tbuckley/cabot-search huggingface dataset:
Gender disparity in breast cancer: A population-based study in the U.S. Department of Veterans Affairs.
Authors: Zainub Ajmal, Abdul Moiz Khan, Fatima Tuz Zahra, Darren Gemoets, Syed Arzoo Mehdi
Journal: Journal of Clinical Oncology (2021)

e12549 Background: Over the last several decades, the mortality for breast cancer has improved, however, there remains a large gender disparity with male patients having worse overall survival. Recent studies have identified increased mortality in male breast cancer (MBC) despite adjusting for age and other clinical factors necessitating a need to evaluate both screening and treatment patterns for MBC. The survival trends in MBC have not been studied across the VA population. Methods: Male and female breast cancer cases between 2000-2018 were identified in National VA Cancer Cube Registry. A total of 1511 cases of MBC and 8081 cases of female breast cancer (FBC) were identified. IRB approval was obtained. Statistical significance was set to 0.05, with significant results noted with an asterisk (*). Results: Our data showed that the number of new MBC cases per year remained stable over the study period while the FBC cases rose by 13.6* per year. The racial distribution of Caucasian and African American (AA) patients was comparable among the two groups. For FBC, the peak incidence was between ages 50-60, while for MBC, the peak incidence was at age greater than 70 years. Males were more likely to present at a later disease stage (stage III and IV) compared to females, (26.94% vs 13.8%) *. They also had a worse performance status (ECOG 3 or higher) at presentation compared to female patients, (3.72% vs 1.32%) *. The survival characteristics and first course of treatment received are summarized in the table below. Our findings show that males have a worse 5-year survival both in early and late-stage disease and across both Caucasian and AA races. This poor survival difference remains when comparing MBC patients older than 50 years but not when comparing the younger subset in both groups. These findings suggest that the overall poor survival of MBC may be related to late detection, advanced age at presentation and subsequent increased comorbidities and poor performance status. Conclusions: Patients with MBC present at a later disease stage and have a worse overall survival when compared to FBC. This difference in survival remained when stratified by age, race and stage at presentation. These results imply the possible underutilization of screening in males as well as differences in the clinical and pathological behavior of male and female breast cancer.[Table: see text]
Abstract GMM-050: IDENTIFICATION OF NOVEL CHROMOSOMAL REARRANGEMENTS IN HIGH-GRADE SEROUS OVARIAN CANCER
Authors: Nanna Sarvilinna, Barun Pradhan, Imrul Faisal, Manuela Tumiati, Amjad Alkodsi, Liisa Kauppi
Journal: Clinical Cancer Research (2019)

Abstract High-grade serous ovarian cancer (HGS-OVCA) is the most common type of ovarian cancer. HGS-OVCA genomes are usually very complex and unstable. Many studies have addressed cytogenetic changes, and with the advent of high-throughput sequencing, complex chromosomal rearrangements. However, little is known about how gene fusions, potentially causing aberrant transcripts and protein products drive tumorigenesis, cell growth and/or metastasis in HGS-OVCA. Patients with the same histological or morphological phenotype of cancer have tumors with diverse genetic backgrounds or molecular phenotypes. There is thus an urgent need to better stratify patients and their tumors and to understand the chemotherapy and other treatment responses at the molecular level. The purpose of this study is to find and charaterize novel recurrent chromosomal rearrangements from HGS-OVCA patient samples. We aim to identify rearrangement hotspots from genomic data. However, not only do we need to identify, characterize and stratify the genomic alterations, but also to find those changes with potentially tumorigenic functions at the RNA and protein levels. We utilise datasets of The Cancer Genome Atlas (https://cancergenome.nih.gov/) and HERCULES Project (http://www.project-hercules.eu/) to identify rearrangement-prone chromosomal regions (putative “breakpoint hotspots”) and complex structural aberrations and variations. We concentrate on exonic aberrations seen in both datasets in at least 2 patients. The findings will be validated using two HGS-OVCA fresh-frozen tumor sample collections from Helsinki and Turku University Hospitals. Clinical data and homologous recombination (HR) score of the tumor samples (HR proficient or HR deficient; Tumiati et al. 2018) will also be analyzed. Preliminary results of this work will be presented. We believe that combining sequencing and clinical data with state-of-the-art molecular level analyses and functional tests will deepen our understanding of HGS-OVCA biology and help to develop new anti-cancer treatment options for this “silent killer”. Citation Format: Nanna Sarvilinna, Barun Pradhan, Imrul Faisal, Manuela Tumiati, Amjad Alkodsi, Liisa Kauppi. IDENTIFICATION OF NOVEL CHROMOSOMAL REARRANGEMENTS IN HIGH-GRADE SEROUS OVARIAN CANCER [abstract]. In: Proceedings of the 12th Biennial Ovarian Cancer Research Symposium; Sep 13-15, 2018; Seattle, WA. Philadelphia (PA): AACR; Clin Cancer Res 2019;25(22 Suppl):Abstract nr GMM-050.
DREAM3R: Durvalumab with chemotherapy as first-line treatment in advanced pleural mesothelioma—A phase 3 randomized trial.
Authors: Patrick M. Forde, Anna K. Nowak, Peey-Sei Kok, Chris Brown, Zhuoxin Sun, Valsamo Anagnostou, Kenneth John O'Byrne, Sonia Yip, Alistair Cook, Willem Joost Lesterhuis, Brett Gordon Maxwell Hughes, Nick Pavlakis, Julie R. Brahmer, Hedy L. Kindler, Anne S. Tsao, Marjorie Glass Zauderer, Suresh S. Ramalingam, Martin R. Stockler
Journal: Journal of Clinical Oncology (2021)

TPS8586 Background: Standard first line treatment for unresectable malignant pleural mesothelioma (MPM) is platinum-based chemotherapy with pemetrexed. Two recent, single-arm, phase 2 trials (DREAM1 and PrE05052) combining the PD-L1 inhibitor durvalumab and standard first line cisplatin and pemetrexed (CP) exceeded pre-specified criteria for proceeding to phase 3. DREAM3R aims to determine the effectiveness of adding durvalumab to first line CP chemotherapy in advanced MPM. Methods: Treatment-naïve patients with advanced MPM will be randomised (2:1) to EITHER durvalumab 1500 mg every 3 weeks plus doublet chemotherapy (cisplatin 75 mg/m2 and pemetrexed 500 mg/m2) every 3 weeks for 4-6 cycles, followed by durvalumab 1500 mg every 4 weeks until disease progression, unacceptable toxicity or patient withdrawal; OR doublet chemotherapy alone for 4-6 cycles, followed by observation. The target sample size is 480 patients (320 durvalumab, 160 control) recruited over 27 months, with follow up for an additional 24 months. This provides over 85% power if the true hazard ratio for overall survival is 0.70, with 2-sided alpha of 0.05, assuming a median survival of 15 months in the control group. Key inclusion criteria: MPM of any histological subtype; measurable disease as per RECIST 1.1 modified for mesothelioma (mRECIST 1.1) without prior radiotherapy to these sites; ECOG PS 0-1; and, adequate hematologic, renal, and liver function tests. Key exclusion criteria: prior systemic anticancer treatment for MPM; diagnosis based only on cytology or fine needle aspiration biopsy; contraindication to immunotherapy; and conditions requiring immunosuppressives or corticosteroids. Stratification: Age (18-70 years vs. &gt; 70), sex, histology (epithelioid vs. non-epithelioid), and region (USA vs. ANZ). The primary endpoint is overall survival. Secondary endpoints include progression-free survival; objective tumour response (by mRECIST 1.1 and iRECIST); adverse events; health-related quality of life; and healthcare resource use. Tertiary correlative objectives are to explore and validate potential prognostic and/or predictive biomarkers (including features identified in the DREAM and PrE0505 studies, PD-L1 expression, tumour mutation burden, nuanced genomic characteristics, and HLA subtypes) in tissue and serial blood samples. An imaging databank will be assembled for validation of radiological measures of response, and studies of possible radiomic biomarkers in mesothelioma. Clinical trial information: NCT04334759. and ACTRN 12620001199909.
The impact of myosteatosis on outcomes following surgery for gastro-intestinal malignancy: A systematic review and meta-analysis.
Authors: Andrew MacCormick, Mark Puckett, Adam Streeter, Somaiah Aroori
Journal: Journal of Clinical Oncology (2021)

e15540 Background: Recent research has demonstrated the impact that body composition parameters can have on the outcomes following cancer surgery. Adipose tissue deposition in muscle, known as myosteatosis, can be detected on pre-operative imaging. This systematic review aims to analyse the impact of pre-operative myosteatosis on long-term outcomes following surgery for gastro-intestinal malignancy. Methods: Using MeSH terms, a systematic search of the databases PubMed MEDLINE, EMBASE, Cochrane, CINAHL and AMED was performed. Studies were included if they reported hazard ratios (HR) analysing the impact of pre-operatively defined myosteatosis, or similar term, on the long-term outcomes following surgery for gastro-intestinal malignancy. A total of 39 full texts articles were reviewed for inclusion, with 19 being included after the inclusion criteria were applied. A sub-group analysis was performed for those studies reporting outcomes for colorectal cancer patients only. Results: The total number of included patients across all studies was 14,481. Patients with myosteatosis had a significantly poorer overall survival, according to univariate (HR 1.82, 95% CI 1.67 – 1.99) and multivariable (HR 1.66, 95% CI 1.49 – 1.86) analysis. This was also demonstrated with regards to cancer-specific survival (univariate HR 1.62, 95% CI 1.18 – 2.22, multivariable HR 1.73, 95% CI 1.48 – 2.03) and recurrence-free survival (univariate HR 1.28, 95% CI 1.10 – 1.48, multivariable HR 1.38, 95% CI 1.07 – 1.77). Conclusions: This review demonstrates that patients with pre-operative myosteatosis have poorer long-term outcomes following surgery for gastro-intestinal malignancy. Therefore, myosteatosis should be used for pre-operative optimisation and as a prognostic tool before surgery. More standardised definitions of myosteatosis and further cohort studies of patients with non-colorectal malignancies are required.
Three versus four cycles of neoadjuvant gemcitabine cisplatin for muscle invasive bladder cancer (MIBC).
Authors: Catherine Kendall Major, Michael Brandon Williams, Mark T. Fleming
Journal: Journal of Clinical Oncology (2021)

e16524 Background: The standard of care for MIBC is neoadjuvant (NAC) cisplatin-based chemotherapy with either 3-4 cycles of dose dense MVAC or 4 cycles of gemcitabine/cisplatin (GC) followed by radical cystectomy. However, due to toxicity some patients are unable to complete intention to treat full course chemotherapy. We aim to identify any variation in overall survival (OS) and progression-free survival (PFS) with 3 vs 4 cycles of neoadjuvant GC in the setting of miUCB. We hypothesize that there will be a statistically significant difference in OS and PFS with three vs four cycles of neoadjuvant GC. Methods: A consecutive retrospective chart review of patients with MIBC treated with three or four cycles of neoadjuvant cisplatin-based chemotherapy from 2009-2020 was performed. R Studio was used to generate Kaplan-Meier curves representing OS and PFS with p-values. Results: One hundred and twenty-one patients were identified. Patient characteristics are described in the table below. Eighty-six patients received 4 cycles of GC and thirty-five patients received 3 cycles. Ninety-five patients proceeded to cystectomy: 93 received a radical cystectomy, 1 received a partial cystectomy, and 1 was aborted due to positive lymph nodes. There was a statistically significant difference in OS between those who got 3 or 4 cycles (p=0.03) and PFS (p=0.014). Median OS for those who got 3 cycles and 4 cycles was 52 months and 92 months respectively. Conclusions: Toxicity can preclude patients from receiving four cycles of GC and this study demonstrates a significant difference in overall OS and PFS between those who receive 3 vs 4 cycles of GC.[Table: see text]
Association of PET/CT response assessment prior to CAR T-cell infusion with outcomes after CAR T-cell therapy in aggressive B-cell lymphomas.
Authors: Alexandra Nader, Hwan Lee, Mark Sellmyer, Daniel Jeffrey Landsburg, Sunita Nasta, James Gerson, Jakub Svoboda, Stefan K. Barta, Elizabeth Weber, Stephen J. Schuster, Elise A. Chong
Journal: Journal of Clinical Oncology (2021)

e19568 Background: Anti-CD19 chimeric antigen receptor modified T-cell therapies (CAR-T) have expanded the treatment possibilities for many patients with relapsed/refractory (R/R) aggressive large B-cell lymphomas (B-NHL) but fails to achieve remissions in a considerable proportion of patients. In this study, we examined whether response to systemic therapy prior to CAR T-cell infusion is associated with outcome. Methods: We analyzed a retrospective dataset of R/R B-NHL patients (pts) treated with commercially available CAR-T at the University of Pennsylvania treated from April 2018 to August 2020. 18F-FDG PET/CT scans obtained directly prior to and after CAR-T therapy were re-evaluated for response by an independent radiologist using the Lugano 2014 criteria. Association between pre-therapy and post-therapy responses were examined using Fisher’s exact test. Results: 50 pts with aggressive R/R B-NHL were enrolled. 34 pts received tisagenlecleucel and 16 received axi-cel. Median age was 61 (range 29-82), and 27 pts (54%) were men. Most pts (n = 48, 96%) had ECOG performance status of 0-1, with a median number of 3 prior therapies (range 1-11). 14 (28%) of pts had LDH elevation at time of CAR T cell infusion. Median time from pre-therapy PET/CT to infusion was 47 days (range: 6-155). Median PFS was 3.4 months. Prior to CAR T cell infusion, responses were as follows: 12 complete response (CR), 9 partial response (PR), 8 stable disease (SD) and 21 progressive disease (PD). Post-therapy responses were: 20 CR, 5 PR, 2 SD, and 23 PD. 67% of pts with a CR pre-therapy had continued CR after CAR T-cell infusion, whereas 32% pf pts without a CR had a CR after infusion (p &lt; 0.05). There was a trend toward CR/PR immediately prior to CAR T cell infusion being significantly associated with CR after CAR-T. We found that high metabolic tumor volume ( &gt; 350cc vs ≤350cc) was associated with poorer PFS (log rank, p = 0.05). We did not find elevated LDH or use of bridging therapy to be associated with response to CAR-T. Conclusions: This is the largest report of lymphoma patients treated with CAR-T while in remission to date and suggests the importance of optimizing clinical response prior to CAR-T. Although patients in CR were excluded from the registrational trials, it is notable that patients in CR prior to CAR-T had a high rate of CR post CAR T cells despite the absence of active lymphoma on imaging. Longer follow-up is needed to confirm these early observations.
Analysis of real-world (RW) data for metastatic breast cancer (mBC) patients (pts) with somatic <i>BRCA1/2</i> (<i>sBRCA</i>) or other homologous recombination (HR)-pathway gene mutations (muts) treated with PARP inhibitors (PARPi).
Authors: Felipe Batalini, Russell Madison, Dean C. Pavlick, Ethan Sokol, Tamara Snow, Arjun Sondhi, Garrett M. Frampton, Colby Jenkins, Judy Ellen Garber, Gerburg M. Wulf, Jeffrey Michael Venstrom, Nadine M. Tung, Emily Castellanos, Alexa Betzig Schrock, Kimberly McGregor
Journal: Journal of Clinical Oncology (2021)

10512 Background: PARPi are approved for treatment of pts w/ HER2-negative mBC and germline BRCA1/2 (g BRCA) pathogenic or likely pathogenic variants (muts); however, clinical benefit has also been demonstrated in mBC pts w/ sBRCA or other HR-pathway gene muts. Using a RW Clinico-Genomic Database (CGDB), we assessed outcomes for pts w/ gBRCA muts compared to pts w/ either s BRCA or other HR-pathway muts treated w/ PARPi. Methods: 6,329 mBC pts from ̃280 US cancer clinics were included in the Flatiron Health (FH) -Foundation Medicine (FM) CGDB, which includes comprehensive genomic profiling (CGP) linked to de-identified, electronic health record (EHR)-derived clinical data. Eligible pts had mBC, received care in the FH network from 1/1/2011-9/1/2020, and had tissue CGP by FM. Pts classified as gBRCA: positive germline result in EHR and BRCA mut predicted germline per FM’s somatic, germline, zygosity algorithm (SGZ) (Sun et al PMID 29415044). Non-g BRCA: negative germline results in EHR and a somatic BRCA (s BRCA) mut per SGZ or BRCA wild-type w/ another HR mut per CGP result. Pts w/o a documented gBRCA result in EHR, unknown FM BRCA SGZ result, or conflicting results were excluded. RW overall survival (rwOS) and RW progression-free survival (rwPFS) from start of PARPi for pts w/ gBRCA and non- gBRCA mBC were compared using Kaplan-Meier analysis and Cox regression adjusted for mBC line number, prior platinum, age at PARPi initiation, race, and receptor status. Results: Among pts who received PARPi in the mBC setting, 44 had gBRCA and 18 had non -gBRCA: 9 s BRCA (5 BRCA1, 4 BRCA2), 4 PALB2, 2 ATM, and 1 each of ATM+CDK12, BARD1+FANCF+RAD54L, and CHEK2. Of HR muts 76% were confirmed biallelic: 33/44 gBRCA (11 unknown), 8/9 sBRCA, 3/4 PALB2, and 3/5 other (1 unknown). Neither median rwPFS nor rwOS from start of PARPi were significantly different between the non-g BRCA and g BRCA cohorts (rwPFS: 7.0 [4.6-11.3] vs 5.5 [4.3-7.2] months (mos), aHR: 1.19 [0.57 – 2.43]; rwOS: 15.0 [7.95-16.3] vs 11.5 [9.46-NA] mos, aHR: 0.85 [0.36-1.98]). For 9 pts w/ sBRCA mut, median rwPFS was 7.1 mos (range 1.4-12.4) and all pts had progressed by data cut off. Conclusions: Despite small pt numbers and limitations from RW data, our results suggest that pts w/ biallelic non-g BRCA mBC may derive similar benefit from PARPi when tumor CGP detects a s BRCA mut or germline or somatic mut in other HR-pathway genes. These findings are consistent w/ the results from TBCRC-048 (Tung et al PMID 33119476) and support further randomized trials exploring the efficacy of PARPi in this population.[Table: see text]
Nuclear dihydroxyacetone phosphate signals nutrient sufficiency and cell cycle phase to global histone acetylation
Authors: Jiao-Jiao Zhang, Ting-Ting Fan, Yun-Zi Mao, Jun-Li Hou, Meng Wang, Min Zhang, Yan Lin, Lei Zhang, Guo-Quan Yan, Yan-Peng An, Jun Yao, Cheng Zhang, Peng-Cheng Lin, Yi-Yuan Yuan, Jian-Yuan Zhao, Wei Xu, Shi-Min Zhao
Journal: Nature Metabolism (2021)
Effect of immunotherapy on survival outcomes in prostate cancer: Systematic review and meta-analysis.
Authors: Vinod solipuram, Kishor Pokharel, Bhanu Prasad Venkatesulu, Harideep Samanapally
Journal: Journal of Clinical Oncology (2021)

e17030 Background: Prostate cancer is one of the leading cancers in men with an estimated 191,930 new cases in 2020 in the USA alone. Treatment options for metastatic castration resistant prostate cancer (mCRPC) have evolved in recent years. Immunotherapy involving vaccines like sipuleucel-T, PROSTVAC and immune checkpoint inhibitors have been evaluated in these patients. We present a systematic review and meta-analysis of the randomized controlled trials (RCTs) testing the effect of immunotherapy in mCRPC. Methods: A systematic search was performed using PubMed, Embase and the Cochrane library without language limitations from inception to January 3, 2021. The primary outcome was overall survival (OS) and secondary outcomes were progression free survival (PFS), prostate specific antigen (PSA) reduction ≥ 50% and incidence of grade 3-4 adverse events. The analysis of OS, PFS was done using random effects hazard ratio (HR) by generic inverse variance method and analysis of PSA reduction ≥ 50% and grade 3-4 adverse events was done using random effects risk ratio (RR) by the Mantel-Haenszel method. Results: 12 RCTs comprising 4109 patients were included in the analysis. There was a statistically significant improvement in OS (HR 0.89; 95% CI (0.81, 0.97)) and PFS (HR 0.83; 95% CI (0.76, 0.92)) in the immunotherapy arm compared to placebo or standard treatment arms with moderate quality of evidence. Patients in the immunotherapy group had significant reduction in PSA ≥ 50% (RR 1.71; 95% CI (1.09, 2.68)) but also had statistically significant increased risk of grade 3-4 adverse events (RR (1.25; 95% CI (1.02, 1.54)) when compared to placebo and the standard treatment group. Subgroup analysis showed that the use of vaccine therapy in prostate cancer leads to significant improvement in OS (HR 0.83; 95% CI (0.74, 0.93)) and PFS (HR 0.80; 95% CI (0.67, 0.95)) compared to placebo and standard treatment. The use of immune checkpoint inhibitors was not associated with statistically significant improvement in OS (HR 0.98; 95% CI (0.88, 1.09)) but is associated with improvement in PFS (HR 0.87; 95%CI (0.81, 0.94)). Conclusions: This meta-analysis showed that immunotherapy led to significant improvement in OS, PFS and PSA reduction of ≥ 50%. However, there is an increased incidence of grade 3-4 adverse events with the use of immunotherapy when compared to other standard therapies and placebo. The improvement in overall survival is limited to the use of vaccine therapy and not to immune checkpoint inhibitors. Careful use of selective forms of immunotherapy in mCRPC can lead to greater improvement in survival.
Survival in male breast cancer (MaBC) over the past three decades.
Authors: Jose Pablo Leone, Rachel A. Freedman, Julieta Leone, Michael J. Hassett, Sara M. Tolaney, Carlos Teodoro Vallejo, Bernardo Amadeo Leone, Eric P. Winer, Nancy U. Lin
Journal: Journal of Clinical Oncology (2021)

569 Background: Breast cancer mortality in women has declined significantly over the past several years. In men, it is unclear whether survival has changed over time. The aim of this study was to evaluate changes in breast cancer-specific survival (BCSS) and overall survival (OS) in MaBC over the past three decades. Methods: We evaluated men diagnosed with breast cancer between 1988 and 2017, with known cause of death reported in the Surveillance, Epidemiology, and End Results registry. Patients were categorized into 3 groups by year of diagnosis: 1988-1997, 1998-2007 and 2008-2017. BCSS and OS were estimated by Kaplan-Meier and differences between groups were compared by log-rank test. Cox proportional hazards regression was used to evaluate the independent association of tumor and patient characteristics with BCSS and OS. Results: We included 8,412 men diagnosed between 1988-1997 (N = 1,033), 1998-2007 (N = 2,938) and 2008-2017 (N = 4,441). Median age for the overall population and within each decade of diagnosis was 68 years. Median follow-up was 23.6 years, 14.3 years and 4.5 years in periods 1988-1997, 1998-2007 and 2008-2017, respectively. Overall, BCSS at 5 years was 83.5%, 83.6% and 84.3% in periods 1988-1997, 1998-2007 and 2008-2017, respectively; p = 0.8. There was no significant difference in BCSS between the three periods of diagnosis within each stage of breast cancer (stage I, II, III and IV). Among all patients, OS at 5 years was 64.7%, 67.2% and 69.3% in periods 1988-1997, 1998-2007 and 2008-2017, respectively; p = 0.01. In multivariate Cox models, older age at diagnosis, black race, grade 3 disease, increasing stage, hormone receptor negative status and no surgery were all independently associated with worse BCSS and OS. In these adjusted Cox models, each additional year of diagnosis had no significant association with BCSS (hazard ratio, 1.0; 95% CI, 0.99 – 1.01; p = 0.78), and a significant improvement in OS (hazard ratio, 0.99; 95% CI, 0.98 – 0.99; p = 0.01). Conclusions: Over the past three decades, there has been no significant improvement in BCSS in MaBC. The changes in OS over time suggest increasing life expectancy. Efforts to improve BCSS in MaBC are warranted.