tbuckley/cabot-search huggingface dataset:
Cardiovascular risk prediction in type 2 diabetes before and after widespread screening: a derivation and validation study
Authors: Romana Pylypchuk, Sue Wells, Andrew Kerr, Katrina Poppe, Matire Harwood, Suneela Mehta, Corina Grey, Billy P Wu, Vanessa Selak, Paul L Drury, Wing Cheuk Chan, Brandon Orr-Walker, Rinki Murphy, Jim Mann, Jeremy D Krebs, Jinfeng Zhao, Rod Jackson
Journal: The Lancet (2021)
Same-day pegfilgrastim or pegfilgrastim-cbqv prophylaxis in miniCHOP chemotherapy based regimens for non-Hodgkin lymphoma.
Authors: Trace Bartels, Ali McBride, Neda AlRawashdh, Logan Moore, Daniel O Persky, Ivo Abraham
Journal: Journal of Clinical Oncology (2021)

e19542 Background: Non-Hodgkin’s lymphoma, specifically, diffuse large B-cell lymphoma (DLBCL) is most frequently diagnosed among older patients. The utilization of a reduced dose of cyclophosphamide, doxorubicin, vincristine, and prednisone (miniCHOP) chemotherapy-based regimen has an improved tolerance and toxicity profile in select patient populations. Prophylaxis with pegfilgrastim or its biosimilar pegfilgrastim-cbqv is administration on the same day of chemotherapy in all patients with MiniCHOP at The University of Arizona Cancer Center (UACC). We report here on the first study to address the safety and efficacy of same day pegfilgrastim administration in lymphoma patients receiving MiniCHOP. Methods: A retrospective, single center, cohort study was conducted at UACC between October 1, 2013 and October 2020 to evaluate lymphoma patients who were treated with miniR-CHOP and given pegfilgrastim or its biosimilar (pegfilgrastim-cbqv) for FN prophylaxis. The primary objective was to compare the incidence of FN across all cycles of chemotherapy and after the first cycle of chemotherapy in DLBCL patients on miniR-CHOP and provided with next-day versus same-day pegfilgrastim administration. Our secondary outcomes of interests were incidence of chemotherapy-induced neutropenia (CIN) grade 3/4; hospitalization; anti-biotics administration; and chemotherapy dose-reduction or delays. Results: A total of 100 cycles of miniR-CHOP were received, of these pegfilgrastim was administered on same-day of chemotherapy in 95 cycles and five cycles on the next-day of chemotherapy. Among all cycles the incidence of FN was 5.3% vs. 0.0 ( P= 1.00); CIN 3/4 was 10.5% vs. 0.0 ( P= 1.00); hospitalization was 10.5% vs. 20.0% ( P= 0.45), anti-biotics administration was 6.3% vs. 40.0% ( P= 0.05) and the chemotherapy dose delays or reductions was 16.8% vs. 0.0% ( P= 0.99). In the first cycle of chemotherapy, the incidence of FN was 14.3% vs. 0.0% ( P= 1.00), CIN 3/4 was 21.4% vs. 0.0 ( P= 1.00), hospitalization 28.6% vs. 25.0% ( P= 0.99), and the anti-biotics administration was 21.4% vs. 50.0% ( P= 0.53) for same-day vs. next-day study groups. Conclusions: In our analysis, we have shown that same-day pegfilgrastim or pegfilgrastim-cbqv was safe and effective in lymphoma patients receiving miniR-CHOP. There was no significant increase in FN or delayed engraftment in either group. Future prospective studies are warranted to address the safety and efficacy profile of same day pegfilgrastim or a pegfilgrastim biosimilars in elderly lymphoma patients.
Efficacy of epirubicin plus cyclophosphamide followed by taxanes versus carboplatin plus taxanes as adjuvant chemotherapy in triple-negative breast cancer: 8.1 years median follow-up on a randomized clinical trial.
Authors: Fangchao Zheng, Feng Du, Yongsheng Wang, Xue Wang, Jiayu Wang, Jian Yue, Fei Ma, Ying Fan, Binghe Xu, Peng Yuan
Journal: Journal of Clinical Oncology (2021)

529 Background: Four cycles of adjuvant taxanes (paclitaxel or docetaxel) after four cycles of adjuvant doxorubicin plus cyclophosphamide (ECT) are considered a standard adjuvant treatment and improves survival outcomes of triple negative breast cancer (TNBC). The purpose of this analysis was to further assess whether adjuvant carboplatin plus taxanes (TP) was non-inferior to or superior to standard ECT chemotherapy in prolonging the survival time. Methods: This randomized, open-label, multicenter clinical trial conducted at three hospital in China from June, 2009 and October, 2015. Eligible early triple-negative breast cancer (TNBC) patients were randomized (1:1) to receive ECT (four cycles of epirubicin 90 mg/m2 + cyclophosphamide 600 mg/m2 followed by four cycles of docetaxel 75 mg/m2 or paclitaxel 175 mg/m2 every 3 weeks, ECT arm, n = 154) or receive TP (six cycles of docetaxel 75 mg/m2 or paclitaxel 175 mg/m2 + carboplatin AUC 5 every 3 weeks; TP arm, n = 154), which was then followed by surgery. Results: Three hundred and eight patients were recruited in this trial and final date of follow-up was January 20, 2021. Baseline characteristics were balanced between ECT arm and TP arm. Median follow-up was 97.6 months. Median disease free survival (DFS) was not reached; 8-year DFS rate was 78.35% with ECT arm and 81.73% with TP arm (hazard ratio [HR] = 0.84; 95% confidence interval [CI] = 0.50 - 1.40; P = 0.496). Median overall survival (OS) was also not reached; 8-year OS rate was 87.15% with ECT arm and 89.14% with TP arm (HR = 0.87; 95% CI = 0.44 - 1.70; P = 0.676). For TNBC patients with DFS &gt; 4 year, TP arm had a longer DFS than ECT ( P = 0.01), and had a tendency with better OS ( P = 0.4). In this subgroup analysis of SPARC &gt; 50%, TP arm had a longer DFS than ECT ( P &lt; 0.05), and also had a tendency with better OS ( P = 0.06). In subgroup analysis of PD-1 (-) and intravascular invasion (+), TP arm had a better DFS ( P = 0.02) and OS ( P = 0.03) than ECT arm. DFS or OS had no significant differences in ECT and TP arm with BRCA mutation or BRCA wild ( all P values &gt; 0.05). Conclusions: TP chemotherapy showed significant non-inferiority for PFS and OS versus ECT in the first-line adjuvant treatment of early TNBC. For some particular subgroup of TNBC, TP may be a more effective chemotherapy than ECT. TP may be considered an effective alternative to early TNBC. Clinical trial information: NCT01150513.
Control arm heterogeneity in trials for unselected advanced triple-negative breast cancer (aTNBC).
Authors: Kinisha Gala, Ankit Kalucha, Samuel Martinet, Anushri Goel, Kalpana Devi Narisetty, Bruno Larvol, Kevin Punie
Journal: Journal of Clinical Oncology (2021)

1082 Background: Primary endpoints of clinical trials frequently include subgroup-analyses. Several solid cancers such as aTNBC are heterogeneous, which can lead to unpredictable control arm performance impairing accurate assumptions for sample size calculations. We explore the value of a comprehensive clinical trial results repository in assessing control arm heterogeneity with aTNBC as the pilot. Methods: We identified P2/3 trials reporting median overall survival (mOS) and/or median progression-free survival (mPFS) in unselected aTNBC through a systematic search of PubMed, clinical trials databases and conference proceedings. Trial arms with sample sizes ≤25 or evaluating drugs no longer in development were excluded. Due to inconsistency among PD-L1 assays, PD-L1 subgroup analyses were not assessed separately. The primary aim was a descriptive analysis of control arm mOS and mPFS across all randomized trials in first line (1L) aTNBC. Secondary aims were to investigate time-to-event outcomes in control arms in later lines and to assess time-trends in aTNBC experimental and control arm outcomes. Results: We included 33 trials published between June 2013-Feb 2021. The mOS of control arms in 1L was 18.7mo (range 12.6-22.8) across 5 trials with single agent (nab-) paclitaxel [(n)P], and 18.1mo (similar range) for 7 trials including combination regimens (Table). The mPFS of control arms in 1L was 4.9mo (range 3.8-5.6) across 5 trials with single-agent (n)P, and 5.6mo (range 3.8-6.1) across 8 trials including combination regimens. Control arm mOS was 13.1mo (range 9.4-17.4) for 3 trials in first and second line (1/2L) and 8.7mo (range 6.7-10.8) across 5 trials in 2L and beyond. R 2 for the mOS best-fit lines across control and experimental arms over time was 0.09, 0.01 and 0.04 for 1L, 1/2L and 2L and beyond, respectively. Conclusions: Median time-to-event outcomes of control arms in 1L aTNBC show considerable heterogeneity, even among trials with comparable regimens and large sample sizes. Disregarding important prognostic factors at stratification can lead to imbalances between arms, which may jeopardize accurate sample size calculations, trial results and interpretation. Optimizing stratification and assumptions for power calculations is of utmost importance in aTNBC and beyond. A digitized trial results repository with precisely defined patient populations and treatment settings could improve accuracy of assumptions during clinical trial design.[Table: see text]
Whole Genome Sequencing in Combination with Transcriptome Sequencing Unravels the Pathogenetic Impact of Rare Balanced Rearrangements in Myeloid Malignancies and May Lead to Novel Personalized Therapeutic Strategies
Authors: Claudia Haferlach, Niroshan Nadarajah, Wencke Walter, Manja Meggendorfer, Wolfgang Kern, Torsten Haferlach
Journal: Blood (2017)
Real-world treatment and outcomes of frontline chemotherapy in patients with metastatic pancreatic cancer.
Authors: Salwan Al Mutar, Muhammad Shaalan Beg, Eric Hansen, Andrew J. Belli, Maegan Vaz, Sudhakar Velamoor, Ming He, Ching-Kun Wang
Journal: Journal of Clinical Oncology (2021)

e16249 Background: The difference between the FOLFIRINOX and gemcitabine/nab-paclitaxel (GnP) regimens’ clinical trial designs limit the ability to generate cross-study comparisons. Therefore, there is a significant need to understand the impact of various demographic and clinical characteristics on the effectiveness of these systemic therapies in the real-world treatment setting. This study seeks to compare the real-world outcomes of patients with metastatic pancreatic cancer treated with frontline FOLFIRINOX or GnP. Methods: Patients with primary metastatic pancreatic cancer who received first-line (1L) FOLFIRINOX or GnP were identified in the COTA real-world database. The COTA database is a de-identified database of real-world data (RWD) derived from the electronic health records of healthcare providers in the United States. Real-world overall response rate (rwORR) was calculated as the proportion of patients achieving complete response (CR) or partial response (PR). Overall survival (OS) was calculated using the Kaplan-Meier method and multivariate analyses utilized Cox proportional hazards. Results: The overall qualified cohort (n=236) was stratified by 1L FOLFIRINOX (n=109) or GnP (n=127). Select patient characteristics are shown in table. Patients treated with 1L FOLFIRINOX showed greater rwORR as compared to those treated with GnP (68.8% vs. 55.9%, p=0.04). Additionally, patients treated with 1L FOLFIRINOX had longer median OS (14.4 vs 11.4 mos, respectively). In univariate analysis, patients treated with GnP had a greater chance of mortality (HR: 1.3, 95% CI: 1.0, 1.8, p=0.05). This relationship strengthened in multivariate analysis (GnP treated HR: 1.6, 95% CI: 1.1, 2.1, p=0.01). Conclusions: Due to lack of enrollment of representative patients in clinical trials and in the absence of a comparative clinical trial, real-world experience with chemotherapy regimens provide critical insights on the outcome of treatments. In our cohort, patients treated with frontline GnP had a significantly greater chance of mortality as compared to patients treated with frontline FOLFIRINOX. The FOLFIRINOX cohort also showed greater rwORR. Future research will continue to expand on treatment patterns in subsequent lines of therapy, as well as emerging therapy types, in order to better understand the optimal treatment sequence in metastatic pancreatic cancer.[Table: see text]
Adverse effects of COVID-19 vaccination among cancer patients: Results from an Internet-based survey.
Authors: Brian Loew, Richard Tsai, John Hervey, Kathleen D. Hoffman, John Novack, Jennifer Johnson, Don S. Dizon, Stuart L. Goldberg
Journal: Journal of Clinical Oncology (2021)

2621 Background: The rapid development of safe and effective vaccines against SARS-CoV-2 may stem the global COVID-19 pandemic. However, since individuals with cancer were under-represented during clinical vaccine trials, experience with COVID-19 vaccines among cancer patients is limited. Methods: An internet-based survey was conducted January 15 - February 10, 2021 among members of the Inspire online health community. The 63-item survey was emailed to members of the Inspire community who had opted-in for research. Results: Out of 19,152 respondents, 4895 (25%) self-reported a cancer diagnosis. Of these, 1337 (27%) were receiving active therapy. Cancer respondents were 66% female, 77% white, 44% college educated, with a median age range 55-65 years. 88% had solid tumors and 12% hematologic malignancies. 241 (5%) had prior COVID-19 and 148 (3%) thought they had had it but were not tested. Among cancer patients with COVID-19 approximately 30% reported ongoing late symptoms. At the time of survey, 1335 (27%) cancer patients had received a COVID-19 vaccine (Moderna 51% Pfizer-BioNTech 46%, Astra-Zeneca 3%, Other/unknown &gt;1%). Following the first injection, 63% had local adverse events (AEs): injection site pain (51%), swelling (8%), redness (6%), and itching (4%). 34% reported systemic AEs including myalgia (32%), fatigue (18%), headache (12%), joint pain (5%), and chills (5%). 199 (15%) had received the second (booster) vaccination. 76% reported local AEs including pain (69%), swelling (14%), itching (8%), and redness (7%). 67% reported systemic AEs including fatigue (49%), myalgia (30%), headache (29%), chills (23%), fever (16%), joint pain (15%), and nausea (12%). AEs were comparable to the clinical trial results obtained from the general population (fda.gov/media/144245/download &amp; 144434/download). Conclusions: In this internet-based survey drawn from the Inspire online health community 1335 cancer patients reported receiving COVID-19 vaccinations. By self-report the vaccines were well tolerated with AEs patterns mimicking clinical trial results conducted in the general population. These safety results should be reassuring to cancer patients although attention to COVID-19 vaccine efficacy is required (and will be studied during follow-up surveys).[Table: see text]
The landscape of mortality during or within 30 days after non-palliative radiotherapy across 11 major cancer types.
Authors: Michael Xiang, Ann C. Raldow, Erqi L. Pollom, Michael L. Steinberg, Amar Upadhyaya Kishan
Journal: Journal of Clinical Oncology (2021)

6570 Background: The rate of peri-RT mortality (death that occurs during or within 30 days after non-palliative radiotherapy) has not been previously characterized. Risk factors and predictors for peri-RT mortality are unknown. Methods: Adult and pediatric patients with non-metastatic cancer who received non-palliative external beam radiation between 2004-2016 were identified in the National Cancer Database for 11 cancer types: breast, prostate, genitourinary (non-prostate), bone/soft tissue, gynecological, head/neck, lymphoma, gastrointestinal, small cell lung, non-small cell lung, and central nervous system (CNS). Multivariable logistic regression was used to identify predictors of peri-RT mortality while controlling for 16 covariates, including patient, tumor, and treatment factors. Results: Approximately 1.32 million patients were identified. Peri-RT mortality was 2.8% overall but spanned 2 orders of magnitude depending on cancer type, ranging from 0.1% for breast cancer to 8.6% for CNS malignancies. Other cancers with &gt; 5% peri-RT mortality were non-prostate genitourinary, small cell lung, and non-small cell lung. Peri-RT mortality steadily improved from 3.5% in 2004 to 2.0% in 2016 ( P &lt;.0001). Major predictors of peri-RT mortality were cancer stage, older age, baseline comorbidity, and lack of private insurance, while male sex, Black race, and geographical region were associated with modestly increased risk (all P &lt;.0001). Conversely, treatment at an academic center, higher patient volume at the treating facility, concurrent chemotherapy, and intensity-modulated radiotherapy were associated with modestly decreased risk (all P &lt;.0001). Among patients receiving stereotactic radiotherapy, peri-RT mortality was 1.0% (adjusted odds ratio 0.27, 95% confidence interval 0.24-0.30, P &lt;.0001), underscoring the excellent safety record of this treatment approach. Conclusions: Peri-RT mortality varied considerably as a function of multiple disease-specific and sociodemographic differences, which highlight potential areas of health disparities. Early recognition of patients at increased risk may facilitate closer monitoring or other prophylactic interventions.
Potential role of dose escalation in overcoming acquired resistance to cabozantinib in metastatic renal cell carcinoma (mRCC).
Authors: Akanksha Sharma, Roy Elias, Alana Christie, Noelle S Williams, Ivan Pedrosa, James Brugarolas
Journal: Journal of Clinical Oncology (2021)

e16568 Background: Cabozantinib is among the most potent tyrosine kinase inhibitors (TKI) approved for use in mRCC. Cabozantinib is available in tablet (CABOMETYX) and capsule (COMETRIQ) formulations at 60 mg daily (RCC and hepatocellular carcinoma) and 140 mg daily (medullary thyroid cancer), respectively. The two formulations are not bioequivalent, and effective drug exposures may be lower with the 60 mg tablet in certain populations. We evaluated cabozantinib 80 mg at the time of progression as salvage therapy. Methods: Using Kidney Cancer Explorer, a centralized database for clinical, pathological and experimental genomic data, we systematically identified all patients (pts) with mRCC at the University of Texas Southwestern Medical Center from Jan 2014 – Mar 2020 who had been prescribed cabozantinib. Results: During this period, we identified 107 mRCC pts prescribed cabozantinib. Two patients and a third subsequently, received 80 mg daily after having previously progressed on cabozantinib 60 mg (Table). Cabozantinib 80 mg was prescribed late in the disease course (fourth - seventh line) as salvage therapy. In the first case, cabozantinib 80 mg as fourth-line therapy resulted in disease control for 18 months. In the second and third cases, cabozantinib 80 mg resulted in deep partial responses (PRs) using RECIST principals ongoing at 20 and 5.5 months respectively. There were no grade III/IV adverse events noted. Conclusions: For mRCC pts with cabozantinib-responsive disease and good tolerability, salvage therapy with cabozantinib 80 mg at progression may be an effective treatment strategy, especially when there are limited alternatives.[Table: see text]
Actual and Missed Opportunities for End-of-Life Care Discussions With Oncology Patients
Authors: Kristin E. Knutzen, Olivia A. Sacks, Olivia C. Brody-Bizar, Genevra F. Murray, Raina H. Jain, Lindsay A. Holdcroft, Shama S. Alam, Matthew A. Liu, Kathryn I. Pollak, James A. Tulsky, Amber E. Barnato
Journal: JAMA Network Open (2021)

<h3>Importance</h3> Early discussion of end-of-life (EOL) care preferences improves clinical outcomes and goal-concordant care. However, most EOL discussions occur approximately 1 month before death, despite most patients desiring information earlier. <h3>Objective</h3> To describe successful navigation and missed opportunities for EOL discussions (eg, advance care planning, palliative care, discontinuation of disease-directed treatment, hospice care, and after-death wishes) between oncologists and outpatients with advanced cancer. <h3>Design, Setting, and Participants</h3> This study is a secondary qualitative analysis of outpatient visits audio-recorded between November 2010 and September 2014 for the Studying Communication in Oncologist-Patient Encounters randomized clinical trial. The study was conducted at 2 US academic medical centers. Participants included medical, gynecological, and radiation oncologists and patients with stage IV malignant neoplasm, whom oncologists characterized as being ones whom they "…would not be surprised if they were admitted to an intensive care unit or died within one year." Data were analyzed between January 2018 and August 2020. <h3>Exposures</h3> The parent study randomized participants to oncologist- and patient-directed interventions to facilitate discussion of emotions. Encounters were sampled across preintervention and postintervention periods and all 4 treatment conditions. <h3>Main Outcomes and Measures</h3> Secondary qualitative analysis was done of patient-oncologist dyads with 3 consecutive visits for EOL discussions, and a random sample of 7 to 8 dyads from 4 trial groups was analyzed for missed opportunities. <h3>Results</h3> The full sample included 141 patients (54 women [38.3%]) and 39 oncologists (8 women [19.5%]) (mean [SD] age for both patients and oncologists, 56.3 [10.0] years). Of 423 encounters, only 21 (5%) included EOL discussions. Oncologists reevaluated treatment options in response to patients' concerns, honored patients as experts on their goals, or used anticipatory guidance to frame treatment reevaluation. In the random sample of 31 dyads and 93 encounters, 35 (38%) included at least 1 missed opportunity. Oncologists responded inadequately to patient concerns over disease progression or dying, used optimistic future talk to address patient concerns, or expressed concern over treatment discontinuation. Only 4 of 23 oncologists (17.4%) had both an EOL discussion and a missed opportunity. <h3>Conclusions and Relevance</h3> Opportunities for EOL discussions were rarely realized, whereas missed opportunities were more common, a trend that mirrored oncologists' treatment style. There remains a need to address oncologists' sensitivity to EOL discussions, to avoid unnecessary EOL treatment.