bluuebunny/crossref_metadata_2025_split huggingface dataset:
The utilization of cryopreserved sperm in males with cancer.
Authors: Reynolds Anna Claire , Ghidei Luwam , Kassab Jordan , Campbell Kevin , Sullivan John , Lipshultz Larry , Mckenzie Laurie 
Published: June 2023

e18791 Background: Ten percent of individuals diagnosed with cancer in the United States are under age 45. Fortunately, improvements in cancer therapy have enabled younger individuals to survive with cancer related deaths decreasing steadily over the past 20 years. The American Society for Clinical Oncology (ASCO) recognizes the importance of future family building for cancer survivors and states healthcare providers should discuss fertility preservation options prior to cancer treatment initiation. Despite these recommendations, the data regarding survivor utilization of cryopreservation sperm is limited. The aim of this study is to assess factors that impact the post treatment utilization of cryopreserved sperm. Methods: 721 patients who underwent sperm cryopreservation for cancer indication from 1/1/2010 – 10/1/2020 at a single institution were included in the retrospective chart analysis. Cancer diagnosis, patient age at time of sperm banking, sample storage duration, and sample disposition were collected. Sample disposition included utilization for pregnancy effort(s), request to discard and/or donate to research, and lost to follow up. Descriptive statistics were employed via Excel. Results: Fifty-two of 721 (7.21%, 95% CI 5.4-9.4%) patients utilized their sperm samples for fertility treatment, and 104 patients (14.42%) subsequently requested their samples be discarded. When stratified by age at time of sperm banking, men who banked between the ages of 36 and 40 years had the highest rate of sample utilization for pursuing fertility treatment (12/68, 17.65%, 95% CI 9.5-28.8%). Importantly, those that cryopreserved sperm and subsequently discarded the samples ranged from 8.97% (21 to 25 years) to 28.13% (41 to 45 years). When analyzed by diagnosis, patients who utilized their samples for fertility treatment had varying cancer diagnoses with percent utilization ranging from 4.11% (skin/connective tissue/musculoskeletal cancers) and 20.0% (lung cancer). Overall, 75.59% of the samples collected are unutilized (545/721, 95% CI of 72.3-78.7%). Only 3% were lost to follow up, defined as inability to contact patient after three attempts. Conclusions: Cryopreserved sperm is widely underutilized with only 7.21% of patients utilizing the samples for future conception. Men between ages 36 to 40 years at time of banking are most likely to utilize their samples and utilization varied by cancer diagnosis. This large cohort (with less than 5% lost to follow up) highlights the importance in identifying additional predictors of cryopreserved sperm utilization in cancer survivors. [Table: see text]
Real-world utilization pattern of pexidartinib in patients with tenosynovial giant cell tumor (TGCT).
Authors: Lin Feng , Tse Jenny , Shaikh Nazneen Fatima , Wang Elizabeth J , Near Aimee , Kwong Jackie , Tap William D. 
Published: June 2023

e18792 Background: In August 2019, pexidartinib became the first and only systemic therapy approved in the US for the treatment of symptomatic TGCT associated with severe morbidity or functional limitations and not amenable to improvement with surgery. As TGCT is a rare condition, real-world pexidartinib utilization data are limited and greatly needed to inform clinical use. Methods: Adults (≥18 years) with ≥1 pexidartinib claim from 8/2/2019 - 1/1/2022 identified in the IQVIA Longitudinal Prescription Claims (LRx) linked with Medical Claims (Dx) databases were analyzed. Patient characteristics 6 months before first (index) pexidartinib claim were summarized. Pexidartinib dosing, interruption, and treatment duration were assessed post-index. Discontinuation was defined as treatment gap of ≥90 days. Results: Of 167 patients treated with pexidartinib (median age, 45 years; 59.9% female), the most common comorbidities were osteoarthritis (10.8%), hypertension (8.4%), and obesity (7.8%); 3 patients (1.8%) had mild liver disease and none had moderate-to-severe liver disease pre-index. Median starting dose was 800 mg/day (Table). Over median follow-up of 17.9 months, median (IQR) dose was 622 (442-750) mg/day. Dose reduction was observed in 57 (34.1%) patients and dose increase in 14 (8.4%) patients. Probability of discontinuation was 24.0%, 38.3% and 53.7% at 3-, 6- and 12-month follow-up, respectively. Median (95% confidence interval [CI]) time to pexidartinib discontinuation was 10.1 (7.1, 13.0) months. Fourteen (8.4%) patients restarted pexidartinib after discontinuation. Overall, median (95% CI) time on treatment was 14.2 (10.1, 18.4) months when treatment duration after restart of therapy was considered. Rate of joint surgery after pexidartinib treatment was low (7.2%, n = 12) with median (IQR) time from index to surgery of 5.4 (4.2-12.5) months and median time from last pexidartinib claim to surgery of 2.7 (1.0-8.2) months. Three patients restarted pexidartinib after surgery. Conclusions: Compared to patients in ENLIVEN, real-world pexidartinib patients had similar demographic characteristics. Real-world average daily dose was lower than the full dose recommended in the prescribing information. Compared to ENLIVEN, rate of discontinuation was higher in first 6 months but similar at 12 months. Findings could inform treatment strategy in clinical practice and future research in TGCT. [Table: see text]
Durvalumab outcomes for patients with PD-L1 positive and negative stage III unresectable non-small cell lung cancer treated at veterans health administration facilities.
Authors: Burton Elizabeth M. , Moore Amanda , Nooruddin Zohra , Cotarla Ion , Simmons Daniel , Davis Laura , Reveles Kelly R , Datta Paromita , Roman Souza Gabriel , Irabor Omoruyi Credit , Franklin Kathleen , Jones Xavier , Frei Christopher R 
Published: June 2023

e18793 Background: Clinical trials and real-world studies have documented the benefit of durvalumab consolidation therapy in patients with stage III unresectable non-small cell lung cancer (UR-NSCLC) following chemoradiotherapy (CRT). Methods: Patients with stage III UR-NSCLC on durvalumab following CRT, at any Veterans Health Administration (VHA) facility from 1/1/17 to 6/30/20, were included. Patients were followed from their durvalumab initiation date through the earliest of their last VHA visit, loss to follow up, death, or end of study. Electronic health record and chart review data were retrospectively collected to determine baseline characteristics, number of durvalumab doses, length of follow-up, and overall survival (OS). Chi-square and Wilcoxon rank sum tests were used to compare baseline characteristics for patients with PD-L1 negative (<1%) and positive (1% or greater) tumors. Kaplan-Meier curves were constructed for OS. Cox proportional hazards regression, with controls for divergent baseline characteristics, were used to compare OS between the two groups. Results: Of 935 available patients, 340 had PD-L1 results: 221 had PD-L1 positive (65%) and 119 had PD-L1 negative (35%) tumors. The two groups of patients were largely similar with respect to baseline characteristics, including age, sex at birth, White race, smoking status, marital status, Charlson Comorbidity Index, ECOG status, histology, stage, EGFR, and RAS mutations (Table). Patients with PD-L1 positive and negative tumors had a similar median (interquartile range [IQR]) number of durvalumab doses (15 [6-24] vs 12 [5-23], p=0.38) and length of follow-up (31.5 [12.1-43.5] vs 28.7 [12.2-40.6] months, p=0.43). Kaplan-Meier survival curves were similar for patients with PD-L1 positive and negative tumors: estimated 12-month OS rates (95% CI) of 84% (78%-88%) vs 89% (81%-93%) and 24-month OS rates of 72% (65%-78%) vs 76% (67%-84%); median OS was not reached in patients with PD-L1 positive tumors and was 47.0 months for the PD-L1 negative group. Cox Proportional Hazards regression analysis also demonstrated similar OS for both groups (p=0.64). Conclusions: In this real-world study of a subpopulation of VHA patients with stage III UR-NSCLC and known PD-L1 levels, survival benefits with durvalumab were consistent with those reported in the PACIFIC trial, despite having worse baseline prognostic factors. Patients with PD-L1 positive and negative tumors experienced similar overall survival, including 12- and 24-month OS rates.[Table: see text]
Did COVID-19 impact national trends of hospitalization and outcomes for neutropenic fever in adults with cancer?
Authors: Bhardwaj Prarthna V , Yadukumar Lekha , Patel Ishani , Pasupula Deepak , Loke Chandravathi , Mehta Kathan , Siddappa Malleshappa Sudeep Kumar 
Published: June 2023

e18799 Background: Neutropenic fever (FN) is an oncologic emergency associated with significant morbidity and mortality. Patients on chemotherapy are at a higher risk of COVID-19-related complications. During the initial phase of the pandemic, healthcare systems were overwhelmed, resulting in shortage of resources and rationing of care. We aimed to assess the impact of the COVID-19 on trends of hospitalization and outcomes in adult emergency department (ED) visits for cancer-related FN in the US between 2019 and 2020. Methods: In this retrospective observational study using the National Emergency Department Sample of adults presenting to ED for cancer-related FN as primary diagnosis (using ICD-10-CM codes), we compared the outcomes between patients presenting in 2019 (pre-pandemic) and 2020. The primary outcome was mortality. Secondary outcomes were incidence of shock, discharge disposition, and length of stay (LOS). A propensity score matching was performed to estimate the effect of COVID-19 on outcomes. Results: There were a total of 95,163 visits to the ED for FN in 2019 and 2020. Both groups had similar demographics, with mainly White (68.1% vs 69.3%) patients presenting to large metropolitan areas (57.6% vs 58.6%) and mostly metropolitan teaching hospitals (74.5% vs 77.2%). More patients presenting in 2020 had a higher Elixhauser comorbidity index (66.6% vs 70.2% for comorbidity of ≥3; p = 0.0002). Although the number of patients who got admitted or died in the ED was similar in 2019 and 2020 (88.4% vs 87.8% for admission and 0.1% for death, p = 0.83), higher number died during their hospitalization (3.4% vs 4.4%, p = 0.002), and were likely to develop shock (6.0 vs 7.1%, p = 0.005) in 2020. More patients were discharged home with services (21.9% vs 17.1%, p < 0.001), while fewer patients went to nursing homes (7.9% vs 8.5%, p < 0.001) in 2020. There were no significant differences in LOS or cost of hospitalization. A propensity score matching was performed to estimate the effect of COVID-19 on outcomes showing higher mortality during hospitalization (13.7% vs 4.6%, p = 0.006) and increased LOS (6 days vs 5 days, p = 0.02) for patients with concurrent COVID-19. Conclusions: Overall, mortality related to FN was higher during the pandemic and more so among patients with concurrent COVID-19. While patients developing shock was higher in 2020, this was not attributable to COVID. Fewer patients were discharged to nursing homes, and more patients went home with services during the pandemic highlighting the constraints imposed on resources during the pandemic. [Table: see text]
Association of COVID-19 pandemic with indolent lymphoma care delivery and outcomes in Ontario, Canada: A population-based analysis.
Authors: Crump Michael , Gong Inna Y. , Ante Zharmaine , Calzavara Andrew , Cheung Matthew , Prica Anca A. 
Published: June 2023

e18800 Background: Due to concern for infection risk, the coronavirus disease 2019 (COVID-19) pandemic presented a unique challenge for optimal management of indolent non-Hodgkin lymphoma (iNHL). We examined treatment (trt) selection, healthcare utilization, and COVID-19 outcomes of pts with iNHL receiving first-line (1L) systemic treatment during pre-pandemic vs. pandemic period. Methods: We performed a retrospective cohort study using administrative databases in Ontario, Canada, comparing outcomes in pts with iNHL who initiated trt from, with end of follow-up Mar 31 2022. The primary outcome was trt pattern (eg, 1L regimen, rituximab [R] maintenance use); secondary outcomes were death, toxicities, healthcare utilization (emergency department visit [ED], hospitalization), SARS-CoV-2 outcomes (infection, ED visit, hospitalization/death). Adjusted hazard ratios (aHR) from cause-specific proportional hazards models were used to estimate associations between factors and outcomes. Results: We identified 4,143 pts (1,079 pandemic, 3,064 pre-pandemic), median age 69 yrs, 44% female. In both pre- and pandemic periods, bendamustine (B)+R was the most frequent prescribed regimen, with no difference in number of cycles or dose delays (Table). During the pandemic, fewer pts received R maintenance and completed the full course (aHR 0.81, 95% confidence interval [CI] 0.71-0.92, p = 0.0010) (Table). Pts treated during the pandemic had less healthcare utilization (ED visit aHR 0.77, 95% CI 0.68, 0.88, p < 0.0001; hospitalization aHR 0.81, 95% CI 0.70-0.94, p = 0.0067) and trt-related complications (infection aHR 0.69, 95% CI 0.57-0.82, p < 0.0001; febrile neutropenia aHR 0.66, 95% CI 0.47-0.94, p = 0.020), with no difference in death (aHR 0.79, 95% CI 0.58-1.08, p = 0.14). R use (first dose to 1 yr post last dose) was associated with higher risk of SARS-CoV-2 infection (aHR 1.56, 95% CI 1.09-2.24, p = 0.015) and COVID-19 complications (ED visit aHR 4.28, 95% CI 1.79-10.26, p = 0.0011; hospitalization/death 1.81, 95% CI 1.11-2.93, p = 0.016). Conclusions: During the pandemic, BR remained the preferred regimen for iNHL trt, while R maintenance use was less. Despite the similar 1L regimen, healthcare utilization and infectious complications were less in the pandemic cohort. R use was associated with nearly 2-fold risk of COVID-19 hospitalization/death. [Table: see text]
Survival in patients with cancer of unknown primary site (CUP): Mayo Clinic experience.
Authors: Suleiman Riham , Duran Mayra , Algarin Perneth Sandra , Loor Torres Ricardo , Soto Jacome Cristian , Gile Jennifer , Graham Rondell P. , Villasboas Jose Caetano , Leon-Ferre Roberto Antonio , Thome Stephan , Halfdanarson Thorvardur Ragnar , Fuentes Bayne Harry E 
Published: June 2023

e18802 Background: CUP is a rare cancer with an incidence of 7–12 cases per 100,000/year. CUP is defined as metastatic cancer with no identifiable primary tumor despite comprehensive evaluation. Despite its heterogeneous clinicopathological presentation, the treatment of CUP has primarily been with platinum-based combination chemotherapies but results are poor and survival is short. Here, we describe survival outcomes in real-world dataset of patients with CUP seen at a tertiary referral center. Methods: Retrospective study of patients treated at Mayo Clinic, Rochester MN, from 2010 to 2021. Survival probabilities were estimated with the Kaplan-Meier method. We used Cox proportional hazard regression with forward modeling to explore the association between each variable and death. Overall survival (OS) analysis was conducted in the entire cohort, and it was stratified by histological subtype. For the hypothesis test, we considered p < 0.05 to be statistically significant; all tests were two-sided. All data were analyzed by the SPSS version 22.0 software (SPSS, Chicago, IL, United States). Results: From a total of 214 patients, 198 patients were included in the survival analysis. The patients were predominantly white (87%), female (50.2%), with a mean age of 63 (SD: 13) without history of smoking (51%). The predominant histology was adenocarcinoma (30%), followed by neuroendocrine neoplasms (NEN) (27%), carcinoma NOS (25%), squamous cell carcinoma (SCC) (10%) and non-classifiable tumors (7%). The median follow-up time was 23 months, and medial OS was 23 months in the entire cohort. OS by histology was as follows: 51 months for NEN, 34 months for SCC, 18 months for carcinomas NOS and 11 months for adenocarcinomas (p < 0.001) (fig.1). Similar OS trends were observed when we restricted the analysis to poorly differentiated tumors. The 3- and 5-year cumulative survival by histology were as follows: 7% and 0% for adenocarcinoma, 25% and 8% for carcinoma NOS, 39% and 17% for SCC, and 56% and 22% for NEN. In Cox regression models we did not identify any prognostic factors among patients with adenocarcinoma. Conclusions: Patients with adenocarcinoma of unknown primary possess a considerable challenge and the OS is short. CUP of other histologies have higher OS. This study highlights the need of accurate tumor identification and better treatment, perhaps as a multiomics therapeutic approach.
Genomic landscape of cancer of unknown primary site (CUP): Mayo Clinic experience.
Authors: Duran Mayra , Suleiman Riham , Algarin Perneth Sandra , Loor Torres Ricardo , Soto Jacome Cristian , Gile Jennifer , Graham Rondell P. , Thome Stephan , Villasboas Jose Caetano , Leon-Ferre Roberto Antonio , Halfdanarson Thorvardur Ragnar , Fuentes Bayne Harry E 
Published: June 2023

e18807 Background: CUP represents both a diagnostic and a management challenge. Despite improvements through sophisticated imaging modalities, specific and sensitive testing using immunohistochemistry, a concrete determination of the site of origin of the primary tumor can still be a diagnostic challenge Hereby, we described the genomic landscape of patients with CUP treated at our institution. Methods: Retrospective study of patients with CUP treated at Mayo Clinic Rochester MN from 2010 to 2021. Next generation sequencing (NGS) information was abstracted, and alterations were ranked into different levels of actionability following the Onco KB framework. All data were analyzed by the SPSS version 22.0 software (SPSS, Chicago, IL, United States). Results: From a total of 214 patients, we identified 67 (32%) patients in whom NGS was performed. Among patients with available NGS the median age was 64 years (range: 35-86) and 51% were female. the most prevalent histology included adenocarcinoma (39%), carcinoma NOS (31%), and neuroendocrine tumors (12%). NGS on tumor (t-NGS) was available in 56 (84 %) patients, circulating tumor NGS (b-NGS) was available in 12 (18%) patients, and only 1 patient had both testing available. Among the 56 patients with available t-NGS, MSI-high was detected in 9 patients, whereas among the 12 patients with available b-NGS, MSI-high was detected in 8 patients; yielding an MSI-high detection rate of 16% and 67% for t-NGS and b-NGS. In this cohort, there were a total of 474 genomic alterations detected from which 103 (22 %) were able to be ranked into one therapeutic level following the OncoKB framework. Genomic alterations were most observed among patients with carcinoma (n = 50, 48.53%) adenocarcinoma (n = 33, 32.03 %), squamous cell carcinoma (n = 3, 2.91 %) and neuroendocrine tumor (n = 2, 1.94%). Following the OncoKB framework, 39-level 1 genomic alterations were detected in a total of 14 genes. The most common level 1 genomic alterations comprised the BRCA2 (20.51%), NF1 ATM (17.95%) and HER2/NEU (ERBB2) (15.38%) genes. Therapeutic level 2 included 51 genomic alterations in 13 genes of which KRAS (17.65%), BRAF (15.69%), and BRCA2 (15.69%) were the most prevalent mutated genes. Additionally, level R comprised 13 genomic alterations in the following genes: KRAS (69.23) NRAS (23.08%) and PDGFRA (7.69%). Conclusions: CUP are malignancies rich in potentially actionable alterations, and NGS of tissue and blood samples can inform systemic therapy decisions. Alteration-specific targeted therapy may be an option for a substantial proportion of patients. NGS of tumor tissue or blood should be considered for all patients with CUP.
Outcome differences by sex in oncology clinical trials.
Authors: Kammula Ashwin V. , Schaffer Alejandro A. , Rajagopal Padma Sheila , Kurzrock Razelle , Ruppin Eytan 
Published: June 2023

e18808 Background: NIH guidance advises clinical trials to analyze participants by sex to improve inclusivity. We performed a systematic analysis of reported differences in outcomes between males and females in a registry of oncology clinical trials to characterize treatment response differences more broadly by sex for future trials. Methods: We analyzed Trialtrove ( https://citeline.informa.com/trials/results ), a trial repository using over 58,000 sources, to search for oncology trials that compared outcomes in male and female participants. We implemented algorithms using Python3 programs to search for all trials that contained terms regarding sex in the context of terms suggesting comparison or outcome and considered these as candidate comparison trials. Candidate trials were manually curated to record comparisons by sex across cancer type, treatment, outcome measure, “similar” or “different” by sex and evidence. Outcomes were classified as either “survival / response / other outcome” (SRO) or side effects (E). Evidence for each comparison was labeled as statistically significant (multivariate or univariate), having non-significant numerical evidence, or having no numerical evidence. We counted only those trials in which all comparisons by sex were consistent. Results: 472 of 89,221 oncology trials in Trialtrove (data freeze 12/23/22) (0.5%) performed 532 post-treatment comparisons by sex. Among 288 trials that did statistical SRO comparisons, 47 (16%) trials reported that males showed better, statistically significant treatment responses, while 122 (42%) trials reported better results for females. We observed the strongest differences by sex for two disease-treatment pairs: EGFR inhibitors (EGFRi) in non-small cell lung cancer (NSCLC) and rituximab in non-Hodgkin’s lymphoma (NHL). In 82 trials with SRO comparisons in NSCLC, 35 (43%) showed better treatment responses in females, and 13 (16%) showed better treatment responses in males. Among the 36 NSCLC trials using EGFRi, 21 (58%) showed better treatment responses in females, versus only 1 (3%) in males. In contrast, among all 46 other NSCLC trials with SRO comparisons, 14 (30%) favored females and 12 (26%) favored males. These results suggest that EGFRi may have treatment-specific benefits in females with NSCLC. Among 33 trials with SRO comparisons in NHL, 20 (61%) showed better treatment response in females, versus only 4 (12%) in males. 13 of these trials used rituximab, among which 10 (77%) favor females and only 1 (8%) favors males. Better response in females to rituximab has been reported in single trials but not characterized in aggregate. Conclusions: Our search identified two clinically important disease-treatment pairs that showed markedly improved outcomes in females versus males. Better understanding of differences in treatment response by sex across clinical trials is needed, both to improve inclusivity and as a basis for potential future combination treatments.