tbuckley/cabot-search huggingface dataset:
Refining the approach to patients with primary soft tissue sarcoma of the extremities and trunk wall (ESTSTS): Outcome improvement over 30 years at a single institution.
Authors: Maria Danieli, Francesco Barretta, Marco Fiore, Stefano Radaelli, Claudia Sangalli, Marta Barisella, Silvia Stacchiotti, Elena Palassini, Rosalba Miceli, Dario Callegaro, Paolo Giovanni Casali, Alessandro Gronchi
Journal: Journal of Clinical Oncology (2021)

e23548 Background: In 2011 we reported the improved outcome of ESTS pts treated between 1987 and 2007 at Istituto Nazionale Tumori (INT), Milan (Italy). We updated the analysis at a later follow-up (FU) to assess possible changes in survival of ESTSTS. Outcomes according to histology were also explored. Methods: Pts with primary localized adult-type ESTSTS surgically treated at INT between 1987 and 2017 were retrospectively reviewed and divided into 6 groups according to the date of primary surgery. Crude cumulative incidence (CCI) of sarcoma-specific mortality (SSM), local relapse (LR), distant metastases (DMs) were calculated for each group in a competing risks framework. DM free survival (DMFS) was calculated for each group taking into account all DMs (occurred as first or later). PostDM survival and all outcomes according to histology were calculated before and after 2002. Results: 2384 pts were included. At a 104-mo m-FU, median post-DM FU was 76 mos. Clinicopathologic characteristics were comparable among groups. The use of preoperative chemo (ChT) and radiotherapy (RT) increased from 18% (1987-92) to 29% (2013-17) and from 1.6% to 26%. The rate of preoperative combined ChT-RT also increased from 0.8% to 14.3%. 1st event before SSM was LR in 17.9% pts, DM in 72.2% pts and synchronous LR-DM in 9.3% pts. Table shows 7-yrs outcomes incidence estimates for each period. CCI-SSM (p &lt; 0.001), CCI-LR (p &lt; 0.001) and DMFS (p = 0.040) improved significantly since 2003. 7-yrs postDM survival before vs. after 2003 increased from 15% to 23.6% (p = 0.012). Outcomes by histology were comparable to overall results. Conclusions: In the time frame analyzed, SSM improved by over 15%. An equal improvement in DMFS, the 50% decrease in CCI-LR (1 pts out of 5 had LR as 1st event before death), and the significant postDM increase might explain SSM improvement. Maximum change was seen since 2003 and was paralleled by an increase in the use of preoperative ChT and RT, that might have contributed to a better local and distant control. Of note, the increase in DMFS was not accompanied by a decrease in CCI-DM. The increase in DMFS might be attributable to combined modalities’ ability to offset the negative prognostic impact of positive surgical margins, while no effect was observed on DMs occurred as first event.[Table: see text]
How to choose your surgeon for colorectal cancer: The influence of fellowship training on outcomes.
Authors: Christopher Thomas Aquina, Adan Z. Becerra, Aslam Ejaz, John R.T. Monson, Fergal J. Fleming
Journal: Journal of Clinical Oncology (2021)

e18603 Background: Rectal cancer has a well-established volume-outcome relationship. However, the impact of fellowship training on outcomes following colorectal cancer resection is unknown. Methods: Patients who underwent stage I-III colorectal adenocarcinoma resection (2004-2014) were identified in the New York State Cancer Registry and Statewide Planning &amp; Research Cooperative System. Hierarchical analyses assessed the association between surgeon American Board of Colorectal Surgery (ABCRS) certification and postoperative outcomes and survival. Derived from volume tertiles, surgeons who performed ≥15 annual colon cancer resections or ≥10 annual rectal cancer resections were characterized as high-volume colon (HVCSs) or rectal (HVRSs) surgeons, respectively. Results: 47,491 colorectal cancer resections (right colon = 23,824, 50.2%; left colon = 18,154, 38.2%; rectal cancer = 5,513, 11.6%) met inclusion criteria. ABCRS-certified HVCSs (N = 92) comprised only 5.5% of the surgeon cohort but performed 20.6% of the colon cancer resections. Similarly, ABCRS-certified HVRSs (N = 31) comprised only 3.8% of the surgeon cohort but performed 16.5% of the rectal cancer resections. Despite no significant difference in complications, ABCRS-certified HVCS/HVRSs overall had better postoperative outcomes and were associated with improved survival following colorectal cancer resection. Conclusions: These results suggest that for the best outcomes and long-term survival following colon and rectal cancer resection, referral to high-volume, ABCRS-certified surgeons may be the best choice.[Table: see text]
Incidence and risk factors for euthanasia or physician-assisted suicide in oncology patients: A systematic review.
Authors: Wei Liu, Luke Liu, Alissa Liu, Sang Jia, Tony Liu, Gabriel Boldt, Melody Qu, Ian Ball
Journal: Journal of Clinical Oncology (2021)

12034 Background: In a growing number of jurisdictions, oncology patients may choose euthanasia or physician-assisted suicide (EPAS). A 2016 systematic review reported that 75% of U.S. and over 70% of Dutch and Belgian EPAS cases involved oncology patients. In the Netherlands and Belgium, the percentage of deaths among oncology patients via EPAS has been increasing. We investigated the incidence and risk factors for EPAS and EPAS requests in oncology patients. Methods: A systematic review was performed following PRISMA guidelines. PubMed, Embase and Cochrane databases were searched for articles from January 2000 to April 2020. Search terms were related to suicide, euthanasia, assisted dying, assisted death, right to die, mercy killing, and cancer. Eligible studies reported incidence and/or risk factors for EPAS/EPAS request based on at least 50 oncology patients. Eligibility for inclusion was independently reviewed by two authors, with discrepancies adjudicated by a third. Data obtained included: study type, country, cancer diagnosis, number of eligible patients, inclusion criteria, follow-up length, incidence of EPAS or EPAS request, and odds ratios (OR) for risk factors for EPAS and EPAS request. ORs and p values were extracted from studies whenever possible and were otherwise calculated based on the data provided using chi-squared test. Results: The search strategy identified 6519 results. 25 abstracts were selected for full-text review and 10 studies were included for analysis. All studies reported incidence of EPAS/EPAS request and 6 studies reported risk factors for EPAS/EPAS request. Six studies were from the Netherlands, 3 from Belgium, and 1 from Canada. Inclusion period for studies spanned from 1996 to 2018. Half of the included studies were prospectively conducted. Incidence of EPAS in cancer patients ranged from 7% to 15% and EPAS requests ranged from 8% to 27%. Factors significantly associated (p&lt;0.05) with EPAS or EPAS request in any study are shown in the Table. Conclusions: Up to 15% of oncology patients choose euthanasia or physician-assisted suicide. Potentially modifiable symptoms including severe nausea, vomiting, and pain are significantly associated with EPAS in oncology patients.[Table: see text]
Frequency and risk factors for metastasis in newly diagnosed appendiceal carcinoma.
Authors: Ahmed Minhas, Sohail A. Minhas
Journal: Journal of Clinical Oncology (2021)

e16281 Background: Appendiceal carcinoma has an insidious clinical presentation, and these tumors are rarely suspected prior to surgery, potentially leading to late diagnosis. The aim of this study is to investigate the prevalence of metastatic disease at initial presentation and potentially associated sociodemographic characteristics. Methods: Patients were identified from the Surveillance, Epidemiology, and End Results (SEER) program using ICD-O-3 histology/behavior codes between 2010-2015. Logistic regression was performed to determine the association of metastasis at presentation with tumor subtype, adjusted for age, race, sex, insurance and marital status, grade, and tumor and nodal stage using the seventh edition of the American Joint Committee on Cancer (AJCC) staging system. Results: We identified a total of 3, 447 patients with known metastatic status. 38.4% had metastatic disease at diagnosis. Compared to colonic-type adenocarcinoma (CA), mucinous adenocarcinoma (MA) was associated with significantly higher odds of presenting with metastasis at diagnosis in unadjusted (OR 3.55; 95% CI [2.97-4.24]) and adjusted (OR 2.97 [2.26-3.89]) regression. Signet ring cell carcinoma (SC) also had higher odds in unadjusted (OR 3.91 [2.99-5.12]) and adjusted (OR 2.05 [1.33-3.15]) regression. Goblet cell carcinoma (GC) was associated with lower odds in unadjusted (OR 0.28 [0.21-0.37]) and adjusted (OR 0.58 [0.36-0.94]) regression. The table describes the association of tumor and nodal stage with metastasis at diagnosis. Women had higher odds in unadjusted (OR 1.59 [1.39-1.82]) and adjusted (OR 1.93 [1.55-2.39]) regression. 90.1% of CA, 84.2% of GC, 42.2% of MA, and 78.5% of SC patients with metastasis at diagnosis had extraperitoneal distant metastasis (M1b). Conclusions: A significant proportion of patients with appendiceal carcinoma had metastasis at diagnosis. Compared to CA, MA and SC were much more likely to present with metastasis at diagnosis, while GC was less likely. Women had almost twice the odds of presenting with metastatic disease as men. T4 and N2 stages showed much higher odds of metastasis at diagnosis compared to T1 and N0 stages, respectively. Surprisingly, T2 and T3 stages were associated with lower odds of metastasis at diagnosis than T1 stage.[Table: see text]
Inferring Population Histories for Ancient Genomes Using Genome-Wide Genealogies
Authors: Leo Speidel, Lara Cassidy, Robert W Davies, Garrett Hellenthal, Pontus Skoglund, Simon R Myers
Journal: Molecular Biology and Evolution (2021)

Abstract Ancient genomes anchor genealogies in directly observed historical genetic variation and contextualize ancestral lineages with archaeological insights into their geography and cultural associations. However, the majority of ancient genomes are of lower coverage and cannot be directly built into genealogies. Here, we present a fast and scalable method, Colate, the first approach for inferring ancestral relationships through time between low-coverage genomes without requiring phasing or imputation. Our approach leverages sharing patterns of mutations dated using a genealogy to infer coalescence rates. For deeply sequenced ancient genomes, we additionally introduce an extension of the Relate algorithm for joint inference of genealogies incorporating such genomes. Application to 278 present-day and 430 ancient DNA samples of &amp;gt;0.5x mean coverage allows us to identify dynamic population structure and directional gene flow between early farmer and European hunter-gatherer groups. We further show that the previously reported, but still unexplained, increase in the TCC/TTC mutation rate, which is strongest in West Eurasia today, was already present at similar strength and widespread in the Late Glacial Period ~10k−15k years ago, but is not observed in samples &amp;gt;30k years old. It is strongest in Neolithic farmers, and highly correlated with recent coalescence rates between other genomes and a 10,000-year-old Anatolian hunter-gatherer. This suggests gene-flow among ancient peoples postdating the last glacial maximum as widespread and localizes the driver of this mutational signal in both time and geography in that region. Our approach should be widely applicable in future for addressing other evolutionary questions, and in other species.
Association of planning target volume with disease progression in inoperable stage III non-small cell lung cancer patients treated with chemoradiotherapy and concurrent and/or sequential immune checkpoint inhibition.
Authors: Julian Taugner, Monika Karin, Lukas Käsmann, Chukwuka Eze, Julian Guggenberger, Benedikt Flörsch, Amanda Tufman, Claus Belka, Farkhad Manapov
Journal: Journal of Clinical Oncology (2021)

e20557 Background: The present study evaluates outcome after chemoradiotherapy (CRT) with concurrent and/or sequential Programmed Cell Death 1 (PD-1) or Ligand 1 (PD-L1) immune checkpoint inhibition (CPI) for inoperable stage III NSCLC patients depending on planning target volume (PTV). Methods: Prospective data of thirty-nine consecutive patients with inoperable stage III NSCLC who completed CRT with sequential durvalumab (72%, 28 patients) or concurrent and sequential nivolumab (28%, 11 patients) were analyzed. Different cut offs for PTV as well as PTV as a continuous variable were evaluated for association with progression-free survival (PFS) and extracranial metastasis-free survival (eMFS). Results: All patients were treated with conventionally fractionated TRT to a total dose of at least 60 Gy (range: 60-63.6Gy), 97% (27 patients) received two cycles of concurrent platinum-based chemotherapy. Median follow-up for the entire cohort was 23.2 (range: 6.0-42.6) months; median overall survival (OS) and eMFS were not reached. Median Progression-free survival (PFS) was 22.8 (95% CI: 10.3-35.2) months. Age (65 years), gender and UICC stage had no significant impact on PFS. There was no significant difference between durvalumab and nivolumab patients. Patients with PTV ≥ 900ccm had a significantly shorter PFS (11.77 vs 26.3 months, p = 0.049) and eMFS (11.7 months vs not reached, p = 0.019). Furthermore, patients with PTV ≥ 900ccm and stage IIIC disease (TNM 8 th Ed.) achieved a dismal median PFS of only 3.6 months (vs. 26.3 months p &lt; 0.001). PTV as a continuous variable showed a trend for association with PFS (p = 0.064) and was a significant negative prognosticator for eMFS (p = 0.030; HR: 4.065; 95%CI: 1.148-14.397). Conclusions: PTV has a significant impact on the PFS and eMFS after CRT combined with concurrent and/or sequential CPI in inoperable stage III NSCLC. Patients with PTV ≥ 900ccm had a significantly shorter PFS and eMFS.
Gasdermin D as a potential prognosis and treatment response prediction biomarker for invasive breast cancer.
Authors: Xianghou Xia, Wenjuan Yin, Jiefei Mao, Jiejie Hu, Dehong Zou, Hongjian Yang, Yang Yu
Journal: Journal of Clinical Oncology (2021)

e12548 Background: Pyroptosis is a type of inflammatory cell death mediated by gasdermins. Pyroptosis is critical for macrophage against pathogen infection. Recently growing evidences show that pyroptosis may affect development and progression of many cancers. We aim to explore the expression and related function of pyroptosis executioner Gasdermin D (GSDMD) in breast cancer. Methods: We investigated the expression level of GSDMD using TNM plotter and Breast Cancer landscape proteome with TCGA, GTEx and TARGET databases, and the prognostic value of GSDMD in invasive breast cancer using Kaplan-Meier plotter with TCGA, GEO and EGA databases. The treatment response prediction values of GSDMD in invasive breast were calculated using ROC-plotter with GEO database. Further validation of the prognostic value and chemotherapy response prediction value of GSDMD were carried out with immunohistochemical staining on tissues from 165 cases of breast cancer patients receiving neoadjuvant chemotherapy in our cancer center. Results: TNM plotter and breast cancer landscape proteome portal analysis shows that overall expression level of GSDMD in invasive breast cancer tissue is 1.67 folds higher than it is in breast normal tissues ( p=1.05*e-06). Expression of GSDMD in LuminalB subtype (p=0.019) and Her2 subtype(p=0.04) is significantly higher than it is in TNBC subtype. Calculations with Kaplan-Meier plotter show expression of GSDMD is negatively correlated with overall survival(OS), HR=0.61(0.4−0.95) p=0.027 and relapse free survival (RFS), HR =0.65(0.58−0.63), p=8.7*e-14 and distant metastasis free survival (DMFS) HR =0.75(0.61−0.91), p=0.0038 in breast cancer patients. ROC-plotter calculations show high GSDMD expression is a powerful endocrine therapy (AUC=0.731 p=6*e-09 ) and chemotherapy response (AUC=0.64 p=8*e-05 ) predictor based on 5-year RFS in overall breast cancer patients. Our IHC staining analysis shows consistent prognostic and chemotherapy prediction value of GSDMD expression in TNBC patients. Conclusions: In conclusion, our findings suggest that high expression of GSDMD is positively correlated with prognosis and therapeutic response in breast cancer. GSDMD is a promising prognostic marker and therapeutic response predictor in invasive breast cancer.
Survival following locoregional recurrence in breast cancer by clinical subtype.
Authors: Kirsten Allen, Caroline A. Lohrisch, Dan Le, Rekha M. Diocee, Caroline Speers, Alan Nichol, Sara Kristina Taylor
Journal: Journal of Clinical Oncology (2021)

543 Background: We sought to explore the impact of locoregional recurrence (LRR) on survival in breast cancer (BC) patients in British Columbia treated in the modern era. Methods: A retrospective cohort study design identified patients diagnosed with stage I-III BC from 04/2005-12/2013 treated with surgery and who had a subsequent LRR. Exclusions were death or distant metastasis within 120 days of LRR, bilateral previous/synchronous BC, and other invasive cancers. After LRR, overall survival (OS) and factors associated with OS, including clinical subtype and adjuvant therapy (AdTx), were examined. We defined clinical subtypes as: Luminal (Lum) A-estrogen receptor (ER) and progesterone receptor (PR) positive, HER2 negative, and grade 1 or 2; Lum B-as Lum A but grade 3, or as Lum A but only one of ER or PR positive; triple negative (TNBC)-ER and PR and HER2 negative; and HER2 positive (with any ER, PR). In the absence of earlier LRR, we defined adequate AdTx as: (a) TNBC: &gt;=50% of planned chemotherapy (Chx), (b) HER2 positive: &gt;=50% of planned Chx and &gt;=8 cycles of anti-HER2 therapy, (c) Lum A, B: &gt;=4 years of endocrine therapy and (d) after partial mastectomy or positive final margins: &gt;=50% of radiation therapy dosage. Results: The final cohort had 492 patients with a median follow-up of 7.2 years from LRR and 11.8 years from diagnosis. LRR was local in 69.3% (n=341) and regional +/- local in 30.7% (n=151). Compared with local only, regional recurrences were associated with higher T and N stage, grade, and Lum status (p&lt;=0.01). Biomarkers were re-evaluated at LRR in 82% and changed from initial diagnosis in 32% of those tested: ER expression 3.8% gain, 6.1% loss; PR expression 9.1% gain, 15.1% loss; HER2 overexpression 3.7% gain and 4.8% loss. Over half of patients (n=255, 52%) did not receive adequate AdTx, either by choice or recommendation. A similar proportion with local vs. regional recurrence had inadequate AdTx. Time to death from 1st LRR did not vary significantly between local vs. regional recurrences (median 2.7 years). OS after LRR was lowest in TNBC (median 3.1 years, 24.2% 10-year OS) and longest in Lum A (median not reached, 64.7% 10-year OS) (Table). Conclusions: Our data provide rates of OS after LRR in the era of modern adjuvant therapy. OS after LRR varied by clinical subtype, with TNBC faring the worst, and Lum A the best. Over half had not received adequate AdTx. Despite similar treatment options, OS after LRR was significantly longer for Lum A than B subtypes, underscoring the need for therapy tailored to biology. OS was low in all other subtypes, emphasizing the importance of avoiding LRR.[Table: see text]
Comparison of Program-centric vs Student-centric National Resident Matching Algorithms
Authors: Briance Mascarenhas, Kartikeya S. Puranam, Michael N. Katehakis
Journal: JAMA Network Open (2021)

<h3>Importance</h3> The current program-centric algorithm for the National Resident Matching Program (NRMP) primarily uses the program’s ranking of students to determine a match. Concerns that the existing algorithm favors programs over students, recent findings that the program’s ranking of applicants is not associated with resident performance, and disruptions of existing screening methods and metrics have prompted reevaluation of the current algorithm relative to a student-centric algorithm, in which student ranking of programs is primary and program ranking of students is secondary. <h3>Objective</h3> To compare program-centric and student-centric algorithms for the NRMP participants. <h3>Design, Setting, and Participants</h3> This cross-sectional study used randomized computer-generated data reflecting the NRMP match for 2018, 2019, and 2020, capturing more than 50 000 students and more than 4000 programs in 23 specialties, to compare the 2 algorithms. <h3>Exposures</h3> The same simulated students, programs, and rankings were exposed to the 2 algorithms, running 2300 simulations in the overall analysis and 1000 simulations in each of 23 specialties. <h3>Main Outcomes and Measures</h3> The percentage of students who did and did not match, the percentage of students who matched to their top-ranked and top-5–ranked programs, and the program’s rank of the last student matched per position were examined. <h3>Results</h3> The 2 algorithms were not different in percentage of students matched overall (eg, for 2020, program-centric: 59% [95% CI, 57%-61%]; student-centric: 58% [95% CI, 56%-60%];<i>P</i> = .73). The student-centric algorithm, relative to the program-centric algorithm, matched a significantly higher percentage of students to their first-ranked program (eg, for 2020, 50% [95% CI, 48%-52%] vs 14% [95% CI, 13%-15%];<i>P</i> &lt; .001) and to their top-5–ranked programs (eg, for 2020, 60% [95% CI, 58%-62%] vs 46% [95% CI, 44%-48%];<i>P</i> &lt; .001). However, the last position was filled with students who had lower program rankings in the student-centric algorithm vs the program-centric algorithm (2 [95% CI, 1-2] vs 8 [95% CI, 6-10];<i>P</i> &lt; .001). <h3>Conclusions and Relevance</h3> In this study, the 2 algorithms were not different in the percentage of students matched overall. However, the student-centric algorithm matched a significantly higher percentage of students to their preferred programs. The program-centric algorithm was associated with a lower program’s last matched student rank. Further research is needed on the algorithms’ associations with cost and time demands in the match, postmatch resident and program performance, and fit with a changing environment.
Association of California’s Prescription Drug Coupon Ban With Generic Drug Use
Authors: Benjamin N. Rome, Joshua J. Gagne, Aaron S. Kesselheim
Journal: JAMA (2021)

COVID-19. 3,5,6Declines in hesitancy were reported alongside an increase in public trust in vaccine development and the governmental approval process.Despite these gains, in March 2021 estimates of vaccine hesitancy remained high, especially among young adults and Black and low socioeconomic status participants.Further steps are needed to build public trust, extend outreach and educational programs, and increase vaccination opportunities to ensure high levels of vaccination uptake.The study is limited by the low UAS panel recruitment rate, participation by community-dwelling adults comfortable completing internet-based surveys in English or Spanish, and reliance on self-reported measures.