tbuckley/cabot-search huggingface dataset:
Discordant response comparing 18F-FDG PET/CT with response assessment by RECIST in patients with advanced melanoma treated with immune checkpoint blockade.
Authors: Milton Jos De Barros E Silva, Marcos Rezende Teixeira, Natasha Carvalho Pandolfi, Vinicius Fernando Calsavara, Thiago Bueno Oliveira, José Augusto Rinck, Monique Celeste Tavares, Daniel Garcia, Joao Paulo SN Lima, Joao Duprat
Journal: Journal of Clinical Oncology (2020)

10046 Background: Immune checkpoint blockade (ICB) has changed the natural history advanced melanoma (AM). Based on phase III trial, which used RECIST criteria, the complete response (CR) rate with anti-PD1 therapy is around 20%. In daily practice, PET/CT is a useful tool to evaluate response to treatment in melanoma patients. Little is known about the number of patients who achieve metabolic CR by PET/CT but with anatomic residual disease and their prognosis. Methods: We conducted a retrospective analysis of patients with AM treated with ICB who achieved metabolic CR by PET/CT but with residual disease on tomography and compared to patients with RECIST CR in a high-volume cancer center. Progression-free (PFS) and overall survival (OS) were obtained by Kaplan Meier method and log-rank test. Results: One hundred seventy pts with AM treated with anti-PD1 (79%) or anti-PD1 + anti- CTLA4 (21%) betweenSeptember 2013 and December 2019 were analyzed. At a median follow-up of 23.6 months, seventy-five (44%) pts achieved CR. RECIST criteria: 22 pts (29.3%) and metabolic CR: 53 pts (70.7%). All patients with metabolic CR had RECIST partial response. The median total time on treatment was 14.8m (95%CI:0.9-42.3). The median time to reach CR was 5.4m (95%CI: 3-39). The median time of treatment after CR was 6.8m (95%CI: 0-21.4). The rate of CR patients off treatment at the moment of this analysis was 69%. The median follow-up after discontinuing treatment was 5.2m. There was no difference in PFS (36 month-rate: 84.4% vs 74%, p:0.64) and OS (36 month-rate: 100% vs 86.3%, p:0.14) between pts with CR based on RECIST or PET-CT, respectively. Median time for PFS and OS have not been reached until the date cut-off. Nine pts have relapsed (12%). Seven of them had residual disease on tomography but with no metabolic active lesion(s) at the time of the end of treatment. Conclusions: Twice more patients achieve complete response considering only metabolic parameters on PET/CT compared to RECIST criteria and they seem to have comparable prognosis.
Deep learning-based immune phenotype analysis reveals distinct resistance pattern of immune checkpoint inhibitor in non-small cell lung cancer.
Authors: Chan-Young Ock, Sehhoon Park, Inwan Yoo, Jisoo Shin, Seungje Lee, Sarah Lee, Kyunghyun Paeng, Yoon La Choi, Tony S. K. Mok, Se-Hoon Lee
Journal: Journal of Clinical Oncology (2020)

3119 Background: Resistance pattern and biological mechanism of immune checkpoint inhibitor (ICI) has been poorly understood. Sine suggested resistance mechanisms would be either innate resistance caused by lack of immune recruitment or acquired immune evasion after durable response of ICI treatment, we hypothesized that resistance pattern of tumor microenvironment would be distinct according to duration of ICI response in non-small cell lung carcinoma (NSCLC). In the current study, we applied deep-learning-based classification of three immune phenotypes (3IP): inflamed, excluded, and desert, to objectively assess the immunologic status of tumor microenvironment. Methods: Deep-learning algorithm of H&amp;E Whole-Slide Images (WSI), called Lunit-SCOPE, was trained with 1,824 H&amp;E WSI of NSCLC from Samsung Medical Center (SMC). WSI was divided into patches and each patch (~10 high-power fields) was classified as inflamed, excluded and desert, based on both quantity and localization of immune cells. Among NSCLC patients treated with ICI in SMC, 87 paired treatment-naïve (Pre, patch N = 15,415) and post-progression (Post, patch N = 18,197) tumor tissues were analyzed for Lunit-SCOPE. Results: In 87-paired samples, proportions of excluded and desert phenotypes were increased in post-progression tumor tissues (excluded; Pre 26.8% versus Post 32.5%, desert; Pre 19.5% versus Post 25.3%). Focused on 29 patients classified as inflamed in treatment-naïve, proportion of immune phenotypes of post-progression were clearly different according to duration of response, divided by median progression-free survival (PFS) of 3.7 m. Patients with rapid progression without ICI response (PFS &lt; 3.7 m) turned into desert type (46.2%), whereas durable responder (PFS ≥ 3.7 m) either still remained on inflamed phenotype (42.9%) or turned into excluded phenotype (21.4%). Patients who remained on inflamed phenotype had favorable overall survival after progression on ICI, compared to turned into desert type (median survival not reached versus 6.6 m, P= 0.0296). Conclusions: Resistance patterns of ICI are distinct according to duration of response in patients with inflamed phenotype. Rapid progressor turns off immune into desert phenotype whereas most durable responder keeps immune recruitment into tumor microenvironment, which needs tailored strategy to overcome ICI resistance.
Effect of cigarette smoking on platelet activation in elderly patients with acute coronary syndrome
Authors: Da-hai Huang
Journal: BMJ (2013)

Fifty six elderly patients with acute coronary syndrome (ACS) were divided into non-smoking group (n=30) and smoking group (n=26). All patients received aspirin 100 mg/d+ Clopidogrel 75 mg/d for 14 d. The expression of glycoprotein Ⅱb/Ⅲa and P-Selectin on the surface of platelets in both groups were assessed with flow cytometry (FCM). The positive expression rates of GPⅡb/Ⅲa and P-Selectin before treatment were (67.86±12.14)%, (70.37±10.15)% in non-smoking group and (79.47±11.62)%, (81.26±9.74)% in smoking group. The positive expression rates of GPⅡb/Ⅲa and P-Selectin after treatment were significantly decreased to (50.18±8.72)%, (49.36±11.43)% in non-smoking group and to (61.15±9.29)%, (57.52±10.81)% in smoking group(P<0.01). Also the degree of decreasing expression rates of GPⅡb/Ⅲa and P-Selectin was more markedly in non-smoking group than that in smoking group (P<0.05). The results indicate that expressions of GPⅡb/Ⅲa and P-Selectin on the surface of platelets are increased in the elderly smoker patients with ACS, and smoking may decrease the effect of anti-platelet agents.


Key words: 
Smoking; Coronary disease
Overview of obesity and breast cancer in Brazil: 24 year of follow up.
Authors: Andrea Z Pereira, Bianca de Almeida Pitito, Rogério Ruscitto do Prado, Andre Mattar, Roberto Hegg, Jorge Yoshinori Shida, Luiz Henrique Gebrim
Journal: Journal of Clinical Oncology (2020)

e13580 Background: Obesity is one of the major public health challenges of the 21st century. The prevalence of obesity is growing exponentially across all age groups and on all continents and it is associated with morbidities such as cardiovascular disease, diabetes mellitus type 2, dyslipidemia, hypertension and cancer. There is a higher risk of developing breast cancer in postmenopausal obese women, and with worse outcome for women of all ages. Objectives: To evaluate obesity prevalence in breast cancer patients and its association with recovering, survival, death, age, Human Epidermal Growth Factor Receptor 2 (HER2) and anti-human KI67 antibody(KI67). Methods: A retrospective cohort study was performed between 1994 and 2018 at the Breast Cancer Department, São Paulo State Government Women's Health Reference Center (Perola Byington Hospital), São Paulo, Brazil with 8824 breast cancer patients. From those, 2899 patients were excluded because they did not have description of weight and/or Body Mass Index (BMI). Survival analysis was performed according to BMI groups. Results: The participants had mean (SD) age of 54 (12.0) years and weight of 70 (15.0) kg. There were 769 (13%) deaths and the mean survival was 20 (2.0) years. 1787 (30%) participants were stratified in obese (BMI≥30Kg/m2) and 4138 (70%) non-obese Obese were older (p &lt; 0,001) and had a higher frequency of HER2 negative (p &lt; 0,04) than non-obese women. There were not a significant difference in frequencies of KI67, recovering and survival between groups. The prevalence of obesity was not different over 24 years. Conclusions: There was a relevant prevalence of obesity in breast cancer patients, which was associated with HER2 negative and age, but not with recovering or survival.
Long-term follow-up of anti-CD19 CAR T-cell therapy for B-cell lymphoma and chronic lymphocytic leukemia.
Authors: Kathryn Cappell, Richard Mark Sherry, James C. Yang, Stephanie L. Goff, Danielle Vanasse, Lori McIntyre, Steven A. Rosenberg, James N. Kochenderfer
Journal: Journal of Clinical Oncology (2020)

3012 Background: T cells expressing anti-CD19 chimeric antigen receptors (CARs) can cause complete remissions of relapsed lymphoma. We conducted the first clinical trial of anti-CD19 CAR T cells to show responses against lymphoma. This CAR was later developed as axicabtagene ciloleucel. Here, we aimed to assess the long-term durability of remissions and the long-term adverse effects after anti-CD19 CAR T-cell therapy. Methods: Between 2009 and 2015, we treated 43 patients with anti-CD19 CAR T cells preceded by conditioning chemotherapy of cyclophosphamide plus fludarabine (NCT00924326). Three patients were re-treated for a total of 46 CAR T-cell treatments. Twenty-eight patients had aggressive lymphoma (diffuse large B-cell lymphoma or primary mediastinal B cell lymphoma), eight patients had low-grade lymphoma (five with follicular lymphoma and 1 each with splenic marginal zone lymphoma, mantle cell lymphoma, and unspecified low-grade non-Hodgkin lymphoma), and seven patients had chronic lymphocytic leukemia (CLL). Patients were treated in three cohorts that differed in the CAR T-cell production process and conditioning chemotherapy dose. Results: Of the 43 treated patients, 63% had chemotherapy-refractory lymphoma. Patients had received a median of 4 previous lines of therapy. The median CAR + T cell dose per kilogram was 2X10^6. The overall remission rate was 76% with 54% complete remissions (CR) and 22% partial remissions (PR). Patients with CR had higher median peak blood CAR levels (86 CAR + cells/µL) than those who did not have CR (16 CAR + cells/µL, P= 0.0041). Long-term adverse effects were rare except for B-cell depletion and hypogammaglobulinemia, which both improved over time. Conclusions: This is the longest follow-up study of patients who received anti-CD19 CAR T cells. Anti-CD19 CAR T cells cause highly durable remissions of relapsed B-cell lymphoma and CLL, and long-term adverse effects of anti-CD19 CAR T cells were rare and usually mild. Clinical trial information: NCT00924326 . [Table: see text]
The association of fitness and body mass index (BMI) on all-cause mortality in cancer survivors: The Henry Ford Exercise Testing Project (The FIT Project).
Authors: Catherine Handy Marshall, Paul A McAuley, Hua-Ling Tsai, Zeina Dardari, Mouaz H Al-Mallah, Clinton A Brawner, Lois E. Lamerato, Steven Keteyian, Jonathan Ehrman, Michael J Blaha
Journal: Journal of Clinical Oncology (2020)

7060 Background: The obesity paradox –i.e. inverse associations between body mass index (BMI) and mortality – has been reported in patients with cancer, heart failure, and diabetes. However, the influence of cardiorespiratory fitness (CRF) on this relationship is not well established. This study assesses the association of BMI and CRF with all-cause mortality among cancer patients. Methods: The Henry Ford (HF) FIT Project is a retrospective cohort study of 69,885 consecutive patients who underwent physician-referred exercise stress testing from 1991 through 2009. Cancer diagnosis was identified through linkage to the HF tumor registry. We included patients 40-70 years old, with BMI recorded, at time of exercise test, with a history of cancer &gt; 6 months prior. BMI was categorized as normal (18.5-24.9kg/m 2 ), overweight (25-29.9kg/m 2 ), or obese ( &gt; = 30kg/m2). All-cause mortality was obtained from the National Death Index. Because of a significant interaction between BMI and cancer type, patients with breast or prostate cancer were excluded. Multivariable adjusted Cox proportional hazard models were used to evaluate the association of CRF andBMI with all-cause mortality; adjusted for age at exercise test, sex, diabetes, smoking, cancer stage, and time from cancer diagnosis to exercise test. Results: Included were 676 patients with a mean age of 58 years (SD 7.5), 51% female, 70% White, 25% Black, with a median of 4.8 years from diagnosis to exercise test and median follow up time of 10.3 years. Among patients achieving &lt; 10 METs, those who are overweight and obese had a lower risk of mortality HR 0.47 (95% CI 0.25,0.86) and HR 0.44 (95% CI 0.26, 0.74, respectively), compared to those with normal BMI. Among patients with METs &gt; = 10, those who were overweight had the lowest risk of all-cause mortality (HR 0.23, 95% CI 0.09-0.62) compared to normal weight, while no statistically significant different risk of mortality was observed when comparing those who are obese to normal weight (HR 0.37, 95% CI 0.13-1.06). In an analysis combining BMI and fitness groups (four categories), those with BMI &gt; = 25 and METs &gt; = 10 had the lowest risk of all-cause mortality (Table). Conclusions: In non-breast/non-prostate cancer patients, increased BMI is associated with improved overall survival in those with METs &lt; 10, while a U-shaped relationship between BMI and all-cause mortality exists among those with METs &gt; = 10. [Table: see text]
门诊教学在全科住院医师规范化培训中的作用
Authors: 任菁菁, 方力争
Journal: BMJ (2008)

全科医学是以人为中心,以维护和促进健康为目标,向个人、家庭与社区提供连续、综合、便捷的基本卫生服务的新型医学学科[1].全科医疗正式引入中国是在20世纪80年代末,我院全科医学科作为全科医学教学培训基地,已培训23名学员。
Growth modulation index (GMI) as a comparative efficacy measure of larotrectinib versus prior systemic treatments for TRK fusion cancer patients.
Authors: Antoine Italiano, David S. Hong, Andrew Briggs, Jesus Garcia-Foncillas, Ulrik Niels Lassen, Gilles Vassal, Shivaani Kummar, Cornelis M. Van Tilburg, Karen N Keating, John A. Reeves, Marc Mardoche Fellous, Barrett H. Childs, Theodore Willis Laetsch, Alexander E. Drilon
Journal: Journal of Clinical Oncology (2020)

e15638 Background: Larotrectinib is a highly selective TRK inhibitor that demonstrated high response rates and durable disease control in three phase I/II single-arm studies of patients (pts) with TRK fusion cancer. While single-arm studies are often used for rare cancer populations, they do not provide comparative data. GMI utilizes pts as their own control and can be used in this setting. GMI is the ratio of progression-free survival (PFS) on the current therapy to time to progression (TTP) on the most recent prior line of therapy. A GMI ≥1.33 has been used as a threshold of meaningful clinical activity. We report GMI for TRK fusion cancer pts treated with larotrectinib. Methods: Data were pooled from 3 clinical trials of pts with TRK fusion cancer treated with larotrectinib. A retrospective, exploratory analysis of GMI was conducted in pts who had been on larotrectinib and followed up for ≥6 mos or pts who discontinued early, and had ≥1 prior line of systemic treatment for locally advanced or metastatic disease. TTP on the prior line of therapy was investigator assessed. PFS on larotrectinib was determined by independent review committee per RECIST 1.1. Pts who had not progressed were not censored from the analysis. Results: As of July 15, 2019, 122 pts were eligible for analysis. Fifteen different tumor types were represented, the most common being soft tissue sarcoma in 26 pts (21%), infantile fibrosarcoma in 22 (18%), and thyroid in 21 (17%). Median GMI was 3.35 (range 0.00–337.00; Table); In metastatic pts (n = 81), the proportion with a GMI ≥1.33 was higher in pts with a complete or partial response vs non-responders (88% vs 42%). In the whole analysis set (N = 122), median TTP on prior line of treatment was 2.7 mos (95% CI 2.0–3.1) and median PFS on larotrectinib was 33.4 mos (95% CI 13.8–NE; HR 0.20 [95% CI 0.14–0.29]). In metastatic pts (n = 81), median TTP on prior line of treatment was 2.3 mos (95% CI 1.9–3.0) and median PFS on larotrectinib was 23.4 mos (95% CI 10.9–NE; HR 0.24 [95% CI 0.16–0.36]). Conclusions: Greater than two-thirds of pts with TRK fusion cancer treated with larotrectinib had a GMI ≥1.33, demonstrating a clinically meaningful improvement in PFS compared to TTP on their prior treatment. Clinical trial information: NCT02122913, NCT02576431, NCT02637687.
Preliminary results of a phase II study of neoadjuvant immune checkpoint inhibitor IMC-001 (anti-PD-L1 monoclonal antibody) in patients with resectable gastrointestinal cancers (NeoChance Study).
Authors: Hyeon-Su Im, Joon Seon Song, Woo Ri Jo, Moon-Won Yoo, Yong-Hee Kim, Hyeong Ryul Kim, Ho June Song, Do Hoon Kim, Kee Don Choi, Jeong Hoon Lee, Ji Yong Ahn, Hee Kyong Na, Ki-won Song, Sook Ryun Park
Journal: Journal of Clinical Oncology (2020)

e16542 Background: Immune checkpoint inhibitors have shown survival benefits in unresectable/metastatic gastric cancer (GC), esophageal cancer (EC), and hepatocellular carcinoma (HCC). Based on scientific rationale for neoadjuvant immunotherapy, including enhanced immune recognition, we initiated a phase II study of IMC-001, a novel PD-L1 targeting fully human monoclonal Ab in the neoadjuvant setting for resectable GC, EC, and HCC. Methods: This is a prospective, open-label, phase II study of neoadjuvant IMC-001 (20 mg/kg iv every 2 weeks for 2 cycles) across three cohorts of resectable gastrointestinal cancers (GC, EC, HCC). The primary endpoint is major pathologic response rate ( &lt; 10% of viable tumor cells) and secondary endpoints include safety, feasibility, R0 resection rate, clinical tumor response rate/disease control rate (DCR), progression-free survival, relapse-free survival, and overall survival. Exploratory endpoints include immune monitoring and biomarker analysis in tumor tissues, blood, and stool. Results: From Sep. 2019 to Feb. 2020, 14 eligible patients (pts) (6 HCC; 5 GC; 3 EC) were enrolled; male (79%), median age = 63 yrs (range, 40-72), clinical stage (AJCC 8 th ) I (57%)/II (21%)/III (21%). 12 pts completed 2 cycles of neoadjuvant IMC-001 and one pt stopped after one cycle due to G3 autoimmune hepatitis, which was only G3 adverse event (AE) and resolved with steroid. Other AE included G2 hyperthyroidism (n = 1), G1 pruritus (n = 2), G1 rash (n = 1), G1 myalgia (n = 1), G1 arthralgia (n = 1), G1 diarrhea (n = 1), G1 cough (n = 1), G1 palate discomfort (n = 1), and G1 chest discomfort (n = 1). So far, 10 clinical response-evaluable pts showed a 100% DCR and underwent surgery, which was all R0 resection. Post-treatment surgery specimens showed various degrees of lymphocyte infiltration in intratumoral or peritumoral areas ranging from 10% to 90%, which was increased compared to pre-treatment biopsies. In HCC pts, adjacent hepatic parenchyma showed mild to moderate, diffuse portal inflammation regardless of Hepatitis B virus status and minimal and moderate fatty change. IHC for PD-L1 using 22C3, SP263 and SP142 clones showed similar results among three Abs with relatively low expression regardless of tumor types (range, 0-20%). Conclusions: Neoadjuvant IMC-001 seems to be well tolerated and have preliminary immune modulating activity in resectable GC, EC, and HCC pts. The study is ongoing and the updated clinical and immunologic results will be presented. Clinical trial information: NCT04196465 .
Qualitative study and its application in health care fields
Authors: Nan Yan
Journal: BMJ (2018)

Qualitative study is a research method applied to investigate human experience, behavior and emotion. It can improve the depth and breadth of patient-centered clinical research, therefore is useful for medical fields. This article summarizes the main process of qualitative study, reviews its development in China, and introduces its application in general medicine as a research tool.


Key words: 
Qualitative research; General medicine
Financial burden of discarded weight-based cancer drugs to payers and patients in private insurance market.
Authors: Ya-Chen T. Shih, Ying Xu, Hui Zhao, James C. Yao
Journal: Journal of Clinical Oncology (2020)

7083 Background: Studies assessing wastage of discarded weight (WT)-based cancer drugs (can-RX) derived their estimates from Medicare Average Sales Prices + 6% mark-up. With higher mark-ups, financial impact of discarded can-RX can be much higher in private insurance market. In addition, no study has examined the financial burden for patients(pts) even though they are subject to out-of-pocket payment (OOP) of the discarded RX. This study fills in these important knowledge gaps. Methods: We obtained the list of WT-based can-RX from the 2017 Centers for Medicare and Medicaid Services Part B Discarded Drug Units Report and gathered information on package size and recommended dose from IBM Micromedex. We identified pts who received WT-based can-RX from 2017 MarketScan data and linked to MarketScan Health Risk Assessment to obtain WT and height for a subset of pts. For each claim, we derived the recommended dose based on pt’s RX and his/her WT or body surface area (calculated from WT and height) and estimated the % of discarded dose. We quantified OOP as the sum of deductible, copayment, and coinsurance, and classified pts’ insurance by their enrollment to high-deductible (HD) plans. For claim-level analysis, we applied beta regression (for fractional outcomes) to determine factors associated with % discarded while accounting for within pts correlations. Covariates were age group (grp) ( &lt; 50, 50-59, &gt; = 60), WT grp ( &lt; 150, 150-199, &gt; = 200lb), HD plan (yes/no), region, cancer type, and can-RX. For pt-level analysis, we calculated the amount payers and pts spent on all and discarded can-RX in 2017 and compared OOP b/t pts in HD and non-HD plans. Results: Of 27,883 claims of WT-based can-RX, the median discarded % was 0.10 (mean 0.19, SD = 0.21). In addition to can-RX and cancer type, significantly higher discarded % was found in the lowest WT grp (0.03, P &lt; 0.001, vs. WT &gt; = 200lb) and significantly lower % was found in the middle age grp (-0.01, P = 0.02 vs. age &lt; 50). Of 1963 pts, 778 (40%) had HD plans. Payments by payers (NETPAY) and pts (OOP) for total and discarded can-RX and the comparison b/t HD and non-HD plans are shown in Table. Conclusions: Payers incurred substantial financial burden from discarded can-RX. While OOP costs were modest for most privately insured pts, 5.3% of pts (~8% in HD plans) paid &gt; $400 for discarded RX. [Table: see text]