key: cord-0842377-ir03tp73
authors: Glasbey, J.; on behalf of the COVIDSurg Collaborative,
title: 1566MO Resilience of elective cancer surgery systems during COVID-19 lockdowns: International, prospective cohort study of planned surgery for 15 tumour types in 61 countries
date: 2021-09-30
journal: Annals of Oncology
DOI: 10.1016/j.annonc.2021.08.1559
sha: 991837e8083126c1bd27a5ef227c6dfc0ab15c4b
doc_id: 842377
cord_uid: ir03tp73

Background: Surgery is the main modality of cure for solid cancers and was prioritised to continue even during SARS-CoV-2 outbreaks. This study aimed to identify immediate areas for system strengthening by comparing the delivery of elective cancer surgery during COVID-19 in periods of lockdown versus light restriction. Methods: This international, prospective cohort study enrolled patients with 15 cancer types who had a decision for surgery during the COVID-19 pandemic up to 31st August 2020. Average national Oxford COVID-19 Stringency Index scores were calculated for each patient during the period they were awaiting surgery, classified into light restrictions (index <20), moderate lockdowns (20-60), and full lockdowns (>60). The primary outcome was the non-operation rate (proportion of patients who did not undergo planned surgery). Cox proportional-hazards regression models were used to explore the associations between lockdowns and non-operation. Results: From 20,006 patients (466 hospitals, 61 countries), 9.1% did not receive surgery after a minimum of 3-months’ follow up (median:23 weeks, IQR:16 to 30 weeks). Light restrictions were associated with a 0.6% non-operation rate, moderate lockdowns 5.5% (adjusted hazard ratio:0.81, 95% confidence interval 0.77-0.84, p<0.001), and full lockdowns with a 15.0% rate (HR:0.51, 0.50-0.53). In sensitivity analyses, this effect was independent of local SARS-CoV-2 rates. Each additional week in lockdown led to a 9% reduction in the likelihood in a patient undergoing their cancer operation. Frail patients, those with advanced cancer, and those in lower-income settings were particularly vulnerable to lockdown effects. Surgery beyond 12-weeks from diagnosis increased during lockdowns (9.1% in light restrictions, 10.4% moderate lockdowns, 23.8% full lockdowns). Conclusions: Cancer surgery systems worldwide were fragile to lockdowns, with one in seven patients not undergoing planned surgery and more preoperative delays. During current and future periods of societal restriction, the resilience of elective surgery systems requires strengthening, which may include ring-fenced surgical units and critical care capacity. Clinical trial identification: NCT04384926. Legal entity responsible for the study: COVIDSurg Collaborate, University of Birmingham, UK. Funding: National Institute for Health Research (NIHR) Global Health Research Unit, the Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, Medtronic, NIHR Academy, Sarcoma UK, The Urology Foundation, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research. Disclosure: All authors have declared no conflicts of interest.

Characterization of COVID-19 vaccination response by antibody (Ab) titer and T-cell receptor (TCR) sequencing in patients (pts) with advanced genitourinary (GU) cancers Background: Preliminary studies have characterized potential adverse effects associated with COVID-19 vaccination in pts with cancer. However, biological characterization of vaccine response has yet to be performed.

Methods: Eligible pts with advanced GU cancers (metastatic/unresectable prostate, bladder and renal cell carcinoma [RCC] ) and had not yet received COVID-19 vaccination. Pts were consented to receive sequential blood draws prior to vaccination and at landmarks of 2, 6, and 12 mos following vaccination. Pts on systemic treatment had additional blood draws coinciding with their first 3 cycles of therapy following vaccination. Ab titers to SARS-CoV-2 were quantified via ELISA and reported as an immune status ratio (ISR). RNA was extracted from PBMC aliquots, converted into cDNA and TCR a/b sequences were selectively amplified. TCR abundance and homology clustering was performed using custom scripts.

Results: As of May 14, 2021, 130 pts had consented to the study of whom 126 pts submitted baseline (BL) specimens. The current analysis focuses on 56 pts who submitted cycle 1 (C1) specimens. Among these, 29, 26, and 1 pts had RCC, prostate and bladder cancer, respectively; 19 were on checkpoint inhibitor (CPI)-based regimens while 37 were on non-CPI regimens. BNT162b2 (Pfizer) was the most commonly administered vaccine in the cohort (n¼29), followed by mRNA-1273 (Moderna; n¼26). COVID-19 Ab titers increased significantly from BL to C1 across the cohort from 0.19 (interquartile range [IQR] 0.12-0.18) to 4.37 (IQR 0.2-6.60; P<0.0001). However, 8/56 pts (14.3%) receiving CPI-based regimens and 8/56 pts (14.3%) receiving non-CPI-based regimens were noted to have negative Ab titers after a median of 18 and 35 days following initial vaccination, respectively. No significant difference was observed in the increase from BL to C1 in pts receiving CPI vs non-CPIbased regimens. Specimen collection is ongoing; updated Ab titer data and TCR sequencing data will be presented.

Conclusions: Our data prompt concern for delayed or insufficient COVID-19 Ab response in a subset of pts with advanced GU cancers.

Legal entity responsible for the study: The authors. Background: Early reports from registry studies demonstrated high vulnerability of cancer patients from COVID-19, with case-fatality rates (CFR) >30% at the onset of the pandemic. With advances in disease management and increased testing capacity, the lethality of COVID-19 in cancer patients may have improved over time.

Methods: The OnCovid registry lists European cancer patients consecutively diagnosed with COVID-19 in 35 centres from Jan 2020 to Feb 2021. We analysed clinical characteristics and outcomes stratified in 5 trimesters (Jan-Mar, Apr-Jun, Jul-Sep, Oct-Dec 2020 and Jan-Feb 2021) and studied predictors of mortality across 2 semesters (Jan-Jun 2020 and Jul 2020-Feb 2021). Background: Surgery is the main modality of cure for solid cancers and was prioritised to continue even during SARS-CoV-2 outbreaks. This study aimed to identify immediate areas for system strengthening by comparing the delivery of elective cancer surgery during COVID-19 in periods of lockdown versus light restriction.

Methods: This international, prospective cohort study enrolled patients with 15 cancer types who had a decision for surgery during the COVID-19 pandemic up to 31st August 2020. Average national Oxford COVID-19 Stringency Index scores were calculated for each patient during the period they were awaiting surgery, classified into light restrictions (index <20), moderate lockdowns (20-60), and full lockdowns (>60). The primary outcome was the non-operation rate (proportion of patients who did not undergo planned surgery). Cox proportional-hazards regression models were used to explore the associations between lockdowns and non-operation.

Results: From 20,006 patients (466 hospitals, 61 countries), 9.1% did not receive surgery after a minimum of 3-months' follow up (median:23 weeks, IQR:16 to 30 weeks). Light restrictions were associated with a 0.6% non-operation rate, moderate lockdowns 5.5% (adjusted hazard ratio:0.81, 95% confidence interval 0.77-0.84, p<0.001), and full lockdowns with a 15.0% rate (HR:0.51, 0.50-0.53). In sensitivity analyses, this effect was independent of local SARS-CoV-2 rates. Each additional week in lockdown led to a 9% reduction in the likelihood in a patient undergoing their cancer operation. Frail patients, those with advanced cancer, and those in lower-income settings were particularly vulnerable to lockdown effects. Surgery beyond 12weeks from diagnosis increased during lockdowns (9.1% in light restrictions, 10.4% moderate lockdowns, 23.8% full lockdowns).

Conclusions: Cancer surgery systems worldwide were fragile to lockdowns, with one in seven patients not undergoing planned surgery and more preoperative delays. During current and future periods of societal restriction, the resilience of elective surgery systems requires strengthening, which may include ring-fenced surgical units and critical care capacity.

Clinical trial identification: NCT04384926. Background: At the height of the first wave of the SARS-COV-2 pandemic, ESMO mobilized to accelerate research for the understanding of COVID-19 in cancer patients (pts). ESMO CoCARE is an international collaborative registry-based, cohort study, gathering real-world data and information from healthcare professionals about the natural history, treatment and outcomes of COVID-19 in cancer pts.

Methods: ESMO CoCARE captures information on pts with any solid or hematologic malignancy (including cancer survivors free of disease for 5 years) presenting with a COVID-19 diagnosis in any of the participating centers. Data collected since 06/2020 include demographics, cancer characteristics and status, co-morbidities, COVID-19 clinical features, course, management and outcome. Factors influencing COVID-19 severity (hospitalization +/-ICU support needed) and recovery are investigated using multivariable logistic regression with backward elimination method. The study is ongoing.

Results: The current analysis includes 1551 registered pts (19 countries; 87% pts from 23 European centers, 7% and 6% pts from 5 Northern African and 7 Asian centers), with COVID-19 diagnosis as of 11/03/2021. Median age was 64 years, with the majority female (52%), cancer stage III/IV (58%), and on active cancer treatment (60%). 65% had severe COVID-19 requiring hospitalization, with 11% receiving intensive care. In multivariable analysis, in addition to demographics (male gender, older age, other ethnicity than Caucasian, lower BMI), co-morbidities and symptomatic COVID-19, severe disease was associated to higher ECOG PS (Odds Ratio (OR) 2 vs 0 ¼5.9, OR 1 vs 0 ¼2.1), hematological malignancies (OR hemvs solid ¼2.0), and active/ progressive cancer status (OR progressivevs no evidence of disease ¼1.6). 98% of pts with mild disease recovered, as opposed to only 70% of those with severe disease. Cancer stage was an additional prognostic factor for recovery (OR I/II vs IV ¼3.4).

Conclusions: Demographic characteristics, type and status of cancer, and symptomatology of COVID-19 increase the probability of severe disease, while advanced cancer stage is also associated with the risk of death.

Funding: ESMO -European Society for Medical Oncology

Investigator-initiated trial: BMS; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: Merck; Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Personal, Invited Speaker: Pierre Fabre. R. Lee: Financial Interests

Advisory Role: Astellas; Financial Interests, Personal and Institutional, Funding: Bristol-Myers Squibb; Financial Interests

Funding: Astellas; Financial Interests, Personal and Institutional, Funding: Servier; Financial Interests, Personal and Institutional, Funding: Five Prime Therapeutics; Financial Interests, Personal and Institutional, Funding: Amgen; Financial Interests, Personal, Other, Travel funding: Merck; Financial Interests

Susnjar: Financial Interests, Personal, Other, Honoraria and/or advisory fees: Roche; Financial Interests, Personal, Other, Honoraria and/or advisory fees: Pfizer; Financial Interests, Personal, Other, Honoraria and/or advisory fees: Novartis

Financial Interests, Personal, Other, Honoraria and/or advisory fees: AstraZeneca; Financial Interests, Personal, Other, Honoraria and/or advisory fees: Amicus. M. Rossi: Financial Interests, Personal, Other, travel and personal fees: Novartis; Financial Interests, Personal, Other, travel and personal fees: Ipsen. O.A. Michielin: Financial Interests, Personal, Other, personal fees

Other, personal fees: Novartis; Financial Interests, Personal, Other, personal fees: Roche; Financial Interests, Personal, Other, personal fees: Amgen; Financial Interests, Personal, Other, personal fees: NeraCare GmbH. G. Pentheroudakis: Financial Interests, Personal, Advisory Board: Amgen; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: Bristol Myers Squibb; Financial Interests, Personal, Advisory Board: Lilly; Financial Interests, Personal, Advisory Board: Merck; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Institutional, Principal Investigator: AbbVie; Financial Interests, Institutional, Research Grant: Amgen; Financial Interests, Institutional, Principal Investigator

Research Grant: Boehringer Ingelheim; Financial Interests, Institutional, Funding: Boehringer Ingelheim

Principal Investigator: Bristol Myers Squibb; Financial Interests, Institutional, Principal Investigator: Debbiopharm; Financial Interests, Institutional, Funding: Enorasis; Financial Interests, Institutional, Funding: Genekor; Financial Interests, Institutional, Funding: Ipsen; Financial Interests, Institutional, Principal Investigator: Ipsen

Funding: Merck; Financial Interests, Institutional, Principal Investigator: Merck; Financial Interests, Institutional, Funding: MSD; Financial Interests, Institutional, Principal Investigator: MSD; Financial Interests, Institutional, Funding: Pfizer; Financial Interests

Receipt of grants/research supports: (Sub)investigator in trials (institutional financial support for clinical trials) sponsored by Amgen

1568P Clinical and laboratory outcomes of solid cancer patients reinfected with SARS-CoV-2

COVID-19 reinfection has been increasingly reported. Immunocompromised patients may be more susceptible to COVID-19 reinfection due to impaired immune responses to the virus. The current study aimed to evaluate the clinical and laboratory outcomes of solid cancer