bluuebunny/crossref_metadata_2025_split huggingface dataset:
Analysis of the relationship between social determinants of health and survival outcomes in gestational trophoblastic neoplasia in the United States.
Authors: Liu Chrissy , James Alecia , Wolf Jennifer , Schmidt Marcia , Mitchell Edith P. , Calixte Rose , Clare Camille A. 
Published: June 2022

e17537 Background: Gestational trophoblastic neoplasia (GTN) is a rare disease with a reported incidence of 1 in 40,000 pregnancies. There have been no studies evaluating the impact of social determinants of health (SDH) on outcomes in GTN. This study seeks to examine the influence of social and biologic prognostic factors related to survival among women with GTN. We hypothesized that older age at diagnosis, lower household income, and marginalized, racial/ethnic groups are associated with worse prognosis. Methods: In this retrospective study, the Surveillance, Epidemiology, and End Results (SEER) database was used to identify women with GTN diagnosed from 2010-2018. Clinical-pathologic characteristics were described including initial stage of disease, presence of brain metastases at diagnosis, treatment with chemotherapy or surgery, and treatment at a Commission on Cancer (CoC) accredited center. Demographic factors were collected, including race/ethnicity, age at diagnosis, marital status, median household income, and rural or urban location. Log-logistic regression models were used to estimate the association between various prognostic factors and the odds of survival. We compared overall survival distributions across race/ethnicity using the log-rank test. Results: Of the 1,149 eligible patients (pts), 36% were non-Hispanic White (NHW), 21% non-Hispanic Black (NHB), 28% Hispanic, and 14% Other (Native American, Alaska Native, Asian, Pacific Islander). Mean age was 33.8 years (range 14-87 years). The majority was in the 21-35 age group (51%). Compared to NHW pts, Hispanic pts had over two times the odds of increased survival (OR 2.11; 95% CI 1.08-3.27; p = 0.032). NHB pts had similar survival compared to NHW pts (OR 1.06; 95% CI 0.50-1.76; p = 0.860). Poor prognostic factors demonstrating decreased odds of survival included age ≥40 years (OR 0.139; 95% CI 0.025-0.478; p < 0.001) and widowed status (OR 0.09; 95% CI 0.018-0.375; p < 0.001). Localized stage (OR 2.94; 95% CI 1.13-5.53; p = 0.03), the absence of brain metastases (OR 4.58; 95% CI 1.96-7.91; p = 0.002), and rural location (OR 5.62; 95% CI 1.25-15.2; p = 0.028) were significantly associated with increased odds of survival. Household income and race/ethnicity were not independent predictors of survival. Conclusions: Compared to NHW pts, Hispanic pts have an increased cause-specific survival for GTN. NHB pts and NHW pts have similar survival. Additionally, rural location was significantly associated with greater odds of survival. Further research is needed to investigate the underlying mechanisms linking race/ethnicity and survival outcomes, considering structural racism, bias, and discrimination. Our findings highlight the importance of recognizing the role of racism and SDH on health disparities and call to attention the need for addressing social inequities in GTN.
Perioperative opioid-sparing multimodal analgesia (OSMMA) in cancer patients.
Authors: Tumanyan Sergey V. , Frantsiyants Elena M. , Rozenko Dmitry A. , Moiseenko Tatiana I. , Menshenina Anna P. , Oros Oksana V. , Popova Natalia N. 
Published: June 2022

e17552 Background: Perioperative (PO) pain management is one of the most important issues in cancer treatment. The purpose of the study was to improve the quality of PO analgesia in cancer patients. Methods: A prospective randomized study of the quality and efficacy of various analgesics included 104 patients aged 34 to 77 years who underwent surgical interventions for ovarian cancer. The patients were divided into 2 groups. Group 1 (n = 49): patient-controlled analgesia with trimeperidine and nonsteroidal anti-inflammatory drugs (NSAIDs); group 2 (n = 55): preemptive analgesia based on a continuous infusion of lidocaine, magnesium sulphate, microdoses of fentanyl (4 µg/h) and NSAIDs. Results and pain syndrome were assessed by the visual analogue scale (VAS), personal and reactive anxiety, levels of glucose, cortisol, insulin, lactate, and the Kerdo index. Results: Analgesic effect of trimeperidine was obtained in 85.7% (p < 0.05). However, the effect was less pronounced, compared to OSMMA, and did not reduce the cognitive component of pain after surgical treatment. In group 2, opioid-sparing analgesic effect was 96.4% (p < 0.05). OSMMA limited the increase of cortisol, glucose, insulin, CRP and lactate (p < 0.05) providing effective PO pain relief. OSMMA did not cause residual sedation, anxiety, depressive effects and cognitive impairments, which showed its advantages over trimeperidine. Therefore, despite the minimal doses of narcotic analgesics in group 2, OSMMA improved the quality of pain relief and the well-being of patients in perioperative period being a significant advantage in minimizing the negative effects of opioids. Conclusions: Lidocaine-based PO analgesia with microdoses of fentanyl can significantly limit endocrine and metabolic changes and improve the quality of pain relief contributing to the early rehabilitation of cancer patients.
Impact of tumor percentage on the assessment of homologous recombination deficiency score using a NGS 523 gene panel and a cytogenetic software in the evaluation of epithelial ovarian tumors.
Authors: Navarro Sanchez Janira , Halford Zan , Kar Shing Pon Jason , Woron Amy M. , Terada Keith Y. , Vierkoetter Koah , Lum Christopher A. 
Published: June 2022

e17567 Background: Platinum-taxane chemotherapy and surgical debulking are the optimal treatment for patients with advanced ovarian cancer. While initial response rates are above 80%, tumor recurrence occurs in about 70 to 80% of patients. Cells with defects in homologous recombination repair (HRR) are susceptible to cell death induced by Poly (ADP-ribose) polymerase inhibitors (PARPi). These drugs are used to treat recurrent neoplasms that have BRCA1 or BRCA2 mutations or homologous recombination deficiency (HRD). Low tumor percentage in test samples, which is common in clinical practice, is often overlooked when addressing HRD tests. The goal of this study was to determine the optimal tumor content rate needed to detect HRD changes. Methods: A total of sixteen ovarian neoplasms were studied. These samples were sequenced using Illumina TSO500 NGS and interpreted using NxClinical software 6.1. In all cases, HRD scores were evaluated. A score of ≥42 was determined to be HR-deficient and a score < 42 was considered HR-proficient. We aimed to identify the optimal tumor percentage needed for detection of HRD alterations. HRD scores were calculated with tumor percentages of 70%, 60%, 40%, and 20%. Additionally, chemotherapy response scores (CRS) were available in 8 of 16 cases. We correlated the CRS with HRD scores. Results: In this project, visualization of a 523-gene cancer exome panel was shown to be 66.7% sensitive and 100% specific for detecting genomic scars (HRD score). 68.75% of cases showed low HRD score and 31.25% of cases showed a high HRD score. Next generation sequencing (NGS) results for most specimens are adequate with a tumor content rate of 70%. CRS1 cases were HR-proficient. For CRS2 and CRS3 we had mixed results. Conclusions: HRD correlates with platinum sensitivity in epithelial ovarian tumors, which has clinical significance as a predictor of sensitivity to PARPi. During treatment, tissue samples are obtained at different times points and sources, some at diagnosis/surgical debulking and some after neoadjuvant therapy. After neoadjuvant treatment, tumor volume is reduced. Cytology specimens are convenient for obtaining tumoral cells, but tumor volumes are usually small. Profiling tumors of low volume decrease the chances of detecting a patient’s eligibility for targeted maintenance. Our next steps will evaluate the performance of tissue microarrays using the Infinium CytoSNP-850K array compared to NGC cytogenomics at low tumor volumes.
Genomic characteristics of homologous recombination deficiency in ovarian cancer.
Authors: Ma Xiaoxue , Li Mingwei , Lou Feng , Cao Shanbo , Wang Huina 
Published: June 2022

e17575 Background: HRD score correlates with sensitivity to PARP inhibitors (PARPi). BRCA1/2 mutations are well-known causes of HRD, but other genetic abnormalities of the homologous recombination repair (HRR) pathway could also cause HRD, although no consensus has been reached. We aimed to analyze HRD score and its relationship with genetic characteristics in ovarian cancer, particularly the HRR-related genes mutations. Methods: Matched tumor/normal DNA from Chinese patients with ovarian cancer (N = 181) were analyzed by Acornmed panel with 98 cancer-related genes. The HRD score is the sum of these scar signature scores, namely, the loss of heterozygosity (LOH), telomeric allelic imbalance (TAI), and large-scale state transitions (LST). HRR genes mutations and clinical outcomes from the TCGA cohort were included. Results: In our cohort, 44.2% patients exhibited HRR genes mutations, yielded an increment of 12.2% than BRCA mutants. The most frequently mutated HRR genes were BRCA1 (25.0%), BRCA2 (8.0%), CDK12 (4.0%), and RAD51D (4.0%). Chinese cohort contained frequently somatic mutation of HRR genes compared with TCGA cohort (22.7% vs 13.6%, p < 0.010). Germline mutations of HRR genes and non-HRR genes occurred in 21.5% and 2.8% of cases detected, respectively. HRD score in HRR-related genes wildtype was lower than tumors with BRCA1/2 mutation and HRR genes mutation without BRCA1/2 carriers (median HRD score 33, 72 and 64; p < 0.001). Interestingly, no difference was observed in HRD scores between patients with somatic BRCA-mut and germline- BRCA mutants. The median HRD score in our cohort was 65 (range from 0 to 96), and 58.6% patients were HRD-high with the cutoff of HRD score ≥ 42. The HRD-high patients covered 89.7% of the BRCA-positive cases, besides, approximately 77.3% of the BRCA-wt/HRR-mut patients also harbored high HRD scores. Six mutated genes were significantly different between HRD-high and HRD-low group. ARID1A was frequently mutated in patients with HRD-low, while significantly more mutations in TP53 were identified among HRD-high patients. Interestingly, in the TCGA cohort, patients with TP53-mut (p = 0.024) and individuals without ARID1A mutation (p < 0.001) had remarkably high survival rates, as compared with the rest of these patients.Furthermore, tumors with HRD-high had a bit higher TMB (median TMB 4.56 vs 2.91, p = 0.018). Conclusions: Our data suggest that HRR genes mutations strongly affect HRD score, which may increase the number of patients who may benefit from PARPi treatment, and combining gene mutations and HRD score could optimize prognosis stratification in ovarian cancer. In addition, the molecular features of HRD provide new opportunities to predict the tumor response to multiple treatments.
Early mortality in epithelial ovarian cancer.
Authors: McMinn Erin , Nasioudis Dimitrios , Latif Nawar A. , Cory Lori , Ko Emily Meichun , Giuntoli Robert 
Published: June 2022

e17585 Background: Investigate the prevalence and characteristics of patients with epithelial ovarian carcinoma (EOC) who experience early mortality defined as death within 90 days of diagnosis. Methods: The National Cancer Database was accessed, and patients diagnosed with a pathologically confirmed EOC between 2004-2015 were identified. Patients who died within 90 days from diagnosis were identified. Clinico-pathological characteristics were compared with the chi-square and Mann Whitney U test. Results: A total of 150064 patients diagnosed with EOC were identified; 13561 (9%) patients died within 90 days from diagnosis with a decreasing incidence per year of diagnosis (from 9.8% in 2004 to 8% in 2015). These patients were older (median 76 vs 61 years, p < 0.001), more likely to be Black (11.4% vs 7.1%, p < 0.001), have government-issued insurance (75.6% vs 45.4%, p < 0.001), median income < 48000$ (45.1% vs 37.9%, p < 0.001), comorbidities (35% vs 19.1%, p < 0.001), reside closer to treatment facility (median 8 vs 12.3 miles, p < 0.001) and present to non-academic facilities (68.5% vs 58.1%, p < 0.001). Incidence of early mortality was 3.6% for patients aged < 65 years, 11.2% for those 65-79 years and 28.6% among those > = 80 years. For patients who experienced early mortality, 6067 (44.7%) did not receive any treatment, 2969 (21.9%) received chemotherapy only, 3345 (24.7%) underwent surgery only and 1180 (8.7%) received both. The rate of patients who did not receive any treatment was higher for patients aged > = 80 years (25.6%) compared to those aged 65-79 (6.9%) and < 65 years (2.5%), p < 0.001. For patients who underwent surgery, median inpatient stay was 9 days while unplanned readmission rate within 30-days from discharge was 10.8%. After controlling for insurance, type of treatment facility, comorbidities, income, race, and stage, octogenarians had higher odds of early mortality (OR 6.02, 95% CI: 5.65, 6.41) compared to those aged < 65 years. Higher odds of early mortality were also observed among octogenarians who received chemotherapy (OR 4.28, 95% CI: 3.84, 4.77) or surgery (OR 5.72, 95% CI: 5.15, 6.35) compared to those < 65 years, after controlling for the aforementioned confounders. Conclusions: Approximately 1 in 10 patients diagnosed with ovarian cancer will expire within 90 days from diagnosis. These patients are older and more likely to have medical comorbidities. More than 1 in 4 octogenarians with ovarian cancer will die within 90 days of diagnosis. Some of these patients may not be candidates for active treatment; however, interventions that facilitate timely presentation, target frailty, and allow medical optimization are greatly warranted.
Cost-effectiveness of Olaparib plus Bevacizumab versus Bevacizumab in the maintenance of patients with HRD+ advanced ovarian cancer after response to first-line platinum-based chemotherapy in Spain.
Authors: Perez-Fidalgo Jose Alejandro , Cercos Lleti Ana Cristina , Manso Luis , Casado Herraez Antonio , Ventayol Bosch Pedro , Garí Carla , Padres Martí Miriam , Cedillo Gomez Sergio 
Published: June 2022

e17591 Background: Olaparib, a poly (ADP-ribose) polymerase inhibitor (PARPi), monotherapy as first-line maintenance treatment has shown to be cost-effective in ovarian cancer (OC) patients with BRCA mutations in Spain. Regardless of BRCA status, patients with homologous recombination deficiency positive (HRD+) also benefit from PARPi following first-line platinum-based therapy. PAOLA-1 trial confirmed that adding Olaparib to bevacizumab (BEV) significantly increased progression-free survival (PFS) in OC patients. The aim of this study was to assess the cost-effectiveness of Olaparib plus BEV versus BEV monotherapy for the maintenance treatment of HRD+ advanced OC patients after response to first-line platinum-based therapy plus BEV from Spanish National Health System perspective. Methods: A lifetime partitioned survival model with monthly cycles and four health states (PFS, first progression, second progression, and death) was developed. Long-term survival defined as 60 months was included in the mixed survival model as a landmark to extrapolate PFS from the PAOLA-1 trial. Weibull distribution was selected as the most accurate survival model for PFS extrapolation. Time to second progression, and overall survival (OS) were extrapolated using parametric survival models. Mortality was obtained from the OS and adjusted by Spanish mortality rates. Health state utilities and adverse event (AE) frequencies were obtained from PAOLA-1. An expert panel validated data and assumptions. Direct costs including drug acquisition and administration, follow-up, subsequent therapies, AE, and end-of-life were obtained from local sources. A 3% annual discount rate was applied to costs and outcomes. The incremental cost-effectiveness ratio (ICER) was calculated as cost per quality-adjusted life-years (QALYs) gained. One-way and probabilistic sensitivity analyses (PSA) were performed to assess the robustness of the model. Results: Base-case analysis of Olaparib plus BEV compared with BEV showed an ICER of €24,371 per QALY gained. Discount rates applied to outcomes and the cost of Olaparib generated the most significant changes in the ICER. PSA demonstrated that Olaparib plus BEV had a 49.5% and 90.3% probability of being cost-effective versus BEV at a willingness-to-pay of €25,000 and €60,000 per QALY gained, respectively. Conclusions: Olaparib plus BEV is a cost-effective maintenance therapy compared with BEV for patients with HRD+ advanced OC in Spain.[Table: see text]
Partner and localizer of BRCA2 (PALB2) pathogenic variants and ovarian cancer: A systematic review and meta-analysis.
Authors: Narayan Priyanka , Ahsan Muhammad Danyal , Beaumont Shanice , Lin Jenny , Perez Luiza , Bull Leslie , Wolfe Isabel , Hickner Andy , Chapman-Davis Eloise , Cantillo Evelyn , Holcomb Kevin , Sharaf Ravi , Frey Melissa Kristen 
Published: June 2022

e17597 Background: Approximately 20% of ovarian cancers are due to an underlying germline pathogenic variant. While several genes have been well-established in the development of hereditary ovarian cancer (e.g. BRCA1/2, RAD51C, RAD51D, BRIP1, mismatch repair genes), there are other genes for which the cancer risk is less certain and management recommendations remain controversial, including partner and localizer of BRCA 2 (PALB2). We sought to evaluate the association between PALB2 germline pathogenic mutations and ovarian cancer in the first meta-analysis on this topic. Methods: We conducted a systematic review and meta-analysis in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines (PROSPERO no.: CRD42021281325). We searched key electronic databases to identify studies evaluating multigene panel testing in patients with ovarian cancer. Eligible trials were subjected to meta-analysis. Results: Thirty-seven studies met inclusion criteria. We found 55,137 cases of ovarian cancer with information available on germline PALB2 pathogenic variant status. Reported histological subtypes included serous adenocarcinoma (74.8%), endometroid (6.5%), clear cell (2.1%), mucinous (3.1%), and other (13.5%). Most ovarian cancers were stages III (73.5%) and IV (22.3%), followed by II (6.0%), and I (4.1%). Among ovarian cancer cases with PALB2 sequencing data available, 0.4% demonstrated a germline pathogenic variant in the PALB2 gene and the pooled odds ratio (OR) for having a PALB2 mutation was 2.31 (95% CI 0.89- 5.98). Among 94 patients with a germline PALB2 pathogenic variant, the pooled odds ratio (OR) for developing ovarian cancer was 2.85 (95% CI 1.58-5.15) relative to 33,855 patients without PALB2 mutations. Conclusions: Our meta-analysis demonstrates that the pooled OR for developing ovarian cancer with an underlying PALB2 germline pathogenic variant was 2.85 (95% CI 1.58-5.15). While this risk is lower than many of the well-established hereditary ovarian cancer genes, it does exceed the baseline population risk of 1-2%. Whether this meets the threshold to consider risk-reducing salpingo-oophorectomy is up for debate. Large population-based studies and evaluation of the combination of PALB2 mutations and cancer family history are needed to improve management recommendations for patients harboring pathogenic mutations in this gene.
Anatomic distribution of local recurrence of nasopharyngeal carcinoma in the Era of IMRT: Suggestion of modification of clinical target volume delineation.
Authors: Ou Xiaomin , Wang Jiazhou , Yan Wenbin , Lu Xueguan , Ying Hongmei , He Xiayun , Hu Chaosu 
Published: June 2022

e18060 Background: Target volume delineation in nasopharyngeal carcinoma (NPC) remains a challenge because of the narrow therapeutic margin. There are no-well established guidelines for clinical target volume (CTV) delineation with long-term follow-up. Current consensus continues to rely heavily on bony structure and experience from conventional two and three- dimensional radiation. The aim of our study, is to clarify different anatomic distribution of local recurrence of NPC based on various T stages and spread patterns, provide a high-risk map of local recurrence of NPC, and thus provide suggestion for modification of CTV delineation based on T stages and spread patterns. Methods: We retrospectively enrolled 869 patients with newly diagnosed nonmetastatic NPC treated with definitive IMRT in our institution. With a median follow-up of 54.4 months, 72 patients developed local failure. All the cases of local failure were reviewed and those of local residual disease were excluded. After that, 52 cases with tracaeble primary radiotherapy plans and MR imaging of local recurrence were included in this study. Gross tumor volume of local recurrence (GTVr) and normal structures were delineated in each recurrent patient on primary CT of radiotherapy. The overlap of normal structures with GTVr were analyzed, as well as the stepwise patterns of tumor spread in NPC, based on different T stages and relapsed risk (≥5%, ≥10%, ≥20%, etc). Results: The anatomic distributions of local recurrence of various primary T stages were compared between early and late stages of NPC. Of note, these structures were significantly highly involved in T3/4 cases, compared with T1/2 cases, including lateral pterygoid muscle, inferior orbital fissure，posterior ethmoid sinus，cavernous sinus as well as hypoglossal canal. As for tumor spread patterns of local relapse, most cases relapsed in the nasopharynx and retropharyngeal lymph node (38.5%), followed by anterior-lateral tumor extension (via nasal cavity-pterygoid process-pterygopalatine fossa, 17.31%), posterior tumor extension (via prevertebral muscle-clivus, 13.46%), anterior-superior extension (via nasal cavity-ethmoid sinus-sphenoidal sinus,13.46%), superior extension(via foramen lacerum-cavernous sinus, 11.54%), etc. Finally, we depicted a map of high-risk area based on different T stages and relapsed risk (≥5%, ≥10%, ≥20%). Conclusions: Comprehensive analysis of local recurrence distributions and tumor spread patterns in real-world IMRT provides important reference for modification of CTV delineation for primary NPC. Certain structures such as cavernous sinus and lateral pterygoid muscle are not routinely recommended in the delineation of high-risk CTV for T1-2 disease. Future individualized delineations should be based on relapsed risk and tumor spread patterns.