The Interplay of Lung Cancer, COVID-19, and Vaccines.

Patients with cancer are more susceptible to a higher risk of coronavirus infection and its severe complications than the general population. In addition, these patients were not included in the pivotal clinical trials for COVID-19 vaccines. Therefore, considerable uncertainty remains regarding the management of cancer patients during the COVID-19 pandemic and the safety of COVID-19 vaccinations in cancer patients. In this review, we summarize the current knowledge generated from the beginning of the COVID-19 pandemic on the vulnerability of cancer patients to the coronavirus disease, as well as the effectiveness of COVID-19 vaccines in this population. We also discuss the available data on the effects of anticancer treatment with immune checkpoint inhibitors on the immune responses to SARS-CoV-2 in cancer patients. Special attention in this review will be given to patients with lung cancer, as such patients are at an increased risk for severe effects from COVID-19.

Predictive model for BNT162b2 vaccine response in cancer patients based on blood cytokines and growth factors.

Background: Patients with cancer, especially hematological cancer, are at increased risk for breakthrough COVID-19 infection. So far, a predictive biomarker that can assess compromised vaccine-induced anti-SARS-CoV-2 immunity in cancer patients has not been proposed. Methods: We employed machine learning approaches to identify a biomarker signature based on blood cytokines, chemokines, and immune- and non-immune-related growth factors linked to vaccine immunogenicity in 199 cancer patients receiving the BNT162b2 vaccine. Results: C-reactive protein (general marker of inflammation), interleukin (IL)-15 (a pro-inflammatory cytokine), IL-18 (interferon-gamma inducing factor), and placental growth factor (an angiogenic cytokine) correctly classified patients with a diminished vaccine response assessed at day 49 with >80% accuracy. Amongst these, CRP showed the highest predictive value for poor response to vaccine administration. Importantly, this unique signature of vaccine response was present at different studied timepoints both before and after vaccination and was not majorly affected by different anti-cancer treatments. Conclusion: We propose a blood-based signature of cytokines and growth factors that can be employed in identifying cancer patients at persistent high risk of COVID-19 despite vaccination with BNT162b2. Our data also suggest that such a signature may reflect the inherent immunological constitution of some cancer patients who are refractive to immunotherapy.

Impact of the First Wave of the COVID-19 Pandemic on the Lyon University Hospital Cancer Institute (IC-HCL).

This article presents the protective measures put in place at the "Institut de Cancérologie des Hospices de Lyon" (IC-HCL) during the first wave of the COVID-19 pandemic in France (spring 2020) and how they impacted IC-HCL clinical activity. Spring 2020 activities were compared to winter 2019-2020. Results showed a decrease of activity of 9% for treatment dispensations, 17% for multidisciplinary team meetings, 20% for head and neck and thoracic surgeries, and 58% for new patient enrolment in clinical trials. Characteristics of patients treated for solid cancer and hospitalized for COVID-19 during spring 2020 were collected in a retrospective study. Mortality was attributed to COVID-19 for half of the cases, 82% being patients above 70 and 73% being stage IV. This is in concordance with current findings concluding that the risk of developing severe or critical symptoms of COVID-19 is correlated with factors co-occurring in cancer patients and not to the cancer condition per se. While a number of routines and treatment regimens were changed, there was no major decline in numbers of treatments conducted at the IC-HCL during the first wave of the COVID-19 pandemic that hit France between March and May 2020, except for clinical trials and some surgery activities.

Blood Cytokine Analysis Suggests That SARS-CoV-2 Infection Results in a Sustained Tumour Promoting Environment in Cancer Patients.

Cytokines, chemokines, and (angiogenic) growth factors (CCGs) have been shown to play an intricate role in the progression of both solid and haematological malignancies. Recent studies have shown that SARS-CoV-2 infection leads to a worse outcome in cancer patients, especially in haematological malignancy patients. Here, we investigated how SARS-CoV-2 infection impacts the already altered CCG levels in solid or haematological malignancies, specifically, whether there is a protective effect or rather a potentially higher risk for major COVID-19 complications in cancer patients due to elevated CCGs linked to cancer progression. Serially analysing immune responses with 55 CCGs in cancer patients under active treatment with or without SARS-CoV-2 infection, we first showed that cancer patients without SARS-CoV-2 infection (n = 54) demonstrate elevated levels of 35 CCGs compared to the non-cancer, non-infected control group of health care workers (n = 42). Of the 35 CCGs, 19 were common to both the solid and haematological malignancy groups and comprised previously described cytokines such as IL-6, TNF-α, IL-1Ra, IL-17A, and VEGF, but also several less well described cytokines/chemokines such as Fractalkine, Tie-2, and T cell chemokine CTACK. Importantly, we show here that 7 CCGs are significantly altered in SARS-CoV-2 exposed cancer patients (n = 52). Of these, TNF-α, IFN-ß, TSLP, and sVCAM-1, identified to be elevated in haematological cancers, are also known tumour-promoting factors. Longitudinal analysis conducted over 3 months showed persistence of several tumour-promoting CCGs in SARS-CoV-2 exposed cancer patients. These data demonstrate a need for increased vigilance for haematological malignancy patients as a part of long COVID follow-up.

Severe acute respiratory syndrome coronavirus 2 vaccination for patients with solid cancer: Review and point of view of a French oncology intergroup (GCO, TNCD, UNICANCER).

The impacts of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic on cancer care are multiple, entailing a high risk of death from coronavirus disease 2019 (COVID-19) in patients with cancer treated by chemotherapy. SARS-CoV-2 vaccines represent an opportunity to decrease the rate of severe COVID-19 cases in patients with cancer and also to restore normal cancer care. Patients with cancer to be targeted for vaccination are difficult to define owing to the limited contribution of these patients in the phase III trials testing the different vaccines. It seems appropriate to vaccinate not only patients with cancer with ongoing treatment or with a treatment having been completed less than 3 years ago but also household and close contacts. High-risk patients with cancer who are candidates for priority access to vaccination are those treated by chemotherapy. The very high-priority population includes patients with curative treatment and palliative first- or second-line chemotherapy, as well as patients requiring surgery or radiotherapy involving a large volume of lung, lymph node and/or haematopoietic tissue. When possible, vaccination should be carried out before cancer treatment begins. SARS-CoV-2 vaccination can be performed during chemotherapy while avoiding periods of neutropenia and lymphopenia. For organisational reasons, vaccination should be performed in cancer care centres with messenger RNA vaccines (or non-replicating adenoviral vaccines in non-immunocompromised patients). Considering the current state of knowledge, the benefit-risk ratio strongly favours SARS-CoV-2 vaccination of all patients with cancer. To obtain more data concerning the safety and effectiveness of vaccines, it is necessary to implement cohorts of vaccinated patients with cancer.

[Vaccination against COVID-19 in patients with solid cancer: Review and point of view from a French oncology inter-group (CGO, TNCD, UNICANCER)]. / Vaccination contre la COVID-19 des patients atteints de cancer solide : revue et préconisations d'un inter-groupe oncologique français (CGO, TNCD, UNICANCER).

The COVID-19 pandemic has a major impact at all stages of cancer treatment. Risk of death from COVID-19 in patients treated for a cancer is high. COVID-19 vaccines represent a major issue to decrease the rate of severe forms of the COVID-19 cases and to maintain a normal cancer care. It is difficult to define the target population for vaccination due to the limited data available and the lack of vaccine doses available. It appears theoretically important to vaccinate patients with active cancer treatment or treated since less than three years, as well as their family circle. In France, patients actually defined at "high risk" for priority access to vaccination are those with a cancer treated by chemotherapy. A panel of experts recently defined another "very high-priority" population, which includes patients with curative or palliative first or second-line chemotherapy, as well as patients requiring surgery or radiotherapy involving a large lung volume, lymph nodes and/or of hematopoietic tissue. Ideally, it is best to vaccinate before cancer treatment. Despite the lack of published data, COVID-19 vaccines can also be performed during chemotherapy by avoiding periods of bone marrow aplasia and if possible, to do it in cancer care centers. It is necessary to implement cohorts with immunological and clinical monitoring of vaccinated cancer patients. To conclude, considering the current state of knowledge, the benefit-risk ratio strongly favours COVID-19 vaccination of all cancer patients.

Cancer History and Systemic Anti-Cancer Therapy Independently Predict COVID-19 Mortality: A UK Tertiary Hospital Experience.

BACKGROUND: The COVID-19 pandemic remains a pressing concern to patients with cancer as countries enter the second peak of the pandemic and beyond. It remains unclear whether cancer and its treatment contribute an independent risk for mortality in COVID-19. METHODS: We included patients at a London tertiary hospital with laboratory confirmed SARS-CoV-2 infection. All patients with a history of solid cancer were included. Age- and sex-matched patients without cancer were randomly selected. Patients with hematological malignancies were excluded. RESULTS: We identified 94 patients with cancer, matched to 226 patients without cancer. After adjusting for age, ethnicity, and co-morbidities, patients with cancer had increased mortality following COVID-19 (HR 1.57, 95% CI:1.04-2.4, p = 0.03). 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) also predicted mortality. Within the cancer cohort, systemic anti-cancer therapy (SACT) within 60 days of COVID-19 diagnosis was an independent risk factor for mortality (HR 2.30, 95% CI: 1.16-4.6, p = 0.02). CONCLUSIONS: Along with known risk factors, cancer and SACT confer an independent risk for mortality following COVID-19. Further studies are needed to understand the socio-economic influences and pathophysiology of these associations.