tbuckley/cabot-search huggingface dataset:
Safety of radiotherapy with concurrent and adjuvant MEDI4736 (durvalumab) in patients with locoregionally advanced head and neck cancer with a contraindication to cisplatin: NRG-HN004.
Authors: Loren K. Mell, Pedro A. Torres-Saavedra, Stuart J. Wong, Steven Chang, Julie Ann Kish, Andy Minn, Richard C. Jordan, Tian Liu, Minh Tam Truong, Julie E. Bauman, Steven Francis Powell, Abderrahim Khomani, Muhammad Kashif Riaz, David Raben, Quynh-Thu Le
Journal: Journal of Clinical Oncology (2019)

6065 Background: MEDI4736 (durvalumab), a PD-L1 inhibitor, has shown promising antitumor activity and safety in head and neck squamous cell carcinoma (HNSCC). A phase II/III trial with lead-in component was designed to evaluate the safety and efficacy of concurrent and adjuvant MEDI4736 with radiation therapy (RT) for HNSCC patients with a contraindication to cisplatin. Safety data for 10 patients on the lead-in study are reported. Methods: Eligible patients had previously untreated locoregionally advanced unresected SCC of the larynx, hypopharynx, oropharynx (OPX), oral cavity, or unknown head/neck primary (AJCC 7 th stage III-IVB). Contraindications to cisplatin included renal or hearing impairment, age ≥ 70 with moderate or severe comorbidity/vulnerability to cisplatin, or age&lt; 70 with severe comorbidity/vulnerability, based on 6 validated indexes. Intravenous MEDI4736 1500 mg was delivered at weeks -2, 2, 6, 10, 14, 18, and 22 with RT (70 Gy in 35 daily fractions weeks 1-7). The primary endpoint was dose-limiting toxicity (DLT), defined as a high-grade adverse event (AE; NCI CTCAE version 4.0) definitely/probably related to MEDI4736 up to 4 weeks following completion of RT; 0-2 DLTs in 8 evaluable patients was considered acceptable. Results: Characteristics of the 10 enrolled patients were: 30% age ≥ 70, 90% male, 100% Caucasian, 40% ECOG performance status 0, 60% modified Charlson Comorbidity Index ≥ 1, 60% &gt;10 pack-years, 20% larynx, 60% p16+ OPX, 50% T3-4 and 80% N2-3 disease. All 10 patients had ≥ 2 contraindications to cisplatin. All 10 patients completed RT and were evaluable. 8 of 10 patients received all 7 doses of MEDI4736 and 1 patient is still on MEDI4736 after 6 doses. 1 patient received 2 doses then discontinued due to AE (diarrhea possibly related to MEDI4736). No DLTs were observed. No grade 4-5 AEs were observed. Grade ≥ 3 AEs possibly related to MEDI4736 were: diarrhea (n=1), nausea (1), and vomiting (1). No grade ≥ 3 AEs were rated as definitely or probably related to MEDI4736. Conclusions: MEDI4736 is safe and feasible to administer concurrently with RT for patients with HNSCC with a contraindication to cisplatin. Clinical trial information: NCT03258554.
Effects of immune architecture on response to adjuvant capecitabine in triple-negative breast cancer (FinXX trial).
Authors: Saranya Chumsri, Karama Asleh, Heather Ann Brauer, Douglas Hinerfeld, Jennifer M. Kachergus, Susanna Lauttia, Henrik Lindman, Torsten Nielsen, Heikki Joensuu, E. Aubrey Thompson
Journal: Journal of Clinical Oncology (2019)

3142 Background: Recent studies have demonstrated a benefit of adjuvant capecitabine, particularly in triple negative breast cancer (TNBC) patients with residual disease after neoadjuvant chemotherapy. However, biomarkers to predict which patients are more likely to benefit from capecitabine are needed. Methods: The nanoString Breast Cancer 360 (BC360) and PanCancer Immunoncology (IO360) panels were used to quantify mRNA expression in TNBC samples in the FinXX trial. FinXX is a phase III trial which randomized high risk patients to receive either 3 cycles of docetaxel followed by 3 cycles of cyclophosphamide, epirubicin, and fluorouracil (Arm A: T+CEF) vs. 3 cycles of docetaxel plus capecitabine followed by 3 cycles of cyclophosphamide, epirubicin, and capecitabine (Arm B: TX+CEX). Gene signature scores were analyzed using prespecified algorithms developed by nanoString. Digital Spatial Profiling was carried out using GeoMX platform. Results: A total of 111 TNBC patients in FinXX trial were included (57 in Arm A and 54 in Arm B) with 10.2 years median follow up. There were 7 cancer- and immune-related gene signatures identified by BC360 and IO360 panels that were significantly associated with improved recurrent free survival favoring an addition of capecitabine. These include cytotoxic cell signature (HR 0.37, 95%CI 0.15-0.92, p 0.03), endothelial signature (HR 0.18, 95%CI 0.04-0.83, p 0.03), mast cell signature (HR 0.43, 95%CI 0.21-0.88, p 0.02), PDL2 gene (HR 0.29, 95%CI 0.09-0.99, p 0.05), immunoproteasome (HR 0.34, 95%CI 0.13-0.89, p 0.02), exhausted CD8 (HR 0.29, 95%CI 0.09-0.97, p 0.04), and PD1 (HR 0.44, 95%CI 0.20-1.02, p 0.05). Conclusions: Analysis of RNA abundance signatures strongly suggests that there are important immune features that are associated with benefit from capecitabine in TNBC. However, analysis of RNA extracted from whole tumor sections lacks spatial discrimination. We anticipate that a more detailed, spatially-defined analysis of protein abundance, using the novel NanoString GeoMX platform, will provide more insights and define specific immune features associated with improved outcome. Additional results of GeoMX will be reported at the meeting. Clinical trial information: NCT00114816.
Update on the Drug Rediscovery Protocol: Expanded use of existing anticancer drugs in patients with a known molecular profile.
Authors: Jade Maxime van Berge Henegouwen, Louisa Rose Hoes, Hanneke van der Wijngaart, Daphne Liselotte Van Der Velden, Alwin Huitema, Edwin P.J.G. Cuppen, Elly J. Lugtenburg, Filip Yves Francine Leon De Vos, Haiko Bloemendal, Katrien Grunberg, Henk M.W. Verheul, Hans Gelderblom, Emile E. Voest
Journal: Journal of Clinical Oncology (2019)

TPS3149 Background: With the emergence of large-scale genetic tumor profiling and the increasing availability of approved targeted therapies, precision medicine has become crucial in cancer treatment. However, for many cancers the relative contribution of either tumor type or genetic aberration to drug sensitivity often remains unknown. Since drug access is generally limited to the on-label indication and outcome of off-label use is not systematically collected in clinical practice, innovative trials facilitating drug access, whilst systematically analyzing treatment outcomes, are urgently needed. Methods: The Drug Rediscovery Protocol (DRUP) is an ongoing, prospective, non-randomized, multi-drug, and pan-cancer trial, in which patients with advanced cancer, who have exhausted all standard of care treatment options, are treated with either targeted or immunotherapy matched to their genetic tumor profile. All submitted patients are reviewed and enrolled in multiple parallel cohorts, preceded by a baseline tumor biopsy for whole genome sequencing to confirm previously identified variants and for exploratory biomarker analyses. Each cohort is defined by a study drug, histologic tumor type, and molecular tumor profile. Efficacy is analyzed per cohort: 8 patients in stage I and 16 more in stage II if ≥ 1 response is observed in the first stage. Primary endpoints include objective response rate, stable disease at 16 weeks, and grade ≥3 adverse events. Since the start of recruitment in September 2016, 870 patients have been submitted for review and 365 patients (42%) have started treatment in one of 101 opened cohorts. Eight cohorts have graduated to the second stage, two cohorts completed accrual in either their first or second stage, and one cohort was closed due to a registered indication. Twenty-two different study treatments (i.e. immunotherapy, monoclonal antibodies, and PARP/small molecule inhibitors), provided by 11 different pharmaceutical companies, are currently available in DRUP. Data sharing with similar trials such as TAPUR and CAPTUR enables to achieve completion of slow accruing cohorts and affirm conclusions. Clinical trial information: NCT02925234.
Ozone-primed neutrophils promote early steps of tumour cell metastasis to lungs by enhancing their NET production
Authors: Natacha Rocks, Céline Vanwinge, Coraline Radermecker, Silvia Blacher, Christine Gilles, Raphael Marée, Alison Gillard, Brigitte Evrard, Christel Pequeux, Thomas Marichal, Agnes Noel, Didier Cataldo
Journal: Thorax (2019)

Background Air pollution, including particulates and gazes such as ozone (O 3 ), is detrimental for patient’s health and has repeatedly been correlated to increased morbidity and mortality in industrialised countries. Although studies have described a link between ambient particulate matter and increased lung cancer morbidity, no direct relation has yet been established between O 3 exposure and metastatic dissemination to lungs. Objectives To outline the mechanisms through which pulmonary O 3 exposure modulates metastasis kinetics in an experimental mouse model of O 3 exposure. Methods Metastatic responses to pulmonary O 3 exposure were assessed using a reliable experimental mouse model of concomitant pulmonary O 3 exposure and tumour cell injection. Roles of neutrophils in O 3 -induced lung metastasis were highlighted using blocking anti-Ly6G antibodies; moreover, the implication of neutrophil extracellular traps (NETs) in metastatic processes was evaluated using MRP8cre-Pad4lox/lox mice or by treating mice with DNase I. Results Pulmonary O 3 exposure strongly facilitates the establishment of lung metastasis by (1) Inducing a pulmonary injury and neutrophilic inflammation, (2) Influencing very early steps of metastasis, (3) Priming neutrophils’ phenotype to release NETs that favour tumour cell colonisation in lungs. The ability of O 3 -primed neutrophils to enhance lung colonisation by tumour cells was proven after their adoptive transfer in Balb/c mice unexposed to O 3 . Conclusions Pulmonary neutrophils induced by O 3 promote metastatic dissemination to lungs by producing NETs. These findings open new perspectives to improve treatment and prevention strategies in patients affected by metastatic diseases.
Health insurance literacy, financial hardship and financial sacrifices among cancer survivors in the United States.
Authors: Jingxuan Zhao, Xuesong Han, Zhiyuan Zheng, Matthew P. Banegas, Donatus U. Ekwueme, K. Robin Yabroff
Journal: Journal of Clinical Oncology (2019)

1560 Background: Rising costs of cancer care have imposed substantial financial burden on cancer survivors. To date, little is known about the associations between potentially modifiable patient characteristics, including health insurance literacy (HIL), on financial burden among cancer survivors. This study aimed to evaluate the associations between HIL and financial hardship and financial sacrifices among adult cancer survivors in the United States. Methods: We identified 914 adult cancer survivors from the 2016 Medical Expenditure Panel Survey Experiences with Cancer Questionnaire. HIL was measured based on the question “Did you ever have a problem understanding health insurance or medical bills related to your cancer, its treatment, or the lasting effects of that treatment?” Medical financial hardship was measured in three domains—1) material (e.g. problems paying medical bills); 2) psychological (e.g. worry about large medical bills); and 3) behavioral (e.g. delay or forego healthcare because of cost). Financial sacrifices were based on questions related to changes in spending on vacation or leisure activities. We used multivariable logistic regression modeling to separately evaluate the associations between HIL problems and 1) financial hardship and 2) financial sacrifices. Results: 18.9% cancer survivors aged 18-64 years and 14.6% survivors ≥65 years reported HIL problems. Regardless of age groups, cancer survivors with HIL problems were more likely to report any material (OR =3.2; 95% CI:1.9-5.2) or psychological (OR=7.2; 95% CI: 4.1-12.7) financial hardship than those without the problems, as well as more likely to delay or forgo multiple medical care due to cost, including prescription medicine (OR=3.6; 95% CI: 1.8-7.1), specialist visit (OR=2.6; 95% CI: 1.2-5.8), and follow-up care (OR=2.1, 95% CI 1.2-4.0). Higher likelihood of reporting all measures of financial sacrifices were observed among those with HIL problems in both age groups (all p&lt;0.05). Conclusions: Cancer survivors with HIL problems were more likely to report financial hardship and financial sacrifices than those without the problems. Improving HIL may help mitigate financial hardship.
Aggressive variant prostate cancer (AVPC) molecular signature in castration-sensitive, <i>de novo</i> metastatic prostate cancer (M1PCa).
Authors: Ana Aparicio, Miao Zhang, Naveen Ramesh, Xuemei Wang, Paul Gettys Corn, Amado J. Zurita, John W. Davis, Curtis Alvin Pettaway, Mehrad Adibi, Sean Eric Mcguire, Shi-Ming Tu, Jennifer Wang, Sumit Kumar Subudhi, Mohamed A Elsheshtawi, Eleni Efstathiou, Christopher Logothetis, Nicholas Navin, Patricia Troncoso, Brian Francis Chapin
Journal: Journal of Clinical Oncology (2019)

5052 Background: AVPC are a subset of prostate cancers (PC) that share clinical features with the small-cell prostate carcinomas, a rare morphological variant with atypical and virulent behavior. They are estimated to represent 30% of lethal PC and are characterized by a molecular signature of combined defects (≥2) in Tp53, RB1 and PTEN (AVPC_MS). The AVPC_MS is associated with androgen indifference in preclinical models and predicts for benefit from the addition of carboplatin to cabazitaxel in men with castration resistant prostate cancer (CRPC). The prevalence and significance of the AVPC_MS in castration sensitive M1PC is unknown. Methods: In a Phase II trial 119 men with M1PC treated with 6 months of standard systemic therapy (SST) were randomized to the addition of local therapy. PCa samples obtained at diagnosis and after 6 months of SST were stained for markers including Tp53, RB1 and PTEN, and subject to whole genome sequencing. Tp53 was considered defective if expressed in ≥ 10% of tumor cells, and RB1 and PTEN if in ≤ 10%. Progression free survival (PFS) was estimated from SST start. Results: To date specimens from 38 men have been evaluated. Immunohistochemistry (IHC) results are shown below. The median PFS of men with AVPC_MS POSITIVE vs AVPC_MS NEGATIVE baseline prostate tumors was 9.3 vs 15 months (HR 1.09, 95%CI 0.42-2.87, P=0.852). Conclusions: The rate at which the AVPC molecular signature is detected in castration sensitive M1PCa appears similar to that in CRPC. This may have therapeutic implications. Updated molecular and outcome data will be presented upon acceptance. [Table: see text]
Incidence of comorbidities on death certificate data in women with gynecological cancers.
Authors: Mary Elizabeth McLaughlin, Gita Suneja, Junzo P. Chino
Journal: Journal of Clinical Oncology (2019)

e17127 Background: Risk factors for the development of gynecological cancers are known to vary; however, the effect on mortality is uncertain. Methods: Using CDC Wonder Database, death certificate data, all women who died of cancer in the United States from 2003-2016 were included if a cancer diagnosis was listed as a primary or contributing cause. Cases were then divided into gynecological (GYN) cancer or not, and thereafter characterized as cervical, ovarian, uterine, or other. Other causes contributing to death (comorbidities were then captured via ICD10 codes listed on death certificates and grouped into similar disease states. Chi-squared and Mann-Whitney U tests were performed for statistical significance. Results: Of 35,324,091 death certificates, 4,177,823 deaths were women with cancer listed as a cause of death. 440,792 were gynecological cancer, with cervical cancer in 62,807; uterine cancer in 134,420; ovarian cancer in 221,119; and other gynecological cancers in 25,946. Women with GYN cancers were more likely to have intestinal obstruction (2.7% vs 0.7%, OR 4.05), ascites (0.7% vs 0.2%, OR 3.30), HIV (0.1% vs 0.05%, OR 1.53), kidney disease (4.7% vs 3.6%, OR 1.33), and thrombo-embolic disorders (4.3% vs 3.5%, OR 1.25) when compared to non-GYN cancers (all p &lt; 0.00001). Uterine cancer was more likely to have diabetes-related comorbidities (6.4% vs 3.8%, OR 1.75), metabolic syndrome (9.5% vs 6.1%, OR 1.60), thrombo-embolic disorders (5.5% vs 3.8%, OR 1.48), ischemic heart disease (5.0% vs 3.6%, OR 1.43), than other GYN cancers (all p &lt; 0.00001). Cervical cancer was more associated with HIV (0.3% vs 0.03%, OR 10.73) and tobacco-related disorders (4.7% vs 1.9%, OR 2.56). Ovarian cancer was more associated with ascites (1.1% vs 0.4%, OR 2.93), intestinal obstruction (3.5% vs 1.8%, OR 2.04), and pleural effusion (1.1% vs 0.6%, OR 1.92) (all p &lt; 0.00001). Conclusions: Comorbidities contributing to death significantly differ amongst gynecological cancers and non-gynecological cancers, which has relevance to strategies that can be differentially employed to reduce mortality. In particular, women with uterine cancer may benefit from reduction in risk of diabetes, ischemic heart disease, and embolic disorders; those with cervical cancer may benefit from smoking cessation and optimal HIV management.
Case 46-1987
Authors: Richard C. Cabot, Robert E. Scully, Eugene J. Mark, William F. McNeely, Betty U. McNeely, Nanette F. Santoro, Mary C.. Hayes
Journal: New England Journal of Medicine (1987)

Presentation of CaseA 31-year-old woman was admitted to the hospital because of secondary amenorrhea and infertility.The patient's menarche occurred at 13 years, when her weight ranged between 43 and 45 kg and her height was approximately 150 cm. Her menstrual cycles were regular at 28 days, with cramps, backache, and breast tenderness just before each period; she experienced occasional right-sided pain two weeks before menses. At 20 years of age an intrauterine device was inserted, but excessive flow and cramps prompted its removal one year later; during the next three years the patient took an oral contraceptive pill. . . .
RUBY: A phase II study testing rucaparib in germline (g) BRCA wild-type patients presenting metastatic breast cancer (mBC) with homologous recombination deficiency (HRD).
Authors: Anne Patsouris, Olivier Tredan, Daniel Nenciu, Alicia Tran-Dien, Loic Campion, Anthony Goncalves, Monica Arnedos, Marie-Paule Sablin, Wilfried Gouraud, Marta Jimenez, Nathalie Droin, Ivan Bieche, Celine Callens, Andrea Loehr, Cecile Vicier, Fabrice Andre
Journal: Journal of Clinical Oncology (2019)

1092 Background: PARP-inhibitors improve PFS in mBC patients (pts) harboring a gBRCA mutation (mut). However, unlike ovarian cancer, there is no evidence until now that this class of agents has efficacy in gBRCA wild-type (WT) pts. In RUBY, we evaluated rucaparib in gBRCA WT mBC pts, and whose tumor present with HRD as assessed by genome-wide Loss of Heterozygosity (LOH) score. Methods: 713 gBRCA WT women with HER2- mBC, initiating a first metastatic chemo, were screened for high (≥18%) genomic tumor LOH generated from a SNP array on metastatic sample. Eligible pts with a high LOH score or somatic (s) BRCA mut and ≥1 prior chemo regimen were proposed to enter RUBY and receive oral rucaparib 600 mg BID continuously in 28-day cycles until disease progression. The primary endpoint was clinical benefit rate (CBR), defined by complete (CR) and partial response (PR) or stable disease (SD) ≥16 weeks. We used a Simon’s two-stage design (p0=20%; p1=40%), responses in ≥4/17 pts were expected to move to second step, and ≥11/37 pts to be considered of clinical interest (α=10% and power of 90%). Whole genome sequencing (WGS) was performed retrospectively to further assess potential biomarkers of PARP inhibitor response. Results: Tumors from 221 (31%) pts were LOH high. 41 pts were enrolled, including 4 pts with sBRCA mut. Median prior metastatic chemo lines was 2 (1-5), 17 pts had TNBC at diagnosis. As of 14 Jan 2019, 16 pts were alive, 5 are still on treatment. The median number of cycles was 2 (1 -20), and 37/40 patients were evaluable for CBR. 5 pts (13.5%) demonstrated clinical benefit (1 CR [LOH high], 3 PR [2 LOH high, 1 sBRCA2] and 1 SD&gt;31 weeks [sBRCA1]). 19 pts had grade 3-4 toxicities. 3 pts discontinued due to toxicity. 4/5 responders pts had their tumor profiled by WGS: preliminary analyses showed that 4 pts presented high large scale state transitions, and 3 presented a somatic biallelic loss of function in HR-related genes. The fifth responder harbored a mut on gPALB2 and sBRCA2 at inclusion. Conclusions: In this study, rucaparib demonstrates antitumor activity in a subset of gBRCA WT mBC pts whose tumor has high LOH. Final analyses of WGS will provide insights about HRD signatures and drivers alterations associated with response. Clinical trial information: NCT02505048.
Racial and socioeconomic disparities in follicular lymphoma survival.
Authors: Richard Stephen Sheppard, Adewumi Adekunle, Stefani Beale, Meena Ahluwalia
Journal: Journal of Clinical Oncology (2019)

e18173 Background: Follicular Lymphoma (FL) is a the second most common Non Hodgkin's Lymphoma (NHL) diagnosed in the United States with 2.6 per 100,000 men and women per year from 2011 to 2015 when age adjusted as per the National Cancer Institute with the number of deaths of 0.5 per 100,000 men and women per year. It known that FL is one of the most clinically indolent NHL and due to this, survival rates are generally more favorable when compared to other B Cell Lymphomas. With this study, we aim to analyse socioeconomic and racial disparities in the survival rates for FL. Methods: The authors identified patients diagnosed with FL between 1973 and 2015 using the Surveillance, Epidemiology, and End Results (SEER) database. Overall survival was estimated and compared between racial/ethnic groups using the log-rank test. Our outcome variables were 1-year, 5-year and mortality. Our independent variables were race and socioeconomic status. We controlled for age, demographic characteristics, time of diagnosis, pathological classification, treatment and socioeconomic status. Results: A total of 66 127 patients were identified; 90% of the patients were White, 4% Black, and 4% Asian. We noted significant differences in disease presentation, socioeconomic status, and outcomes. Asian/Pacific Islander had the lowest survival with a mean of 228 survival months, Blacks had a mean survival months of 237, and Whites had a mean survival months of 234. Conclusions: Disparities exist in the care and outcomes of FL. A low socioeconomic status is correlated with decreased survival.