tbuckley/cabot-search huggingface dataset:
Superior therapy response predictions for patients with low-grade glioma (LGG) using Cellworks Singula: MyCare-009-04.
Authors: Manmeet Singh Ahluwalia, Drew Watson, Shweta Kapoor, Rajan Parashar, Kunal Ghosh Ghosh Roy, Aftab Alam, Swaminathan Rajagopalan, Anuj Tyagi, Diwyanshu Sahu, Rakhi Purushothaman Suseela, Naga Ganesh, Prashant Nair, Shivgonda Birajdar, Karthik Sundara Raju, Reshma Gopi, Poornachandra G, Neha Gupta, Neelesh Lunkad, Vivek Patil, Patrick Y. Wen
Journal: Journal of Clinical Oncology (2020)

2569 Background: Despite using cytogenetic and molecular-risk stratification and precision medicine, the current overall outcome of LGG patients remains relatively poor. Therapy selection is often based on information considering only a single aberration and ignoring other patient-specific omics data which could potentially enable more effective treatments. The Cellworks Singula report predicts response for physician prescribed therapies (PPT) using the novel Cellworks Omics Biology Model (CBM) to simulate downstream molecular effects of cell signaling, drugs, and radiation on patient-specific in silico diseased cells. We test the hypothesis that Singula is a superior predictor of progression-free survival (PFS) and overall survival (OS) compared to PPT. Methods: Singula’s ability to predict response was evaluated in an independent, randomly selected, retrospective cohort of 137 LGG patients aged 14 to 73 years treated with PPT. Patient omics data was available from TCGA. Singula uses PubMed to generate protein interaction network activated and inactivated disease pathways. We simulated the PPT for each patient and calculated the quantitative drug effect on a composite LGG disease inhibition score based on specific phenotypes while blinded to clinical response. Univariate and multivariate proportional hazards (PH) regression analyses were performed to determine if Singula provides predictive information for PFS and OS, respectively, above and beyond age and PPT. Results: In univariate analyses, Singula was a significant predictor of both PFS (HR = 3.587, p &lt; 0.0001) and OS (HR = 3.044, p = 0.0007). In multivariate PH regression analyses, Singula (HR = 3.707, p &lt; 0.0001) remained an independent predictor of PFS after adjustment for PPT (p = 0.3821) and patient age (p = 0.0020). Singula (HR = 2.970, p = 0.0013) was also a significant independent predictor of OS after adjustment for PPT (p = 0.0540) and patient age (p &lt; 0.0001). Results indicate that Singula is a superior predictor of both PFS and OS compared to PPT. Singula provided alternative standard of care therapy selections for all 34 disease progressors. Conclusions: Singula is a superior predictor of PFS and OS in LGG patients compared to PPT. Singula can correctly identify non-responders to PPT and provide alternative therapy selections.
冷疗法治疗炎性外痔的临床观察
Authors: 苏清伦, 周锡阳, 吴叶荣
Journal: BMJ (2009)

痔是肛垫病理性肥大、移位及肛周皮下血管丛血流瘀滞形成的团块[1].痔疮是肛肠科的常见病,其患病率在成人约为58.4%,占肛肠疾病的87.2%,其中炎性外痔是痔疮中的常见急症,严重影响患者的生活和工作,以往多采用手术切除,但由于手术创伤大,疗程长,不易为患者接受,目前趋向于保守治疗[2].冷疗法治疗痔疮尚未见报道,本研究采用此方法治疗炎性外痔15例,现报告如下。
Assisting decision making on the use of carboplatin for metastatic breast cancer.
Authors: Juan Luis Gomez Marti, Margaret Q. Rosenzweig, Adam Brufsky
Journal: Journal of Clinical Oncology (2020)

e13008 Background: Metastatic breast cancer (MBC) is currently treated with chemotherapy, often in combination with targeted or hormonal therapies. Current guidelines indicate the use of paclitaxel in combination with HER2-targeted therapy for HER2+ disease. Platins are often used in combination with taxanes for HER2+, and rarely for HER2(-), metastatic disease. While some studies reported no benefit from carboplatin (Carbo), others showed an additive effect in combination with a taxane (Txn). At this time, it is not clear if platins are an effective course of treatment for HER2+bone only disease. Therefore, this study investigates in a real-world clinical setting the utility of Carbo after the diagnosis of a first metastasis. Methods: Clinical information was obtained using a database with MBC patients seen at Magee Women’s Hospital from 1999-2019. After a chart review, patients were initially classified according to their molecular status and first metastatic location. Overall survival (OS) and time to next therapy (TTNT) were measured (months) and compared between those who received Txn and those who received Carbo in combination with a Txn after first metastatic diagnosis. Treatment response was investigated in either bone or visceral (lung or liver) MBC. Log ranks were used to estimate survival. Results: From 1,723 patients, 36.15% developed first metastasis to bone, 8.7% to lung, 12.63% to lymph node, 9.46% to liver, 4.17% to brain, and 23.33% to other sites. We found that HER2+ patients firstly diagnosed with visceral metastasis benefited from Carbo+Txn vs Txn only (OS 53.27 vs 38.17, P = 0.034), but not those who were HER2(-) (OS 23.20 vs 25.03, P = 0.307), or with bone metastasis, regardless of HER2 status (OS 38.57 vs 37.13, P = 0.718). However, patients with bone metastasis showed an increased TTNT with Carbo+Txn vs Txn alone (13.68 vs 8.167, P = 0.007). Finally, patients with liver metastasis who received Carbo+Txn had an increased OS (51.7 vs 20.4, P = 0.01) and TTNT (17.33 vs 8.63, P = 0.02) compared to Txn only. Looking separately at HER2 status, we found a nonsignificant trend towards Carbo+Txn efficacy in both subtypes. No differences in OS were found when looking at lung as the first metastatic location (Carbo+Txn vs Txn, 30.67 vs 27.03, P = 0.75). Conclusions: Patients whose first metastasis is to the liver, and those who are HER2+ and develop visceral metastasis, might benefit from carboplatin in combination with a taxane and HER2-targeted therapies. There is no benefit from adding carboplatin for bone metastasis. Further studies with larger datasets could validate these results.
Multi-institutional collaboration in sarcoma and central nervous system tumors.
Authors: Jacob Gillingham, Brittany Siontis, Steven Ian Robinson, Scott H. Okuno
Journal: Journal of Clinical Oncology (2020)

e23544 Background: Rare diseases are defined as conditions that affect less than 200,000 people annually in the United States. Around 17000 cases of sarcoma will be diagnosed in 2020. Collaboration among institutions is needed to best understand rare diseases such as sarcoma. One measure of collaboration is publications with multiple institutions as authors. We sought to determine if collaboration in sarcoma has increased since 2011 and compared that to another rare disease, CNS tumors based on multi-institution-authored abstracts presented at ASCO. Methods: All sarcoma and CNS oral abstracts, clinical science symposia, poster presentations, poster discussions, and published-only ASCO Annual Meetings from 2011 to 2019 were reviewed. Collaboration was determined if the abstract authors were from more than one institution. Results: 2,134 abstracts were reviewed. Collaboration for sarcoma ranged from 0.603 to 0.720 and 0.582 to 0.755 for CNS. From 2011-2019 a positive linear trend in collaboration was found in CNS (P &lt; 0.05), but not in sarcoma (P = NS). There was no significant trend in the incidence of collaboration in Sarcoma based on the type of presentation at ASCO. There was no difference in collaboration between bone or soft tissue sarcoma abstracts or median number of institutions collaborating between sarcoma and CNS. There were more international collaborations and absolute number of institutions in sarcoma vs CNS. Conclusions: Sarcoma collaboration has remained constant from 2011-2019 with greater number of institutions and more international collaborations as compared to CNS. CNS collaboration has increased from 2011-2019. Sarcoma collaboration at ASCO is robust and reflects the need for multi-institutional partnership.
Biliary hitch and ride technique for blind pancreatic duct cannulation
Authors: Juan J. Vila, Juan Carrascosa, Ignacio Fernández-Urién, Paul Yeaton, Gonzalo González, Leire Aburruza, José Manuel Zozaya
Journal: Endoscopy (2020)

Endoscopic pancreatic therapy is indicated in several pancreatic disorders [1] [2]. Selective pancreatic cannulation can be challenging when pancreatic inflammatory changes are extended to the duodenal wall, as the papilla might be very difficult to identify with the duodenoscope.
Real-world hematologic toxicities in patients &gt; 70 versus &lt; 69 with ER positive metastatic breast cancer on CDK 4/6 inhibitors: Single-institution retrospective study.
Authors: Coral Olazagasti, Wingsze Liu, Chung-Shien Lee, Taylor Decina, Karalyn Pappas, Kit Cheng
Journal: Journal of Clinical Oncology (2020)

e13039 Background: Since 2015, CDK4/6 inhibitors (CDKi) have become part of standard of care in the treatment ER-positive, Her2Neu negative of metastatic breast cancer (MBC). Hematologic toxicity from CDKi are common. Pooled analysis of prior randomized trials did not show hematologic toxicity between younger and older adult age groups. We sought to review generalizability of these findings to our community population. Methods: We conducted a retrospective single institution retrospective study on patients who were treated with CDKi from 2015 to 2019. Patients were stratified according to age &gt; 70 years and &lt; 69 years. Data from absolute neutrophil count, hemoglobin and platelet count on Days 1 and 15 of the first 2 cycles were graded for hematologic toxicity according to CTCAE v 5.0. Our primary objective was to assess any difference in grade of hematologic toxicities in the different age groups. Our secondary objective was to analyze the association between hematologic toxicities with the presence or absence of bone metastasis and/or prior chemotherapy exposure. Results: A total of 220 patients were reviewed, 140 were &lt; 69 years and 80 &gt; 70 years. There was no significant effect of time (p = 0.91) with respect to the outcome of hematologic toxicity adjusting for age (p = 0.16). Seventy-seven percent (171/220) of patients had evidence of bone marrow (BM) involvement. There was no significant difference in the grade of any hematologic toxicities over time (p = 0.97) and underlying BM disease (p = 0.20). On the other hand, 50% (111/220) patients had previously received an average of one line of chemotherapy. There was significant positive correlation between lines of therapy and grade of neutropenia (r S = 0.25, p = 0.0028). Overall, the estimated median progression free survival (PFS) was 19.1 months. The median overall survival could not be estimated. Conclusions: Our single institution experience does not show significant hematologic toxicity between patient age groups nor evidence of bone metastasis. However, prior exposure to chemotherapy can have a significant effect in the grade of neutropenia. Our study revealed that there is no difference in PFS according to dosing or age which correlates with current literature.
Final results of a randomized, open label, perioperative phase II study evaluating nivolumab alone or nivolumab plus ipilimumab in patients with resectable HCC.
Authors: Ahmed Omar Kaseb, Hop Sanderson Tran Cao, Yehia I. Mohamed, Aliya Qayyum, Luis M. Vence, Jorge M. Blando, Shalini Singh, Sunyoung S. Lee, Kanwal Pratap Singh Raghav, Lina Altameemi, Asif Rashid, Jean-Nicolas Vauthey, Kristen Carter, Ching-Wei David Tzeng, Yun Shin Chun, James C. Yao, Robert A. Wolff, James Patrick Allison, Padmanee Sharma
Journal: Journal of Clinical Oncology (2020)

4599 Background: In resectable hepatocellular carcinoma (HCC) surgical resection is associated with high recurrence rates. However, there is no approved neoadjuvant or adjuvant therapies yet. Neoadjuvant immunotherapy effect has never been reported in this setting in HCC. Methods: This is a randomized phase II trial of nivolumab (Arm A) or nivolumab + ipilimumab (Arm B) as peri-operative treatment for patients (pts) with HCC who are eligible for surgical resection. Pts in Arm A are given nivolumab 240 mg iv, every 2 weeks (wks) for a total of 3 doses followed by surgery on week 6. Pts in Arm B are treated with nivolumab per same schedule as arm A plus concurrent ipilimumab 1 mg/kg on day 1. Adjuvant part of study starts 4 weeks after surgery, with Nivolumab at 480 mg iv every 4 weeks for 2 years in arm A. Pts in Arm B are treated with nivolumab per same schedule as arm A plus concurrent ipilimumab 1 mg/kg every 6 weeks times 4 doses after resection. The primary objective was the safety/tolerability of nivolumab +/- ipilimumab. Secondary objectives include overall response rate, pathologic complete response (pCR) rate and time to progression. Exploratory objectives include evaluating the pre- and post-treatment immunological changes in tumor tissues and peripheral blood. Results: 30 patients were enrolled, 2 patients withdrew consent, one patient was not eligible at time of therapy, and 27 randomized (13 to Arm A and 14 to Arm B). 21 patients proceeded with resection as planned and surgery was aborted for 6 patients; 1 for frozen abdomen due to old surgery, 2 for small residual volume, and 3 for progressive disease. Pts age ranged between 32-83 yo, 75 % were males, 7 pts had HCV, 7 had HBV and 7 had no hepatitis. Pathologic complete response (pCR) was observed in 5/21 pts (24% pCR rate) – 2 in Arm A and 3 Arm B, and 3/21 pts (16%) – 1 in Arm A, 2 in Arm B, achieved major pathologic response (necrosis effect of 50-99%). 5 patients in Arm B and 1 in Arm A experienced grade 3 or higher toxicity prior to surgery. No grade 4 or higher toxicity were observed and surgery was not delayed or cancelled due to oxicity. Conclusions: Our study reached its primary endpoint of safety. Importantly, we report a 40% pathologic response rate = pCR rate of 24%, and major necrosis rate of 16% for resectable HCC after preoperative immunotherapy in a randomized phase II pilot trial. After future validation, these promising results may contribute to a paradigm shift in the perioperative treatment of resectable HCC. Clinical trial information: NCT03222076 .
Evaluation the global and regional myocardial function of patients with hypertrophic cardiomyopathy by two-dimensional speckle tracking imaging
Authors: Jia-bao Yin, Rui-qiang Guo, Jin-ling Chen
Journal: BMJ (2011)

Two-dimensional speckle tracking imaging(2D-STI)can accurately evaluate myocardial strain with non-angle dependent and good reproducibility. In this study, 16 patients with hypertrophic cardiomyopathy (HCM), 18 athletes and 20 normal subjects underwent 2D-STI examination. The global longitudinal strain (GLS) and regional peak systolic strain (PSS) were assessed by 2D-STI in the apical four-chamber-view. Compared to athletes and normal subjects, GLS in patients with HCM was significantly reduced [GLS: -(8. 0±3.6)% , P ＜ 0. 01]. There was no significant difference in GLS between athletes and the controls, but GLS in basal or middle segments of interventricular septum and middle segments of lateral wall; PSS in basal, middle or apical segments of interventricular septum and basal or middle segments of lateral wall of the normal controls were significantly higher than those of the athletes. A cut-off value of less than -10% in GLS for diagnosis of pathologic hypertrophy resulted in a sensitivity of 84. 0% and a specificity of 94. 0%. The results suggest that 2D-STI can quantify global and regional myocardial function and may be used for the differentiation between physiological and pathologic LVH.

Key words: 
Echocardiography;  Cardiomyopathy, hypertrophic
Minimally invasive partial nephrectomy versus percutaneous cryoablation for stage Ia renal cell carcinoma: A cost-effectiveness analysis.
Authors: Xiao Wu, Johannes Uhlig, Brian M. Shuch, Kevin Kim
Journal: Journal of Clinical Oncology (2020)

e17066 Background: Minimally invasive partial nephrectomy (PN) and percutaneous cryoablation (Cryo) are treatment strategies for renal cell carcinoma (RCC). The purpose of this study is to assess the cost-effectiveness of PN and Cryo for stage Ia RCC. Methods: A decision-analysis model was constructed over 5 years from a health care sector’s perspective using TreeAge Pro Suite 2019 (TreeAge Software LLC, Cambridge, MA). The two evaluated strategies were PN and Cryo. The model incorporated the clinical course of stage Ia RCC after either treatment, including costs and quality of life associated with major complications, imaging surveillance (based on 2014 National Comprehensive Cancer Network guidelines), local and metastatic recurrences, and cancer-specific mortality. All clinical parameters were derived from the literature. A willingness-to-pay threshold of $100,000/quality adjusted life year (QALY) was used. 1 QALY is equivalent to 1 year of life in perfect health. Outcomes were measured by incremental effectiveness ratio. Base case calculations, Monte Carlo Simulations with 10,000 iterations using bootstrapping for parameters from their distributions, and multiple sensitivity analyses were performed. Results: Five-year local recurrence-free, metastasis-free, and cancer-specific survival from recent literature were 97.7% versus 95.9% ( p = 0.18), 98.0% versus 100% ( p = 0.14), 99.3% versus 100% % ( p = 0.7) for PN and Cryo. PN and Cryo yielded similar health benefits of 3.63 QALY and 3.64 QALY. Overall costs were $26,343 and $19,346 for PN and Cryo. A total of 89.28% of the 10,000 simulations showed higher cost-effectiveness of Cryo than PN. One-way sensitivity analyses varying long-term outcomes after Cryo while keeping outcomes after PN constant, revealed that Cryo is more cost-effective than PN when its local recurrence risk is &lt; 3.94% per year (18.2% over 5 years), metastasis risk is &lt; 1.51% per year (7.33% over 5 years), or cancer-specific mortality risk is &lt; 0.96% per year (4.7% over 5 years). PN is more cost-effective if Cryo local recurrence risk is 3.5% higher than PN per year, when the metastasis risk is 1.1% higher than PN per year, or when its cancer-specific mortality is more than 0.9% higher than PN per year. Cryo is more cost-effective than PN if its cost is not more than $1,000 higher than PN. Conclusions: Our study showed that Cryo is more cost-effective than PN for stage Ia RCC patients with comparable effectiveness at a lower cost, based on multiple probabilistic and deterministic sensitivity analyses.
Needs and demands of continuing medical education for general practitioners after completion of residency training
Authors: Jian Wang, Hua Yang, Qi Zhao, Shanzhu Zhu, Zhigang Pan
Journal: BMJ (2018)

Objective
To assess the needs and demand of continuing medical education (CME) for general practitioners (GPs) after completion of residency training.


Methods
A series of surveys were carried out from July 2015 to December 2015 using a questionnaire on needs and demands of CME among 152 GPs, who completed residency training in Zhongshan Hospital from September 2000 to July 2013.


Results
One hundred and fifty two valid questionnaires were received with a retrieval rate of 100%. Among 512 participants, 53 (34.9%) regarded CME as necessary, 129 (84.9%) were willing or very willing to receive CME, 87 (68.9%) stated that they were willing to receive CME even without credits, 120 of them (78.9%) stated that the primary purpose of receiving CME was to update professional knowledge; 87(57.2%) stated lack of certain knowledge and 52 (34.2%) stated lack of certain skills to some extent; 8 (5.3%) thought that the previous CME they received did not completely meet their needs, 105 (69.1%) thought that it partially met their needs; 136 (89.5%) thought that only high level experts were suitable for CME teaching; the teaching methods they preferred were problem-based learning (PBL), followed by case study, clinical demonstration and instruction, and systematic lectures focused on common clinical problems; 88 (57.9%) preferred short term training with an average length of 5.01 days (91.4%, 139/152); 111(75.0%) preferred CME course to be offered on both workdays and off hours. The factors influencing willingness to attend CME included length of time (87.5%, 133/152), lack of suitable program (64.5%, 98/152), monotonous way of training, impractical training contents and its inconsistency with actual need (60.3%, 91/52).


Conclusion
The needs and demands of continuing medical education for GPs completing residency training are high. The results of this study would provide useful information for effective implementation of continuing medical education for GPs.


Key words: 
General Practitioner; Standardized training; Questionnaires
Phase II trial of SAR439859 vs endocrine monotherapy in pre- and post-menopausal, estrogen receptor-positive (ER+)/human epidermal growth factor receptor 2-negative (HER2-), locally advanced or metastatic breast cancer (BC) with prior exposure to hormonal therapies.
Authors: Sara M. Tolaney, Irfan Cicin, Rafael Betancourt, Arlene Chan, Diego Kaen, Peter A. Kaufman, Suzette Delaloge, Qianying Liu, Sylvaine Cartot-Cotton, Amele Amrate, Vasiliki Pelekanou, Katharine Ellen Cuff
Journal: Journal of Clinical Oncology (2020)

TPS1107 Background: Endocrine therapy (ET) targeting ER signaling is the mainstay of care for ER+ metastatic BC. There remains an unmet need in patients (pts) whose tumors become resistant to currently available ET. Selective ER degraders (SERDs) were developed to overcome resistance to existing ER-directed therapies by both competitively antagonizing and degrading ERs, while exploiting continued dependence of the tumor on ER signaling. SAR439859 is a potent SERD with robust preclinical ER degrading activity. In a Phase I dose escalation trial, SAR439859 demonstrated a favorable safety profile with no dose-limiting toxicities across all doses (20–600 mg QD). ER occupancy generally exceeded &gt; 87% with plasma concentrations &gt; 100 ng/mL. Overall response rate was 6.3% and clinical benefit rate was 50% (Campone. SABCS 2019. P5-11-02). The recommended Phase II monotherapy dose was 400 mg QD. Methods: This international, prospective, open-label, randomized Phase II study (NCT04059484; ACT16105) assesses safety and efficacy of SAR439859 in pts with ER+ (&gt; 1%)/HER2- metastatic or locally advanced BC progressing on ≥ 6 months of continuous ET (0–2 lines in the metastatic setting). Prior CDK inhibitors are allowed. Exclusion criteria include Eastern Cooperative Oncology Group performance status (ECOG PS) ≥ 2, life expectancy &lt; 3 months, &gt; 1 chemotherapy or targeted therapy in the metastatic setting, concomitant illness and factors potentially affecting SAR439859 absorption. Pts are randomized 1:1 to SAR439859 400 mg QD orally or physician’s choice of endocrine monotherapy (fulvestrant, tamoxifen, aromatase inhibitor). Pts receive 28-day cycles until unacceptable toxicity, progression, death, investigator decision or pt request. Stratification factors include visceral metastases, prior CDK4/6 inhibitors, and ECOG PS. Primary endpoint is progression-free survival (RECIST v1.1). Secondary endpoints include overall survival, response rate, duration of response, clinical benefit, pharmacokinetics, quality of life and safety. Target enrollment: n = 282; current enrollment: n = 9. Funding: Sanofi Clinical trial information: NCT04059484 .