with a cluster of pneumonia cases in Wuhan, a city within the central part of China, and has rapidly evolved into a global pandemic [1]. The putative pathogen is a novel coronavirus that presents a close resemblance to a known bat coronavirus termed BatCoV RaTG13, thus favoring a bat-to-human transmission hypothesis before eventually identifying human-to-human transmission [2,3]. It presents a high transmission rate with one new infected case producing an average of 2.9 new secondary cases and a fatality rate of 2.3% [4,5]. As a result, thousands of severe cases have died every day worldwide due to the pressure on the healthcare system and lack of specific treatments. Not surprisingly, cancer patients, compared with the general population, are regarded as a highly vulnerable group because of their immunosuppressive state due to malignancy, chemotherapy and comorbidities. Thus, oncologists are obliged to reconsider anticancer treatments while taking into consideration the risk of complication and cancer progression [6]. An updated WHO report demonstrates a mortality of 7.6% among patients with cancer [7]. Subsequently, several societies have issued conservative guidelines inviting oncologists to consider, on a case-by-case basis, the possibility of delaying treatment administration [8][9][10][11][12]. In this paper, we provide the oncologists with the available evidence concerning COVID-19 in cancer patients to better guide management decisions. COVID-19 infections in cancer patientsAs China was the first epicenter for the pandemic, the Chinese epidemiological data constitutes the bulk of published literature reporting COVID-19 infections. The early case series including a total of 300 COVID-19 patients identified 2 cancer patients only [4,13]. Later case series by Liang et al. (18 cases), Zhang et al. (28 cases) and Zhang et al. (67 cases) reported a higher prevalence of cancer patients with COVID-19 infections compared with the overall population (1 vs 0.29%) [14], a higher median age at diagnosis (63-66 vs 49 years) [14][15][16] and a male predominance (61%) [15,16]. Lung cancers (22-25%), gastrointestinal cancers (14-16%) and breast cancers (11%) were the most commonly encountered tumors [15,16]. The clinical features included fever (80-82%), dry cough (75-81%) and dyspnea (50-66%) [15,16]. Dyspnea was more frequently noted at admission in severe cases (56.3 vs 11.4%) and in nonsurvivors (66.7 vs 20.4%) whereas the other symptoms were similar between mild and severe cases [16]. Laboratory tests showed hypoproteinemia (89%), lymphopenia (82%), increased level of CRP (82%) and anemia (75%) [15]. In comparison with patients without cancer, cancer patients had a higher risk of adverse events (39 vs 8%; p = 0.0003) and deteriorated more rapidly (13 vs 43 days, HR = 3.56; 95% CI: 1.65-7.69) [14]. Severe events were reported in 48-54% of cases (versus 16% in the overall population), notably among patients receiving anticancer treatment within the previous 2 weeks (OR = 4.079; 95% CI: 1.086-15.322) [14][15][16]. Compa...
BackgroundA synergy between radiotherapy and anti-cytotoxic-T-lymphocyte-associated antigen 4 (anti-CTLA-4) monoclonal antibody has been demonstrated preclinically. The Mel-Ipi-Rx phase 1 study aimed to determine the maximum tolerated dose (MTD) and safety profile of radiotherapy combined with ipilimumab in patients with metastatic melanoma.Patients and methodsA 3+3 dose escalation design was used with 9, 15, 18 and 24 Gy dose of radiotherapy at week 4 combined with 10 mg/kg ipilimumab every 3 weeks for four doses. Patients with evidence of clinical benefit at week 12 were eligible for maintenance with ipilimumab 10 mg/kg every 12 weeks starting at week 24 until severe toxicity or disease progression. The database lock occurred on April 30, 2019. Tumor growth rate of irradiated lesions and non-irradiated lesions were analyzed to assess the systemic immunologic antitumor response. Blood immune monitoring was performed before and during treatment to determine if radiotherapy could modify ipilimumab pharmacodynamics.Results19 patients received ipilimumab between August 2011 and July 2015. Nine patients received the four doses of ipilimumab. All patients received the combined radiotherapy. Grade 3 adverse events occurred in nine patients, the most common being colitis and hepatitis. No drug-related death occurred. Dose limiting toxicity occurred in two of six patients in the cohort receiving 15 Gy. The MTD was 9 Gy. Two patients had complete response, three had partial response response and seven had stable disease, giving an objective response rate of 31% and a clinical benefit rate of 75% at week 24. The median duration of follow-up was 5.8 years (Q1=4.5; Q3=6.8). The median overall survival (95% CI) was estimated at 0.9 years (0.5–2). The median progression-free survival (PFS) (95% CI) was 0.4 (0.2–1.4). Radiotherapy combined with ipilimumab was associated with increased CD4+ and CD8+ICOS+ T cells. Increased CD8+ was significantly associated with PFS.ConclusionWhen combined with ipilimumab at 10 mg/kg, the MTD of radiotherapy was 9 Gy. This combination of ipilimumab and radiotherapy appears to be associated with antitumor activity. Increased CD8+ was significantly associated with PFS. Thus, immune biomarkers may be useful for early response evaluation.Trial registration numberNCT01557114.
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