tbuckley/cabot-search huggingface dataset:
Maintenance olaparib after platinum-based chemotherapy in patients (pts) with newly diagnosed advanced ovarian cancer (OC) and a BRCA mutation (BRCAm): Efficacy by surgical and tumor status in the Phase III SOLO1 trial.
Authors: Cara Amanda Mathews, Kathleen N. Moore, Nicoletta Colombo, Giovanni Scambia, Byoung-Gie Kim, Ana Oaknin, Michael Friedlander, Alla Sergeevna Lisyanskaya, Anne Floquet, Alexandra Leary, Gabe S. Sonke, Charlie Gourley, Susana N. Banerjee, Amit M. Oza, Antonio González-Martín, Carol Aghajanian, William Hampton Bradley, Elizabeth S. Lowe, Ralph Bloomfield, Paul Disilvestro
Journal: Journal of Clinical Oncology (2019)

5541 Background: In SOLO1 (NCT01844986), maintenance olaparib significantly improved progression-free survival (PFS) vs placebo (HR 0.30; 95% CI 0.23–0.41; Moore et al. N Engl J Med 2018) in pts with newly diagnosed advanced OC and a BRCAm. This analysis evaluates olaparib efficacy by timing of surgery, presence of residual tumor following surgery and response status after completion of chemotherapy in SOLO1. Methods: Pts underwent cytoreductive surgery and were in clinical complete response (CR) or partial response (PR) after platinum-based chemotherapy. Pts were stratified by response and received olaparib tablets 300 mg twice daily or placebo. Investigator-assessed PFS and objective response were assessed using modified RECIST v1.1. Results: 260 pts were randomized to olaparib and 131 to placebo; one pt did not receive placebo. Median follow-up was 41 months in both arms. 63% and 35% of pts underwent upfront and interval surgery, 21% and 76% had residual and no residual macroscopic disease after surgery, and 74% and 26% entered the study in clinical CR and PR (based on electronic case report form [eCRF] data). PFS was significantly improved regardless of the timing of surgery, residual disease status after surgery or response after platinum-based chemotherapy (Table). In pts with baseline radiologic evidence of disease (n=80; eCRF), the objective response rate was 43% for olaparib (CR, 28%) and 23% for placebo (CR, 12%). Conclusions: Maintenance olaparib improved outcomes compared with placebo in pts with newly diagnosed advanced OC and a BRCAm, regardless of surgical or tumor status. Clinical trial information: NCT01844986. [Table: see text]
Overestimation of tumor mutational burden (TMB) using algorithms compared to germline subtraction.
Authors: Kaushal Parikh, Robert Huether, Kevin White, Derick Hoskinson, Haidong Dong, Alex A. Adjei, Aaron Scott Mansfield
Journal: Journal of Clinical Oncology (2019)

2621 Background: TMB is an emerging predictor of survival with immunotherapy. TMB is determined by taking the difference between somatic and germline datasets when tumor-normal pairs are available. In the case of commonly utilized tumor-only sequencing, additional steps are needed to estimate the somatic alterations. Computational tools have been developed that determine germline contribution based on sample copy state, purity estimates and occurrence of the variant in population databases. Given the potential bias of population datasets, we hypothesized that tumor-only filtering approaches may overestimate the actual TMB. Methods: We assessed the TMB from 50 tumors in 10 diseases including all missense, indels, and frameshift variants with an allelic fraction (AF) ≥5% and Coverage ≥100X within the tumor. Tumor-only TMB was evaluated against the gold standard of matched germline subtracted TMB at three levels. Level 1 removed all the tumor-only variants with AF in the non-TCGA ExAC database ≥1%. Level 2 removed all variants observed in population databases simulating a naive approach of removing germline variation. Level 3 used an internal tumor-only pipeline for calculating TMB. Results: There were significantly higher estimates of TMB with Level 1, Level 2 and Level 3 tumor-only filtering approaches than that determined by germline subtraction, resulting in significant bias. Whereas there was no correlation between TMB estimates and tumor-germline TMB for Level 1 filtering, there were improvements in correlations for Level 2 and Level 3. Conclusions: The tumor-only approaches that filter variants in population databases overestimate TMB compared to that determined by germline subtraction. Despite improved correlations with more stringent filtering approaches, these falsely elevated estimates may result in the inappropriate categorization of tumor specimens and negatively impact clinical trial results and patient outcomes. [Table: see text]
Real-world assessment of healthcare costs for patients with metastatic pancreatic cancer following first-line chemotherapy initiation.
Authors: Andrea J. Bullock, Christopher G Rowan, Nina Hill, Homa Yeganegi, E. Gabriela Chiorean
Journal: Journal of Clinical Oncology (2019)

e15710 Background: Nab-paclitaxel-gemcitabine (AG) and FOLFIRINOX (FFX) are commonly used regimens for the treatment of metastatic pancreatic cancer (mPDA). This descriptive study aimed to report total healthcare costs following first line (1L) exposure to AG/FFX among patients with mPDA. Methods: Retrospective cohorts of 1L AG and FFX initiators with mPDA were constructed from the MarketScan database (study period 2014-2017). The index date was the date of 1L AG or FFX initiation. Included patients had continuous insurance enrollment. Total healthcare costs (outpatient, inpatient, emergency department, chemotherapy, pharmacy) were assessed at 0-1, 0-3, 0-6, and 0-12 months post-index among patients who remained uncensored (using the last claim date) through the last month of each follow-up interval. Results: 2199 patients initiated AG (N=1352) or FFX (N=847) as their 1L regimen. Compared with AG initiators, FFX patients were younger (59 vs 63 years) and had better baseline health status (FFX/AG): diabetes 43%/57%; cerebrovascular disease 21%/27%. Median time to censoring was 5.4 (AG) and 7.2 (FFX) months. Median treatment duration was 2.1 (AG) and 2.3 (FFX) months. FFX costs were higher than AG costs during each follow-up interval, with the cost differential increasing over time (Table). Conclusions: Higher total healthcare costs were observed for patients with mPDA who initiated 1L FFX compared with 1L AG. Further research using comparative methodology is warranted to fully elucidate these findings and understand cost drivers. [Table: see text]
Accelerated Approval of Cancer Drugs—Righting the Ship of the US Food and Drug Administration
Authors: Sarah S. P. DiMagno, Aaron Glickman, Ezekiel J. Emanuel
Journal: JAMA Internal Medicine (2019)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Internal Medicine journal
Machine learning for CT texture analysis in chemosensitivity of colorectal liver metastases: Initial results.
Authors: Yuji Miyamoto, Takeshi Nakaura, Yukiharu Hiyoshi, Hideo Baba
Journal: Journal of Clinical Oncology (2019)

e15148 Background: Despite advances in cancer treatment over the last decades, more efficacious biomarkers are needed in patients with metastatic colorectal cancer. Several studies have reported that CT texture analysis is a useful prognostic biomarker for patients with colorectal cancer liver metastases (CRLM), however, little study has been done to explore those efficacies using machine learning methods. The present study aimed to evaluate the clinical efficacy of CT texture analysis using machine learning methods as a predictive marker of systemic chemotherapy in patients with CRLM. Methods: Sixty-four patients with CRLM who received first-line chemotherapy were included. Texture analysis was performed on 92 features (First Order Statistics, Gray Level Cooccurrence Matrix, Gray Level Run Length Matrix, Gray Level Size Zone Matrix, Neighbouring Gray Tone Difference Matrix and Gray Level Dependence Matrix) using CT within 1 month before treatment. We evaluated the association between those features and chemotherapeutic response by RECIST (CR+PR vs. SD+PD+NE). We performed eXtreme gradient boost (XGBoost) as a machine learning method to predict the chemotherapeutic response and used the receiver operating characteristic curves to evaluate this prediction model. Results: Main characteristics were the following: male/female = 36/28; median age = 63.5. Patients were treated with oxaliplatin-based chemotherapy (80% of patients), bevacizumab (77%) and anti-EGFR antibody (23%). Thirty-nine patients had confirmed responders, for an overall response rate of 61%, whereas 25 patients (39%) were classified as non-responders (CR: PR: SD: PD: NE = 0: 39: 20: 4: 1). The area under curve of this prediction model was 0.771. Conclusions: We confirmed that CT texture analysis using machine learning for CRLM was feasible. Further analyses are ongoing.
Morbidity and mortality in a national cohort of pediatric patients with hemophagocytic lymphohistiocytosis.
Authors: Steven William Allen, Meghan McCormick, Ram Kalpatthi, Louis Rapkin
Journal: Journal of Clinical Oncology (2019)

10062 Background: Despite significant advances in diagnosing and treating hemophagocytic lymphohistiocytosis (HLH) in the pediatric population, survival remains low and the extent of disease morbidity and health care utilization is poorly characterized. Thus, we sought to investigate morbidity, mortality, and the health care burden of HLH in a pediatric population. Methods: We queried the Pediatric Health Information System (PHIS) for children admitted with HLH and treated with etoposide and dexamethasone between 1/1/2004 – 9/30/2018. Collected data included demographics and clinical variables associated with morbidity and mortality. Results: A total of 493 patients (10.5 per 100,000 patients admitted) met inclusion criteria during the study period. The majority of patients (n = 284, 58%) were less than 5 years of age. A total of 331 patients were readmitted after the initial hospitalization, with 29% of readmissions complicated by infections. Median cost for initial hospitalization was $101,906 (IQR: $47,552 – $271,822). A significant number of patients required ICU care during both the initial admission (60%) and readmission (57%). Hematopoietic stem cell transplant (HSCT) was performed in 136 patients (28%) with a median time to HSCT of 126 days (IQR: 75-193 days). Overall mortality was 32% (n = 158), half occurring during the initial admission. There was a trend towards increased mortality in younger age groups. Median time to death during and after the initial admission was 45 days (IQR: 20-84 days) and 198 days (IQR: 108-368 days), respectively. Post-HSCT mortality rate was 35%. Conclusions: This represents the largest cohort of pediatric patients treated for HLH. Overall and post-HSCT mortality was consistent with prior publications. We observed significant morbidity and increased health care resource utilization in our cohort. These findings emphasize the need for novel therapeutic approaches to improve not only patient survival but also long-term quality of life. Planned future analysis of the PHIS data will be aimed at assessing treatment variability, morbidity and mortality depending on treatment, and risk factors associated with mortality in pediatric patients with HLH.
The effects of mindfulness meditation and progressive muscle relaxation on fatigue and quality of life in breast cancer patients receiving adjuvant paclitaxel: A three-arm randomized trial.
Authors: Zehra Gok Metin, Nur Izgu, Canan Karadas, Leyla Ozdemir, Umut Demirci
Journal: Journal of Clinical Oncology (2019)

e12051 Background: Breast cancer patients often suffer from fatigue during adjuvant paclitaxel regimen which frequently impairs quality of life (QOL). Therefore, this three-arm randomized controlled study aimed to examine the effects of mindfulness-based stress reduction (MBSR) and progressive muscle relaxation (PMR) on fatigue and QOL in breast cancer patients receiving adjuvant paclitaxel. Methods: Participants were randomly assigned to either a MBSR (n = 20), (PMR) (n = 19) or control group (CG) (n = 15). Participants in the intervention groups were instructed on MBSR and PGE, the steps of interventions were recorded a voice recorder and a WhatsApp group was designed by the principal investigator. Participants were asked to listen the recorded audio files during exercises. The intervention groups continued MBSR or PMR 20 min. each day, totally 12 weeks at their home. The CG received only an attention placebo education on breast cancer. Data collection tools included Brief Fatigue Inventory (BFI) and Functional Living Index-Cancer (FLIC). Data were collected at three time points: baseline (T1), week 12 (T2), and week 14 (T3) for follow-up assessment. Kruskal Wallis tests was used for data analysis. Results: BFI scores were significantly lower in the MBSR, PMR groups compared with the CG at T2 and at T3 (p &lt; .01). As for FLIC scores, there were no significant differences between the study groups at T2 and at T3 (p &gt; 0.05). Conclusions: A brief, MBSR and PMR initiated concurrently with adjuvant paclitaxel regimen decreased fatigue severity. Based on the results, MBSR and PMR can be recommended as supportive therapies for breast cancer patients receiving adjuvant paclitaxel.
Implementing strain imaging to identify early childhood cancer survivors at risk for cardiovascular disease.
Authors: Wendy Bottinor, Justin Godown, Gary Coburn, Jonathan Soslow, Scott C. Borinstein
Journal: Journal of Clinical Oncology (2019)

e23070 Background: In patients receiving active chemotherapy, myocardial strain has prognostic utility for risk of subsequent cardiomyopathy. We hypothesized a decrement in strain in early off-treatment childhood cancer survivors (CCS) is prognostic for developing cardiomyopathy. Methods: Retrospective analysis was performed in 22 CCS. Global longitudinal strain (GLS) and global circumferential strain (GCS) were assessed at baseline and on the first end-of-treatment study with adequate imaging quality. Parametric methods assessed the association between changes in GLS/GCS and cardiovascular outcomes. Results: All CCS had normal echocardiograms at baseline and on the first end-of-treatment study . On long-term follow up 5/22 developed echocardiographic abnormalities defined as either left ventricular ejection fraction &lt; 55% (n = 4) and/or left ventricular mass Z score &lt; -2.0 (n = 4). Mean age at diagnosis was (mean ± SEM) 13.0 ± 1.3 and 10.7 ± 1.2, p = 0.37 for those without and with long-term abnormalities respectively. Patients who developed long-term echocardiographic abnormalities had a greater decrement in GCS between baseline and fist end-of-treatment echocardiograms (-6.9 ± 0.9% vs -0.7 ± 1.2%, p = 0.011) and a trend towards greater decrement in GLS (-1.5 ± 1.3% vs 1.2 ± 0.7%, p = 0.069). In early off-therapy CCS an absolute change in GCS of 7% was associated with subsequent cardiovascular dysfunction within 10 years. Conclusions: Change in GCS of 7% or greater from baseline to first end-of-treatment echocardiogram may identify CCS at risk for cardiomyopathy on long-term follow up and offer a window for early intervention. Strain imaging may provide an early method of identifying CCS at higher risk for developing cardiomyopathy on long-term follow up. These survivors may benefit from increased surveillance or early intervention with cardioprotective therapies.
Case 28-1984
Authors: Richard C. Cabot, Robert E. Scully, Eugene J. Mark, Betty U. McNeely
Journal: New England Journal of Medicine (1984)

Presentation of Case A 39-year-old man was admitted to the hospital because of gas in the tissue of the forearm. Seventeen years earlier the patient sustained a gunshot wound to the left forearm, followed by repeated incision and drainage for osteomyelitis and several skin grafts and other reconstructive procedures. Four years before admission he was treated elsewhere for gas gangrene ofthe forearm, with infection that spread proximally as far as the left shoulder and an interval of coma. Thereafter he was well until five days before admission, when he struck his left arm on the gearshift of a truck and . . .
Ectopic prolactin production by lung cancer cells as an indicator of aggressive nature of tumors.
Authors: Vladislav M. Legostaev, Tamara G. Ayrapetova, Oleg I. Kit, Elena M. Frantsiyants, Valeria A. Bandovkina, Oleg M. Babenkov, Anna V. Chubaryan, Maria Ezhova, Maksim N. Duritskiy
Journal: Journal of Clinical Oncology (2019)

e20021 Background: Cancer cells use many unexpected molecular mechanisms to ensure their malignancy, and a comprehensive understanding of cancer cannot be achieved without a global consideration of all oncogenic events. Ectopic activation of tissue-specific hormones accompanies malignant transformation in many cancers. The aim of the study was to determine prolactin (PRL) levels in the blood, tumor and surrounding lung tissues in lung cancer patients of both sexes. Methods: Levels of PRL were measured in the blood and 10% homogenates of the tumor, perifocal tissues and intact lung tissues by radioimmune method using Immunotech kits (Czech Republic). The study included 33 men and 22 women with central and peripheral lung adenocarcinomas (T 2-3 N 0-1 M 0 ), mean age 62±3.4 years, all women were menopausal. The comparison group included non-cancer patients (13 men and 12 women) operated on for chronic inflammatory lung diseases. Results: PRL levels in peripheral blood in 74% of men were increased by 3.7 times, and in 85% of women by 5.7 times. Peripheral cancer in men and women had no significant differences in prolactin levels; the hormone distribution was similar in the tumor, perifocal and intact tissues and was on average 1.5 times higher than in lung tissues in patients with inflammatory processes. Women with central cancer were characterized by higher tumor levels of PRL compared to men. In general, both in men and women, PRL levels in perifocal tissues and in intact lung tissue distant from the tumor focus were similar to tumor levels, which could indicate a general change in the organ metabolism, and not a local hormone synthesis by tumor tissues. Conclusions: The detected increase in the PRL content in lung tissues and in the blood may indicate the dysfunction of central regulatory mechanisms and a change in lung metabolism, being one of the links in the causal mechanisms of tumor development.
Initiation of sacubitril/valsartan in haemodynamically stabilised heart failure patients in hospital or early after discharge: primary results of the randomised TRANSITION study
Authors: Rolf Wachter, Michele Senni, Jan Belohlavek, Ewa Straburzynska‐Migaj, Klaus K. Witte, Zhanna Kobalava, Candida Fonseca, Eva Goncalvesova, Yuksel Cavusoglu, Alberto Fernandez, Said Chaaban, Ellen Bøhmer, Anne‐Catherine Pouleur, Christian Mueller, Christophe Tribouilloy, Eva Lonn, Jehad A.L. Buraiki, Jacek Gniot, Maria Mozheiko, Malgorzata Lelonek, Adele Noè, Heike Schwende, Weibin Bao, Dmytro Butylin, Domingo Pascual‐Figal
Journal: European Journal of Heart Failure (2019)

To assess tolerability and optimal time point for initiation of sacubitril/valsartan in patients stabilised after acute heart failure (AHF).TRANSITION was a randomised, multicentre, open-label study comparing two treatment initiation modalities of sacubitril/valsartan. Patients aged ≥ 18 years, hospitalised for AHF were stratified according to pre-admission use of renin-angiotensin-aldosterone system inhibitors and randomised (n = 1002) after stabilisation to initiate sacubitril/valsartan either ≥ 12-h pre-discharge or between Days 1-14 post-discharge. Starting dose (as per label) was 24/26 mg or 49/51 mg bid with up- or down-titration based on tolerability. The primary endpoint was the proportion of patients attaining 97/103 mg bid target dose after 10 weeks. Median time of first dose of sacubitril/valsartan from the day of discharge was Day -1 and Day +1 in the pre-discharge group and the post-discharge group, respectively. Comparable proportions of patients in the pre- and post-discharge initiation groups met the primary endpoint [45.4% vs. 50.7%; risk ratio (RR) 0.90; 95% confidence interval (CI) 0.79-1.02]. The proportion of patients who achieved and maintained for ≥ 2 weeks leading to Week 10, either 49/51 or 97/103 mg bid was 62.1% vs. 68.5% (RR 0.91; 95% CI 0.83-0.99); or any dose was 86.0% vs. 89.6% (RR 0.96; 95% CI 0.92-1.01). Discontinuation due to adverse events occurred in 7.3% vs. 4.9% of patients (RR 1.49; 95% CI 0.90-2.46).Initiation of sacubitril/valsartan in a wide range of heart failure with reduced ejection fraction patients stabilised after an AHF event, either in hospital or shortly after discharge, is feasible with about half of the patients achieving target dose within 10 weeks.ClinicalTrials.gov ID: NCT02661217.