tbuckley/cabot-search huggingface dataset:
Assessment of the Role of Carotid Atherosclerosis in the Association Between Major Cardiovascular Risk Factors and Ischemic Stroke Subtypes
Authors: Sarah Parish, Matthew Arnold, Robert Clarke, Huaidong Du, Eric Wan, Om Kurmi, Yiping Chen, Yu Guo, Zheng Bian, Rory Collins, Liming Li, Zhengming Chen
Journal: JAMA Network Open (2019)

<h3>Importance</h3> A better understanding of the role of atherosclerosis in the development of ischemic stroke subtypes could help to improve strategies for prevention of stroke worldwide. <h3>Objective</h3> To assess the role of carotid atherosclerosis in the association between major cardiovascular risk factors and ischemic stroke subtypes. <h3>Design, Setting, and Participants</h3> The prospective China Kadoorie Biobank cohort study was conducted in the general population of 5 urban and 5 rural areas in China, with a baseline survey obtained between June 2004 and July 2008. A random sample of 23 973 participants with no history of cardiovascular disease at enrollment who had carotid artery ultrasonographic measurements recorded at a resurvey from September 2013 to June 2014 were included. Data analysis was performed from July 1, 2016, to April 10, 2019. <h3>Exposures</h3> Major cardiovascular risk factors (ie, blood pressure [BP], blood lipid levels, smoking, and diabetes). <h3>Main Outcomes and Measures</h3> Carotid ultrasonographic measures of plaque burden (derived from number and maximum size of carotid artery plaques at resurvey) and first ischemic stroke during follow-up (n = 952), with subtyping (data release, August 2018) as lacunar (n = 263), probable large artery (n = 193), probable cardioembolic (n = 66), or unconfirmed (n = 430). Associations between cardiovascular risk factors, carotid plaque burden, and ischemic stroke subtypes were adjusted for age, sex, and geographic area. <h3>Results</h3> The 23 973 participants in the study had a mean (SD) age of 50.6 (10.0) years, and 14 833 (61.9%) were women. Systolic BP had a stronger association (odds ratio [OR] per SD, 1.51; 95% CI, 1.42-1.61) than plaque burden (OR per SD, 1.34; 95% CI, 1.26-1.44) with ischemic stroke, and the associations of systolic BP with each subtype of ischemic stroke were modestly attenuated by adjustment for plaque burden. After adjustment for BP, plaque burden had a stronger association with probable large artery stroke (OR, 1.43; 95% CI, 1.24-1.63) than with lacunar stroke (OR, 1.25; 95% CI, 1.10-1.43) but was not associated with probable cardioembolic stroke (OR, 1.06; 95% CI, 0.83-1.36). <h3>Conclusions and Relevance</h3> Although BP was an important risk factor for all ischemic stroke subtypes, carotid atherosclerosis was an important risk factor only for large artery and lacunar strokes, suggesting that drug treatments targeting atherosclerosis may reduce the risk of stroke subtypes to different extents.
Immune-stimulatory gene expression in stroma cells of African-American prostate cancer tissues.
Authors: Dan Mercola, Farah Rahmatpanah, Anshu Agrawal, Zhenyu (Arthur) Jia, Xiaolin Zi, Michael B. Lilly, Michael McClelland
Journal: Journal of Clinical Oncology (2019)

e16544 Background: Prostate cancer (PCa) of African Americans (AA) has a two-fold higher mortality compared to PCa of European Americans (EA). PCa-adjacent stroma cells from these two populations were examined for differences in their cytokine secretion and gene transcription. Methods: Primary PCa-adjacent stroma cells (carcinoma-associated fibroblasts (CAFs)) and PCa-distant normal fibroblasts of the same gland (dNFs) from 15 AA and 27 EA patients were grown to passage 5. A multiplex immunoassay was then used to measure the secretion of 30 cytokines/chemokines in conditioned medium. In addition, RNA-Seq was performed on four AA and four EA CAF lines, and on PCa-adjacent stroma FFPE tissues of seven AA and five EA patients. Self-identified ethnicity was confirmed using the LASER program and SNPs present in the RNA-Seq. Results: Conditioned media from 42 AA and EA CAFs and dNFs were assayed for 30 immuno-regulatory cytokines/chemokines and growth factors, 20 of which (66%) were secreted at lower levels ( p &lt; 0.05) in AA vs. EA CAFs. Remarkably, dNFs did not show this difference. RNA-Seq analysis of AA vs EA CAFs in culture identified 413 upregulated and 893 downregulated genes (FDR &lt; 0.05, ≥ ±1.5 fold). Several interleukins, interferons, and 120 of 154 differentially transcribed interferon-stimulated genes were downregulated in AA vs. EA CAFs. RNA-Seq of PCa-adjacent stroma from FFPE tissues of seven AA and five EA patients revealed significantly reduced transcription of many immunomodulatory genes in AA stroma, including type I IFN-stimulated genes (ISGs). CIBERSORT analysis of the FFPE RNA-Seq data indicated the presence of significantly less numbers of dendritic cells and higher levels of naïve CD4 T h cells in AA vs. EA stroma. Conclusions: We observed reduced transcription of immunomodulators in CAFs of AA vs. EA, accompanied by profound decreases in the levels of many secreted cytokines and chemokines. These differences may indicate reduced innate and adaptive immune responses in AA PCa, compared to EA PCa. The differences observed here in primary cell lines may permit functional studies of the underlying mechanism(s) of the striking dissimilarity in disease outcome of AA PCa compared to EA PCa
Case 52-1987
Authors: Richard C. Cabot, Robert E. Scully, Eugene J. Mark, William F. McNeely, Betty U. McNeely
Journal: New England Journal of Medicine (1987)

Presentation of Case A 20-year-old woman was admitted to the hospital because of a diagnosis of central Cushing's disease. She was well until a year and a half earlier, when hypertension developed in the third trimester of pregnancy and was managed by diet alone. After delivery her weight decreased to 54.5 kg. She was able to nurse the child, and normal menses resumed, but during the next few months her weight increased inexorably so that one year before admission she weighed 81.8 kg. A diet and exercise were prescribed but did not reverse the process. She also began to experience . . .
Machine learning algorithm analysis using a commercial 592-gene NGS panel to accurately predict tumor lineage for carcinoma of unknown primary (CUP).
Authors: Jim Abraham, Amy B. Heimberger, Zoran Gatalica, Wolfgang Michael Korn, David Spetzler
Journal: Journal of Clinical Oncology (2019)

3083 Background: The diagnosis of a malignancy is typically informed by clinical presentation and tumor tissue features including cell morphology, immunohistochemistry, cytogenetics, and molecular markers. However, in approximately 5-10% of cancers, ambiguity is high enough that no tissue of origin can be determined and the specimen is labeled as a Cancer of Occult\Unknown Primary (CUP). Lack of reliable classification of a tumor poses a significant treatment dilemma for the oncologist leading to inappropriate and/or delayed treatment. Methods: 40,000 tumor patients with NGS data were used to construct a multiple parameter lineage-specific classification system using an advanced machine learning approach. The dataset for each classifier was split 50% for training and the other 50% for testing. The training task for each classifier was to identify the cases that were similar to the cases it was trained on against a backdrop of randomly selected cases of other histological origins. Results: Tumor lineage classifiers predicted the correct classifications where the primary site was known with accuracies ranging between 85% and 95%. When applied to CUP cases (n = 500), an unequivocal result could be obtained 100% of the time. Conclusions: Lineage predictors can render a histologic diagnosis to CUP cases that can inform treatment and potentially improve outcomes.
Remnant pancreatic volume to predict short-term and long-term outcomes in patients with resected pancreatic cancer.
Authors: Ryoichi Miyamoto, Yukio Oshiro, Nobuhiro Ohkohchi
Journal: Journal of Clinical Oncology (2019)

e15713 Background: Remnant pancreatic volume (RPV) is a well-known marker for short-term outcomes in patients with resectable pancreatic cancer. However, in terms of the long-term outcomes, the significance of the RPV remains unclear. Here, we addressed whether the RPV is a predictor of long-term outcomes in pancreatic cancer patients by comparing various cancer-, patient-, and surgery-related prognostic factors and systemic inflammatory response markers in a retrospective cohort. Methods: The RPV was measured on the 3D image, revealing the actual pancreatic parenchymal remnant volume. Ninety-one patients who underwent pancreaticoduodenectomy (PD) were retrospectively enrolled. We divided the cohort into high- and low-RPV groups based on a cut-off value ( &gt; 35.5 cm 3 , n = 66 and ≤ 35.5 cm 3 , n = 25, respectively). The patient characteristics, perioperative outcomes and median survival times (MSTs) were respectively compared between the two groups. Using multivariate analysis, the RPV and other well-known prognostic factors were independently assessed. Results: A significant difference in the RPV value was observed with respect to the incidence of postoperative pancreatic fistula (high, 18 [55%] vs. low, 9 [16%], p &lt; 0.001). The MSTs (days) were significantly different between the two groups (high, 823 vs. low, 482, p = 0.001). Multivariate analysis identified the RPV (≤ 31.5 cm 3 ) (hazard ratio [HR], 2.015; p = 0.011), lymph node metastasis (HR, 8.415; p = 0.002), adjuvant chemotherapy (HR, 5.352; p &lt; 0.001), presence of stage III/IV disease (HR, 2.352; p = 0.029), and pathological fibrosis (HR, 1.771; p = 0.031) as independent prognostic factors. Conclusions: The present study suggests that the RPV is an additional useful predictor of both long-term and short-term outcomes in pancreatic cancer patients after PD.
Multi-institution quality improvement in supportive oncology: Results of the Coleman Supportive Oncology Collaborative (CSOC).
Authors: Paramjeet Khosla, Julia Rachel Trosman, Betty Roggenkamp, Teresa Lillis, Joanna Martin, Shelly S. Lo, Mary Pasquinelli, Eileen Knightly, Anne Bowman, Selina Lai-ming Chow, Urjeet Patel, Rosa Berardi, Aidnag Diaz, Sheetal Mehta Kircher, Christine B. Weldon
Journal: Journal of Clinical Oncology (2019)

6606 Background: The Institute of Medicine and Commission on Cancer recommend systematic delivery of supportive oncology care for cancer patients. The CSOC is focused on quality improvement (QI) of supportive care across Chicago cancer centers (Weldon ASCO ’17). Supportive oncology includes distress, practical, family, physical, nutrition, pain, fatigue and care concerns. To support QI, cross-institution teams developed unique, relevant tools, methods, care delivery processes, patient handouts and online training. Methods: Ten centers (5 academic, 1 VA, 1 public, 2 safety net, 1 community) implemented supportive oncology screening and care delivery quality improvements. Centers collected data for relevant Quality Oncology Practice Initiative (QOPI) metrics. Analyses used simple frequencies and Fishers exact test. Results: Five of six QOPI measures were improved at statistically significant levels from 2014 to 2017, p &lt; .00001. Improvements are more modest in 2016 &amp; 2017 as 4 of the centers started this QI in 2017. Conclusions: The CSOC achieved significant improvements in supportive oncology screening and identifying and addressing patients’ needs and concerns. Additional work is needed to improve these measures to achieve the best quality of cancer care possible for every patient based on their needs and concerns. [Table: see text]
The impact of simultaneous dose escalation VMAT to the focal lesion micro boost of localized prostate cancer.
Authors: Radwa Fawzy Saleh Ahmed, Raafat Ragaie Abdel Malek, Mohamed Metwaly, Omar Abdel Aziz, Samy Al sirafy, Ahmed Seleem
Journal: Journal of Clinical Oncology (2019)

e16592 Background: Dose Escalation to the prostate is showing promising results of increasing local control. The study aims to assess biochemical failure free survival (BFF) after dose escalation to the prostate 78 Gy with simultaneous integrated boost (SIB) 87 Gy to the focal lesion. Genito-urinary (GU) &amp; gastro-intestinal (GI) toxicity was assessed by comparing investigational toxicity score &amp; patient outcome reports. Methods: Thirty intermediate &amp; high risk localized prostate cancer patients were treated with dose escalated VMAT protocol of 78 Gy /35 fractions to prostate &amp; 87 Gy boost to focal lesion detected by baseline multi-parametric MRI &amp; TRUS as well. Neo-adjuvant, Concurrent &amp; adjuvant hormonal therapy was applied. Risk structures dose statistics were matched to modified Quantec with EQD 2 equation. For each patient, daily online fiducial markers image guided verification was done. Toxicity profile was assessed by RTOG for subjective assessment and FACIT quality of life protocol for objective assessment during the radiotherapy course &amp; follow up period. Results: About 80% of patients received the pre-determined protocol, however three patients received 76 Gy to prostate &amp; 84 Gy to the focal lesion to comply with the risk structure constrains. At median follow up period of 18 months-BFF was 93.3 %. By the end of radiotherapy, 80% developed G3 GU toxicity while 30% developed G2 GI toxicity. Correlation between bladder V40 (≥or≤ 40%) &amp; GU toxicity (≤ G3 vs G3) was of border line statistical significance (P = 0.05). After radiotherapy, GU toxicity dropped to 17.2% G2 &amp; 13% G3 at the 3 rd month while 0 % G3 afterwards. Three patients developed G4 rectal toxicity (bleeding per rectum); one at 9 th month of ending treatment &amp; two at 12 th month; two of them needed cautery for angio-dysplasia as post radiation sequelae confirmed by colonoscopy. However, the correlation between V40 of the rectum ≥ 40% was significant with rectal toxicity (G0 vs G4) (P = 0.02). Comparing FACIT assessment during radiotherapy or in follow up showed no significant difference affecting the quality of life. Conclusions: Dose Escalation with SIB should be done using advanced technique like VMAT with image guidance. Re-validation of risk structure &amp; rectal dose constrains should be considered especially for dose escalation ≥ 72 Gy . Clinical trial information: NCT03384199.
Outcomes of adolescent males with extracranial malignant germ cell tumors compared with children and young adults: A report from the Malignant Germ Cell Tumors International Consortium (MaGIC) group.
Authors: Furqan Shaikh, Daniel P. Stark, Ha Dang, Caihong Xia, Mark D. Krailo, Sally Patricia Stenning, Farzana D. Pashankar, Carlos Rodriguez-Galindo, Thomas Arthur Olson, Juliet Hale, Sarita Depani, Sara Stoneham, James Nicholson, Matthew Murray, James F. Amatruda, Deborah F Billmire, Adriana Fonseca, A. Lindsay Frazier
Journal: Journal of Clinical Oncology (2019)

10022 Background: Adolescents with extracranial malignant germ cell tumors (GCTs) are often treated on the same regimens developed for children, but more closely resemble the clinical characteristics of young adult patients. We sought to determine whether event-free survival (EFS) for adolescents with GCTs was more like that of children or young adults. Methods: We assembled an individual patient database of ten GCT trials: seven conducted by pediatric cooperative groups and three by an adult group. We selected male patients aged 0-30 years old treated with platinum-based chemotherapy for non-seminomatous malignant GCTs of the testis, retroperitoneum, or mediastinum. We categorized age-group as children (0 to &lt; 11 years), adolescents (11 to &lt; 18 years), or young adults (18 to &lt; 30 years old). We compared EFS among age groups, and adjusted for calculated IGCCCG risk-group using Cox proportional hazards analysis. Results: 593 patients met inclusion criteria, of whom 90 were children, 109 were adolescents, and 394 were young adults. The 5-year EFS for adolescents (72%; CI = 62-79%) was significantly lower than for children (90%; CI = 81-95%, p = 0.003) and for young adults (88%; CI = 84-91%, p &lt; 0.001). Risk-group was significantly associated with EFS in the adolescent age-group (p = 0.002). In a Cox multivariable analysis, the difference between adolescents and children remained statistically significant (HR = 0.30, p = 0.001), but the difference between adolescents and young adults did not (HR 0.66, p = 0.114). Conclusions: EFS for adolescent patients with extracranial malignant GCTs was similar to young adults but significantly worse than children. This finding may have important implications for how adolescent patients are treated.
Penalties and Rewards for Safety Net vs Non–Safety Net Hospitals in the First 2 Years of the Comprehensive Care for Joint Replacement Model
Authors: Caroline P. Thirukumaran, Laurent G. Glance, Xueya Cai, Yeunkyung Kim, Yue Li
Journal: JAMA (2019)

This study compared monetary penalties and rewards among safety net vs non–safety net hospitals under Medicare's Comprehensive Care for Joint Replacement (CJR) model, a bundled payment plan for hip and knee replacements intended to incentivize health care quality and savings, in 2016 and 2017.
Patient reported outcome measures (PROMs) in patients (pts) with locally advanced rectal cancer (LARC) managed with a watch and wait (W&amp;W) approach after a clinical complete response to chemoradiotherapy (CRT).
Authors: Sina Vatandoust, Gang Chen, Luigi Sposato, David Wattchow, Amitesh Chandra Roy, Myron Klevansky, Dayan de Fontgalland, John Leung, Bogda Koczwara, Paul Hollington, Carlene Wilson, Ingrid Flight, Dania Ruminski-Smith, Christos Stelios Karapetis
Journal: Journal of Clinical Oncology (2019)

e15173 Background: PROMs have not been adequately studied in LARC pts who are managed with W&amp;W after a clinical complete response to CRT. The objectives of this study were to evaluate: quality of life measures, bowel function, Fear of Cancer Recurrence (FCR) and survivors’ needs, in this population. Methods: Data were collected from the Flinders Medical Centre W&amp;W prospective database. Questionnaires including Self-Administered Comorbidity (SCQ), EORTC QLQ-C30 and -CR29, EQ-5D-5L, MSKCC Bowel Function Instrument (MBFI), Low Anterior Resection Syndrome (LARS) score, Fear of Cancer Recurrence Inventory-Short Form (FCRI-SF), Cancer Survivors’ Unmet Needs (CaSUN) and Response Efficacy Score (RES) were sent via mail to eligible pts according to a Tailored Design Method. Descriptive statistical analyses were conducted. Results: Of 40 eligible pts, 21 (52.5%) responded: 15 (71%) were male, median age at diagnosis was 66 years (34-81). 5 developed local re-growth (1 had local excision and 4 had ultra-low anterior resection). Median time from end of CRT to data collection was 39.8 months (6.0-77.5). The mean SCQ score was 5.7 (SD 5.5). Mean EQ-5D-5L utility score was 0.84 (SD 0.13), mean EQ-VAS score was 81.9 (SD 12.7) and mean EORTC QLQ global health status score was 76.2 (SD 19.2). The most common symptoms were fatigue (90%), pain (67%) and flatulence (67%). In pts without a re-growth (n = 16), the mean MBFI total score was 27.9 (SD 7.7); based on LARS score: 6 (38%) had no LARS, 5 (31%) had minor LARS and 5 (31%) had major LARS. Mean FCRI-SF score was 11.8 (SD 6.1), clinical level FCR was reported by 2 (9.5%) [cut-off 22] and 4 (19%) pts [cut-off 16]. 10 (47%) reported unmet needs: the most common area was Comprehensive Cancer Care n = 9 (42%). On RES, of 20 responders, 19 (95%) believed W&amp;W was a worthwhile and effective strategy. Conclusions: The most commonly reported symptoms included fatigue, pain and flatulence. LARS was common: in the absence of surgery, LARS is due to CRT. Clinical FCR was uncommon. The majority believed W&amp;W was worthwhile and effective. Larger comparative studies are needed in this group of pts.
Anti-HER2/Neu antibody therapy can reduce the immunosuppressive activity of MDSCs in breast tumor model.
Authors: Il-Hwan Kim
Journal: Journal of Clinical Oncology (2019)

e14181 Background: Myeloid-derived suppressor cells (MDSCs) are a heterogeneous cell populations that play a critical role in tumor associated immune suppression. MDSCs consist of immature cells with myeloid lineage markers CD11b and Gr1 in mice and accumulate in large numbers in tumor bearing mice including HER2/neu + breast cancers. This study was conducted to test whether anti-neu antibody treatment can affect on MDSC populations and immunosuppressive functions. Methods: Female BALB/c mice(5–6weeks of age) were used. The TUBO mammary carcinoma cell line was cloned from a spontaneous mammary tumor in a BALB Neu Tg mouse, as cell lines and reagents. Tumor-infiltrating lymphocyte (TIL) populations were evaluated by flow cytometry. The RT2 Profiler PCR array was used for cytokine expression analysis according to the manufacturer’s instructions. Results: Total number of MDSC in tumor and spleen were decreased within 3 days after anti-neu antibody treatment, but percentage of MDSC in tumor (day2) was reduced more quickly than percentage of MDSC in spleen (day3). The relative populations of MDSC in CD45.2 + cells were significantly decreased such as MO-MDSC. Immunosuppressive activity of MDSC was also reduced by anti-neu antibody treatment. MDSC reduced by anti-neu antibody was due to inhibition of the immunosuppressive factors Arg1 and IDO. In addition, combination therapy with 5-FU may enhance MDSC reduction. Conclusions: MDSC can be a potential therapeutic target in anti-neu antibody treated therapeutic model and the effect of anti-neu antibody could be further improved using other therapeutic treatment to target MDSC.
Initial Therapy in Older Patients with Multiple Myeloma
Authors: Jacob Laubach
Journal: New England Journal of Medicine (2019)

Multiple myeloma affects adults of all ages, but it is primarily a disease of older persons. The highest burden of myeloma-related deaths occurs among persons between 65 and 84 years of age.1 As is the case with other types of cancer, the management of multiple myeloma in older patients is often challenging owing to impaired organ function and coexisting frailty, both of which increase the risk of chemotherapy-related toxic effects and often lead to a reduction in the intensity of chemotherapy.2 These epidemiologic and biologic considerations have motivated ongoing efforts to expand treatment options and improve overall outcomes in this . . .