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: During the SARS-COV-2 pandemic, cancer patients (pts) who are infected may develop severe disease if their systemic treatment is not temporarily stopped. Nasopharyngeal swab was not extensively available to screen cancer pts for SARS-COV-2 infection in northern Italy, the most area in the country most affected by the pandemic. From the beginning of the outbreak onwards, all pts admitted to the Medical Oncology Unit at Spedali Civili Hospital, Brescia, underwent a triage investigating the presence of symptoms and signs suggestive of SARS-COV-2 infection. Triage results were used to decide which pts should continue antineoplastic treatments. Methods: All consecutive cancer pts being admitted for systemic treatment from February 24th to April 21st 2020 were considered. Triage, performed by a trained nurse, consisted of questions regarding the presence of fever, cough, dyspnea, anosmia, dysgeusia, headache, nasal congestion, conjunctival congestion, sore throat, diarrhoea, nausea and vomiting, measurement of body temperature and pulse oximetry. All enrolled pts were followed-up for overt SARS-COV-2 development until May 18th. Results: Overall, 1180 pts were included, 54% female and median age 65 years. Most represented primary malignancies were breast (32%), gastroenteric (18%) and lung (16.5%). Thirty-one (2.5%) presented with clinically evident SARS-COV-2 disease and infection was proven by positive nasopharyngeal swab and/or radiological imaging. The triage identified 69 (6%) “grey zone” pts, with suspicious symptoms (i.e. fever 41%, cough 30%, dyspnea 19%). The nasopharyngeal swab was negative in 48% of them and was not performed in the remaining 52% of pts, as well as in all pts who were triage negative. Both SARS-COV-2 positive and “grey zone” pts did not receive treatment and were addressed to hospitalisation or home quarantine. All the 1080 pts (91.5%) who resulted negative at triage continued their antineoplastic therapy as scheduled, none of them presenting symptoms of SARS-COV-2 infection during the follow-up. Conclusions: Accurate triage allowed safe continuation of anticancer treatment in 91.5% of pts during the SARS-COV-2 outbreak. Legal entity responsible for the study: The authors. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.