bluuebunny/crossref_metadata_2025_split huggingface dataset:
Patient human leukocyte antigen (HLA) genotype may predict response to anti-programmed death receptor 1 (anti-PD1) in advanced melanoma.
Authors: Oey Oliver , Khattak Muhammad Adnan , Abed Afaf , Meniawy Tarek , Reid Anna , Calapre Leslie , Millward Michael , Gray Elin 
Published: June 2021

e21512 Background: Anti-PD-1 therapy has improved the outcome of advanced melanoma patients with a 5-year survival rate of about 40-45%. However, biomarkers predictive of response to immune checkpoint blockade therapy are lacking. There is limited data on the utility of host germline human leucocyte antigen (HLA) genotype as a predictor of response to anti-PD-1 therapy in advanced melanoma. Here, we investigate the prognostic value of HLA in predicting survival outcomes of patients with unresectable locally advanced, metastatic melanoma on anti-PD-1 therapy. Methods: Blood was collected from 113 metastatic melanoma patients who were treated with anti-PD-1 therapy at two major oncology centres in Western Australia. High quality DNA was extracted from white blood cells and subsequently HLA-I and HLA-II typed using clinically validated assay. Univariate analyses were conducted using Cox regression model correlating homozygosity at HLA-I and HLA-II loci with overall survival (OS). HLA-A and HLA-B were classified into 12 supertypes and correlated with OS. Multivariate analyses were performed while controlling for age, gender, prior therapy, BRAF mutation status, ECOG performance status and presence of liver and brain metastases. Results: Homozygosity at HLA-I or HLA-II loci was not associated with OS. However, the absence of HLA-B62 supertype was associated with a trend towards improved OS (HR: 0.53 [95% CI:0.25-1.10]; P = 0.09) as reported previously. Notably, the absence of HLA-B27 supertype was associated with improved OS which was statistically significant (HR: 0.45 [95% CI:0.24-0.85]; P = 0.01). In multivariate analyses, the prognostic value of HLA-B27 supertype (HR: 0.38 [95% CI:0.19-0.76]; P = 0.006) was maintained, whereas the prognostic value of HLA-B62 supertype significantly improved (HR: 0.42 [95% CI:0.19-0.94]; P = 0.03). Conclusions: Our results suggest a limited role of HLA homozygosity in predicting survival of melanoma patients treated with anti-PD-1 therapy. However, we identified that the absence of HLA-B62 and HLA-B27 supertype is associated with improved survival benefit. Therefore, HLA-B27 and HLA-B62 supertype may be used as adjunct biomarkers of response to anti-PD-1 therapy in patients with melanoma in addition to PD-L1 status, pending validation in prospective randomised clinical trials.
Incidence of immune-related adverse events with pembrolizumab in advanced melanoma and correlation with treatment response: A single institution review of irAEs.
Authors: Myrdal Caitlyn N. , Mehta Paras , Smith Eric , Briones Kimberly , Albright Jason , Curiel-Lewandrowski Clara , McBride Ali , Sundararajan Srinath 
Published: June 2021

e21519 Background: Anti-PD-1 therapy has become a mainstay of advanced melanoma treatment. However, associated irAEs are common and contribute to significant delays or cessation of treatment. In this retrospective cohort study, we aim to characterize the real-world irAE profile of pembrolizumab at our institution and its prognostic implications. Methods: We evaluated unresectable stage III-IV melanoma patients treated with pembrolizumab between 2011 and 2016 at the University of Arizona Cancer Center (UACC). Information regarding demographics, treatment, irAEs, and hospitalizations were recorded. Adverse events were graded using the common terminology criteria for adverse events v.4.0 (CTCAE). Results: Seventy-three patients were identified, 4 (5.5%) with unresectable stage III and 69 (94.5%) with stage IV melanoma. The median age was 68; 48 (65.8%) patients were male and 25 (34.2%) were female. Nineteen patients (26.0%) had a preexisting autoimmune disorder. 171 irAEs were identified in 58 of the patients. 141 (82.5%) were Grade 1, 24 (14.0%) were Grade 2, and 6 (3.5%) were Grade 3. Incidence and time to onset of significant events is displayed in Table. Eleven (15%) patients were hospitalized, and 8 patients (11.0%) stopped treatment due to an irAE. Sixteen (84.2%) patients with a preexisting autoimmune condition experienced an irAE versus 78% of patients without an autoimmune condition. Twelve patients (75%) had an exacerbation of their autoimmune condition. Response could be assessed in 67 patients . 30 patients of the 67 (45%) had a CR or a PR and 37 patients (55%) had progressive disease (PD). 58 of 67 (87%) experienced an irAE. 29 (50%) of the 58 irAE patients had PD, while 8 (88.9%) of the 9 non-irAE patients had PD. The relative risk of progression in patients who experienced an irAE versus who did not was 0.56 (95% CI: 0.39-0.79, p= 0.001). Conclusions: Experience with pembrolizumab at our institution suggests a similar irAE profile compared to landmark trials, though we observed a higher percentage of patients who required discontinuation of pembrolizumab (11% versus 5% in Phase III trials). In our retrospective study, the risk for progression was significantly higher in patients without irAE versus with any irAE, suggesting that development of irAE could be a positive prognostic sign.[Table: see text]
RECQL5 mutations as a potential efficacious predictor of immunotherapy in melanoma patients.
Authors: Zhao Yun , Fan Dandan , Huang Xiaochun , Huang Mengli , Chen Yaoxu , Bei Ting 
Published: June 2021

e21547 Background: Gene mutations in DNA damage repair (DDR) pathway were reported to affect the clinical response to immune checkpoint inhibitors (ICIs) by driving mutagenicity. Previous studies showed that RECQL5 is involved in RAD51-mediated strand invasion for homologous recombination DNA damage repair (HR-DDR). RECQL5 encoding RecQ protein-like 5 (RECQL5) is a member of RecQ helicase family and was discovered to play a tumor-suppressive or oncogenic role in various cancers. However, the association between RECQL5 mutation and ICI efficacy has not been revealed. Methods: Data of nine publicly independent cohorts of NSCLC, melanoma, and pan-cancer were retrieved (Rizvi, MSKCC, OAK/POPLAR, Van Allen, Hugo, Synder, Miao and Samstein cohorts) to investigate the correlation between RECQL5 mutations and clinical events including overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and clinical benefit rate (CBR). Wilcoxon test was used for comparing tumor mutational burden (TMB) between RECQL5-mutated patients and their wild-type counterparts. In addition, the correlation between infiltration of immune cells and RECQL5 mutation status was also analyzed by QUANTISEO using data of SKCM cohort (n=466) from TCGA database. Statistical significance was set at P = 0.05. Results: RECQL5 mutations were most commonly seen in melanoma patients and the detection rate was 4%-8% in melanoma patients from cohort Van Allen, Hugo, Synder, and Miao. RECQL5 mutation was not detected in other cancers except for one lung cancer case. In the three melanoma cohorts (Van Allen, Synder, Miao) with OS data available, the OS of the RECQL5-mutated patients was 2 to 3 times longer than that of the RECQL5-wt patients. In Synder cohort, the difference in OS between these two subsets was statistically significant (53.9 months vs 25.0 months, P = 0.045). In addition, the occurrence of RECQL5 mutations was correlated with higher CBR both in Miao ( P = 0.017) and Synder cohorts ( P = 0.011). No difference was observed in the PFS or ORR between these two subsets. Notably, RECQL5 mutations were associated with higher TMB levels both in Miao (32.6 mut/Mb vs 7.9 mut/Mb, P = 0.016) and Synder cohorts (1124 mut/Mb vs 358 mut/Mb, P = 0.033). Moreover, RECQL5 mutations were found to be correlated with increased infiltration of CD4+ T cells (no-regulatory) ( P = 0.037), B cells ( P = 0.13) and decreased infiltration of regulatory CD4+ T cells ( P = 0.02) in RECQL5-mutated tumors over RECQL5-wt tumors. Conclusions: RECQL5 mutations can serve as a potential predictor for a durable response to ICIs in melanoma. Moreover, the occurrence of RECQL5 mutations was correlated with higher TMB level as well as infiltration of immune cells, indicating the underlying mechanism of its predictive effect.
Effect of time to surgical intervention in stage 3 cutaneous melanoma.
Authors: Pairawan Seyed Saeed , Selleck Matthew J. , Caba Molina David , Solomon Naveenraj Livingstone , Reeves Mark Evan , Garberoglio Carlos A. , Namm Jukes P. 
Published: June 2021

e21571 Background: Delay in surgical resection has been found to be associated with poorer overall survival (OS) in patients with stage 1 cutaneous melanoma. However, the impact of surgical timing on survival in stage 3 cutaneous melanoma remains unknown, especially in the era of immunotherapy. We sought to evaluate to the effect of time to definitive surgical intervention on OS in stage 3 cutaneous melanoma at Commission on Cancer accredited institutions. Methods: The National Cancer Database (2012-2016) was used to identify patients who underwent biopsy and definitive surgical intervention of cutaneous melanoma. Time to intervention (TTI) was analyzed from the time of initial biopsy to definitive surgical resection and classified into quartiles, (Q1≤22 days; Q2 = 23-33 days; Q3 = 34-49 days; Q4≥50 days) using χ2 and multivariable logistic regression. Survival was analyzed using Kaplan-Meier and Cox proportional hazard models. Results: We analyzed 4560 patients with a median age of 61 years (18-90) and most patients being non-Hispanic white and male (91.6% and 63%, respectively). Median Breslow thickness was 2.8 mm (0-9.8 mm). Median TTI was 33 days (0-352 days) with a mean OS of 52, 49.8, 48.4, 48.3 months for Q1 to Q4 respectively (p = 0.008). Age ≤50 years, treatment at a comprehensive community cancer center and only 1 positive lymph node (LN) were all associated with Q1 TTI (p = 0.002, p < 0.001 and p < 0.001, respectively). Black race, treatment at an academic facility, > 4 LN positive, > 4 mm thickness, and no administration of immunotherapy were all associated with Q4 TTI (p = 0.002, p < 0.0001, p < 0.0001, p < 0.0001 and p < 0.0001 respectively) on univariate analysis. Patients in Q4 TTI were more likely to be older (OR 1.01, 95% CI 1.00-1.02, p = 0.01), have T2-T4 tumors (OR 1.6, 95% CI 1.2-2.2, p < 0.001), and be treated at an academic facility (OR 2.4, 95% CI 1.8-3.5, p < 0.001) on multivariable analysis. In the survival analysis, multiple positive LNs (2, 3-4, > 4 LNs; HR 1.4, 1.6 and 2.9, p < 0.001), lymphovascular invasion (HR 1.4, p < 0.001), Breslow thickness > 4 mm (HR 1.7, p < 0.001), Charlson-Deyo score ≥2 (HR 1.5, p < 0.001), increasing age (HR 1.03, p < 0.001), and longer TTI (Q3-Q4) (HR 1.2, p = 0.001) were all associated with worse OS. There was no difference in survival based on TTI in patients who had received adjuvant immunotherapy in Q1-Q2 vs Q3-Q4 (p = 0.3). Conclusions: In stage 3 cutaneous melanoma, longer TTI ( > 33 days) was associated with worse OS but may be due to older age, higher T stage, and barriers to access. However, adjuvant immunotherapy may offer protection from delays in definitive surgery.
Improved risk stratification in an adjuvant radiation therapy (ART) eligible cutaneous squamous cell carcinoma (cSCC) patient population by integration of the 40-gene expression profile prognostic test (40-GEP).
Authors: Koyfman Shlomo A. , Wysong Ashley , Arron Sarah , Somani Ally-Khan B. , Siegel Jennifer , Fitzgerald Alison , Kurley Sarah J. , Goldberg Matthew S. , Schmults Chrysalyne , Newman Jason 
Published: June 2021

e21589 Background: Although cure rates are high for cSCC, an estimated 2-6% of cSCC patients will develop regional/distant metastasis and due to high incidence, mortality levels are similar to melanoma. ART is used for high-risk cSCC (HRcSCC) patients to reduce the risk of recurrence and/or metastasis, but guidelines are confounding and lack clarity regarding which patients may benefit from ART. The 40-GEP test has been validated to predict a patient’s risk for regional/distant metastasis: Class 1-low; Class 2A-moderate; and Class 2B-high risk for metastasis. We hypothesize that a 40-GEP Class result could help further stratify patient risk within an ART-eligible population. Methods: Using criteria within NCCN guidelines and other high-risk features to determine ART-eligibility, 86 cases of the 420 HRcSCC patients having known outcomes from the 40-GEP multicenter validation cohort were identified. Criteria included patients presenting with two or more risk factors: tumor diameter ≥2 cm, poor differentiation, perineural invasion ≥0.1 mm, invasion beyond subcutaneous fat, and immunosuppression. Kaplan-Meier survival analysis and log rank test were used to assess metastasis free survival (MFS). Univariate Cox regression compared metastasis rates between 40-GEP Class results. Results: The 3-year MFS rate for the overall ART-eligible cohort was 65% (n = 86, 32 events, 95% CI: 56 – 76%). The 40-GEP demonstrated statistically significant stratification of risk with MFS rates of 79%, 63% and 33% for Class 1, Class 2A and Class 2B, respectively (p = 0.005). Cox regression was significant between Class 1 and Class 2B 40-GEP results (p = 0.002), with Class 2B having a 4.59-fold increase in metastases. 40% (34/86) of the cohort received a Class 1 result, highlighting HRcSCC patients who may be considered for reduction or avoidance of ART. In 14% (12/86) of cases with a Class 2B result, 2 of 3 patients went on to have metastasis and thus may be appropriate for more aggressive intervention in the setting of a clinical trial. Those cases meeting eligibility for 40-GEP testing but not ART-criteria (n = 334) and with a Class 2B result (n = 11) had a 64% MFS rate, similar to the ART-eligible population. Conclusions: The 40-GEP test stratifies a patient’s risk of regional and/or distant metastasis in patients for whom ART is typically considered. Incorporation of 40-GEP testing may help guide patient management decisions in HRcSCC by potentially decreasing over-treatment of patients with HRcSCC and identifying patients with otherwise lower risk disease who may benefit from ART and/or other adjunctive therapies.
Extremity bone sarcoma: Evolution from primary amputation to limb salvage surgery (LSS).
Authors: Rao Bhaskar N. , Neel Michael D. , Abdel-Hafeez Hafeez , Murphy Sandra 
Published: June 2021

e22012 Background: Primary Extremity Bone Sarcomas (PEBS) were historically managed by upfront amputation. Early success rates utilizing neoadjuvant chemotherapy followed by LSS showed promise in halting disease progression and achieving local control. This prompted surgical oncologists to consider LSS in more patients. In anatomic locations for which no functional reconstruction exists, amputation is still considered the best option. Oncologic control, patient satisfaction and improved function are the primary goals of LSS. Three Dimensional CT and MRI have made for more accurate surgical planning, ensuring adequate margins and improved local control. Methods: Between January 1983 and December 2019 the senior author (BNR) has performed, or mentored over 590 LSS worldwide.Improvement in imaging modalities has been the most important advancement contributing to decreasing tumor margins. Initially bone scans determined the margins at 7cm. In the 1970s CT became the modality used to determine local tumor extent. The resection margins were reduced to 5 cm. The early 90’s saw MRI as the main imaging modality. Margins are now set at 1-2cm.LSS was initiated in the mid 80’s using the strict criteria of age > 13, no metastasis, intramedullary extension less than 50%, and small extraosseus extent. Results: Of the 134 cases enrolled through 1990, the local control rate was 90%. Between July 1991 through December 2019, 388 patients enrolled in bone sarcoma protocols, 354 patients underwent LSS ( > 95%). The primary site was the femur (171 cases, 43%) Histological Diagnosis was OS in 93%. Ages ranged from 3-25 years (median 10.8 years) The average length of tumor resection was 7cms(range 1-38cms). 5 patients presented with pathological fracture. All successfully underwent LSS without an increase in local recurrence. Intraoperative complications included, excessive hemorrhage defined as > 10%of blood volume in 88 patients, 25%, Vascular injuries requiring repair in 9 patients, post operative neuropraxia in 28 patients. Mid and late term complications included, Superficial wound infection in 45 patients (19 requiring some surgical intervention), Deep wound problems were identified in 11 patients ( 3 required subsequent amputation), 9 patients had their prosthesis revised due to refractory infection, Local relapse in 5 patients , < 1%. Long term implant related complications, loosening of the prosthesis in 16 , Stem fracture in 13, nonunion of the allograft in 3 patients. Conclusions: Disadvantages are the need for repeat surgeries consequent to either growth discrepancy, loosening, or implant fracture.LSS is feasible in over 95% of patients, complications are generally manageable. Successful oncologic results, satisfaction and function are readily obtained. Early rehabilitation is key to functional success.
Evaluation of age, gender, prenatal characteristics, and treatment results of 380 babies with infantile hemangioma.
Authors: Suzen Orhan Eda , Unal Emel Cabi , Tacyildiz Nurdan , Dincaslan Handan 
Published: June 2021

e22018 Background: Infantile hemangiomas' incidence is 5% & are locally proliferated vascular structures. Methods: Fourhundred cases were analyzed,380 are presented. Results: Majority pts dx between 0-3 mos(88.8%), females (64.5 %), 26.6% had preterm birth,21.8% lbw 2500g. Maternal characteristics 17.1% were > age35, 8.5% multipar, 61.5% multiple gestation. Placental anomaly in 5.5%, preeclampsia in 10.3%, gestational diabetes in 7%, intervention in pregnancy 4.9%, smoking 7.6%, hyperemesis 29.9%. Treatment modality was topical timolol drops in 41.9%, oral propranolol solution in 37.6%, wait&see group 13.5%,surgical excision in 5.6%. Conclusions: Hemangioma, a multifactorial disease, lbw is an important risk factor.Oral propranolol solution for the babies <1yr of age avoided the use of intralesional steroids. It is essential to treat the babies especially who have the risk of developing amblyopia or other functional/cosmetic sequelae.
Pediatric cancer registry in Turkey 2009-2020 (TPOG & TPHD).
Authors: Kutluk M. Tezer , Yeşilipek Akif 
Published: June 2021

e22519 Background: Global actions on pediatric cancer control is targeting to improve the survival rates in low and middle income countries which already exceeded 80% in high income countries. Almost 300.000 pediatric cancer cases annually are expected in children and adolescents aged 0-14 globally. Pediatric cancer registry must be a priority within the pediatric cancer control programs. Here, we present the most updated results of the pediatric cancer registry in Turkey. Methods: Pediatric cancer registry has been established by the Turkish Pediatric Oncology Group and Turkish Pediatric Hematology Association in 2002. The childhood cancer cases registered between 2009-2020 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 12 years from 2009 to 2020, 21792 cases were registered. For all cases, median age was 6.7 year (0-19; M/F 12198/9584, 4 hermaphrodite, 6 unknown). Age distribution was 0-4 yrs, 40.9%; 5-9 yrs, 23.7%; 10-14 yrs, 23.4%; 15-19 yrs, 12.0%) The distribution of the tumor types were [number of cases, percentage of total, median age yrs, M/F]: Leukemia (5208, 23.9%, 5.5, 3004/2204); Lymphoma & other RES tumors (4103, 18.8%, 9.8, 2733/1367, 1 hermaphrodite & 2 unknown); CNS [brain & spinal] (3269, 15.0%, 6.8, 1794/1474, 1 unkown); Symphatetic system (1794, 8.2%, 2.4, 933/861); Retinoblastoma (610, 2.8%, 1.4, 339/271); Renal (1079, 5.0%, 3.1, 524/553, 1 hermaphrodite & 1 unknown); Liver (376, 1.7%, 2.2, 216/160); Malignant bone (1448, 6.6%, 12.5, 787/661); Soft tissue sarcomas (1554, 7.1%, 7.6, 888/666); Germ cell (1461, 6.7%, 9.3, 547/910, 2 hermaphrodite, 2 unknown); Carcinoma & other malignant epithelial (745, 3.4%, 13.5, 362/383); Other/non-specific malignant (145, 0.7%, 7.9, 71/74). Five year survival rate was found as 72%. Conclusions: This registry shows the imrovement of survival rates to 72% in Turkey which is comparable with middle income countries. The pediatric cancer control community is investing on the control of childhood cancer for further improvement and this registry became a valuable source for pediatric oncology community at national and international level.
The impact of an expert exchange-based educational initiative on urologist confidence and knowledge in implementing immunotherapy for bladder cancer.
Authors: Gitzinger Susan H. , Taylor Bryan Carson , Fowler Joan B. , Carranza Vanessa , Weaver Rebecca 
Published: June 2021

e23001 Background: The rapid and robust emergence of the immunotherapy era in bladder cancer has prompted a paradigmatic shift in both early and late-stage bladder cancer management. Given this change, it is imperative that members of the bladder cancer care team, most notably urologists, medical oncologists, and urologic oncologists, be well-equipped to safely and effectively integrate immune checkpoint inhibitors into the treatment armamentarium. Methods: CEC Oncology delivered education at select meetings throughout 2019-2021 including ASCO GU, AUA, and SUO Annual Meetings; in addition to live presentations, the content was streamed live and on-demand on www.ceconceptslive.com and endured on myCME.com. Learning and knowledge was objectively assessed by analyzing pre- and post-test results before and after the educational activities. To determine retention of knowledge over time, follow-up assessments were sent to participants after each live activity. Assessment questions in the form of case studies were utilized to gauge whether participants translated knowledge into practice at follow-up. Statistical testing between pre- and post-tests and from pre-test to follow-up were conducted via chi square analysis with a priori significance set at 0.05. Results: Executed five live educational activities and a spin-off enduring component hosted on myCME.com. 765 total clinicians educated across the live elements of the curriculum. Across the curriculum, over 70% of attendees indicated at post-activity assessment that they would use systemic immunotherapy either primarily or exclusively in their practice compared to just 25% at pre-activity. Among urologists practicing at academic medical centers, confidence in appropriate implementation of immunotherapy increased for all participants, and more specifically, for clinicians practicing at academic medical centers (on a 4-point scale, All Participants demonstrated a confidence increase from 2.70 to 2.91; Academic Medical Center clinicians demonstrated an increase of 2.75 to 3.00); 97% said that the initiative increased their knowledge of ongoing ICI clinical trials in bladder cancer; Attendee ability to appropriately manage an irAE increased substantially from pre-test to post-test assessment (37% vs. 63%; P=.057). Clinicians practicing in community settings are the only attendees who did not exhibit an increase in mean confidence in appropriately implementing immunotherapy at post-activity assessment. Conclusions: Our Expert Exchange Bladder Cancer Curriculum precipitated substantive practice advances related to appropriate implementation of ICI therapy. Many of these advances, however, were specific to academic urologists and urologic oncologists; outcomes analyses have revealed tangible educational gaps among community-based urologists.