bluuebunny/crossref_metadata_2025 huggingface dataset:
Trends, sociodemographic and hospital-level factors associated with inpatient palliative care utilization among malignant melanoma patients: A 5-year National Inpatient Sample (NIS) study.
Authors: Olafimihan Ayobami Gbenga , Jackson Inimfon , Vakil Jay , Kanemo Philip Onyekaoso , Litvin Rafaella , Obeidat Khaldun , Turk Ekrem , Ibrahim Muhammad Bilal , Gajjar Rohan , Batra Kunnal
Published: June 2023

e21526

Background: Palliative care improves the quality of life in cancer patients; however, there is no literature on specific factors that predict its use in patients with malignant melanoma. We explored the prevalence trends, and predictors of palliative care utilization among hospitalized patients with malignant melanoma. Methods: Retrospective analyses were conducted using the National Inpatient Sample (NIS) data collected between 2016 and 2020. Descriptive analyses and multivariable regression models were used to investigate the prevalence trends, and sociodemographic and hospital-level factors associated with palliative care utilization in hospitalized malignant melanoma patients. Results: Of the 9,760 hospitalizations with a diagnosis of malignant melanoma over the study duration, 14% utilized palliative care during their hospital stay. Overall, 9.2% of malignant melanoma patients used palliative care and were discharged alive. There was a stable trend of palliative care use over the 5-year period (14%). Compared to patients on Medicare, those on Medicaid were twice (adjusted odds ratio (AOR): 2.12; 95% confidence interval (CI): 1.263.64) more likely to utilize palliative care. Relative to other regions in the US, patients hospitalized in the West were 40% less likely to receive the service of the palliative team (AOR: 0.61; 95% CI: 0.38-0.96). Those admitted to teaching hospitals (AOR: 0.55; 95% CI: 0.40-0.77) had lower odds of having palliative care consultations when compared to non-teaching hospitals. Patients admitted to urban hospitals had 50% (AOR: 0.51; 95% CI: 0.270.98) lesser odds of getting palliative care when compared to their counterparts in rural hospitals. Individuals who were either discharged to a facility/with home health (AOR: 8.81; 95% CI: 5.8813.23) or died during hospitalization (AOR: 128.42; 95% CI: 72.10228.77) had higher odds of utilizing palliative care when compared to those with a routine discharge. Conclusions: The prevalence of palliative care utilization was low, and factors associated with utilization in our population were identified. Our findings emphasize the necessity to improve awareness among medical oncologists and primary inpatient teams on the importance of involving the palliative care service early in the management of hospitalized patients with malignant melanoma.
Immune checkpoint inhibitors in cutaneous squamous cell carcinoma: A systematic review of clinical trials.
Authors: Anwar Muhammad Yasir , Aiman Wajeeha , Ali Muhammad Ashar , Dhanesar Gurneel , Zafar Maha , Omar Zainab , Afzal Fatima , Guron Gunwant K. , Shaaban Hamid Salim , Maroules Michael
Published: June 2023

e21529

Background: Cutaneous squamous cell carcinoma (cSCC) with high-risk features is primarily treated with radiations or surgically. However, locally advanced (LA) or metastatic cSCC (mcSCC) may not be managed surgically and require systemic therapy. In this systematic review, we will assess the efficacy of immune checkpoint inhibitors (ICIs) in patients with resectable, LA, or mcSCC. Methods: A literature search was performed on PubMed, Embase, and clinicaltrials.gov with keywords, “cutaneous squamous cell carcinoma” and “immune checkpoint inhibitor” from the inception of data till 12/31/22. After screening of 883 articles, 8 clinical trials (N = 513) were included. Results: In 8 clinical trials (N = 513), 205 patients had LA cSCC, 99 patients had resectable cSCC, and 209 patients had mcSCC. 81 patients were newly diagnosed while 432 patients were relapsed/refractory (RR). Cemiplimab was used to treat 262 patients, pembrolizumab for 227 patients, and nivolumab for 24 patients. In 2 clinical trials (N = 142) on RR LA cSCC, complete response (CR), partial response (PR), overall response (OR), and progressive disease (PD) were 13-17%, 31-33%, 44-50%, and 12-17%, respectively, in patients treated with ICIs. In 3 clinical trials (N = 175) on RR mcSCC, CR, PR, OR, and PD were 7-18%, 25-41%, 36-64%, and 16-26%, respectively. In two clinical trials (N = 81) on ND cSCC patients, CR, PR, OR, and PD were 0-7%, 35-58%, 42-58%, and 32-20%, respectively. In 2 clinical trials (N = 99) on resectable cSCC, pathological CR, pathological major response, and PD were 51-75%, 13-20%, and 10%, respectively, in patients treated with ICIs. Table. Conclusions: ICIs including cemiplimab, pembrolizumab, and nivolumab were effective in the treatment of resectable, LA, and mcSCC. ICIs were effective in the treatment of both R/R and treatment naïve mcSCC. However, no results were available for randomized clinical trials and large-scale randomized studies are needed to confirm these results. [Table: see text]
Real-world efficacy and safety data of anti-PD-1 plus anti-CTLA-4 combination therapy in Chinese patients with advanced melanoma.
Authors: Wen Xizhi , Zhang Xiaoshi , Ding Ya , Li Dandan , Li Jingjing
Published: June 2023

e21530

Background: Combination of anti-PD-1 plus anti-CTLA-4 has shown superior efficacy over monotherapy in advanced melanoma among Caucasian populations. However, it has not been evaluated in Chinese patients, and data on acral and mucosal melanoma are limited. We aimed to assess the efficacy and safety of anti-PD-1 antibody plus ipilimumab therapy in Chinese patients with advanced melanoma in clinical practice. Methods: Advanced melanoma patients treated with anti-PD-1 antibody combined with ipilimumab in Sun-Yat sen University Cancer Center from May 2015 to October 2022 were retrospectively assessed. Patient baseline characteristics, tumor responses (RECIST), progression-free survival (PFS), and overall survival (OS) were estimated using Kaplan-Meier analysis. Toxicity was assessed to estimate safety. Results: Altogether, 86 patients were included. The primary site was cutaneous, acral, mucosal, uveal and central nervous system (CNS) in 34, 21, 20, six and five patients, respectively. Among them, 21 patients were treatment-naive, 65 patients were previously treated, and 54 patients progressed of front-line ani-PD-1 therapy. 12 patients received ipilimumab 3mg/kg combined with low dose anti-PD-1 (Nivolumab 80mg or Pembrolizumab 1mg/kg) Q3w for four doses, and the other 74 patients received standard dose of anti-PD-1 plus ipilimumab 1mg/kg Q3w therapy. There were 25(29%) patients with liver metastasis and 26(30.2%) patients with CNS metastasis at baseline. The overall response rate (ORR) was 15.1% in the whole cohort, with complete response observed in six (6%) patients, partial response in 7 (8.1%), stable disease in 28 (32.6%). The response rate in the treatment-naive and prior systemic therapy group was 23.8% and 12.3%, respectively. For those treated with anti-PD-1 followed by the anti-PD-1+ ipilimumab as subsequent therapy after disease progression, the ORR was 11.1%. The response rate for cutaneous melanoma was 23.5%, and 37.5% in the naïve group. Response rates for acral, uveal, CNS and mucosal melanoma were 19.0%, 16.7%,0% and 0% respectively. The median progression-free survival (PFS) and overall survival (OS) in all patients was 4.5 (3.6-5.4) months and 22.0 (12.4-31.6) months, respectively. The 3-year OS were 100% in patients who achieved ORR. There were no significant differences in PFS or OS for patients with cutaneous or acral melanoma. mucosal primary tumor type, liver metastasis and elevated LDH were predictive of shorter PFS and OS. CNS metastasis, previous treatment, BRAF/NRAS mutation status and sex were not found to be related to survival. Adverse events occurred in 71% of patients and 13% were grade 3 or worse. Conclusions: The efficacy of anti-PD-1+ ipilimumab combination therapy in Chinese patients tended to be inferior compared to global studies but was well tolerated. OS were good in cases with CR or PR.
Neoadjuvant versus adjuvant therapy in patients with stage III or IV resectable melanoma: A systematic review and meta-analysis.
Authors: Madeira Thiago , Vilbert Maysa , Priantti Jonathan N , Moraes Francisco Cezar A , Koch Hein Erica C. , Ribeiro Mauricio Fernando , Cavalcante Ludimila , Lawson David H.
Published: June 2023

e21542

Background: Neoadjuvant therapy (NAT) has emerged as a promising strategy to treat resectable melanoma patients by generating a robust immune response and longer immunologic memory. We performed a systematic review and meta-analysis evaluating the survival benefit of NAT compared to standard adjuvant therapy (AT) for melanoma patients. Methods: We searched for randomized clinical trials (RCT) comparing NAT versus AT in resectable stages IIIB/C or IV melanoma patients on PubMed, Scopus, and Cochrane Library databases. We assessed event-free survival (EFS), distant metastasis-free survival (DMFS), overall survival (OS), and safety. Studies included were limited to RCTs with an adjuvant control arm and reporting at least one of the outcomes of interest. Heterogeneity was examined with the I2 statistics, and the random effects model was fitted. Results: Four RCTs met inclusion criteria for a total of 504 patients. Most patients had stage IIIB/C (79.1%), and received NAT with immunotherapy (66%), target therapy (4.2%) and talimogene laherparepvec (TVEC) (29.8%). In the pooled analysis of 2-year follow-up: 71.3% of patients in the NAT arm and 53.2% in AT arm were event-free [Risk Ratio (RR): 0.57 95%Cl 0.39-0.83 p=0.003]. Albeit the difference in therapies, NAT decreased by 44% the risk of death compared to AT, with 89.4% and 81.2% of patients alive at two years, respectively (RR 0.56 95%Cl 0.36-0.87 p=0.01). DMFS was reported in three studies (n=191). Patients on NAT had numerically higher DMFS rate (44%) compared to AT (28.6%) (p=0.23). Two studies (n=170) have published 5-year follow-up results: OS rate has remained statistically significant, favoring NAT (RR 0.58 95%Cl 0.34-0.97 p=0.04). Significant differences were not observed in EFS (p=0.06) and DMFS (p=0.08). Adverse events were similar in both groups, and there were no treatment-related deaths. In these studies, there were no significant delays in surgery due to toxicity or unexpected perioperative complications. Combined immunotherapy caused the highest incidence of grade 3/4 toxicity (90%) among the therapies. Conclusions: This systematic review and meta-analysis indicate a significant survival benefit from NAT for stages IIIB/C and resectable stage IV melanoma. NAT induces better anti-tumor activity, leading to improved EFS and OS compared to AT, with similar safety profile. Phase 3 clinical trials with longer follow-up are warranted. [Table: see text]
Assessment of HER2 status in extramammary Paget disease and its implication for disitamab vedotin, a novel humanized anti-HER2 antibody-drug conjugate (ADC) therapy.
Authors: Si Lu , Jia Jia , Mao Lili , Lin Jing , Yuan Pei , Li Wen Yu , Dai Jie , Li Zhong-Wu , Bai Xue , Li Caili , Guo Lei , Chen Yu , Ying Jianming , Guo Jun
Published: June 2023

e21544

Background: Evaluation of HER2 status in extramammary Paget disease (EMPD) has been reported in a few studies with a small number of samples, and the HER2 overexpression rate ranges from 15% to 60%. The prognosis of advanced EMPD is poor and the treatment options is limited. Disitamab Vedotin (DV) is a novel humanized anti-HER2 antibody-drug conjugate (ADC), has been approved for metastatic urothelial carcinoma and gastric cancer in China. To determine the HER2 status and the efficacy of DV in advanced EMPD patients (pts) harboring HER2 expression, we conducted this multicenter retrospective study. Methods: Paraffin-embedded blocks, clinic-pathological data, and survival data of EMPD pts were retrospectively collected from 3 centers in China. HER2 IHC scoring and gene amplification evaluation were carried out according to the (ASCO/CAP) 2018 guidelines. The results of FISH and IHC were analyzed by two pathologists independently in a double-blinded manner. Data analysis was performed using SPSS v.26, Prism 8 and R version 3.6.5. Results: Finally, 129 cases with detailed data were enrolled between 2006 and 2022. Among them, HER2 IHC was performed in 102 cases, and FISH in 46 cases. HER2 expression was detected in 93.1% samples, with scores of 1+, 2+, and 3+ in 47.1% (48/102), 37.3% (38/102), and 8.7% (9/102) respectively. HER2 gene amplification was detected in eight cases (8/46, 17.4%), including all the cases with IHC 3+ (5/5, 100%), two with IHC 2+ (2/18, 11.1%), and one with IHC 1+ (1/22, 4.5%). For the subgroup of HER2 2+/3+, a higher frequency of lymph node metastasis (66.7% vs 33.3%, P = 0.034) and reduced survival time were detected than in HER2 1+/0. Two elderly male pts with advanced EMPD (one HER1+ /FISH-, one HER 2+/FISH-), who failed with chemo of paclitaxel, received 4 doses of DV infusion (2mg/kg every 2 weeks), and achieved partial responses both with tolerable toxicity. Conclusions: According to the study, the expression rate of HER-2 was very high in EMPD, indicating that it may be used as a routine treatment target. DV showed efficacy in these patients and need further validation.
Factors associated with overall survival in patients with melanoma leptomeningeal disease (M-LMD): A single institution retrospective review.
Authors: Nyman Karl , Kundalia Ronak , Ospina Oscar , Wallace Gerald Carter , Pina Yolanda , Smalley Inna , Forsyth Peter A. J.
Published: June 2023

e21548

Background: Leptomeningeal disease (LMD) is characterized by tumor metastasis to the membranes and cerebrospinal fluid (CSF) surrounding the brain and spinal cord. This devastating complication confers a poor overall survival (OS) measured in weeks for untreated patients. Melanoma has one of the highest rates of dissemination to the leptomeninges. The advances in targeted and immune therapies have revolutionized OS for patients with melanoma systemic metastases and there is a growing number of individual case reports showing clinical responses to these agents in patients with melanoma-LMD (M-LMD) . However, few studies have examined the association between these and other therapies with the OS of a large cohort of melanoma-LMD (M-LMD) patients. Methods: M-LMD patients treated at Moffitt Cancer Center between 2011 and 2020 were retrospectively identified. M-LMD diagnosis was confirmed radiographically via magnetic resonance imaging (MRI) and/or positive CSF cytology indicating the presence of malignant cells. Demographic data and pre/post LMD diagnosis treatment data were collected and analyzed using the Kaplan-Meier method to determine factors that improve OS. Results: 86 M-LMD patients were identified. 50 were male and 36 were female, but patient gender did not have an impact on OS. 53 patients were diagnosed via MRI only and 33 patients had positive CSF cytology confirming M-LMD diagnosis. 34 patients did not receive any treatment post-LMD diagnosis and had a median OS of 3.72 weeks, while 52 patients receiving treatment (i.e. systemic, intrathecal [IT], and/or whole brain radiation therapy [WBRT]) had a median OS of 10.80 weeks (p < 0.0001). More specifically, 30 patients receiving targeted BRAF/MEKi treatment had an 18.8 week median OS compared to 6.68 weeks for the 56 patients who did not receive such treatments (p = 0.0015). Furthermore, 44 patients received immune therapy and had a median OS of 12.00 weeks compared to 5.88 weeks for those who did not (p = 0.002). The 16 Patients that received IT chemotherapy had a prolonged median OS when compared to the 70 patients who did not (9.72 weeks vs 4.72 weeks, p = 0.009). Furthermore, WBRT also improved median OS in the 22 patients that received the therapy (15.72 weeks vs 7.88 weeks, p = 0.0007). The 36 patients that received BRAF/MEKi treatment prior to their LMD diagnosis had a slightly shorter OS (7.00 weeks) compared to the 46 patients that did not receive such treatment beforehand (10.80 weeks, p = 0.005). Conclusions: The current data supports the use of systemic, IT, and radiation therapies to prolong OS for M-LMD patients; however, the OS for these patients remains grim despite advances in such therapies. Further research is necessary to understand the pathophysiology of LMD, and new clinical trials are urgently needed to identify novel therapies that improve M-LMD prognosis.
Long-term efficacy of BRAFi/MEKi rechallenge in metastatic melanoma: Report of 9 years of clinical practice.
Authors: Czarnecka Anna Malgorzata , Cybulska-Stopa Bozena , Plachta Iga , Rogala Pawel , Galus Łukasz , Piejko Karolina , Dziura Robert , Bal Wieslaw , Kubiatowski Tomasz , Teterycz Pawel , Wisniewska Magdalena , Zietek Marcin , Brandys Piotr , Kempa-Kamińska Natasza , Borkowska Aneta , Suwiński Rafał , Kamińska-Winciorek Grażyna , Mackiewicz Jacek , Rutkowski Piotr
Published: June 2023

e21550

Background: First line BRAFi/MEKi therapy in metastatic melanoma eventually result in drug resistance and disease progression. Because drug resistance develops at least partially by epigenetic mechanisms, it may potentially be reversed after BRAFi/MEKi discontinuation. Therefore we aim to explore the clinical efficacy of BRAFi/MEKi rechallenge in 3 line treatment. Moreover the reports on the efficacy of BRAFi/MEKi after immunotherapy were contradictory, so we enrolled patients treated sequentially to explore this clinical scenario. Methods: In country-wide multicenter retrospective analysis 86 patients with metastatic BRAF-mutated melanoma were enrolled since 1/Jan/2014. Patients were treated with 1st line BRAFi/MEKi, 2nd line immunotherapy (anti-PD-1 or anti-CTLA-4) and were rechallenged with BRAFi/MEKi. Survival analyses were performed using the Kaplan-Meier method, log-rank and chi-square tests were used for comparison between groups. Data cut-off was 31/Dec/2022. Results: Median age at BRAFi/MEKi rechallenge was 50 (range: 20-81 y/o). Median overall survival (OS) from the start of the first BRAFi/MEKi therapy and from rechallenge BRAFi/MEKi treatment was 34 and 9 months, respectively; whereas median progression-free survival (PFS) was 10.5 and 4.4 months respectively. At the time of analysis 88% progressed on third line therapy and 78% patients died. Six-month, one-year, and two-year OS rates were: 99%, 93% and 70% on first line treatment; and 65%, 40% and 2% on BRAFi/MEKi rechallenge. Objective response rate and disease control rate on first line BRAFi/MEKi and rechallenge were 57% and 28%; and 91% and 64%, respectively. A lower toxicity rate was noted with BRAFi/MEKi rechallenge. The most common treatment sequence was dabrafenib/trametinib – immunotherapy – encorafenib/binimetinib. Conclusions: Rechallenge with BRAFi/MEKi after second line immunotherapy results in a clinically significant benefit in majority of eligible patients. Third line treatment should be considered for fit patients. [Table: see text]
Long-term outcomes of PD-1 blockade in metastatic or unresectable cutaneous squamous cell cancer.
Authors: Ali Shawn Ahmed , McGillivray Erin Elizabeth , Savage David James , Bollin Kathryn Blount , Swanson Mark , Kokot Niels , Hu Jenny , Ito Fumito , In Gino Kim
Published: June 2023

e21551

Background: Cutaneous squamous cell carcinoma (CSCC) is the 2nd most common malignancy in the US. Approximately 10% of patients will experience either recurrent or metastatic disease, leading to worsened morbidity and mortality. In 2019, anti-PD1 therapy was FDA approved for metastatic or unresectable CSCC, and has been established as the standard frontline systemic therapy for this disease. Here we present our long-term, follow-up data investigating the efficacy, safety, and durability of PD-1 therapy for CSCC. Methods: This is a retrospective cohort study of metastatic or unresectable CSCC patients treated with PD-1 therapy at the University of Southern California Norris Comprehensive Cancer Center and the Scripps MD Anderson Cancer Center between June 2016 and January 2023. Patient demographics, tumor characteristics, and treatment related variables were collected. Objective response (ORR) was collected per RECIST criteria. Kaplan-Meier curves were used to estimate progression free survival (PFS) and overall survival (OS). For patients receiving salvage therapy post-PD1, progression free survival 2 (PFS2) and objective response rate 2 (ORR2) were also calculated. Toxicities were graded per CTCAE v5.0. Results: A total of 39 patients diagnosed with CSCC received at least one cycle of PD-1 therapy; among these 8 were excluded from efficacy analysis. Patients were on average 68 years old (range 22-97), predominantly male (69.2%) and Caucasian (74.4%). The most common primary tumor location was head/neck (64.1%), followed by extremity (15.4%). The mean tumor diameter was 6.0 cm (4.5-7.5, 95% CI). The majority of tumors were either moderately (33.3%) or poorly (28.2%) differentiated. The most common sites of metastatic disease included lymph node (41.0%), skin/soft tissue (33.3%) and bone (25.6%). Patients received on average 7 cycles of PD-1 therapy (range 1-26) and were followed for median 13.8 months. ORR for all patients was 39.0%, including CR and PR in 7 (22.6%) and 4 (13.0%) patients, respectively; 10 patients (32.2%) achieved stable disease (SD), while 7 patients (22.6%) had progression of disease (PD). Median PFS was 6.8 months, while OS was 26.7 months. Among 10 patients receiving salvage therapy after PD-1, 6 (60.0%) received a platinum-containing regimen. Median PFS2 was 4.4 months, while ORR2 was 10.0% with 1 PR, 4 SD, and 5 with PD. PD-1 therapy was well tolerated with 13 patients (33.3%) experiencing Grade 1-2 toxicity and 2 patients (5.2%) experiencing Grade 3-4. Conclusions: In this study of long-term outcomes of CSCC patients treated with PD-1 blockade, we found that initial responses to PD-1 therapy were durable, although PFS2 was less durable for patients who required salvage therapy and ORR2 was low. Novel treatment options are needed for patients with advanced CSCC who do not achieve durable responses to PD-1 based therapy.
Real-world experience of tebentafusp for uveal melanoma via an Australian access program.
Authors: Inderjeeth Andrisha Jade , Hurwitz Josh , Joshua Anthony M. , Kee Damien
Published: June 2023

e21554

Background: Uveal melanoma (UM) is a rare melanoma subset, with distinct biology, genetics, and limited active therapies. Tebentafusp (tebe) has demonstrated a survival advantage however low response rates and a toxicity profile making real-world administration challenging. Methods: Data was retrospectively collected for patients (pt) enrolled into a tebentafusp access program at two tertiary Australian centres. Data fields included: baseline patient, disease and prior treatment characteristics; and tebe administration, response, toxicity and survival outcomes. Results: From May 2021 to February 2023, 19 pt received tebe for UM: 7 males, average age 61 years (range 39-86). All pt presented with local disease at diagnosis, with time to metastases greater than 12 months (mo) in 15/19. Prior to tebe, all patients had hepatic and 6/19 extra-hepatic metastases (6 bone, 4 lymph node, 2 peritoneal, 2 dermal and/or subcutaneous). Baseline PET scan demonstrated FDG-avid disease in 13/14. Primary disease treatment included enucleation (7/19) and radiotherapy 13/19). For advanced disease, prior systemic therapies included: none (12/19); anti-PD1 (3) or anti-CTLA4 (2) as monotherapy; or in combination (5); and anti-PD1 with anti-LAG3 (2). Prior to tebe baseline LDH was elevated in 10/19 (53%) and average neutrophil to lymphocyte ratio was 9.22 (range 0.9-49.5). The median time receiving tebe was 5.5 mo (range < 1-18). The median progression free survival (PFS) was < 3mo. 5 pt remain on tebe with 2 pt treated with tebe beyond 12 and 18mo duration. Best response obtained by PET or cross-sectional imaging was: a partial response in 4/19, stable/mixed in 4/19, progressive disease in 8/19, and unknown/not evaluable in 3/19. The majority of patients ceased tebe due to disease progression (10), change of therapy (4) or death (2). Only one patient ceased due to toxicity. At last review 14/19 (74%) patients were still alive and 4/19 had received one or more lines of systemic therapy after tebe including immunotherapy (1), targeted therapy (1) and/or clinical trials (4). Common adverse events included: rash (63%), hypotension (47%), pruritis (42%) and pyrexia (32%). Supportive measures were required (e.g. hydration, antihistamines, topical steroids) for 13 patients. Cytokine release syndrome (CRS) was reported in 63% (12/19) with only 3 demonstrating grade 2 severity. CRS management included oral (1) or intravenous steroids (2) and zero patients required additional immunosuppression. The median number of cycles administered as an inpatient was 3 (range 2-10). Conclusions: Within experienced tertiary centres tebe could be safely administered outside of a clinical trial setting. Median time on treatment greatly exceeds progression free survival, likely due to unique response characteristics and limited access to subsequent therapy. Identifying features that enrich for clinical benefit remain necessary for optimising tebe use.
Distant stage melanoma incidence among US adult women.
Authors: Johnson Caitlin Ruth , Liao Cheng-I , Obiakor Bianca , Jiang Ruolin Lorraine , Kapp Daniel Stuart , Chan John K
Published: June 2023

e21555

Background: To examine trends in distant stage melanoma incidence among U.S. women. Methods: Demographic and clinical data were obtained from the United States Cancer Statistics (USCS) Database from 2001-2019. SEER*Stat 8.3.9.2 and Joinpoint regression program 4.9.0.0 were used to calculate cancer incidences and trends per 100,000. Average annual percentage change (AAPC) was used to describe trends. Age-adjusted incidences were adjusted by the U.S. 2000 standard population. Results: From 2001-2019, 543,051 women were diagnosed with distant stage melanoma. Over this period, incidence rose from 0.37 to 0.59/100,000 with an increasing annual rate of 2.58% per year (p < 0.0001). In 2019, non-Hispanic White women had disproportionately higher incidence rates at 0.76/100,000 compared to Hispanic (0.26/100,000), non-Hispanic Black (0.17/100,000), and non-Hispanic Asian (0.08/100,000) women. Regarding race, the largest increase in distant melanoma incidence was observed in White women with an average annual increase of 2.92% (p < 0.0001). Among age groups, incidence was highest among those aged ≥45 (1.54/100,000) and 40-44 (0.53/100,000) years. However, the largest increases in distant melanoma incidence were found among 30-34-year-olds at a rate of 3.91% per year (p = 0.004) and 40-44-year-olds at 2.78% per year (p = 0.003). When examined by race and age, annual incidence rates were highest among White women aged 40-44 years at 3.68% per year (p < 0.0001). Regarding U.S. state, incidence was highest in Florida (1.34/100,000), West Virginia (1.32/100,000), and Oklahoma (1.20/100,000). The largest annual increases in distant melanoma incidence rates were observed in Nebraska at 8.63% (p = 0.001), Kentucky at 6.18% (p < 0.0001), and West Virginia at 6.06% (p = 0.001). When performing an intersection analysis of race, age, and U.S. stage, White women living in Nebraska aged ≥45 had the largest increase in distant melanoma at a rate of 8.12% annually (p = 0.004). In 2019, White women in Utah had the highest incidence of distant melanoma at 3.45/100,000. Conclusions: Distant stage melanoma is disproportionally increasing among adult women aged 30-44 years, especially among White populations. Further studies are warranted to understand the environmental and socioeconomic implications behind these trends.
Correlation of low B7-H6 expression with efficacy of immunotherapy inpatients with melanoma.
Authors: Chen Jian , Li Deqin , Zhang Weiwei , Song Shujie , Sun Dengjun , Luo Ningning , Yi Huan , Qi Yingxue , Li Mengmeng , Sun Tingting , Qi Chuang
Published: June 2023

e21556

Background: B7-H6 (NCR3LG1) can bind to NKp30 to trigger antitumor NK cell activation and cytokine secretion. Our previous studies have shown that in gastric cancer, B7-H6 high expression was associated with better prognosis and the low expression of B7-H6 group was correlated with better immune microenvironment. However, the effect of B7-H6 expression on immunotherapy is unknown. Herein, we used the data from a clinically annotated cohort of melanoma patients treated with ICI to analyze the influence of B7-H6 expression on immunotherapy. Methods: The gene expression profile, gene mutation information and clinical data were extracted from the supplementary data in melanoma cohort (PMID: 31792460). Maximally selected rank statistics was used to select the optimum threshold for B7-H6 expression, and the patients was divided into two groups according to the expression of B7-H6, high group and low group. Kaplan-Meier survival analysis was used to evaluate the influence of B7-H6 expression on OS prognosis. Associations between variables and OS survival were tested using univariate and multivariate Cox and displayed by forest (R package). Results: We selected 3.14 as the optimum threshold of B7-H6 expression, and the patients was divided into high group (B7-H6 expression＞3.14) and low group (B7-H6 expression≤3.14). The results showed that low group was significantly associated with longer overall survival (p value = 0.048) in cohort of melanoma patients treated with anti-PD1 ICI, which was consistent with our previous results that low expression of B7-H6 group was correlated with better immune microenvironment. We selected primary lesion type, TMB and the expression of B7-H6 factors for univariate and multivariate analysis. TMB-H (top 25%) (p value = 0.051) and B7-H6 (p value = 0.051) low expression were associated with a better OS. Then the patients were divided into four groups according to the TMB and B7-H6 expression and analyzed the difference in the four groups. The results showed that in patients with TMB-L, B7-H6 low group had significant better OS than the B7-H6 high group (p value = 0.032). Conclusions: The low B7-H6 expression was correlated with better efficacy immunotherapy. The effect of B7-H6 expression on immunotherapy needs to be further prospective trial validation.
Influence of follow-up time on outcome of children and adolescents with atypical Spitz tumor/Spitz melanoma (AST/SM): Results from the MACMEL registry.
Authors: Kacar Marija , Yuan Xiaomeng , Pan Haitao , McPherson Valerie , Pappo Alberto S.
Published: June 2023

e21558

Background: Pediatric melanoma is a rare and challenging diagnosis, requiring an integrated clinicopathologic and genomic approach to optimize diagnosis and clinical care. The Molecular Analysis of Childhood Melanocytic Tumors (MACMEL) registry (Pappo A Cancer. 2021 Oct 15;127(20):3825-3831) was developed to better characterize pediatric melanocytic lesions by including clinical information, central pathology review, and genomic analysis. The AST/SM subtype of melanocytic lesions often affects younger patients, have a high incidence of nodal involvement, and are genomically characterized by copy number aberrations and kinase fusions. Methods: A review of the MACMEL registry data for patients with AST/SM enrolled from May 2016 to December 2022. Patient data included demographics (age, sex, ethnicity), anatomic location of lesion, sentinel node involvement, AJCC staging, genomic and germline findings, therapy, and disease outcomes. Results: We identified 60 patients with AST (n=17) and SM (n=43). 28 patients had stage III disease and 16 had stage IIIC disease. There were 38 females, and 22 males. The most common primary sites were the extremities and the most common gene rearrangements included MAP3K8 (n= 10) and ALK (n= 12). Other genomic alterations identified included kinase fusions NTRK, ROS1, BRAF, FLOT2-ARAF, RAC1, BRIP1, SDHAF2, ATM, GPNMB-ERBB2, and CDKN2B. None of the 55 patients that underwent TERT promoter analysis had a mutation. Adjuvant treatment was given to 8 patients (interferon 3, pembrolizumab 4, larotrectinib 1). The median follow-up time for the cohort is 3.1 years, with 57 patients alive with no evidence of disease. 1 patient had a local relapse treated with wide local excision and is currently alive with no evidence of disease. 3 patients were lost to follow up. Event free survival (EFS) for the cohort is 98% and overall survival (OS) is 100%. Conclusions: Patients with AST/SM comprise the largest subtype of melanocytic lesions enrolled on the MACMEL registry and have an excellent clinical outcome. This supports our previous observations that patients with AST/SM who lack TERT promoter mutations may be able to be managed conservatively and that an integrated diagnostic approach incorporating genomic information is vital for optimal diagnosis and clinical management. [Table: see text]
Prognostic value of BRAF and RAS mutations in radically resected patients (pts) with stage I-III melanoma: Preliminary results from a retrospective study.
Authors: Brugnara Sonia , Sicher Mariacristina , Girlando Salvatore , Bonandini Maria Elena , Barbareschi Mattia , Frisinghelli Michela , Mangiola Daniela , Caffo Orazio
Published: June 2023

e21567

Background: Although BRAF and RAS mutations in radically resected pts with stage I- II and III melanoma could have a prognostic value, conflicting evidences are still available. The present retrospective study was aimed to investigate this controversial issue. Methods: We retrospectively evaluated a consecutive series of 201 pts with stage I-III melanoma (AJCC 8th) who have undergone radical surgery from 2005 and 2010. For each pt we retrieved the clinical record and collected data concerning the clinical history. In addition, we evaluated the mutation status of somatic BRAF, KRAS and NRAS on a tissue sample obtained from primary surgery material. We describe the expression rate of such mutations and their relationship with pts’ survival outcomes. Results: To date they are evaluable data on 100 pts (M/F 62/38): the median age was 66 yrs (range 36-91), most of the pts was in stage I-II (66 %). The detected mutations is described in the table. Conclusions: From our preliminary results, it appears that BRAF and RAS mutations did not have prognostic value in the assessed population. The final report of the analyses carried on the whole population will increase the study ability to assess the role of these mutations in predicting the outcomes of radically resected stage I-III melanoma. [Table: see text]
Effect of lymph node dissection and adjuvant therapy in patients with sentinel node+ melanoma: An observational multicenter study.
Authors: Ogata Dai , Iwata Mai , Kato Hiroshi , Fukushima Satoshi , Maekawa Takeo , Nakamura Yasuhiro , Tsutsumida Arata , Suyama Takayuki , Kitagawa Hiroshi , Nakamura Yoshio , Takenouchi Tatsuya , Matsushita Shigeto , Oashi Kohei , Kato Junji , Fujiwara Susumu , Maeda Taku , Nishizawa Aya , Kawahara Yu , Yamazaki Naoya , Namikawa Kenjiro
Published: June 2023

e21569

Background: Currently, lymph node dissection (LND) is not mandatory for patients with sentinel node (SN)+ melanoma. Anti-programmed cell death receptor-1 (PD-1) monotherapy and dabrafenib/trametinib combination (for BRAF mutations) are standard adjuvant treatments for patients who undergo definitive surgery for melanoma. However, the effects of this approach remain unclear in patients with stage III melanoma in real-world clinical settings. We investigated the effects of the aforementioned therapeutic approaches on the prognosis of stage III melanoma in a Japanese cohort. Methods: We retrospectively analyzed clinical data of patients with SN+ melanoma treated with or without anti-PD-1 monotherapy or combination dabrafenib/trametinib therapy obtained from 39 independent institutions in Japan between 2018 and 2021. Survival outcomes (recurrence-free survival [RFS] and overall survival [OS]) were compared with regard to LND, adjuvant therapy type, and clinical factors. Results: We investigated 357 patients; 35.9% (128/357) of patients underwent LND, of whom 70.3% (90/128) received adjuvant therapy. LND was not performed in 64.1% (229/357) of patients, of whom 74.7% (171/229) received adjuvant therapy. RFS and OS did not differ between patients with and without LND (2-year RFS 54.5% vs. 51.5%, p = 0.98; 2-year OS 84.1% vs. 86.5%, p = 0.39). RFS and OS did not differ between patients with and without adjuvant therapy (2-year RFS 54.5% vs. 50.4%, p = 0.90; 2-year OS 83.4% vs. 89.8%, p = 0.33). Multivariate analysis of RFS after adjustment for adjuvant therapy, clinical subtype, tumor thickness, ulceration, and BRAF status showed significant differences between patients with and without adjuvant therapy (hazard ratio 3.06 [95% confidence interval 1.39–6.76]). Data analysis in 261 patients who received adjuvant therapy showed no difference between patients with and without LND (2-year RFS 55.9% vs. 52.6%, p = 0.74; 2-year OS 83.4% vs. 83.6%, p = 0.73). Regarding adjuvant therapy type, RFS and OS were significantly longer in patients who received BRAF/MEK inhibitors than in those treated with PD-1 monotherapy (2-year RFS 75.0% vs. 42.2%, p < 0.01; 2-year OS 89.3% vs. 79.5%, p = 0.01). Conclusions: Our study revealed that LND did not affect prognosis and adjuvant therapy reduced the recurrence of stage III melanoma in a Japanese cohort. Although the follow-up period was short, with regard to drug selection, RFS and OS were significantly longer in patients treated with BRAF/MEK inhibitors than in those who received PD-1 monotherapy. Factors contributing to the lower effectiveness of PD-1 monotherapy remain unclear and warrant further investigation.
Epidemiology and outcomes of anorectal melanomas: A national database analysis.
Authors: Wang Yating , Yu Qian , Chang Kevin Wei-Lun , Reap Leo Edward , Terebelo Howard R. , Yu Zhiyong , Lyons Susan Elizabeth
Published: June 2023

e21572

Background: Anorectal melanoma is a rare but aggressive type of melanoma, arising primarily from the mucosal epithelium from the anorectal tract. Knowledge of this rare etiology has been limited given its low incidence. This study aims to characterize the epidemiology and treatment outcomes of anorectal melanoma using a national database. Methods: The Surveillance, Epidemiology and End Results (SEER) Database was queried to identify patients with biopsy-proven anorectal melanoma. The following information was retrieved: tumor site, grade, stage, intervention, lymph node histology, and survival information for oncology codes as per the international classification of diseases. Statistical analysis was performed with Stata 15.1 (STATA Corp., College Station, TX, USA). Results: The age-adjusted anorectal melanoma annual incidence rates have been stable approximately 0.4-0.5 per 1 million from 2000 to 2019. Of the 823 biopsy-proven confirmed cases of anorectal melanoma from 2000 to 2018, 150 (18.2%) received chemotherapy, 182 (22.1%) received radiotherapy, 55 (6.7%) received chemoradiation, while 619 (75.2%) of the population received surgery alone or combined with chemotherapy and/or radiotherapy. Statistically significant improvement in survival was noted in treatment strategies that utilized surgery with and without chemotherapy and/or radiotherapy (median survival time 22 vs 9 months, p < 0.0001). Patients with positive regional lymph nodes on pathology were associated with worse prognosis (median survival time 15 vs 37 months, p < 0.0001). Outcomes did not differ based on sex (p = 0.810) and race (p = 0.372). Conclusions: Incidence of anorectal melanoma in the United States has been stable in the last twenty years. Treatment strategies including surgical resection should be adopted if possible to achieve improved survival outcomes.
Investigating the clinical relevance of RNA editing events and their derived neoantigens in patients with melanoma treated with immunotherapy.
Authors: Zhang Xiaodong , Wang Wei , Zhou Wenhao , Lu Qicheng , Ding Tian , Fan Ligang
Published: June 2023

e21580

Background: RNA editing (RE) is a post-transcriptional modification occurring in RNA, which promotes transcriptome and proteome diversity. Peptides translated from RE sites may represent a new source of neoantigens in cancer (RE-derived neoantigens, RED-neoantigens) that could be presented on tumor surface by human-leukocyte-antigen (HLA) and recognized by specific T-cells, leading to an improved response to immune checkpoint inhibitors (ICIs). However, the clinical significance of both RE events and RED-neoantigens in melanoma patients with ICIs therapy has not been systematically characterized. Methods: The WES and transcriptome data with immunotherapy response of melanoma were obtained from the GEO and SRA database. Vardict and VEP were used to identify and annotate the somatic mutations. Polysover was applied to identify the HLA genotype. RNA editing events were identified by Reditools2 and filtered by a custom pipeline. miRTar2GO was implemented to predict the RE event whether located in miRNA targets within the 3' UTR region. NetMHCpan and NetCTLpan were used to identify and characterize RED-neoantigens. K-M survival analysis was performed on the training set to investigate the clinical relevance of RNA editing events and RED-neoantigens in melanoma patients treated with immunotherapy. The independent melanoma dataset was used to validate this clinical relevance. Results: In total, 7,116 RE events were identified, most of which were A-to-I events. 34% of RE sites in 3'UTR and 15% in 5' UTR were located in the seed regions of miRNA targets and transcription factor binding sites (TFBS), respectively, suggesting the different functional effects of the RE events. Furthermore, using our custom pipeline, 631 RED-neoantigens were identified that show a significantly greater peptide-MHC affinity, and facilitate epitope processing and presentation than wild-type peptides. Meanwhile, we found that patients exhibiting a high RED-neoantigens burden correlated with an increased OS, and a significantly higher RED-neoantigens burden was observed in responders. The area under the curve (AUC) of the RED-neoantigen was 0.831 of OS and 0.686 of responsiveness. Conclusions: The findings in this study provide a more insightful view and resource for investigating the neoantigens in cancer as well as for novel cancer immunotherapies and biomarker development.
Academic medical center access and outcomes in Kaposi sarcoma.
Authors: Swedek Michelle , Silberstein Peter T. , Vardell Victoria
Published: June 2023

e21582

Background: Kaposi sarcoma (KS) is a soft tissue tumor commonly affecting the skin. It is seen in patients in immunosuppressed states, such as those with HIV/AIDS or organ transplant history. Treatment may include excision, chemotherapy, or radiotherapy depending on the location and spread of lesions. Prior studies indicate that treatment at academic facilities, which offer higher treatment volume, and access to specialized care, clinical trials, and a greater number of ancillary services, is associated with improved survival in other skin cancers, such as melanoma. In this study we aim to compare the survival and sociodemographic factors for KS patients between academic and non-academic facilities, using the largest dataset of these patients yet examined. Methods: We conducted a retrospective analysis of the National Cancer Database from 2004 to 2019 for subjects with KS, identified by ICD code 9140 (n=5,233). Factors were compared between patients seen at non-academic (NAC) (n=2,278) versus academic centers (AC), (n=2,955). Overall survival (OS) was estimated using Kaplan Meier analysis with pairwise log-rank tests for significance. Multivariate analysis was performed using binary logistic regression. Results: Most individuals in the study were White (70.1%), male (87.1%), not of Spanish or Hispanic origin (82.7%), and had government insurance (54.3%). Treatment at AC was associated with improved survival compared to NAC (median OS 184 vs. 98 months, p<0.001). AC patients were younger compared to NAC patients (mean age 56.1 vs. 60.9 years old, p<0.001). On adjusted logistic regression, AC were more likely to treat minority patients, including Black patients (OR 1.23, 95% CI 1.06-1.43, p=0.005) and Spanish/Hispanic patients (OR 1.26, 95% CI 1.06-1.48, p=0.007). AC were more likely to manage uninsured patients compared to patients with private (OR 0.48, 95% CI 0.39-0.60, p<0.001) or government insurance (OR 0.69, 95% CI 0.55-0.86, p=0.001). Compared to the East Coast, patients in the Central U.S. (OR 0.81, 95% CI 0.71-0.93, p=0.003) and West Coast (OR 0.83, 95% CI 0.71-0.96, p=0.015) were less likely to use AC. Patients residing in high education zip codes were less likely to be treated at academic centers (p<0.001). Patients in the top income quartile were more likely to be treated at AC (OR 1.42, 95% CI 1.15-1.75, p=0.001). Conclusions: Treatment at AC is associated with improved overall survival compared to NAC in KS. AC were more likely to treat younger patients, and those from racial and ethnic minorities, as well as those in the top income quartile. Less academic center use was seen in areas of higher educational attainment and by individuals with government or private insurance. While specialized care and clinical trial access may play a role in this survival benefit, access to AC may also be a surrogate marker of social determinants of health that play a role in KS outcomes. Our study supports the ongoing need for access to comprehensive care in KS.