tbuckley/cabot-search huggingface dataset:
Planned drug holiday in a cohort study exploring the effect of lenvatinib on differentiated thyroid cancer.
Authors: Makoto Tahara, Hiroshi Takami, Yasuhiro Ito, Takahiro Okamoto, Iwao Sugitani, Kiminori Sugino, Shunji Takahashi, Hiroshi Takeyama, Hidemitsu Tsutsui, Hisato Hara, Ayako Mitsuma, Hiroyuki Yamashita, Yasuo Ohashi, Tsuneo Imai
Journal: Journal of Clinical Oncology (2021)

6070 Background: Lenvatinib is now available for unresectable radioactive iodine (RAI)-refractory differentiated thyroid cancer (DTC). However, toxicities are considerable and require frequent dose interruption and modification. Recently, planned drug holidays, which are dose interruptions in accordance with the timing of severe or intolerable adverse events, have been proposed to avoid severe adverse events due to lenvatinib (Tahara M.ESMO Open 2018). Our retrospective study demonstrated that progression-free survival (PFS) and overall survival (OS) were significantly longer in patients who used planned drug holidays than those who did not (Matsuyama C et.al, 2020 Annual Meeting of the Japan Association of Endocrine Surgeons). Methods: In this prospective observational study, patients with curatively unresectable and progressive RAI-refractory DTC were treated with lenvatinib in a real-world clinical setting. Lenvatinib was administered orally at a dose of 24 mg daily. Dose modification for toxicities were permitted. Primary endpoint was OS, and secondary endpoints were time to treatment failure (TTF), time to failure of strategy (TFS), PFS with clinical progressive disease, response rate, quality of life, safety, and patient reports. This study was registered with UMIN Clinical Trials Registry (UMIN000022243). Results: 262 patients were accrued. Of 255 evaluable, 153 were female; median age was 70 (range 27.0-88.0); histology was papillary thyroid carcinoma/follicular thyroid carcinoma/poorly DTC in 204/45/4; previous therapy was surgery/RAI/molecular targeted drug in 246/164/14; reason for initiation of lenvatinib was disease progression/unsuitable for RAI in 241/4. 1-year OS was 85.6% (95%CI: 80.6-89.4%); 1-year TTF rate was 74.9% (95%CI: 69.1-79.8%); 1-year TFS rate was 80.8% (95%CI: 75.4-85.2%); and 1-year PFS rate was 84.4% (95%CI: 79.3-88.4%). Overall response by RECIST was 3 (1.2%) in CR and 151 (61.9%) in PR. Most common grade 3 or 4 toxicities were hypertension (61.4%), hand foot syndrome (10.2%), fatigue (9.1%), anorexia (8.3%) and diarrhea (4.7%). Grade 5 toxicities occurred in 4 patients (fistula, hypoxia, respiratory failure, trachea stenosis). Of 253 patients evaluable for efficacy, 73 used planned drug holidays. TTF, TFS and PFS were significantly longer in patients who used planned drug holiday than those who did not (Table). Conclusions: Planned drug holiday for lenvatinib demonstrated significantly better clinical outcomes, including TTF, TFS and PFS, than daily oral administration. These data further support use of a planned drug holiday in RAI-refractory DTC patients receiving lenvatinib. Clinical trial information: 000022243. [Table: see text]
Prioritizing the Role of Major Lipoproteins and Subfractions as Risk Factors for Peripheral Artery Disease
Authors: Michael G. Levin, Verena Zuber, Venexia M. Walker, Derek Klarin, Julie Lynch, Rainer Malik, Aaron W. Aday, Leonardo Bottolo, Aruna D. Pradhan, Martin Dichgans, Kyong-Mi Chang, Daniel J. Rader, Philip S. Tsao, Benjamin F. Voight, Dipender Gill, Stephen Burgess, Scott M. Damrauer
Journal: Circulation (2021)

Lipoprotein-related traits have been consistently identified as risk factors for atherosclerotic cardiovascular disease, largely on the basis of studies of coronary artery disease (CAD). The relative contributions of specific lipoproteins to the risk of peripheral artery disease (PAD) have not been well defined. We leveraged large-scale genetic association data to investigate the effects of circulating lipoprotein-related traits on PAD risk. Genome-wide association study summary statistics for circulating lipoprotein-related traits were used in the mendelian randomization bayesian model averaging framework to prioritize the most likely causal major lipoprotein and subfraction risk factors for PAD and CAD. Mendelian randomization was used to estimate the effect of apolipoprotein B (ApoB) lowering on PAD risk using gene regions proxying lipid-lowering drug targets. Genes relevant to prioritized lipoprotein subfractions were identified with transcriptome-wide association studies. ApoB was identified as the most likely causal lipoprotein-related risk factor for both PAD (marginal inclusion probability, 0.86; P=0.003) and CAD (marginal inclusion probability, 0.92; P=0.005). Genetic proxies for ApoB-lowering medications were associated with reduced risk of both PAD (odds ratio,0.87 per 1-SD decrease in ApoB [95% CI, 0.84-0.91]; P=9×10-10) and CAD (odds ratio,0.66 [95% CI, 0.63-0.69]; P=4×10-73), with a stronger predicted effect of ApoB lowering on CAD (ratio of effects, 3.09 [95% CI, 2.29-4.60]; P<1×10-6). Extra-small very-low-density lipoprotein particle concentration was identified as the most likely subfraction associated with PAD risk (marginal inclusion probability, 0.91; P=2.3×10-4), whereas large low-density lipoprotein particle concentration was the most likely subfraction associated with CAD risk (marginal inclusion probability, 0.95; P=0.011). Genes associated with extra-small very-low-density lipoprotein particle and large low-density lipoprotein particle concentration included canonical ApoB pathway components, although gene-specific effects were variable. Lipoprotein(a) was associated with increased risk of PAD independently of ApoB (odds ratio, 1.04 [95% CI, 1.03-1.04]; P=1.0×10-33). ApoB was prioritized as the major lipoprotein fraction causally responsible for both PAD and CAD risk. However, ApoB-lowering drug targets and ApoB-containing lipoprotein subfractions had diverse associations with atherosclerotic cardiovascular disease, and distinct subfraction-associated genes suggest possible differences in the role of lipoproteins in the pathogenesis of PAD and CAD.
Cervical cancer screening: Twelve years experience of the Kazakhstan National Screening program.
Authors: Raikhan Bolatbekova, Dilyara Kaidarova, Alma Zhylkaidarova, Tolkyn Sadykova, Yerlan Kukubassov, Alima Satanova, Askar Aidarov
Journal: Journal of Clinical Oncology (2021)

e17520 Background: Cervical cancer (CC) is the most common gynecological cancer in Kazakhstan (KZ). Standardized incidence rate of CC was 16.7 per 100, 000, while the mortality rate was 5, 9 per 100, 000, in 2020. The National Cervical Screening program in KZ uses cytology (Pap test) from 2008, which is free of charge for women aged 30 to 70 years of age with an interval of 4 years. In 2017 Experts from ImPact Mission and analyzed existing CC screening revealed a number of recommendations aimed at reducing the screening interval and increasing the coverage. The purpose of this study was to analyze results of CC screening in KZ and his impact on CC incidence and mortality. Methods: Coverage, the number of screened women, the level of pre-cancer detection and cervical cancer during screening have been obtained from specific reports (form № 025, № 08) for 2008-2020. Results: The total number of screened women for 2008 were 554 283 women. There is a decrease in screening coverage to 45.9% in 2017 due to a decrease in funding. in this regard, in 2017, a number of changes were made to the existing screening program. In 2020 after the CC screening improvement 786 690 women were examined during the screening program, coverage rate was 66, 2%, . Analysis of screening results showed a marked increase in the detection of precancerous lesion from 0, 136 in 2008 to 0, 87 with an increasing by 37%. The analysis of CC incidence revealed significant changes: after the introduction of screening, an increase in the incidence rate is noted from 15.5 in 2008 to 20.1 per 100, 000 female population in 2015. Since 2015, there has been a significant decrease to 16.7 per 100, 000 women. Conclusions: Despite the positive results of screening, an increse the screening coverage, improvement in the detection of the initial stage of CC, mortality rate from CC and a one-year mortality remain high, which makes it necessary to improve the screening of CC in KZ through the introduction of HPV-screening
Real-world response and outcomes in NSCLC patients with EGFR exon 20 insertion mutations.
Authors: Sai-Hong Ignatius Ou, Huamao Mark Lin, Jin-Liern Hong, Yu Yin, Shu Jin, Jianchang Lin, Minal Mehta, Danny Nguyen, Joel W. Neal
Journal: Journal of Clinical Oncology (2021)

9098 Background: There is currently no targeted therapy approved for patients with EGFR exon 20 insertion mutations (exon20ins) in NSCLC. Real world treatment outcome evidence for this rare population is limited. This study describes treatment patterns and outcomes in US patients with advanced NSCLC with EGFR exon20ins. Methods: The nationwide Flatiron Health electronic health record-derived deidentified database (cut-off 29 Feb 2020) was used to select 4 separate cohorts: (1) first-line (1L): patients receiving 1L therapy after documented exon20ins (1L start date as index date); (2) second or later line (≥2L): patients receiving ≥2L therapy after documented exon20ins (start date of ≥2L as index date); (3) ≥2L trial-aligned: ≥2L patients with baseline characteristics aligned with the key eligibility criteria of mobocertinib Trial NCT02716116 Part 3; and (4) ≥2L post platinum: ≥2L trial-aligned patients previously treated with platinum-based chemotherapy. Real-world endpoints were: confirmed overall response rate (cORR), PFS, and OS. Additional analyses were conducted for patients treated with immune-oncology therapy (IO). Results: Of 237 EGFR exon20ins patients, 129 patients were included in 1L cohort and 114 were in ≥2L cohort, including 63 ≥2L trial-aligned and 50 ≥2L post platinum patients. In 1L patients, EGFR TKI (28.7%) and platinum-based chemotherapy ± IO (56.6%) were the most common 1L regimens. In ≥2L patients, 28.1% received IO monotherapy, 17.5% received EGFR TKI, and 23.7% received platinum-based chemotherapy ± IO as index treatment. In the 1L setting, median PFS (mPFS) was 5.7 months for platinum-based chemotherapy and 4.5 months for IO + platinum-based chemotherapy. In the ≥2L setting, mPFS was 3.7 months for any therapy and 2.3 months for IO monotherapy. Full effectiveness data are provided in the accompanying table. Conclusions: This real world study provided a benchmark on the treatment outcome in patients with advanced NSCLC with EGFR exon20ins. Platinum-based chemotherapy was the most common 1L therapy and provided the longest mPFS. Immunotherapy, either as monotherapy or in combination with chemotherapy, appeared less effective for treatment of NSCLC with EGFR exon20ins. There is an unmet medical need for improved therapeutic options.[Table: see text]
Osimertinib as neoadjuvant treatment for resectable stage II-IIIB EGFR mutant lung adenocarcinoma (NEOS).
Authors: Chao Lyu, Wentao Fang, Haitao Ma, Jia Wang, Wenjie Jiao, Rui Wang, Nan Wu, Shi-Dong Xu, Yue Yang
Journal: Journal of Clinical Oncology (2021)

8524 Background: Neoadjuvant treatment has demonstrated efficacy in several types of cancer and is increasingly used for the treatment of early-stage cancers with the potential of cancer downstaging to enhance complete surgical resection and to improve clinical outcomes. Recent evidences have demonstrated that the neoadjuvant use of first/second-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) may provide clinically meaningful improvement in EGFRm non-small cell lung cancer (NSCLC) patients, however, limited data were reported on osimertinib, the third-generation EGFR-TKI, in the neoadjuvant setting. Here we present an interim analysis of osimertinib as neoadjuvant treatment for resectable EGFRm NSCLC. Methods: NEOS is a prospective, multi-center, single-arm study to evaluate the efficacy and safety of osimertinib as neoadjuvant treatment in resectable EGFRm (19del/L858R) lung adenocarcinoma. Eligible patients were treated with osimertinib 80 mg orally per day for six weeks followed by surgery. Assessment of response to neoadjuvant therapy was performed according to RECIST 1.1. The primary endpoint was response rate. Secondary endpoints included safety, R0 surgical resection rate, quality of life, major pathologic response (MPR) rate, pathological complete response (pCR) rate, and N2 downstaging rate. Results: As of Dec. 17, 2020, 18 eligible patients (median age 61 [range 46-73], 27.8% male, 22.2% ECOG PS 1) have been enrolled. Patients with clinical stages IIa, IIb, and IIIa (8th AJCC) accounted for 16.7%, 22.2% and 61.1%, respectively. Half (9/18) of the patients had EGFR exon 21 L858R mutations and the other half (9/18) had EGFR exon 19del mutations. Amongst all 15 patients who completed efficacy assessment after neoadjuvant osimertinib, the response rate (RR) was 73.3% (11/15) and the disease control rate (DCR) was 100% (15/15). R0 surgical resection was performed in 93.3% (14/15) patients. Pathological downstaging occurred in 53.3% (8/15) patients. 42.9% (3/7) of the patients with confirmed N2 lymph nodes experienced downstaging to N0 disease after receiving neoadjuvant osimertinib. One patient was identified with a pCR. Adverse events (AEs) were reported in 66.7% (12/18) of patients, with the most common AE being rash (8/18, 44.4%), oral ulceration (8/18, 44.4%), and diarrhea (5/18, 27.8%). No grade 3-5 AEs or serious AEs were reported. Conclusions: Interim analysis from this study indicated neoadjuvant osimertinib as an effective and feasible treatment in patients with resectable stage II-IIIB EGFRm NSCLC. The trial is ongoing and the final results will be provided in the future. Clinical trial information: ChiCTR1800016948.
The influence of clinical stage, race, and gender on factors which impact quality of life in multiple myeloma.
Authors: Meghan Luhowy, Katrina Binion, Tiffany Warfield, Rebecca Bosley, Elizabeth Krauss, Ashraf Badros
Journal: Journal of Clinical Oncology (2021)

e24126 Background: Multiple myeloma (MM) is unique among hematologic malignancies as an incurable disease. Patients are affected long-term by the disease symptoms as well as psychological, financial burden, and social impact, which may affect overall quality of life (QOL). The current literature related to QOL in MM is largely limited to a single clinical stage, impact concurrent with a specific treatment regimen, or focused on a single QOL factor. Changes in impact on QOL based on longitudinal follow up during the disease course have not been readily assessed. Here, we evaluated patient-reported QOL measures utilized by one time validated questionnaires. Methods: The study enrolled 100 participants in a sequential manner from the Myeloma Clinic at UMGCC with a diagnosis of plasma cell disorders at various stages: MGUS, smoldering myeloma, or multiple myeloma: newly diagnosed, maintenance, relapsed. Participants provided verbal responses to a series of questions listed in Table. Questions aligned with three main domains: physical symptoms and function, mental health, and social systems. The following is an interim analysis of the first 50 patients. Results: This sample of myeloma patients (N=50; males n=26), felt their QOL was impacted by myeloma symptoms (70%). More African American participants reported impact from financial burden (6, 50%) in comparison to Caucasian and other races (10, 26%). Interestingly, males reported less impact on sexual intimacy (3, 15%) than females (6, 43%). Females also reported more impact from financial burden (10, 42%) compared to males (6, 23%). Conclusions: Changes to impact on QOL as a function of clinical MM stage, race, and/or gender will be fully evaluated. Planned analyses include correlation statistics by age and social demographics to determine patterns in patient-reported outcomes. Finally, second interviews with current participants will be conducted to determine changes to impact across the same QOL variables over time.[Table: see text]
Nivolumab plus cabozantinib (N+C) versus sunitinib (S) for advanced renal cell carcinoma (aRCC): Outcomes by baseline disease characteristics in the phase 3 CheckMate 9ER trial.
Authors: Andrea B. Apolo, Thomas Powles, Mauricio Burotto, Maria Teresa Bourlon, James J Hsieh, Umberto Basso, Amishi Yogesh Shah, Cristina Suarez, Camillo Porta, Carlos H. Barrios, Howard Gurney, Elizabeth R Kessler, Margitta Retz, Saby George, Bernard Escudier, Joshua Zhang, Burcin Simsek, Christian Scheffold, Robert J. Motzer, Toni K. Choueiri
Journal: Journal of Clinical Oncology (2021)

4553 Background: First-line N+C significantly improved progression-free survival (PFS), overall survival (OS), and objective response rate (ORR) vs S in aRCC patients (pts) in the phase 3 CheckMate 9ER trial, leading to FDA approval of N+C in this setting. A deeper understanding of how baseline disease characteristics may impact clinical outcomes with N+C vs S may inform clinical decision making. Methods: Pts with clear cell aRCC were randomized to N 240 mg IV Q2W + C 40 mg PO QD vs S 50 mg PO QD (4 weeks of 6-week cycles). In this post hoc exploratory analysis, PFS, OS, and ORR were evaluated across pt subgroups defined by baseline IMDC risk status, organ sites of metastases (mets), number of organs with any lesions, or target lesion size. Consistent with primary/secondary efficacy endpoints in ITT pts, PFS and ORR were evaluated per RECIST v1.1 by blinded independent central review in subgroups. Results: Median follow-up in ITT pts was 23.5 months. PFS, OS, and ORR (including complete response [CR]) outcomes are summarized in the table across subgroups: IMDC risk (favorable [FAV], intermediate [I], poor [P]); number of organs with ≥ 1 target/nontarget lesion (T/NT; 1 and ≥ 2); sum of diameters of target lesions (sDTL; &lt; and ≥ median [72.1 mm]), and in pts with liver, bone, or lung mets. The PFS HR favored N+C vs S and median (m) PFS was longer with N+C vs S across all subgroups. The OS HR also favored N+C vs S across most subgroups. ORR ranged from 38%–66% (N+C) vs 10%–44% (S) across subgroups, and CR benefits were seen with N+C in most subgroups. Additional outcomes including landmark OS and response details in subgroups will be reported. Conclusions: Consistent with outcomes in ITT pts, efficacy benefits with N+C vs S were observed regardless of IMDC risk status, organ site of mets, or extent of tumor burden at baseline. These results support N+C as a new first-line treatment option for pts with aRCC. Clinical trial information: NCT03141177. [Table: see text]
Association of Cardiovascular Disease Risk Factors with Late Cardiotoxicity and Survival in HER2-positive Breast Cancer Survivors
Authors: Xuexin He, Jiali Ji, Xiaolan Dai, Aiham Z. Qdaisat, Francisco J. Esteva, Gabriel N. Hortobagyi, Sai-Ching J. Yeung
Journal: Clinical Cancer Research (2021)

Abstract Purpose: Breast cancer and cardiovascular (CV) diseases often share the same risk factors. It is increasingly important to identify risk factors for CV events in patients with high-risk breast cancer and explore optimal treatment regimens. Experimental Design: Early HER2-positive breast cancer patients at our institution between January 1998 and October 2009 were reviewed. Primary outcome was late-severe-CV-event-free survival, and late severe CV events were defined as cardiovascular death, cardiomyopathy, symptomatic heart failure, and myocardial infarction developing 2+ years after breast cancer diagnosis. Kaplan–Meier plots, Cox proportional hazard regressions, and restricted mean survival time were used to evaluate outcomes. Results: We identified 2,448 consecutive eligible patients with a median follow-up time of 111.0 months (interquartile range, 52.0–151.8 months). One hundred and thirty-six patients had late severe CV events and 752 died of any cause [533 (70.9%) died of primary breast cancer; 12 (1.6%) died of cardiovascular disease]. Hypertension [HR, 1.546; 95% confidence interval (95% CI), 1.030–2.320; P = 0.036] and history of coronary artery disease (CAD; HR, 3.333; 95% CI, 1.669–6.656; P &amp;lt; 0.001) were associated with worse late-severe-CV-event-free survival. Anthracycline-containing regimens (HR, 1.536; 95% CI, 0.979–2.411; P = 0.062) was not a significant risk factor for CV events in multivariate analysis. Regimens containing both anthracycline and anti-HER2 therapy were prognostic for better OS (HR, 0.515; 95% CI, 0.412–0.643; P &amp;lt; 0.001). Conclusions: Hypertension and CAD history were independent prognostic factors for late severe CV events. Adding anti-HER2 agents to anthracycline-containing regimens did not substantially increase the risk for late severe cardiotoxicity and conferred better overall survival.
A network analysis approach to the needs of oncological patients.
Authors: Alessandro Rossi, Maria Marconi, Stefania Mannarini, India Minelli, Claudio Verusio
Journal: Journal of Clinical Oncology (2021)

e24128 Background: In recent years, an ever greater importance is given to the needs of cancer patients which could impact medical treatments, adherence and compliance, and patients’ quality of life (Teo et al. 2019; NCCN, 2015). However, recognizing and addressing the needs of patients may not be enough. Indeed, on one hand, needs that clinicians might consider as 'important' could play a marginal role, and – on the other hand – needs that clinicians may perceive as 'unimportant' may be central for patients. An innovative approach – psychometric network analysis (PNA; Epskamp, 2017) – was used to assess the network among needs ( nodes). Notably, the more a central node (need) is modified (addressed), the more a cascade change will occur in all the other nodes (needs). This study aimed to evaluate: (A) the structure of relationships among needs ( edges) of cancer patients, (B) which needs ( nodes) are the most relevant ( central), and (C) play a key role in the network. Methods: Patients ( n = 511; mean age = 65.95, SD = 12.72; 280 males) were enrolled at the Oncology Day Hospital at the “Presidio Ospedaliero” of Saronno, ASST Valle Olona, Italy. Patients were tested with the Need Evaluation Questionnaire (NEQ) which is composed of 23 items that investigate as many needs – divided into 4 areas: (1) information about diagnosis/prognosis, (2) information about exams and treatment, (3) communicative, and (4) relational needs. Results: Preliminary analysis revealed that all of the items were informative (SD item &lt; 2.5SD all_itemsSD ) and there was no redundancy between items (redundancy index &lt; 0.25). An Ising model (5,000 nonparametric bootstraps) with LASSO regularized nodewise logistic regression was performed. PNA showed a high accuracy: CS-coefficient = 0.56. On one hand, PNA showed that item#2 ( “I need more information about my future condition”; z = 2.039), item#17 ( “I need to speak with a psychologist”; z = 1.209), and item#13 ( “I need to be reassured more by the doctors”; z = 1.201) were the strongest (central) nodes. On the other hand, item#14 ( “ I need the hospital to provide better services”; z = -2.261) was the weakest node in the network. Conclusions: These findings show useful implications for clinical practice. Clinical interventions should address the needs showing the strongest connections in the network. These central nodes can influence all the other connected needs, thus representing important needs to be targeted by clinicians – allowing to tailoring more targeted and efficient therapeutic approaches to meet patients’ needs, with beneficial effects for medical treatments and quality of life.