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: The COVID-19 (C19) pandemic has prompted alterations to systemic anti-cancer therapy (SACT) due to concerns of immunosuppression and healthcare exposure. However, the effects of SACT on mortality in patients who acquire C19 are not well understood. As a national cancer centre within a major C19 hotspot, we seek to address these risks at scale. Method(s): Patients with a history of solid cancers and laboratory confirmed C19 (1 Mar to 31 May 2020) were included. Haematological malignancies were excluded. The primary outcome was time from C19 diagnosis to death. The last follow-up date was 22 Jun 2020. Result(s): We identified 94 cancer patients;62 males (median age 73, BMI 24.9), and 32 females (median age 68.5, BMI 25.7). Genitourinary (n = 24) cancers were the most common, followed by gastrointestinal (n = 23), thoracic (n = 15), and gynaecological (n = 9) cancers. 25 patients received SACT: chemotherapy (n = 15), endocrine therapy (n = 8), immunotherapy (n = 4), and targeted anti-cancer therapy (n = 2). 16 patients received SACT with palliative intent. Patients on SACT had a greater incidence of metastatic disease (48.0% vs 10.6%, p 0.001) and were younger (median age 62.5 vs 73.0, p = 0.01). They were also more likely to have renal impairment (p = 0.02), lymphopaenia (p = 0.01) and anaemia (p = 0.04) compared to those not on SACT. The univariate analysis showed age and co-morbidities were associated with mortality (Table). Adjusting for age, ethnicity, co-morbidities and the presence of metastatic cancer, SACT was an independent risk factor for C19 mortality (HR 2.46, 1.09 - 5.5, p = 0.03). Age, South Asian ethnicity, hypertension and cerebrovascular disease were also independent risk factors for C19 mortality. [Formula presented] Conclusion(s): C19 infection poses a substantial risk to cancer patients and our data suggests that SACT is an independent risk factor for mortality in C19 infection. These findings call for a nuanced approach to C19 risk, focusing on established risk factors such as age and co-morbidities to guide treatment decisions. Legal entity responsible for the study: University College London Hospital. Funding(s): Has not received any funding. Disclosure: All authors have declared no conflicts of interest. Copyright © 2020
ABSTRACT
Background: The COVID-19 pandemic remains of pressing concern for patients with cancer. Mortality from COVID-19 is predicted by age and co-morbidities, but the relative contribution of cancer is poorly understood. As a tertiary academic hospital serving a large general and cancer population in a COVID-19 epicentre, we are uniquely placed to investigate this. We report data from our study, comparing cancer patients to an age- and sex-matched non-cancer cohort. Methods: Patients with laboratory confirmed COVID-19 from 1 March to 31 May 2020 were included. Patients with a history of solid cancer were compared to an age- and sex-matched non-cancer cohort. Patients with haematological malignancies were excluded. Results: We identified 94 patients with cancer and 226 patients without cancer. In univariate analysis, age, South Asian ethnicity and co-morbidities predicted mortality (see table). More in the cancer cohort had died compared to the non-cancer cohort (43.6% vs 34.1%). The higher mortality among cancer patients was statistically significant among those aged 70 years and above (OR 2.28, 1.14-4.50, p = 0.02). After adjusting for age, ethnicity and co-morbidities, a history of cancer was an independent predictor of mortality following COVID-19 (HR 1.57, 95% CI:1.04-2.4, p = 0.03). Patients with active malignancy also had similarly increased adjusted mortality (HR 1.64, 95% CI: 1.03 – 2.6, p = 0.04). Increasing age (HR 1.49 every 10 years, 95% CI:1.25-1.8, p <0.001), South Asian ethnicity (HR 2.92, 95% CI:1.73-4.9, p <0.001) and cerebrovascular disease (HR 1.93, 95% CI:1.18-3.2, p = 0.008) were also confirmed as independent predictors of mortality. [Formula presented] Conclusions: Along with known risk factors, cancer confers an independent risk for mortality in COVID-19. Taken together, our findings support the need to continue ‘shielding’ patients with cancer from exposure to COVID-19 infection. Increasing age and co-morbidity should take precedence when weighing up risk factors for severe COVID-19 infection in cancer patients. Legal entity responsible for the study: University College London Hospitals NHS Foundation Trust. Funding: Has not received any funding. Disclosure: H.M. Shaw: Advisory/Consultancy, Speaker Bureau/Expert testimony: Novartis, BMS, MSD;Advisory/Consultancy: Immunocore, Idera, Iovance, Genmab, Sanofi Genzyme/Regeneron, Macrogenics, Roche;Speaker Bureau/Expert testimony: Sanofi Genzyme. All other authors have declared no conflicts of interest.