Johan Pluvy

Background: Prophylactic cranial irradiation (PCI) is recommended to decrease the incidence of brain metastases (BM) in extensive-stage small-cell lung cancer (ESSCLC) without BM after response to chemotherapy. However, PCI is associated with significant neurocognitive effects, and new studies are debating its benefits. Moreover, the introduction of immunotherapy in the management of the disease has raised new questions, and there is a lack of data on PCI and immunotherapy. We report a single-center retrospective study evaluating the impact of omitting PCI from real-life treatment, including immunotherapy, of patients with ES-SCLC. Methods: We identified patients followed at APHM between January 2014 and January 2021 for ES-SCLC without BM with an indication for PCI. The main assessment criteria considered in this study were overall survival (OS) and brain metastasis-free survival (BMFS) between patients who received PCI and those who did not. Results: 56 patients were included, 25 receiving PCI and 31 without PCI. The median follow-up was 16 months. Eighteen patients received immunotherapy, mostly in the group without PCI (p = 0.024). The median OS and BMFS were, respectively, 11.7 and 13.4 months in patients with PCI, and 20.3 and 10.7 months in patients without PCI, without any significant statistical difference (p = 0.412, p = 0.336). The prognostic factors highlighted in multivariate analysis were initial performance status (PS) < 2 for OS (HR = 2.74 (IC95% [1.23; 6.13])) and monocyte lymphocyte ratio (MLR) < 0.12 for BMFS (HR = 1.21 (IC95% [1.01; 1.45])). A recursive partitioning analysis (RPA) found PS, immunotherapy, and age to be influential factors for OS but not PCI. Conclusions: The clinical results of our study showed no benefit of PCI in terms of OS and BMFS for patients with ES-SCLC. This can be explained by the lack of benefit of PCI or by the introduction of immunotherapy.

Walking speed (WS) has emerged as a potential predictor of mortality in elderly cancer patients, yet data involving non-small-cell lung cancer (NSCLC) patients are scarce. Our prospective exploratory study sought to determine whether WS would predict early death or toxicity in patients with advanced NSCLC receiving first-line systemic intravenous treatment. Overall, 145 patients of ≥70 years were diagnosed with NSCLC over 19 months, 91 of whom displayed locally-advanced or metastatic cancer. As first-line treatment, 21 (23%) patients received best supportive care, 13 (14%) targeted therapy, and 57 (63%) chemotherapy or immunotherapy. Among the latter, 38 consented to participate in the study (median age: 75 years). Median cumulative illness rating scale for geriatrics (CIRS-G) was 10 (IQR: 8–12), and median WS 1.09 (IQR: 0.9–1.31) m/s. Older age (p = 0.03) and comorbidities (p = 0.02) were associated with Grade 3–4 treatment-related adverse events or death within 6 months of accrual. Overall survival was 14.3 (IQR: 6.1-NR) months for patients with WS < 1 m/s versus 17.3 (IQR: 9.2–26.5) for those with WS ≥ 1 m/s (p = 0.78). This exploratory study revealed WS to be numerically, yet not significantly, associated with early mortality in older metastatic NSCLC patients. Following these hypothesis-generating results, a larger prospective, multicenter study appears to be required to further investigate this outcome.

In cancer patients, ERBB4 fusions have been reported in the literature with various gene partners (IKZF, B4GALT5 and EZR) [1–3] allowing dimerisation and constitutive activation of the ERBB4 tyrosine kinase domain. Here, we report a new fusion of ERBB4 with the coiled-coil domain encoded by KIF5B, a universal partner in lung cancer gene fusions, in a patient with a stage IV lung adenocarcinoma.

Background: The optimal treatment for patients with severe coronavirus-19 disease (COVID-19) and hyper-inflammation remains debated. Material and methods: A cohort study was designed to evaluate whether a therapeutic algorithm using steroids with or without interleukin-1 antagonist (anakinra) could prevent death/invasive ventilation. Patients with a ≥5-day evolution since symptoms onset, with hyper-inflammation (CRP≥50mg/L), requiring 3–5 L/min oxygen, received methylprednisolone alone. Patients needing ≥6 L/min received methylprednisolone + subcutaneous anakinra daily either frontline or in case clinical deterioration upon corticosteroids alone. Death rate and death or intensive care unit (ICU) invasive ventilation rate at Day 15, with Odds Ratio (OR) and 95% CIs, were determined according to logistic regression and propensity scores. A Bayesian analysis estimated the treatment effects. Results: Of 108 consecutive patients, 70 patients received glucocorticoids alone. The control group comprised 63 patients receiving standard of care. In the corticosteroid±stanakinra group (n = 108), death rate was 20.4%, versus 30.2% in the controls, indicating a 30% relative decrease in death risk and a number of 10 patients to treat to avoid a death (p = 0.15). Using propensity scores a per-protocol analysis showed an OR for COVID-19-related death of 0.9 (95%CI [0.80–1.01], p = 0.067). On Bayesian analysis, the posterior probability of any mortality benefit with corticosteroids+/-anakinra was 87.5%, with a 7.8% probability of treatment-related harm. Pre-existing diabetes exacerbation occurred in 29 of 108 patients (26.9%). Conclusion: In COVID-19 non-ICU inpatients at the cytokine release phase, corticosteroids with or without anakinra were associated with a 30% decrease of death risk on Day 15.