Evaluation of COVID-19 impact on DELAYing diagnostic-therapeutic pathways of lung cancer patients in Italy (COVID-DELAY study): fewer cases and higher stages from a real-world scenario.

INTRODUCTION: COVID-19 has disrupted the global health care system since March 2020. Lung cancer (LC) patients (pts) represent a vulnerable population highly affected by the pandemic. This multicenter Italian study aimed to evaluate whether the COVID-19 outbreak had an impact on access to cancer diagnosis and treatment of LC pts compared with pre-pandemic time. METHODS: Consecutive newly diagnosed LC pts referred to 25 Italian Oncology Departments between March and December 2020 were included. Access rate and temporal intervals between date of symptoms onset and diagnostic and therapeutic services were compared with the same period in 2019. Differences between the 2 years were analyzed using the chi-square test for categorical variables and the Mann-Whitney U test for continuous variables. RESULTS: A slight reduction (-6.9%) in newly diagnosed LC cases was observed in 2020 compared with 2019 (1523 versus 1637, P = 0.09). Newly diagnosed LC pts in 2020 were more likely to be diagnosed with stage IV disease (P < 0.01) and to be current smokers (someone who has smoked more than 100 cigarettes, including hand-rolled cigarettes, cigars, cigarillos, in their lifetime and has smoked in the last 28 days) (P < 0.01). The drop in terms of new diagnoses was greater in the lockdown period (percentage drop -12% versus -3.2%) compared with the other months included. More LC pts were referred to a low/medium volume hospital in 2020 compared with 2019 (P = 0.01). No differences emerged in terms of interval between symptoms onset and radiological diagnosis (P = 0.94), symptoms onset and cytohistological diagnosis (P = 0.92), symptoms onset and treatment start (P = 0.40), and treatment start and first radiological revaluation (P = 0.36). CONCLUSIONS: Our study pointed out a reduction of new diagnoses with a shift towards higher stage at diagnosis for LC pts in 2020. Despite this, the measures adopted by Italian Oncology Departments ensured the maintenance of the diagnostic-therapeutic pathways of LC pts.

Evaluation of COVID-19 impact on DELAYing diagnostic-therapeutic pathways of lung cancer patients in Italy: Real-world evidence from the COVID-DELAY study

Background: The coronavirus disease 2019 (COVID-19) had an unprecedent impact on the global health care system since March 2020. Lung cancer (LC) patients (pts) represent a vulnerable population, and diagnostic/therapeutic delays might affect the years to come. Aim of the multicenter, real-world, Italian COVID-DELAY study was to evaluate how the 2020 COVID-19 pandemic impacted on LC pts' access to diagnosis and treatment compared to pre-pandemic time. Patients and methods: All consecutive newly diagnosed LC pts referred to 25 Italian Oncology Departments between March and December 2020 were reviewed. Monthly access rate and temporal intervals between date of symptom onset, diagnosis and treatment start were analyzed and compared to the same period of 2019. Differences between the two years were analyzed using Fisher's exact test or chi-square test for categorical variables and unpaired Student t test, or the Mann-Whitney U test for continuous variables. Results: Less LC cases (1523 vs 1637, -6.9%) were diagnosed during the 2020 pandemic compared to 2019. LC pts in 2020 were more likely to be diagnosed with stage IV disease (p < 0.01) and to be current smokers (p < 0.01). A major drop of new LC cases was seen during the lockdown period (percentage drop -13.2% vs -5.1%) compared to the other months included. Moreover, a geographic migration was observed with more LC patients referring to low/ medium volume hospital in 2020 compared to 2019 (p = 0.01). Looking at pts management, no differences emerged in terms of interval between symptom onset and radiological diagnosis (p = 0.94), symptom onset and cytohistological diagnosis (p = 0.92), symptoms onset and treatment start (p = 0.40), treatment start and first radiological revaluation (p = 0.36). However, less LC patients were treated in the context of clinical trials during 2020 (5% vs 7%, p = 0.07). Conclusions: Our study pointed out a decrease of new LC cases and a shift towards a higher stage at diagnosis in 2020. Despite this, the efforts put in place by the Italian Oncology Departments ensured the maintenance of the diagnostic-therapeutic pathways of LC patients.

Developing a risk assessment score for cancer patients during covid-19 pandemic

Background: Data on the novel coronavirus (CoV) respiratory disease (COVID19) in cancer patients (pts) are limited. In some individuals, CoV infection triggers an aberrant immune response, leading to lung tissue damage. Cancer pts treated with immunotherapy (IT) may be more at risk for COVID19 and its complication. Methods: We performed a thorough review of the literature on CoV pathogenesis and cancer. We selected shared features of the two disease entities to develop a riskassessment score quantifying both the risk of infection and that implied in cancer treatment delay. Results: The score includes clinical and laboratory variables (Table 1). Pts' characteristics include: age, comorbidities (hypertension, cardiovascular disease, diabetes, chronic obstructive pulmonary disease, chronic systemic infections), obesity, sex, Eastern Cooperative Oncology Group (ECOG) performance status (PS), and concomitant steroid treatment (>10 mg/day of prednisone equivalent, lasting for >1-month period). Disease characteristics include: lung cancer diagnosis, history of thoracic radiotherapy (RT) (only for pts with extra-thoracic tumor). Treatment characteristics include: line of treatment, type (IT or combined IT/chemotherapy [CT] considered high-risk, followed by CT, and other anticancer drugs), history of immune-related adverse events (irAEs). Laboratory tests include levels of neutrophil-tolymphocite ratio (NLR), lactate-dehydrogenase (LDH), and C-reactive protein (CRP). Based on the resulting score, pts are divided in the following risk categories: low (score <4), intermediate (score 4-6), and high risk (score >7). Conclusions: There is a strong rationale supporting these variables as potential risk factors for COVID19 in cancer pts. The present score is currently undergoing validation on a wide population of cancer pts, to confirm its role and potentially help physicians' treatment decisions.

The appropriateness of invasive ventilation in covid-19 positive cancer patients: The hardest decision for oncologists

Background: Over the last two months we have frequently been contacted to estimate the prognosis of cancer patients (pts) affected by COVID-19 infection. Until now, there have been no clear markers to guide decision making regarding the appropriateness of invasive ventilation (IV) in COVID-19 cancer pts. Therefore, we developed a practical tool which encompasses a prognostic score in order to identify a subgroup of pts likely to have a better outcome and therefore may be potential candidates for IV. Methods: The Milano Policlinico ONCOVID-ICU score includes three different groups of variables. In the first group we included sex, age, body mass index (BMI) and comorbidities. The second group includes oncological variables, such as the treatment intent (adjuvant or metastatic), life expectancy in months and treatment status (on/ off). Furthermore, we included the SOFA score [1] and the d-dimer values, previously reported as risk factors for mortality in the presence of COVID-19 infection. Results: We identified three different groups. We recommend that pts with a low risk score should be offered IV if necessary, while high-risk pts are best managed with best supportive care. Pts in the intermediate-risk group deserve a case-by-case discussion to derive a decision (Table 1). Conclusions: A considerable proportion of oncology pts may experience clinical deterioration due to the worsening course of the infection. These cases require a comprehensive evaluation before considering ICU admission and IV. The division between groups is arbitrary and the score needs further validation. Therefore, we plan to assess the clinical history of all cancer pts admitted to Milano Hospital Maggiore Policlinico's ICU and retrospectively apply the score to this cohort.

Incidence of influenza-like illness (ILI) in cancer patients during covid-19: The oncovid prospective observational study

Background: There are limited data on cancer patients (pts) and the novel coronavirus (SARS-CoV2) respiratory disease (COVID19). Fever and/or respiratory symptoms (influenza-like illness, ILI) is a common finding in cancer pts. We aim to evaluate the frequency of ILI in cancer pts during the pandemic and to identify high-risk subjects to test for COVID19. Materials and methods: From March 20th to April 17th 2020 we collected data of cancer pts in a prospective clinical trial approved by the local ethics committee. The primary endpoint was to estimate the cumulative incidence of ILI in the study population. The secondary endpoint was to estimate which proportion of pts with ILI had COVID19 diagnosis. A triage procedure with questionnaires was performed in pts accessing the hospital, with laboratory tests (complete blood count, C-reactive protein) in pts on active treatment. Non-urgent visits were converted into telehealth visits and triage: pts with symptoms were addressed to general practitioners. Based on a diagnostic algorithm, pts with ILI symptoms underwent an infectious disease specialist's evaluation and SARS-CoV2 swab. The LepuMedical SARS-CoV2 immunoassay technique was used in pts with suspect symptoms or altered laboratory tests, not falling into the diagnostic algorithm. Results: Overall, 562 pts were enrolled: 13 (2%) pts had a positive SARS-CoV2 swab, none of which performed on the basis of triage procedures or questionnaires, rather detected through telephone communications and triage;52 (9%) pts reported suspect symptoms and/or laboratory tests. Forty-five (8%) SARS-CoV2 swab positive, or with suspect symptoms and/or laboratory tests pts underwent SARS-CoV2 antibody tests;20 (3%) pts were excluded for poor clinical conditions (n=10), death (n=4), or pts' refusal (n=6). Four out of 41 (10%) suspect pts had IgG+ (n=3), or IgM+/IgG+ (n=1);4 out of 4 COVID-19 positive pts had IgG+ (100%). Antibody tests were negative in the remaining 37 pts. Conclusions: In our experience, triage procedures and questionnaires were not helpful in detecting COVID19 in cancer pts. The incidence of both COVID19 diagnosis (2%), and SARS-CoV2 antibody positivity in pts tested on the basis of suspect symptoms (<1%), were similar to those observed in the general population.

Developing a risk assessment score for cancer patients during the COVID-19 pandemic

Background: Data on the novel coronavirus (CoV) respiratory disease (COVID-19) in cancer patients (pts) are limited. In some individuals, CoV infection triggers an aberrant inflammatory response, leading to lung tissue damage. Cancer pts treated with immunotherapy (IT) may therefore be more at risk for COVID-19 infection and related complications. Methods: We performed a thorough review of the literature on CoV pathogenesis and cancer, selecting shared features of the two disease entities to develop a risk-assessment score to quantify both the risk of infection and the risk implied in cancer treatment delays. Results: The score includes clinical and laboratory variables (Table). Pts' characteristics include: age, presence of comorbidities (hypertension, cardiovascular disease, diabetes, chronic obstructive pulmonary disease, chronic systemic infections), obesity, sex, Eastern Cooperative Oncology Group (ECOG) performance status (PS), and concomitant steroid treatment (>10 mg daily of prednisone equivalent, lasting for >1-month period). Disease characteristics include: lung cancer diagnosis, history of thoracic radiotherapy (RT) (only for pts with extra-thoracic tumours). Treatment characteristics include: line of treatment, type (IT or combined IT/chemotherapy [CT] considered high-risk, followed by CT, and other anticancer drugs), history of immune-related adverse events (irAEs). Laboratory tests include: levels of neutrophil-to-lymphocite ratio (NLR), lactate-dehydrogenase (LDH), and C-reactive protein (CRP). Based on the resulting score, pts can be divided in the following categories of risk: low (score <4), intermediate (score 4-6), and high risk (score >7). [Formula presented] Conclusions: There is a strong rationale supporting the presented data as potential risk factors for COVID-19 in cancer pts. The present score is currently undergoing validation on a wide population of cancer pts to confirm its role and potentially help physicians’ treatment decisions. Legal entity responsible for the study: The authors. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.

Incidence of influenza-like illness (ILI) in cancer patients during COVID-19: The ONCOVID prospective observational study

Background: There are limited data on cancer patients (pts) and the novel coronavirus (SARS-CoV2) respiratory disease (COVID-19). Fever and/or respiratory symptoms (influenza-like illness, ILI) is a common finding in cancer pts. We aim to evaluate the frequency of ILI in cancer pts during the pandemic, and to identify high-risk subjects to test for COVID-19. Methods: From March 20th to April 17th 2020 we collected data of cancer pts in a prospective trial approved by the local ethics committee. The primary endpoint was to estimate the cumulative incidence of ILI in the study population. The secondary endpoint was to estimate which proportion of pts with ILI had COVID-19 diagnosis. A triage procedure with questionnaires was performed in pts accessing the hospital, with laboratory tests (complete blood count, C-reactive protein) in pts on active treatment. Non-urgent visits were converted into telehealth visits and triage: pts with symptoms were addressed to general practitioners. Based on a diagnostic algorithm, pts with ILI symptoms underwent an infectious disease specialist’s evaluation and SARS-CoV2 swab. The LepuMedical SARS-CoV2 immunoassay technique was used in pts with suspect symptoms or altered laboratory tests, not falling into the diagnostic algorithm. Results: Overall, 562 pts were enrolled: 13 (2%) pts had a positive SARS-CoV2 swab, none of which performed on the basis of triage procedures or questionnaires, rather detected through telephone communications and triage;52 (9%) pts reported suspect symptoms and/or laboratory tests. Forty-five (8%) SARS-CoV2 swab positive, or with suspect symptoms and/or laboratory tests pts underwent SARS-CoV2 antibody (Ab) tests;20 (3%) pts were excluded for poor clinical conditions (n=10), death (n=4), or pts’ refusal (n=6). Four out of 41 (10%) suspect pts had IgG+ (n=3), or IgM+/IgG+ (n=1);4 out of 4 COVID-19 positive pts had IgG+ (100%). Ab tests were negative in the remaining 37 pts. Conclusions: In our experience, triage procedures and questionnaires were not helpful in detecting COVID-19 in cancer pts. The incidence of both COVID-19 diagnosis (2%), and SARS-CoV2 Ab positivity in pts tested on the basis of suspect symptoms (<1%), were similar to those observed in the general population. Legal entity responsible for the study: Dr. Francesco Grossi, MD. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.

The appropriateness of invasive ventilation in COVID-19 positive cancer patients: The hardest decision for oncologists

Background: Over the last two months we have frequently been contacted to estimate the prognosis of cancer patients (pts) affected by COVID-19 infection. Until now, there have been no clear markers to guide decision making regarding the appropriateness of invasive ventilation (IV) in COVID-19 cancer pts. Therefore, we developed a practical tool which encompasses a prognostic score in order to identify a subgroup of pts likely to have a better outcome and therefore may be potential candidates for IV. Methods: The Milano Policlinico ONCOVID-ICU score includes three different groups of variables. In the first group we included sex, age, body mass index (BMI) and comorbidities. The second group includes oncological variables, such as the treatment intent (adjuvant or metastatic), life expectancy in months and treatment status (on/off). Furthermore, we included the SOFA score [1] and the d-dimer values, previously reported as risk factors for mortality in the presence of COVID-19 infection. Results: We identified three different groups. We recommend that pts with a low risk score should be offered IV if necessary, while high-risk pts are best managed with best supportive care. Pts in the intermediate-risk group deserve a case-by-case discussion to derive a decision (Table). [Formula presented] Conclusions: A considerable proportion of oncology pts may experience clinical deterioration due to the worsening course of the infection. These cases require a comprehensive evaluation before considering ICU admission and IV. The division between groups is arbitrary and the score needs further validation. Therefore, we plan to assess the clinical history of all cancer pts admitted to Milano Hospital Maggiore Policlinico’s ICU and retrospectively apply the score to this cohort. [1] Ferreira FL et al. JAMA 2001;286:1754-8. Legal entity responsible for the study: The authors. Funding: Financed by Italian fiscal contribution "5x1000" 2016 devolved to Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico. Disclosure: All authors have declared no conflicts of interest.