tbuckley/cabot-search huggingface dataset:
Efficacy and safety analysis of anlotinib combined with etoposide plus cisplatin/carboplatin as first-line therapy for extensive-stage small cell lung cancer (SCLC): The final results from a phase II single-arm trial.
Authors: Tiandong Kong, Lu Chen, Fangfang Duan, Xiaoxia Hou, Liuyan Wang, Hanli Zhou, Lanrong Wang, Shanshan Hu, Danna Liu
Journal: Journal of Clinical Oncology (2021)

8560 Background: In recent years, the therapeutic regimens of extensive-stage small cell lung cancer (ES-SCLC) have progressed a lot. The most significant clinical studies include IMpower133 and CASPIAN. However, the relevant results showed that the combination of PD-L1 monoclonal antibody and EC regimen chemotherapy as first-line treatment of small cell lung cancer have a median PFS (progession-free survival) of about 5 months, which is comparable to that of simple chemotherapy. Therefore, the EP/EC is still the standard treatment for extensive-stage small cell lung cancer. Meanwhile, we noticed that anlotinib (multi-target small molecule oral VEGF inhibitor) has a curative effect on patients with extensive-stage SCLC as a third-line or above treatment in the ALTER 1202 study in China. Therefore, we tried to add anlotinib to the first-line treatment with EP/EC regimen in patients with ES-SCLC to observe the efficacy and safety. Methods: Eligible ES-SCLC pts (18̃75 years old, initial treatment, no obvious heart, liver and kidney dysfunction) were received anlotinib (12mg QD from day 1 to 14 of a 21-day cycle) + etoposide(100mg/m 2 , d1̃3 of a 21-day cycle)+CBP (AUC = 4̃5,d1,Q3W) or DDP (70̃75mg/m 2 , d1,Q3W) for 4̃6 cycles, then anlotinib maintenance (12mg QD from day 1 to 14 of a 21-day cycle) until the disease progresses or intolerable adverse reactions occur. During the treatment, dose reduction of anlotinib was permitted, which could be reduced to 10mg or 8mg if it was intolerable. The main observation endpoints were ORR, PFS and adverse events. Results: Between January 2019 and August 2020, a total of 20 patients with extensive-stage SCLC were enrolled in the study, with an average age of 66.2 ± 8.1(45-75) years old, 17 males (85%) and 3 females (15%). The median PFS was 10 months (95% CI: 7.809-12.191), median OS was 15 months (95%CI:10.639-19.361), ORR (objective remission rate) was 90% and DCR (disease control rate) was 100%. The most common grade 3 or 4 adverse events related to the trial regimen included: neutropenia was 10/20 (50.0%), thrombocytopenia was 5/20 (25.0%), anemia, nausea and fatigue were all 2/20 (10%), hypertension, transaminase elevation and hoarseness were all 1/20 (5%). Conclusions: Anlotinib combined with EP/EC regimen has better PFS, OS, ORR and DCR for the initial treatment of extensive-stage SCLC, and a manageable safety profile. A randomized, controlled phase III clinical study will be conducted to confirm this conclusion. Clinical trial information: ChiCTR2000035043.
Breast cancer ER, PR, and HER2 expression variance by germline cancer predisposition genes.
Authors: Grace Wei, Marilin Rosa, Maxine Chang, Brian J. Czerniecki, Xia Wang
Journal: Journal of Clinical Oncology (2021)

10526 Background: The association between breast cancer characteristics and survival with estrogen receptor (ER) and progesterone receptor (PR) expression has been primarily studied via binomial categories, ER-positive and ER-negative. In order to better characterize germline genetic influences on these markers, we investigated their IHC expression semi-quantitatively in cancer predisposition germline pathogenic variant (PV) carriers of the following genes: BRCA1, BRCA2, PALB2, TP53, PTEN, CDH1, ATM, CHEK2, and Lynch syndrome genes. The HER2 expression was also analyzed. Methods: We conducted a retrospective chart review of patients with germline panel genetic testing for cancer predisposition genes at Moffitt Cancer Center’s GeneHome clinic. Inclusion criteria included 1) women ≥18 years old, 2) breast cancer diagnosis, 3) cancer predisposition germline panel genetic test results, 4) available ER and PR expression levels, and 5) available HER expression and/or amplification status. ER, PR, and HER2 status were compared between PV carriers and non-PV carriers via Mann-Whitney U at p&gt;0.05. Results: A total of 847 cases were reviewed for the study. Among 658 patients with a breast cancer diagnosis and complete ER PR data, 365 cases (55.5%) were non-PV carriers and 293 cases (44.5%) carried a PV in at least one of the genes listed above. Among 635 cases with available HER2 expression/amplification status, 355 (55.9%) cases were non-PV carriers and 288 (45.4%) cases were PV-carriers. When compared with non-PV carrier controls, BRCA1 PV carriers’ breast tumors had significantly lower ER and/or PR expression. Further, BRCA2 and TP53 PV tumors also displayed moderately lower ER expression. Contrarily, CHEK2 tumors displayed higher ER and PR expression compared to controls. Further, BRCA1 and BRCA2 PV carriers were more likely to have HER2- breast cancers. Conclusions: Differences in ER, PR, HER2 expression levels were observed in germline PV carrier breast cancers, signaling differential impacts by germline PVs on the tumor evolution process. It is likely that tumor differences in PV carriers influence responses to therapies, including hormone therapy, anti-HER2 therapy, and subsequent survival.[Table: see text]
Gender, Race, Ethnicity, and Sexual Orientation of Editors at Leading Medical and Scientific Journals
Authors: James W. Salazar, Jennifer D. Claytor, Anand R. Habib, Vinay Guduguntla, Rita F. Redberg
Journal: JAMA Internal Medicine (2021)

multivariable model included variables reaching a significance level of P < .10 on univariable analysis.Results | Since the start of the COVID-19 outbreak, a weighted 36.7% of enrollees reported feeling less socially connected with friends and family.Decreased social connection was reported by 41.2% of female, 31.2% of male, 24.6% of Black non-Hispanic, and 38.9% of White non-Hispanic beneficiaries (Table 1).On multivariable analysis (Table 2), demographic characteristics that were independently associated with feeling less socially connected included female (PP, 40.4%; 95% CI, 38.6%-42.2%)vs male sex (PP, 33.2%; 95% CI, 31.2%-35.1%;P < .001),White non-Hispanic (PP, 38.1%; 95% CI, 36.6%-39.7%)vs Black non-Hispanic race/ethnicity (PP, 30.4%; 95% CI, 25.9%-34.9%;P < .001),income of $25 000 or greater (PP, 38.5%; 95% CI, 36.8%-40.1%)vs less than $25 000 (PP, 34.2%; 95% CI, 31.4%-37.1%;P = .02),no Medicaid eligibility (PP, 38.1%; 95% CI, 36.5%-39.6%)vs full Medicaid dual eligibility (PP, 28.6%; 95% CI, 23.5%-33.7%;P = .002),history of non-skin cancer (PP, 40.8%; 95% CI, 38.0%-43.6%)vs none (PP, 36.3%;95% CI, 34.9%-37.7%;P = .005),and depression (PP, 41.6%; 95% CI, 39.0%-44.3%)vs none (PP, 35.5%; 95% CI, 33.9%-37.1%;P < .001).Behaviors that were associated with feeling less socially connected included performing all 6 assessed anti-COVID-19 social distancing measures (PP, 38.8%; 95% CI, 37.4%-40.2%)vs 4 or fewer (PP, 30.5%; 95% CI, 26.2%-34.8%;P < .001),computer ownership (PP, 38.4%; 95% CI, 36.6%-40.2%)vs not (PP, 34.4%; 95% CI, 32.2%-36.6%;P = .01),and use of internet teleconferencing software (PP, 40.2%; 95% CI, 38.5%-42.0%)vs not (PP, 33.3%; 95% CI, 31.1%-35.5%;P < .001).Among other variables, metropolitan (PP, 37.6%; 95% CI, 36.1%-39.1%)vs nonmetropolitan residence (PP, 35.9%; 95% CI, 33.3%-38.5%;P = .23)and geographic region were not independently associated with reported social connectivity.Discussion | More than one-third of Medicare beneficiaries reported feeling less socially connected to friends and family since the start of the COVID-19 pandemic.Medicare beneficiaries who were women, had higher incomes, were not of Black non-Hispanic race/ethnicity, and had a history of cancer or depression were more likely to report a negative association of the pandemic with perceptions of social connectedness.The likelihood of reporting decreased social connection was widespread nationally and was associated with practicing more social distancing measures.The limitations of this study include an inability to assess the magnitude of the decreased connection reported and survey exclusion of the subset of Medicare-beneficiaries who are not community dwelling.The public health benefits and psychosocial costs of prolonged social distancing measures should be balanced carefully in this doubly vulnerable population.
Performance characteristics of brief family history questionnaire to screen for Lynch syndrome in women with newly diagnosed ovarian cancers.
Authors: Rachel Soyoun Kim, Alicia Tone, Raymond Kim, Matthew Cesari, Blaise Clarke, Lua Ruhiyyih Eiriksson, Hart Tae, Alice Lytwyn, Manjula Maganti, Steven Gallinger, Marcus Bernardini, Amit M. Oza, Bojana Djordjevic, Jordan Lerner-Ellis, Emily Van de Laar, Danielle Vicus, Trevor J. Pugh, Aaron Pollett, Sarah E. Ferguson
Journal: Journal of Clinical Oncology (2021)

e22525 Background: Ovarian cancer (OC) is the third most common Lynch syndrome (LS)-associated cancer in women but there is no established screening strategy to identify LS in this population. An adequate family history may identify patients suspected of LS, prompting a referral to genetic assessment. We have previously validated the 4-item brief Family History Questionnaire (bFHQ) in endometrial cancers. The objective of this study was to assess whether bFHQ can be used as a screening tool to identify women with OC at risk of LS. Methods: Prospective cohort study recruited women with newly diagnosed non-serous/non-mucinous OC from three cancer centers in Ontario, Canada. Participants completed bHFQ, extended Family History Questionnaire (eFHQ; encompassing Amsterdam II criteria, Society of Gynecologic Oncology 20-25% criteria and Ontario Ministry of Health criteria), immunohistochemistry (IHC) for mismatch repair (MMR) proteins and universal germline testing for LS. The performance characteristics were compared between bFHQ, eFHQ, and IHC. Results: Of 215 participants, 169 (79%) were evaluable with both bFHQ and germline mutation status; 12 of these 169 were confirmed to have LS (7%). Nine of 12 patients (75%) with LS were correctly identified by bFHQ, compared to 6 of 11 (55%) by eFHQ and 11 of 13 (85%) by IHC. The sensitivity, specificity, positive predictive values and negative predictive values of bFHQ were 75%, 66%, 15% and 98%, compared to 55%, 92%, 35% and 96% for eFHQ and 85%, 90%, 39% and 99% for IHC respectively. IHC was the most sensitive and specific approach. The 4-item bFHQ was more sensitive than eFHQ and took less than 10 minutes for each patient to complete. Conclusions: Patient-administered bFHQ may serve as an adequate screening tool to triage women with OC for further genetic assessment for LS, especially in centers without access to universal tumor testing for IHC for MMR.[Table: see text]
Activity of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKIs) in patients (pts) with NSCLC with uncommon <i>EGFR</i> mutations: A real-world cohort study (UpSwinG).
Authors: Satoru Miura, Te-Chun Hsia, Jen-Yu Hung, Hyun Ae Jung, Jin-Yuan Shih, Cheol-Kyu Park, Seung Hyeun Lee, Tatsuro Okamoto, Hee Kyung Ahn, Yong Chul Lee, Yuki Sato, Sung Sook Lee, Celine Mascaux, Hasan Daoud, Angela Maerten, Sanjay Popat
Journal: Journal of Clinical Oncology (2021)

9072 Background: EGFR TKIs are an established treatment (tx) option for pts with EGFR mutation-positive NSCLC with common mutations (Del19 or L858R); however, 7–23% of NSCLC tumors harbor uncommon EGFR mutations, where EGFR TKI efficacy is less established. These mutations are highly heterogeneous, and developments in detection by NGS are helping to identify mutations with little or no clinical data. Methods: In this non-interventional, global, multi-center study (NCT04179890), existing medical or electronic health records were identified for consecutive EGFR TKI-naïve pts with uncommon EGFR mutations (T790M, ex20ins, major uncommon [G719X, L861Q or S768I], ‘other’ or compound mutations) treated with erlotinib, gefitinib, afatinib, osimertinib or other systemic therapy. Endpoints were time to tx failure (TTF), ORR, OS and duration of response (DoR). Results: Overall, 246 pts (median age: 69.5 yrs; Asian: 84%; brain metastases: 8%; ECOG PS ≥2: 16%) were recruited from 9 countries. Most pts (n=226; 92%) received an EGFR TKI as 1st-line therapy; 132 (54%), 105 (43%) and 7 (3%) received afatinib, 1st-gen TKIs and osimertinib, respectively. 57% of pts received &gt;1 line of therapy. Most pts (73%) had a major uncommon mutation, 9% had other mutations and 33% had a compound mutation; these were detected using PCR (75%) or sequencing (25%), mainly based on tissue biopsy (86%). Pathology reports varied in quality, often lacking detail on specific mutations e.g. 21% of ex18 and 72% of ex20ins were undefined. Median TTF and OS with EGFR TKIs were 9.9 and 24.4 mos; ORR was 42%. In pts treated with 1st-line chemotherapy (n=20), median TTF and ORR were 6.6 mos and 41%. Outcomes were most favorable in major uncommon and compound mutations (Table). TTF appeared to be higher with afatinib vs 1st-gen EGFR TKIs. In most mutation categories, median OS was &gt;2 yrs, possibly reflecting high subsequent therapy uptake. Conclusions: In a real-world setting, EGFR TKIs were the preferred tx option in pts with uncommon EGFR mutations; strongest outcomes were seen in major uncommon and compound mutations, and in pts treated with afatinib. Data were in line with recent analyses of afatinib in uncommon mutations. Tx with an EGFR TKI should be considered as standard for most pts with uncommon mutations. Optimal tx for pts with uncommon mutations requires improvements in pathology reports, with more emphasis on NGS methodology and precise definition of mutations. Clinical trial information: NCT04179890. [Table: see text]
COVID-19–Related Lung Parenchymal Uptake on 18F-PSMA-1007 PET/CT
Authors: Ayah A. Nawwar, Julie Searle, Jes S. Green, Iain D. Lyburn
Journal: Clinical Nuclear Medicine (2021)

A 70-year-old man with newly diagnosed prostate cancer underwent 18F-PSMA-1007 PET/CT for staging. PSMA-avid primary prostatic malignancy was identified. Incidental intense patchy peripheral lung uptake was also noted. The patient tested positive for COVID-19 infection.
Effect of sacubitril/valsartan vs. enalapril on changes in heart failure therapies over time: the <scp>PARADIGM‐HF</scp> trial
Authors: Ankeet S. Bhatt, Muthiah Vaduganathan, Brian L. Claggett, Jiankang Liu, Milton Packer, Akshay S. Desai, Martin P. Lefkowitz, Jean L. Rouleau, Victor C. Shi, Michael R. Zile, Karl Swedberg, Orly Vardeny, John J.V. McMurray, Scott D. Solomon
Journal: European Journal of Heart Failure (2021)

Sacubitril/valsartan improves morbidity and mortality in patients with heart failure and reduced ejection fraction (HFrEF). Whether initiation of sacubitril/valsartan limits the use and dosing of other elements of guideline-directed medical therapy for HFrEF is unknown. We examined the effects of sacubitril/valsartan, compared with enalapril, on β-blocker and mineralocorticoid receptor antagonist (MRA) use and dosing in a large randomized clinical trial.Patients with full data on medication use were included. We examined β-blocker and MRA use in patients randomized to sacubitril/valsartan vs. enalapril through 12-month follow-up. New initiations and discontinuations of β-blocker and MRA were compared between treatment groups. Overall, 8398 (99.9%) had full medication and dose data at baseline. Baseline use of β-blocker and MRA at any dose was 87% and 56%, respectively. Mean doses of β-blocker and MRA were similar between treatment groups at baseline and at 6-month and 12-month follow-up. New initiations through 12-month follow-up were infrequent and similar in the sacubitril/valsartan and enalapril groups for β-blockers [37 (9.0%) vs. 42 (10.2%), P = 0.56] and MRA [127 (7.6%) vs. 143 (9.2%), P = 0.10]. Among patients on MRA therapy at baseline, there were fewer MRA discontinuations in patients on sacubitril/valsartan as compared with enalapril at 12 months [125 (6.2%) vs. 187 (9.0%), P = 0.001]. Discontinuations of β-blockers were not significantly different between groups in follow-up (2.2% vs. 2.6%, P = 0.26).Initiation of sacubitril/valsartan, even when titrated to target dose, did not appear to lead to greater discontinuation or dose down-titration of other key guideline-directed medical therapies, and was associated with fewer discontinuations of MRA. Use of sacubitril/valsartan (when compared with enalapril) may promote sustained MRA use in follow-up.
Predictors of survival after metastasectomy of oligometastatic recurrence following gastroesophageal cancer treatment.
Authors: Malcolm MacKenzie, Lucy Xiaolu Ma, Osvaldo Epsin-Garcia, Chihiro Suzuki, Yvonne Bach, Michael J Allen, Gail Elizabeth Darling, Carol Jane Swallow, Savtaj Singh Brar, Jonathan Yeung, Sangeetha Kalimuthu, Rebecca Wong, Elan David Panov, Patrick Veit-Haibach, Eric Xueyu Chen, Elena Elimova, Raymond Woo-Jun Jang
Journal: Journal of Clinical Oncology (2021)

e16060 Background: Recurrent gastroesophageal (GE) carcinomas carry a poor prognosis and are usually treated with palliative chemotherapy (CTX). However, recent studies suggest that certain patients with oligometastatic recurrence can have long term survival after metastasectomy. Appropriate patient selection for metastasectomy remains a challenge, as few predictors of overall survival (OS) after metastasectomy have been identified. Our primary aim was to identify predictors of OS following metastasectomy in GE cancers. Methods: We conducted a retrospective study of GE cancer patients treated from 2007 to 2015 using the Princess Margaret Hospital Cancer Registry. We included patients who underwent curative-intent surgery or definitive chemoradiation (CRT) for localized GE cancer who then had single organ recurrence treated with metastasectomy. The probability of OS from date of recurrence was estimated with the Kaplan Meier method. Predictors of OS after metastasectomy for isolated recurrence were determined using Cox proportional hazards analysis. Covariates included time to recurrence (interval from curative-intent surgery or completion of definitive CRT), site of recurrence (lung/non-lung), sex, age and race (Asian/Non-Asian). Within the multivariable model, predictors with a p-value less than 0.05 were deemed significant. Results: Of 44 patients, median age was 58 years (28-78), and 59% were male. Primary sites were: esophagus 25%, GE junction 41% and gastric 34%. Treatment of the primary was: surgery alone 13%, surgery and (neo)adjuvant CTX 76%, and CRT 11%. Recurrent sites were brain 22%, ovary 20%, lung 18%, bone 7%, adrenals 7%, liver 7%, distant lymph node 6%, and other 13%. The median follow up time was 38.9 months. The 1, 3 and 5-year (yr) OS following metastasectomy were 79% (95% CI 68-92%), 40% (27-58%) and 28% (16-49%). Univariable analysis revealed that time to recurrence greater than 1 yr (HR=0.45 95% CI 0.21-0.93, p=0.032) and lung site recurrence (HR=0.16 95% CI 0.04-0.67, p=0.012) were associated with longer OS. On multivariable analysis, only lung site recurrence was significant (HR=0.12 95% CI 0.03-0.54, p=0.0056). The 1, 3 and 5-yr OS for patients after resection of isolated lung recurrence were 100% (95% CI 100-100%), 86% (63-100%) and 69% (40-100%). Conclusions: In our study, patients with isolated pulmonary recurrences demonstrated prolonged overall survival following metastasectomy. These patients could be considered for resection following recurrence of GE cancer. [Table: see text]
Correction to: FLT3 inhibitor lestaurtinib plus chemotherapy for newly diagnosed KMT2A-rearranged infant acute lymphoblastic leukemia: Children’s Oncology Group trial AALL0631
Authors: Patrick A. Brown, John A. Kairalla, Joanne M. Hilden, ZoAnn E. Dreyer, Andrew J. Carroll, Nyla A. Heerema, Cindy Wang, Meenakshi Devidas, Lia Gore, Wanda L. Salzer, Naomi J. Winick, William L. Carroll, Elizabeth A. Raetz, Michael J. Borowitz, Donald Small, Mignon L. Loh, Stephen P. Hunger
Journal: Leukemia (2021)
Outcome of patients with an ultralow risk 70-gene signature in the MINDACT trial.
Authors: Josephine Lopes Cardozo, Caroline Drukker, Marjanka Schmidt, Laura van 't Veer, Annuska Glas, Anke Witteveen, Fatima Cardoso, Martine J. Piccart-Gebhart, Coralie Poncet, Emiel J. Rutgers
Journal: Journal of Clinical Oncology (2021)

500 Background: Gene signatures have proven successful in identifying patients with a low risk of distant recurrence who could forego chemotherapy (CT) and are currently included in international treatment guidelines for breast cancer. For the 70-gene signature (MammaPrint) an additional threshold was established within the low risk category to identify patients with an ultralow risk of distant recurrence. In independent cohorts, these patients had excellent breast cancer specific survival at 15 years, suggesting that ultralow risk cancers represent indolent disease (Esserman, JAMA Oncol 2017, Delahaye, BC Res Treat 2017). Here we evaluate survival of patients with an ultralow risk 70-gene signature who participated in the randomized phase 3 MINDACT trial (Piccart, Lancet Oncol 2021). Methods: Of the 6,693 patients enrolled in the MINDACT trial (EORTC 10041/BIG 3-04) between 2007-2011, profiling revealed an ultralow risk 70-gene signature in 1,000 patients (15%). We assessed 5- and 8-year distant metastasis free interval (DMFI) and breast cancer specific survival (BCSS) in patients stratified by 70-gene signature result (high, low, ultralow), and within the ultralow risk group stratified by clinical risk. For these exploratory analyses, we used Kaplan-Meier estimates for time to event endpoints and Cox-regression models to calculate hazard ratio’s (HR). Results: Median follow-up was 8.7 years. Among the ultralow risk patients (n = 1,000), 67% were ≥50 years, 81% had tumors &lt; 2cm, 80% were lymph node negative, 96% had grade 1 or 2 tumors and 99% were ER-positive. Systemic therapy was received by 83% of patients (69% endocrine therapy (ET), 14% ET + CT) and 16% received no adjuvant systemic treatment (AST). Survival estimates for all endpoints are shown in the table; 8-year DMFI was 97.0% (95% CI 95.8-98.1) for ultralow risk. The 8-year DMFI in ultralow risk patients who received no AST or ET only was 97.8% (95% CI 95.3-100) and 97.4% (95% CI 96.1-98.7), respectively. The HR for DMFI was 0.66 (95% CI 0.46-0.95) for ultralow vs low risk, after adjusting for tumor and treatment characteristics (preliminary results). Conclusions: In this prospective study, patients with an ultralow risk 70-gene signature have an excellent prognosis with 8-year BCSS above 99% regardless of clinical risk status, and with an 8-year DMFI of 95-98%.[Table: see text]