bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multicenter analysis of melanoma recurrence pattern and management after adjuvant immunotherapy.
Authors: Martínez Recio Sergio , Molina Maria Alejandra , Muñoz-Couselo Eva , Sevillano Tripero Alberto Rafael , Martin-Liberal Juan , Orrillo Mayra , Fernandez Luis Antonio , Quindós Varela Maria , Lesta Rocio , Barba Andrés , Sullivan Ivana , Majem Margarita 
Published: June 2023

e21573 Background: PD-1 inhibitors improve outcomes in resected stage II-IV melanoma. However, recurrence patterns and prognostic factors are less known. Methods: We conducted a retrospective study in resected stage II-IV melanoma patients (p) treated with adjuvant PD-1 inhibitors (clinical practice or clinical trials) from 5 centers. Demographic, disease characteristics, adjuvant therapy, recurrence, treatment at relapse and outcome were recorded. Descriptive assessment for recurrence patterns and analysis for prognostic factors were performed. Results: From June 2017 to June 2022, 181 p were included. Median age was 59 years [22-81], 57% were male, 85% had cutaneous melanoma, 28% had BRAFV600E mutation. 9 p (5%) presented stage II, 147 (81%) stage III and 25 (14%) stage IV. Ulceration was present in 59% p, mitotic rate >1/mm2 in 84%, Breslow index >3 mm in 65% and elevated LDH in 51%. 81% p received PD-1 inhibitors alone and 19% in combination with other immunotherapies. 52% of p completed treatment, 12% discontinued due to toxicity and 26% due to relapse. 13% of p presented grade 3-4 adverse events and there was a grade 5 myocarditis. With a median follow-up of 18,1 months, 68 (37%) p recurred (Table). Median relapse free survival (RFS) was 48,8 months (95% CI 31,1-66,4). Recurrence was significantly associated with a higher stage, mitotic rate, LDH level and Breslow index, BRAFV600E mutation, non-cutaneous melanoma and delayed initiation of adjuvant immunotherapy in univariate analysis (p<0,05). Stage, non-cutaneous melanoma and initiation of immunotherapy >3 months (16% p) were associated with higher recurrence in multivariate analysis (<0,05). Locoregional recurrence was treated in 23 p with surgery (14p), surgery + RT (7p) or RT alone (2). Systemic recurrence was treated in 50 p: all BRAF mutant p received targeted therapy (24p, 43%) with a disease control rate (DCR) of 91% and a median progression free survival (PFS) of 56 months (95% CI 24,1-NR); BRAF wild type p (26p, 47%) were treated with anti-PD-1 alone (9p) or in combination (7p), anti-CTLA-4 (2p), chemotherapy (1p) or best supportive care (7p), with DCR of 33% and a median PFS of 8 months (95% CI 6,9-10,8). Conclusions: We observed a 37% relapse rate and systemic recurrence were more frequent than locoregional recurrence. Treatment at relapse with targeted therapy in BRAF mutant p achieved higher DCR and PFS than immunotherapy in BRAF wild type p; with better outcomes than previously reported.[Table: see text]
HLA discordance between blood and tumor: A treatment conundrum?
Authors: Seedor Rino S. , Orloff Marlana M. , Pancholy Pariseema , Terai Mizue , Sato Takami 
Published: June 2023

e21577 Background: Tebentafusp is a bispecific gp100 peptide-HLA-directed CD3 T cell engager that is now FDA approved for HLA-A*02:01 patients with unresectable or metastatic uveal melanoma (UM). Tebentafusp requires the targeted gp100 peptide to be presented by the major histocompatibility complex Class I complex HLA-A*02:01 allele for optimal cell killing. HLA-A*02:01 has been reported to be carried by approximately 50% of the North American and Western European population. The clinical trials for tebentafusp all required central blood tests to determine HLA status. In March of 2021, Caris Life Sciences began the launch of HLA Genotype as a standard reporting element for patient tumors profiled by Caris. Somatic HLA mutations have been described in different tumor types and has strong implications for a possible mechanism of immune evasion. Tumor heterogeneity between tumors and within tumors may also impact HLA tumor testing. As more novel drugs that rely on HLA genotyping are developed, understanding the relationship between blood and tumor HLA testing has become crucial. Methods: A single institution retrospective analysis was performed of patients who had tumor HLA genotyping performed as part of their tumor profiling by Caris Life Sciences. HLA Genotyping by Caris was performed using Whole Exome Sequencing of the tumor. Of the patients who had tumor HLA genotyping results, patients who also had blood HLA typing were identified. The concordance rate of HLA-A status between blood testing and tumor testing was determined. The prevalence of HLA-A*02:01 in our patients was also determined (either blood or tumor). Results: Forty-seven patients with both tumor and blood HLA genotyping were identified (37 UM, 8 cutaneous melanoma, 1 mucosal melanoma, 1 renal cell carcinoma). The majority of the patients were Caucasian (n = 44), with only two Asian patients and one African patient. There were two UM patients whose tumor and blood HLA genotyping were discordant (concordance rate of 95.7%). One patient was found to be HLA-A*01:01, *026:01 by blood but tumor genotyping revealed HLA- A*01:01, A*02:01. The other patient was found to be HLA-A*02:01, A*01 by blood but tumor genotyping revealed HLA-A*03:01, A*33:03. The prevalence of HLA-A*02:01 in the entire group was 34%, while the prevalence of HLA-A*02:01 in the Caucasian patients was 36.4%. None of the non-Caucasian patients were HLA-A*02:01 by blood or tumor genotyping. Conclusions: Among our 47 patients with both tumor and blood HLA genotyping, we found two patients with discordant HLA results. Neither of the discordant UM patients had received tebentafusp yet, but it brings up a crucial question about how these patients may respond to a therapy that relies on the HLA-A*02:01 complex. Our study highlights the importance of continuing to use blood HLA genotyping as the standard test to determine eligibility for a treatment such as tebentafusp, as the concordance rate with tumor genotyping is high but not 100%.
Impact of disadvantaged socioeconomic and demographic status on survival in Kaposi sarcoma.
Authors: Swedek Michelle , Wu Xinxin , Silberstein Peter T. , Vardell Victoria 
Published: June 2023

e21581 Background: Kaposi sarcoma (KS) is a soft tissue tumor that affects a wide variety of patient populations, though it is typically seen in immunocompromised patients, including those living with organ transplant or HIV/AIDS. Patients from traditionally underserved socioeconomic and demographic populations have historically had poor outcomes across malignancies, however these populations have never been studied on a large national scale in KS. To examine how socioeconomic and demographic status affects survival in KS, we examined the National Cancer Database (NCDB); a large oncology database that includes approximately 75% of newly diagnosed cancers across the United States. Methods: We conducted a retrospective analysis of the NCDB for KS patients diagnosed from 2004 to 2019. Cases missing data for variables of interest were excluded. Overall survival (OS) was examined using Kaplan-Meier and multivariate Cox regression. Results: A total of 5,233 patients with KS were identified, with a mean age of 58 years. Most patients were male (87.1%), White (70.1%), not Spanish/Hispanic (82.7%), and had government insurance (54.3%). Comorbid conditions were described using the Charlson-Deyo Comorbidity Score (CDS), and a substantial number of patients had a score above 3 (28.6%). The mean OS for all patients was 122 months. On adjusted Cox regression, decreased OS was seen in patients over 85 years old (HR 2.14, 95% CI 1.82-2.53, p<0.001) compared to patients aged 40-54 years old. Compared to White patients, Black patients had decreased OS (HR 1.24, 95% CI 1.11-1.38, p<0.001); mean survival in Black patients was 113 months compared to 124 months in White patients (p<0.001). Improved OS was seen in patients of Spanish/Hispanic origin (HR 0.80, 95% CI 0.70-0.91, p<0.001). Any CDS greater than 1 was associated with poor OS (HR 1.46 for CDS 1, 95% CI 1.26-1.70, p<0.001), and treatment at an academic facility had a protective effect (HR 0.75, 95% CI 0.69-0.82, p<0.001), as did private insurance (HR 0.65, 95% CI 0.55-0.77, p<0.001). Biological sex, education, income, and facility location did not independently impact survival. Conclusions: When adjusted for key demographic covariates, advanced age, Black race, and presence of comorbidities were each independently associated with decreased OS in KS patients. Improved OS was seen with Spanish/Hispanic ethnicity, treatment at an academic facility, and private insurance. To our knowledge, our study is the first to describe demographic and socioeconomic features impacting survival for KS patients at this scale. We revealed important disparities in survival and highlight the need for equitable care in KS, especially for patients of Black race.
Interim analysis of MelaRisk, a biomarker assay validation study in stage IB/IIA melanoma tissue.
Authors: Forchhammer Stephan , Chatziioannou Eftychia , Sinnberg Tobias , Niessner Heike , Leiter Ulrike M. , Keim Ulrike , Forschner Andrea , Garbe Claus , Flatz Lukas , Amaral Teresa Maria Santos 
Published: June 2023

e21591 Background: Adjuvant therapy for melanoma patients (pts) is now available for pts from stage IIB onwards. Pts with cutaneous melanoma in early stages stage IB/IIA have low risk of relapse. However, this group still contributes to the most melanoma deaths in absolute numbers. Therefore, it is important to identify pts in stage IB/IIA that could benefit from adjuvant therapy. One promising biomarker is a proprietary 7-protein immunohistochemistry (7-P-IHC) signature (Immunoprint). Based on primary tumor tissue analysis, the 7-P-IHC has shown very high sensitivity and risk enhancement ability in previous prospective and retrospective validations.1,2 The 7-P-IHC test result indicates a risk score predicting relapse-free and melanoma-free survival (RFS, MSS), thereby allocating most relapses to the high score risk group. To further validate its key parameters, the MelaRisk trial was started in 2022, aiming to analyze up to 500 tissue samples with Immunoprint. Here we present its interim analysis and a combined analysis of all available data for Immunoprint in stage IB/IIA. Methods: All pts with available formalin-fixed paraffin-embedded blocks of the Central German Melanoma Registry diagnosed from 2005-16 and AJCC v8 stage IB/IIA were screened. Tumor tissue samples from 119 pts (83/IB; 36/IIA) were available; the 7-P-IHC was used to determine a risk group. Results: 7-P-IHC assigned 68 pts to the low-risk (57%) and 51 (43%) to the high-risk group. Median follow-up was 76 months. 15/17 relapses after 5-years were detected, resulting in a sensitivity of 88%. 5-years RFS event rate of the cohort according to AJCC v8 was 12% and 19% for stages IB and IIA, respectively. This was enhanced to a risk of recurrence of 30% (stage IB) and 29% (stage IIA) in the respective high score group. 5y-RFS rate was 97% for pts with 7-P-IHC low score risk and 71% for pts with 7-P-IHC high score risk (p=0.0001). 7-P-IHC was the only significant factor in a multivariate Cox analysis for RFS (HR 10.78 (2.38-48.74), p=0.002) and could detect 4/5 MSS events. Combined analysis including these and previous Immunoprint results in stage IB/IIA are summarized in the table. Conclusions: 7-P-IHC could concentrate 88% of stage IB/IIA RFS events in a small high score risk group. This group entails 43% of pts of the total cohort, correctly identifying pts needing adjuvant therapy. Immunoprint should be used to select pts in future studies in the adjuvant setting if these promising interim results can be confirmed in the final analysis. 1. Meyer et al. (2023) EJC; 2. Reschke et al. (2021). [Table: see text]
A national analysis of demographic trends in gynecological cases of basosquamous carcinoma.
Authors: Tuman Jaylin , Hsia Beau , Keirns Darby , Malan Augustus , Silberstein Peter T. , Wu Xinxin 
Published: June 2023

e21598 Background: Basosquamous carcinoma (BSC) is an aggressive form of basal cell carcinoma. Research on BSC is minimal because of its rare nature and the lack of clinical features that distinguish BSC from other forms of basal cell carcinoma, meaning that a diagnosis is only confirmed following biopsy. BSC is distinct because it has features of squamous cell carcinoma, making it more locally invasive, more likely to metastasize and has a recurrence rate of 12 - 51% following surgical excision. While BSC most frequently presents in the head and neck, it can also occur in gynecological cases and this subset of cases has not been studied in literature. In order to more thoroughly understand the distinguishing features and epidemiological trends of this rare cancer, the National Cancer Database (NCDB) was analyzed to determine demographic factors in patients diagnosed with cases of BSC in the breast, vagina and vulva. Methods: The National Cancer Database (NCDB) was utilized to complete a retrospective cohort analysis from 2004 – 2020 that included all patients with histologically-confirmed gynecological cases of BSC (N = 211). Descriptive statistics were analyzed for demographic factors including age, sex, race, income level, insurance status, and Charlson-Deyo score. Results: Between 2004 and 2020 there were 211 identified gynecological cases of BSC. The average age of diagnosis was 71.1 years (SD = 14.6, range = 22 – 90 years) with the majority being non-Hispanic (89.1%) and White (86.3%). The primary site in the vast majority of cases was the vulva (88.6%) and remaining cases originated in other female organs including the breast, vagina and cervix (11.4%). Despite the older age of diagnosis, the majority of individuals (72.0%) had Charlson-Deyo comorbidity scores of 0. The greatest proportion of patients (38.8%) were in the top quartile of household income ( > $74,063) with 15.7% in the lowest income quartile ( < $46,277). Additionally, most patients were insured by Medicare (64.9%) which aligns with the older age of diagnosis. Conclusions: Classifying and fully understanding BSC has proved difficult due to the challenge of differentiating it from other forms of basal cell carcinoma. To further the overall understanding of this aggressive cancer and those that it impacts, this study specifically focuses on a unique subset of BSC cases that have not been well studied. To the best of our knowledge, this is the first NCDB analysis on gynecological cases of BSC. The majority of BSC patients are non-Hispanic and White with an average age of over 70 years old which is supported by the finding that most patients rely on Medicare to fund their treatment. Additional research is needed to better understand the sociodemographic factors, treatments, and overall survival of patients with BSC in aberrant locations.
Association between the primary site of disease and the stage at diagnosis for merkel cell carcinoma: A population-based analysis.
Authors: Gor Rajvi , Gwalani Pranav , Gor Dhairya , Vegivinti Charan Thej Reddy , Gwalani Twinkle , Narvel Hiba , Adhikari Anurag , Deshpande Shweta , Dongre Yutika , Musunuru Tejo Niharika 
Published: June 2023

e21600 Background: Merkel cell carcinoma [MCC] is a rare, aggressive skin cancer with a high rate of recurrence, metastasis, and poor prognosis. It commonly involves the head and neck (HN) region (41% of diagnosed cases), followed by the upper and lower extremities and trunk in decreasing frequency. We used the Survival, Epidemiology, and End Results [SEER] November 2021 database to assess the incidence, cause-specific survival, and the association between the primary site of disease and the stage at diagnosis for primary MCC. Methods: Using the SEER-November 2021 (17 registry) database, a retrospective analysis was performed on the 4120 cases of pathologically confirmed MCC (ICD-O-3 code 8247), diagnosed between 2004-2015. Baseline characteristics were assessed using the Chi-squared test and the Kruskal-Wallis test. Multivariate multinomial logistic regression was performed to evaluate the association, with alpha at 0.05. Analysis was performed using SEERStat and SAS 9.4. Results: The overall age-adjusted incidence rate (IR) of MCC was 0.4 cases per 100,000 with an observed 5-year survival [OS] of 47.8% and cause-specific 5-year survival [CSS] of 68.7%. The median age at diagnosis was 79 years (interquartile range - 66,83) with a male preponderance (60.4%). At baseline, males had higher odds of being diagnosed at stages III or IV (p < 0.001). The odds of being diagnosed at stages II, III, or IV were significantly higher in patients with the trunk as the primary site compared to the HN region with an OR 3.8 (p < 0.001), 2.4 (p < 0.001), and 2.2 (p = 0.001), respectively. For patients with the upper limb as the primary site, the odds of being diagnosed at stage II were 1.4 times higher than the HN region (p = 0.0095), and stage IV was 0.4 times (p = 0.03) higher. For the lower limb and hip, the odds of being diagnosed at stages II, III, or IV were significantly higher than the HN region with an OR 2.6 (p < 0.001), 1.6 (p < 0.0005), and 1.5 (p = 0.04), respectively. Conclusions: While less prevalent than the MCC of the HN region, patients with MCC of the trunk, upper or lower extremities had a higher probability of being diagnosed with an advanced-stage malignancy compared to the former. Additional prospective studies are required to investigate this association further and explore its significance in site-specific treatment approaches and survival factors. [Table: see text]
Protective effect of the dexrazoxane against cardiotoxicity of the anthracycline in the treatment of the childhood cancers.
Authors: Tacyildiz Nurdan , Turker Nazmiye , Ucar Tayfun , Incesoy Ozdemir Sonay , Dincaslan Handan , Yaman Ortakoylu Melek , Ramoglu Mehmet Gokhan , Yavuz Gulsan , Unal Emel Cabi 
Published: June 2023

e22001 Background: Cardiovascular diseases have become the most important cause of morbidity and mortality in the long-term follow-up of childhood cancer survivors. Dexrazoxane (DEX) is the only FDA-approved drug to prevent Anthracycline-induced cardiotoxicity. In this study, we aimed to evaluate the cardioprotective efficacy of DEX in patients using Anthracycline in the treatment of childhood cancer. Methods: 142 patients aged 0-18 years, who were treated with cancer diagnosis in Ankara University Faculty of Medicine, Department of Pediatrics, Department of Pediatric Oncology, and who had been treated with Anthracycline group agents, were evaluated retrospectively. The cardiac functions of 87 patients who received only Anthracycline between November 2009 and March 2019 and 55 patients who received DEX + Anthracycline between March 2019 and June 2021 were compared. An ejection fraction (EF) of less than 50% in cardiac evaluation was defined as 'cardiac dysfunction'. Results: The group that received anthracycline with DEX; While 50.9% were girls, 49.1% were boys, and the mean age was 98.42 months, 48.3% of the group that took only Anthracycline was girls and 51.7% were boys, with a mean age of 105.75 months. There was no difference between the two groups in terms of diagnosis distribution. EF values of both groups before anthracycline were normal. While none of the patients in the DEX + Anthracycline group developed cardiac dysfunction during the follow-up, 11 (12.6%) patients in the Anthracycline group with no DEX had cardiac problems. Six Of the 11 patients (54.5%) who developed cardiac dysfunction died(p=0.012). There was a significant difference between the two groups with or without DEX patients in the manner of cardiac dysfunction(p=0.006) and death(p=0.009). Cardiac dysfunction development and mortality rates were higher in patients using only Anthracycline. Conclusions: In this study, it has been shown that DEX is very effective for preventing Anthracycline-related cardiac dysfunction, which is one of the most important causes of mortality and morbidity in childhood cancer survivors.
Pediatric cancer registry in Turkey 2002-2022: 21 years of achievement (TPOG & TPHD).
Authors: Kutluk M. Tezer , Yeşilipek Akif 
Published: June 2023

e22004 Background: Each year 413.000 new pediatric cancer cases are expected in children and adolescents aged 0-14 globally. The access to care is still a barrier to improve the survival rates in low and middle income countries (LMICs). Pediatric cancer registry is the essential element of pediatric cancer control. Here, we present the results of the 21 years of the pediatric cancer registry from Turkey. Methods: Turkish Pediatric Oncology Group and Turkish Pediatric Hematology Association has established the pediatric cancer registry in 2002. The childhood cancer cases registered between 2002-2022 was included in this analysis. International Childhood Cancer Classification System was used for the classification. Essential demographic findings, ICD-O-3 morphology and topography codes were recorded for each case. Results: During the 21 years from 2002 to 2022, 46067 cases were registered. For all cases, median age was 6.5 year (0-19; M/F 25079/20176, 6 hermaphrodite, 6 unknown). Age distribution was 0-4 yrs, 41.5%; 5-9 yrs, 24.7%; 10-14 yrs, 23.0%; 15-19 yrs, 10.7%) The distribution of the tumor types were [number of cases, percentage of total, median age yrs, M/F]: Leukemia (13190, 28.6%, 5.6, 7640/5550); Lymphoma & other RES tumors (8194, 17.8%, 9.1, 5435/2756, 1 hermaphrodite & 2 unknown); CNS [brain & spinal] (6606, 14.3%, 6.8, 3670/2935, 1 unkown); Symphatetic system (3411, 7.4%, 2.3, 1755/1656); Retinoblastoma (1386, 3.0%, 1.5, 726/660); Renal (2095, 4.5%, 3.1, 1032/1061, 1 hermaphrodite & 1 unknown); Liver (681, 1.5%, 2.1, 400/281); Malignant bone (2809, 6.1%, 12.5, 1569/1240); Soft tissue sarcomas (3209, 7.0%, 7.3, 1810/1399); Germ cell (2663, 5.8%, 8.6, 957/1700, 4 hermaphrodite, 2 unknown); Carcinoma & other malignant epithelial (1494, 3.2%, 13.0, 721/773); Other/non-specific malignant (329, 0.7%, 7.4, 164/165). Five year survival rate was found as 70.8% Conclusions: This is a successful example of a pediatric cancer registry from a middle income country covering the period of more than 20 years. The survival rates for children and adolescents have been improved to 70% which is comparable for middle income countries and reflects the level of the pediatric cancer care in Turkey. It became a valuable source for stakeholders in national and international level.