Consolidative thoracic radiation therapy for extensive-stage small cell lung cancer in the era of first-line chemoimmunotherapy: preclinical data and a retrospective study in Southern Italy

BackgroundConsolidative thoracic radiotherapy (TRT) has been commonly used in the management of extensive-stage small cell lung cancer (ES-SCLC). Nevertheless, phase III trials exploring first-line chemoimmunotherapy have excluded this treatment approach. However, there is a strong biological rationale to support the use of radiotherapy (RT) as a boost to sustain anti-tumor immune responses. Currently, the benefit of TRT after chemoimmunotherapy remains unclear. The present report describes the real-world experiences of 120 patients with ES-SCLC treated with different chemoimmunotherapy combinations. Preclinical data supporting the hypothesis of anti-tumor immune responses induced by RT are also presented.MethodsA total of 120 ES-SCLC patients treated with chemoimmunotherapy since 2019 in the South of Italy were retrospectively analyzed. None of the patients included in the analysis experienced disease progression after undergoing first-line chemoimmunotherapy. Of these, 59 patients underwent TRT after a multidisciplinary decision by the treatment team. Patient characteristics, chemoimmunotherapy schedule, and timing of TRT onset were assessed. Safety served as the primary endpoint, while efficacy measured in terms of overall survival (OS) and progression-free survival (PFS) was used as the secondary endpoint. Immune pathway activation induced by RT in SCLC cells was explored to investigate the biological rationale for combining RT and immunotherapy.ResultsPreclinical data supported the activation of innate immune pathways, including the STimulator of INterferon pathway (STING), gamma-interferon-inducible protein (IFI-16), and mitochondrial antiviral-signaling protein (MAVS) related to DNA and RNA release. Clinical data showed that TRT was associated with a good safety profile. Of the 59 patients treated with TRT, only 10% experienced radiation toxicity, while no ≥ G3 radiation-induced adverse events occurred. The median time for TRT onset after cycles of chemoimmunotherapy was 62 days. Total radiation dose and fraction dose of TRT include from 30 Gy in 10 fractions, up to definitive dose in selected patients. Consolidative TRT was associated with a significantly longer PFS than systemic therapy alone (one-year PFS of 61% vs. 31%, p<0.001), with a trend toward improved OS (one-year OS of 80% vs. 61%, p=0.027).ConclusionMulti-center data from establishments in the South of Italy provide a general confidence in using TRT as a consolidative strategy after chemoimmunotherapy. Considering the limits of a restrospective analysis, these preliminary results support the feasibility of the approach and encourage a prospective evaluation

Long-Term Follow-Up of Catheter Ablation for Premature Ventricular Complexes in the Modern Era: The Importance of Localization and Substrate

Background: Large-scale studies evaluating long-term recurrence rates in both idiopathic and non-idiopathic PVC catheter ablation (CA) patients have not been reported. Objective: To evaluate the efficacy and safety of idiopathic and non-idiopathic PVC CA, investigating the predictors of acute and long-term efficacy. Methods: This retrospective multicentric study included 439 patients who underwent PVC CA at three institutions from April-2015 to December-2021. Clinical success at 6 months’ follow-up, defined as a reduction of at least 80% of the pre-procedural PVC burden, was deemed the primary outcome. The secondary aims of the study were: clinical success at the last available follow-up, predictors of arrhythmic recurrences at long-term follow-up, and safety outcomes. Results: The median age was 51 years, with 24.9% patients being affected suffering from structural heart disease. The median pre-procedural PVC burden was 20.1%. PVCs originating from the RVOT were the most common index PVC observed (29.1%), followed by coronary cusp (CC) and non-outflow tract (OT) LV PVCs (23.1% and 19.0%). The primary outcome at 6 months was reached in 85.1% cases, with a significant reduction in the 24 h% PVC burden (−91.4% [−83.4; −96.7], p < 0.001); long-term efficacy was observed in 82.1% of cases at almost 3-year follow-up. The presence of underlying structural heart disease and non-OT LV region origin (aHR 1.77 [1.07–2.93], p = 0.027 and aHR = 1.96 [1.22–3.14], p = 0.005) was independently associated with recurrences. Conclusion: CA of both idiopathic and non-idiopathic PVCs showed a very good acute and long-term procedural success rate, with an overall low complication. Predictors of arrhythmic recurrence at follow-up were underlying structural heart disease and non-OT LV origin

Patients with Cardiac Implantable Electronic Device Undergoing Radiation Therapy: Insights from a Ten-Year Tertiary Center Experience

Background: The number of patients with cardiac implantable electronic devices (CIEDs) receiving radiotherapy (RT) is increasing. The management of CIED-carriers undergoing RT is challenging and requires a collaborative multidisciplinary approach. Aim: The aim of the study is to report the real-world, ten-year experience of a tertiary multidisciplinary teaching hospital. Methods: We conducted an observational, real-world, retrospective, single-center study, enrolling all CIED-carriers who underwent RT at the San Raffaele University Hospital, between June 2010 and December 2021. All devices were MRI-conditional. The devices were programmed to an asynchronous pacing mode for patients who had an intrinsic heart rate of less than 40 beats per minute. An inhibited pacing mode was used for all other patients. All tachyarrhythmia device functions were temporarily disabled. After each RT session, the CIED were reprogrammed to the original settings. Outcomes included adverse events and changes in the variables that indicate lead and device functions. Results: Between June 2010 and December 2021, 107 patients were enrolled, among which 63 (58.9%) were pacemaker carriers and 44 (41.1%) were ICD carriers. Patients were subjected to a mean of 16.4 (±10.7) RT sessions. The most represented tumors in our cohort were prostate cancer (12; 11%), breast cancer (10; 9%) and lung cancer (28; 26%). No statistically significant changes in device parameters were recorded before and after radiotherapy. Generator failures, power-on resets, changes in pacing threshold or sensing requiring system revision or programming changes, battery depletions, pacing inhibitions and inappropriate therapies did not occur in our cohort of patients during a ten-year time span period. Atrial arrhythmias were recorded during RT session in 14 patients (13.1%) and ventricular arrhythmias were observed at device interrogation in 10 patients (9.9%). Conclusions: Changes in device parameters and arrhythmia occurrence were infrequent, and none resulted in a clinically significant adverse event

Innovative biomarkers in psychiatric disorders: a major clinical challenge in psychiatry

Introduction: Currently, the diagnosis of psychiatric illnesses is based upon DSM-5 criteria. Although endophenotype-specificity for a particular disorder is discussed, the identification of objective biomarkers is ongoing for aiding diagnosis, prognosis, or clinical response to treatment. We need to improve the understanding of the biological abnormalities in psychiatric illnesses across conventional diagnostic boundaries. The present review investigates the innovative post-genomic knowledge used for psychiatric illness diagnostics and treatment response, with a particular focus on proteomics. Areas covered: This review underlines the contribution that psychiatric innovative biomarkers have reached in relation to diagnosis and theragnosis of psychiatric illnesses. Furthermore, it encompasses a reliable representation of their involvement in disease through proteomics, metabolomics/pharmacometabolomics and lipidomics techniques, including the possible role that gut microbiota and CYP2D6 polimorphisms may play in psychiatric illnesses. Expert opinion: Etiologic heterogeneity, variable expressivity, and epigenetics may impact clinical manifestations, making it difficult for a single measurement to be pathognomonic for multifaceted psychiatric disorders. Academic, industry, or governmentâ\u80\u99s partnerships may successfully identify and validate new biomarkers so that unfailing clinical tests can be developed. Proteomics, metabolomics, and lipidomics techniques are considered to be helpful tools beyond neuroimaging and neuropsychology for the phenotypic characterization of brain diseases

Parents' Perspective of Antibiotic Usage in Children: A Nationwide Survey in Italy

Antibiotics represent the most widely prescribed drugs in children worldwide, both in hospital and community settings. A comprehensive approach to understanding the reasons and determinants of antibiotic prescription in the pediatric age is needed. This study aimed to assess parents' attitudes and perspectives about antibiotic use

Inflammation as a Predictor of Recurrent\ua0Ventricular Tachycardia After Ablation in Patients With Myocarditis

Little is known about the risk stratification of patients with myocarditis undergoing ventricular tachycardia (VT) ablation