this series, about one in 18 are usually in that class two. So about 6% or whatever the number is there. Traditional staging are the two methods, AJCC and Brigham and women's hospital staging. And basically they have different high risk factors to do this. I like the brigade one because I'm quantitative, but it's a number of risk factors. It makes it pretty easy to figure out where it fits with this. But both of them work to some extent. But what's nice about this is, again, I showed you this before the data for the melanomas, but in squamous cell, the same thing. If you use that model of how many risk factors there are, again, having the data here, a two a two b or a one a really divides the initial black dots significantly in terms of assessing the risk for metas addict disease to do this. So again, you could use treatment plans here from low intensity to moderate intensity to high intensity for this. And basically it really helps in managing these patients. So we've got through these cases. Thank you very much and hope you enjoyed it. Thank you. Thank you. Thank.

Describe the current recommendations of the National Academies on the effect of UV filters on aquatic environment and health


Explain the concept of personalized photoprotection

Recognize why sunscreens fail and how they should be applied for optimal photoprotection

Explain why sunscreens produce heat on the skin surface 

2023 Virtual Grand Rounds Session 8: May 31, 2023 - Skin Cancer Prevention

Skin Cancer

WEDNESDAY, April 17, 2024 -- For detection of malignant melanoma (MM), performance is more consistent when clinicians' work is supported by artificial intelligence (AI), according to a review published online April 8 in Cancers.Ian Miller, from Southern Cross University in Bilinga, Australia, and colleagues conducted a systematic review to report the performance metrics of commercially available convolutional neural networks tasked with detecting MM. Data were included from 16 articles reporting MM, with 1,160 melanomas detected and 33,010 nonmelanoma lesions.The researchers found that for classification of melanoma, performance of market-approved technology and clinician performance were highly heterogeneous, with sensitivity, specificity, and accuracy ranging from 16.4 to 100.0 percent, 40.0 to 98.3 percent, and 44.0 to 92.0 percent, respectively. When clinicians worked together with AI, less heterogeneity was seen, with sensitivity, specificity, and accuracy varying from 83.3 to 100.0 percent, 83.7 to 87.3 percent, and 86.4 to 86.9 percent, respectively."The implementation of AI in clinical practice to assist in the early detection of melanoma remains promising, particularly with the prospect of improved diagnostic accuracy," the authors write. "However, the heterogeneity of studies reporting on AI performance for classifying melanoma in clinical practice indicates it currently cannot be recommended as a reliable tool for clinicians."

Less heterogeneity in sensitivity, specificity, accuracy seen when clinicians worked in unison with artificial intelligence

Best Results for Classifying Malignant Melanoma Seen When Clinicians Work With AI

WEDNESDAY, April 3, 2024 -- A prediction model and nomogram can predict the risk for five-year recurrence-free and melanoma-specific survival, according to a study published in the April issue of The Lancet Oncology.Robert C. Stassen, M.D., from the Erasmus Medical Centre Cancer Institute in Rotterdam, Netherlands, and colleagues developed a tool to predict patient-specific outcomes in people with melanoma rather than classification according to disease stage. Patients with confirmed primary melanoma were included in the development cohort (4,071 patients), and external validation was performed (4,822 patients). In patients with stage pT1b or higher melanomas, a prognostic model and nomogram were developed to predict five-year recurrence-free survival.The researchers found that five-year recurrence-free survival was 73.5 percent and five-year melanoma-specific survival was 86.5 percent in the development cohort. The corresponding estimates were 66.1 and 83.3 percent in the validation cohort. Six prognostic factors were included in the final model: sentinel node status, Breslow thickness, presence of ulceration, age at sentinel lymph node biopsy, primary tumor location, and maximum diameter of the largest sentinel node metastasis. The area under the receiver operating characteristic curve (AUC) was 0.80 and 0.81 for prediction of recurrence-free and melanoma-specific survival, respectively, in the development cohort. External validations showed good calibration, with AUCs of 0.73 and 0.76, respectively."The model that we developed not only offers patient-specific risk predictions for recurrence-free and melanoma-specific survival but will also enable physicians to calculate the risk of recurrence at which it is judged necessary to start adjuvant therapy," the authors write.Several authors disclosed ties to the pharmaceutical industry.

Final model composed of six prognostic factors showed good prediction in development cohort and external validation

Model, Nomogram Predict Recurrence-Free, Melanoma-Specific Survival

WEDNESDAY, April 3, 2024 (HealthDay News) -- Patients with primary cutaneous B-cell lymphomas (PCBCLs) have an increased risk for second primary malignancies (SPMs), according to a study published online March 19 in the Journal of the American Academy of Dermatology.Lauren Banner, from Thomas Jefferson University in Philadelphia, and colleagues used the Surveillance, Epidemiology, and End Results database from 2000 to 2020 to generate a cohort of 5,435 PCBCL patients to examine their risk for development of subsequent cancers, defined as SPM.The researchers found that 16 percent of the patients received diagnoses of a second malignancy, which was higher than in the general population (standardized incidence ratio, 1.54). Women had an increased risk for thyroid, renal, and lung cancers (standardized incidence ratios, 3.06, 2.13, and 1.69, respectively). Men had the highest risk for melanoma, bladder, and prostate cancers (standardized incidence ratios, 1.49, 1.42, and 1.29, respectively). The risks for all SPMs were highest within the first year of PCBCL diagnosis and decreased with time (standardized incidence ratios within the first year: 21.11 for thyroid cancer for women; 2.09 for prostate cancer for men). The risk for all SPMs decreased with patient age; a threefold higher risk for all SPMs was seen for patients aged 40 to 49 years (standardized incidence ratio, 3.07)."Dermatologists may educate PCBCL patients on the symptoms and screening guidelines for these six malignancies and refer for further consultation if concerning symptoms are present," the authors write.<a target="_blank" rel="noopener noreferrer" href="https://www.jaad.org/article/S0190-9622(24)00505-X/abstract">Abstract/Full Text (subscription or payment may be required)</a>

Women have increased risk for thyroid, renal, lung cancers; men have highest risk for melanoma, bladder, prostate cancers

Second Primary Malignancy Risk Increased After Cutaneous B-Cell Lymphoma

WEDNESDAY, March 27, 2024 -- For patients with primary cutaneous melanoma undergoing sentinel lymph node (SLN) biopsy and for those who progressed to an unresectable stage, regression of melanoma is associated with improved prognosis, according to a study published in the April issue of the Journal of the American Academy of Dermatology.Nikolaus B. Wagner, M.D., from Kantonsspital St. Gallen in Switzerland, and colleagues conducted a retrospective review of 1,179 patients with newly diagnosed melanoma undergoing SLN biopsy between 2010 and 2015 and with available information on histopathologic regression.The researchers found that patients with regressive melanoma showed favorable relapse-free, distant metastasis-free, and melanoma-specific survival (hazard ratios, 0.52, 0.56, and 0.35, respectively). There was an association observed for regression with negative SLN (odds ratio, 0.48). Regression was associated with favorable progression-free survival under immune checkpoint inhibition (hazard ratio, 0.43) in patients who progressed to an unresectable stage, but not under targeted therapy or chemotherapy."In our opinion, presence or absence of regression could be used to improve prognostic risk stratification in patients who are candidates for SLN biopsy," the authors write.Several authors disclosed ties to the pharmaceutical industry.

Findings seen in patients with primary cutaneous melanoma undergoing SLN biopsy and those who progressed to unresectable stage

Improved Prognosis Seen With Regression of Primary Cutaneous Melanoma

WEDNESDAY, March 20, 2024 -- A wearable ultraviolet (UV) dosimeter may reduce the incidence of nonmelanoma skin cancer among elderly patients with a history of actinic keratoses (AK), according to a study published online March 1 in Frontiers in Medicine.Emmanuel L.P. Dumont, Ph.D., from Shade in Nutley, New Jersey, and colleagues conducted a prospective randomized trial involving 97 elderly patients with a history of AK who were followed over six months. Fifty of the patients received a wearable UV dosimeter that provided real-time and cumulative UV exposure as well as UV counseling from a dermatologist, while 47 received only UV counseling from a dermatologist.More than 75 percent of the participants recorded UV exposure once a week or more during the summer. The researchers found that after six months of intervention, there was a nonsignificant 20 percent lower ratio of incidence rates of AKs when comparing the device group with the control group and a significant 95 percent lower ratio of incidence rates of nonmelanoma skin cancer. There was a significant increase of 1.2 observed in the control groups' score in self-perceived ability to participate in social activities, while the score decreased nonsignificantly, by 0.9, in the device group. No changes or between-group differences were seen in anxiety and depression surveys."The clinical advantages observed in this pilot study indicate that using wearable UV sensors could enhance traditional UV-prevention strategies," the authors write.Several authors are shareholders of Shade, a startup manufacturing wearable UV sensors and the sponsor of this clinical trial.

No significant reduction seen in incidence rates of actinic keratoses; no changes observed in anxiety, depression surveys

Wearable UV Dosimeter May Reduce Nonmelanoma Skin Cancer in Elderly

WEDNESDAY, March 13, 2024 -- Melanoma patients face an increased risk for developing second primary malignancy (SPM), according to a study presented at the annual meeting of the American Academy of Dermatology, held from March 8 to 12 in San Diego.Using data from Surveillance, Epidemiology, and End Results-17 cancer registries, Thomas Z. Rohan, from Thomas Jefferson University in Philadelphia, and colleagues describe the risk for SPM after a melanoma diagnosis (January 2000 to December 2020). Data were included for 283,435 primary melanoma patients. The standardized incidence ratio (SIR) of observed to expected cases was used to calculate relative risk.The researchers found that 16.3 percent of the primary melanoma patients developed an SPM. The risk for developing any subsequent cancer was increased compared with the general population (SIR, 1.57). Overall, 61.5 percent of the patients received their cancer diagnosis between the ages of 50 and 79 years; there was an inverse relationship noted between the risk for SPM and age at melanoma diagnosis until age 80+ years. More than half of the melanomas were on the trunk or upper limbs; head and neck was the location associated with the highest risk for developing an SPM (SIR,1.65). There was a positive correlation seen for initial tumor thickness with SIR. Melanoma survivors had the greatest risk for cutaneous melanoma, ocular melanoma, thyroid, brain, and prostate cancers (SIRs, 9.65, 2.31, 1.89, 1.3, and 1.22, respectively)."Melanoma patients should remain under continued surveillance for both subsequent melanoma and other cancers," the authors write.

Melanoma survivors at greatest risk for cutaneous melanoma, ocular melanoma, thyroid, brain, prostate cancers

AAD: Risk for Second Primary Malignancy Increased for Melanoma Patients

WEDNESDAY, March 6, 2024 -- There has been a considerable increase in the use of immunohistochemistry (IHC) staining for melanoma diagnosis, according to a study published online March 6 in JAMA Dermatology.Kenechukwu Ojukwu, M.D., from the David Geffen School of Medicine at the University of California in Los Angeles, and colleagues examined trends in the use of IHC for examination of skin biopsies in incident melanoma cases diagnosed between January 2000 and December 2017 in a retrospective cross-sectional study. The analysis used the Surveillance Epidemiology, and End Results-Medicare linked database, which included data from 17 population-based registries, and focused on melanoma diagnosed in patients aged 65 years and older.The final sample included 132,547 melanomas in 116,117 distinct patients. The researchers found that 33 percent of these diagnoses had accompanying IHC claims. Among these cases, 65 percent were diagnosed in men and 44, 38, and 18 percent were diagnosed in patients aged 65 to 74, 75 to 84, and 85 years and older, respectively. Overall, 11 percent of melanoma cases had claims for IHC at or near the time of diagnosis in 2000; this proportion increased annually and reached 51 percent in 2017. Increasing use of IHC was seen for all melanoma stages, including in situ melanoma. In all 17 registries, claims for ICH increased, but at different rates. Across registries, use of IHC for melanoma diagnosis varied from 39 to 68 percent in 2017."Given the extensive use of IHC in clinical practice, studies examining the resulting outcomes of IHC on different domains, such as symptom burden, quality of life, and mortality, are crucial," the authors write.

11 percent of melanoma cases had claims for ICH at or near diagnosis in 2000; this number increased to 51 percent in 2017

Use of Immunohistochemistry in Melanoma Diagnosis Increased From 2000 to 2017

WEDNESDAY, Feb. 28, 2024 -- To achieve tumor clearance, melanoma in situ (MIS) on the head and neck often requires margins &gt;5 mm, according to a study published online Jan. 20 in the Journal of the American Academy of Dermatology.Jesalyn A. Tate, M.D., from the University of Texas Southwestern Medical Center in Dallas, and colleagues examined margins required for optimal cure rates with excision of MIS on the head and neck in a retrospective chart review performed on 846 MIS cases on the head and neck treated during a 126-month period.The researchers found that 62 percent of the MIS cases were cleared with 5-mm margins. To achieve a 97 percent clearance rate, 15-mm margins were required. There was a significant difference observed in clearance rates between margin thresholds. There was a correlation seen for tumor location on the cheek and larger preoperative size with requiring &gt;5-mm margins to achieve tumor clearance."This study demonstrates that MIS on the head and neck often requires margins &gt;5 mm to achieve tumor clearance," the authors write. "When Mohs micrographic surgery is not possible, excision margins of ≥10 mm are likely necessary for head and neck tumors."

Tumor location on cheek, larger preoperative size linked to requiring margins &gt;5 mm to achieve tumor clearance

Margins >5 mm Often Needed to Achieve Tumor Clearance for Melanoma in Situ

WEDNESDAY, Feb. 21, 2024 -- The risk for subsequent cutaneous squamous cell carcinomas (cSCCs) increases with the number of prior cSCCs, while the time interval decreases with each subsequent cSCC, according to a study published in the March issue of the Journal of the American Academy of Dermatology.Celeste J. Eggermont, M.D., from the Erasmus MC Cancer Institute in Rotterdam, Netherlands, and colleagues examined the cumulative incidence and timing of subsequent cSCCs using data from patients with a first cSCC in 2007 to 2008 from the Netherlands Cancer Registry linked to the Netherlands Pathology Registry for subsequent cSCCs and the Netherlands Organ Transplant Registry.The researchers found that 4,325; 2,010; 1,138; 739; and 501 of the 12,345 patients had second to sixth cSCCs, with median time intervals of 1.4, 1.2, 0.9, 0.6, and 0.5 years, respectively, after the previous cSCC. At five years, the cumulative incidences of a subsequent cSCC increased from 28 to 67 percent for the second to sixth cSCC. The cumulative incidences increased from 74 to 92 percent for solid organ transplant recipients and from 41 to 64 percent for patients with hematologic malignancy."The majority of nonimmunocompromised patients with cSCC could benefit from more personalized follow-up schedules, taking into account the number of prior cSCCs and potentially reducing the total volume of follow-up visits," the authors write.One author disclosed ties to Sanofi Genzyme.

Median time interval after the previous cutaneous squamous cell carcinoma decreases after each subsequent cutaneous squamous cell carcinoma

Risk for Subsequent Squamous Cell Carcinomas Rises With Number of Prior Ones

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</div>Iovance Biotherapeutics, Inc, has achieved a significant milestone with the FDA approval of its revolutionary T cell therapy, AMTAGVI (lifileucel). This therapy marks the first FDA-approved T cell treatment for solid tumor cancer, specifically addressing advanced melanoma following anti-PD-1 and targeted therapy.&nbsp;AMTAGVI utilizes tumor-infiltrating lymphocytes (TIL) to recognize and combat cancer. The treatment, administered through intravenous infusion, is a one-time, individualized T cell therapy, making it a unique and personalized approach for patients.&nbsp;The therapy is designed for adult patients with unresectable or metastatic melanoma who have previously received PD-1 blocking antibody treatment, and if BRAF V600-mutation positive, a BRAF inhibitor with or without a MEK inhibitor.&nbsp;Clinical trial insights&nbsp;Accelerated approval by the FDA was supported by results from the C-144-01 trial, a global, multicenter Phase 2 study that enrolled patients with metastatic melanoma who had been previously treated with at least one systemic therapy, including a PD-1 blocking antibody, and if BRAF V600 mutation positive, a BRAF inhibitor or BRAF inhibitor with MEK inhibitor.&nbsp;Approval was supported by the overall response rate and duration of response seen in clinical trials, and ongoing trials, such as TILVANCE-301, aim to confirm its clinical benefits.&nbsp;Mechanism of action&nbsp;AMTAGVI is manufactured using a proprietary process to collect and expand a patient’s unique T cells from a portion of their tumor. AMTAGVI returns billions of the patient’s T cells back to the body to fight their cancer. The specific mechanism of action is unknown.&nbsp;Safety profile&nbsp;Safety considerations include warnings for treatment-related mortality, prolonged severe cytopenia, severe infection, and cardiopulmonary and renal impairment.&nbsp;Future outlook&nbsp;AMTAGVI will be manufactured in Philadelphia at the Iovance Cell Therapy Center, with plans for significant expansion to accommodate more patients in the coming years. The therapy will be administered in Authorized Treatment Centers (ATCs), and over 30 ATCs are prepared to collect and ship tumor tissue for AMTAGVI manufacturing.

FDA grants accelerated approval for the first T cell therapy for a solid tumor cancer

LAUNCH ALERT: Lifileucel (AMTAGVI) Approved for Treatment of Advanced Melanoma 

WEDNESDAY, Feb. 14, 2024 -- Many survivors of localized melanoma have a clinical fear of cancer recurrence, according to a study published online Feb. 14 in JAMA Dermatology.Ayisha N. Mahama, M.D., M.P.H., from the Dell Medical School at the University of Texas in Austin, and colleagues explored the lived experiences and fear of cancer recurrence among survivors of localized cutaneous melanoma in a qualitative and survey-based study using semistructured interviews and the Fear of Cancer Recurrence Inventory short form (FCRI-SF) survey tool.Fifty-one patients with a history of localized melanoma completed the interview and survey; 33 percent had survived a diagnosis of stage 0 melanoma and the rest had at least one invasive melanoma (stage I to IIA) diagnosis. The researchers identified themes in the semistructured interviews: emotions surrounding follow-up appointments; intensity of melanoma surveillance; lifestyle change relating to sun exposure; and thoughts regarding life and death. Of the participants, 38 had an FCRI-SF score above the threshold for clinical fear of cancer recurrence."These findings underscore the importance of addressing the psychological well-being of patients with early melanoma and potentially implementing supportive interventions," the authors write.

Thirty-eight of 51 survivors had FCRI-SF score above the threshold for clinical fear of cancer recurrence

Many Survivors of Localized Melanoma Fear Recurrence

MONDAY, Feb. 12, 2024 (HealthDay News) -- For patients with clinical stage I and II melanoma, smoking is associated with an increased risk for melanoma-associated death, according to a study published online Feb. 6 in JAMA Network Open.Katherine M. Jackson, M.D., from the Saint John's Cancer Institute at Providence Saint John's Health Center in Santa Monica, California, and colleagues examined the association of smoking with survival in patients with early-stage primary cutaneous melanoma in a post-hoc analysis of data from the randomized, multinational first and second Multicenter Selective Lymphadenectomy Trials. Participants were aged 18 to 75 years and had clinical stages I or II melanoma with a Breslow thickness of 1.00 mm or greater or Clark level IV to V. Data were included for 6,279 patients: 17.2, 27.0, and 55.9 percent were current, former, and never smokers, respectively.The researchers found that in a multivariable analysis for the entire study, current smoking was associated with a greater risk for melanoma-associated death (hazard ratio, 1.48), but former smoking was not. Patients with sentinel lymph node biopsy (SLNB)-negative melanoma had the greatest increased risk for melanoma-specific mortality associated with current smoking (hazard ratio, 1.85), and an increased risk was also seen for patients with SLNB-positive melanoma and nodal observation (hazard ratios, 1.29 and 1.68, respectively). For patients with SLNB-negative disease, smoking at least 20 cigarettes per day doubled the risk for death due to melanoma (hazard ratio, 2.06)."Because smoking could be considered a risk factor for disease progression, increased vigilance in the management of patients who smoke may be warranted," the authors write.Several authors disclosed ties to the pharmaceutical industry.<a target="_blank" rel="noopener noreferrer" href="https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2814571">Abstract/Full Text</a><a target="_blank" rel="noopener noreferrer" href="https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2814573">Editorial</a>

Greatest increased risk for melanoma-specific mortality seen for patients with SLNB-negative disease

Smoking Linked to Melanoma-Associated Death in Early-Stage Melanoma

WEDNESDAY, Feb. 7, 2024 -- Adjunctive, handheld reflectance confocal microscopy (RCM) improves diagnostic accuracy of lesions clinically suspicious for basal cell carcinoma (BCC), according to a study published online Jan. 29 in the Journal of the American Academy of Dermatology.Caterina Longo, M.D., Ph.D., from the University of Modena and Reggio Emilia in Italy, and colleagues examined the additional benefit of handheld RCM in terms of diagnostic accuracy for skin cancer in a prospective study conducted in three skin cancer reference centers in Italy. A total of 1,005 lesions with clinical-dermoscopic suspicion of BCC were included.The researchers found that of the lesions, 474 were histopathologically confirmed and 531 were diagnosed by clinical-dermoscopic-RCM correlation, confirmed with two years of follow-up. Seven hundred forty of the lesions were confirmed BCCs. For dermoscopy alone, the sensitivity and specificity were 93.2 and 51.7 percent, respectively, with a positive predictive value (PPV) and negative predictive value (NPV) of 84.4 and 73.3, respectively. Higher rates were seen with adjunctive RCM, with sensitivity and specificity of 97.8 and 86.8 percent, respectively, and PPV and NPV of 95.4 and 93.5, respectively."The results of our prospective, multicenter study, carried out on 1,005 lesions suspicious of BCC at clinical examination, provides real-life diagnostic accuracy of dermoscopy for BCC, as a standalone tool and with adjunctive handheld-RCM assessment," the authors write.

Adjunctive handheld RCM improves diagnostic accuracy of lesions clinically suspicious for basal cell carcinoma

Does Reflectance Confocal Microscopy Increase Diagnostic Accuracy for BCC?

FRIDAY, Feb. 2, 2024 (HealthDay News) -- Within the sexual and gender minority (SGM) population, gender minority adults are more likely to report discomfort during full body skin examinations (FBSEs), according to a research letter published online Jan. 31 in JAMA Dermatology.Michelle Verghese, from the Pritzker School of Medicine at the University of Chicago, and colleagues used data from a sample of SGM individuals aged 18 years or older to examine perspectives surrounding FBSEs.Overall, 175 participants completed the survey and 42.8 percent reported ever having had a FBSE. The researchers found that 33.3 percent of those who underwent a FBSE reported discomfort during the examination. Discomfort was more likely to be reported by gender nonconforming, gender queer, and nonbinary (gender queer) and transgender individuals compared with sexual minority cisgender females and males (57.7 versus 25.6 percent). Compared with sexual minority cisgender males, sexual minority cisgender females were also more likely to report discomfort (37.5 versus 11.1 percent). Reasons related to undressing during the examination were more likely to be a reason for discomfort among gender queer, sexual minority cisgender female, and transgender respondents than sexual minority cisgender males; they were also more likely to report discrimination or nonaffirming interactions with medical practitioners and staff. Gender queer and transgender respondents were more likely to cite being misgendered during the appointment and to experience uncomfortable examination maneuvers."Our findings suggest that stigma and discrimination can negatively affect skin cancer screening experiences for SGM patients, serving as a substantial barrier," the authors write.<a target="_blank" rel="noopener noreferrer" href="https://jamanetwork.com/journals/jamadermatology/article-abstract/2814375">Abstract/Full Text (subscription or payment may be required)</a>

Gender queer and transgender individuals more likely to report discomfort than sexual minority cisgender females, males

Gender Minority Adults Are Vulnerable During Full Body Skin Exam

MONDAY, Jan. 29, 2024 (HealthDay News) -- For patients with advanced melanoma, early 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) imaging can identify metabolic changes that may predict response to pembrolizumab, according to a study published online Jan. 24 in Clinical Cancer Research.Thomas M. Anderson, M.D., from the Perelman School of Medicine at the University of Pennsylvania in Philadelphia, and colleagues prospectively enrolled 19 patients with advanced melanoma scheduled to receive pembrolizumab. At baseline and approximately one week after starting treatment, FDG PET/CT imaging was performed. These scans were assessed for changes in the maximum standardized uptake value (SUVmax); receiver operating curve analysis was used to identify thresholds, with metabolic flare (MF) defined as &gt;70 percent increase in tumor SUVmax and metabolic response (MR) defined as &gt;30 percent decrease in tumor SUVmax.The researchers found that six of 11 responders and zero of eight nonresponders had an MF or MR, with an objective response rate of 100 and 38 percent in the MF-MR group and the stable metabolism (SM) groups, respectively. There was an association seen for MF or MR with T-cell reinvigoration in the peripheral blood and immune infiltration in the tumor. Overall survival at three years was 83 and 62 percent in the MF-MR and SM groups, respectively. The median progression-free survival was &gt;38 and 2.8 months in the MF-MR and SM groups, respectively."An MF or MR was predictive of response, and strongly correlated with progression-free survival, suggesting that response assessment by early FDG PET/CT is robust," the authors write.Several authors disclosed ties to pharmaceutical companies, including Merck, which manufactures pembrolizumab and funded the study.<a target="_blank" rel="noopener noreferrer" href="https://aacrjournals.org/clincancerres/article-abstract/doi/10.1158/1078-0432.CCR-23-2390/733627/FDG-PET-CT-Imaging-1-Week-after-a-Single-Dose-of">Abstract/Full Text (subscription or payment may be required)</a>

Metabolic changes associated with progression-free survival in patients receiving pembrolizumab

Early FDG PET/CT Can ID Metabolic Changes in Advanced Melanoma

WEDNESDAY, Jan. 24, 2024 -- Among Black patients, most melanomas are located on acral skin, according to a study published online Jan. 24 in JAMA Dermatology.Sophia N. Wix, from the University of Texas Southwestern Medical Center in Dallas, and colleagues identified patient- and tumor-level characteristics of melanoma in Black patients in a case series conducted at two tertiary care centers affiliated with a single institution. Data were included for 48 Black patients (median age at diagnosis, 62 years).The researchers found that 30 of the 40 primary cutaneous melanomas were located on acral skin, although only 10 of these 30 were histologically classified as acral lentiginous melanomas. Patients with nonacral cutaneous melanoma were more likely to be immunocompromised (40 versus 7 percent) or have a personal history of cancer (60 versus 17 percent) than those with acral disease; all three patients with superficial spreading melanoma had a history of both. None of the patients had more than one confirmed primary melanoma. Overall, 27 percent of Black patients with melanoma developed stage IV disease; 12 of these 13 patients died due to disease progression. None of the patients with nonacral cutaneous melanomas developed distant metastases or died of melanoma. Patients with advanced acral melanoma, mucosal/ocular melanoma, or melanoma of unknown primary did not have actionable sequence variations, were not responsive to immunotherapy, and had the worst outcomes."Focusing research efforts to improve therapeutic and prevention strategies for these poorly studied subtypes has potential to improve melanoma mortality in Black patients," the authors write.

Patients with nonacral cutaneous melanomas more likely to be immunocompromised, have personal history of cancer

Most Melanomas in Black Patients Located on Acral Skin

THURSDAY, Jan. 18, 2024 (HealthDay News) -- The first medical device powered by artificial intelligence and designed to help doctors catch skin cancer has been approved by the U.S. Food and Drug Administration.Although not meant to be used as a primary screening tool, the technology further evaluates skin lesions that doctors have already flagged as suspicious, the FDA noted in an agency <a target="_blank" rel="noopener noreferrer" href="https://www.fda.gov/news-events/press-announcements/fda-roundup-january-16-2024">news release</a>. &nbsp;The handheld device uses AI-powered spectroscopy to assess the characteristics of lesions at both the cellular level and beneath the skin's surface.“We are entering the golden age of predictive and generative artificial intelligence in healthcare, and these capabilities are being paired with novel types of technology, like spectroscopy and genetic sequencing, to optimize disease detection and care,” DermaSensor Inc. co-founder and CEO Cody Simmons said in a company <a target="_blank" rel="noopener noreferrer" href="https://www.businesswire.com/news/home/20240117116417/en/FDA-Clearance-Granted-for-First-AI-Powered-Medical-Device-to-Detect-All-Three-Common-Skin-Cancers-Melanoma-Basal-Cell-Carcinoma-and-Squamous-Cell-Carcinoma">news release</a>. “Equipping PCPs [primary care physicians], the most abundant clinicians in the country, to better evaluate the most common cancer in the country has been a major, long-standing unmet need in medicine.”The device, also called DermaSensor, provides real-time results using an algorithm based on data culled from more than 4,000 malignant and benign lesions, according to the company."The device should be used in conjunction with the totality of clinically relevant information from the clinical assessment, including visual analysis of the lesion, by physicians who are not dermatologists," the FDA said, adding that DermaSensor is for use in patients ages 40 and up.Along with helping to spot melanoma, the most deadly form of skin cancer, the device can also assess moles for basal cell carcinoma and squamous cell carcinoma.One in five Americans will have developed a form of skin cancer by the age of 70, according to the <a target="_blank" rel="noopener noreferrer" href="https://www.aad.org/media/stats-skin-cancer">American Academy of Dermatology</a>, which puts the cost of treatment in the United States at more than $8 billion. Most skin cancers are curable if detected early.The FDA added that it is requiring additional validation testing in patients from representative demographic groups, including those who are at lower risk of skin cancer.More informationThe Skin Cancer Foundation has more on<a target="_blank" rel="noopener noreferrer" href="https://www.skincancer.org/"> skin cancer</a>.SOURCE: U.S. Food and Drug Administration, news release, Jan. 16, 2024; DermaSensor Inc., news release, Jan. 17, 2024

The first medical device powered by artificial intelligence and designed to help doctors catch skin cancer has been approved by the U.S. Food and Drug Administration

FDA Approves AI Device That Helps Spot Skin Cancer

WEDNESDAY, Jan. 17, 2024 -- For patients with nonmelanoma skin cancers (NMSCs), hypofractionated superficial X-ray therapy (SXRT), administered at an average dose of 35.7 Gy over 5.47 fractions, yields tumor recurrence rates of up to 10.5 percent at 10 years, according to a research letter published online Jan. 12 in the Journal of the American Academy of Dermatology.Alexzandra Mattia, from the Florida State University College of Medicine in Tallahassee, and colleagues evaluated the use of hypofractionated SXRT in the management of nonaggressive NMSCs in a single-institution 22-year retrospective analysis of 2,490 biopsy-proven NMSCs from 1,082 elderly patients treated between Jan. 1, 2000, and June 1, 2022.The researchers found that during a span of 22 years, the two-, five-, and 10-year tumor recurrence rates were 2.2, 6.0, and 10.5 percent, respectively. The average dose administered was 35.7 Gy over 5.47 fractions; most of the treatment protocols used 40 to 45 Gy over 10 to 15 fractions."Our study highlights the utility of hypofractionated SXRT as a well-tolerated and less expensive treatment alternative for select NMSCs in nonsurgical patients," the authors write.

Over 22 years, two-, five-, and 10-year tumor recurrence rates were 2.2, 6.0, and 10.5 percent, respectively

What Are the Skin Cancer Recurrence Rates for Superficial X-Ray Therapy?

WEDNESDAY, Jan. 10, 2024 -- A considerable number of patients with advanced melanoma start systemic therapy in the 30 days or three months before death, according to a study published online Dec. 11 in the Journal of Dermatology.Pieter E.A. van Lith, from the Netherlands Comprehensive Cancer Organization in Utrecht, and colleagues examined the timing of systemic therapies within 30 days and three months before death in patients diagnosed with advanced melanoma (July 2017 to June 2020) who died before July 2020.Sixty-eight percent of the 1,097 patients received systemic therapy. Almost 25 and 10 percent started a new therapy within 90 and 30 days before death, respectively. The researchers found that the odds of receiving immune therapy were reduced in association with female sex, elevated lactate dehydrogenase, BRAF mutation, poor Eastern Cooperative Oncology Group performance status, and high comorbidity index. The odds of receiving both targeted and immune therapies were highest for patients younger than 40 years."It is crucial to carefully consider the potential benefits and drawbacks of initiating these novel therapies in the final stages of life, emphasizing the importance of shared decision-making between patients and their health care providers," the authors write.One author disclosed ties to the pharmaceutical industry.

Reduced odds of receiving immune therapy seen in association with female sex, elevated LDH, BRAF mutation, poor ECOG performance status

Some Advanced Melanoma Patients Start Systemic Therapy Shortly Before Death

WEDNESDAY, Jan. 3, 2024 -- Variants in certain DNA repair and cancer-predisposing genes are associated with early-onset Merkel cell carcinoma (MCC), according to a study published online Jan. 3 in JAMA Dermatology.Noreen Mohsin, M.D., from the National Institutes of Health in Bethesda, Maryland, and colleagues prospectively enrolled participants with early-onset and later-onset MCC, defined as disease occurring in individuals younger than 50 years and at age 50 years or older, respectively, to identify genetic risk factors for early onset MCC via genomic sequencing. The analysis included 37 participants with early-onset MCC, 45 with later-onset MCC, and 930 unrelated controls.The researchers found that 19 percent of the patients with early-onset MCC had well-described variants in genes associated with cancer predisposition; six of the seven patients had variants associated with hereditary cancer syndromes (ATM, BRCA1, BRCA2, and TP53), and one had a variant associated with immunodeficiency and lymphoma (MAGT1). The early-onset cohort was significantly enriched for cancer-predisposing pathogenic or likely pathogenic variants in these five genes compared with unrelated controls (odds ratio, 30.35). In the patients with later-onset MCC, no germline disease variants were identified in these genes. Among patients with MCC, additional variants were identified in DNA repair genes."Genetic counseling and cascade testing of potentially affected family members should be considered for patients diagnosed with MCC at age younger than 50 years, with a focus on detecting pathogenic variants in ATM, BRCA1, BRCA2, TP53, MAGT1, or DNA repair genes," the authors write.One author disclosed being the founder of Moonlight Bio.

19 percent of patients with early-onset Merkel cell carcinoma have well-described variants in genes associated with cancer predisposition

Variants in Cancer-Predisposing Genes Linked to Early-Onset Merkel Cell Carcinoma

MONDAY, Dec. 18, 2023 (HealthDay News) -- Patients with lower extremity (LE) lymphedema have an increased risk for skin cancer, especially basal cell carcinoma, according to a study published online in the November issue of Mayo Clinic Proceedings.Nimay C. Anand, M.D., from Meharry Medical College in Nashville, Tennessee, and colleagues conducted a retrospective cohort study including patients with LE lymphedema examined from Jan. 1, 2000, through Dec. 31, 2020. The study included 4,437 patients with LE lymphedema and age-, race-, and sex-matched controls without lymphedema. The time to development of the first skin cancer was compared for the lymphedema and control cohorts.The researchers found that the lymphedema group had a significantly increased risk for skin cancer compared with the matched control group. The lymphedematous extremity was 2.65 times as likely as the nonlymphedematous LE to have skin cancer, especially basal cell carcinoma, in a subset of patients with unilateral lymphedema."Future studies are needed to understand the pathogenesis of cancer in this population and to help guide individualized management of skin cancer in patients with lymphedema, particularly to determine whether cancers on lymphedematous LEs are histologically and prognostically different from cancers on nonlymphedematous LEs," the authors write.Several authors disclosed ties to the pharmaceutical industry.<a target="_blank" rel="noopener noreferrer" href="https://www.mayoclinicproceedings.org/article/S0025-6196(23)00117-9/fulltext">Abstract/Full Text (subscription or payment may be required)</a>

Lymphedematous extremity 2.65 times as likely as the nonlymphedematous extremity to have skin cancer

Risk for Skin Cancer Increased for Patients With Lower Extremity Lymphedema

WEDNESDAY, Dec. 13, 2023 -- Phototherapy is not associated with an increased risk for skin cancer, according to a study published online Dec. 7 in the Journal of the American Academy of Dermatology.Elle Wang, from the University of British Columbia in Vancouver, Canada, and colleagues conducted a retrospective cohort study of patients treated at a teaching-hospital phototherapy center from 1977 to 2018. Age-standardized incidence rates (ASIR) of skin cancer were assessed for gender, skin phototype, diagnosis, ultraviolet modality, and anatomical site and were compared with provincial population incidence rates. Data were included for 3,506 patients treated with broadband-ultraviolet-B (UVB), narrowband-UVB, and/or combined UVAB, who were followed for a mean of 7.3 years.Most patients had psoriasis or eczema (60.9 and 26.4 percent, respectively); patients received a median of 43 treatments. The researchers identified 170 skin cancers in 79 patients (17 melanoma, 33 squamous cell carcinoma [SCC], and 120 basal cell carcinoma [BCC]). The patient- and tumor-based ASIR of skin cancer was 149 and 264 per 100,000 person-years, respectively. No significant difference was seen between tumor-based ASIRs for melanoma, SCC, and BCC versus the general population, or in patients with psoriasis or eczema, or in those using immunosuppressants. There was no cumulative dose-response correlation noted between UVB and skin cancer."No increased risk of melanoma, SCC, and BCC compared to the general population was found in patients receiving phototherapy," the authors write. "This suggests ultraviolet phototherapy can be considered a relatively safe treatment option."

No significant difference seen between tumor-based age-standardized incidence rates of skin cancer compared with general population

Is Phototherapy Linked to Increased Risk for Skin Cancer?

WEDNESDAY, Dec. 6, 2023 -- An elastic-scattering spectroscopy (ESS) device can aid skin cancer detection, according to a study published online Oct. 10 in JAAD International.Danielle Manolakos, D.O., M.P.H., from the Gold Coast Dermatology Center in Delray Beach, Florida, and colleagues examined the safety and effectiveness of an ESS device in evaluating lesions that are suggestive of skin cancer in a prospective, multicenter clinical validation study. Patients with skin lesions suggestive of melanoma and nonmelanoma skin cancers were assessed clinically by expert dermatologists and with a device using artificial intelligence algorithms comparing current ESS lesion readings with training data sets.The researchers found that overall device sensitivity was 97.04 percent, with subgroup sensitivity of 96.67, 97.22, and 97.01 percent for melanoma, basal cell carcinoma, and squamous cell carcinoma, respectively. The device and dermatologist performance did not differ significantly. Overall device specificity was 26.22 percent, and negative and positive predictive values were 89.58 and 57.54 percent, respectively."The ESS device is an intuitive, noninvasive, safe, and effective handheld device that may assist primary care clinicians in the assessment of clinically suspicious lesions," the authors write. "Proper use of this device may aid in the reduction of morbidity and mortality associated with skin cancer through expedited and enhanced detection and intervention."Several authors disclosed financial ties to DermaSensor, which developed the ESS device used in the study and provided funding.

Device has high sensitivity for detection of melanoma, basal cell carcinoma, squamous cell carcinoma

Can an Elastic-Scattering Spectroscopy Device Aid Skin Cancer Detection?

WEDNESDAY, Nov. 29, 2023 (HealthDay News) -- A mobile phone-powered artificial intelligence (AI) technology is effective for diagnosing suspicious skin lesions, according to a study published in the October issue of The Lancet Digital Health.Scott W. Menzies, Ph.D., from the University of Sydney, and colleagues compared the accuracy of AI algorithms and clinicians for the diagnosis and management of pigmented skin lesions. For the diagnostic study, the analysis included 172 suspicious pigmented lesions from 124 patients, while the management study included 5,696 pigmented lesions from 66 high-risk patients. &nbsp;The researchers found that the diagnoses of the seven-class AI algorithm were similar to the specialists' diagnoses (absolute accuracy difference, 1.2 percent) and significantly superior to the novice clinicians' diagnoses (21.5 percent). Diagnoses based on the International Skin Imaging Collaboration AI algorithm were significantly inferior to the specialists' diagnoses (–11.6 percent) but significantly superior to the novices' diagnoses (8.7 percent). The best seven-class management AI was significantly worse than specialists' management (absolute accuracy difference in correct management decision, –0.5 percent for dismissal and –0.4 percent for biopsy). For novice clinicians' management, the seven-class management AI was significantly inferior (–0.4 percent for dismissal), but significantly superior (0.4 percent) for biopsy."An AI algorithm that was superior in experimental studies was significantly inferior to specialists in a real-world scenario, suggesting that caution is needed when extrapolating results of experimental studies to clinical practice," the authors write.The study was funded by MetaOptima Technology.

AI may be less accurate than clinicians in usage for management decisions

AI Accurate in Diagnosing Suspicious Skin Lesions

WEDNESDAY, Nov. 29, 2023 -- Age-adjusted incidence rates of keratinocyte carcinomas (KC) are much lower for patients with skin of color than non-Hispanic Whites, according to a research letter published online Nov. 29 in JAMA Dermatology.Lucy J. Navsaria, M.B.B.Ch., M.P.H., from the University of Texas MD Anderson Cancer Center in Houston, and colleagues reported KC incidence and patient demographics by race and ethnicity among a random sample of Medicare beneficiaries age 65 years or older with claims from 2009 to 2018.The researchers found that 15.7 percent of the 4,999,999 eligible beneficiaries had at least one treated KC; 97.6 and 2.4 percent were non-Hispanic White and had skin of color, respectively. Compared with non-Hispanic White patients, those with skin of color were more likely to be female (55.2 versus 51.9 percent) and older at first KC diagnosis (mean age, 77.7 versus 76.7 years). Overall, 2,498,805 KCs were identified: 98.3 and 1.7 percent in non-Hispanic Whites and patients with skin of color, respectively. The age-adjusted incidence was 1,158.2 and 11,493.2 per 100,000 person-years in patients with skin of color and non-Hispanic Whites, respectively. The age-adjusted incidence rates for basal cell carcinoma were 378.9 and 3,492.0 per 100,000 person-years for patients with skin of color and non-Hispanic Whites, respectively; the corresponding rates for squamous cell carcinoma were 453.5 and 4,881.2."We found differences in demographics and KC incidence between non-Hispanic White patients and patients with skin of color," the authors write. "This finding may be valuable in KC surveillance and risk factor differentiation."

Incidence rates in patients with skin of color are about 10 percent of that seen for non-Hispanic Whites

Is the Incidence of Keratinocyte Carcinoma Lower for Patients of Color?

MONDAY, Nov. 20, 2023 (HealthDay News) -- Occupational exposure to solar ultraviolet radiation (UVR) is associated with a substantial burden of nonmelanoma skin cancer (NMSC), according to a study published in the November issue of Environment International.Frank Pega, from the World Health Organization in Geneva, and colleagues presented WHO and International Labour Organization (ILO) estimates of global, regional, national, and subnational occupational exposures to UVR for 195 countries/regions and the global, regional, and national attributable burdens of NMSC for 183 countries for 2000, 2010, and 2019. Using 166 million observations from 763 cross-sectional surveys for 96 countries/areas, occupational exposure to UVR was modeled via proxy of occupation with outdoor work. By applying population-attributable fractions (PAFs) from estimates of the population occupationally exposed to UVR and the risk ratio for NMSC, the attributable NMSC burden was estimated.The researchers found that in 2019, 1.6 billion workers were occupationally exposed to UVR globally, representing 28.4 percent of the working-age population. The PAFs for NMSC deaths and disability-adjusted life years (DALYs) were 29.0 and 30.4 percent, respectively; attributable burdens were 18,960 deaths and 0.5 million DALYs. A larger burden was seen for men and older age groups. Attributable deaths and DALYs almost doubled during 2000 to 2019."WHO and the ILO estimate that occupational exposure to UVR is common and leads to substantial numbers of deaths and of DALYs from NMSC," the authors write.

Attributable burdens were 18,960 deaths and 0.5 million disability-adjusted life years, which almost doubled from 2000 to 2019

Occupational Exposure to Solar UVR Linked to Nonmelanoma Skin Cancer

MONDAY, Nov. 20, 2023 -- For patients with clinically localized Merkel cell carcinoma, preoperative staging with cross-sectional imaging does not influence surgical management, according to a study published in the November issue of SKIN.Natalie Garcia, from the University of Alabama at Birmingham Heersink School of Medicine, and colleagues examined how preoperative staging with cross-sectional imaging influences management of patients with clinically localized Merkel cell carcinoma in a study involving 97 patients evaluated between Jan. 1, 2012, and Dec. 31, 2020. Eighty-four of the patients had preoperative staging studies.The researchers found that the clinical characteristics of the patients did not differ based on whether staging was performed. Positron emission tomography/computed tomography (PET/CT), CT, and magnetic resonance imaging were performed in 52, 51, and 31 patients (67, 62, and 41 percent, respectively). Five patients had indeterminate findings (all on PET/CT); no patients were identified for whom preoperative staging changed the plan for surgical resection."Based on these findings, more selective use of preoperative imaging staging may be warranted," the authors write. "Future work should seek to characterize risk factors for clinically occult metastases which could be used to refine current guidelines for preoperative staging."

Preoperative staging with cross-sectional imaging does not influence management in localized Merkel cell carcinoma

Does Preop Staging With Imaging Impact Management of Merkel Cell Carcinoma?

WEDNESDAY, Nov. 15, 2023 -- The Mohs appropriate use criteria (AUC) score can help to ascertain whether a keratinocyte carcinoma (KC) warrants Mohs micrographic surgery (MMS), according to a review published in the November issue of SKIN.Richard H. Hope, M.D., from Texas Tech University Sciences Center in Lubbock, and colleagues conducted a retrospective review of 11,145 consecutive KCs between January 2017 and December 2021 to stratify KC by treatment modality and compare the associated Mohs AUC score with the treatment modality.The researchers found that the average Mohs AUC score was 7.1 for all KCs combined, with 78.2 percent of the KCs qualifying for MMS via AUC score. However, only 32.3 percent of KCs underwent MMS. Of the KCs, excisional surgery was used to treat 41.1 percent; 24.9 percent were treated with electrodesiccation and curettage (ED&amp;C), and 6.6 percent were treated with biopsy only. Overall, 70.7, 70.7, and 72.4 percent of those KCs treated with excision, ED&amp;C, or biopsy, respectively, reached an "appropriate" Mohs AUC sore for MMS."We can determine that just because a KC reaches the Mohs AUC score for MMS does not necessarily mean that MMS is the best treatment option for that particular patient and tumor based on the patient's clinical status and the clinician's evaluation [of] the lesion," the authors write.

Mohs micrographic surgery was only done on 32.3 percent of the keratinocyte carcinomas that qualified based on AUC score

Can Mohs Appropriate Use Criteria Score Help Determine Keratinocyte Carcinoma Treatment?

FRIDAY, Nov. 3, 2023 (HealthDay News) -- Artificial intelligence (AI) is increasingly accurate in detecting skin cancer, according to a study presented at the annual meeting of the European Academy of Dermatology and Venereology, held from Oct. 11 to 14 in Berlin.Kashini Andrew, M.B.B.S., from the University Hospitals Birmingham NHS Foundation Trust in the United Kingdom, and colleagues examined improvement in the sensitivity of the detection of skin cancers with continued improvement of the AI algorithm (upgraded twice since May 2020) using previously collected data (22,356 patients assessed over 2.6 years).The researchers found that the latest version of AI software was highly sensitive in detecting all skin cancers (99.5 percent), precancers (92.5 percent), and melanoma (100 percent), with improved sensitivity observed over time. Out of 190 cancers, AI missed one cancer diagnosis -- a basal cell carcinoma identified at the second read by the safety-net dermatologist. The latest algorithm also showed a high specificity in identifying benign lesions (75.3 percent). Compared with version 1, the researchers note a slight drop in specificity for benign lesions, a potential trade-off for increased sensitivity for malignant lesions. The rate of overturn of the diagnosis from benign to skin cancer was 0.1 percent, which was a significant improvement from version 1. The investigators estimated that the latest version prevented more than 2,000 face-to-face appointments in secondary care."The role of AI in dermatology and the most appropriate pathway are debated," Andrew said in a statement. "Further research with appropriate clinical oversight may allow the deployment of AI as a triage tool. However, any pathway must demonstrate cost-effectiveness, and AI is currently not a standalone tool in dermatology. Our data shows the great promise of AI in future provision of health care."

Software improvements show high sensitivity across skin cancer types, including melanoma

AI Getting Better at Detecting Skin Cancer

WEDNESDAY, Oct. 25, 2023 -- For patients with basal cell carcinoma (BCC) unable to tolerate the traditional vismodegib dosing regimen, an alternative regimen provides therapeutic effects without intolerable side effects, according to a research letter published in the September issue of SKIN.Timothy Orlowski, M.D., from the University of Alabama at Birmingham, and colleagues conducted a retrospective review of side effects, safety, and efficacy of an alternative vismodegib dosing pattern in six patients from a single institution who were unable to tolerate the traditional dosing regimen. The patients were prescribed vismodegib 150 mg daily for seven days, followed by a 21-day drug holiday.The researchers found that improvement or resolution of adverse events was reported by all patients on this alternative treatment regimen; patients continued on this regimen for an average of 30.7 months. No new BCC development was seen for four patients, and their existing BCCs shrunk in size. A single BCC was developed by one patient with basal cell nevus syndrome 24 months into treatment; another patient developed a single BCC during a drug holiday for radiation therapy of lung squamous cell carcinoma."Our alternative long-term dosing schedule of vismodegib 150 mg daily for seven days followed by a 21-day drug holiday may provide therapeutic effects without intolerable side effects," the authors write. "It's not clear what maintenance schedule of vismodegib is ideal for patients requiring long-term treatment; however, future prospective studies may elucidate a regimen that minimizes both BCC burden and adverse effects."

Alternative regimen of vismodegib 150 mg daily for seven days followed by 21-day drug holiday provides therapeutic effect

Is Alternative Vismodegib Dosing Regimen Tolerable for Basal Cell Carcinoma?

WEDNESDAY, Oct. 18, 2023 (HealthDay News) -- The U.S. Food and Drug Administration has approved Opdivo (nivolumab) for the adjuvant treatment of completely resected stage IIB/C melanoma in patients ages 12 years and older.The approval was based on results from the CHECKMATE-76K randomized, double-blind trial. The trial included 790 patients with stage IIB/C melanoma who were randomly assigned (2:1) to nivolumab 480 mg or placebo by intravenous infusion every four weeks for up to one year or until disease recurrence or unacceptable toxicity. At the time of the approval, median recurrence-free survival was not reached in either the nivolumab arm or the placebo arm.The recommended nivolumab dose for patients weighing ≥40 kg is 240 mg every two weeks or 480 mg every four weeks until disease progression or unacceptable toxicity for up to one year. For pediatric patients weighing &lt;40 kg, the recommended dose is 3 mg/kg every two weeks or 6 mg/kg every four weeks.The most common adverse reactions (reported in at least 20 percent of patients) included fatigue, musculoskeletal pain, rash, diarrhea, and pruritis.Approval of nivolumab was granted to Bristol Myers Squibb.

Approval granted for patients aged 12 years and older with stage IIB/C disease

FDA Approves Nivolumab as Adjuvant Treatment for Melanoma

WEDNESDAY, Oct. 18, 2023 -- The global melanoma incidence in 2020 was 324,635, resulting in 57,043 deaths, while nonmelanoma skin cancer (NMSC) led to 63,731 deaths, according to a study presented at the annual meeting of the European Academy of Dermatology and Venereology, held from Oct. 11 to 14 in Berlin.Samir Salah, from Laboratoire Dermatologique La Roche-Posay in Levallois Perret, France, and colleagues conducted an epidemiological analysis of skin cancer using World Health Organization International Agency for Research on Cancer data.The researchers found that global melanoma incidence was 324,635 in 2020, resulting in 57,043 deaths. Europe bore the heaviest burden (150,000 cases and 26,360 deaths), while Africa had the highest mortality-to-incidence ratio (0.25 versus 0.026 for Europe). Despite the lower mortality likelihood, NMSC led to 63,731 deaths in 2020 due to a significantly higher incidence; there were 11,281 deaths in Africa. There was wide variation seen in dermatologist densities among 59 countries with data (0.33 per 100,000 in Pakistan to 15.15 in Greece), with no linear correlation to wealth or melanoma incidence noted. Countries with fair-skinned and elderly populations had high skin cancer incidence, including the United States, Germany, and the United Kingdom. Higher mortality-to-incidence ratios were seen in countries with low dermatologist density (India, China, Turkey, Korea, and Morocco), while high ratios were seen in Japan, Russia, and Argentina, despite high dermatologist density."We have to get the message out that not only melanoma can be fatal, but NMSC also," coauthor Thierry Passeron, M.D., Ph.D., from the Nice University Hospital Center in France, said in a statement. "It's crucial to note that individuals with melanin rich skin are also at risk and are dying from skin cancer."This work was conducted by the L'Oréal Dermatological Beauty Corporate and Social Responsibility team, in conjunction with La Roche-Posay experts.

Global melanoma incidence was 324,635 in 2020, resulting in 57,043 deaths, while 63,731 NMSC deaths were reported

Is Nonmelanoma Skin Cancer Causing More Deaths Than Melanoma?

WEDNESDAY, Oct. 18, 2023 -- Extensive perineural invasion (ePNI) seems to be the best prognostic measure for cutaneous squamous cell carcinoma (CSCC), according to a study published online Oct. 18 in JAMA Dermatology.Paul R. Massey, M.D., M.P.H., from the Cheyenne Skin Clinic in Wyoming, and colleagues compared four assessments of PNI (nerve caliber, number of involved nerves per section, PNI maximal depth, and PNI location) with respect to tumor in patients with primary, localized, invasive CSCC in a retrospective cohort study performed at a single tertiary care institution. Data were included for 140 patients with CSCC.The researchers found that only involvement of multiple nerves was associated with poor outcomes. Independent associations were seen for PNI of five or more distinct nerves (ePNI) with local recurrence, disease-specific death, and any poor outcome (subhazard ratios, 13.83, 6.20, 10.21, respectively). Compared with current Brigham and Women's Hospital (BWH) staging criteria that use nerve caliber as the measure of PNI, a revised BWH staging system with substitution of ePNI for large-caliber PNI resulted in improved area under the curve and test characteristics."Although these findings require further validation in other cohorts, inclusion of ePNI as a high-risk factor in CSCC staging may optimize recurrence risk assessment and patient selection for surgical treatment modality and postoperative adjuvant interventions," the authors write.One author disclosed ties to the pharmaceutical industry.

Perineural invasion of five or more nerves independently linked to local recurrence, disease-specific death, any poor outcome

Is Extensive Perineural Invasion Best Prognostic Measure for Cutaneous Squamous Cell Carcinoma?

WEDNESDAY, Sept. 27, 2023 -- Clinical and dermatoscopic examination combined with optical coherence tomography (CDE-OCT) has higher ability to detect recurrent/residual basal cell carcinoma (BCC) than CDE alone after topical treatment, according to a study published in the October issue of the Journal of the American Academy of Dermatology.Tom Wolswijk, M.D., from Maastricht University Medical Center in the Netherlands, and colleagues compared the diagnostic accuracy of CDE to that of CDE-OCT for detecting recurrent/residual BCC after topical treatment of superficial BCC in 100 patients. The suspicion level for recurrence or residue was recorded on a 5-point confidence scale. Patients with high suspicion were referred for punch biopsy, while those with low suspicion were asked to undergo a control biopsy. Verification of CDE and CDE-OCT diagnoses was based on histopathological results of the biopsy.A histopathological recurrent/residual BCC was detected in 20 patients. The researchers found that sensitivity for recurrence or residue detection was 100 and 60 percent, respectively, for CDE-OCT and CDE, and specificity was 95 and 96.3 percent, respectively. The area under the curve was 0.98 and 0.77 for CDE-OCT and CDE, respectively."Use of CDE-OCT at the follow-up appointment after topical treatment may result in the detection of subclinical recurrences or residues," the authors write. "Early detection of recurrent or residual BCC may prevent tumor progression and may prevent additional follow-up appointments if no recurrence or residue is seen."

Area under curve 0.98 for clinical and dermatoscopic examination combined with OCT and 0.77 for clinical and dermatoscopic examination alone

Does Adding Optical Coherence Tomography Increase Detection of Recurrent, Residual BCC?

FRIDAY, Aug. 18, 2023 (HealthDay News) -- Since 1996, there has been an increase in the percentage of women in Mohs micrographic surgery (MMS) fellowships and program directors (PDs), according to a research letter published online Aug. 9 in JAMA Dermatology.Sophie Gart, from the University of Nebraska Medical Center College of Medicine in Omaha, and colleagues examined trends in the percentage of women comprising MMS matriculants and PDs using self-reported gender data from Accreditation Council for Graduate Medical Education (ACGME)-registered dermatology residents and fellows from 1996 to 2021. In addition, MMS PDs' and fellows' genders were retrieved from the American College of Mohs Surgery (ACMS) for 1996 to 2022.The researchers found that female representation within all groups increased over time. The total number of MMS ACMS fellows increased from 29 in 1996 to 84 in 2021; the percentage of female fellows increased from 24 to 42 percent. Female MMS ACGME fellows increased from 20 in 2004 to 78 in 2021, and female MMS PDs increased from 30 to 83. The percentage of female PDs increased from 3 to 28 percent during the study period. Within all groups, there was a significant positive trend observed between the percentage of female representation and year."This study shows the significant demographic shift for women in MMS fellowship and PD roles," the authors write. "The increase in percentage of female PDs is particularly encouraging, as having females in leadership positions positively correlates with more females in faculty positions."One author disclosed receiving grants from Castle Biosciences.

Significant positive trend seen between percentage of female representation and year since 1996

Percentage of Women Mohs Fellows, Program Directors Has Increased

WEDNESDAY, Aug. 9, 2023 (HealthDay News) -- Incorporating human preferences into an image-based diagnostic algorithm can improve artificial intelligence (AI)-based decision support, according to a study published online July 27 in Nature Medicine.Catarina Barata, Ph.D., from the Instituto Superior Técnico in Lisbon, Portugal, and colleagues examined whether human preferences can improve diagnostic AI-based decision support using the example of skin cancer diagnosis. Nonuniform rewards and penalties based on expert-generated tables were utilized, balancing the benefits and harms of diagnostic errors; these were applied using reinforcement learning to find a strategy that maximized cumulative rewards while considering both clinician and patient preferences.The researchers found that the reinforcement learning model improved the sensitivity for melanoma from 61.4 to 79.5 percent and for basal cell carcinoma from 79.4 to 87.1 percent compared with supervised learning. There was a reduction noted in AI overconfidence, while accuracy was maintained. The rate of correct diagnoses made by dermatologists increased by 12.0 percent with reinforcement learning; the rate of optimal management decisions increased from 57.4 to 65.3 percent."The AI learned to take into account not only image-based features, but also consequences of misdiagnosis in the assessment of benign and malignant skin manifestations," lead author Harald Kittler, M.D., from the Medical University of Vienna, said in a statement. "This, in turn, helps physicians make more accurate decisions tailored to individual patients in complex medical scenarios."Several authors disclosed financial ties to medical technology companies.

Correct diagnoses made by dermatologists increased with reinforcement learning, incorporating human preferences into AI model

Reinforced Learning Model Can Improve Sensitivity of Skin Cancer Diagnosis

WEDNESDAY, Aug. 2, 2023 -- For patients with nonfacial basal cell carcinomas (BCCs), curettage and cryosurgery with standardized protocols provide excellent clinical clearance rates with one and two freeze-thaw cycles, according to a research letter published online June 8 in the Journal of the American Academy of Dermatology.Eva Backman, M.D., from the University of Gothenburg in Sweden, and colleagues compared clearance rates after one year for curettage and cryosurgery in one (C&amp;Cx1) versus two free-thaw cycles (C&amp;Cx2) for nonfacial BCCs with clinically nodular features. Curettage with a 4-mm or 7-mm curette was followed by cryosurgery with an open-cone spray technique, aiming for a halo thaw time of ≥60 seconds. The second freeze was performed after complete thawing of the lesion in lesions randomly assigned to C&amp;Cx2. The analysis included 202 lesions in 116 patients.The researchers identified a single recurrence in the C&amp;Cx1 group at one year, resulting in clearance rates of 99 versus 100 percent, proving noninferiority with an absolute difference of &lt;8 percent. For oozing wounds, the mean time was 1.0 and 1.2 weeks for C&amp;Cx1 and C&amp;Cx2. Overall, 71 percent of the wounds still had crusts, 13 percent still had oozing, and 11 percent were completely healed at four to six weeks, with no significant differences noted between the groups. The only relevant factor that significantly increased wound healing times was larger lesion size. After one year, 105, one, and four patients reported satisfaction with their scars, were unsatisfied, and felt neutral, respectively."This investigation increases the evidence for curettage plus cryosurgery, a low-cost and time-saving treatment for BCCs with nodular features," the authors write.

Curettage and cryosurgery provide excellent clinical clearance rates with one and two free-thaw cycles in nonfacial basal cell carcinomas

Do Curettage and Cryosurgery Provide Clearance for Basal Cell Carcinomas?

WEDNESDAY, July 19, 2023 -- Organ transplant recipients (OTRs) with cutaneous squamous cell carcinoma (cSCC) have increased rates of second cSCC, metastasis, and death from cSCC, according to a study published online July 19 in JAMA Dermatology.Petter Gjersvik, M.D., Ph.D., from the University of Oslo in Norway, and colleagues examined the rates of second cSCC, metastasis, and death from cSCC in patients with and without organ transplant-associated immunosuppressive treatment in a population-based nationwide cohort study involving 47,992 individuals diagnosed with cSCC at age 18 years or older. Data were included for 1,208 OTRs and 46,784 non-OTRs.The researchers found that the rate of a second cSCC was 30.9 and 250.6 per 1,000 person-years in non-OTRs and OTRs, respectively, with a 4.3-fold increased rate for OTRs in the adjusted analysis. Per 1,000 person-years, the metastasis rate was 2.8 and 4.8 in non-OTRs and OTRs, respectively, with a 1.5-fold increased rate for OTRs in the adjusted analysis. There were 30,451 deaths reported; 98.2 percent were from causes other than cSCC. Death from cSCC was seen in 1.1 and 3.3 percent of non-OTRs and OTRs, respectively. The rate of death from cSCC was 1.7 and 5.4 per 1,000 person-years in non-OTRs and OTRs, respectively, with a 5.5-fold increased rate among OTRs in the adjusted analysis."These findings have implications for the clinical follow-up of individual patients and for skin cancer care policies," the authors write.

Transplant recipients have increased rates of second cutaneous squamous cell carcinoma, metastasis, death from cutaneous squamous cell carcinoma

 Do Organ Transplant Recipients With cSCC Have Worse Outcomes?

WEDNESDAY, July 5, 2023 -- The perceived risk of opioid addiction affects patients' choice of pain medications after Mohs surgery, with patients favoring over-the-counter medications (OTCs) if the opioid addiction risk profile was high, according to a study published online July 5 in JAMA Dermatology.Shannon T. Nugent, M.D., from the Sidney Kimmel Medical College at Thomas Jefferson University in Philadelphia, and colleagues examined patient preferences for pain management with only OTCs or OTCs plus opioids among patients undergoing Mohs surgery in a prospective discrete choice experiment.The researchers found that of the 295 respondents, 34 percent stated that they would never consider opioids for pain management, regardless of the level of pain experienced; 50 percent expressed concern regarding possible opioid addiction. Overall, 76 percent of respondents preferred only OTCs versus OTCs plus opioids for pain control across all scenarios. Given pain levels of 6.5 on a 10-point scale, half of the respondents expressed a preference for OTCs plus opioids when the theoretical risk of addiction was low (0 percent). At higher opioid addiction risk profiles (2, 6, and 12 percent), the preference for OTCs plus opioids and only OTCs was not equal; patients favored only OTCs despite experiencing high levels of pain in these scenarios."These findings may spur research investigating the risk of long-term opioid use after Mohs micrographic surgery and provide a framework for Mohs surgeons to engage in shared decision-making discussions with patients moving forward," the authors write.One author disclosed ties to Regeneron.

Half of patients with pain level of 6.5 of 10 expressed preference for OTCs plus opioids when theoretical risk of addiction was low

Does Addiction Risk Affect Patient Choice of Pain Meds After Mohs Surgery?

WEDNESDAY, June 14, 2023 -- Squamous cell carcinomas (SCCs) in organ transplant recipients (OTRs) have worse prognostic features than SCCs in the general population, according to a study published online June 14 in JAMA Dermatology.Nirmala Pandeya, Ph.D., from the QIMR Berghofer Medical Research Institute in Brisbane, Australia, and colleagues examined the extent to which major high-risk features of SCC in OTRs differ from SCCs in the general population in a dual-cohort study, which included one cohort of OTRs at high risk for skin cancer (Skin Tumours in Allograft Recipients study) and a population-based cohort (QSkin Sun and Health Study). A total of 741 SCCs excised from 191 OTRs and 2,558 SCCs from 1,507 persons in the general population were included.The researchers found that in OTRs, the SCCs developed most frequently on the head/neck (38.6 percent), while in the general population, they developed most frequently on arms/hands (35.2 percent). Perineural invasion was more than twice as common in OTRs as in population cases after adjusting for age and sex (prevalence ratio, 2.37), as was invasion to/beyond subcutaneous fat (prevalence ratio, 2.37). OTRs had more than a threefold increased prevalence of poorly versus well-differentiated SCCs (prevalence ratio, 3.45), while the prevalence of tumors &gt;20 mm versus ≤20 mm was moderately higher in OTRs (prevalence ratio, 1.52)."This finding, along with the greater multiplicity of SCCs in OTRs, warrants intensive surveillance of affected OTRs optimally with multidisciplinary specialist care, at the same time recognizing that all SCCs with high-risk features warrant intensive therapy and follow-up," the authors write.Several authors disclosed ties to industry; one author holds a patent.

Organ transplant recipients have increased prevalence of poorly versus well-differentiated SCCs, and of tumors >20 mm versus ≤20 mm

Do SCCs Have Worse Prognostic Features in Organ Transplant Recipients?

WEDNESDAY, May 24, 2023 (HealthDay News) -- For patients undergoing skin cancer surgery, microdosed incisional clindamycin reduces the rate of surgical site infections (SSIs), according to a study published online May 24 in JAMA Surgery.Maple Goh, M.B.Ch.B., from the University of Auckland in New Zealand, and colleagues conducted a randomized controlled trial to examine whether microdosed incisional antibiotics reduce the rate of SSIs among adult patients undergoing any form of skin cancer surgery. Patients received an incision site injection of buffered local anesthetic alone (control) or buffered local anesthetic with microdosed flucloxacillin (500 μg/mL) or microdosed clindamycin (500 μg/mL). A total of 681 patients returned for postoperative assessments (721 presentations and 1,133 total lesions).The researchers found that the proportion of lesions exhibiting a postoperative wound infection score of 5 or greater was 5.7, 5.3, and 2.1 percent in the control, flucloxacillin, and clindamycin arms, respectively. After adjustment for baseline differences among the arms, the results were similar. Significantly fewer lesions in the clindamycin and flucloxacillin arms required postoperative systemic antibiotics compared with lesions in the control arm (2.1 and 4.0 percent, respectively, versus 8.0 percent)."These results establish evidence-based guidelines for antibiotic prophylaxis in one of the most common surgical interventions performed worldwide, where they have been previously absent," the authors write.

Significantly fewer lesions receiving microdosed clindamycin, flucloxacillin required postoperative systemic antibiotics

Microdosed Incisional Clindamycin Cuts SSI After Skin Cancer Surgery

WEDNESDAY, May 3, 2023 -- Cooperation of dermatologists with a convolutional neural network (CNN) improves diagnostic performance for suspect melanocytic lesions, according to a study published online May 3 in JAMA Dermatology.Julia K. Winkler, M.D., from the University of Heidelberg in Germany, and colleagues conducted a prospective diagnostic study in which dermatologists performed skin cancer screenings using naked-eye examination and dermoscopy. Suspect melanocytic lesions were graded by the probability of malignancy. Dermoscopic images of suspect lesions were then examined using a market-approved CNN. Reference diagnoses were based on histopathologic examination in 54.8 percent of lesions or on clinical follow-up and expert consensus in the case of nonexcised lesions.Twenty-two dermatologists detected 228 suspect melanocytic lesions in 188 patients. The researchers found that when dermatologists additionally integrated CNN results into decision-making, diagnostic sensitivity and specificity improved significantly (mean sensitivity improved from 84.2 to 100.0 percent; mean specificity from 72.1 to 83.7 percent; mean accuracy from 74.1 to 86.4 percent; mean receiver operator characteristic area under the curve from 0.895 to 0.968). For classifying melanocytic lesions, CNN alone achieved comparable sensitivity, higher specificity, and higher diagnostic accuracy than dermatologists alone. Furthermore, unnecessary excisions of benign nevi were reduced by 19.2 percent with dermatologist cooperation with CNN. The most diagnostic improvement was seen for dermatologists with less dermoscopy experience cooperating with the CNN compared with more experienced dermatologists."These results indicate that a broader application of this human with machine approach, particularly in nonspecialized institutions, could be beneficial to clinicians and patients," the authors write.Two authors disclosed financial ties to the pharmaceutical and medical device industries. &nbsp;

The most diagnostic improvement was seen for dermatologists with less dermoscopy experience cooperating with the CNN

Convolution Neural Network Aids Diagnosis for Melanocytic Lesions by Dermatologists

Local recurrence rates are low for patients with invasive head and neck melanoma treated with Mohs micrographic surgery (MMS), according to a study published online Jan. 12 in the
 
 Journal of the American Academy of Dermatology
 
 .




 Brandon T. Beal, M.D., from Jacksonville Skin Cancer Specialists in Florida, and colleagues examined local recurrence, nodal recurrence, and distant recurrence rates and disease-specific survival for invasive melanoma of the head and neck treated with MMS in a retrospective multicenter study involving 785 cases.




 The researchers found that the local recurrence, nodal recurrence, and distant recurrence rates were 0.51, 1.0, and 1.1 percent, respectively, in the overall cohort. Local recurrence was 0.16, 1.18, 2.22, and 5.26 percent for T1, T2, T3, and T4 tumors, respectively. Disease-specific survival was 96.8 and 93.4 percent at five and 10 years, respectively.




 "These data support modification to the National Comprehensive Cancer Network guidelines for the treatment of invasive melanoma of the head and neck," the authors write. "The clear advantage of MMS revolves around complete peripheral and deep margin assessment. Applying this paradigm to the treatment of melanoma, and surgical oncology in general, will improve oncological cure rates and outcomes for our patients."




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Disease-specific survival was 96.8 and 93.4 percent at five and 10 years, respectively

Local Recurrence Rate Low With Mohs for Invasive Head, Neck Melanoma

In an expert consensus panel report published in the January issue of
 
 SKIN,
 
 clinical management recommendations are presented for the use of gene expression profile (GEP) testing in the assessment of cutaneous melanoma (CM).




 Danny Zakria, M.D., from the Icahn School of Medicine at Mount Sinai in New York City, and colleagues created updated guidelines and consensus statements for optimal use of commercially available GEP tests, used in prognostic assessment of CM. Twenty-two articles were included that validated the 31-GEP test, two that validated the 11-GEP test, and seven that validated the 8-GEP clinicopathologic test.




 The researchers generated six usage guidelines and five consensus statements, which were unanimously approved. Usage guidelines with a Strength of Recommendation Taxonomy (SORT) level of A included integration of GEP results for patients with T1a tumors at least 0.3 mm in depth, T1b tumors, or any tumor in which there is significant uncertainty about adequacy of microstaging to improve prognostic assessment. For traditionally assessed low-risk patients, a high-risk subset for recurrence, distant metastasis, or death can be identified by GEP testing. GEP testing provides useful information to augment risk-aligned management decisions to rule in or rule out the need for sentinel lymph node biopsy and subsequent management plans. Guidelines with a SORT level of B include adding GEP results to clinicopathologic information to improve CM prognosis assessment and adding GEP results to the American Joint Committee on Cancer classification to improve prognostic assessment of cutaneous melanoma.




 "The expert consensus guidelines and support statements presented here will hopefully provide a framework for the clinician to integrate GEP testing into their CM patient management," the authors write.




 Several authors disclosed financial ties to biopharmaceutical companies, including Castle Biosciences, which partially funded the study.




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GEP results can improve prognostic assessment for patients with tumors with uncertainty about adequacy of microstaging

Guidelines Issued for Gene Expression Profiling in Cutaneous Melanoma

For patients with a history of facial keratinocyte carcinoma (KC), nonablative fractional laser (NAFL) treatment is associated with a reduced risk for subsequent development of facial KC, according to a study published online Dec. 6 in
 
 Dermatologic Surgery
 
 .




 Travis A. Benson, M.D., from Harvard Medical School in Boston, and colleagues conducted a retrospective cohort study involving patients with a history of facial KC treated between 2005 and 2021 to examine whether NAFL treatment is associated with a decrease in subsequent facial KC development. The study included 43 NAFL-treated patients with a history of facial KC and 52 matched controls.




 The researchers found that the rate of subsequent facial KC development was 20.9 and 40.4 percent in NAFL-treated patients and controls. Compared with NAFL-treated patients, controls developed new facial KC significantly earlier. Controls were more likely to develop new facial KC than NAFL-treated patients when controlling for age, gender, and skin type (hazard ratio, 2.65).




 "These findings suggest that NAFL treatment may have an important role in protecting against subsequent keratinocyte carcinomas," a coauthor said in a statement. "While the mechanism of NAFL's protective effect is not completely understood, it is suspected that NAFL treatment reduces the overall burden of photo damaged keratinocytes and may promote a wound healing response, which gives healthy skin cells a selective advantage."




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Nonablative fractional laser-treated patients had lower rate of subsequent facial keratinocyte carcinoma development

Risk for Subsequent Facial Keratinocyte Carcinoma Lower With Laser Treatment

The Melanocytic Pathology Assessment Tool and Hierarchy for Diagnosis (MPATH-Dx) has been revised to simplify diagnoses into four classes, according to a consensus statement published online Jan. 11 in
 
 JAMA Network Open
 
 .




 Raymond L. Barnhill, M.D., from the Institut Curie in Paris, and colleagues revised the MPATH-Dx version 1.0 classification tool using feedback from dermatopathologists and members of the International Melanoma Pathology Study Group. All feedback was integrated into an updated and refined MPATH-Dx version 2.0.




 The researchers note that in order to improve diagnostic concordance and provide more explicit guidance for treatment, the new MPATH-Dx version 2.0 schema simplifies the original five-class hierarchy into four classes. Histopathological criteria for classification of classes I and II lesions are clearly defined in the new version; specific provisions are made for the most frequently encountered low-cumulative sun damage pathway of melanoma progression and other less common pathways to melanoma; guidance is provided for classifying intermediate class II tumors versus melanoma; and a subset of pT1a melanomas with very low risk is recognized.




 "We expect that the implementation of the new revised MPATH-Dx V2.0 schema into routine practice will provide a robust tool and adjunct for standardized diagnostic reporting of melanocytic lesions and management of patients to the benefit of both health care practitioners and patients," the authors write.




 Several authors disclosed financial ties to the biotechnology and pharmaceutical industries.




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Updated version simplifies original five-class hierarchy into four classes, including clearly defining classes I and II lesions

MPATH-Dx Version 2.0 Simplifies Classification of Melanoma

Adolescents and young adults (AYA) with melanoma have worse survival than older adults, according to a study published online Jan. 4 in the
 
 Journal of the American Academy of Dermatology
 
 .




 Katherine Y. Wojcik, Ph.D., from the Fred Hutchinson Cancer Research Center in Seattle, and colleagues examined factors associated with differences in melanoma survival among AYA (ages 15 to 39 years) and older adults (ages 40 to 64 years) in a population-based registry study involving 81,597 cases of melanoma diagnosed from 2004 to 2015.




 The researchers found that AYA with stage IV melanoma had worse survival than that seen for older adults in the adjusted age group-specific models (hazard ratios for all-cause death, 20.39 versus 10.79). For AYAs, thicker tumors and public insurance were also associated with worse survival than that observed in models for older adults. When detected at earlier stages, AYAs experienced better survival.




 "Although more aggressive tumors were present in AYA patients, there was no overall delay in time to treatment, suggesting potentially delayed diagnosis," the authors write. "A public health campaign to improve awareness of AYA melanoma, including in young persons of color, may disrupt potential delays in diagnosis and reduce the excess burden of mortality in young people."




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Adolescents and young adults with stage IV melanoma have worse survival than that seen for older adults in adjusted age group-specific models

Is Melanoma Survival Worse for Adolescents, Young Adults Versus Older Adults

Survival rates for children and adolescents with melanomas are high, according to a study published online Dec. 9 in the
 
 Journal of the American Academy of Dermatology
 
 .




 Mary-Ann El Sharouni, Ph.D., from the University of Sydney, and colleagues assessed clinicopathologic features and survival of 62 children (aged 11 years and younger) and 452 adolescents (aged 12 to 19 years) diagnosed with melanoma.




 The researchers found that melanoma subtypes were conventional melanoma (superficial spreading, nodular, desmoplastic, and acral lentiginous; 428 patients), spitzoid melanoma (78 patients), and melanoma associated with a congenital nevus (eight patients). Ten-year recurrence-free survival (RFS) was similar in children (91.5 percent) and in adolescents (86.4 percent), as was 10-year overall survival (OS; 100 and 92.7 percent, respectively). In adolescents, ulceration status and anatomic site were associated with RFS and OS, while age, sex, mitotic index, sentinel node status, and melanoma subtype were not. Worse RFS was seen with Breslow thickness &gt;4 mm.




 "Our data suggest that adolescent melanomas are often similar to adult-type melanomas, whilst those which occur in young children frequently occur via different molecular mechanisms," the authors write. "In the future it is likely that further understanding of these molecular mechanisms and ability to classify melanomas based on their molecular characteristics will assist in further refining prognostic estimates and [possibly] guiding treatment for young patients with melanoma."




 Two authors disclosed financial ties to the pharmaceutical industry.




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Primary tumor ulceration, head/neck location, and Breslow thickness &gt;4 mm predict worse survival in teens

Survival Rates High for Children, Teens With Melanoma

Several risk factors have been identified that are associated with poor outcomes in primary cutaneous squamous cell carcinoma, according to a systematic review and meta-analysis published online Dec. 28 in
 
 JAMA Dermatology
 
 .




 George A. Zakhem, M.D., M.B.A., from NYU Langone Health in New York City, and colleagues examined all evidence-based reports of patient risk factors and tumor characteristics associated with poor outcomes in primary cutaneous squamous cell carcinoma. The meta-analysis included data from 129 studies with 137,449 patients with primary cutaneous squamous cell carcinoma and 126,553 tumors.




 The researchers identified several patient risk factors and tumor characteristics that were associated with local recurrence, nodal metastasis, distant metastasis, disease-specific death, and all-cause death. Among the factors reported by more than one study, the risks for local recurrence and disease-specific death were highest in association with tumor invasion beyond subcutaneous fat (risk ratios, 9.1 and 10.4, respectively), while the risk for any metastasis was highest in association with perineural invasion (risk ratio, 5.0). The lowest incidence of nearly all poor outcomes was seen for patients who received Mohs micrographic surgery.




 "These tumor characteristics should be considered in future staging systems, workup protocols, and treatment algorithms," the authors write.




 Several authors disclosed financial ties to the pharmaceutical and other life science industries.




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Risks for local recurrence, disease-specific death highest in association with tumor invasion beyond subcutaneous fat

Can Certain Factors Predict Poor Outcomes in Cutaneous Squamous Cell Carcinoma?

Two pharmaceutical companies said Tuesday that they have made notable progress with a vaccine that could prevent melanoma.




 Moderna, well known for its work on the COVID-19 vaccine, and Merck, which makes the cancer immunotherapy drug Keytruda (pembrolizumab), announced that the combination performed well in a small study of patients who had the cancer surgically removed.




 "Today's results are highly encouraging for the field of cancer treatment. mRNA has been transformative for COVID-19, and now, for the first time ever, we have demonstrated the potential for mRNA to have an impact on outcomes in a randomized clinical trial in melanoma," Moderna CEO Stéphane Bancel said in a company news release. "We will begin additional studies in melanoma and other forms of cancer with the goal of bringing truly individualized cancer treatments to patients."




 Study participants experienced a statistically significant improvement in survival with a combination of the vaccine and Keytruda before the cancer returned in patients who had advanced melanoma.




 "These positive findings represent an important milestone in our collaboration with Moderna," said Dean Li, M.D., president of Merck Research Laboratories. "Over the last six years, our teams have worked closely together combining our respective expertise in mRNA and immuno-oncology with a focus on improving outcomes for patients with cancer."




 Researchers compared the combination of the vaccine and Keytruda to Keytruda alone in a midstage clinical trial that included 157 patients. Those who had the combination had a 44 percent reduction in the risk for death or the cancer returning when compared with Keytruda alone. Researchers administered the treatments for about a year in both groups, with exceptions made for severe side effects or disease return.




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Companies announced that the vaccine performed well in a small study of patients who had the cancer surgically removed

Moderna, Merck Report on Promising Melanoma Vaccine

The introduction of new melanoma treatments coincided with a reduction in the melanoma mortality rate (MMR) in the United States, according to a study published online Dec. 6 in
 
 JAMA Network Open
 
 .




 Navkirat Kahlon, M.D., M.P.H., from the University of Toledo College of Medicine and Life Sciences in Ohio, and colleagues reviewed changes in the long-term MMR trends in adult patients in the United States using data from the Surveillance, Epidemiology, and End Results database. Outcomes were examined in association with U.S. Food and Drug Administration approval of new drugs for melanoma.




 The researchers found that for the first time in the past 40 years, there was a significant reduction in MMR from 2013 to 2017, after the introduction of new treatments in 2011 (most after 2013). From 1975 to 1988, the rates increased (annual percent change, 1.65 percent; 95 percent confidence interval, 1.30 to 2.00 percent; P &lt; 0.001). From 1988 to 2013, there was no significant change in MMR (annual percent change, 0.01 percent; 95 percent confidence interval, −1.10 to 0.12 percent; P = 0.85). From 2013 to 2017, there was a significant decrease in MMR (annual percent change, −6.28 percent; 95 percent confidence interval, −8.52 to −3.97 percent; P &lt; 0.001).




 "The effectiveness of new and innovative therapeutics for melanoma is likely represented by the remarkable and statistically significant drop in population-level melanoma mortality in the last decade," the authors write. "These are very encouraging data and support the continued development of such therapies."




 One author disclosed financial ties to the pharmaceutical industry.




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Significant reduction seen in mortality rate from 2013 to 2017, after the introduction of new treatments in 2011 (most after 2013)

2013 to 2017 Saw Significant Drop in U.S. Melanoma Mortality Rates

A high number of moles and a high genetic predisposition are more strongly associated with second than first primary melanomas, according to a study published online Nov. 23 in
 
 JAMA Dermatology
 
 .




 Catherine M. Olsen, Ph.D., from the QIMR Berghofer Medical Research Institute in Herston, Australia, and colleagues compared the clinical characteristics of first and second melanomas in a prospective cohort study involving men and women aged 40 to 69 years recruited in 2011 and followed until December 2018. Data were included for 38,845 patients.




 The researchers found that 3.1 and 0.6 percent of participants had a single primary melanoma diagnosis and a second primary melanoma diagnosis, respectively, during a median follow-up of 7.4 years. Compared with first melanomas, second melanomas were more likely to be in situ; for invasive tumors, second versus first melanomas were more likely to be thin (≤1 mm). Having many moles at age 21 years was more strongly associated with second than first primary melanomas (hazard ratio, 6.36 versus 3.46). Furthermore, a high genetic predisposition was more strongly associated with second versus first melanoma (hazard ratio, 3.28 versus 2.06). A history of multiple skin cancer excisions was also more strongly associated with second versus first melanomas (hazard ratio, 2.63 versus 1.86). Similarly elevated associations with first and second melanomas were seen for all other phenotypic characteristics and sun exposure measures.




 "Findings suggest that people who develop second primary melanomas have more nevi and greater genetic risk than people who develop only one melanoma," the authors write.




 Two authors disclosed financial ties to pharmaceutical companies.




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Association stronger with second versus first primary melanoma for having many moles at age 21 years, high genetic predisposition

Nevi, Genetic Predisposition More Strongly Linked to Second Melanoma

Melanoma diagnosis is associated with increased risk of subsequent prostate cancer, according to a study published online Nov. 1 in the
 
 British Journal of Cancer
 
 .




 Sam Egger, from the University of Sydney, and colleagues recruited men from 2006 to 2009 to examine the association between cutaneous melanoma and subsequent risk of prostate cancer. Data were included from 96,548 eligible men, of whom 1,899 were diagnosed with melanoma during the melanoma diagnosis period. During follow-up, 3,677 incident prostate cancers were diagnosed.




 The researchers found that the risk of a subsequent prostate cancer diagnosis was increased for men with a melanoma diagnosis versus those with no melanoma (fully adjusted hazard ratio, 1.32; 95 percent confidence interval, 1.09 to 1.60). Weak evidence was seen for higher risks of a subsequent prostate cancer diagnosis for men diagnosed with more than one versus one melanoma. The association was also seen if first melanoma diagnosis was 10 to 15 years before study recruitment (fully adjusted hazard ratio, 2.05; 95 percent confidence interval, 1.35 to 3.12).




 "Our study is the first to show that the positive association between melanoma and the subsequent risk of prostate cancer diagnosis is unlikely to be due to confounding from increased medical surveillance after a melanoma diagnosis," the authors write. "The positive association remained significant even after the over-adjustment for rate of prostate-specific antigen monitoring tests
 
 ."
 




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More than twofold increased risk of prostate cancer seen for men with first melanoma diagnosed 10 to 15 years before study recruitment

Melanoma Diagnosis Linked to Increased Risk of Prostate Cancer

For patients with high-risk resected melanoma, adjuvant pembrolizumab improves quality of life (QOL) compared with standard of care with ipilimumab or high-dose interferon α 2b (HDI), according to a study published online Nov. 23 in JAMA Oncology.

 Joseph M. Unger, Ph.D., from the Fred Hutchinson Cancer Center in Seattle, and colleagues compared QOL in patients with resected melanoma at high risk for relapse who were treated with adjuvant pembrolizumab or standard of care. A total of 832 patients from the S1404 phase 3 randomized clinical trial were included and were evaluable for the primary QOL end point at cycle 3.

 The researchers found that the adjusted Functional Assessment of Cancer Therapy (FACT) Biological Response Modifiers (FACT-BRM) trial outcome index (TOI) score at cycle 3 was 9.6 points higher for pembrolizumab versus ipilimumab/HDI, which exceeded the prespecified clinically meaningful difference. Differences by arm exceeded 5 points in favor of pembrolizumab in linear-mixed models through cycle 7. FACT-BRM TOI scores favored the pembrolizumab arm compared with the subset of patients receiving ipilimumab or HDI (differences, 6.0 and 17.0 points, respectively) in post-hoc analyses.

 "Physicians should be encouraged to incorporate and discuss treatment-related QOL issues with patients when making shared decisions regarding the risks and benefits of adjuvant therapy in resected melanoma," the authors write.

 Several authors disclosed financial ties to pharmaceutical companies, including Merck, which manufactures pembrolizumab and partially funded the study.




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Quality of life favored the pembrolizumab arm versus standard-of-care arm receiving ipilimumab, high-dose interferon α 2b

QOL Up With Pembrolizumab Versus Ipilimumab, HDI in Resected Melanoma

The Skin and UV Neoplasia Transplant Risk Assessment Calculator (SUNTRAC) is valid for assessing the risk for skin cancer among solid organ transplant recipients (SOTRs), according to a study published online Nov. 23 in JAMA Dermatology.

 Álvaro Gómez-Tomás, M.D., from Hospital Universitari Vall d'Hebron in Barcelona, Spain, and colleagues conducted a retrospective external validation study using data from European SOTRs from transplant centers in the Netherlands and Spain to validate the SUNTRAC tool. The discriminative ability of the SUNTRAC tool was examined and calibration was assessed by comparing projected skin cancer incidences.

 "Having a tool that can quickly and correctly stratify SOTRs according to their relative skin cancer risk is a great aid for the clinician and a fundamental step in defining guidelines to ensure adequate screening and dermatological follow-up of these patients," the authors write.

 Two authors disclosed financial ties to the pharmaceutical industry.

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SUNTRAC risk assessment calculator predicted incidence of skin cancer with predicted and observed incidence of 6.2 and 7.0 percent, respectively

Can Risk for Skin Cancer Be Predicted in Solid Organ Transplant Recipients?

For patients with previously untreated metastatic or unresectable melanoma, the combination of relatlimab nivolumab continues to demonstrate a progression-free survival (PFS) benefit over nivolumab alone, according to updated study results presented March 14 as part of the American Society for Clinical Oncology Plenary Series.




 Georgina V. Long, M.D., Ph.D., from the Melanoma Institute Australia at the University of Sydney, and colleagues randomly assigned patients with previously untreated metastatic or unresectable melanoma to receive either relatlimab nivolumab or nivolumab alone, given intravenously every four weeks (355 and 359 patients, respectively). Patients were followed for a median of 19.3 months.




 The researchers found that the updated median PFS was 10.2 and 4.6 months with relatlimab nivolumab and nivolumab alone, respectively (hazard ratio, 0.78; 95 percent confidence interval, 0.6 to 0.9). Median overall survival was not reached with relatlimab nivolumab and was 34.1 months with nivolumab alone (hazard ratio, 0.80; 95 percent confidence interval, 0.6 to 1.0; P = 0.0593). The overall survival rates were 77.0 and 71.6 percent at 12 months and 63.7 and 58.3 percent at 24 months, for relatlimab nivolumab and nivolumab alone, respectively. The confirmed overall response rates were 43.1 and 32.6 percent, respectively. More grade 3/4 treatment-related adverse events occurred in patients receiving relatlimab nivolumab versus nivolumab alone (21.1 versus 11.1 percent).




 "These findings provide additional evidence of the benefit of two checkpoint inhibitors over only one and supports the combination of nivolumab and relatlimab, which had a manageable safety profile, as a potential new treatment option for patients with advanced melanoma," Long said in a statement.




 Several authors disclosed financial ties to biopharmaceutical companies, including Bristol Myers Squibb, which manufactures relatlimab and funded the study.




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Progression-free survival prolonged with relatlimab nivolumab versus nivolumab alone for previously untreated advanced melanoma

Update Shows Relatlimab   Nivolumab Slows Advanced Melanoma

For older adults, vitamin D supplementation does not reduce the incidence of keratinocyte cancer (KC) or other actinic lesions, according to a study published in the November issue of the
 
 British Journal of Dermatology
 
 .




 Sitwat Ali, from QIMR Berghofer Medical Research Institute in Brisbane, Australia, and colleagues examined the effect of vitamin D supplementation on the risk for developing KC using data from the D-Health Trial, involving Australians aged 60 years and older. Participants were randomly assigned to receive either vitamin D supplementation or placebo. KC outcomes were captured through linkage to a national dataset for 20,334 participants (95 percent).




 The researchers found no reduction in the incidence of KC lesions treated by excision, the incidence of actinic lesions treated using other methods, or the time to first histologically confirmed KC excision with randomization to vitamin D supplementation. However, in a subgroup analysis, vitamin D was found to increase the incidence of KC excisions in adults aged 70 years and older.




 "Routine supplementation with vitamin D, including in those at highest risk of KC, is unlikely to reduce the very high incidence seen in the Australian population," the authors write.




 Several authors disclosed financial ties to the pharmaceutical industry.




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Researchers find no evidence that vitamin D supplementation reduces incidence of keratinocyte cancer

Can Vitamin D Supplementation Cut Incidence of Keratinocyte Cancer?

A subset of melanoma patients with stage I lesions and negative clinical nodes with very low risk for mortality from melanoma has been identified, according to a study published online Nov. 7 in
 
 Cancer
 
 .




 Megan M. Eguchi, M.P.H., from the David Geffen School of Medicine at the University of California in Los Angeles, and colleagues selected melanoma patients diagnosed in 2010 and 2011 with stage I lesions ≤1.0 mm thick and negative clinical lymph nodes from the Surveillance, Epidemiology, and End Results database. Models were developed and validated for identifying patients with a very low risk for death from melanoma within seven years.




 The researchers found that a subset comprising 25 percent of the patients had a risk of &lt;1 percent for seven-year mortality from melanoma compared with an overall seven-year mortality from melanoma of 2.5 percent. In all models, younger age at diagnosis and Clark level II were associated with a low risk for death. Associations were also seen with lower mortality for Breslow thickness less than 0.4 mm, absence of mitogenicity, absence of ulceration, and female sex. A small subset of high-risk patients was also identified, with &gt;20 percent risk for death.




 "This study suggests there is a real subset of patients with very%u2010low risk of melanoma death; we hope this serves as a baseline to further develop the classification criteria to establish use of the melanocytic neoplasms of low malignant potential term in clinical practice," the authors write.




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Younger age at diagnosis, Clark level II linked to low risk for death among patients with stage I lesions, negative clinical nodes

Subset of Stage I Melanoma Patients ID'd With Very Low Mortality

For patients with resectable clinical stage III or oligometastatic stage IV melanoma, neoadjuvant relatlimab and nivolumab combination immunotherapy results in a 57 percent pathologic complete response rate, according to a study published online Oct. 26 in
 
 Nature
 
 .




 Rodabe N. Amaria, M.D., from The University of Texas MD Anderson Cancer Center in Houston, and colleagues examined the efficacy of relatlimab and nivolumab combination immunotherapy in patients with resectable clinical stage III or oligometastatic stage IV melanoma. Pathologic complete response was measured as the primary end point.




 The researchers found that among 30 patients treated, the combination resulted in 57 percent pathologic complete response rate and 70 percent overall pathologic response rate. Using Response Evaluation Criteria in Solid Tumors 1.1, the radiographic response rate was 57 percent. In the neoadjuvant setting, there were no grade 3 to 4 immune-related adverse events reported. The one- and two-year recurrence-free survival rate was 100 and 92 percent and 88 and 55 percent for patients with any and without a pathologic response, respectively. There were associations observed for increased immune cell infiltration at baseline and a reduction in M2 macrophages during treatment with pathologic response.




 "We're very pleased to see that the combination of relatlimab and nivolumab balanced safety and efficacy, and it did not result in any delays to surgery," Amaria said in a statement. "We want to provide patients with a treatment option that will help reduce the risk of their cancer returning after surgery."




 Several authors disclosed financial ties to pharmaceutical companies, including Bristol Myers Squibb, which manufactures nivolumab and relatlimab and funded the study.




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In phase 2 study, relatlimab and nivolumab combination immunotherapy resulted in pathologic complete response rate of 57 percent

Neoadjuvant Combo Immunotherapy Studied in Resectable Melanoma

For patients with advanced melanoma, response-adapted treatment de-escalation is cost-effective and offers an incremental net monetary benefit of $28,849 versus standard of care, according to a study published online Oct. 19 in
 
 JAMA Dermatology
 
 .




 Zachary Cartun, M.D., from University Hospital, LMU Munich in Germany, and colleagues conducted a cost-effectiveness analysis using data from the ADAPT-IT and CheckMate 067 trials as well as published literature to determine the cost-effectiveness of ipilimumab discontinuation for patients with interim imaging-confirmed tumor response in advanced melanoma treatment. A total of 355 patients with previously untreated melanoma were included in the analysis: 41 from the ADAPT-IT trial and 314 from the CheckMate 067 trial.




 The researchers found that in 94.0 percent of scenarios, response-adapted treatment was the cost-effective option based on Monte Carlo simulations, with a dominant incremental cost-effectiveness ratio and an incremental net monetary benefit of $28,849 versus standard of care. The estimated cost savings were $19,891 per patient compared with standard of care. Current standard of care was only considered as a cost-effective option under best survival assumptions in scenario analyses and if the willingness-to-pay threshold exceeded $630,000/quality-adjusted life year.




 "Response-adapted de-escalation of immunotherapy, as proposed by the ADAPT-IT trial, has the potential to alleviate the financial burden for patients with advanced melanoma," the authors write. "We hope that this study can inform future trial design to identify novel and more affordable treatment strategies."




 Several authors disclosed ties to the pharmaceutical industry.




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Response-adapted de-escalation of immunotherapy yielded incremental net monetary benefit of $28,849 versus standard of care

Response-Adapted Treatment De-escalation Cost-Effective in Melanoma

For patients with treatment-naive BRAFv600 mutant metastatic melanoma, treatment first with combination nivolumab/ipilimumab yields better overall survival than dual BRAF/MEK inhibition with dabrafenib/trametinib, according to a study published online Sept. 27 in the
 
 Journal of Clinical Oncology
 
 .




 Michael B. Atkins, M.D., from the Georgetown Lombardi Comprehensive Cancer Center in Washington, D.C., and colleagues examined the optimal treatment sequence between combination nivolumab/ipilimumab checkpoint inhibitor immunotherapy and combination dabrafenib/trametinib molecularly targeted therapy for patients with treatment-naive BRAFv600 mutant metastatic melanoma. A total of 265 patients were randomly assigned to receive combination nivolumab/ipilimumab (arm A) or dabrafenib/trametinib (arm B) in step 1, and 73 received alternative therapy in step 2: dabrafenib/trametinib (arm C) or nivolumab/ipilimumab (arm D; 27 and 46 patients, respectively).




 Due to achievement of a clinically significant end point, the study was stopped early. The researchers found that two-year overall survival was 71.8 and 51.5 percent for those starting in arm A and arm B, respectively. Step 1 progression-free survival favored arm A. The objective response rates were 46.0, 43.0, 47.8, and 29.6 percent for arms A, B, C, and D, respectively. The median duration of response was not reached in arm A and was 12.7 months in arm B. In 52 percent of patients with documented disease progression, crossover occurred.




 "Combination immunotherapy, in contrast to targeted therapy, produces more long-lasting tumor shrinkage, reduces the risk of disease progression in the central nervous system, and doesn't interfere with the subsequent effectiveness of the alternative treatment approach," Atkins said in a statement.




 Bristol Myers Squibb and Novartis provided the study medications.




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Two-year overall survival higher for those initiating treatment with combo nivolumab/ipilimumab versus dual BRAF/MEK inhibition

Treatment Sequence Studied for Advanced BRAF-Mutant Melanoma

High sunburn frequency throughout life and a high-to-low trajectory are associated with an increased risk for cutaneous melanoma and squamous cell carcinoma (cSCC), according to a study published online Oct. 5 in
 
 JAMA Dermatology
 
 .




 Simon Lergenmuller, M.D., from the Cancer Registry of Norway in Oslo, and colleagues examined the lifetime trajectories of sunburns and compared the association between these trajectories and the subsequent risk for cutaneous melanoma and cSCC in a population-based cohort, established in 1991 with follow-up through 2018. Baseline questionnaires were administered in 1991 to 2007; follow-up questionnaires were completed every five to seven years.




 Of the 172,472 women who returned questionnaires, 169,768 completed questions about sunburns at study inclusion. The researchers identified five classes of individual lifetime sunburn trajectories (stable low, low-moderate-low, low-to-high, high-to-low, and stable high) in three samples up to 39 years, 49 years, and 59 years (159,773, 153,297, and 119,170 women, respectively). In the three samples, mean follow-up ranged from 14.3 to 19.5 years, during which 1,252 to 1,774 and 739 to 871 women were diagnosed with incident primary melanoma and cSCC, respectively. Compared with the stable low trajectory, the stable high and high-to-low trajectories showed statistically significant increased melanoma and cSCC risks across all samples (melanoma: hazard ratios, 1.50 and 1.44; cSCC: hazard ratios, 1.51 and 1.47, respectively, for up to 39 years).




 "Importantly, the present results suggest that childhood is a more susceptible phase with regard to sunburns and subsequent risk of these skin cancers. It is therefore crucial to emphasize the importance of avoiding sunburns throughout life, and in particular in childhood," the authors write.




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Stable high and high-to-low trajectories had increased risks compared with stable low trajectory

High Sunburn Frequency Through Life Linked to Melanoma, cSCC Risk

For patients with clinical stage IIB/C cutaneous melanoma, sentinel lymph node (SLN) biopsy provides essential prognostic information, according to a study published in the October issue of the
 
 Journal of the American Academy of Dermatology
 
 .




 Richard J. Straker III, M.D., from the University of Pennsylvania in Philadelphia, and colleagues examined the prognostic significance of SLN staging on disease-specific survival for clinical stage IIB/C primary cutaneous melanoma in the preimmunotherapy era. The analysis included patients who underwent excision of clinical stage IIB/C cutaneous melanoma, identified through the Surveillance, Epidemiology, and End Results database (2004 to 2011). Propensity-matched patients who did and did not undergo SLN biopsy wre compared; matched patients were then further stratified by SLN positive (SLN ) or negative (SLN–) status.




 The researchers report that 70.3 percent of patients (6,021 of 8,562) underwent SLN biopsy. There was a significant association observed between SLN positivity and reduced five-year disease-specific survival among matched patients who underwent SLN biopsy (47.1 percent SLN versus 75.5 percent SLN–). Even across matched T-stages, five-year disease-specific survival remained significantly different: T3b (54.2 percent SLN versus 64.8 percent SLN–), T4a (55.5 percent SLN versus 71.6 percent SLN–), and T4b (38.6 percent SLN versus 60.9 percent SLN–).




 "For patients with clinical stage IIB/C cutaneous melanoma, SLN status provides essential prognostic information and is an important factor for collective decision-making regarding adjuvant therapy administration based on risk assessment," the authors write.




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SLN positivity significantly associated with lower five-year disease-specific survival among patients with clinical stage IIB/C cutaneous melanoma

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