No abstract

Introduction: The outbreak of COVID-19 poses an unprecedented challenge to global public health. Patients with cancer are at a higher risk during the SARS-CoV-2 pandemic. Patients with lung cancer and COVID-19 were compared to those without cancer and those with other malignancies for the main outcome of this study. The aim of this study was to evaluate the differences in susceptibility, disease severity, and mortality between lung cancer patients and the general population. Methods: Using PRISMA reporting guidelines, we conducted a systematic review and meta-analysis of the published literature. The Cochrane Library database, PubMed, EMBASE, and PubMed Central were comprehensively searched for published papers until 31 May 2022. A pooled risk ratio (OR) with 95% CI was presented as the result of this meta-analysis. Results: We included 29 studies involved 21,257 patients with lung cancer and SARS-CoV-2 infection. Analysis data showed that mortality in patients with lung cancer was significantly higher than that in patients without cancer (HR = 2.00 [95%CI 1.52, 2.63], p < 0.01) or with other malignancies (HR = 1.91 [95%CI 1.53, 2.39], p < 0.01). In addition, we also observed a higher risk of severe infection in terms of life-threatening or required ICU admission/mechanical ventilation for lung cancer patients (HR = 1.47 [95%CI 1.06, 2.03], p = 0.02) than for patients with no cancer or other malignancies. Regarding lung cancer as a risk factor for acquiring SARS-CoV-2 infection, we could not reach statistical significance (hazard ratio [HR] =2.73 [95%CI 0.84, 8.94], p = 0.1). Conclusion: Lung cancer represents an important comorbidity and modifies COVID-19 prognosis in terms of disease severity and mortality. More patients experience severe or even fatal events. Considering their inherent fragility, patients with lung cancer, and generally all oncological populations, should be treated more carefully during the COVID-19 pandemic.

Background: The immune system (innate and adaptive) is influenced by vitamin D3, which affects gene expression and inflammatory pathways. An umbrella review was conducted to evaluate the power and accuracy of data connecting vitamin D3 to the outcomes of COVID-19 infection and to appraise the proof provided by published meta-analyses. Methods: MEDLINE, Embase, and the Cochrane Library were searched from database inception to 31 May 2022. Meta-analyses of prospective or retrospective observational studies and randomized trials were included. Evidence of association was graded according to the established criteria: strong, highly suggestive, suggestive, weak, or not significant. Results: From 74 publications, 27 meta-analyses described five associations between vitamin D3 levels and supplementation and COVID-19 outcomes. Low levels of vitamin D3 were significantly associated with severity (highly suggestive evidence; OR = 1.97 [95% CI, 1.55–2.51], p < 0.01; I2 = 77%, p < 0.01) and mortality risk due to COVID-19 disease (OR = 1.83 [95% CI, 1.55–2.16], p < 0.01; I2 = 50%, p < 0.01). Vitamin D3 supplementation, after a diagnosis of COVID-19 infection, was associated with significantly reduced infection severity (e.g., ICU admission) and mortality. Conclusions: This umbrella review of the available evidence suggests that insufficient vitamin D3 may increase COVID-19 infection risk, severity, and mortality, in addition to showing a highly suggestive association between vitamin D3 supplementation and reduced severity and mortality among infected patients.

Purpose Breast cancer (BC) patients’ (pts) management was affected by a global reorganization after Coronavirus disease 2019 (COVID-19). Our multicenter study aimed to assess the impact of COVID-19 on access to diagnosis, staging and treatment for BC pts compared to pre-pandemic. Methods Medical records of all consecutive newly diagnosed BC pts referred to 6 Italian Institutions between March and December 2020 were assessed. Monthly access rate and temporal intervals between date of symptoms onset, radiological, cytohistological diagnosis and treatment start were analyzed and compared with those of 2019. Results A reduction (25%) in newly diagnosed BC pts was observed compared to 2019 (666 vs 890). New BC pts in 2020 were less likely to be diagnosed with early stage (stage 0-I-II) BC (77% vs 83%, p<0.01), had a worse ECOG PS (19.8% had PS>0 in 2020 vs 16.5% in 2019, p<0.01) and fewer patients were asymptomatic at diagnosis in 2020 (54% vs 71%, p<0.01). COVID-19 did not negatively impact in terms of access to diagnosis, staging and treatment. Time intervals between symptom onset and radiological diagnosis, symptom onset and cytohistological diagnosis, cytohistological diagnosis and treatment start were maintained or even improved. However, less BC cases were discussed in multidisciplinary tumor meetings during 2020 (60% vs 73%, p<0.01). Conclusions Our data proved an alarming reduction of BC early stage diagnoses in 2020. Despite the upheaval generated by COVID-19, our study shed light on the effective performance delivered by Italian Oncology Departments to guarantee diagnostic-therapeutic pathways.

3569 Background: Encorafenib plus cetuximab is a standard option in the treatment of BRAF V600E mut mCRC pts pre-treated with at least one systemic therapy. RNF43 is a negative regulator of WNT pathway. A recent study showed that RNF43 mutation is associated with better outcome among pMMR/MSS BRAF V600E mut mCRC patients treated with TT but not in an independent cohort of pts not treated with TT (Elez et al. Nat Med 2022). However, no comparison is available between TT vs CT as second-line (2L) treatment for pMMR/MSS BRAF V600E mut mCRC according to RNF43 mutational status. Methods: The predictive impact of RNF43 mut was evaluated in a real-life dataset of 126 pMMR/MSS BRAF V600E mut mCRC pts treated with TT (consisting of BRAF inhibitor + anti-EGFR antibody ± MEK inhibitor) vs CT ± target agent as 2L treatment. A cohort of 36 pts receiving TT after 2L was also analyzed. Results: Thirty-one (25%) and 95 (75%) out of 126 pMMR/MSS BRAF V600E mut tumours were RNF43 mut and RNF43 wt, respectively. In the RNF43 mut group 14 (45%) received CT and 17 (55%) TT; in the RNF43 wt group, 56 (59%) and 39 (42%) received CT and TT, respectively. Among RNF43 mut pts, those treated with TT reported longer PFS (7.1 vs 3.0 months, HR: 0.35 95%CI: 0.16-0.76, p = 0.006) and higher ORR (42% vs 0%, p = 0.009) than those receiving CT. On the other hand, no significant difference was observed among RNF43 wt patients in terms of PFS (4.3 vs 3.7 months, HR: 0.69 95% CI: 0.45-1.05, p = 0.080) and ORR (28% vs 16%, p = 0.24). However, no significant interaction between treatment effect and RNF43 mutational status was reported in terms of PFS (pinteraction= 0.17) and ORR (pinteraction= 0.96). After excluding 36 pts in the CT group that received TT after 2L, no interaction effect was observed also in terms of OS (pinteraction= 0.53). However, among RNF43 mut pts, those treated with TT reported longer OS (16.5 vs 10.1 months; HR: 0.34 95% CI: 0.11-1.00, p = 0.049), while no significant difference was observed among RNF43 wt pts (10.6 vs 6.6 months; HR: 0.66 95% CI: 0.39-1.11; p = 0.12). In the group receiving TT after 2L, 9 (25%) out of 36 cases were RNF43 mut and achieved higher ORR (78% vs 26%, p = 0.014) and longer PFS (10.1 vs 4 months; HR: 0.35 95%CI: 0.14-0.88; p = 0.020) and OS (11.7 vs 7 months; HR: 0.35 95%CI: 0.15-0.82; p = 0.012) than RNF43 wt (N = 27). Conclusions: pMMR/MSS BRAF V600E mut mCRC patients achieve benefit from TT vs CT independently of RNF43 mutational status, but a higher magnitude of benefit from TT is observed among those with RNF43 mut tumors. These findings deserve confirmation in past and current randomized trials (i.e. BEACON and BREAKWATER).