tbuckley/cabot-search huggingface dataset:
Overall survival between African-American (AA) and Caucasian (C) men with metastatic castration-resistant prostate cancer (mCRPC).
Authors: Susan Halabi, Sandipan Dutta, Catherine M. Tangen, Mark Rosenthal, Daniel Peter Petrylak, Ian Murchie Thompson, Kim N. Chi, Johann S. De Bono, Abderrahim Fandi, John C. Araujo, Mario A. Eisenberger, Christopher Logothetis, David I. Quinn, Karim Fizazi, Celestia S. Higano, Daniel J. George, Michael J. Morris, Eric Jay Small, Ian Tannock, William Kevin Kelly
Journal: Journal of Clinical Oncology (2018)

LBA5005 Background: Reports have suggested that African-American (AA) men with metastatic castration-resistant prostate cancer (mCRPC) have shorter overall survival (OS) than Caucasian (C) men. Prior reports have been limited by small sample size. The primary goal of this analysis was to compare OS in AA men to Caucasian men treated with docetaxel/prednisone or a docetaxel/prednisone containing regimen. Methods: Individual patient data from 8,871 mCRPC men randomized on nine phase III trials to docetaxel/prednisone (DP) or a DP containing regimen were combined. Race used in the analysis was based on self-report. The primary endpoint is OS, defined as the time between randomization and death or date of last follow-up if patients were alive. The proportional hazards model was used to assess the prognostic importance of race (AA vs. C) adjusting for established risk factors that were common across the trials (age, PSA, performance status, alkaline phosphatase, hemoglobin, and sites of metastases). Results: Of 8,871 patients, 7,528 (85%) were C, 500 (6%) were AA, 424 were Asian (5%) and 419 (4%) had race unspecified. The last two groups were deleted from the analysis leaving 8,452 pts. Median age was 69 years and 94% had performance status 0-1. Median hemoglobin, PSA and alkaline phosphatase were 12.9 g/dL, 86 ng/mL and 139 U/L, respectively. Pattern of metastatic spread were: 72% bone disease with or without lymph nodes, 9% lung disease, 9% liver disease and 7% lymph nodes only. Median OS were 21.0 (95% CI = 19.4-22.5) vs. 21.2 months (95% CI = 20.8-21.7) in AAs and C, respectively. In multivariable analysis adjusting for established risk factors, the pooled hazard ratio (HR) for AAs vs. Caucasians was 0.81 (95% CI = 0.72-0.92, p-value = 0.001) in all patients. Similar results were observed in 4,172 of patients who were treated with DP. Conclusions: We observed a statistically significant increased OS in AA vs. C men with mCRPC who were eligible to be enrolled on these clinical trials. Further understanding the biological variation by race in men with mCRPC treated with DP is warranted.
An open-label, multicenter, phase Ib study to evaluate RC48-ADC in patients with HER2-positive metastatic breast cancer.
Authors: Binghe Xu, Jiayu Wang, Qingyuan Zhang, Yunjiang Liu, Ji Feng Feng, Wenxiang Wang, Jianmin Fang
Journal: Journal of Clinical Oncology (2018)

1028 Background: RC48-ADC is a novel HER2-targeting antibody–drug conjugate (ADC) that selectively delivers anticancer agent MMAE into HER2-overexpressing tumor cells. A Phase I study (NCT02881138) has preliminary demonstrated that RC48-ADC is well tolerated and has clear clinical activity in patients (pts) with metastatic breast cancer (MBC). Methods: This was a phase Ib, open-label, multicenter study with 3 dose cohorts (1.5, 2.0 and 2.5mg/kg, Q2W). Eligible pts (18-70 years) were assessed HER2-positive (IHC 2+/FISH +, or IHC 3+) MBC, with relapsed/refractory to prior standard treatment. Results: From Dec, 2016 to Jan, 2018, 30 female pts (6 IHC2+/FISH+; 24 IHC 3+) pretreated with trastuzumab/chemotherapy were enrolled for 1.5 and 2.0 mg/kg cohorts. Median age was 53 years (range: 26-62). 19 pts (63.3%) received HER2-targeting agents. 16 pts (53.3%) received three or more previous chemotherapy regimens in metastatic setting. Disease control (CR+PR+SD) was observed in 29 of 30 evaluable pts who received RECIST 1.1 assessment (96.7%), with 11 PR (ORR: 36.7%; 30-76% regression) and 18 SD (60.0%) with tumor regression. CBR (CR + PR + SD ≥6 months) was presented in 14 pts (46.7%). ORR was 26.7% and 46.7% in the 1.5mg/kg and 2.0 mg/kg cohorts, respectively; it was 57.1% in trastuzumab-naive pts and 33.3% in trastuzumab-pretreated pts (12 pts treated with≥3 prior chemotherapy). The common treatment-related adverse events (TRAEs) reported were AST elevation (50.0%), ALT elevation (43.3%), leucopenia (33.3%), neutropenia (33.3%), numbness (23.3%); most were Grade 1-2 in severity. Only 3 pts (10%) reported Grade≤2 thrombocytopenia. Grade 3 TRAEs occurred in 4 pts (13.3%), including neutropenia (10%), leucopenia (6.7%), AST elevation (3.3%), ALT elevation (3.3%). No Grade ≥4 AE was observed. Pharmacokinetic analyses showed dose-dependent exposure with 1-1.5 d half-life. Conclusions: RC48-ADC has showed manageable safety and encouraging efficacy profiles in pts with HER2-positive MBC. Investigation of 2.5 mg/kg expansion cohort has not yet been started. Results obtained from Phase I study will determine whether 2.5mg/kg cohort expansion is performed. Clinical trial information: NCT03052634. Clinical trial information: NCT03052634.
PREPARE: A new clinical prognostic model for survival of Asian early breast cancer patients.
Authors: Lei Lei, Soa-Yu Chen, Yi-Ping Lin, Xiao-Jia Wang, Hung-Chun Cheng
Journal: Journal of Clinical Oncology (2018)

e12532 Background: The top three ethnic groups of breast cancer in the United State are White, Black, and Asian with Asian women having the best survival rate. No well-established prognostic tool is available for Asian women. This study aims to develop and validate a prognostic model for predicting overall survival of Asian early breast cancer (EBC) patients. Methods: Using the Taiwan Cancer Registry Data (TCRD) in a cancer center at Taipei as the derivation dataset, information was collected for 6,847 women who had surgery for invasive breast cancer from 1990 to 2014. An external dataset of 12,519 Asian and 117,485 white from the 2010 - 2013 Surveillance, Epidemiology, and End Results (SEER) EBC database was used for validation. Multivariate Cox proportional hazards model was used for analyzing potential prognostic factors for the overall survival. Results: This model was built according to the age at diagnosis, T and N stage, tumor grade, PR status, ER/PR (+) with hormonal therapy, HER2 (+) with Herceptin, chemotherapy, and radiotherapy. Difference between the 3-year observed and predicted events is 2.7% (161 vs. 165.4, p = 0.73), 0.4% (95 vs. 95.3, p = 0.97), and -39.3% (1908 vs. 1158.7, p <.00001) for the TCRD, SEER Asian, and SEER White dataset, respectively. The integrate area under receiver-operator-characteristic curve is 0.75, 0.77, and 0.77, respectively. Difference between the 10-year observed and predicted events is 0.6% for TCRD (238 vs. 236.5, p=0.92). Model calibration was pretty good at 10 years for the TCRD and 3 years in both the TCRD and SEER Asian datasets. This Asian model underestimated the risk of mortality of white EBC in all subsets of patients. Conclusions: By using the SEER dataset, this Asian EBC model is well calibrated and validated in SEER Asian but not in SEER white women. The different prognostic power for different races suggests that race-specific survival prediction model is needed for EBC.
Abnormalities of Striatal Projection Neurons and<i>N</i>-Methyl-D-Aspartate Receptors in Presymptomatic Huntington's Disease
Authors: Roger L. Albin, Anne B. Young, John B. Penney, Barbara Handelin, Rosemary Balfour, Keith D. Anderson, Dorene S. Markel, Wallace W. Tourtellotte, Anton Reiner
Journal: New England Journal of Medicine (1990)

HUNTINGTON'S disease is an autosomal dominant disease characterized by slowly progressive personality changes, dementia, and movement disorders.1 , 2 The average age at onset is 30 to 40 years, and the disease lasts for an average of 15 to 20 years. Analysis with restriction-fragmentlength polymorphisms (RFLPs) has localized the Huntington's disease gene close to the telomere of the short arm of chromosome 4.1 2 3 Prominent striatal atrophy with loss of striatal neurons and relative sparing of fibers of passage and afferent axons is the pathological hallmark of Huntington's disease.4 Recent studies have demonstrated a distinct pattern of vulnerability of striatal neurons in Huntington's . . .
Bridging the Critical Divide in Pain Management Guidelines From the CDC, NCCN, and ASCO for Cancer Survivors
Authors: Salimah H. Meghani, Neha Vapiwala
Journal: JAMA Oncology (2018)

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 Oncology 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 Oncology journal
Delivery of survivorship care from rural primary care and oncology practices.
Authors: Jennifer R. Klemp, Becky N. Lowry, Judy A Johnston, Kyla Alsman, Danielle Peereboom, Trish Long, Susan Krigel, Hope Krebill, Allen Greiner
Journal: Journal of Clinical Oncology (2018)

85 Background: While evidence-based guidelines for survivorship care exist, implementation in oncology and primary care practices has fallen short. There is little evidence of the barriers preventing successful implementation in rural primary care and oncology practices. We sought to assess knowledge gaps and barriers to successful implementation of evidence-based survivorship care guidelines in rural Kansas practices. Methods: Midwest Cancer Alliance, outreach arm of the University of Kansas Cancer Center, and Kansas Patients and Providers Engaged in Prevention Research, completed interviews in rural primary care and oncology practices. Results: Primary Care (n=7) and Oncology Practices (n=4): Interviews with primary care physicians, medical oncologists, advanced practice providers, nurses, tumor registrar, outreach coordinator, and office management &amp; staff. Conclusions: Rural primary care and oncology practices experienced barriers to delivering survivorship care including: educational gaps, communication of history, treatment, and recommendations, EHR integration, and lack of resources. Next steps focus on a unified approach to state-wide survivorship education of patients, primary care and oncology practices. [Table: see text]
Sunitinib Alone or after Nephrectomy in Metastatic Renal-Cell Carcinoma
Authors: Arnaud Méjean, Alain Ravaud, Simon Thezenas, Sandra Colas, Jean-Baptiste Beauval, Karim Bensalah, Lionnel Geoffrois, Antoine Thiery-Vuillemin, Luc Cormier, Hervé Lang, Laurent Guy, Gwenaelle Gravis, Frederic Rolland, Claude Linassier, Eric Lechevallier, Christian Beisland, Michael Aitchison, Stephane Oudard, Jean-Jacques Patard, Christine Theodore, Christine Chevreau, Brigitte Laguerre, Jacques Hubert, Marine Gross-Goupil, Jean-Christophe Bernhard, Laurence Albiges, Marc-Olivier Timsit, Thierry Lebret, Bernard Escudier
Journal: New England Journal of Medicine (2018)

Cytoreductive nephrectomy has been the standard of care in metastatic renal-cell carcinoma for 20 years, supported by randomized trials and large, retrospective studies. However, the efficacy of targeted therapies has challenged this standard. We assessed the role of nephrectomy in patients with metastatic renal-cell carcinoma who were receiving targeted therapies.
Analyses on expression of trimethylation of histone H3 at lysine 27 and DNA methylation at CCGG sites in smoking and nonsmoking non-small cell lung cancer patients and their clinical significance.
Authors: Xiaohui Chen, Yujie Deng, Kunshou Zhu, Takeshi Nagayasu, Dan Hu, Chunwei Xu, Gen Lin, Cheng Huang, Gang Chen, Xiongwei Zheng, Yibin Cai, Jian-ping Lu, Guibin Weng
Journal: Journal of Clinical Oncology (2017)

e23179 Background: Smoking usually leads to epigenetic alterations like DNA methylation and histone modifications. We analyzed the effect that smoking had on DNA methylation level at CCGG sites and expression of trimethylation of histone H3 lysine 27 (H3K27me3), enhancer of zeste homolog 2 (EZH2) and their interactions in non-small cell lung cancer (NSCLC) patients. Methods: 42 NSCLC patients, 22 adenocarcinomas and 20 squamous cell carcinomas were enrolled. Expression of H3K27me3, EZH2 and PCNA were immunohistochemically detected. Apoptotic index in NSCLC with different smoking status was evaluated via TUNEL method. DNA methylation at CCGG sites was evaluated by HELMET method. Their correlation with clinicopathological data were calculated in relation to different smoking status. Results: Compared to the nonsmokers, smoker NSCLC patients were found more often of lower level of DNA methylation at CCGG sites, lower H3K27me3 expression and higher EZH2 expression, and lower apoptotic cell index ( P&lt; 0.05). DNA methylation level at CCGG sites negatively correlated to the Binkman Index( P= 0.017). Further, trend of H3K27me3 and EZH2 expression was in the same direction in most smokers, while in nonsmokers, their expression trend was mostly in the opposite direction ( P= 0.015). Trend of PCNA and EZH2 expression was in the opposite direction in most smokers, while in nonsmokers, their expression trend was mostly in the same direction ( P= 0.048). In addition, trend of CCGG methylation ratio and immunohistochemical expression of H3K27me3 was in the same direction in most smokers, while in nonsmokers, the trend was mostly in the opposite direction ( P= 0.049). Conclusions: NSCLC patients of different smoking status exhibit completely different epigenetic characteristics, and DNA methylation at CCGG sites would probably determine the expression trend of H3K27me3, EZH2 and PCNA.
Association Between Vitamin D Supplementation During Pregnancy and Offspring Growth, Morbidity, and Mortality
Authors: Wei Guang Bi, Anne Monique Nuyt, Hope Weiler, Line Leduc, Christina Santamaria, Shu Qin Wei
Journal: JAMA Pediatrics (2018)

<h3>Importance</h3> Whether vitamin D supplementation during pregnancy is beneficial and safe for offspring is unclear. <h3>Objective</h3> To systematically review studies of the effects of vitamin D supplementation during pregnancy on offspring growth, morbidity, and mortality. <h3>Data Sources</h3> Searches of Medline, Embase, and the Cochrane Database of Systematic Reviews were conducted up to October 31, 2017. Key search terms were<i>vitamin D</i>,<i>pregnancy</i>,<i>randomized controlled trials</i>, and<i>offspring outcomes</i>. <h3>Study Selection</h3> Randomized clinical trials of vitamin D supplementation during pregnancy and offspring outcomes. <h3>Data Extraction and Synthesis</h3> Two authors independently extracted data, and the quality of the studies was assessed. Summary risk ratio (RR), risk difference (RD) or mean difference (MD), and 95% CI were calculated using fixed-effects or random-effects meta-analysis. <h3>Main Outcomes and Measures</h3> Main outcomes were fetal or neonatal mortality, small for gestational age (SGA), congenital malformation, admission to a neonatal intensive care unit, birth weight, Apgar scores, neonatal 25-hydroxyvitamin D (25[OH]D) and calcium concentrations, gestational age, preterm birth, infant anthropometry, and respiratory morbidity during childhood. <h3>Results</h3> Twenty-four clinical trials involving 5405 participants met inclusion criteria. Vitamin D supplementation during pregnancy was associated with a lower risk of SGA (RR, 0.72; 95% CI, 0.52 to 0.99; RD, −5.60%; 95% CI, −0.86% to −10.34%) without risk of fetal or neonatal mortality (RR, 0.72; 95% CI, 0.47 to 1.11) or congenital abnormality (RR, 0.94; 95% CI, 0.61 to 1.43). Neonates with prenatal vitamin D supplementation had higher 25(OH)D levels (MD, 13.50 ng/mL; 95% CI, 10.12 to 16.87 ng/mL), calcium levels (MD, 0.19 mg/dL; 95% CI, 0.003 to 0.38 mg/dL), and weight at birth (MD, 75.38 g; 95% CI, 22.88 to 127.88 g), 3 months (MD, 0.21 kg; 95% CI, 0.13 to 0.28 kg), 6 months (MD, 0.46 kg; 95% CI, 0.33 to 0.58 kg), 9 months (MD, 0.50 kg; 95% CI, 0.01 to 0.99 kg), and 12 months (MD, 0.32 kg; 95% CI, 0.12 to 0.52 kg). Subgroup analysis by doses showed that low-dose vitamin D supplementation (≤2000 IU/d) was associated with a reduced risk of fetal or neonatal mortality (RR, 0.35; 95% CI, 0.15 to 0.80), but higher doses (&gt;2000 IU/d) did not reduce this risk (RR, 0.95; 95% CI, 0.59 to 1.54). <h3>Conclusions and Relevance</h3> Vitamin D supplementation during pregnancy is associated with a reduced risk of SGA and improved infant growth without risk of fetal or neonatal mortality or congenital abnormality. Vitamin D supplementation with doses of 2000 IU/d or lower during pregnancy may reduce the risk of fetal or neonatal mortality.
Response to salvage chemotherapy following exposure to immune checkpoint inhibitors in patients with non-small cell lung cancer.
Authors: Paul Denis Leger, Sasha Rothschild, Emily Castellanos, Rathi Narayana Pillai, Sally Jane York, Leora Horn
Journal: Journal of Clinical Oncology (2017)

9084 Background: Immune checkpoint inhibitors are active for patients with stage IV NSCLC who have progressed following platinum-based chemotherapy. We evaluated responses to chemotherapy in patients who had progressed on a checkpoint inhibitor. Methods: Eligible patients were adults with NSCLC who received salvage chemotherapy following PD-1/PD-L1 inhibitors (cases) versus no PD-1/PD-L1 inhibitors (controls). CT-imaging was done within 4 weeks of initiation of salvage chemotherapy and every 6 weeks thereafter. Revised RECIST guidelines were used to define response. Clinical and imaging data were abstracted from review of electronic medical records. Multivariate logistic regression analysis was used to calculate probability of response. Results: Three-hundred and fifty patients’ charts were reviewed and 82 patients met eligibility criteria. Among evaluable patients, 46 were males. Sixty-seven patients were cases versus 15 controls. Fifty-six patients received nivolumab, 7 pembrolizumab and 4 atezolizumab. Sixty-three (77%) had adenocarcinoma, 18 (22%) squamous cell carcinoma and 1 (1%) large cell carcinoma. The mean number of chemotherapy regimens prior to salvage chemotherapy was 2.37 (95% C.I. 2.10-2.64)) in cases versus 1.93 (95% C.I: 1.32-2.54) in controls. Salvage drugs included docetaxel (62%), pemetrexed (20%), gemcitabine (12%), paclitaxel (6%). Eighteen (27%) cases had partial response to chemotherapy versus 1(7%) controls. Fifteen (22%) cases had progressive disease versus 6 (40%) controls. Thirty-four (51%) cases had stable disease versus 8 (53%) controls. The odd ratio for achieving a partial response was 0.30 (95% CI: 0.18 to 0.50, P = 0.000). In multiple logistic regression model, age, gender, number of prior chemotherapy regimens, tumor histology, smoking status, different salvage chemotherapy regimens were not associated with the likelihood of achieving a partial response. Conclusions: The odds of achieving a partial response to salvage chemotherapy were more than 3 times higher inpatients with prior exposure to PD-1/PD-L1 inhibitors. Ongoing investigations include the duration of response as well as evaluation of toxicity.
A young man with a mass on the neck
Authors: Shing Fung Lee, Ting Ying Ng, Frank Chi Sing Wong, Stewart Yuk Tung
Journal: BMJ (2018)

A 25 year old man was referred to the oncology unit with a three week history of a neck lump that was progressively increasing in size, and atypical lymphoid cells on fine needle aspiration cytology. The patient also reported mild exertional dyspnoea and drenching night sweats, but no weight loss, occupational exposure to harmful substances, recent travel, or high risk sexual behaviour. He had smoked cigarettes since he was 16.

On examination, the right supraclavicular lymph node was palpable and measured 3 cm in diameter. Chest radiography showed a widened mediastinum but no lung lesions. Contrast enhanced computed tomography of the thorax was performed (fig 1). Core biopsy of the node showed partial effacement of nodal architecture by scattered large cells in a background of reactive lymphocytes, eosinophils, and plasma cells with some collagen fibrosis. These large cells stained positive for CD15 and CD30 and negative for CD45. Figure 2 shows an example micrograph from biopsy (not from the patient described).



Fig 1 
Axial contrast enhanced computed tomography of the thorax showing an anterior mediastinal mass, with a central hypodense area suggestive of necrosis (red arrow)





Fig 2 
Micrograph showing a Reed-Sternberg cell and normal lymphocytes. Reed-Sternberg cells are often binucleated with prominent nucleoli, having an …
The Value of Neoadjuvant Chemotherapy in Localized High-Risk Soft-Tissue Sarcoma of the Extremities and Trunk
Authors: Alessandro Gronchi, Robin L. Jones
Journal: JAMA Oncology (2018)

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 Oncology 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 Oncology journal