bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prediction of immunotherapy response by integrating immune infiltration and neoantigen presentation score in late-stage melanoma.
Authors: Li Bailiang , Abbott Charles , McDaniel Lee , Pyke Rachel Marty , Navarro Fabio , Anbunathan Hima , Bartha Gabor , Harris Jason , Snyder Michael , Jang Sekwon , Boyle Sean Michael , Chen Richard 
Published: June 2022

e21554 Background: Single modality biomarkers such as tumor mutational burden (TMB) fail to reliably predict response to immune checkpoint blockade (ICB) in part due to their incomplete characterization of complex tumor-immune interactions impacting response. We previously developed the composite biomarker, neoantigen presentation score (NEOPSTM), which integrates neoantigen processing and presentation information and showed it outperformed TMB and other single analyte biomarkers in predicting response in melanoma. Here we combined NEOPS with tumor immune infiltration analysis, and demonstrated further improved patient stratification for ICB response. Methods: We assessed the effect of 17 different immune and stromal cells on NEOPS using logistic regression with interactions in a retrospective cohort of 45 stage III/IV melanoma patients who underwent anti-PD-1 therapy. NEOPS and immune cell infiltration status were both generated using Personalis’ ImmunoID NeXT Platform®. The identified immune-selected phenotype that had a significant effect on NEOPS performance was validated in a cohort of 109 anti-PD1 treated late-stage melanoma patients. Results: The predictive strength of NEOPS was enhanced by considering the infiltration status of 4 distinct immune cell types derived from expression signatures: naïve CD4/CD8 T, exhausted CD8 T, and CD8 T cells. Highly correlated cells were aggregated into naïve (naïve CD4/8 T) and CD8 (exhausted and CD8 T) features. Both features independently boosted the accuracy of NEOPS in the validation cohort (naïve: Pint. = 0.048; CD8: Pint. = 0.11). In immune-selected patients in the validation cohort displaying both high naïve and CD8 features, NEOPS achieved an improved accuracy of 77.2% (vs 69.7% baseline performance, P = 0.013) and an AUC of 0.74 (vs 0.66, P = 0.055). In anti-CTLA4 treatment naïve patients, the immune-selected group attained even better NEOPS performance, with an accuracy of 81.8% (vs 70.6%, P = 0.015) and an AUC of 0.89 (vs 0.68, P = 0.005) in the validation cohort. A separate approach integrating NEOPS with naïve and CD8 features into a single composite biomarker resulted in an AUC of 0.82 (cross validation: 0.78 vs 0.71 baseline). Conclusions: Stratifying immune-selected patients based on cellular composition of the tumor microenvironment significantly increased the accuracy of our neoantigen-based biomarker of ICB response, NEOPS. These data highlight the potential for combining tumor microenvironment information with neoantigen analysis into a composite biomarker to provide more sensitive prediction of immunotherapy response.[Table: see text]
A tool to predict survival outcomes and guide adjuvant immunotherapy recommendations for patients with stage II melanoma.
Authors: Varey Alexander , Long Georgina V. , Scolyer Richard A. , Gershenwald Jeffrey E. , Simon Julie , Thompson John F. , Lo Serigne N. 
Published: June 2022

e21556 Background: Patients diagnosed with AJCC stage II melanoma have a 10-year melanoma specific survival (MSS) of 84%, ranging from 88% for stage IIA to 75% for stage IIC. The 12%-25% rate of melanoma mortality correlates with the rate of recurrence for these patients. Current prognostic tools are based on the AJCC 8th Edition (AJCC-8), which gives MSS based on tumor thickness and ulceration status but does not consider any other patient or tumor characteristics. The rate of recurrence-free survival (RFS) may be more important than MSS in deciding whether a patient should be offered adjuvant immunotherapy. We have therefore developed a risk prediction tool to assist in this process. Methods: Data were extracted from a large Australian melanoma treatment center research database for patients diagnosed with stage II melanoma (n = 3243). Parameters included: age, sex, tumor thickness, mitotic rate, ulceration status, lymphovascular invasion, presence of tumor infiltrating lymphocytes, regression, sentinel node status, presence of satellites, body site, recurrence (including time to event) and date of last follow-up. Multivariable Cox regression analyses were performed to develop models for survival prediction. These were then externally validated using a dataset from a large US melanoma treatment center (n = 703). Discrimination and calibration of each model were assessed using the C-statistics and calibration plots respectively. Results: The table shows the C-statistics for the Australian RFS model and the AJCC-8 staging, along with validations. These demonstrated statistically significant discrimination gains by using the Australian model over the AJCC model, which ranged from 8.3% to 12.2%. The Australian model was well calibrated. Conclusions: There was good discrimination of the RFS model for individual patients over both 5 and 10 years, which held true on external validation. This model offers considerable improvement in discriminative accuracy for predicting RFS compared to using the AJCC-8 staging and therefore may be clinically useful to guide adjuvant immunotherapy recommendations. An online tool will be made available at www.melanomarisk.org.au.[Table: see text]
The drug targets genomic alterations detected in female tumor tissue with melanoma.
Authors: Li Zhongwu , Wang Xintong 
Published: June 2022

e21558 Background: Due to the rapid development of next-generation sequencing (NGS) and precision medicine, molecularly driven targeted therapy, for different tumor types, plays an important role in cancer patients with drug targets. mucosal melanoma (MM) is aggressive disease with a poor prognosis. there are few studies focusing on its target drug. Methods: We enrolled female patients with melanoma (n = 24) from 2019.** to 2021.** cancer database with a gynecological tumor site. Subsequently, we chose to use WES sequencing to predict possible targets in patients. Results: In all mutations of the 24 melanoma patients, we screen the mutations about the drug targets. And the result shown that BRAF somatic mutations were identified in 6 of the 24 samples (25%), which are the highest frequency drug targets. V600E substitutions accounted for 3 (50%) of these mutations as target drug. Other activating mutations at NRAS codons 61 and 12/13 were lower frequent (Q61*, n = 3; G13D, n = 1; G12A, n = 1). TP53 and TOP2B were mutated in 4(16%) tumors were found as drug targets. Conclusions: This study aimed to analyze the target drug interaction of MM in China and lay a support for targeted therapy. NGS in MM is feasible with potential impact in half of our cohort. Earlier testing and improved trial drug from drug bank database access is necessary to increase the like hood that MM patients may benefit from drug target guided therapy.
Real-world changes in the clinical management of resected stage III melanoma at high risk of local recurrence in the era of modern systemic therapies.
Authors: Kibel Seth , Kuehne Nathan , Ribeiro Mauricio , Pimentel Muniz Thiago , Wong Philip , Spreafico Anna , Hogg David , Saibil Sam , Sun Alexander , Mak David Y. , Gray Diana , Butler Marcus O. 
Published: June 2022

e21575 Background: Adjuvant systemic therapies (ST) for patients with resected stage III melanoma have improved relapse-free survival; however, the role of adjuvant radiotherapy (RT), previously the mainstay adjuvant treatment, is undefined in the modern ST era. Real-world data detailing clinical practice changes and its impact on outcomes are needed to help inform the choice of adjuvant therapy for patients with resected stage III melanoma. Methods: In this single-center retrospective study, patients from Princess Margaret Cancer Centre with resected stage III cutaneous melanoma treated between 2010 and 2019 and fitting the 2016 Cancer Care Ontario guidelines for adjuvant RT were included. Demographic, pathological, and clinical data were abstracted from electronic medical records. PFS was defined as the time from lymph node dissection to local-regional recurrence in the treated nodal basin or distant recurrence. OS was defined as time from lymph node dissection to death by any cause. The Log-rank method was applied to assess survival endpoints. A p-value < 0.05 was considered statistically significant. Results: From 4,959 records reviewed, 109 patients were identified. Median age at time of surgical resection was 59.4 years (23.6-89.8), and 74 (68%) were male. Type of adjuvant therapy and number of local-regional recurrences (LR) are expressed in the table. The median follow-up among those alive at last follow-up was 54.2 months (range 1.9-122). The proportion of patients receiving adjuvant RT was higher between 2010 and 2014 than it was between 2015 and 2019 (59% to 26%), whilst the proportion of those receiving adjuvant ST progressively grew (3% to 50%). LR > 90 days following lymph node dissection as the first site of relapse or synchronously with progression to metastatic disease was rare in patients treated with either adjuvant RT (6.8%) or adjuvant ST (14.3%, chi-square p = 0.33). Median progression free survival was 12.3 months in patients treated with adjuvant RT and 43.8 months in patients treated with adjuvant ST (p = 0.007). Overall survival was not significantly different (p = 0.08). Conclusions: The advent of ST has changed our institution’s clinical practice with ST replacing RT as the primary adjuvant treatment modality. Our data suggests that in the current adjuvant treatment landscape, omission of RT does not seem to increase rates of local-regional recurrences, and patients with resected stage III melanoma can be safely spared from adjuvant RT without detrimental effect on survival.[Table: see text]
The association of Ki67 level and adjuvant treatment options in mucosal melanoma.
Authors: Wei Xiaoting , Tang Lirui , Li Caili , Bai Xue , Mao Lili , Chi Zhihong , Cui Chuanliang , Lian Bin , Tang Bixia , Du Yu , Wang Xuan , Sheng Xinan , Yan Xieqiao , Li Siming , Zhou Li , Kong Yan , Dai Jie , Guo Jun , Si Lu 
Published: June 2022

e21582 Background: Both chemotherapy and high-dose IFN-α2b (HDI) are effective treatment options in adjuvant setting for patients with resectable mucosal melanoma (MM). However, it is still unknown whether Ki67 level affects the selection of chemotherapy and HDI. Methods: Data from resected MM patients diagnosed as MM in Peking Cancer Hospital, were retrospectively collected and analyzed. Key inclusion criteria were: (1) diagnosed as resectable MM, with the date between Jan. 1, 2010, and Dec. 31, 2018; (2) Ki67 was identified by immunohistochemical staining; (3) received TMZ-based adjuvant chemotherapy or HDI. All patients were divided into two subgroups according to the Ki67 level proposed by previous publications: low (< 30%), high (> = 30%). Relapse-free survival (RFS) and melanoma-specific survival (MSS) were compared across different subgroups by log-rank tests. Multivariate Cox proportional hazards models were used to calculate hazard ratios (HRs), controlling for age, sex, primary site, lymphatic metastasis, LDH level, and gene mutational status (BRAF, c-KIT and NRAS). Results: In total, 1106 MM patients were screened and 175 met the inclusion criteria for analysis. 100 and 75 patients received temozolomide (TMZ)-based adjuvant chemotherapy and HDI therapy, respectively. Patients who received adjuvant chemotherapy had a superior RFS (21.0 vs. 9.6 months, HR = 0.47, P = 0.002) as compared to those with HDI, but no significant difference for MSS (45.9 vs. 37.6 months, HR = 0.63, P = 0.396). Longer RFS and MSS were observed in the ki67-low subgroup (HRs were 0.51, 95%CI 0.34-0.76 and 0.41, 95%CI 0.24-0.68 for RFS and MSS, respectively). For patients with low Ki67 (< 30%), two regimens showed no statistically different RFS (33.9 vs. 22.7 months, HR = 0.76, P = 0.329) and MSS (114.5 vs. 61.4 months, HR = 1.23, P = 0.967). However, for those with high Ki67, TMZ-based chemotherapy achieved an extended RFS compared with HDI (18.0 vs. 6.7 months, HR = 0.36, P < 0.001) and a trend toward improvement for MSS (41.4 vs. 25.1 months, HR = 0.47, P = 0.067). Conclusions: Ki67 level is an independent negative prognostic factor and impacts the selection of adjuvant treatment options for MM patients. Chemotherapy should be considered as the preference for patients with Ki67 > = 30%.
Optic pathway gliomas in children: Demographic, clinical characteristics, and results of an adapted protocol.
Authors: Kebudi Rejin , Yıldırım Ulku Miray , Iribas Ayca , Tuncer Samuray 
Published: June 2022

e22016 Background: Optic pathway gliomas (OPG) constitute 1-5% of childhood brain tumors. The presence of neurofibromatosis type 1 (NF-1) is generally associated with more indolent disease. The aim of this study is to evaluate patients with optic pathway gliomas diagnosed/treated/ followed in a single center over 32 years. Methods: The medical files of 85 patients with OPG diagnosed/treated between 1990-2021 in the Istanbul University, Oncology Institute were retrospectively assessed for demographic, clinical characteristics, treatment and outcome. Results: The median age of the 85 patients (42 male, 43 female) was 60 (1-216) months, 53 (62.4%) had NF-1. Seven had diencephalic syndrome (8.2%). According to Dodge classification, 23 (27.1%) had Dodge 1, 30 (35.3%) Dodge 2 and 32 (37.6%) Dodge 3 disease. Median follow up time was 10.5 years (1-31 years). Twenty (23.5%) patients had stable disease and were followed without treatment, 14 patients underwent surgery (5 gross total tumor resection, 2 subtotal resection, 3 ventriculoperitoneal shunt operation, 4 excision/biopsy). 7 patients recieved radiotherapy (RT), none had NF1. 56 patients received chemotherapy (CT) due to severe/progressive clinical symptoms (such as diencephalic syndrome, visual impairment, nystagmus) or radiologic progressive disease. Chemotherapy consisted of an adapted SIOP-LGG regimen: vincristine (VCR) 1.5 mg/m²/dose and carboplatinum 550 mg/m²/dose every 21 days for three courses with weekly VCR, followed by VCR and carboplatinum every 28 days for a total of 12 cycles (3 cycles induction, 9 cycles consolidation). Vinblastin or cisplatinum with etoposide were used for second line or further treatment in progressive disease. One of the seven patients who had diencephalic syndrome and two of the 3 patients with leptomeningeal metastasis died. Ocular findings were recorded in 47 patients: vision was stable in 30 (63.8%), improved in 15 (31.9%), detoriated in 2 (4.3%). Radiology (MRI) revealed stable disease/regression of tumor in 41 patients, and complete regression of spinal metastasis in 1 patient. Endocrinologic follow-up was done and 13(15.2%) recieved hormonal treatment. Ten year overall survival(S) in all patients, in patients with NF1 and without NF1 were 96.5%, 96.1% and 95%, respectively; 10 year event free survival (EFS) in all patients, in patients with NF1 and without NF1 were 80.6%, 90.5% and 60% (p:0.001) respectively. Conclusions: OPG may remain indolent for many years after diagnosis, especially in patients with NF 1. However, these tumors develop progressive characteristics and can cause visual disturbances, endocrine dysfunction, blindness and even death among some of the patients. In young children who are symptomatic/have progressive disease, chemotherapy with an adapted regimen consisting of vincristine and carboplatinum seems to be effective and provides a relatively good quality of life.
Pediatric Cancer Registry in Turkey 2009-2021 (TPOG & TPHD).
Authors: Kutluk M. Tezer , Yeşilipek Akif 
Published: June 2022

e22020 Background: The pediatric cancers is in the global agenda to improve the survival rates which is still low in LMICs although it is more than 80% in HICs. More than 300.000 pediatric cancer cases annually are expected in children and adolescents aged 0-14 globally. Registry is the first step of an efficient cancer control. Here, we present the most updated results of the pediatric cancer registry fromTurkey. Methods: Turkish Pediatric Oncology Group and Turkish Pediatric Hematology Association has established the pediatric cancer registry in 2002. The childhood cancer cases registered between 2009-2021 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 13 years from 2009 to 2021, 24080 cases were registered. For all cases, median age was 6.7 year (0-19; M/F 13461/10609, 4 hermaphrodite, 6 unknown). Age distribution was 0-4 yrs, 40.8%; 5-9 yrs, 23.8%; 10-14 yrs, 23.3%; 15-19 yrs, 12.1%) The distribution of the tumor types were [number of cases, percentage of total, median age yrs, M/F]: Leukemia (5819, 24.2%, 5.5, 3366/2453); Lymphoma & other RES tumors (4446, 18.5%, 9.8, 2956/1487, 1 hermaphrodite & 2 unknown); CNS [brain & spinal] (3730, 15.5%, 6.8, 2061/1668, 1 unkown); Symphatetic system (1965, 8.2%, 2.3, 1010/955); Retinoblastoma (675, 2.8%, 1.4, 375/300); Renal (1160, 4.8%, 3.1, 557/601, 1 hermaphrodite & 1 unknown); Liver (409, 1.7%, 2.2, 234/175); Malignant bone (1584, 6.6%, 12.6, 864/720); Soft tissue sarcomas (1726, 7.2%, 7.7, 983/743); Germ cell (1593, 6.6%, 9.6, 588/1001, 2 hermaphrodite, 2 unknown); Carcinoma & other malignant epithelial (804, 3.3%, 13.5, 381/423); Other/non-specific malignant (169, 0.7%, 7.9, 86/83). Five year survival rate was found as 72.3%. Conclusions: The registry shows that the survival rates for children and adolescents have been improved to 72% which reflects the status of the pediatric cancer care in Turkey. The data from this work became a valuable source for all stakeholders in national and international level working on improvement the pediatric cancer control.
Symptom profiles and health care utilization in long-term survivors of Survivors of Childhood Childhood Cancer Survivor (CCSS) study.
Authors: Webster Rachel Tillery , Liu Wei , McGrady Meghan Eileen , Alberts Nicole M. , Brinkman Tara M. , Ness Kirsten K. , Fuemmeler Bernard , Kunin-Batson Alicia , Srivastava Deokumar , Huang I-Chan , Armstrong Gregory T. , Howell Rebecca M. , Green Daniel M. , Yasui Yutaka , Krull Kevin R. 
Published: June 2022

e22024 Background: Physical and psychological symptoms co-occur among survivors of childhood cancer, and subgroups with high symptom burden may be at increased risk for problematic healthcare utilization (HCU). Methods: Childhood Cancer Survivor Study participants (N = 17,231; Mean [SD] age = 27.4 [5.98]; 79% non-Hispanic White; 48% female) self-reported sensory, motor, cardiac, respiratory, pain, gastrointestinal, fatigue, memory, depression, and anxiety symptoms at baseline evaluation and latent class analysis identified symptom profiles. Chronic health conditions (CHCs) at baseline (graded per CTCAE 1-2 [mild or moderate; reference] vs 3-4 [severe-life threatening or disabling). HCU (no health care, general care, oncology-focused, long-term follow-up, emergency room visit) for the past 2 years was assessed 6.3 median years after baseline. Logistic regressions examined associations between class membership and follow-up HCU, adjusted for sex, age, health insurance and CHCs. Results: Five symptom classes were identified: 1) Global symptoms (global; 7.7%); 2) emotional distress and pain (distress-pain; 13.3%); 3) neurologic and pain (neuro-pain; 10.6%); 4) cardiopulmonary and pain (cardio-pain; 5.3%); 5) non-elevated symptoms (norm; 63.1%). Bone tumor survivors had higher risk of falling into global, neuro-pain and cardio-pain groups (p’s < .001), and CNS tumor survivors had higher risk of falling into global and neuro-pain group (all p < .001) compared to leukemia survivors. Radiation, Grade 3-4 CHCs, female sex, and older age increased risk of global, distress-pain, neuro-pain and cardio-pain membership compared to norm (all p’s < .001). Oncology-focused care was more common in cardio-pain and global symptom groups, while long-term follow-up care was more common in neuro-pain and global groups (Table). All elevated symptoms groups were more likely to have emergency room visits compared to norm group. Conclusions: Adjusting for insurance, CHCs and older age, elevated symptoms are associated with future emergency room use. Pain is prevalent in all high symptom groups, and suggests an important intervention target.[Table: see text]
Effect of anticancer therapy on mortality and COVID-19 severity in cancer patients with COVID-19.
Authors: Myint Phyo Thazin , Thet Aye 
Published: June 2022

e22510 Background: Cancer patients are more susceptible to severe complications and high mortality from Coronavirus disease 2019 (COVID-19). There is no solid evidence of whether anti-cancer therapy plays a significant role in increasing COVID-19 severity or mortality in cancer patients. Also, there is no definitive US guideline on how to justify anti-cancer treatment in cancer patients with COVID-19. Therefore, we conducted a systematic review and meta-analysis of the effect of anti-cancer therapy in cancer patients infected with COVID-19. Methods: A systematic search of Pubmed and Cochrane databases was conducted and two reviewers screened the articles independently. Previously published review articles were also evaluated to include the studies not identified in the Pubmed and Cochrane. Any clinical study of adults was included if it contains data on mortality or COVID-19 severity in cancer patients, both treated and untreated within 3 months before COVID diagnosis. Pooled odds ratio (OR) and 95% confidence intervals (CI) were calculated by employing the random-effects model, Mantel-Hazel method. Review Manager (RevMan) Version 5.4, The Cochrane Collaboration 2020 was used. Results: Out of 1690 studies identified from the databases and 8 studies from previous review articles, 22 studies (4777 patients) were included for analysis of the effect on mortality, and 12 studies (1898 patients) were included for the effect on COVID-19 severity. There were no significant differences in mortality between patients receiving anticancer treatment and those not (OR 1.17, 95% CI: [0.92-1.49], I2 = 56%, p = 0.21). There were no significant differences in mortality between patients receiving chemotherapy and those not receiving anticancer treatment but there was a trend towards higher mortality in patients receiving chemotherapy. (OR 1.43, 95% CI: [0.96-2.15], I2 = 68%, p = 0.08). There were no significant differences in COVID-19 severity between patients receiving anticancer treatment (OR 1.43, 95% CI: [0.96-2.15],, I2 = 10%, p = 0.27) and those not and between patients receiving chemotherapy and those not receiving anticancer treatment (OR 1.17, 95% CI: [0.83-1.65], I2 = 10%,p = 0.36). Conclusions: The results of our study were similar to previous meta-analyses despite more clearly defining anti-cancer treatment recency (anti-cancer treatment within 3 months before COVID diagnosis). There was low heterogeneity among studies for COVID-19 severity but high heterogeneity among studies for mortality. Most of the studies we analyzed were conducted in the 2020 and pre-vaccine era. Novel COVID-19 treatments and vaccination will likely affect outcomes in cancer patients with or without anti-cancer treatment. We need updated research and more detailed guidelines on anti-cancer therapy in COVID-19 infections.