tbuckley/cabot-search huggingface dataset:
Case 4-1964
Authors: Kurt J. Isselbacher, Robert E. Scully
Journal: New England Journal of Medicine (1964)

Presentation of Case* First admission. A forty-eight-year-old engineer entered the hospital because of diarrhea.The patient had been well until four years previously, when he began to pass 3 or more unformed stools per day; they were occasionally flecked with blood but did not contain mucus. Five months before admission barium-enema and sigmoidoscopic examinations at another hospital were reported to show ulcerative colitis. Three months later he experienced a two-day illness characterized by fever, watery diarrhea and the passage of grossly bloody stools. The diarrhea gradually subsided, and he again began to pass 3 or more soft stools daily.Physical . . .
Longitudinal treatment patterns and adverse events (AEs) in younger patients (Pts) with metastatic triple-negative breast cancer (mTNBC): A real-world landscape analysis.
Authors: Nicole Maria Kuderer, Della Varghese, Kala Hill, Gary H. Lyman, Marc Botteman
Journal: Journal of Clinical Oncology (2019)

e12562 Background: While no uniform standard of care exists for mTNBC, conventional chemotherapy remains the treatment mainstay. This retrospective analysis of U.S. commercial claims data was conducted to characterize real-world longitudinal chemotherapy treatment patterns and predictors of AEs in mTNBC. Methods: We assessed all pts with mTNBC aged 18-60 years starting first-line (1L) chemotherapy from 01/01/2011 to 12/31/2015 in the IMS LifeLink database, which does not report on investigational therapies. Longitudinal treatment patterns, treatment duration, and AEs were characterized by line-of-therapy (LOT). The primary and secondary endpoints were any AE and treatment duration. Multivariable logistic and Cox regression analyses were used to identify clinical risk factors for AEs and predictors of longer treatment duration, respectively. Results: 1,447 mTNBC pts receiving ≥1 LOT were identified (median [range] age, 51 [24-60] years), of which 54% received ≥2 and 8% ≥3 LOT. Combination therapy (combi-Tx) was used as 1L for 73%, second-line (2L) for 22%, and third-line (3L) for 32% of pts. The most common combi-Tx was cyclophosphamide/doxorubicin (1L: 40%; 2L: 5%), and carboplatin/gemcitabine in 3L (17%). The most common 1L and 2L monotherapies (mono-Tx) were taxanes (10% and 66%), and 3L capecitabine (13%). Median treatment duration for 1L to 3L was 56-58 days, and for combi- vs mono-Tx in 1L, 50 vs 71 days. The proportion of pts experiencing any AE was 34% during 1L, 38% during 2L, and 56% during 3L therapy. After adjusting for key confounders including Charlson comorbidity index, independent risk factors for AEs were later LOT, 3L vs 1L (OR = 3.20, 95%CI: 2.13-4.79), and younger age groups vs age 55-60 (OR = 1.94, 95%CI: 1.48-2.55). Additional analysis will assess independent predictors of treatment duration. Conclusions: This real-world study reveals considerable treatment heterogeneity and short treatment durations even with conventional combination chemotherapies. Among non-Medicare mTNBC pts, younger age is a risk factor for AEs possibly due to more aggressive therapies. More treatment options are needed for pts with mTNBC.
Prevalence and penetrance of breast cancer-associated mutations identified by multiple-gene sequencing in the Women’s Health Initiative.
Authors: Allison W. Kurian, Elisha Hughes, Ryan Bernhisel, Katie Larson, Jennifer Lee Caswell-Jin, Aladdin H. Shadyab, Heather Ochs-Balcom, Kathy Pan, Lihong Qi, Kerryn Reding, Anne-Renee Hartman, Johnathan M. Lancaster, Jean Y. Tang, Marcia L. Stefanick
Journal: Journal of Clinical Oncology (2019)

1513 Background: Next-generation sequencing enables rapid analysis of many inherited cancer susceptibility genes. Little is known about the prevalence and penetrance of pathogenic variants (PVs) in such genes among post-menopausal women with breast cancer, who comprise the majority of all breast cancer patients. Methods: The Women’s Health Initiative enrolled post-menopausal women from 1993-1998. We conducted a nested case-control study using banked DNA samples of 2,195 women who subsequently developed invasive breast cancer (cases) and 2,322 cancer-free controls. Sequenced genes were APC, ATM, BARD1, BMPR1A, BRCA1, BRCA2, BRIP1, CDH1, CDK4, CDKN2A (p16INK4a and p14ARF) , CHEK2, EPCAM, GREM1, MLH1, MSH2, MSH6, MUTYH, NBN, PALB2, PMS2, POLD1, POLE, PTEN, RAD51C, RAD51D, SMAD4, STK11, and TP53. PV were defined using American College of Medical Genetics criteria. PV prevalence is reported as proportions and penetrance as the odds ratio (OR) and 95% confidence interval (CI) of PV versus none among cases versus controls. Results: Among cases, the median age at diagnosis was 73 years; 66% were White, 18% Black, 6% Hispanic, 6% Asian and 4% other. The prevalence of PVs in any gene was significantly higher in cases (6.61%, 95% CI 5.57-7.65%) versus controls (4.09%, 95% CI 3.29-4.90%). The prevalence of BRCA1/2 PVs was 1.2% in cases and 0.22% in controls. Among cases, the prevalence of PVs in other breast cancer-risk genes was 2.3% ( ATM, CDH1, BARD1, BRIP1, CHEK2, NBN, and PALB2 collectively), two-fold higher than PVs in BRCA1/2. Prevalence of BRCA1/2 PVs decreased with age among cases, while prevalence of ATM, CHEK2 and PALB2 PVs did not. Statistically significant ORs for breast cancer penetrance were observed for BRCA1 (5.43, 95% CI 1.19-51.52), BRCA2 (4.71, 95% CI 1.84-15.08), BARD1 (9.78, 95% CI 1.04-1295.87) and PALB2 (6.30, 95% CI 1.93-31.94). Conclusions: Approximately 7% of women diagnosed with post-menopausal breast cancer carry a PV in a cancer susceptibility gene. In contrast to studies of younger breast cancer patients, PVs in other breast cancer-related genes were two times more common than in BRCA1/2. Results may guide genetic testing of women with post-menopausal breast cancer.
Spatial heterogeneity of <i>KRAS</i> mutations in colorectal cancers: A population-based study in northern France.
Authors: Anne Ploquin, Michael Genin, Mohamed Hebbar, Florent Occelli, Caroline Lanier, Clotilde Decarpentries, Diane Pannier, Anthony Turpin
Journal: Journal of Clinical Oncology (2019)

e15101 Background: Somatic mutations in the KRAS gene are present in about 40% of tumors from colorectal cancer (CRC) patients and are associated with a resistance to anti-EGFR therapies. However, no clinical features have been linked to KRAS mutations in CRC. In this study, we attempted to identify the potential geographical population clusters of KRAS mutations in CRC patients in northern France. Methods: All patients with CRC who were identified to have KRAS mutations performed by pyrosequencing between 2008 and 2014 at the Regional Molecular Biology Platform at Lille University Hospital were included. We retrospectively collected demographic and geographic data from these patients. The proportions of KRAS mutation were smoothed to take into account the variability related to low frequencies and spatial autocorrelation. Geographical clusters were searched using spatial scan statistical models. Then, we made an ecological study. Results: 2,486 patients underwent a KRAS status available. A mutation of KRAS codon 12 or 13 performed by pyrosequencing was found in 1,018 patients (40.9%). We report 5 clusters of over-incidence but only one elongated cluster that was statistically significant ranging from the city of Tourcoing to the city of Marquion (Cluster 1; smoothed proportion of KRAS mutation: 0.4570; RR = 1.29; p = 0.0314). The ecological study did not highlight a significant association between KRAS mutations and the distance to the Closest Waste Incineration Plant , and between KRAS mutations and The French Ecological Deprivation Index. There was a greater frequency of KRAS mutations in some areas close to major highways and big cities in northern France. Conclusions: There is a spatial heterogeneity of KRAS codon 12 or 13 mutations in CRC in northern France. These data demand deeper epidemiological investigations to identify environmental factors such as air pollution as key factors in the occurrence of KRAS mutations.
Stereotactic radiotherapy for stage I renal cell carcinoma: Overall survival and treatment trends compared to thermal ablation and surgical resection.
Authors: Annemarie Uhlig, Johannes Uhlig, Lutz Trojan, Hyun S. Kim
Journal: Journal of Clinical Oncology (2019)

e16111 Background: Stereotactic radiotherapy (SRT) is a non-invasive treatment modality that is currently evaluated for use in renal cell cancer (RCC). We aimed to evaluate current utilization of SRT for stage I RCC and compare associated overall survival with thermal ablation (TA) and partial nephrectomy (PN). Methods: The 2004-2015 United States National Cancer Database was searched for histopathologically approved stage I RCC treated with PN, cryoablation (CRA), radiofrequency- or microwave-ablation (RFA/MWA) or SRT. Patients were propensity score matched to account for potential confounders. Overall survival (OS) was evaluated with Kaplan-Meier plots, log-rank tests and Cox proportional hazards models. Results: A total of 91,965 patients were included (SRT n = 174; PN n = 82,913; CRA n = 5,446; RFA/MWA n = 3,432).Stage I SRT patients tended to be older females with fewer comorbidities and treated at non-academic centers in New England states. After propensity score matching, a cohort of n = 660 patients was obtained with well-balanced distribution of confounders between the different treatment strategies. In the matched cohort, OS following SRT was inferior to PN and thermal ablation (PN vs. SRT HR = 0.33, 95% CI: 0.22-0.50, p &lt; 0.001; CRA vs. SRT HR = 0.44, 95% CI: 0.30 – 0.66, p &lt; 0.001; RFA/MWA vs. SRT HR = 0.53, 95% CI: 0.36-0.77, p &lt; 0.001). OS following CRA was comparable to PN (HR = 1.35, 95% CI: 0.84-2.18, p = 0.216), while OS following RFA/MWA was inferior to PN (HR = 1.61, 95% CI: 1.01-2.56, p = 0.046). OS rates are summarized in table 1. Conclusions: Only a minority of RCC patients receive SRT. In stage I RCC, current renal SRT protocols yield lower overall survival compared to thermal ablation and resection, while CRA and PN show comparable outcomes. Based on the current body of evidence, SRT for RCC should be reserved for clinical trials or exceptional clinical circumstances.[Table: see text]
Searching for lymphoma: An analysis of internet and social network activity and engagement.
Authors: John Patrick Galvin, Anne Catherine Meier, David J. Peace
Journal: Journal of Clinical Oncology (2019)

e18102 Background: Online search engines, forums and social networks can offer an important space to ask questions and share experiences. Online searches, forums and social networks have become one of the most common ways patients learn about their lymphoma. However, not much is known about which sites and online sources engage people on the topic of lymphoma and which social networks are used to learn and/or share experiences. Methods: Our objective was to analyze the sites with the most engagement online on the topic of lymphoma. We used an online analytical research program (BuzzSumo), which can assess specific content and identify sites that generate the greatest frequency of engagement across social platforms. Our analysis covered activity from 2/2014-2/2019. Results: From the analysis of 9,141 online articles on the topic of lymphoma and 662,690 engagements, we found that the social network that was used the most was Facebook and to a much lesser extent Twitter. The Pinterest and Reddit platforms were not engaged on this topic. Most engagements were with “List” and “What you should know” articles on lymphoma for both Facebook and Twitter with a significantly lesser amount of engagement for video content. Articles on lymphoma less than 2000 words had the most engagement. A number of different types of sites generated the most engagements -- ranging from media outlets, lymphoma foundations and large medical centers. An analysis of 28,863 Facebook posts on lymphoma with 4,765,956 total engagements revealed that video posts generated the most engagements and that posts that were &gt; 300 characters generated more engagement. An analysis of questions asked online mentioning lymphoma revealed that the most common topics were that of “diagnosis” and associated emotions – “worried” or “scared.” Conclusions: Online articles and social networks have become integrated into our daily lives. It is important that we start to understand how these information sources are being used by patients, caregivers and health care providers. Our analysis of online engagement on the topic of lymphoma is an example of how analytical programs can be used to help understand where and how people are engaging to learn and share their experiences with lymphoma.
CBT for Body Dysmorphic Disorder
Authors: Anita Slomski
Journal: JAMA (2019)

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A safety study of nivolumab in patients with recurrent and/or metastatic platinum-refractory squamous cell carcinoma of the head and neck (R/M SCCHN): Interim analysis on 199 patients—The TOPNIVO study on behalf of the GORTEC and the Unicancer Head &amp; Neck Group.
Authors: Caroline Even, Amaury Daste, Esma Saada-Bouzid, Gautier Lefebvre, Jerome Fayette, Sylvie Zanetta, Marie-Christine Kaminsky, Didier Cupissol, Alain Prevost, Elodie Vauleon, Alison Claire Johnson, Sebastien Salas, Frederic Rolland, Miruna Timar David, Isabelle Jallut, Jessy Delaye, Jean Bourhis, Joel Guigay, Matthieu Texier, Anne Auperin
Journal: Journal of Clinical Oncology (2019)

6032 Background: In the randomized phase III Study CA209141, Nivolumab (N) demonstrated significant overall survival (OS) benefit with favorable safety profile for platinum refractory R/M SCCHN and is now approved for these patients (pts). The objectives of the study are to provide additional insight into the frequency of high-grade AEs related to N and the efficacy of N in real life. Methods: Between August and December 2017, 203 pts were included in the multicenter, non-controlled phase II TOPNIVO. The main inclusion criteria were patients with platinum refractory R/M SCCHN with progressive disease, ECOG 0-2. Pts received N 3mg/kg every 2 weeks intravenously over 30 minutes. Four pts did not receive N. We report here the safety during the first 6 months (mo) after inclusion and OS results on the first 199 treated pts. Results: Median age was 62 yr, 83% were male, 84% were ECOG 0-1, 16% 2. The primary site of cancer was oral cavity 26%, oropharynx 38%, larynx 16%, hypopharynx 21%. 33% had loco regional relapse, 32% metastatic disease and 35% both. 49% had received one prior line of chemotherapy and 30% two prior lines. 157 (79%) pts ended their treatment within the first six mo: 5 for AE related to N (pneumonitis 3 pts, hepatitis 1 pt, diarrhea 1 pt), 107 for progression, 33 for death (24 related to progression, 9 to intercurrent disease), 12 other. 132 pts (66%) experienced at least 1 AE grade ≥3. On the 226 AEs grade 3-4, 21 (mainly pneumopathy, lipase increase and asthenia) were related to N and occurred in 18 pts. On the 51 AEs grade 5, 3 were considered related to N (2 pneumonitis, 1 cardiac arrest). The median OS was 7.7 mo (CI 95% [6.0; 9.5]) in the whole population; 9.2 mo [6.8; 12.1] in the 167 pts with ECOG 0-1, 3.0 mo [1.1; 6.0] in the 32 pts with ECOG 2; 12.1 mo [7.6; NR] in the 64 pts with metastatic disease, 7.7 mo [5.0; 9.6] in the 66 pts with locoregional disease and 4.6 mo [3.1; 7.9] in the 69 pts with both. OS was similar in pts older or younger 70 yr. Conclusions: The interim analysis of the TOPNIVO study shows no additional toxicities of N compared to what has been described previously, confirms the previous results of OS and provides new survival data in subgroups of pts. Clinical trial information: NCT03226756.
Predictors associated with development of pleural and pericardial effusions in patients with small cell lung cancer treated with third-line therapy.
Authors: Rui Jiang, Martina Koch, Scott Gulbranson, Philip B. Komarnitsky, Eros Papademetriou, Jerzy Edward Tyczynski
Journal: Journal of Clinical Oncology (2019)

e20088 Background: Pleural (Pl) and pericardial (Pc) effusions are often encountered clinical problems in patients with lung cancer, contributing to a poor quality of life. Population-based data on predictors for Pl and Pc effusions in small cell lung cancer (SCLC) are scarce, particularly, in later lines. Methods: We estimated the predictors for treatment-emergent Pl and Pc effusions in SCLC patients treated with third-line of therapy (LOT) using Optum’s electronic health records (EHR) de-identified database. Of 8,291 patients with newly diagnosed SCLC between 01/01/2008 and 09/30/2016, 428 patients received 3 rd LOT. Pc/Pl effusions were identified by a combination of ICD-9/ICD-10 codes, procedures, or natural language processing (NLP) SDS term and sentiment. Each patient contributed to follow-up time from start of 3 rd LOT to the day prior to start of next LOT or earlier of (loss to follow-up date or 365 days from end of 3 rd LOT) if there was no subsequent LOT, or first occurrence for those with an outcome event. Stepwise Cox regression with sle = 0.25 and sls = 0.10 was applied for variable selection. Results: At start of 3 rd LOT, median age was 65, 46% were male, 97% had extensive disease (excluding n = 53 with missing staging). Cardiac history, pulmonary history, renal impairment (eGFR &lt; 60 mL/min/1.73m 2 ), prior Pl and Pc effusion, albumin levels below 3.5 g/dl, sodium levels below &lt; 136 mmol/l, treatment regimens (others except platin-containing vs. topotecan mono) was each associated with increased risk of Pl effusions. Cardiac history, prior Pl and Pc effusion, and region (South vs. Midwest/West) was each associated with increased risk of Pc effusions. When the stepwise Cox regression was applied, cardiac history, prior Pl effusion, and treatment regimens were selected as significant predictors of Pl effusions (p &lt; 0.05). Prior Pc effusion and cardiac history were selected as significant predictors of Pc effusion (p &lt; 0.05). Conclusions: Awareness of the determinants associated with development of Pl and Pc effusions in SCLC patients treated in third-line therapy may aid in earlier recognition of patients at risk and lower the risk of developing Pl/Pc effusions in this group of patients.
Clinical Trial in Progress: The FLEX Big Data Platform explores new gene expression profiles and investigator-initiated protocols in early-stage breast cancer.
Authors: Sarah Untch, Gordan Srkalovic, Adam Brufsky, Jennifer A. Crozier, Mehran Habibi, Pat W. Whitworth, Charles E. Cox, Nina D'Abreo, William Audeh, Erin Yoder, Ian Grady
Journal: Journal of Clinical Oncology (2019)

TPS3155 Background: Genomic signatures are revolutionizing the definition, identification, and treatment of breast cancer. To precisely stratify breast cancers into actionable subgroups, full genome expression data and matching clinical data must be aggregated into a large data set. Such a data set will accelerate research and discovery, especially for smaller patient subsets who are not as widely represented within the current body of literature. Methods: FLEX is a multicenter, prospective, population-based, observational trial for patients with Stage I, II, and III breast cancer. All patients with stage I to III breast cancer who receive MammaPrint, with or without BluePrint on a primary breast tumor are eligible for enrollment. The study’s primary aim is to create a large scale, population-based registry of full genome expression data matched with clinical data to investigate new gene associations with prognostic and/or predictive value. Secondary objectives include utilizing the shared study infrastructure to examine and generate hypotheses for targeted subset analyses and/or trials based on full genome expression data. The design of FLEX allows targeted sub-studies and sub-analyses to be added as appendices after the initial baseline study is opened. Patients enrolled in the initial study are also eligible for inclusion in sub-studies where they meet all criteria and additional consent is not required. Additional clinical data will be collected as specified in the appendix protocols. The FLEX collaborative platform allows participating investigators the opportunity to author their own sub-study protocols, as approved by the FLEX Steering Committee of their peers. 13 sub-studies have already been identified and are under development. Eligibility: The study will enroll a minimum of 10000 patients aged ≥18 years with histologically proven invasive stage I-III breast cancer who signed informed consent. Enrollment began April 2017 and 1506 patients have been enrolled. Clinical trial information: NCT03053193.
Nivolumab monotherapy in patients with advanced platinum-resistant urothelial carcinoma: Efficacy and safety update from CheckMate 275.
Authors: Arlene O. Siefker-Radtke, Ari David Baron, Andrea Necchi, Elizabeth R. Plimack, Sumanta K. Pal, Jens Bedke, Yousef Zakharia, Marc-Oliver Grimm, Sergio Bracarda, Margitta Retz, Chikara Ohyama, Gary Grossfeld, Sandra Collette, Padmanee Sharma, Matt D. Galsky
Journal: Journal of Clinical Oncology (2019)

4524 Background: In the open-label, single-arm, phase 2 CheckMate 275 trial, objective response rate (ORR) for patients (pts) with metastatic urothelial carcinoma (mUC) with nivolumab (NIVO) was 20.4% with minimum follow-up of 21.3 mo. Here, we report updated efficacy and safety data with minimum follow-up of 33.7 mo. Methods: Pts with platinum-resistant locally advanced or metastatic urothelial carcinoma received NIVO 3 mg/kg until disease progression or unacceptable toxicity. The primary endpoint was ORR by blinded independent review committee (BIRC) by RECIST v1.1 (including duration of response [DOR]). Secondary endpoints included progression-free survival (PFS) by BIRC, overall survival (OS), and ORR per investigator. Efficacy was evaluated in all treated pts and by tumor PD-L1 expression. Safety and PFS by investigator were exploratory endpoints. Results: ORR by BIRC was 20.7% (95% CI 16.1–26.1) including 18 (7%) complete responses (CR; with 1 additional CR since the last report; Table). ORR per investigator was similar (24.8%). Median DOR by BIRC was 20.3 mo (95% CI 11.5–31.3). Of 56 pts with best overall response (BOR) of CR or partial response (PR), 59% had a DOR ≥12 mo. Median PFS (mPFS) was 1.9 mo per BIRC (95% CI 1.9–2.3; Table) and 2.0 mo per investigator (95% CI 1.9–2.5). Median OS (mOS) was 8.6 mo (95% CI 6.1–11.3; Table). 12, 24, and 36-mo OS rates were 40%, 30%, and 22%. While efficacy was numerically higher in pts with tumor PD-L1 expression ≥1%, efficacy was observed in all pts (Table). Any-grade treatment-related adverse events occurred in 69% of pts (grade 3–4, 25%), mostly (59%) within the first 3 mo of initiating therapy. Conclusions: With long-term follow-up from CheckMate 275, NIVO continues to provide durable antitumor activity in pts with mUC. No new safety signals were noted. Clinical trial information: NCT02387996. [Table: see text]