tbuckley/cabot-search huggingface dataset:
A retrospective analysis of antibiotics usage and effect on overall survival and progressive free survival in patients with metastatic pancreatic cancer.
Authors: Chirayu Mohindroo, Jane E. Rogers, Merve Hasanov, Jonathan Mizrahi, Michael J. Overman, Gauri Rajani Varadhachary, Robert A. Wolff, Milind M. Javle, David R. Fogelman, Shubham Pant, Florencia McAllister
Journal: Journal of Clinical Oncology (2019)

e15781 Background: Recent studies have shown that the pancreatic ductal adenocarcinoma (PDAC)-associated gut microbiome can play a major in modulating responses to therapies. Antibiotics (ATB) can potentially alter the tumor and gut microbiota diversity and composition leading to modified responses to chemotherapeutic/immune therapy regimens and hence the survival. Methods: We retrospectively analyzed the clinical data of 148 patients (pts) with documented metastatic PDAC seen at MD Anderson Cancer (MDACC) from 2009 to 2017. Along with demographic and chemotherapy regimen details the duration, type and reason for antibiotic consumption for more than 3 days were recorded. Overall survival (OS) and Progression free survival (PFS) were calculated. Log-rank test and Gehan-Breslow-Wilcoxon test were used to check the statistical significance for OS and PFS. Confounding variables were also accounted. Results: We analyzed the data of 148 metastatic pancreatic cancer pts[mean age 62.73, 50.67% males 49.32% females, 75.6% white] out of which 135 patients received antibiotics. The infectious sources consisted of intraabdominal (n = 68), urinary (n = 36), respiratory (n = 57), skin/soft tissue infections (n = 26), blood related (n = 24), and others (n = 76). Beta lactams (n = 96) and Quinolones (n = 96) were the most commonly prescribed antibiotics. When comparing outcomes, we found out that the median OS for pts taking macrolides (n = 24) was 541 days compared to 341 days for pts not taking macrolides (n = 144) (HR = 0.6384, p value = 0.0191) . Median PFS for pts taking macrolides was 178 days versus 124 days in those not taking macrolides (HR = 0.6331, p value = 0.0188). The potential confounders were having a respiratory infection or the type of chemotherapy regimen. Conclusions: Macrolide consumption for &gt; 3 days leads to a prolonged OS and PFS. Consistent with the preclinical evidence our data suggests a potential role for some antibiotics in modulating PDAC-associated gut microbiome. Hence, having implications on the survival of PDAC pts. [Table: see text]
Case 44-1984
Authors: Richard C. Cabot, Robert E. Scully, Eugene J. Mark, Betty U. McNeely
Journal: New England Journal of Medicine (1984)

Presentation of Case A 15-year-old girl was admitted to the hospital because of a question of chronic active hepatitis. She was well until 1 1/2 years earlier, when she began to experience fatigue, malaise, and arthralgia in the elbows and knees. One year before admission a physician made a diagnosis of infectious mononucleosis and prescribed prednisone, without improvement. Eight months before entry orthodontic braces were fitted, and she began to notice bleeding gums. Five months before admission anemia was found. A physician made a diagnosis of mycoplasma infection, but the administration of iron and an antibiotic had no effect. The . . .
Rates and patterns of uninsured cancer survivors before and after implementation of the Affordable Care Act, 2000-2017.
Authors: Nina Niu Sanford, Miranda Lam, David J. Sher, Santino Butler, Chul Ahn, Ayal Aaron Aizer, Brandon Arvin Virgil Mahal
Journal: Journal of Clinical Oncology (2019)

e18105 Background: Cancer survivors experience difficulties in maintaining healthcare coverage, however the reasons and risk factors for lack of insurance are poorly defined. We sought to assess self-reported reasons for not having insurance and to assess demographic and socioeconomic factors associated with non-insurance among cancer survivors, before and after implementation of the Affordable Care Act (ACA) in 2014. Methods: We used the National Health Interview Survey to identify adult participants (18-64 years) reporting a cancer diagnosis between 2000-2017. Multivariable logistic regression was used to define the association between demographic and socioeconomic variables and odds being uninsured. The prevalence of the most common self-reported reasons for not having insurance (unemployment, employment-related reason, family-related) were estimated, with AORs for each of the reasons defined by multivariable logistic regression. Results: Among 17,806 survey participants, 10.3% reported not having health insurance. Individuals surveyed in 2000-2013 had higher odds of not having insurance as compared to those surveyed in 2014-2017 (10.6% vs. 6.2%, AOR 1.75, 95% CI 1.49-2.08). Variables associated with higher odds of non-insurance throughout the entire study interval included younger age, annual family income below the poverty threshold, black race, Hispanic ethnicity, non-citizen status and current smoking (p &lt; 0.001 for all). After implementation of the ACA, increasing interval from cancer diagnosis and black race were no longer associated with not having insurance. The most commonly cited reason for not having insurance were cost followed by unemployment, both of which decreased after ACA implementation (cost: 49.6% vs. 37.6%, AOR 0.62, 95% CI 0.46-0.85; unemployment: 37.1% vs. 28.5%, AOR 0.62, 95% CI 0.45-0.87). Conclusions: The proportion of uninsured cancer survivors decreased after implementation of the ACA, however certain subgroups remain at greater risk of being uninsured. Cost remains the primary barrier to obtaining insurance, although more than half of cancer survivors reported other barriers to coverage. Given the growing number of cancer survivors in conjunction with rising health costs, efforts addressing barriers to insurance coverage are needed for this population.
Safety of neoadjuvant chemoradiation (CRT) in combination with avelumab (A) in the treatment of resectable esophageal and gastroesophageal junction (E/GEJ) cancer.
Authors: Nataliya Volodymyrivna Uboha, James D. Maloney, Daniel McCarthy, Dustin A. Deming, Noelle K. LoConte, Kristina Matkowskyj, Jens C. Eickhoff, Philip Emmerich, Malcolm M. DeCamp, Sam Joseph Lubner, Anita Ahmed Turk, Michael Frederick Bassetti
Journal: Journal of Clinical Oncology (2019)

4041 Background: Neoadjuvant CRT followed by surgery is the standard of care (SOC) for patients (pts) with stage II/III E/GEJ cancer. However, recurrence rates are high. Immunotherapy has demonstrated promising activity in advanced E/GEJ cancer. This trial evaluates safety and efficacy of perioperative A with CRT in resectable E/GEJ cancer. Methods: This is a 2-part phase I/II trial. Part 1 is a run-in phase with 6 pts for safety evaluation. Part 2 will enroll additional 18 pts in the expansion cohort. Pts with E/GEJ cancer of any histology receive CRT (41.4 Gy in 23 fractions) with carboplatin and paclitaxel as per SOC. Three doses of A (10 mg/kg, q14 days) are administered starting on day 29 of treatment, to coincide with the last chemotherapy dose. Surgery is performed ~8 weeks after CRT completion. Pts receive 6 doses of A after resection. Dose-limiting toxicity (DLT) evaluations are completed on the first post-operative clinic visit, 2-4 weeks post resection. Results: Between 6/2018 and 2/2019, 6 pts (all male, median age 62) enrolled in part 1: 6 adenocarcinoma (100%); 1 E, 3 Siewert 1, 2 Siewert 2; 1 cT2N0, 2 cT3N0, 3 cT3N1. All pts underwent successful resection with negative surgical margins. 1/6 pts had R1 resection due to tumor extension to inked adventitial surface without invasion of surrounding structures. There were no unexpected surgical complications. At resection, 2 pts had ypT0N0, 2 ypT1N0, 1 ypT2N0, and 1 ypT3N1 disease. Combination of CRT and A had an acceptable toxicity profile. No DLTs were seen in the first 5 pts, so expansion cohort is open to enrollment. No grade ≥3 immune-related AEs were observed. Immune-related hypothyroidism was seen in 1 patient (grade 2). 6/6 pts had reversible grade 3 or 4 lymphopenia; 1/6 had grade 3 neutropenia. Correlative studies are ongoing and will be presented at the meeting. Conclusions: Perioperative CRT with A is well tolerated with no unexpected toxicities. Additional safety and correlative data will be presented at the meeting. This study is actively enrolling pts to an expansion cohort at University of Wisconsin. Clinical trial information: NCT03490292.
Adherence enhancing program for patients with metastatic, castration-resistant prostate carcinoma treated with abiraterone acetate plus prednisone: A cluster randomized trial.
Authors: Henrik Suttmann, Susan Feyerabend, Jochen Gleissner, Andreas Hübner, Tim Mathes, Werner Baurecht, Katrin Krützfeldt, Hussein Sweiti
Journal: Journal of Clinical Oncology (2019)

e16520 Background: Abiraterone acetate plus prednisone (AA+P) is an effective treatment for patients (pts) with metastatic, castration-resistant prostate carcinoma (mCRPC). Adherence is an important factor for the success of AA+P treatment. Research has shown that adherence in pts taking oral anti-cancer agents is often lower than required. The objective of this cluster randomized trial (CRT) was to assess the influence of an adherence enhancing program (AP) for AA+P in pts with mCRPC. Methods: This was a pragmatic parallel CRT of pts with mCRPC performed under real-world conditions. The study sites were randomly assigned to AP or no-AP (1:1) using a computer generated random schedule. The AP consisted of an educational video and reminder telephone calls. The primary endpoint was “rate of therapy discontinuation after 3 months for reasons other than disease progression or start of a new cancer therapy” (discontinuation). A secondary outcome was medication adherence (Morisky Scale; MMAS-4). Results: In the final intention-to-treat analysis, 47 sites comprising 360 men were allocated to AP and 40 sites comprising 315 men to no-AP. Baseline characteristics and results for each group are presented in the table. The odds ratio (OR) for discontinuation, adjusted for baseline adherence was 1.16 (95%CI: 0.63 to 2.11) and 1.21 (95%CI: 0.74 to 1.97) for 3 and 6 months, respectively. The OR for medium/low medication adherence, adjusted for baseline adherence, was 0.56 (95%CI: 0.26 to 1.21) and 0.84 (95%CI: 0.36 to 1.97) for 3 and 6 months, respectively. Conclusions: The rate of treatment discontinuation in the first 3 and 6 months was low and similar in both study arms. Medication adherence at baseline was generally high, but with some difference between both arms. The adjusted OR for medication adherence at 3 and 6 months revealed a trend towards a slower drop in medication adherence for the AP arm, compared to the no-AP arm, but with a wide confidence interval. Table Clinical trial information: 284. [Table: see text]
Low-coverage whole genome sequencing of FFPE-derived-DNA and extracellular vesicle-associated DNA in patients with metastatic cancer.
Authors: Bella Hai Nguyen, Nick Wong, Timothy Semple, Olivia Ruhen, Stephen Q Wong, Connull Leslie, Bob Mirzai, Michael Millward, Katie Meehan, Annette May Ling Lim
Journal: Journal of Clinical Oncology (2019)

e14523 Background: Low-coverage whole genome sequencing (LC-WGS) of tumors provides valuable insight into molecular changes driving oncogenesis. A novel liquid biopsy source of tumor DNA for analysis is from extracellular vesicles (EV) obtained from blood. This study compared copy number alteration (CNA) profiles generated from LC-WGS of Formalin-Fixed Paraffin-Embedded (FFPE) DNA and EV-associated DNA in cancer patients. Methods: Three metastatic base of tongue (BOT), two of which were Human Papillomavirus-related (HPV+) and two metastatic cutaneous squamous cell carcinoma (cSCC) patients were included. EV were isolated using ultracentrifugation from patients’ plasma. DNA was extracted from FFPE tumor tissue and EV. LC-WGS aiming for 0.5-1X coverage was performed using a validated method. CNA profiles were generated using the QDNAseq package, with gains defined as a log 2 ratio ≥0.15 and losses &lt; -0.15. Results: CNA profiles of FFPE samples from BOT patients demonstrated significant variation regardless of HPV status, with a mean of 20 regions containing 125 CNA (amplifications or deletions) per sample. The cSCC FFPE samples demonstrated a mean of 23 regions containing 189 CNA per sample. Overall, EV-associated DNA CNA profiles had limited similarity with primary FFPE. EV-associated DNA showed a lower number of CNA regions and CNA, with a mean of 3.7 CNA regions and 11.4 CNA for BOT samples and 6.5 regions and 15.9 CNA for cSCC samples. The HPV-BOT sample showed 2/3 EV-CNA regions matched corresponding FFPE-CNA profile (n = 15). The two HPV+ samples were less consistent with only 1/3 and 1/5 EV-CNA regions matching FFPE-CNA profiles (n = 39 and n = 6, respectively). The two cSCC cases showed more consistency with 4/6 and 6/7 EV-CNA regions matching FFPE-CNA profiles (n = 21 and n = 25, respectively). In the matched CNA regions, the mean CNA in EV-associated DNA was 7.5 and in FFPE-DNA was 97. Conclusions: Although selected EV-associated DNA CNA regions reflected the primary tumors, these were limited in number and did not globally reflect the FFPE derived CNA profiles.
Case 10-1986
Authors: Richard C. Cabot, Robert E. Scully, Eugene J. Mark, Betty U. McNeely, Leslie W. Ottinger, Austin L. Vickery
Journal: New England Journal of Medicine (1986)

Presentation of CaseA 65-year-old woman was admitted to the hospital because of abdominal masses.She was in a stable state of health until one month earlier, when a routine examination showed a mass in the left upper abdominal quadrant. She was referred to this hospital, where examination revealed a firm, movable, nontender mass, 5 cm in diameter, deep to the fascia in the left upper abdominal quadrant; the liver and spleen were not felt. Rectal examination was negative, and a stool specimen gave a negative test for occult blood. A barium-enema examination disclosed a round soft-tissue mass, 5 cm . . .
Effect of early nutrition intervention on advanced nasopharyngeal carcinoma patients receiving chemoradiotherapy.
Authors: Lingbin Meng, Xiaochun Xu, Xin Jiang, Tarek Mekhail
Journal: Journal of Clinical Oncology (2019)

e17504 Background: Patients with nasopharyngeal carcinoma (NPC) frequently developed the problem of malnutrition at the time of diagnosis. Chemoradiotherapy (CRT) can even worsen the situation. Therefore, nutritional intervention should be applied to prevent CRT-associated weight loss and interruption of CRT. However, it is still controversial if early nutritional intervention is beneficial to NPC patients with CRT. This study is to investigate the influence of early nutritional intervention on advanced NPC patients with CRT by evaluating the nutritional status and CRT treatment tolerance. Methods: A cohort of 78 stage III-IV nasopharyngeal carcinoma patients was divided into early (n = 46) and late (n = 32) nutrition intervention groups. The early group of patients received nutritional support at the beginning of CRT, whereas the late group received such a support until development of the side effects, like 50% required oral dietary intake or &gt; 10% weight loss. The data were collected and statistically analyzed. Results: There was no significant difference in baseline clinical characteristics between these two groups, suggesting that no selection bias occurred. Both groups of patients had weight loss at the end of CRT and 3 months thereafter. However, at the later time point, the early group started to regain their weight, while the late group continued to lose weight. At both time points, the early group had a lower percentage of weight loss than the late group. Similar results were also obtained for BMI, albumin, and pre-albumin levels (All p&lt; 0.05). Besides, the early group showed a lower rate of advanced mucositis, a lower percentage of patients with more than 3 days RT breaks, fewer days of RT delayed for toxicity, and a lower percentage of patients with unplanned hospitalizations (All p&lt; 0.05). A linear correlation was also found between the percentage of weight loss and the number of days of RT delayed. Conclusions: Early nutritional intervention provides beneficial outcomes to NPC patients by maintaining their nutritional status and enhancing CRT treatment tolerance. Our results also indicated early nutrition intervention may reduce the hospital cost and improve patients’ life quality.
Association of body mass index (BMI) with clinical outcomes in 203 metastatic clear cell renal cell carcinoma (ccRCC) patients (pts) treated with immuno-oncology (IO) agents.
Authors: Yasser Ged, Chung-Han Lee, Alejandro Sanchez, Cihan Duzgol, Joshua Chaim, Maria Isabel Carlo, Ashley Foster, Oguz Akin, Darren R. Feldman, A. Ari Hakimi, Sujata Patil, Robert J. Motzer, Helena Furberg, Martin Henner Voss
Journal: Journal of Clinical Oncology (2019)

e16103 Background: Obesity is a known risk factor for the development of ccRCC. For malignant melanoma, higher BMI was recently associated with improved outcomes to IO therapy (McQuade, Lancet Onc, 2018), a potential explanation being an obesity-associated inflammation effect. The association of BMI and clinical outcomes in mccRCC pts treated with IO therapy is unknown. Methods: Baseline characteristics and outcomes on therapy were retrospectively collected for pts with mccRCC who received IO-only regimens for at least 4 weeks at our institution. BMI and IMDC risk categories were determined for all pts at IO initiation. The log-rank statistic was used to test the associations between BMI with overall survival (OS) and progression free survival (PFS) and the chi-square test for the association with objective response rates (ORR). Results: Of the 203 eligible pts, 31% were normal weight, 36.5% were overweight, and 32.5% were obese. 24% of pts received IO as first line treatment. IMDC favorable vs intermediate/poor risk was 11 vs 89% in normal weight pts, 20 vs 80% in overweight pts and 20 vs 80% in obese pts. Median follow up time for survivors was 28.6 months (3.4-88). Obese and overweight pts experienced longer OS than those who were normal weight (P=0.01) (normal weight vs. obese, HR 2.0, 95% CI 1.20-3.37). However, this association became non-significant after adjusting for IMDC risk. RECIST evaluations were available for 107 pts. A higher ORR was seen in obese (41%) compared to overweight (15%) or normal weight (28%) pts (P=0.03). We found no association between BMI and PFS. Findings are summarized in the table below. Conclusions: In mccRCC pts treated with IO, obesity associates with superior outcomes, but does not appear to be independent of IMDC risk score. Research into the underlying mechanisms of obesity as a possible biomarker of IO clinical benefit is warranted. [Table: see text]
A phase I study of mirvetuximab soravtansine (IMGN853) and gemcitabine (G) in patients with FOLR1-positive recurrent epithelial ovarian (EOC), endometrial cancer (EC), or triple-negative breast cancer (TNBC).
Authors: Mihaela C. Cristea, Paul Henry Frankel, Timothy W. Synold, Joanne E. Mortimer, Daphne B. Stewart, Edward Wenge Wang, Alex Jung, Sharon P. Wilczynski, Gottfried E. Konecny, Dia Parungao, Melissa Eng, Lindsay Kilpatrick, Yi-Jen Chen, Scott Glaser, Ernest Soyoung Han, Thanh Hue Dellinger, Amy Hakim, Stephen Lee, Robert Morgan, Mark Tsuneo Wakabayashi
Journal: Journal of Clinical Oncology (2019)

3009 Background: IMGN853 is an antibody-drug conjugate targeting the folate receptor alpha (FOLR1), linked to maytansinoid, DM4. IMGN853 has promising single agent activity in FOLR1+ EOC. The recommended phase 2 dose (RP2D) is 6 mg/kg, based on adjusted ideal body weight (AIBW) IV every 3 wks. This study evaluates IMGN853 and G. Methods: Patients (pts) with FOLR1+ tumors including: platinum resistant EOC with ≤4 prior chemotherapy (CT) regimens, EC with ≤2 CT and TNBC ≤4 CT are eligible. FOLR1 + is defined as ≥25% of tumor staining (all tumors) ≥2+ intensity (EOC, EC) and ≥1+ (TNBC). A standard 3+3 design combines IMGN853 and G. EOC pts undergo one research biopsy to assess intratumoral vs. circulating DM4 level and biopsy vs. archival tissue FOLR1 expression. Dose-limiting toxicity (DLT) is assessed during cycle 1. Responses as per RECIST 1.1 are assessed at 12 wks. and adverse events (AEs) are evaluated by CTCAE v4.0. Results: From 10/2017 to 1/2019 a total of 15 pts. were treated (3 additional pts have consented on dose level [DL] 4):10 EOC, 3 EC and 2 TNBC. One pt. on DL1 had grade (G) 4 thrombocytopenia (PLT) DLT. Three pts were inevaluable for DLT and were replaced: 1 pt. at DL1 with G4 neutropenia without fever of unknown duration due to delayed follow up blood work, 1 pt. at DL2 and 1 pt. at DL3 due to incomplete cycle 1. No DLTs were observed on DL2-3. Day 8 cycle 1 dose modifications were required in 3 of 4 patients on DL3 (for mucositis [1 pt.], and PLT [2 pts]). We are now enrolling at the RP2D for both agents, and MTD will be determined prior to May 2019. Conclusions: IMGN853 in combination with G is achievable at clinically relevant doses and the recommended Phase 2 dose and MTD will be reported. Support: NCCN grant; with support from ImmunoGen Corp and Cancer Center Support Grant P30CA033572. Clinical trial information: NCT02996825. [Table: see text]
Risk of second primary neoplasia in patients with oropharyngeal carcinoma: Role of HPV status in the outcome.
Authors: Antonio Lopez-Pousa, Montserrat Lopez V, Jacinto Garcia, Nuria Farre, Oscar Gallego Rubio, Katerina Majercakova, Daniela Camacho, Maria Borrell, Consolacion Molto, Mariona Riudavets, Raul Terés, Aida Bujosa, IVANA GABRIELA SULLIVAN, Miquel Quer, Xavier Leon
Journal: Journal of Clinical Oncology (2019)

e17544 Background: Patients with HPV-positive oropharyngeal cancer (OPC) have better prognosis and a lower risk of appearance of second primary neoplasm (SPN) than HPV-negative OPC patients. The aim of our study was to analyze the risk of developing SPN in a large group of patients with OPC according to HPV status in the primary tumor and its relationship with toxic habits. Methods: This study includes patients from a prospective data-base: 484 OPC patients were treated from 1991 to 2017 for which the HPV DNA positivity was evaluated by PCR in available tumor specimens. HPV DNA positive samples were further tested for HPV E6*I mRNA detection and/or p16 INK4a immunohistochemistry. The mean follow-up of patients included in the study was 4.9 years (SD 5.1 years). We estimated the incidence of SPN in all cancer sites and in cancer sites related to tobacco and alcohol consumption according to the HPV status in the primary tumor. Results: Ninety-nine (20.5%) out of 484 OPCs included in the study were HPV-related. During the follow-up period, 127 patients with HPV-negative tumors (33.0%) and 19 patients with HPV-positive tumors (19.2%) had a SPN. Considering only the tobacco/alcohol-related SPNs, 106 of the patients with HPV-negative tumors (27.5%), and 12 patients with HPV-positive tumors (12.1%) had a tobacco/alcohol-related SPN (P &lt; 0.0001). Five-year and 10-year SPN-free survival for HPV-negative versus HPV-positive OPC patients was 61.0% versus 81.5%, and 37.6% versus 73.8%, respectively (P &lt; 0.001). When restricting the analyses to tobacco/alcohol-related SPNs, the corresponding survival rates were 66.6% versus 86.8% and 45.9% versus 83.5% for 5-year and 10-year survival rates, respectively (P &lt; 0.0001). The frequency of tobacco/alcohol-related SPNs occurrence throughout the follow-up period for patients with HPV-negative OPC was 27.5%, for patients with HPV-positive tumors with a previous history of severe tobacco and/or alcohol use was 21.4%, and for patients with HPV-positive tumors without a history of severe tobacco and/or alcohol consumption it was 8.5% (P &lt; 0.0001). Conclusions: HPV status and previous toxic habits might allow classifying patients regarding the risk of tobacco/alcohol-related SPNs. HPV-related OPC patients without previous history of severe tobacco and/or alcohol use have a significant low risk of SPN development, particularly in those locations related to tobacco use or alcohol consumption