tbuckley/cabot-search huggingface dataset:
Outcomes of VAC temporization following the excision of microinvasive sarcomas pending negative formal pathologic margins.
Authors: Mitchell Stephen Fourman, Duncan C. Ramsey, Erik T. Newman, Joseph H. Schwab, Yen-Lin Chen, Thomas F. DeLaney, John Thomas Mullen, Kevin Raskin, Santiago Lozano-Calderon
Journal: Journal of Clinical Oncology (2021)

e23559 Background: Microinvasive sarcomas can yield a high number of false negative intraoperative pathology margin analyses. Additional oncologic resection after soft tissue coverage is technically challenging and oncologically inaccurate. As a result the rate of local recurrence for these histologies can be 25% or higher. In select patients we have temporized the sarcoma tumor bed with a wound VAC pending final pathologic margins. If positive, the patient can return to the OR for a tumor bed excision. If negative, soft tissue coverage can proceed. Here we evaluate our outcomes using this approach. Methods: We retrospectively studied patients with primary sarcomas managed with a VAC temporizing approach from from 1/1/2003 to 12/1/2019 with a minimum of 2 years of oncologic follow-up. Patients with unplanned ("oopsie") excisions were also included. Our primary outcome was local recurrence. Data is presented as percentages or mean ± standard deviation where appropriate. Results: Sixty-three patients were included (Table). Mean age was 62.3 ± 22.3 (median 67.3) years, 23 (36.5%) were female, and mean age-adjusted charlson comorbidity index was 5.3 ± 1.9. Twenty-four (38.1%) had undergone “oopsie” excisions. R0 margins were achieved in 59 (93.7%) patients, while the other 4 were known R1 resections due to patient tolerance or anatomy. Five local recurrences (7.9%) were diagnosed 3.2 ± 1.5 years after surgery, of which 3 had known positive margins. Free flaps were needed in 17 (27.0%) patients. Metastatic disease was diagnosed in 8 (12.7%) patients, who all died of disease. Mean follow-up was 4.4 ± 2.9 years. Conclusions: VAC temporization results few local recurrences in patients with formally confirmed negative margins. This technique is particularly useful in the treatment of microinvasive disease or in the management of vulnerable hosts who may not be able to tolerate additional surgery in the future.[Table: see text]
Correlative Lightsheet and Electron Microscopy Applied to a Zebrafish Model of Fetal Bone Marrow: Resolving the Ultrastructure of a Single Hematopoietic Stem Cell in the Niche
Authors: Sobhika Agarwala, Keun-Young Kim, Eric A Bushong, Mark H Ellisman, Jonathan E Henninger, Leonard I. Zon, Owen J Tamplin
Journal: Blood (2017)
Utilization of hepatocellular carcinoma surveillance programs in patients with cirrhosis: A systematic review and meta-analaysis.
Authors: Jameel Kenneth Singh, Daryl Ramai, Nicola Tartaglia, Antonio Ambrosi, Shahab R. Khan, Saurabh Chandan, Antonio Facciorusso
Journal: Journal of Clinical Oncology (2021)

e16141 Background: Patients with cirrhosis are advised to undergo hepatocellular carcinoma (HCC) surveillance every six months. Routine screening is associated with early tumor detection and improved survival. However, surveillance is underutilized. We aimed to characterize the impact of HCC surveillance interventions on patient uptake and concomitant detection of HCC. Methods: We performed a comprehensive literature search of major databases (from inception to October 2020) to identify studies which assess the impact of HCC surveillance programs in patients with cirrhosis. Our primary endpoint was uptake of screening defined as having an abdominal sonogram every at least every 6 months. Secondary endpoint was the detection of HCC following screening. Pooled data was assessed using a random-effects model expressed in terms of odds ratio (OR) and 95% confidence interval (CI). Results: Nine studies were included for meta-analysis which involved 5,021 patients with cirrhosis. Patients with a history of hepatitis B or C accounted for 40.5% of the study cohort. Comparing both screening and control groups, patients were 5 times more likely to undergo abdominal sonography if they participated in surveillance programs versus usual care (OR 4.69; CI: 2.41 – 9.13, I2: 94%). Overall, the mean difference in patients who did undergo screening versus those who did not participate in surveillance was 30.6% (CI: 19.2% – 41.9%, P &lt; 0.001). Comparing both screening and control groups, patients were 1.5 times more likely to be diagnosed with HCC if they participated in surveillance programs (OR 1.49; CI: 0.57 – 3.89, I2: 65%). On subgroup analysis, comparing type of intervention program, dedicated surveillance programs showed a higher uptake compared to clinical reminders, though not statistically significant (dedicated programs OR 62.6, CI: 1.53 – 2559.5 vs clinical reminders OR 2.63, CI: 1.82 – 3.79). Conclusions: Patient uptake in HCC surveillance remains underutilized. Interventions such as dedicated surveillance programs and clinical reminders systems can significantly increase uptake of abdominal sonography and cancer detection.
Cachexia in treatment-naïve gynecological cancer patients: Prevalence, predictors, and clinical associations.
Authors: Niamh O'Donoghue, Charlie Sullivan, Claire Thompson, Feras Abu Saadeh, Waseem Kamran, Tom D’Arcy, Noreen Gleeson
Journal: Journal of Clinical Oncology (2021)

e17576 Background: Cancer cachexia is associated with considerable morbidity and mortality, yet its prevalence in gynaecological malignancy is unknown. Prevalence of cachexia in de novo gynaecological cancer patients and the impact of cachexia on clinical parameters and patient-reported outcomes were investigated. Methods: A prospective, exploratory study of newly diagnosed gynaecological cancer patients was conducted at St. James’s Hospital, the largest treatment provider for gynaecological malignancy in the Republic of Ireland. Patients recently diagnosed with a gynaecological cancer were eligible. Demographics, oncological history, Clavien Dindo Classification and length of stay were collected from participants’ medical record. A questionnaire completed by participants on 3 consecutive days collected data on height, weight, weight history, recent dietary intake, nutritional impact symptoms and functional status. Cachexia was defined using the criteria established in 2011 (Fearon and Strasser et al, 2011). Participants’ staging computed tomography scans were utilised for body composition analysis. Descriptive statistics, Mann Whitney U tests and Chi-square were used to summarise and identify significant associations between variables. Logistic regression was used to model predictors of cachexia. The European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Core Questionnaire in conjunction with EORTC gynaecological cancer-specific modules assessed quality of life. Results: A total of 94 participants were recruited. All five gynaecological cancers were represented. Prevalence of cachexia was 21.4% and was highest in patients with cervical cancer. Any weight loss in the previous month was predictive of developing cachexia. Low albumin and anorexia were associated with cachexia, although neither reached significance. Median post-operative length of stay for cachectic patients was 5 days (range 1-57) compared to 4 days (range 0-27) for non-cachectic patients (p = 0.682). 60% of cachectic patients had some post-operative complication. Cachectic patients were more symptomatic and had lower functional status in all quality of life categories, with the exception of emotional function. Conclusions: As prevalence of cachexia in this population is at least 22%, we strongly recommend screening for cachexia at all clinical assessments. Although weight loss and body mass index can identify the majority of cachectic patients, skeletal muscle mass index should also be included where possible. Its incorporation into standard radiology assessment of cancer patients would be optimal. Further research is warranted in a larger population to fully elucidate the predictors of cachexia. Quality of life is a useful means to monitor symptoms and functional status which may contribute to or exacerbate cachexia.
Next generation sequencing of sarcomas: Response to crizotinib in two cases with MET amplification.
Authors: Adrienne I. Victor, Olga Alvarez, Megan Ann Baumgart, Gaurav Goyal, Deepak M. Sahasrabudhe
Journal: Journal of Clinical Oncology (2021)

11538 Background: Sarcoma subtypes are often defined by recurrent molecular alterations. The purpose of this study is to review the utility of next generation sequencing (NGS) in sarcoma patients and report clinical outcomes to matched therapies. Methods: The records of all patients seen at the University of Rochester Medical Center (URMC) with sarcoma and NGS profiling between 8/2013 and 3/2020 were reviewed. Responses to agents targeting reported alterations were analyzed. In patients with fluorescent-in-situ hybridization (FISH) testing, fusion events by NGS were compared with FISH results. All highlighted pathogenic alterations on the NGS profile report as well as variants of uncertain significance (VUS) were recorded. Results: Seventy-five patients met inclusion criteria. Of these, 25 received a treatment based on identified alterations; 1 had a complete response (CR), 4 had partial responses (PR), and 4 experienced disease stabilization (SD). We identified two patients with MET amplified sarcoma that responded to treatment with crizotinib. One other patient with a diagnosis of leiomyosarcoma was found to have an unusually high total mutational burden (TMB) and experienced complete pathologic response to dual checkpoint blockade. In 4 cases, testing resulted in a change in subtype diagnosis. Several rare and novel fusions were identified; a sarcoma with TPM4-NTRK3 fusion responded to larotrectinib, while a sarcoma with PML-JAK1 fusion did not respond to ruxolitinib, and a sarcoma with IL7R-BCL2 fusion progressed on venetoclax. Table summarizes matched therapies in responders. Conclusions: NGS profiling led to a targeted therapy with a clinical benefit rate of 12% in this cohort. NGS profiling led to a change in diagnosis in 5% of this cohort. Multi-institutional collaborations to track outcomes of matched therapy would help determine the utility of therapies in rare cancers and unusual alterations.[Table: see text]
PD-1 antibody (Camrelizumab) for metastatic EBV positive gastric cancer: A prospective single-arm, open-label, phase 2 trial.
Authors: Miaozhen Qiu, De-Shen Wang, Yu-Ting Sun, Qi Zhao, Wen-Long Guan, Rui-hua Xu
Journal: Journal of Clinical Oncology (2021)

e16014 Background: Programmed cell death 1 (PD-1) inhibitors have been approved as third line therapy for patients with metastatic gastric cancer (mGC). Epstein–Barr virus (EBV)-positive is a potential predictor to response of PD-1 inhibitors. The aim of this study was to assess the efficacy and safety of camrelizumab as salvage treatment in metastatic EBV positive GC patients and explored the potential biomarkers associated with response (NCT03755440). Methods: In this prospective single-arm, phase II study, stage IV EBV positive GC patients received 200 mg camrelizumab by intravenous infusion every 2 weeks until disease progression or unacceptable toxicity. The primary endpoint was objective response rate (ORR), which were based on RECIST V.1.1. Secondary endpoints were progression free survival (PFS), overall survival (OS), disease control rate (DCR), durationn of response (DoR), and toxicity. Exploratory analysis included association between response and tumor mutational burden (TMB) and cell death ligand-1 (PD-L1) expression. Results: According to Simon’s optimum two-stage design with α = 0.05 and β = 0.20. P0 = 15% (null hypothesis), the presence of at least 1 success in the 6 patients enrolled in the first stage allowed the trial to proceed to the second stage in which 13 more patients were needed to be enrolled for the minimum total of 20 patients (5% lost to follow-up calculated). Six eligible patients were enrolled at the first stage. All the patients were HER2 negative and pMMR. None of the patients had an objective response. The DCR was 66.7%. The median PFS was 2.2 months (95% CI: 1.5 months-not reached (NR)) and median OS was 6.8 months (95% CI: 1.7 months-NR). The most common treatment-related adverse event (TRAE) was reactive cutaneous capillary endothelial proliferation. No grade 3 or worse TRAEs were found. Only one patient had PD-L1 combined positive score (CPS) ≥1 but got disease progression. Three patients were TMB &gt; 10Mb and two of them got stable disease while one got disease progression. Conclusions: EBV positive is not a good predictor for response to PD-1 inhibitors. Potential biomarkers are needed to identify EBVaGC patients who might respond to PD-1 inhibitors. Clinical trial information: NCT03755440.
Implementation of mandatory ERCP registration in The Netherlands and compliance with European Society of Gastrointestinal Endoscopy performance measures: a multicenter database study
Authors: Felix Theunissen, Sophia E. van der Wiel, Pieter C. J. ter Borg, Arjun D. Koch, Rob J. T. Ouwendijk, Rob M. E. Slangen, Peter D. Siersema, Marco J. Bruno
Journal: Endoscopy (2021)

Abstract Background In 2018, the European Society of Gastrointestinal Endoscopy (ESGE) and United European Gastroenterology (UEG) published quality performance measures for endoscopic retrograde cholangiopancreatography (ERCP). Since January 2016, all endoscopists in the Netherlands have been required to register all ERCP procedures in a nationwide quality registry. This study aimed to evaluate the procedural success rates of ERCP after the implementation of mandatory national registration and to compare these with the ESGE quality performance measures. Methods This study was conducted with data from a multicenter endoscopy database. Data from 2019 and 2020 were analyzed. The primary outcome was ERCP procedural outcome. ESGE performance measures that could be evaluated were the percentage of successful bile duct cannulations in patients with virgin papillary anatomy; successful stent placement for a biliary obstruction located below the liver hilum; and complete removal of bile duct stones (&lt; 10 mm). Result In total, 5295 ERCPs performed in 11 centers were included for analysis. The overall procedural success rate was 89.1 %. Successful biliary cannulation in patients with a virgin papilla was 90.3 % in nonacademic and 92.4 % in academic centers. The rates of successful stent placement in patients with a biliary obstruction located below the liver hilum were 97.0 % in nonacademic and 98.2 % in academic centers, and of successful bile duct stone extraction were 97.9 % in both nonacademic and academic centers. Conclusions The quality of ERCPs performed met five of the six evaluated ESGE performance measures. The 95 % target for successful biliary cannulation in patients with virgin papillary anatomy in academic centers was not met. Mandatory registration provides valuable insight into ERCP performance rates.
The efficacy and safety of irinotecan plus doxorubicin liposome in relapsed/refractory Wilms’ tumors: A retrospective study.
Authors: Juan Wang, Lian Zhang, Yi Que, Zijun Zhen, Jia Zhu, Feifei Sun, Suying Lu, Junting Huang, Liuhong Wu, Ruiqing Cai, Yizhuo Zhang, Xiaofei Sun
Journal: Journal of Clinical Oncology (2021)

e22007 Background: To evaluate the efficacy of the regimen of combination of irinotecan and doxorubicin hydrochloride liposome in relapsed/refractory pediatric Wilms’ tumor. Life quality and toxicity are seriously considered and assessed. Methods: The project stipulated 5-day course of irinotecan 50 mg/m 2 (90-minute infusion) and doxorubicin hydrochloride liposome 40mg/m 2 every 3 weeks. Granulocyte colony-stimulating factor was applied when the number of neutrophil count was lower than 1,000/ L. Results: 16 patients received 1to 8 courses (median, 3 courses) of this regimen, including 8 males and 8 females, with a median age of 4.2 years old (range, 0.5-11) . 2 patients were not assessable for response (1were treated in third CR, and 1with refractory WT received only one course as part of complex salvage regimens). Of 14 patients treated for relapsed or refractory Wilms’ tumor and accessed for response, 2 patients had complete responses (CR), 5 patients had partial responses (PR). Of 2 patients had stable diseases (SD), including 1 patient showed objective response on pulmonary lesion. The disease control rate was 64% (2 CR, 5 PR, and 2 SD), and the objective response rate was 50% (2 CR, 5 PR). The median progression-free survival was 3.5 months (range 0.5-12), and the median survival duration was 8 months (range 1-28). Myelosuppressive and gastrointestinal adverse effects were self-limited and clinically controllable with routinely intervention, and this therapeutic regimen was generally continued without delayed therapy. Multiple courses of this regimen had no cumulative toxicity and achieved disease control in relapsed or refractory Wilms’ tumor. Conclusions: The regimen of combination of irinotecan and doxorubicin hydrochloride liposome has positive effect on relapsed/refractory Wilms’ tumor with gentle toxicity without reducing the efficacy, and achieves good quality of life.
Phase 3 study of pembrolizumab with concurrent chemoradiation therapy followed by pembrolizumab with or without olaparib versus concurrent chemoradiation therapy followed by durvalumab in unresectable, locally advanced, stage III non-small cell lung cancer: KEYLYNK-012.
Authors: Salma K. Jabbour, Byoung Chul Cho, Emilio Bria, Terufumi Kato, Jaishree Bhosle, Justin F. Gainor, Noemi Reguart, Luhua Wang, Daniel Morgensztern, Ellen Gurary, Tanya B. Ashraf, Humberto Lara-Guerra, Martin Reck
Journal: Journal of Clinical Oncology (2021)

TPS8580 Background: Pembrolizumab, an anti‒PD-1 antibody is standard of care therapy for metastatic non‒small-cell lung cancer (NSCLC) as monotherapy and in combination with chemotherapy. Durvalumab, an anti–PD-L1 antibody, is approved for unresectable, stage III NSCLC without disease progression following concurrent chemoradiation therapy (CCRT). Early trials of pembrolizumab in combination with chemoradiotherapy, either concurrently or as consolidation, showed acceptable tolerability and promising PFS in patients with unresectable stage III NSCLC. Early data suggest the combination of poly(ADP-ribose) polymerase (PARP) plus anti–PD-(L)1 inhibition can enhance treatment effects. KEYLYNK-012 (NCT04380636) is evaluating pembrolizumab plus CCRT followed by pembrolizumab with/without the PARP inhibitor olaparib vs CCRT followed by durvalumab in patients with unresectable, locally advanced, stage III NSCLC. Methods: This global phase 3, randomized, placebo- and active-controlled, double-blind study is enrolling patients aged ≥18 y with previously untreated, pathologically confirmed, stage IIIA–C NSCLC, an ECOG PS of 0 or 1, and a tumor sample available for PD-L1 evaluation. Patients are randomized 1:1:1 to CCRT (platinum-doublet chemotherapy [cisplatin plus pemetrexed or etoposide; or carboplatin plus paclitaxel] plus radiotherapy 60 Gy over 6 wks [cycles 2–3]) with pembrolizumab 200 mg Q3W (groups A and B) or CCRT alone (group C) for 3 cycles. This is followed by pembrolizumab 200 mg Q3W for 17 cycles plus placebo (group A) or olaparib 300 mg BID (group B); or durvalumab 10 mg/kg Q2W for 26 cycles (group C). Randomization is stratified by disease stage (IIIA vs IIIB/IIIC), tumor histology (squamous vs nonsquamous), PD-L1 tumor proportion score (≥50% vs &lt; 50%) and region (East Asia vs North America/Western Europe/UK vs other). PFS (RECIST v1.1 by blinded independent central review [BICR]) and OS are dual primary endpoints. Secondary endpoints include ORR, duration of response, safety and tolerability, and quality-of-life outcomes. Tumor response will be evaluated per RECIST v1.1 by BICR after CCRT and at regular intervals throughout the study until disease progression, new cancer therapy, study withdrawal, or death. AEs will be graded by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0. Enrollment began July 6, 2020 and is ongoing at 204 sites in 24 countries. Clinical trial information: NCT04380636.
Concerns About Recommendations for Perioperative Cannabis Use
Authors: Elyad M. Davidson, Noa Raz, Aharon M. Eyal
Journal: JAMA Surgery (2021)

To the Editor We read with great interest the Review article by Stewart and Fong.1 We completely agree with the concluding remarks that there is a critical need for additional research on the effects of perioperative cannabis. However, we have some concerns.
RARE COMPLICATIONS OF TYPHOID FEVER.
Journal: JAMA (1898)

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Efficacy of Iron Therapy on Fatigue and Work Capacity in Non-Anemic Iron Deficient Adults: A Systematic Review of Randomized Controlled Trials
Authors: Brett L. Houston, Daryl Hurrie, Jeff Graham, Brittany Perija, Emily Rimmer, Rasheda Rabbani, Charles N. Bernstein, Alexis Turgeon, Dean Fergusson, Donald S. Houston, Ahmed M. Abou-Setta, Ryan Zarychanski
Journal: Blood (2017)