ABSTRACT
We sought to determine parameters of the acute phase response, a feature of innate immunity activated by infectious noxae and cancer, deranged by Covid-19 and establish oncological indices' prognostic potential for patients with concomitant cancer and Covid-19. Between 27/02 and 23/06/2020, OnCovid retrospectively accrued 1,318 consecutive referrals of patients with cancer and Covid-19 aged 18 from the U.K., Spain, Italy, Belgium, and Germany. Patients with myeloma, leukemia, or insufficient data were excluded. The neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), prognostic nutritional index (PNI), modified Glasgow prognostic score (mGPS), and prognostic index (PI) were evaluated for their prognostic potential, with the NLR, PLR, and PNI risk stratifications dichotomized around median values and the pre-established risk categorizations from literature utilized for the mGPS and PI. 1,071 eligible patients were randomly assorted into a training set (TS, n=529) and validation set (VS, n=542) matched for age (67.9±13.3 TS, 68.5±13.5 VS), presence of 1 comorbidity (52.1% TS, 49.8% VS), development of 1 Covid-19 complication (27% TS, 25.9% VS), and active malignancy at Covid-19 diagnosis (66.7% TS, 61.6% VS). Among all 1,071 patients, deceased patients tended to categorize into poor risk groups for the NLR, PNI, mGPS, and PI (P<0.0001) with a return to pre-Covid-19 diagnosis NLR, PNI, and mGPS categorizations following recovery (P<0.01). In the TS, higher mortality rates were associated with NLR>6 (44.6% vs 28%, P<0.0001), PNI<40 (46.6% vs 20.9%, P<0.0001), mGPS (50.6% for mGPS2 vs 30.4% and 11.4% for mGPS1 and 0, P<0.0001), and PI (50% for PI2 vs 40% for PI1 and 9.1% for PI0, P<0.0001). Findings were confirmed in the VS (P<0.001 for all comparisons). Patients in poor risk categories had shorter median overall survival [OS], (NLR>6 30 days 95%CI 1-63, PNI<40 23 days 95%CI 10-35, mGPS2 20 days 95%CI 8-32, PI2 23 days 95%CI 1-56) compared to patients in good risk categories, for whom median OS was not reached (P<0.001 for all comparisons). The PLR was not associated with survival. Analyses of survival in the VS confirmed the NLR (P<0.0001), PNI (P<0.0001), PI (P<0.01), and mGPS (P<0.001) as predictors of survival. In a multivariable Cox regression model including all inflammatory indices and pre-established prognostic factors for severe Covid-19 including sex, age, comorbid burden, malignancy status, and receipt of anti-cancer therapy at Covid-19 diagnosis, the PNI was the only factor to emerge with a significant hazard ratio [HR] in both TS and VS analysis (TS HR 1.97, 95%CI 1.19-3.26, P=0.008;VS HR 2.48, 95%CI 1.47- 4.20, P=0.001). We conclude that systemic inflammation drives mortality from Covid-19 through hypoalbuminemia and lymphocytopenia as measured by the PNI and propose the PNI as the OnCovid Inflammatory Score (OIS) in this context.
ABSTRACT
Background: Cancer p represent a high-risk population for severe COVID-19. Cancer-associated immunosuppression may hinder in the development of anti-SARS-CoV-2 antibodies. Methods: Data regarding baseline characteristics (age, cancer type, cancer activity, cancer treatment), COVID-19 infection and anti-SARS-CoV-2 IgG were collected from p with solid tumors who tested positive for COVID-19 (PCR+) between 10th March and 9th December 2020 at Catalan Institute of Oncology. We prospectively assessed anti-SARS-CoV-2 IgG seroprevalence at different timepoints (<2, 2-6, >6 months [m] since first PCR+) and explored factors associated with long-term IgG positivity. Results: Out of 79 registered p, 19 died without IgG testing (all of them <3 months after a PCR+), and 8 refused to participate, leaving 52 tested for IgG. Tested and not-tested p were similar according to baseline characteristics, cancer treatment and COVID-19. At the 1st timepoint, 19/23p were IgG+;at the 2nd, 29/33p were IgG+ and 1 inconclusive;at the 3rd timepoint, 18/22 were IgG+ (median time from PCR + to 3rd timepoint determination was 9.4 m (Interquartile range [IQR]: 8.5-9.7). Importantly, 1 p changed from IgG+ (2nd timepoint) to IgG- (3rd timepoint), and 1 inconclusive result (2nd timepoint) changed to negative (3rd timepoint). Potential factors associated to IgG+ >6 m are shown in the table. [Formula presented] Conclusions: High seroprevalence of anti-SARS-CoV-2 IgG was observed at several timepoints after COVID-19 diagnosis in solid tumor p. P with IgG+ at >6 m were older, and more likely to have required hospitalization and oxygen during prior COVID-19 in comparison to IgG- p >6m, suggesting that infection severity may promote durable immunity. Frequency of active cancer and active chemotherapy at COVID-19 diagnosis were higher among p with IgG- >6m, suggesting deeper immunosupression. Legal entity responsible for the study: The authors. Funding: Has not received any funding. Disclosure: E. Felip: Financial Interests, Personal, Other: Pfizer;Financial Interests, Personal, Other: Lilly;Financial Interests, Personal, Other: Eisai;Financial Interests, Personal, Other: Novartis;Financial Interests, Personal, Sponsor/Funding: Pfizer. M. Romeo Marin: Financial Interests, Personal, Advisory Board: MSD;Financial Interests, Personal, Advisory Board: MSK;Financial Interests, Personal and Institutional, Other: MSD;Financial Interests, Personal and Institutional, Principal Investigator: AZ;Financial Interests, Personal and Institutional, Principal Investigator: GSK Tesaro;Financial Interests, Personal and Institutional, Principal Investigator: Merck. All other authors have declared no conflicts of interest.
ABSTRACT
Background: There is uncertainty as to the contribution of cancer patients' features on severity and mortality from Covid-19 and little guidance as to the role of anti-cancer and anti-Covid-19 therapy in this population. Method(s): OnCovid is a retrospective observational study conducted across 19 European centers that recruited cancer patients aged >18 and diagnosed with Covid-19 between 26/02 and 01/04/2020. Uni- and multivariable regression models were used to evaluate predictors of Covid-19 severity and mortality. Result(s): We identified 890 patients from UK (n=218, 24%), Italy (n=343, 37%), Spain (n=323, 36%) and Germany (n=6, 1%). Most patients were male (n=503, 56%) had a diagnosis of solid malignancy (n=753, 84%) and 556 (62%) had active disease. Mean (+/-SD) patient age was 68+/-13 years, and 670 (75%) had >1 co-morbidity, most commonly hypertension (n=386, 43%). Commonest presenting symptoms were fever (n=569, 63%) and cough (n=448, 50%), beginning 6.3 (+/-9.5 SD) days before diagnosis. Most patients (n=565, 63%) had >1 complication from Covid-19, including respiratory failure (n=527, 59%) and acute respiratory distress syndrome (n=127, 22%). In total, 110 patients (14%) were escalated to high-dependency or intensive care. At time of analysis, 299 patients had died (33%). Multi-variate logistic regression identified male gender, age>65 (p<0.0001) presence of >2 comorbidities (p=0.001) active malignancy (p=0.07) as predictors of complicated Covid-19. Mortality was associated with active malignancy (p<0.0001), age>65 and co-morbid burden (p=0.002). Provision of chemotherapy, targeted therapy or immunotherapy was not associated with higher mortality. Exposure to anti-malarials alone (chloroquine/hydroxychloroquine, n=182, p<0.001) or in combination with anti-virals (n=195, p<0.001) or tocilizumab (n=51, p=0.004) was associated with improved mortality compared to patients who did not receive any of these therapies (n=446) independent of patients' gender, age, tumour stage and severity of Covid-19. Conclusion(s): This study highlights the clinical utility of demographic factors for individualized risk-stratification of patients and supports further research into emerging anti Covid-19 therapeutics in SARS-Cov-2 infected cancer patients. Clinical trial identification: NCT04393974. Legal entity responsible for the study: Imperial College London. Funding(s): Has not received any funding. Disclosure: D.J. Pinato: Speaker Bureau/Expert testimony: ViiV Healthcare;Advisory/Consultancy, Travel/Accommodation/Expenses: Bayer;Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution), Travel/Accommodation/Expenses: BMS;Honoraria (self), Advisory/Consultancy: MiNa Therapeutics;Advisory/Consultancy: Eisai;Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Roche;Advisory/Consultancy: AstraZeneca;Research grant/Funding (institution): MSD. All other authors have declared no conflicts of interest.Copyright © 2020 European Society for Medical Oncology
ABSTRACT
Background: Treatment (ttm) of cancer patients (pts) was compromised during the first wave of COVID19 pandemic due to collapse of healthcare systems. Standard of care (SOC) for LA-HNSCC pts had to be adapted as operating rooms were temporarily unavailable, and to reduce risk of COVID19 exposure. The IMPACCT study evaluated the outcome of LA-HNSCC pts treated at the Catalan Institute of Oncology during the first semester of 2020 and compared it to a control cohort previously treated in the same institution. Methods: Retrospective single institution analysis of two consecutively-treated cohorts of newly-diagnosed HNSCC pts: from January to June of 2020 (CT20) and same period of 2018 and 2019 (CT18-19). Pt demographics and disease characteristics were obtained from our in-site prospective database. Ttm modifications from SOC as per COVID19- contingency protocol in CT20 for LA-HNSCC were collected. Chi-squared was used to compare variables and ttm response between cohorts. One-year recurrence-free survival (1yRFS) and overall survival (1yOS) of LA-HNSCC pts were estimated by Kaplan-Meier method and compared by Log-rank test. Results: A total of 306 pts were included: CT20=99;CT18- 19=207. Baseline characteristics were balanced between cohorts (Table1). In pts treated with conservative ttm (non-surgical approach), persistence disease was higher in CT20 vs CT18- 19 (26 vs. 10% p=0.02). Median follow-up of CT20 and CT18-19 was 6.8 months (IQR 5.1-7.9) and 12.3 (6.7-18.4), respectively. A trend towards lower 1yRFS and 1yOS was observed in CT20 vs CT18-19 (72 vs 83% p=0.06;80 vs 84% p=0.07), respectively. Within CT20, 37 pts (37%) had one or more ttm modifications: switch from surgery to conservative ttm (n=13);altered radiotherapy fractionation (n=14);reduced cisplatin cumulative dose to 200mg/m2 (n=19);no adjuvant ttm (n=1). Pts who received modified ttm had no differences in 1yRFS vs those who did not (80 vs 66% p=0.31), but higher 1yOS was observed (97 vs 67% p<0.01). When stratified by stage, 1yOS difference remained significant in stage III/IVA (100 vs 61% p<0.01) but not in I/II (100 vs 77% p=0.28) or IVB (67 vs 50% p=0.54). Conclusions: COVID19 pandemic had a negative impact on ttm outcomes and survival in LA-HNSCC pts when compared to our historical cohort. Ttm modifications based on COVID19-contingency protocol did not compromise ttm efficacy in terms of RFS and was associated with better OS in Stage III/IVA.
ABSTRACT
Background: Cancer patients (pts) represent a high-risk population for severe COVID-19. Cancer-associated immunosuppression may hinder in the development of anti-SARS-CoV-2 antibodies. Methods: Data regarding baseline characteristics, COVID-19 and anti-SARS-Cov2 IgG were collected from cancer pts (solid tumors) who tested positive for COVID-19 (PCR+) between March and April 2020 at Catalan Institute of Oncology. We prospectively assessed anti-SARS-Cov2 IgG seroprevalence at 3 and 9 months post infection and explored clinico-pathologic factors associated with IgG positivity. We explored the impact of potential factors influencing antibody production at >9 months. Results: Of 49 pts registered between 10 March-26 April 2020, 21 died <3 months after the infection and 5 pts refused to participate, leaving 23 eligible pts for IgG testing. With respect to those not tested, IgG tested cohort was younger (median age: 64.0 vs 72.9 years, p = 0.001) and presented oncologic remission in 68.2% of cases (vs 34.6%, p = 0.043) at COVID-19 diagnosis. Median time from PCR+ to first and second IgG determination was 3.2 months (Interquartile range [IQR]: 2.9-4.1) and 9.5 months (IQR: 8.8-9.8), respectively. Out of 23 pts, 15 had both determinations and 8 had only one (3 in the first time point, 5 in the second one). We identified 16/18 pts IgG+ (88.9%) at 3 months and 17/20 pts IgG+ (85%) at 9 months. One IgG+ pt became IgG-at the second determination, one was IgG-at both timepoints, and one had an inconclusive result at the first but negative at the second timepoint. Key characteristics of patients by IgG result 9 months after COVID-19 diagnosis are shown in the table. Conclusions: We describe a high seroprevalence of anti-SARS-CoV-2 IgG at 3 and 9 months after COVID-19 diagnosis in solid tumour patients, irrespective of anti-cancer therapy exposure. Pts who were IgG+ at 9 months were older, and more likely to have required oxygen during prior COVID-19 in comparison to IgG-pts suggesting that infection severity may promote durable immunity. Frequency of early stage cancers was higher among IgG+ pts, suggesting less cancerrelated immunosupression. Older (>70 years) and advanced cancer pts were underrepresented in this series, warranting confirmation of these preliminary results in a larger cohort.