ABSTRACT
Background: Neoadjuvant chemo-immunotherapy (CheckMate 816 regimen) has become a standard of care in treatment of resectable non-small cell lung cancer (NSCLC) patients in some countries. Addition of radiation therapy (RT) may further improve local control in locally advanced NSCLC patients. Here, we report the primary endpoint, major pathologic response (MPR), of the SQUAT trial (WJOG 12119L, JapicCTI- 195069)-a multicenter, prospective, single-arm, phase II trial of neoadjuvant concurrent chemo-immuno-radiation therapy followed by surgical resection and adjuvant immunotherapy for resectable stage IIIA-B N2 NSCLC. Method(s): Patients with resectable stage IIIA-B N2 NSCLC received concurrent chemoradiotherapy [weekly paclitaxel (40 mg/m2)/carboplatin (AUC 2) for 5 weeks plus involved-field RT 50 Gy] and immunotherapy [durvalumab (1500 mg) Q4W for 2 cycles] followed by surgical resection and adjuvant immunotherapy (durvalumab for up to 1 year). The primary endpoint was MPR rate according to an independent central review (ICR). We assumed the threshold of the MPR rate to be 40% and the expected rate to be 65% with a significance level alpha=0.05 (one-sided) and power 0.8. The sample size was 31 patients, including the 10% ineligible patients. Result(s): Between Jan 2020 and Feb 2022, 31 patients were enrolled from 10 institutions in Japan. Thirty-one patients were evaluated for safety, and 30 patients for efficacy. Of 30 patients (median age, 64 years), 70% and 63% had clinical stage IIIA and non-squamous histology, respectively. The MPR and pathological complete response (pCR) rates by ICR were 63% (90% CI, 47-78, 95% CI, 44-80) and 20% (95% CI, 8-39), respectively. Complete resection was not performed due to adverse events (2 pts) and disease progression (3 pts). Among 25 patients who received complete resection, the MPR and pCR rates were 76% (95% CI, 55-91) and 24% (95% CI, 9-45), respectively. No 30-day postoperative mortality was reported. Conclusion(s): The primary endpoint of MPR rate was met in SQUAT trial. This result suggests that this treatment strategy is promising for resectable stage IIIA-B N2 NSCLC. Clinical trial identification: JapicCTI-195069. Legal entity responsible for the study: WJOG (West Japan Oncology Group). Funding(s): AstraZeneca. Disclosure: T. Miyoshi: Financial Interests, Institutional, Research Grant: AstraZeneca. A. Hamada: Financial Interests, Personal, Invited Speaker: AstraZeneca, Chugai, Ono Pharmaceuticals;Financial Interests, Personal, Advisory Board: AstraZeneca;Financial Interests, Institutional, Research Grant: AstraZeneca. J. Soh: Financial Interests, Personal, Invited Speaker: Ethicon, Covidien, Intutive;Financial Interests, Institutional, Research Grant: AstraZeneca. A. Hata: Financial Interests, Institutional, Research Grant: MSD, Eli Lilly, Boehringer Ingelheim, AstraZeneca;Financial Interests, Personal, Invited Speaker: Eli Lilly, Chugai, Pfizer, AstraZeneca, Boehringer Ingelheim. Y. Yatabe: Financial Interests, Personal, Invited Speaker: MSD, Chugai-pharma, AstraZeneca, Pfizer, Thermo Fisher Science, ArcherDx, Novartis, Elli-Lily, Daiichi Sankyo, Jansen-Pharma, Amgen;Financial Interests, Institutional, Research Grant: Thermo Fisher Science, ArcherDx, AstraZeneca. J. Suzuki: Financial Interests, Institutional, Research Grant: AstraZeneca. M. Tsuboi: Financial Interests, Personal, Invited Speaker, Lecture: Johnson & Johnson Japan;Financial Interests, Personal, Advisory Board, Lectures, Advisory boards: AstraZeneca KK, Chugai Pharmaceutical Co.,Ltd, MSD;Financial Interests, Personal, Invited Speaker, Lectures: Eli Lilly Japan, Bristol Myers Squibb KK, Teijin Pharma, Taiho Pharma, Medtronic Japan, ONO Pharmaceutical Co.,Ltd;Financial Interests, Personal, Advisory Board, Advisory boards: Novartis;Financial Interests, Personal, Invited Speaker: Daiichi Sankyo company limited, MSD, AstraZeneca, Novartis;Financial Interests, Institutional, Research Grant: Beohringer-Ingelheim Japan, MSD, AstraZeneca KK, Ono Pharmaceutical Co.,Ltd, Bristol Myers Squibb KK, Novartis;Financial Interests, Institutional, Invited Speaker: Eli Lilly Japan. H. Horinouchi: Financial Interests, Personal, Invited Speaker: AstraZeneca, Eli Lilly, BMS/ONO, Merck Sharp & Dohme, Roche/Chugai, Novartis, Pfizer, Boehringer Ingelheim, Kyowa-Kirin, Nihon Kayaku, AbbVie, Roche/Chugai;Financial Interests, Personal, Advisory Board: AstraZeneca, Eli Lilly, BMS/ONO, Merck Sharp & Dohme, Roche/Chugai, Amgen, Nihon Kayaku;Financial Interests, Institutional, Research Grant: Roche/Chugai, Merck Sharp & Dohme, Daiichi Sankyo, ONO pharmaceutical, AstraZeneca;Financial Interests, Institutional, Invited Speaker: AbbVie. I. Yoshino: Financial Interests, Institutional, Research Grant: AstraZeneca. T. Masayuki: Financial Interests, Institutional, Research Grant: AstraZeneca. S. Toyooka: Financial Interests, Personal, Invited Speaker: Chugai, Taiho, Ono Pharmaceuticals, Kyorin, Daiichi Sankyo, Medtronic, Johnson and Johnson;Financial Interests, Personal, Advisory Role: Kyorin;Financial Interests, Institutional, Research Grant: Illumina, Eurofins, Taiho, Chugai, Eli Lilly, AstraZeneca. M. Okada: Financial Interests, Institutional, Research Grant: AstraZeneca. T. Go: Financial Interests, Institutional, Research Grant: AstraZeneca. M. Yamashita: Financial Interests, Institutional, Research Grant: AstraZeneca. N. Yamamoto: Financial Interests, Personal, Invited Speaker: MSD K.K, AstraZeneca, Ono Pharmaceutical Co., Ltd., Thermo Fisher Scientific, Daiichi Sankyo Co., Ltd., Taiho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., Chugai Pharmaceutical Co., Ltd., Eli Lilly Japan K.K., Boehringer Ingelheim, Novartis, Pfizer Inc., Bristol Myers Squibb, Nippon Kayaku, GlaxoSmithKline K.K., Sanofi K.K., Hisamitsu Pharmaceutical Co.,Inc., Merk biopharma;Financial Interests, Personal, Advisory Board: AstraZeneca, Daiichi Sankyo Co., Ltd., Taiho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., Chugai Pharmaceutical Co., Ltd., Eli Lilly Japan K.K., Boehringer Ingelheim, Novartis, Bristol Myers Squibb, Nippon Kayaku, Life Technologies Japan Ltd., Amgen Inc., Guardant Health Japan, Janssen Pharmaceutical K.K.;Financial Interests, Institutional, Research Grant: MSD K.K;Financial Interests, Institutional, Invited Speaker: AstraZeneca, Ono Pharm ceutical Co., Ltd., Taiho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., Pfizer Inc., Amgen Inc., Janssen Pharmaceutical K.K.;Financial Interests, Institutional, Funding: Daiichi Sankyo Co., Ltd., Taiho Pharmaceutical Co., Ltd., Chugai Pharmaceutical Co., Ltd., Toppan printing, Terumo. K. Nakagawa: Financial Interests, Personal, Invited Speaker: Ono Pharmaceutical Co., Ltd., Eli Lilly Japan K.K., Amgen Inc., Nippon Kayaku Co., Ltd., AstraZeneca K.K., Chugai Pharmaceutical Co., Ltd., MSD K.K., Pfizer Japan Inc., Nippon Boehringer Ingelheim Co., Ltd., Taiho Pharmaceutical Co.,Ltd., Bayer Yakuhin, Ltd., CMIC ShiftZero K.K., Life Technologies Japan Ltd., Neo Communication, Merck Biopharma Co., Ltd., Kyowa Kirin Co., Ltd., Takeda Pharmaceutical Co., Ltd., 3H Clinical Trial Inc., Care Net, Inc., Medical Review Co., Ltd., Medical Mobile Communications co., Ltd, Yodosha Co., Ltd., Nikkei Business Publications, Inc., Japan Clinical Research Operations, CMIC Co., Ltd., Novartis Pharma K.K., Taiyo Pharma Co., Ltd.;Financial Interests, Personal, Advisory Board: Ono Pharmaceutical Co.,Ltd., Eli Lilly Japan K.K.;Financial Interests, Institutional, Other, patents sales fee: Daiichi Sankyo Co., Ltd.;Financial Interests, Institutional, Research Grant: Parexel International Corp., Pra Healthsciences, Eps Corporation., Kissei Pharmaceutical Co., Ltd., EPS International Co.,Ltd,., Daiichi Sankyo Co., Ltd., Taiho Pharmaceutical Co.,Ltd., MSD K.K., Ono Pharmaceutical Co.,Ltd., PPD-SNBL K.K, SymBio Pharmaceuticals Limited., IQVIA Services Japan K.K., Syneos Health Clinical K.K., Nippon Kayaku Co.,Ltd., EP-CRSU Co., Ltd., Mebix, Inc., Bristol Myers Squibb K.K., Janssen Pharmaceutical K.K., Eisai Co., Ltd., AstraZeneca K.K., Mochida Pharmaceutical Co., Ltd., Covance Japan Inc., Japan linical Research Operations, Takeda Pharmaceutical Co.,Ltd., GlaxoSmithKline K.K., Sanofi K.K., Chugai Pharmaceutical Co.,Ltd., Nippon Boehringer Ingelheim Co.,Ltd., Sysmex Corporation, Medical Reserch Support, Eli Lilly Japan K.K., Amgen Inc., Novartis Pharma K.K., Novartis Pharma K.K., Srl, Inc. T. Mitsudomi: Financial Interests, Personal, Invited Speaker: AstraZeneca, Chugai, Novartis, MSD, Bristol Myers Squibb, Ono, Pfizer, Eli Lilly, Merck Biopharma;Financial Interests, Personal, Advisory Board: AstraZeneca, Boehringer Ingelheim, Chugai, Novartis, MSD, Bristol Myers Squibb, Ono, Pfizer, Amgen, Janssen, Takeda, Eli-Lilly;Financial Interests, Institutional, Invited Speaker: Boehringer Ingelheim, AstraZeneca, Chugai, MSD, Taiho, Daiichi Sankyo, Ono;Non-Financial Interests, Personal, Leadership Role: Interanational Association for Study of Lung Cancer. All other authors have declared no conflicts of interest. Copyright © 2022 European Society for Medical Oncology
ABSTRACT
Background: In patients with COVID-19 and respiratory failure, class 3 obesity (body mass index > 40 kg/m2) has been associated with worse survival. Obese patients on mechanical ventilation with progressively more severe acute respiratory syndrome (ARDS) may be offered venovenous (VV) extracorporeal membrane oxygenation (ECMO) therapy. The impact of morbid obesity on the outcome of COVID-19 patients supported with VV ECMO has been underexplored. Methods: This is a multicenter, retrospective observational cohort analysis of critically ill adults with COVID-19 ARDS requiring advanced mechanical ventilation with or without VV ECMO. Data was collected from 236 international institutions forming the COVID-19 Critical Care Consortium international registry. Patients were admitted between January 2020 to December 2021. Included patients were stratified by ECMO status and a BMI threshold at 40 kg/m2. Median values with interquartile range (IQR) were used to summarize continuous variables and multi-state analysis was used to explore the effect of Class 3 obesity on the study endpoints of patient survival to discharge or death. Results: Complete data was available on 8851 of 9059 patients on mechanical ventilation, of which 767 patients required VV ECMO. For the entire study group, older age and male gender were associated with an increased risk of death. The demographics and comorbidities of the higher BMI (H >40 kg/m2) and lower BMI (L ≤40 kg/m2) cohorts were similar with the exception of age and weight. Patients with a higher BMI were younger. The median age of the H, non-ECMO cohort was 56 years (46-64), and the H, ECMO cohort was 41 years (35-51) versus the L, non-ECMO cohort of 64 years(55-71), and the L, ECMO cohort of 53years (45-60). Patients requiring VV ECMO had higher SOFA scores, experienced longer ICU and hospital lengths of stay, and a longer duration of total mechanical ventilation. Table The median time to intubation was longer in the mechanical ventilation only group (2 versus 0 days). Predictors for requiring ECMO included younger age, higher BMI and male gender. Risk factors for death included advancing age (every 10 years), male gender and increasing BMI (every 5kg/m2). The association between BMI and a higher rate of death was reduced in the mechanical ventilation only group (HR 0.92, 95% confidence interval 0.85 to 0.99). Conclusion: In patients with severe ARDS due to COVID-19 requiring mechanical ventilation, the likelihood of progressing to VV ECMO therapy or experiencing death is impacted by age, gender and higher BMI. The cohort of COVID-19 patients that ultimately required ECMO appear to be sicker at time hospital admission owing to the shorter time until mechanical ventilation. It appears the association between increasing BMI and death differs among the ECMO and mechanical ventilation alone cohorts. We would advocate for a prospective study to determine the benefit of VVECMO for the obese patient requiring VV-ECMO for COVID-19 ARDS. (Figure Presented).
ABSTRACT
Objective: To evaluate breast density notification legislation (BDNL) on breast imaging practice patterns, risk assessment, and supplemental screening. Methods: A 20-question anonymous web-based survey was administered to practicing Society of Breast Imaging radiologists in the U.S. between February and April 2021 regarding breast cancer risk assessment, supplemental screening, and density measurements. Results were compared between facilities with and without BDNL using the two-sided Fisher's exact test. Results: One hundred and ninety-seven radiologists from 41 U.S. states, with (187/197, 95%) or without (10/197, 5%) BDNL, responded. Fifty-seven percent (113/197) performed breast cancer risk assessment, and 93% (183/197) offered supplemental screening for women with dense breasts. Between facilities with or without BDNL, there was no significant difference in whether risk assessment was (P = 0.19) or was not performed (P = 0.20). There was no significant difference in supplemental screening types (P > 0.05) between BDNL and non-BDNL facilities. Thirty-five percent (69/197) of facilities offered no supplemental screening studies, and 25% (49/197) had no future plans to offer supplemental screening. A statistically significant greater proportion of non-BDNL facilities offered no supplemental screening (P < 0.03) and had no plans to offer supplemental screening compared to BDNL facilities (P < 0.02). Conclusion: Facilities in BDNL states often offer supplemental screening compared to facilities in non-BDNL states. Compared to BDNL facilities, a statistically significant proportion of non-BDNL facilities had no supplemental screening nor plans for implementation. Our data suggest that upcoming federal BDNL will impact how supplemental screening is addressed in currently non-BDNL states.
ABSTRACT
Background: Owing to the spread of coronavirus disease 2019 (COVID-19), people have refrained from going out unnecessarily and have been maintaining social distance. These new lifestyle approaches have affected people physically, psychologically, and socially. Patients with heart failure (HF) are more likely to have social frailty, physical frailty, cognitive impairment, and depressive symptoms, and an overlap of these conditions leads to adverse events. Therefore, multi-domain assessment and understanding of the condition of patients with HF are important for disease management. The spread of COVID-19 is a predicted risk factor for these events, but its impact in patients with HF has not been investigated. Purpose: We investigated whether the spread of COVID-19 is associated with the development of the multi-domain of frailty in patients with HF. Methods: Patients who were independent in their daily activities before admission were included in the study. The presence of social frailty (Makizako's five items), physical frailty (Fried phenotype model), cognitive impairment (Mini-Cog), and depressive symptoms (the Patient Health Questionnaire-2) in patients with HF were assessed at hospital discharge. Logistic regression analyses were used to examine the impact of the spread of COVID-19 on the development of the multi-domain of frailty in patients with HF. Results: We included 482 patients in this study. Median patient age was 74 years, and 64.5% were male. In multivariate logistic regression analyses, the spread of COVID-19 was significantly associated with the development of social frailty (odds ratio [OR]: 1.15, 95% confidence interval [CI]: 1.02-1.30) and depressive symptoms (OR: 1.14, 95% CI: 1.02-1.27) but not with the development of physical frailty (OR: 1.24, 95% CI: 0.51-3.02) and cognitive impairment (OR: 1.72, 95% CI: 0.80-3.73). Conclusion: The spread of COVID-19 was associated with the development of social frailty and depressive symptoms in patients with HF. Evaluation of social frailty and depressive symptoms during hospitalization would support disease management and understand their social and psychological conditions specific to the spread of COVID-19. (Table Presented).
ABSTRACT
Background: The virus responsible for COVID-19 enters human cells by binding angiotensinconverting enzyme 2. The influence of renin-angiotensin-aldosterone system (RAAS) inhibitors, including angiotensin-converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARBs), remains uncertain. Aim: To examine the role of ACEi / ARB exposure on outcomes in COVID-19 patients with preexisting hypertension (HTN) admitted to intensive care units (ICU). Methods: The COVID-19 Critical Care Consortium is a prospective, observational cohort study of patients requiring ICU admission for active COVID-19 spanning 354 participating sites in 54 countries. Patients >18 years old with pre-existing HTN requiring antihypertensive therapy were analysed. Length of stay and in-hospital mortality to 90 days post ICU admission were analysed as time-to-eventoutcomes by multistate survival analysis, and the influence of ACEi / ARB use on the hazards of death and discharge by multi-state Cox proportional hazard modelling and sensitivity analysis. Results: From December 1, 2019 through December 30, 2020, 663 eligible patients were registered. Of these, 480 patients had received ACEi and / or ARB therapy (median age 65 years, 67% male) in the 2 weeks before ICU admission, while 183 had not (66 years, 61% male). Average lengths of ICU and general ward stays were longer in the ACEi / ARB than non-ACEi / ARB group (20.8 days and 6.5 days vs. 15.5 and 6.0 days, respectively). ACEi / ARB use was associated with a decreased hazard of death (HR, 0.69, 95% CI, 0.54 -0.88) that persisted after adjusting for propensity scores (0.67, 0.53 -0.86). Cumulative probabilities (unadjusted for baseline characteristics) for death and discharge post ICU admission are depicted in the figure for ACEi/ARB (red) and non-ACEi / ARB (blue) patients. Conclusions: In 663 critically ill COVID-19 patients with pre-existing HTN, RAAS inhibition pre-ICU admission was linked to reduced in-hospital mortality.