tbuckley/cabot-search huggingface dataset:
Effect of performance status on survival with pembrolizumab monotherapy in advanced non-small cell lung cancer (NSCLC).
Authors: Kartik Sehgal, Poorva Bindal, Anita Geevarghese Koshy, Ritu R. Gill, Danielle C McDonald, Deepa Rangachari, Daniel Botelho Costa
Journal: Journal of Clinical Oncology (2020)

9533 Background: Pembrolizumab (P) is now widely used as standard of care (SOC) in advanced NSCLC. We sought to identify prognostic factors influencing survival with it in a real-world setting. Methods: We conducted a retrospective cohort study of with advanced NSCLC patients who initiated treatment with SOC P monotherapy at our center from 2/11/16 to 10/15/19 (data cutoff 1/15/20). Patient demographic, clinicopathologic, therapeutic and outcomes data were extracted. Survival time was defined from start of P. Cox proportional hazards and logistic regression were utilized. Results: Of 74 patients with median follow up of 83.9 weeks, 30 (40.5%) were alive at cutoff. Patient characteristics at start of therapy were: 36 (48.6%) female, median age 68.5 yr (range 33-87), 10 (13.5%) with symptomatic brain metastases; 54 (72.9%) treatment-naïve, 29 (39.2%) with ECOG performance status (PS) ≥2. Tumor characteristics were: 53 (71.6%) with PD-L1 tumor proportion score (TPS) ≥50%, median PD-L1 TPS 75% (range 1-100), tumor mutational burden (TMB) tested in only 37 (50%) patients, median TMB 8 mut/mB (range 1-62). Any grade immune-related adverse events (irAE) occurred in 33 (44.6%) patients, while 16 (21.6%) received systemic steroids. Median survival was 43.3 wks (95% CI 29-104.1). Multivariable regression showed ECOG PS of ≥2 as the strongest risk factor for death (Table). We next evaluated differences in characteristics of patients who were alive vs dead within 12 wks of starting P, by which initial response assessments are completed in routine practice. ECOG PS was the only significantly different baseline variable, even after multivariable adjustment (p = 0.002). Conclusions: ECOG PS of ≥2 is a poor prognostic risk factor associated with P monotherapy in advanced NSCLC. Though comprising a clinically significant subset of patients in real-world, they were not included in landmark trials (KEYNOTE-024 &amp; 042). Prospective evaluation is warranted. [Table: see text]
CanAssist breast: An affordable breast cancer prognostic test validated on Asian patients.
Authors: Poonam Patil, Manjiri Manohar Bakre, Chetana Basavaraj, Sukriti Malpani, Aparna Gunda, Chandra Prakash, S.P. Somashekhar
Journal: Journal of Clinical Oncology (2020)

541 Background: Treatment decisions for early stage HR+/HER2neu- breast cancer patients in the West routinely depend on prognostic tests that predict risk of recurrence. However, such tests are rarely used in Asia due to prohibitive costs and lack of validation data on Asian patients. Chemotherapy is thus often a default treatment leading to physiological and financial toxicity. To address these, we have developed CanAssist Breast (CAB) as an affordable IHC-based prognostic test, retrospectively validated on ~1400 patients, 63% South Asians and rest Caucasians. To date CAB has been prescribed by 180+ doctors across 30 cities in India for ~600 patients in clinics, enabling personalized treatment decisions. Methods: Primary surgical FFPE blocks and clinical follow-up data were obtained from hospitals. GraphPad Prism and MedCalc were respectively used for Kaplan-Meier survival analyses and Cox logistic regression to calculate hazard ratios. Results: The median age of diagnosis in the validation cohort was 56 years, 63% patients with stage II disease and 60% node negative tumors. Distant Metastasis Free Survival (DMFS) in the low-risk category of the validation cohort was 95%, and 84% in high-risk (P &lt; 0.0001). Similar results were obtained with the Caucasian subgroup, as also with the chemotherapy-naive subgroup (30% of the cohort), demonstrating that risk stratification by CAB is unaffected by race or chemotherapy. Next, the performance of CAB was compared with Oncotype DX (ODX). 83% patients stratified as low risk by ODX (RS 0-25) in a sub-cohort of 109 were also stratified as low-risk by CAB. To assess the impact of CAB in treatment decision making, we assessed the data of 589 patients who have undergone CAB testing so far, 288 were identified as low-risk. 93% of these CAB low-risk patients were not given chemotherapy, demonstrating the clinical impact of CAB. Conclusions: CAB is the first test of its kind to be retrospectively validated in Asia. It shows high concordance with ODX in risk stratification of patients. CAB has been in clinical practice in India and near-India markets for 2 years and is helping clinicians and patients in making affordable treatment decisions.
The value of bendamustine dose and cycles, sIL-2R, and LDH in follicular lymphoma patients treated with bendamustine plus rituximab.
Authors: Tatsuro Jo, Masatoshi Matsuo, Jun Taguchi, Kuniko Abe, Kazuto Shigematsu
Journal: Journal of Clinical Oncology (2020)

e20055 Background: Bendamustine plus rituximab therapy (BR) is one of the mainstays of therapy for follicular lymphoma (FL) patients (pts). Adverse events such as lymphopenia, neutropenia, and skin lesions sometimes prevent the completion of six cycles of BR. Till date, the bendamustine dose, treatment cycle of BR, and prognostic markers of FL response to BR have not been analyzed sufficiently. Methods: We retrospectively evaluated 56 FL pts treated with BR from January 2011toJanuary 2019 at our hospital; 19 pts and 37 pts received BR as first-line therapy and salvage therapy, respectively. Results: There was no statistical difference in the response rate, OS, and PFS between the first-line group and the salvage group. The table summarizes the survival analyses. Comparing the OS and PFS according to FL grades 1, 2, and 3 in all pts, there were significant differences in both OS (P = 0.0028) and PFS (P = 0.0058). Patients were divided into two groups based on a cutoff sIL-2R value of 682 U/mL; survival benefits were observed in the sIL-2R-low group in OS (P = 0.0226) and PFS (P = 0.0265). Similarly, on dividing the pts into two groups based on a cutoff LDH value of 225 U/L, survival benefits were observed in the LDH-low group in OS (P = 0.0375) and PFS (P = 0.0453). The LDH value was significantly high in pts with progression of disease within 24 months (POD24) compared to pts without POD24 (P = 0.0134). However, there was no statistical relationship between sIL-2R and POD24.The rate of treatment cycles ≧4 was 69%, and the mean number of treatment cycles was 4.3. Survival benefits were observed in pts who were treated for more than 3 cycles in OS (P = 0.0094) and PFS (P = 0.0103). The mean bendamustine dose was 78.5 mg/m 2 . Conclusions: Approximately 30% pts could not receive more than 3 cycles of BR, probably because of adverse events and preexisting bone marrow suppression with previous chemotherapy, suggesting that 90 mg/m 2 of bendamustine in BR may be excessive, especially in pts requiring salvage therapy. Our data suggest that 75−80 mg/m 2 of bendamustine may be appropriate. Our survival data also suggest that new treatment strategies may be needed for FL pts with high levels of sIL-2 ( &gt;682 U/mL) and LDH ( &gt;225 U/L) and grade 3 disease. [Table: see text]
Management of bronchopulmonary carcinoid: NCDB database analysis.
Authors: Mojun Zhu, Harry E Fuentes, Gustavo Figueiredo Marcondes Westin, Mohamad Bassam Sonbol, Konstantinos Leventakos, Dennis A. Wigle, Dawn E. Jaroszewski, Julian R. Molina, Thorvardur Ragnar Halfdanarson
Journal: Journal of Clinical Oncology (2020)

e21007 Background: There is a lack of data to guide the management of resectable bronchopulmonary carcinoid tumors (BCTs). Methods: The NCDB database was retrospectively reviewed to analyze the roles of surgery, chemotherapy and radiation. Patients with a diagnosis of clinically staged T1-2/N0-1 typical carcinoid (TC) and atypical carcinoid (AC) between 2004-2012 were included. Kaplan-Meier methods and multivariable analysis were performed. Results: A total of 2148 patients (TC 1874 &amp; AC 274; T1/1648 &amp; T2/500) were identified. The median age was 59 (range 18-89). There was a female (69.7%) and right lung (56.9%) predominance. Fifty-three patients received pneumonectomy, 68 chemotherapy, and 84 radiation therapy. The impact of age, histology (TC vs. AC), medical comorbidities (Charlson/Deyo score 0 vs. ≥1) and type of surgery [sublobar resection (SR) vs. lobectomy vs. lobectomy with mediastinal lymph node dissection (L/MLND)] were subsequently examined. AC, older age, and comorbidities were associated with shorter overall survival (OS) by both univariate and multivariable analysis. Patients who underwent lobectomy had longer OS (119 months) than those with SR (109 months) or L/MLND (115 months). However, this association was not significant by multivariable analysis with age incorporated as either a categorical ( &lt; 60 vs. ≥60) or a continuous variable (Table). In the subgroup analysis of patients with T1, T2, TC and AC respectively, type of surgical resection was not significantly associated with OS by multivariable analysis. Conclusions: Patients with resectable BCTs have excellent OS. Atypical histology, older age, and comorbidities predicted inferior OS. There were insufficient data to support the use of perioperative chemotherapy or radiation therapy. Lobectomy was associated with prolonged OS by univariate analysis but this was not significant in the multivariable model, suggesting that SR is a reasonable approach for patients who cannot tolerate lobectomy. MLND did not seem to provide additional survival benefits. [Table: see text]
肺朗格汉斯细胞组织细胞增生症三例
Authors: 李晓静, 罗本芳, 易祥华, 李霞, 程晓明, 曾郁
Journal: BMJ (2012)

回顾性分析3例肺朗格汉斯细胞组织细胞增生症( PLCH)的临床和病理特点,并结合文献进行探讨.3例均为男性,有吸烟史.2例以气胸为主要症状,3例肺活检病理均见明显朗格汉斯细胞聚集灶。
Clinical characteristics and anti-PD-(L)1 treatment outcomes of KRAS-G12C mutant lung cancer compared to other molecular subtypes of KRAS-mutant lung cancer.
Authors: Kathryn Cecilia Arbour, Hira Rizvi, Andrew J. Plodkowski, Darragh Halpenny, Matthew David Hellmann, Glenn Heller, Andrea Knezevic, Helena Alexandra Yu, Marc Ladanyi, Mark G. Kris, Maria E. Arcila, Charles M. Rudin, Piro Lito, Gregory J. Riely
Journal: Journal of Clinical Oncology (2020)

9596 Background: KRAS mutations are identified in approximately 30% of NSCLC. There are no FDA approved targeted therapies for patients with KRAS-mutant non-small cell lung cancer (NSCLC) but novel direct inhibitors of KRAS G12C have shown some activity in early phase clinical trials. We hypothesized that patients with KRAS-G12C mutations may have distinct clinical characteristics and responses to systemic therapies compared to patients with non-G12C subtypes. Methods: We identified patients with KRAS-mutant lung cancers who underwent next-generation sequencing with MSK-IMPACT, between January 2014 and December 2018. Baseline characteristics were compared with the Chi-square and Fisher’s exact test for categorical data and Wilcoxon rank-rum test for continuous data. Overall survival was calculated from time of diagnosis of metastatic/recurrent disease to date of death or last follow up, with left truncation to account for time of MSK-IMPACT. Overall survival was compared between groups using the Cox proportional-hazards model. Response evaluations where performed by independent thoracic radiologists according to RECIST 1. and compared between group with the Fisher’s exact test. Results: We identified 1194 patients with KRAS -mutant NSCLC, 772 with recurrent or metastatic disease. Of patients with advanced disease, 46% (352/772) had mutations in KRAS-G12C and 54% harbored non-G12C mutations (15% G12D, 16% G12V, 8% G12A, 4% G13D). Co-mutation patterns were similar with respect to KEAP1 (p=0.9) and STK11 (p=1.0). Patients with non-G12C mutations had a higher proportion of never smokers (10% vs 1.4% p&lt;0.001). The median OS from diagnosis was 13 months for G12C and non-G12C patients (p=0.99). 45% (347/772) received 1L or 2L line treatment with PD-(L)1 inhibitor. RECIST measurements were available for 290/347 cases (84%). ORR with anti-PD-(L)1 treatment was 24% vs 28% in G12C vs non-G12C patients (p=0.5). In patients with PD-L1 50% (n=103), ORR was 39% for G12C vs 58% non-G12C patients (p=0.06). Conclusions: KRAS G12C mutations are present in 12% of patients with NSCLC and represent a relevant subtype of NSCLC given KRAS G12C inhibitors now in clinical development. Baseline characteristics including co-mutation patterns are similar between patients with G12C and non-G12C, except for smoking history. The efficacy of KRAS G12C direct inhibitors will need to be compared to other available therapies for KRAS mutant NSCLC (chemotherapy and PD-(L)1 inhibitors) to identify most effective therapeutic strategy.
Factors related to choice of community health service centers in standardized training general practitioners in Shanghai
Authors: Man Li, Zhigang Pan, Shanzhu Zhu, Libing Shao
Journal: BMJ (2015)

Objective
To investigate the factors related to choice of  health service centers (CHSCs) in standardized training general practitioners (GPs) in Shanghai.


Methods
Totally 152 GPs, (including those of Traditional Chinese Medicine) who completed the residency training in 2013 and signed employment contract with  in  were surveyed with a self-designed questionnaire.


Results
Among all the participants, 113 (74.3%) attached the greatest importance to the salary level when choosing CHSC, 58 (38.2%) expected annual salary more than 120 000 Yuan during the first 3 years. GPs tended to work in the city center(40.1%) or CHSCs near to their home(38.2%), mainly because of the job commuting (59.9%). Considering career development, the CHSCs with high level comprehensive service (51.3%) and with large population (5.0%) were more attractive. GPs paid more attention to the national demonstration community (57.2%) and CHSCs with member of Shanghai outstanding young physician training program(51.7%). In this survey, household register was the main influencing factor for choosing CHSCs,  natives paid more attention to the location of the  than those not  natives (61.8% vs. 34.2%), more inclined to CHSCs that close to their house (55.3% vs. 21.1%), non-Shanghai natives preferred authorized strength (51.3% vs. 28.9%). GPs of Western medicine expected higher salary than GPs of TCM (χ2=13.648, P<0.05), Males expected higher salary than females (χ2=7.799, P<0.05),


Conclusions
GPs pay the most attention on salaries and tend to work in the city central area, prefer CHSC with high level comprehensive service and large served population. The main factor influencing GPs to chose CHSCs is the household register, the category of Gps and gender.


Key words: 
Community health service centers; Employment; General practitioners
Sentinel-Lymphnode Biopsy in primary breast cancer: 99mTc versus ICG—A prospective, randomized trial.
Authors: Peter Kern, Ann-Kathrin Bittner, Oliver Hoffmann, Rainer Kimmig, Ariane Schoffer, Stephanos Moukas, Kay Friedrichs
Journal: Journal of Clinical Oncology (2020)

575 Background: Sentinel-Lymphnode Biopsy (SLNB) is the standard procedure in primary breast cancer, routinely performed with 99mTechnetium radioactive tracers. Awareness of nuclear waste, costs and time consumption lead to the desire of breast surgeons to find safe and effective alternative options for detection of sentinel lymph nodes (SLN) in breast cancer and melanoma. Indocyaningreen is a tracer which emits fluorescence with near-infrared light of 780-810 nm when injected in the peritumoral or periareolar region, enabling surgeons to detect SLN and lymphatic pathways at the breast. Methods: We performed a prospective, randomized trial with patients with primary breast cancer. Both detection methods have been applied to patients of the study cohort comparing the preparation time, time to identify, concordance of the two methods and costs. Reference method was preoperative lymphszintigraphy. Results: 55 patients have been analyzed in this first report. Preparation time was 75,8 min (range 60-120 min) for 99mTc-tracer and a standard of 20 min for ICG. Time to identify SLN at a mean of 3,8 min(range 1-15 min) for 99mTc and 3 min (range 1-8 min) for ICG. Concordance rates were 98,2 % for the 1st SLN, 93,8 % both for 2nd and 3rd SLN. After neoadjuvant chemotherapy, all SLN have been been detected by both techniques, in 3 patients additional SLN have been found by ICG. Costs have been cut down to 1/10 with the use of ICG, coming up to saving of 27 000 US-$ per each 100 SLNB procedures performed. Conclusions: We report a high concordance rate between the 2 techniques - 99mTechnetium and ICG with near-infrared - for detection of SLN in breast cancer. Preparation time is cut down to less than 30 %, and costs to less the 10 % of radioactive labelling. Clinical trial information: 18-8054-BO .
Identification of clinical features to predict the consistency of mutational profiles obtained from plasma and tissue of advanced non-small cell lung cancer (NSCLC) patients.
Authors: Xiaodong Jiao, Bao-Dong Qin, Ke Liu, Ying Wu, Jun Liu, Xi He, Mingqin Lin, Yan Lin, Xiaopeng Duan, Haozhe Wang, Lin Shao, Jingjing Zheng, Yuan-Sheng Zang
Journal: Journal of Clinical Oncology (2020)

e21537 Background: Due to its non-invasiveness and advantage in overcoming tumor heterogeneity, plasma-based genomic profiling is widely used in advanced NSCLC patients for treatment guidance. However, whether the mutational profile derived from ctDNA comprehensively represents that in tumor tissue is the major concern for the application. It has been reported that a variety of factors influence the consistency of mutational profile between plasma and tissue samples. This study explores clinical features which predict the concordance between tissue and plasma samples. Methods: Paired tissue and plasma samples were collected from 79 (stage III and IV) NSCLC patients. Samples were profiled using a 520-cancer-related gene panel. Serum markers such as CEA, CA199, SCC and NSE were collected. Results: All tissue samples except for 1 (98.7%) had mutations detected from this panel. 68 plasma samples (86%) had mutations detected from this panel. The overall concordance of mutation between plasma and tissue samples was 43%; and the concordances for point mutation and copy number variations were 60.2% and 15%, respectively. The concordance for 8 classic lung cancer driver genes and druggable mutations were 77.2% and 34.2%, respectively. Next, we explore the correlation of serum biomarkers and the concordance rate. Univariate analyses revealed that CA19-9 (P &lt; 0.001) and CEA (P = 0.01) were significantly associated with the concordance rate of actionable mutations. Using CEA &gt; 5ng/ml as a cutoff, 43.1% patients having higher CEA level harbored an identical mutation profile between plasma and tissue vs only 20.8% patients with lower CEA level had an identical mutation profile (p = 0.01). Furthermore, 75% patients with CA 19-9 &gt; 39U/ml harbored an identical mutation profile between plasma and tissue vs 22.8% patients with CA19-9 £ 39U/ml (P &lt; 0.001). Combining both CEA and CA19-9 can effectively predict the concordance (p &lt; 0.001); 85.7% of patients with CEA and CA19-9 levels above the cutoff have identical mutation profile and only 34.2% patients with either one or both below the cutoff have identical mutation profile (p &lt; 0.001). Conclusions: We identified the clinical and molecular factors which showed promising value in predicting the consistency of mutational profile between plasma and tissue in NSCLC patients. Plasma samples of patients with high CEA ( &gt; 5ng/ml) and CA19-91 ( &gt; 39U/ml) can comprehensively reflect the mutation profile of tumor samples. Tissue biopsy is not necessary for such patients.
4R program results: What is the impact of 4R care delivery model on patient self-management and which patients benefited?
Authors: Julia Rachel Trosman, Christine B. Weldon, Della F. Makower, Bruce D. Rapkin, Moreen Bozier, Claudia Beth Perez, Swati Kulkarni, Cathleen M. Schaeffer, Kent Hoskins, Christopher Gallagher, Shelly S. Lo, Cathy Grace-Louthen, Alyssa Throckmorton, Editha A. Krueger, Jennifer Van Horn, Arliene Ravelo, Elaine Yu, Lidia Schapira, Al Bowen Benson, William John Gradishar
Journal: Journal of Clinical Oncology (2020)

139 Background: We previously proposed a 4R model of teamwork and patient self-management (pSM) in cancer care (NCI ASCO Teams Project, Trosman JOP 2016). 4R (Right Info/Care/Patient/Time) enables patient and care team to manage complex care with an innovative 4R Care Sequence plan, including a novel visual feature describing timing and sequence of care. We report final results of a program which tested 4R at 5 safety net and 5 non safety net US centers from 2016 to 2019. Methods: Patients with stage 0-III breast cancer received 4R plans (4R Cohort). We surveyed 4R cohort and a historical control cohort of patients receiving care at same centers pre-4R. We assessed the usefulness of 4R to the 4R cohort and the impact on pSM in 4R cohort compared to historical cohort. Results: Survey response rates: 63%, 422/670 (4R cohort); 47%, 466/992 (control). 4R significantly increased the composite pSM score and 5 of 7 pSM metrics vs control (Table). The increase was not influenced by patient age, stage or whether treated at safety net site. pSM scores increased in 4R vs control cohort to a similar extent for patients &lt; 65 years old (74% vs 51%, p = .0001) as for patients ≥ 65 years old (78% vs 57%, p = .0002). pSM improved similarly for patients with stage 0 or I breast cancer (77% vs 56%, p = .0001) as for patients with stage II or III breast cancer (72% vs 54%, p = .0001). Safety net patients showed pSM increase (77% vs 51%, p = .0001) similar to non safety net patients (74% vs 58%, p = .0002). Within the 4R cohort, 80% found 4R useful for organizing care and 70% found the novel visual feature useful to manage care timing and sequence. Usefulness was similar for age groups and stages, but higher for safety net than non safety net patients (88% vs 74%, p = .0008). Conclusions: 4R markedly improved patient self-management in early breast cancer across age groups and cancer stages, but further enhancements are needed to benefit as many patients as possible. 4R benefits in safety net setting indicate that 4R may reduce disparities. [Table: see text]