bluuebunny/crossref_metadata_2025_split huggingface dataset:
Survey of carboplatin desensitization therapy: JCOG Gynecologic Cancer Study Group multicenter retrospective study.
Authors: Komatsu Hiroaki , Matsumoto Koji , Nishio Shin , Morita Mitsunori , Nagasawa Takayuki , Nishio Hiroshi , Suzuki Jiro , Ishikawa Mitsuya , Satoh Toyomi 
Published: June 2023

e17631 Background: The purpose of the present study was to investigate the real-world experience with carboplatin desensitization (CD) therapy in Japan, along with its safety, and establish a strategy to address carboplatin-induced hypersensitive reactions (HSRs). Methods: The present study included patients diagnosed with gynecologic cancer (ovarian, endometrial, or cervical cancer, i.e., OC, EC, and CC, respectively) who underwent CD therapy between 2016 and 2020 at Japan Clinical Oncology Group Gynecologic Cancer Study Group (JCOG-GCSG) participating centers. CD therapy was performed at each institution, and cases of implementation were registered in online case report forms. We examined patient information, treatment regimens, frequency and dose of carboplatin administration, administration rates, and CD practices. This study was approved by the Ethics Committee of the Tottori University. Results: Overall, 20 of 51 JCOG-GCSC-participating facilities performed CD therapy. The present study enrolled 136 patients (OC, 108; EC, 17; CC, 11). Of these, 37 (27.2%) patients had pre-existing allergies, and 29 (20.5%) exhibited prodromal symptoms at the time of treatment prior to the onset of HSRs. The most common symptoms were erythema and itching. At the onset of HSRs, erythema was the most common symptom, occurring in 93 (68.4%) patients, followed by itching in 72 (52.9%), reduced oxygen saturation in 43 (31.6%), and loss of consciousness in 3 (2.2%). The onset of HSRs was most common during treatment of the first recurrence (47%). The mean total carboplatin dose until the appearance of HSRs was 7331 (2620–18282) mg, and the mean number of doses was 14 (4–63). Six centers discontinued CD therapy owing to the appearance of breakthrough HSRs. CD therapy was completed in 75% of patients, with 25% (34/136) experiencing breakthrough HSRs. HSR-related mortality was not observed. The associated risk factors with HSR were not selected in the present study. Conclusions: Although patients who undergo CD therapy in Japan have a high probability of safely completing planned therapy, erythema and pruritus are important signs of breakthrough HSRs. Breakthrough HSRs were most frequent during the first cycle of desensitization. [Table: see text]
Uterine sarcoma patients who underwent morcellation: Who are they? Results of the prospective intergroup real-world registry for gynecological sarcoma in Germany (REGSA- NOGGO RU1).
Authors: Roser Eva , Mirbach Rebecca , Reichardt Peter , Zocholl Dario , Klar Maximillian , Harter Philipp , Kommoss Stefan , Ulrich Uwe Andreas , Mustea Alexander , Wimberger Pauline , Weigel Michael , Frank Matthias , Schmalfeldt Barbara , Hanker Lars Ch. , Flörcken Anne , Arndt Tjadina , Pietzner Klaus , Sehouli Jalid 
Published: June 2023

e17632 Background: Uterine sarcomas represent a group of rare malignant mesenchymal neoplasms with most types of them being associated with poor prognosis. In clinical practice, it is challenging to distinguish them from the most common benign tumors in women, so-called leiomyomas. Due to erroneous diagnosis, there is a risk of morcellating an occult sarcoma. This often leads to the distribution of malignant tissue in the abdominal cavity and a worse prognosis in most of the patients. In order to better understand this high-risk group of patients we analyzed their characteristics and management based on data of the real-world German registry for gynecological sarcoma (REGSA). Methods: REGSA is a real-world multicenter prospective registry including patients with gynecologic sarcomas in the primary and the recurrent situation of disease. For this work, we performed a descriptive analysis with data from all available patients with documented morcellation of uterine sarcoma. Results: 8.7% (n=76) of a total of 874 patients (registration period 09/2015-05/2022) were morcellated. Those 76 patients had a median age of 50.5 years. Thirty-seven patients (48.7%) were ≥50 years of age at the time of surgery. Leiomyosarcoma was the most common histopathological subtype (n=42; 50.3%). Fifty-eight patients (76.3%) had laparoscopic operations. A subtotal hysterectomy was the most common procedure used in 40.8% (n=31). Diagnostic curettage was performed in 5.3% of all cases (n=4). The predominant preoperative symptom was "bleeding disorders" in 19 patients (25.0%). Follow-up treatment after morcellation was heterogeneous. 17 patients received chemotherapy, with docetaxel and gemcitabine being the most frequently used regimen (n=8; 47.1%), followed by combinations with anthracyclines in 5 patients (29.4%). Conclusions: Many patients were over 50 years of age at the time of morcellation, although it is undisputed that the risk of morcellating occult uterine sarcoma increases with age. Whether curettage has diagnostic value needs to be further investigated. There is a high clinical need to define a consensus on further management of this high-risk group, regarding adjuvant therapy and follow-up care for there seems to be a great deal of uncertainty regarding adjuvant management.
Genomic characterization of vulvar squamous cell carcinoma to reveal differential gene expression based on clinical outcome.
Authors: Gordinier Mary E. , Schau Geoffrey , Pollock Shanna Brotzge , Shields Lisa , Talwalkar Sameer S. 
Published: June 2023

e17633 Background: The greatest challenge in the management of vulvar squamous cell carcinoma (VSCC) is treatment of recurrent disease where options for surgery and radiation have been exhausted, or treatment of disease where distant metastasis is present. Identification of mutations differentially expressed between tumor from patients who died of aggressive disease and tumor from patients with an indolent course could reveal novel prognostic indicators and guide development of therapeutic drugs. Methods: From 202 consecutive patients with VSCC, patients who recurred and died of disease (group A) were identified and matched by age, tumor size, depth of invasion and nodal status with those whose disease did not recur (group B). Tumor and matched normal samples from 21 patients were assayed by a broad NGS panel covering 648 genes, including whole exome and transcriptome sequencing. Immunohistochemistry (IHC) for PD-L1 (22C3) and p16 was also performed. Results: Whole transcriptome data revealed 6 genes that were strongly differentially expressed between the aggressive and indolent groups: ACVR2A, TGM3, ROS1, NFEL2, CCND1 and BCL6. Biologically relevant DNA mutations were significantly greater in the aggressive cohort versus the indolent cohort: 7 vs 2.3 mutations per patient. The most common genomic alterations were mutations in TP53 and the promoter region of TERT. TP53 alterations occurred almost exclusively in group A. Other common genomic events include alterations of FAT1, CDKN2A, PIK3CA, CCND1, and LRP1B. All samples were MSI stable, and tumor mutational burden was similar in groups A and B. Most VSCC specimens (81%) were positive for PD-L1. Conclusions: We report that TGM3 and ACVR2A genes are significantly under-expressed in tumors with poor outcome. Further investigation into the silencing of these genes may advance knowledge of the pathogenesis of VSCC and potentially yield therapeutic targets. Clinical outcome of VSCC appears independent of MSI, TMB or PD-L1 status. [Table: see text]
Clinical characterization of responders to first line (chemo)immunotherapy in platinum-sensitive recurrent/metastatic head and neck squamous cell carcinoma (RM HNSCC).
Authors: Buriolla Silvia , Cavalieri Stefano , Franza Andrea , Rota Simone , Bergamini Cristiana , Alfieri Salvatore , Nuzzolese Imperia , Colombo Elena , Ottini Arianna , Licitra Lisa F. , Resteghini Carlo 
Published: June 2023

e18017 Background: RM HNSCC patients (pts) with combined positive score (CPS) ≥1 benefit from immunotherapy (IO), either alone or with chemotherapy (CIO). No survival outcome indicators are available. We aim to characterize a real world cohort of RM HNSCC pts treated at a tertiary cancer center. Methods: We analyzed 37 consecutive RM HNSCC pts treated with IO or CIO from 2016 to 2022. We divided pts in responders (R) and non responders (NR) if they achieved an objective response or disease stability/progression as best response. For group comparisons, we considered the following clinical variables: age, gender, smoking status, primary HNSCC site, HPV status, ECOG performance status, disease sites at RM diagnosis (local, regional, distant), time to RM diagnosis (TTR). For categorical variables, we compared the clinical characteristics of the 2 groups using the chi squared or Fisher’s exact tests, as appropriate. For age we used the Mann-Whitney test. For TTR we used the Cox proportional hazard model. Outcomes (progression free and overall survival, PFS and OS, respectively) were assessed with Kaplan Meier method and compared with log-rank test. Statistical significance was set at 0.05. Results: Clinical characteristics are reported in the table. Objective response rate (ORR) was 32%, median DoR 7.5 months (95% confidence interval, CI 2.07-not reached). None of the examined clinical variables were significantly different in the groups (R vs NR in the overall population, in IO- and CIO-treated pts). The only major difference between cohorts was survival, which was significantly longer in R vs non-R (Table). Conclusions: With the limits of a retrospective analysis, we observed a longer survival in R compared to NR. None of the main clinical characteristics were predictive of objective response to (C)IO. Further studies are needed to define predictive factors of response, and to enhance the ORR in first-line IO-based treatments. [Table: see text]
Impact of EBV positivity on clinical outcomes in nasopharyngeal cancer.
Authors: Ghimire Bipin , Karki Ujjwal , Herrman Emma , Thapa Shrinjaya , Shrotriya Shiva , Poudel Shyam K. , Anusim Nwabundo Ifeyinwa , Ezekwudo Daniel , Jaiyesimi Ishmael A. 
Published: June 2023

e18021 Background: Nasopharyngeal carcinoma (NPC) is a rare malignancy with unique geographical distribution. Epstein Barr virus (EBV) plays a key role in the pathogenesis of NPC, with pre and post-treatment serum EBV DNA level as an established prognostic indicator. However, evidence regarding the impact of the tumor cells’ EBV positivity on clinical outcomes is inconsistent. Methods: After IRB approval, we performed a retrospective chart review on NPC patients aged above 18 years seen at Corewell Health William Beaumont University Hospital between July 2015 and December 2020. The Epstein Barr encoding region in-situ hybridization from the biopsy sample determined EBV positivity. We compared progression-free survival (PFS) and overall survival (OS) based on EBV positivity status. Results: A total of 60 NPC patients were included: 19 were EBV-positive, 20 were EBV-negative, and 21 were EBV-unknown. The median age at diagnosis was 50.7 years, and 58.3 years in EBV-positive and negative groups respectively. Most patients in both groups were male (68.4% vs 65%) and had advanced (stage III or stage IV) disease (84.2% vs 75%). The median follow-up duration was 37.3 months. Median PFS and OS were 41 months and 114 months respectively in EBV-negative patients, while median PFS and OS were not reached in EBV-positive patients. There was no significant difference in PFS (0.944) and OS (0.117) among the EBV-positive and negative groups. Among advanced-stage patients, the median PFS was 33 months and 31 months in EBV-negative and EBV-positive groups, respectively, while median OS was not reached in both groups; the difference in PFS (p = 0.821) and OS (0.240) was statistically non-significant. When compared among patients with EBV-positive, negative, and unknown status, PFS was statistically non-significant (p = 0.347) but there was a statistical difference in OS (0.027). Conclusions: Our analysis suggests that the EBV status of the tumor cells does not predict clinical outcomes (PFS or OS) in NPC patients. Even though the OS trend favored EBV-positive patients overall and among those with advanced disease, it was not statistically significant. A difference in OS was seen when patients with unknown status were included and analyzed together with EBV-positive and negative patients, which raises the question of whether the outcome would be different if the majority of patients with unknown status belonged to either the EBV-positive or negative group. With studies in the literature reporting disparate findings, larger prospective studies are needed to better illustrate the impact of tumor cells' EBV positivity on clinical outcomes in NPC.
Adenocarcinoma in villous adenoma: Demographics analysis.
Authors: Sinai Erin , Hsia Beau , Cook Madison , Luker Andrew , Wu Xinxin , Silberstein Peter T. , Keirns Darby 
Published: June 2023

e18024 Background: Adenocarcinoma in Villous Adenoma (AVA) is a metastatic disease that arises from villous adenomas. These adenocarcinomas can arise from different tissues, particularly this analysis looked at AVA arising from the head and neck region. Treatment for otolaryngological AVA varied depending on grade, but the majority of patients received surgery or radiation. Despite its rarity, 16.7% of patients pass within 90 days after receiving surgery for this cancer. Given the rarity, data analysis of demographic findings could provide important information regarding its occurrence and distribution in the population. Methods: Patients from the National Cancer Database (NCDB) with a confirmed diagnosis of otolaryngological AVA from 2004–2017 were used in a retrospective cohort analysis (N = 33). Factors analyzed by descriptive statistics and regression analysis include sex, race, average household income, Charlson-Deyo score, palliative care obtained, and year of diagnosis. Results: A total of 33 patients were identified in the database with a confirmed diagnosis of AVA in the head and neck between 2004 – 2017 with a steady incidence of patients diagnosed per year (R2 = 0.0). The average age of diagnosis was 69 years (SD = 9.7, range = 51-85 years). The top primary site was the esophagus (90.9%). Most individuals (60.6%) had Charlson/Deyo comorbidity scores of 0. The majority of the patients were Non-Hispanic and White (97.0%). There was an equal distribution of income earners in the first and second quartile (33.3% and 33.3%) compared to those in the third or fourth quartiles (upper and middle quartiles are defined as over $74,063 and $57,857 to $74,062, respectively). A higher percentage of patients were insured by Medicare (57.0%) or privately insured (36.4%), compared to those who were uninsured. Most patients lived in metropolitan counties with a population greater than 1 million (51.6%). The majority of patients were treated in a comprehensive community cancer program (54.5%). Most patients did not receive palliative care (97.0%) and 16.7% of patients died within 90 days of receiving surgical treatment. Conclusions: With most data showing extensive data analysis on AVA stemming from the colon, this is the only analysis of demographic data from this cancer originating from the head and neck region. From the NCDB data, the majority of patients are non-Hispanic and White with a primary-site diagnosis presenting in the esophagus. This is the first time that specific AVA socio-economic data has been analyzed: patients with this cancer tend to be in upper or middle income brackets, live in crowded metropolitan areas, and have Medicare as their insurance coverage. To further our understanding of otolaryngological AVA, it would be necessary to examine the relationship between demographic and socioeconomic factors, and the diagnosis, treatment options, and survival rates for individuals with AVA.
Induction and concomitant chemoradiotherapy (CCRT) using modified TPF (docetaxel, cisplatin and 5-FU) for the patients with stage IVB advanced head and neck cancer.
Authors: Shiga Kiyoto , Katagiri Katsunori , Saitoh Daisuke , Oikawa Shin-ichi , Tuchida Kodai , Kusaka Takahiro , Ohashi Yu 
Published: June 2023

e18031 Background: Efficacy of TPF chemotherapy has been reported mainly in the induction chemotherapy (IC) for head and neck squamous cell carcinoma (HNSCC) so far. The aim of this study was to determine the safety and efficacy of CCRT using modified TPF protocol in patients with Stage IVB HNSCC. Methods: Patients with previously untreated, histologically proven Stage IVB disease of the head and neck were eligible for the study. Twenty-six patients of the HNSCC were enrolled between January 2018 and October 2021 including 6 HPV(-) oropharyngeal, 5 hypopharyngeal, 4 ethmoid, 4 maxillary, 2 primary unknown and 5 other cancers. There were 14 T4b and 13 N3b tumors. CCRT consisted of radiotherapy administered once daily to a total dose of 70 Gy, concomitant with 120-hour infusions of 5-FU (600 mg/m2/day), Docetaxel (50 mg/m2, day 2) and Cisplatin (60 mg/m2, day 2) given during first and fifth week of radiotherapy. These drug doses were determined from the results of our former phase I study to assess the dose limiting toxicity of this protocol. Median follow-up period was 21 months. Results: Eight patients with Stage IVB HNSCC underwent IC and CCRT with this modified TPF protocol. Eight patients underwent CCRT using 2 courses of modified TPF. Five patients underwent CCRT with CDDP, three of them underwent arterial infusion of CDDP by super-selective angiography via external carotid artery. Three other patients underwent CCRT using other protocols and two underwent RT without chemotherapy. Bone marrow suppression was the most common adverse event observed through this study. Although all patients showed dermatitis and mucositis at any grade, other grade 3 or 4 adverse events in these patients were not common. Complete response was obtained in all patients except four patients. The progression-free and over-all survival rates at 24 months of all the patients with Stage IVB HNSCC in our series were 53.4% and 59.1%, respectively. Those of the patients who underwent IC and CCRT with modified TPF protocol were 58.3% and 80.0%, respectively and significantly better than those of the patients with other treatment protocols. Conclusions: Our results suggested that IC followed by CCRT using modified TPF was feasible and very effective in patients with Stage IVB HNSCC.
Radiation-sensitive genetic prognostic model to identify individuals at risk for radiation resistance in head and neck squamous cell carcinoma.
Authors: You Peimeng , Li Qiaxuan , Zhou HaiYu 
Published: June 2023

e18042 Background: The advantages of radiotherapy for head and neck squamous cell carcinoma (HNSCC) depend on the radiation sensitivity of the patient. Here, we established and verified radiological factor-related gene signature and built a prognostic risk model to predict whether radiotherapy would be beneficial. Methods: Data from The Cancer Genome Atlas, Gene Expression Omnibus, and RadAtlas databases were subjected to LASSO regression, univariate COX regression, and multivariate COX regression analyses to integrate genomic and clinical information from patients with HNSCC. HNSCC radiation-related prognostic genes were identified, and patients classified into high- and low-risk groups, based on risk scores. Variations in radiation sensitivity according to immunological microenvironment, functional pathways, and immunotherapy response were investigated. Results: We built a clinical risk prediction model comprising a 15-genes signature and used it to divide patients into two groups based on their susceptibility to radiation: radiation-sensitive and radiation-resistant. Overall survival was significantly greater in the radiation-sensitive than the radiation-resistant group. Further, our model was an independent predictor of radiotherapy response, outperforming other clinical parameters, and could be combined with tumor mutational burden, to identify the target population with good predictive value for prognosis at 1, 2, and 3 years. Additionally, the radiation-resistant group was more vulnerable to low levels of immune infiltration, which are significantly associated with DNA damage repair, hypoxia, and cell cycle regulation. Tumor Immune Dysfunction and Exclusion scores also suggested that the resistant group would respond less favorably to immunotherapy. Conclusions: Our prognostic model based on a radiation-related gene signature has potential for application as a tool for risk stratification of radiation therapy for patients with HNSCC, helping to identify candidates for radiation therapy and overcome radiation resistance.
Prognosis-related molecular subtyping of nasopharyngeal carcinoma.
Authors: Ding Qin , Chen Xiaochuan , Qiu Sufang 
Published: June 2023

e18047 Background: Nasopharyngeal carcinoma (NPC) is a highly invasive and metastatic cancer, with diverse molecular characteristics and clinical outcomes. This study aims to dissect the molecular heterogeneity of NPC, followed by the construction of a mRNA -based prognostic model for prediction of treatment efficacy. Methods: We retrospectively collected a total of 193 NPC tissue samples from 2016 to 2018 for mRNA sequencing. Consensus clustering was performed to identify new molecular subgroups based on the ssgsea algorithm. Then, weighted gene co-expression network analysis (WGCNA) was used to recognize molecular subtype-associated hub genes. Finally, Cox regression analysis was applied to constructing a prognostic model for predicting risk of recurrence and metastasis. Results: Three NPC subtypes (immune, proliferation and metabolism) were identified that are molecularly distinct and clinically relevant, of which proliferation subtype is associated with poor prognosis. Immune subtype characterized by higher expression of immune checkpoint, immune cells infiltration and immunesore. Interestingly, compared with other cells, tumor cells in TME exhibited the most active metabolism pathway in single-cell sequencing analyses. The Cox regression model built on hub genes showed a close correlation with outcome (AUC = 0.81). We further validated the results using the GEO database. Conclusions: Based on biological characteristics, NPC can be novelly stratified into three subtypes. Our study identified and validated a promising prognostic model associated with molecular subtype, which may accurately anticipate the survival of NPC patients.