tbuckley/cabot-search huggingface dataset:
Does the quality of patient-reported outcomes (PROs) assessment in randomized controlled trials (RCTs) differ across cancer types and over time? A pooled analysis of 610 RCTs published between 2004 and 2018.
Authors: Francesco Sparano, Neil K Aaronson, Mirjam A.G. Sprangers, Peter Fayers, Andrea Pusic, Jacobien M Kieffer, Jonathan Rees, Chonghua Wan, Mike Pezold, Sarah Fuzesi, Sumit Isharwal, Amelie Anota, Emilie Charton, Marco Vignetti, Francesco Cottone, Jane M. Blazeby, Fabio Efficace
Journal: Journal of Clinical Oncology (2019)

e18218 Background: PRO endpoints are increasingly being used in cancer RCTs. However, the PRO assessment in such trials often suffers from serious methodological shortcomings, and the results seldom impact on clinical policy or practice. Methods: We performed a systematic review to identify RCTs with a PRO endpoint in breast, colorectal, lung, prostate, gynaecological and bladder cancer. A checklist score for quality of PRO reporting (ranging between 0-100), based on that of the International Society for Quality of Life Research (ISOQOL) and the CONSORT PRO extension, was computed for each RCT. Analyses were also conducted by type of PRO endpoint (primary versus secondary) and year of publication (i.e. before and after the publication of the CONSORT PRO extension). Results: We identified 610 RCTs with a total of 323,482 patients. PROs were most frequently used in RCTs of breast (N = 176), followed by lung (N = 123), prostate (N = 108), colorectal (N = 103), gynaecological (N = 83) and bladder (N = 17) cancer. Quality of PRO reporting (mean score: 56.4) was highest in RCTs conducted in prostate cancer (PCa) (Table). Regardless of cancer type, quality of reporting was typically higher in RCTs where PROs were primary endpoints. Quality of reporting was higher for RCTs published after the CONSORT PRO Extension (2013), with the exception of RCTs conducted in PCa, where quality was stable over time. Conclusions: PRO reporting of RCTs conducted in PCa has better quality than in the other cancer sites that were reviewed. Regardless of cancer site, quality of PRO reporting has improved after the publication of the CONSORT PRO Extension. [Table: see text]
Genetic predisposition to breast cancer among African American women.
Authors: Julie R Palmer, Chunling Hu, Steven Hart, Rohan David Gnanaolivu, Chi Gao, Hoda Anton-Culver, Amy Trentham-Dietz, Leslie Bernstein, Jeffrey N. Weitzel, Susan M. Domchek, David Goldgar, Katherine Nathanson, Tuya Pal, Esther M John, Mia Gaudet, Christopher Haiman, Song Yao, Peter Kraft, Eric Polley, Fergus Couch
Journal: Journal of Clinical Oncology (2019)

104 Background: The identification of pathogenic mutations in breast cancer susceptibility genes through clinical genetic testing leads to focused screening and prevention strategies for women at increased risk of cancer. However, the frequency of mutations and the risks of cancer associated with breast cancer predisposition genes has not been established for the African American population. Methods: Germline DNA samples from African American women (5,054 breast cancer cases and 4,993 age-matched unaffected controls) from 10 U.S. studies were tested for mutations in 20 established breast cancer predisposition genes using a QIAseq multiplex amplicon panel as part of the “CAnceR RIsk Estimates Related to Susceptibility” (CARRIERS) study. The frequency of mutations in each gene and associations between mutations and breast cancer risk, adjusted for study design, age, and first-degree family history of breast cancer, were evaluated. Results: The mean age at diagnosis of breast cancer cases was 54.4 years and the mean age of controls was 55.2 years. 18.2% of cases and 10.8% of controls reported a first-degree family history of breast cancer. Pathogenic mutations in any of the 20 breast cancer predisposition genes were identified in 7.6% of breast cancer cases and 2.4% of controls. In multivariable analyses, mutations in BRCA1, BRCA2, and PALB2 were associated with high risks of breast cancer (odds ratio (OR) &gt; 5.0). Mutations in CHEK2 were associated with moderate risks of breast cancer (OR &gt; 2.0), whereas mutations in ATM had lower clinical relevance (OR = 1.8). Mutations in BRCA1, BRCA2, PALB2, and RAD51D, but not CHEK2 or ATM, were associated with increased risks of estrogen receptor negative breast cancer. Conclusions: Cancer predisposition genes confer similar risks of breast cancer in the African American population as in non-Hispanic Whites. These studies provide important insights into the risks of breast cancer associated with predisposition gene mutations in the African American population.
Real-world outcomes of underrepresented patient populations treated with immune checkpoint inhibitors (ICIs): African American descent, poor ECOG performance status, and chronic viral infections.
Authors: Neil J. Shah, Matthew Blackburn, Michael R Cook, Anas Belouali, Michael Serzan, William Kelly, Athanasios Bikas, Chul Kim, Subha Madhavan, Stephen V. Liu, Michael B. Atkins
Journal: Journal of Clinical Oncology (2019)

2587 Background: ICIs have now become standard of care treatment for multiple malignancies. However, patients (pts) who are African American decent (AA), have a poor ECOG performance status (PS) or chronic viral infections [human immunodeficiency virus (HIV), hepatitis B (HBV) and hepatitis C (HCV)] were underrepresented in early clinical trials with ICIs and outcome data in these pt populations is not well reported. Methods: We performed a retrospective analysis of pts treated with ICIs (anti-PD(L)-1, anti-CTLA-4, or combination ICIs) across five MedStar Health hospitals from January 2011 to April 2018. Investigator-assessed best responses were noted. CTCAE v4.03 was used to capture immune-related adverse events (irAEs). Results: We identified 765 pts treated with 829 unique ICIs therapies across different malignancies. A total of 203 AA pts, 178 pts with a pre-treatment ECOG PS ≥2, 21pts with HIV, and 50 pts with HBV/HCV were noted. Any grade and grade ≥ 3 irAEs in the HIV cohort were 24% and 10% with an ORR of 29%. Any grade and grade ≥ 3 irAEs in HBV/HCV were 50% and 26% with an ORR of 21%. No viral reactivation or changes in pts anti-viral medications were noted during ICIs treatment. The ORR in AA pts was 35%. Any grade and grade ≥ 3 irAEs in the AA cohort were 27% and 8%, respectively. The ORR in pts with ECOG PS ≥2 was 14%. Any grade and grade ≥ 3 irAEs in this cohort were 20% and 4%. Similar trends were seen in the subset of patients with NSCLC treated with anti-PD(L)1 monotherapy (Table). Outcomes of NSCLC pts treated with anti-PD(L)-1 monotherapy. Conclusions: ICI therapy was not associated with any new safety signal in the above underrepresented populations. Prospective studies are needed to validate this data.[Table: see text]
Monthly parts a and b costs by service and line of therapy for FDA-approved/NCCN category 1 treatments for patients with metastatic pancreatic cancer.
Authors: L. Daniel Muldoon, Jared Hirsch, Gabriela Dieguez, Paul Cockrum
Journal: Journal of Clinical Oncology (2019)

e18365 Background: Real-world evidence is lacking regarding costs for FDA-approved/NCCN Category 1 treatments for patients with metastatic pancreatic cancer (m-PANC). We analyzed costs by service in the Medicare fee-for-service (FFS) population by chemotherapy regimen and line of therapy (LOT). Methods: Patients with m-PANC were identified using ICD-9/10 diagnosis codes in the 2013-2017 Medicare 100% Limited Data Set claims, which include all Medicare paid FFS claims, except professional services, for 45 million Medicare FFS beneficiaries. We studied mean monthly costs by service category, regimen, and LOT. Patients in our study had two or more claims with a pancreatic cancer (PANC) diagnosis more than 30 days apart and one or more claims with a secondary malignancy (metastasis) diagnosis on or after the first PANC diagnosis date. We defined index date as the earliest metastasis diagnosis date. We excluded patients with pre-index non-PANC malignancies and those without 6 months pre-index and 3 months (or until death, if earlier) post-index Medicare FFS enrollment. LOTs were assigned based on therapies used. LOTs ended the day before a new chemotherapy began, 28 days after the last chemotherapy (if no new chemotherapy), or upon death. We analyzed the FDA-approved/NCCN Category 1 treatments used most commonly in first line (1L): gemcitabine monotherapy, gemcitabine/nab-paclitaxel, and FOLFIRINOX; and in second or third line (2L, 3L): liposomal irinotecan. Results: Mean monthly Parts A and B (excluding professional) costs for 1L gemcitabine monotherapy were lower than gemcitabine/nab-paclitaxel or FOLFIRINOX ($5,267, $9,116, and $8,046, respectively). Part B drug costs other than chemotherapy were higher for FOLFIRINOX than gemcitabine/nab-paclitaxel or gemcitabine monotherapy ($3,881, $1,155, and $827, respectively). Inpatient services were similar across 1L regimens ($2,721-$3,303). Despite disease progression, mean monthly 2L and 3L costs for liposomal irinotecan were $10,809 and $12,225, respectively. Part B drugs other than chemotherapy ($2,133-$2,509) were comparable to 1L regimens, but inpatient services ($2,306-$2,405) were lower. Conclusions: The mean monthly cost increased by LOT for m-PANC FDA-approved/NCCN category 1 regimens. Interestingly, Part A inpatient costs decreased in 2L and 3L, while Part B drug costs other than chemotherapy were comparable.
Racial disparities in clinico-pathological features and survival rates of early-onset colorectal cancer.
Authors: Ana Acuna Villaorduna, Meghan Kaumaya, Sanjay Goel
Journal: Journal of Clinical Oncology (2019)

e15089 Background: Early-onset colorectal cancer (EO-CRC) incidence is increasing disproportionately among minorities compared to Non-Hispanic Whites (NHW). EO-CRC have aggressive features such as higher grade and advanced stages. The appropriate age to start screening colonoscopy (SC) in NHW and minorities remains controversial; varying between 45 and 50 years old. We aim to compare EO-CRC clinico-pathological characteristics and survival rates by race groups. Methods: Patients with colorectal adenocarcinoma (CRC) with available race and stage as per AJCC 6 th edition were identified using the SEER registry (1973-2010). EO-CRC was defined as CRC before age 50 years. Clinico-pathological features, overall survival (OS) by Kaplan Meier curves and mortality predictors by multivariate analysis were evaluated by race groups. Results: 180 605 patients with CRC were identified; 10.2% had EO-CRC. Mean age of diagnosis was 42.7 years and EO-CRC frequency was higher in minorities (Hispanics (H):16.7%, Non-Hispanic Black (NHB):12.7% and Asian (A): 12.8%) compared to NHW (8.7%). EO-CRC in NHB was predominantly seen in females. The rectum was the most common location for all races. Two-thirds of tumors were located between the sigmoid and anal regions in all races except NHB that had higher frequencies of right-sided tumors. Compared to other races, NHB had worse OS at all stages and tumor locations. NHB was associated with 72% increased risk of death by multivariate analysis. Conclusions: Our data suggest that EO-CRC frequency, pathological features and OS differ by race group; hence SC guidelines should be tailored accordingly. SC would be considered early; especially in minorities. Complete colonoscopy should be considered for NHB given higher rates of right-sided tumors and worse OS; while sigmoidoscopy may be adequate for others up to age 50, given higher rates of tumors located in the sigmoid to anal region. [Table: see text]
First-in-human first-in-class phase I trial of murlentamab, an anti-Mullerian-hormone receptor II (AMHRII) monoclonal antibody acting through tumor-associated macrophage (TAM) engagement, as single agent and in combination with carboplatin (C) and paclitaxel (P) in AMHRII-expressing advanced/metastatic gynecological cancer patients (pts).
Authors: Alexandra Leary, Ahmad Awada, Jean-Pierre Delord, Anne Floquet, Isabelle Laure Ray-Coquard, Cyril Abdeddaim, Michel Fabbro, Elsa Kalbacher, Ignace Vergote, Susana N. Banerjee, François-Xavier Frenois, Grégory Noël, Olivier Lantz, Lydie Cassard, Agnès Coste, Marine Villard, Fanny Lemee, Isabelle Marie Tabah-Fisch, Christophe Le Tourneau
Journal: Journal of Clinical Oncology (2019)

2521 Background: Membranous expression of AMHRII is found in ~70% of gynecological tumors. Murlentamab (M) binds with high affinity both AMHRII (at cell membrane) and CD16 (on macrophage, via its low fucose Fc). M reprograms TAMs, restoring their antitumoral functions (phagocytosis) resulting in cytotoxic T cell reactivation. Methods: Pts with advanced/metastatic AMHRII-expressing ovarian, cervical or endometrial cancer with measurable disease and performance status ≤ 1 received M as single agent (SA) in 8 dose escalating and 2 expansion cohorts. Combination with CP was studied in 2 escalating cohorts. Safety, recommended dose determination, antitumor activity, pharmacodynamics (PD) effects (circulating immune cells and tumor microenvironment (TME) from paired biopsies) were assessed. Results: 68 heavily pretreated (median 4 prior lines) pts received M for 0.5 to 11 months (mo) (59 pts M SA and 9 pts M + CP). No dose limiting toxicity was reported. Most common toxicity was G1-2 asthenia (29 %). Eight pts (12%) had G ≥ 3 reversible toxicities (asthenia, nausea/vomiting, anorexia, arthralgia). No antidrug antibody was detected. One partial response (PR) was achieved with M SA in a granulosa pt. In CP combination, 4/9 pts (44%) responded to treatment (1 Complete Response and 3 PRs). Overall, 22/67 (33%) pts were progression-free at 4 mos. Among 17 pts treated ≥ 6 mos, 6/9 (67%) granulosa pts with M SA and 4/5 (80%) endometrium and cervix with CP combination had a longer PFS than under previous regimen. PD blood assessment of 25 pts treated with M SA showed an increase in classical monocytes, and T cells and neutrophils activation. Changes in TME under M will be presented. Conclusions: Murlentamab was very well tolerated, demonstrated immune PD effects and showed hints of antitumor activity. These results together with its innovative immunological mode of action support development of M in AMHRII-expressing cancers, in combination with chemotherapy or other immune oncology drugs. Clinical trial information: NCT02978755.
Costs associated with acute respiratory illness and select virus infections in hospitalized children, El Salvador and Panama, 2012–2013
Authors: Jorge H. Jara, Eduardo Azziz-Baumgartner, Tirza De Leon, Kathia Luciani, Yarisa Sujey Brizuela, Dora Estripeaut, Juan Miguel Castillo, Alfredo Barahona, Mary Corro, Rafael Cazares, Ofelina Vergara, Rafael Rauda, Rosalba González, Danilo Franco, Marc-Alain Widdowson, Wilfrido Clará, Juan P. Alvis-Estrada, Christian Travis Murray, Ismael R. Ortega-Sanchez, Fatimah S. Dawood
Journal: Journal of Infection (2019)

Background and objectivesAlthough acute respiratory illness (ARI) is a leading cause of hospitalization among young children, few data are available about cost of hospitalization in middle-income countries. We estimated direct and indirect costs associated with severe ARI resulting in hospitalization among children aged <10 years in El Salvador and Panama through the societal perspective.MethodsDuring 2012 and 2013, we surveyed caregivers of children hospitalized with ARI about their direct medical (i.e., outpatient consultation, medications, hospital fees), non-medical (transportation, childcare), and indirect costs (lost wages) at discharge and 7 days after discharge. We multiplied subsidized hospital bed costs derived from administrative data by hospitalization days to estimate provider costs.ResultsOverall, 638 children were enrolled with a median age of 12 months (IQR 6–23). Their median length of hospitalization was 4 days (IQR 3–6). In El Salvador, caregivers incurred a median of US$38 (IQR 22–72) in direct and indirect costs per illness episode, while the median government-paid hospitalization cost was US$118 (IQR 59–384) generating an overall societal cost of US$219 (IQR 101–416) per severe ARI episode. In Panama, caregivers incurred a median of US$75 (IQR 39–135) in direct and indirect costs, and the health-care system paid US$280 (IQR 150–420) per hospitalization producing an overall societal cost of US$393 (IQR 258–552).ConclusionsThe cost of severe ARI to caregivers and the health care system was substantive. Our estimates will inform models to estimate national costs of severe ARI and cost-benefit of prevention and treatment strategies.
Treatment outcome and safety of anti-PD-1 antibody against elderly non-small cell lung cancer.
Authors: Toshio Sakatani, Aya Saihara, Hiroaki Ikushima, Hideyuki Takeshima, Yuri Taniguchi, Masayuki Hojo, Kazuhiro Usui
Journal: Journal of Clinical Oncology (2019)

e14249 Background: The anti-PD-1 antibodies, Pembrolizumab (Pem) and Nivolumab (Nivo), have become available for practical clinical use in Japan, and many patients are benefiting from them. Lung cancer is predominantly a disease of the elderly people. However, the validity and safety of anti-PD-1 antibodies against the elderly are insufficient. Methods: From February 2016 to November 2018, 66 patients with non-small cell lung cancer who received anti-PD-1 antibody therapy (23 Pem and 43 Nivo) were evaluated for progression-free survival (PFS), overall survival (OS), and safety were compared between groups between the aged ≥75 years (≥75 yrs) and &lt; 75 years ( &lt; 75 yrs). Results: The median age (width) was 67 years (46-87 years). 46 patients were &lt; 75 yrs and 20 patients were ≥75 yrs. PFS was 3.3 months (m) vs. 4.4 m ( &lt; 75 yrs vs. ≥75 yrs)(p = 0.214). OS was 11.7 m vs. 16.7 m ( &lt; 75 yrs vs. ≥75 yrs)(p = 0.212). Similar analysis was carried out for each anti-PD-1 antibody. In Pem, 15 patients were &lt; 75 yrs and 8 patients were ≥75 yrs, and there was no significant difference between PFS and OS (p = 0.46, p = 0.17, respectively). In Nivo, 31 patients &lt; 75 yrs, 12 patietns &gt; 75 yrs, and there was no significant difference in PFS and OS (p = 0.49, p = 0.44, respectively). Immunity-related adverse events (irAE) was expressed in 25 patients (37.9%). Among 66 patients, 19 in 46 (41%) were &lt; 75 yrs, 6 in 20 (30%) were ≥75yrs. There were not many irAEs even in the elderly people (χ 2 = 0.757, p = 0.384). Conclusions: Pem and Nivo proved to be effective and safe for the elderly patients even in the clinical setting.
Impact of no treatment vs other nonsurgical treatments in Pancreatic Adenocarcinoma National Cancer Database: 2004-2014.
Authors: Sukamal Saha, Mohamed Elgamal, Meghan Cherry, Robin Buttar, Kiran Devisetty, Hesham Gayar, David Wiese, Sandeep Singh Grewal, David S. Eilender, Madan L. Arora
Journal: Journal of Clinical Oncology (2019)

e15795 Background: Surgery remains the only curative treatment option in pancreatic adenocarcinoma, yet in more than 50% of the patients (pts) the disease is too advanced or at very high risk and considered inoperable. They are either managed with no treatment or other nonsurgical methods. Hence, we analyzed a large cohort of pancreatic adenocarcinoma pts undergoing No Treatment vs Chemotherapy, Radiation or Chemoradiation to determine their impact on survival. Methods: Only pancreatic adenocarcinoma pts who had no surgery in the National Cancer Database (NCDB) from 2004–2014 were included. Of that group, patients with unknown or missing data about chemotherapy or radiation treatment or less than 3 years of survival data were excluded. Pts were stratified into 4 groups: Chemotherapy, Radiation Therapy, Chemoradiation and No Treatment. Overall 1-, 2- and 3-year survival was calculated and the groups were compared using Pearson’s chi-squared. Results: Of the total 309,709 pancreatic cancer pts in the NCDB 2004–2014, 111,421 (36.0%) remained after application of the study criteria. Of these, 43,203 (38.8%) received chemotherapy only, 2,453 (2.2%) received radiation only, 15,764 (14.1%) received chemoradiation and 50,001 (40.0%) had no treatment. Overall survival for 1, 2, and 3 years was best in the chemoradiation group with a 1 year survival of (40.0%) compared to chemotherapy only (22.4%), radiation only (14.9%) and no treatment (9.6%). Overall, only (19.0%) of pts survived for 1 year, (5.4%) survived for 2 years and (2.3%) survived for 3 years. (Table) Conclusions: Survival in pancreatic adenocarcinoma pts remains dismal without surgery. Best survival in nonsurgical pts was seen after combination Chemoradiation therapy and worst survival in No Treatment group. Hence, whenever possible, a combination Chemoradiation should be offered even as palliation in non-surgical pancreatic adenocarcinoma pts.[Table: see text]
Practice patterns and outcomes following radiation dose de-escalation for oropharyngeal cancer: A National Cancer Database analysis.
Authors: Richard White, Stephen Abel, Shaakir Hasan, Vivek Verma, Larisa Greenberg, Athanasios Colonias, Rodney E Wegner
Journal: Journal of Clinical Oncology (2019)

e17508 Background: Numerous trials are evaluating radiotherapy (RT) de-escalation for HPV-mediated (HPV+) oropharyngeal squamous cell carcinoma (OPSCC). Herein, we evaluated the degree to which de-escalated RT is delivered in the United States, as well as, comparative outcomes with full-dose RT, as stratified for HPV status. Methods: We identified patients diagnosed with OPSCC in the National Cancer Database, excluding those with stage I/II disease, unknown HPV status, receiving surgery or not receiving EBRT to the primary site, receipt of radiation doses &gt; 75 or &lt; 54 Gy, radiation treatment course duration &lt; 25 or &gt; 75 days, and unknown or inadequate ( &lt; 2 months) follow-up. Multivariable logistic regression analysis identified variables associated with delivery of de-escalated RT ( &lt; 66 Gy). Overall survival of HPV+ and HPV- disease was compared between full-dose and de-escalated approaches. Results: Altogether, 617 and 551 patients were HPV+ and HPV-, respectively. De-escalated RT was delivered in 16.9% HPV+ and 15.2% of HPV- disease, respectively. Older patients and those not receiving systemic therapy were more likely to receive de-escalated RT. In HPV+ patients, 3- and 5-year survival rates were 83% and 80% in the de-escalated cohort versus 83% and 78% in the full-dose group (p = 0.83). In HPV- patients, corresponding 3- and 5-year survival rates were 29% and 23% versus 61% and 51% (p = 0.001). Conclusions: National utilization of de-escalated RT for OPSCC is low (15-20%), but does not seem to impact overall survival in HPV+ (but not HPV-) patients. The caveats of this heterogeneous, retrospective analysis require corroboration from a number of ongoing randomized trials.