tbuckley/cabot-search huggingface dataset:
Correlation of HRD status with clinical and survival outcomes in patients with advanced-stage ovarian cancer.
Authors: Travis T. Sims, Anil K. Sood, Shannon Neville Westin, Bryan M. Fellman, Jenna Unke, Kelly M Rangel, Tyler Hilton, Nicole D. Fleming
Journal: Journal of Clinical Oncology (2021)

5568 Background: Nearly 50% of patients with high grade ovarian cancer (HGOC) harbor a germline or somatic mutation in BRCA1/BRCA2 or have tumors characterized by homologous recombination deficiency (HRD). HRD is associated with response to poly(ADP-ribose) polymerase inhibitors (PARPi) in HGOC. Although PARPi show great promise, there is interest in investigating how HRD status affects outcomes and can be used to objectively tailor other treatment strategies. We aimed to compare clinical and survival outcomes in HGOC stratified by HRD status. Methods: We performed a retrospective analysis of all advanced HGOC from April 2013 to June 2019. Patients were included if germline BRCA and HRD status was known. Clinical outcomes were analyzed and stratified by (1) germline BRCA+ (2) germline BRCA - and somatic BRCA/HRD+, or (3) BRCA-/HRD-. Progression free (PFS) and overall survival (OS) were estimated using Kaplan-Meier methods stratified by HRD status and modeled via Cox proportional hazards regression. Results: 1271 patients with advanced HGOC presented during the study period of which 187 met inclusion criteria. 106 patients had germline BRCA mutation, 26 somatic BRCA/HRD+, and 55 BRCA/HRD-. Patients who had HRD- tumor had older median age at diagnosis (63 vs. 54 and 60 years, p&lt;0.001), white race (89% vs. 74% and 68%), non-serous histology (20% vs. 6% and 0%, p=0.04), required more NACT chemotherapy cycles (4 vs. 3 and 3 cycles, p=0.03), and less complete gross resection (R0) at tumor reductive surgery (TRS) (60% vs. 83% and 77%, p=0.02). Patients who had BRCA/HRD- tumor had worse PFS (14.9 months) compared to germline BRCA+ (23.5 months) or somatic BRCA/HRD+ (20.2 months, p&lt;0.001). Patients with BRCA/HRD- disease also had worse OS (42.3 months) compared to germline BRCA+ (68.8 months) or somatic BRCA/HRD+ (69.2 months). Multivariate analysis for PFS revealed that age (HR 1.02, 95% CI 1.00-1.04), p=0.01), stage (HR 5.7, 95% CI 1.39-23.4, p=0.02), R0 resection at TRS (HR 0.41, 95% CI 0.21-0.83, p=0.01), and BRCA/HRD- status (HR 1.63, 95% CI 1.07-2.48, p=0.02) were significant factors impacting PFS. Multivariate analysis for OS revealed that age (HR 1.07, 95% CI 1.03-1.10, p&lt;0.001) and R0 resection at TRS (HR 0.19, 95% CI 0.08-0.44, p&lt;0.001) were significant factors impacting OS. Conclusions: Germline BRCA-mutant, somatic BRCA/HRD+ HGOC was associated with improved PFS and OS regardless of primary TRS or NACT. BRCA-/HRD- was a negative prognostic factor for survival in HGOC.
A phase Ib/II study of selinexor in combination with imatinib in patients with advanced gastrointestinal stromal tumor (GIST): SeliGIST/GEIS-41 trial.
Authors: Cesar Serrano, Claudia Valverde, Josefina Cruz Jurado, Javier Martinez-Trufero, Xavier Guri, Martina Giuppi, Andrés Redondo, Beatriz Suarez-Paniagua, Cleofe Romagosa, Virginia Martinez
Journal: Journal of Clinical Oncology (2021)

11534 Background: KIT or PDGFRA oncogenic activation drives GIST progression throughout the disease course. Accordingly, currently approved agents in metastatic GIST focus on the therapeutic suppression of these receptors. However, the clinical benefit after imatinib (IM) progression is still modest, suggesting the co-operation of KIT/PDGFRA-independent mechanisms in GIST cell survival. Selinexor is an oral, selective inhibitor of XPO1-mediated nuclear export, and preclinical studies evidenced antitumoral activity in GIST as single agent and in combination with IM in both IM-sensitive and IM-resistant models. Methods: The phase Ib portion studied IM 400 mg daily plus weekly selinexor in patients (pts) with IM-resistant, advanced GIST. Prior intolerance to IM was not allowed. A standard 3+3 dosing schema was utilized to determine the recommended phase II dose (RP2D) of this combination. Investigator-assessed response was evaluated every 8 weeks using RECIST 1.1. Results: At data cutoff of Sep 25, 2020, 12 pts were enrolled and received treatment with IM 400 mg and selinexor once weekly at dose levels (DL) 1 (60 mg), DL2 (80 mg) and DL3 (100 mg). Median age 57 (range 46-77), 42% female, median prior therapies 4 (range 2-7). Although only 1/6 pts developed a dose limiting toxicity (DLT) at DL3, the RP2D was defined at DL2 (IM 400 mg daily and selinexor 80 mg once weekly) based on activity data in the DL2 and the need for dose reductions in 5/6 pts at DL3 after the DLT window. All pts were evaluable for toxicity and response. One DLT occurred at DL3 (G3 nausea). Non-DLT G3/4 toxicities were anemia (1/12 pts), neutropenia (1/12 pts), vomiting (1/12 pts) and fatigue (2/12 pts). Common G1/2 toxicities were nausea (11/12 pts), vomiting (10/12 pts), neutropenia (5/12 pts) and anemia, fatigue, diarrhea, and periorbital edema (4/12 pts each). No unexpected toxicities were observed. Overall response rate in the 12 pts evaluable for response was 67% (95% CI 0.349-0.901), with 2 pts achieving PR (17%) and 6 pts SD (50%) as the best response. Clinical benefit rate (CBR = CR, PR, SD) ≥ 16 weeks was 42% (95% CI 0.157-0.723). Median progression free survival was 3.5 months (95% CI 1.7-7.3). Four pts remain on trial at data cutoff. Conclusions: IM and selinexor combination is well-tolerated and has clinical activity in heavily pretreated GIST pts. The trial is currently exploring selinexor as single agent in the IM-resistant GIST population. Clinical trial information: NCT04138381.
Development of the oncology opportunity cost assessment tool.
Authors: Nathan Handley, Adam F Binder, Alexandra Gentsch, Rachel Granberg, Arianna Heyer, Garrison Davis, Garrison Nord, Kristin Rising
Journal: Journal of Clinical Oncology (2021)

e13502 Background: While awareness of direct patient-level costs of cancer care are growing, less is known about the patient-level opportunity cost of care. Opportunity costs of care may include time spent seeking care, lost wages, lost leisure time, and other indirect costs associated with seeking care. Despite acknowledgment of the importance of considering patient opportunity costs in care treatment decisions, assessment of opportunity costs experienced by individual patients or caregivers is not routinely performed by healthcare providers in general, or oncology providers in particular. The purpose of this work was to develop an instrument, the Oncology Opportunity Cost Assessment Tool (OOCAT), to evaluate patient opportunity cost of seeking oncology care. Methods: Survey development was an iterative process with multiple rounds of stakeholder engagement. First the research team developed a list of potential opportunity cost themes informed by their own experiences. Next, we met with an established patient advisory group within the cancer center to expand this list of themes. We then conducted focus groups with patients and caregivers to explore in further depth their logistical and financial considerations related to seeking care. Findings were used to further expand the list of opportunity cost themes, with this list reviewed in real time with the focus group participants to ensure perspectives were appropriately captured. We then generated a set of survey items to represent each of the themes listed. We generated two items to represent each unique theme. The first item of the instrument sought to quantify the opportunity cost of the theme (e.g. time spent parking); the second component ascertained the patient-perceived importance of the theme using a 7-point Likert scale. Upon drafting of the initial OOCAT, we performed cognitive interviews with a random sampling of patients in order to ensure content validity and clarity of instrument items. Results: We completed 4 virtual focus groups with a total of 23 participants (17 patients and 6 caregivers) followed by cognitive interviews with 13 patients. The resulting OOCAT consists of 17 items that examine time requirements, financial implications, and logistical and quality of life challenges for both patients and caregivers associated seeking oncology care. Conclusions: The OOCAT is a 17-item instrument designed to quantify patient-level opportunity costs of seeking oncology care. Further studies work is needed to validate the OOCAT survey and assess the impact of incorporating quantified assessment of opportunity cost into decision regarding when and where to seek oncology care.
Inhibition by free radical scavengers and by cyclooxygenase inhibitors of pial arteriolar abnormalities from concussive brain injury in cats.
Authors: E PWei, H AKontos, W DDietrich, J TPovlishock, E FEllis
Journal: Circulation Research (1981)

We studied the role of prostaglandins and free radicals in the induction of the functional and morphological pial arteriolar abnormalities produced by concussive brain injury. Anesthetized cats equipped with a cranial window for the observation of the pial microcirculation were subjected to concussive brain injury using a fluid-percussion device following administration of cyclooxygenase inhibitors (indomethacin or AHR-5850) or the vehicle for the solution of these agents (NaCl or Na2CO3 solution). Pial arterioles from vehicle-treated animals displayed sustained dilation, reduced responsiveness to the vasoconstrictor effect of arterial hypocapnia, and a high density of endothelial lesions. Animals pretreated with cyclooxygenase inhibitors showed less pronounced vasodilation, normal responsiveness to hypocapnia, and a significantly reduced number of lesions. The vasodilation and reduced responsiveness to the vasoconstrictor effects of hypocapnia after brain injury also were inhibited by topical application...
Paclitaxel versus docetaxel-based neoadjuvant chemotherapy and risk of lymphedema in breast cancer patients.
Authors: Yirong Zhu, Tamer Refaat Abdelrhman, Yvonne D. Ho, Tarita Thomas, William Small, Constantine Godellas, Faaiza Vaince, Hanh P. Mai
Journal: Journal of Clinical Oncology (2021)

e12620 Background: Neoadjuvant chemotherapy (NAC) is commonly utilized in women with locally advanced breast cancer, usually followed by surgery and radiation therapy (RT). Many studies aimed to address the risk factors contributing to a higher incidence of lymphedema in patients with breast cancer. Our group previously reported the extent of surgery increases the risk of lymphedema. Adjuvant chemotherapy with taxane-based regimens are associated with an increased risk of lymphedema likely due an increase in interstitial extracellular fluid volume therefore resulting in fluid retention. This study aims to directly compare and characterize the risk of lymphedema in patients receiving paclitaxel versus docetaxel-based NAC. Methods: This is a retrospective study approved by our institutional review board. The study included women with breast cancer treated consecutively at our institution with taxane-based NAC followed by surgery and RT from 2006 to 2018. Patients and tumor characteristics including age, race, body mass index (BMI), clinical stage, hormone receptor, HER2 status, type of surgery, RT techniques, and type of NAC (Paclitaxel versus Docetaxel), and its association to risk of lymphedema were analyzed using univariable and multivariable binary logic regression tests. Lymphedema was assessed before RT and at follow up visits, and was identified by &gt;2.0-cm increase in arm circumference, or &gt;10% increase in limb volume, or new self-reported lymphedema symptoms. Results: A total of 263 patients treated with either paclitaxel or docetaxel-based NAC were identified and analyzed. At a median follow up of 28.4 months (range 3.5-158.7 months). 26.2% (69/263) of patients developed lymphedema. On a multivariable analysis, patients who underwent axillary lymph node dissection (ALND) had a significantly higher rate of lymphedema (42.6%) compared to those who had only a sentinel lymph node biopsy (SLNB, 10.5%, p&lt;0.05). Regardless of the type of surgery, there was no significant difference in rates of lymphedema between patients who received paclitaxel versus docetaxel-based NAC (28.7% vs 21.3%). However, among high-risk patients who underwent mastectomy with ALND, NAC with Paclitaxel was associated with a significantly higher rate of lymphedema compared to docetaxel (56.8% vs 22.7%, RR 2.50, p&lt;0.05). Conclusions: This represents one of the largest studies examining the impact of taxane-based NAC on the risk of lymphedema in women with breast cancer. In this study, paclitaxel-based NAC was associated with a significantly higher risk of lymphedema in women who underwent mastectomy and ALND compared to docetaxel based chemotherapy. A larger, balanced, prospective study is warranted to verify this previously unidentified lymphedema risk from paclitaxel and guide individualized NAC decision.
Clinical characteristics and outcomes of adult lymphoma-associated hemophagocytic lymphohistiocytosis (HLH).
Authors: Christina Y. Lee, Beatriz Wills, Santosha Adipudi Vardhana, Alison J. Moskowitz
Journal: Journal of Clinical Oncology (2021)

e19526 Background: Lymphoma is a major cause of secondary HLH, a life-threatening hyperinflammatory syndrome due to immune dysregulation. This study examines the clinical and biological characteristics, management, and outcomes of patients with lymphoma and HLH. Methods: We retrospectively reviewed 44 adult patients with combined diagnoses of lymphoma and HLH at Memorial Sloan Kettering Cancer Center between June 2012 and September 2020. Overall survival (OS) was measured from the date of HLH diagnosis to the date of death or last follow-up. We evaluated the association of demographic, clinical, laboratory, and treatment variables on survival using log-rank tests and Cox proportional hazards model. Results: Of the 44 patients, 30 (68%) had T and NK-cell lymphoma, 12 (27%) had B-cell lymphoma, and 2 (5%) had Hodgkin lymphoma. All but one patient received HLH therapy including corticosteroids (95%), etoposide (68%), and intravenous immunoglobulin (18%), which was initiated within 1 day of diagnosis in 84% of cases. Twenty-five patients (57%) received lymphoma-directed therapy with etoposide (n = 17) or without etoposide (n = 8). Five of the 15 patients who underwent targeted tumor-sequencing of 400 genes harbored a TP53 mutation and all were refractory to frontline therapy, while 7 of 10 patients without TP53 mutation demonstrated initial treatment response ( p= 0.03). The median OS (mOS) of the entire cohort was 1.4 months, with a 30-day cumulative mortality incidence of 36.4%. Most deaths were attributed to relapsed or refractory HLH (n = 25/36, 69%) and lymphoma progression (n = 6/36, 17%). Patients with T/NK-cell lymphoma-associated HLH had a mOS of 1.4 months compared to 9.2 months in B-cell lymphomas ( p= 0.09). Ten patients (23%) were diagnosed with HLH within 60 days of their initial lymphoma diagnosis and had an improved prognosis (mOS 12.8 vs 1.3 months, p= 0.006). Treatment with etoposide, either alone or as part of a lymphoma-directed regimen, was associated with significantly improved survival (HR 0.48, 95% CI 0.24-0.96) whereas lymphoma-directed therapy with or without etoposide was not (HR 0.66, 95% CI 0.34-1.29). Significant predictors of mortality included age ≥60 years, non-white race, and concurrent infection during the hospitalization. Conclusions: In this large cohort from a single U.S. institution, there was a wide range of lymphoma subtypes associated with HLH. Despite increased disease recognition and prompt initiation of standard HLH and lymphoma-directed therapies, the prognosis remains very poor. Patients treated with etoposide had improved survival, highlighting the importance of controlling hyperinflammation during initial management. Notably, TP53 mutation was associated with primary refractory HLH. Future studies will aim to elucidate the pathophysiology of lymphoma-associated HLH in order to inform novel therapeutic approaches.
An analysis of content of lay-press articles focused on cancer from leading U.S. newspapers from 2010 to 2019.
Authors: Abena A. Adwetewa-Badu, Ryan M O'Keefe, Joseph X. Callahan, Catherine A. Taylor, Chris P. Gjino, Christine E. Hill-Kayser
Journal: Journal of Clinical Oncology (2021)

e24032 Background: Newspaper coverage of cancer-related topics has historically focused on research, treatment, survival, and impact of tobacco and diet on risk, with less coverage of prevention, death, and palliation/hospice. Coverage tends to be driven by celebrity and other seminal events, and highest during awareness-months, with over and under representation of breast and lung cancers, respectively, based on incidence. We sought to understand evolving trends in coverage over the last decade at 3 major U.S newspapers to identify areas for improvement for education, inclusion, and public health messaging. Methods: On 10/13/20, Factiva was queried with the keyword “cancer” for articles &gt; 150 words published by NYTimes, Washington Post, and Wall Street Journal between 2010-2019. The top 100 articles by “relevance” were selected for each, representing 14.9% of all the 2016 hits. A coding scheme was created using articles from the same query for 2020; inter-rater reliability analysis between coders was conducted with a sample of 30 articles (10% of final set), and kappa-fleiss scores were calculated. Articles were excluded if they did not focus on cancer, or were an obituary, financial report, or editorial. Results: 230 articles were included. Kappa-fleiss scores were 0.74 - 1, suggesting excellent agreement between coders. 102 (44.3%) focused on research, 50 (21.7%) individual disease narratives, 22 (9.6%) drug development, 15 (6.5%) policy or regulation. 136 articles focused on one sub-type; breast (53, 39.0%) was most common, followed by colorectal (13, 9.6%), leukemia/ lymphoma (12, 8.8%), prostate (11, 8.1%), pancreatic (9, 6.6%), and lung (8, 5.9%). 154 articles discussed research; 22 (14.3%) non-human research. Commonly covered topics included pharmaceuticals (128, 55.7%), risk factors (71, 30.9%), cost of care (66, 28.7%) and adverse effects (58, 25.2%). Risk factors discussed included smoking (22, 31.0%), diet (21, 29.5%), and alcohol (7, 9.9%). Less common topics were radiation (18.7%), insurance coverage (13.9%), celebrities (12.6%), death (8.7%), race (4.3%), and disparities (3.9%). 156 (67.8%) provided quotes from HCPs/researchers, 59 (25.7%) patients, 17 (7.4%) families or other supports. 22 (9.6%) titles had “war” terminology; 13 (5.7%) had the word “may”. Conclusions: Most articles focused on research or personal narratives, most commonly in context of breast, colorectal, and leukemia/lymphoma. Pharmaceutical treatments were the most discussed content topic. Compared with previous analyses, risk factors, adverse effects, and cost of care were discussed more often. However, race, disparities, death, and end-of-life topics remain uncommon. There was good representation from the healthcare and scientific community; opportunities exist to include more educational information on risk and adverse events, as well as patient and family perspectives.
A phase III study (APROMISS) of AL3818 (Catequentinib, Anlotinib) hydrochloride monotherapy in subjects with metastatic or advanced synovial sarcoma.
Authors: Brian Andrew Van Tine, Sant P. Chawla, Jonathan C. Trent, Breelyn A. Wilky, Rashmi Chugh, Bartosz Chmielowski, Shivaani Kummar, Atrayee Basu Mallick, Neeta Somaiah, Lee D. Cranmer, Mark Agulnik, Vicki Leigh Keedy, Silvia Stacchiotti, Bruno Vincenzi, Giuseppe Badalamenti, Brittany L Siontis, Steven Attia
Journal: Journal of Clinical Oncology (2021)

11505 Background: AL3818 (Catequentinib, Anlotinib) is a novel, orally administered, small molecule tyrosine kinase inhibitor. The primary objective of this Phase 3 study is to evaluate the efficacy of AL3818 monotherapy in patients (pts) with synovial sarcoma (SS) comparing with dacarbazine in randomization setting. Methods: Patients with a diagnosis of synovial sarcoma requiring second line or further line treatment were eligible for enrollment. The regimen was a 21-day cycle with oral AL3818 administered on 14 days on and 7 days off. This phase 3 trial is randomized in 2:1 ratio of AL3818 comparing to dacarbazine with option of crossover after PD of dacarbazine treatment. Progression free survival (PFS) with Log Rank test is the primary endpoint and this trial for SS is currently completed enrolled in US and Italy. Results: Total 79 pts initiated treatment and are evaluable, 52 received AL3818 as treatment arm (T), and 27 received dacarbazine (D) as control arm (C). Arms T/C median ages were 40.5/42.0 years (range: 18-70+) and 20/16 (38.5%/59.3%) were male. Overall, PFS was 2.89 months (95% CI: 2.73 – 6.87) for AL3818 and 1.64 (95% CI: 1.45 – 2.70) for D. The PFS of study met the primary endpoint with a p-value of 0.0015 and a HR of 0.449 (95% CI: 0.270– 0.744). At the month 4, 6, and 12, the percentages of progression free patients for AL3818 were 48.1%, 42.3% and 26.9%; and for D were 14.85%, 11.1% and 3.7%. For grade 3 treatment-related adverse events, 12(23.1%) of pts experienced for AL3818 and 7(25.9%) of pts experienced for D. The most common AL3818 related grade 3 AEs were diarrhea (5.8%) and hypertension (3.8%). Conclusions: This phase III trial demonstrates improved disease control and superior progression free survival for AL3818 vs dacarbazine in advanced SS. In addition, the study further confirms the acceptable benefit-risk profile of AL3818 from the prior randomized Phase 2b soft tissue sarcoma study (NCT02449343). AL3818 is a meaningful treatment option for pts with advanced SS. Clinical trial information: NCT 03016819 Clinical trial information: NCT03016819.
Delivery of a spheroids-incorporated human dermal fibroblast sheet increases angiogenesis and M2 polarization for wound healing
Authors: Sung-Won Kim, Gwang-Bum Im, Gun-Jae Jeong, Sangyul Baik, Jiyu Hyun, Yu-Jin Kim, Changhyun Pang, Young Charles Jang, Suk Ho Bhang
Journal: Biomaterials (2021)
Abstract GMM-052: EVIDENCE FOR APOBEC MUTAGENESIS IN CLEAR CELL OVARIAN CARCINOMA
Authors: Artur S. Serebrenik, Matthew C. Jarvis, Prokopios P. Argyris, William B. Brown, Reuben S. Harris
Journal: Clinical Cancer Research (2019)

Abstract Clear cell ovarian carcinoma (CCOC) accounts for 1-12% of ovarian epithelial cancers and, notwithstanding early diagnosis, often has poor clinical outcomes. CCOC genomic sequences show strong cytosine to thymine (C-to-T) transition mutation biases (Wang et al., 2017, Nature Genetics; Maru et al., 2017, Gynecologic Oncology; Shibuya et al., 2018, Genes Chromosomes Cancer). Many of these mutations occur in APOBEC signature motifs (5'-TCA or TCT), implicating at least one of the nine APOBEC DNA cytosine deaminase family members in CCOC mutation and evolution. Three of the nine family members associate with cancer mutagenesis, but only one, APOBEC3B (A3B), correlates in multiple cancer types with worse clinical outcomes including overall and metastasis-free survival. Here, we further investigate the specific involvement of APOBEC mutagenesis in CCOC. First, we show that tumors positive for APOBEC signature mutations associate with poor clinical outcomes in comparison to those that do not. Second, we perform a comprehensive analysis of mutation signatures from new whole genome sequences and APOBEC expression profiles from tumor and normal tissues, including RTqPCR for mRNA quantification and immunohistochemistry to distinguish APOBEC protein expression in tumor cells from surrounding connective tissue and immune cells. Our results indicate a significant role for APOBEC mutagenesis in CCOC warranting further studies including evaluation of APOBEC as a prognostic biomarker. Citation Format: Artur S. Serebrenik, Matthew C. Jarvis, Prokopios P. Argyris, William B. Brown, Reuben S. Harris. EVIDENCE FOR APOBEC MUTAGENESIS IN CLEAR CELL OVARIAN CARCINOMA [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-052.