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Stereotactic body radiotherapy has been established as a viable treatment option for inoperable early-stage non-small cell lung cancer or secondary lesions mainly in oligoprogressive/oligometastatic scenarios. Treating lesions in the so-called "no flight zone" has always been challenging and conflicting data never cleared how to safely treat these lesions. This is truer considering ultra-central lesions, i.e., directly abutting or whose PTV is overlapping critical mediastinal organs. While historical retrospective data are abundant but mostly heterogenous in terms of the definition of ultra-central lesions, dosing regimens and outcomes, prospective data remain scarce, even though recently published studies have given new encouraging results for such delicate treatment scenarios. For this reason, we aimed to review and summarize current knowledge on stereotactic radiation treatment for ultra-central thoracic lesions, highlighting the most recent advances and the messages that can be taken from them. Lastly, we propose a workflow of the necessary steps to identify and treat such patients, therefore helping in elucidating the advantages and caveats of such treatment options.

Background (1): Our goal was to investigate if and how pre-operative inflammatory status can influence the long-term prognosis of patients undergoing lung surgery for cancer. Materials and Methods (2): This prospective observational study includes the agreement of all operable patients to the study, who were referred to our department between 1 January 2017 and 30 December 2018. The inflammatory pre-operative status of the patients was investigated by calculating albumin, CPR (c-protein reactive), complete blood count (neutrophils, lymphocytes, platelets, hemoglobin), and some other indexes referring to inflammatory status, namely the HALP amalgamated index, platelet-to-lymphocyte ratio (PLR), neutrophil-to-lymphocytes ratio (NLR), systemic immune-inflammation index (SII), and advanced lung cancer inflammation Index (ALI). The follow-up ended in November 2021. Patient overall survival was assessed using the Kaplan-Meier method. The log-rank test was used to compare survival rates. Variables significantly associated with survival at univariate analysis were entered int Cox multivariate analysis (stepwise mode) to assess their independent character. Hazard ratios and their 95% confidence intervals were calculated. Variables associated with p < 0.05 were considered significative. Results (3) : We enrolled 257 patients in our study. The overall survival of the cohort was as follows: 1 year, 96.1%; 3 year, 81.3%; and 4 year, 74.2%. Univariate analysis showed risk factors for overall survival as follows: Thoracoscore ≥ 2 ( p = 0.002); histology ( p = 0.002); HALP < 32.2 ( p = 0.0002); SII ≥ 808.9 ( p = 0.0004); ALI < 34.86 ( p = 0.0005); NLr ≥ 2.29 ( p = 0.01); hemoglobin < 13 g/dl ( p = 0.01); PLR ≥ 196.1 ( p = 0.005); pN+ ( p < 0.0001); pleural invasion ( p = 0.0002); and presence of vascular or lymphatic tumor emboli ( p = 0.0002). Multivariate Cox analysis (stepwise model) identified Thoracoscore ≥ 2 ( p = 0.02); histology, HALP < 32.2 ( p = 0.004), and pN ( p < 0.0001) as independent predictors of death. Conclusion (4): Pre-operative inflammatory status strongly influences long-term prognosis in patients affected by NSCLC and undergoing surgery.

Biochemical recurrences after radical prostatectomy (RP) can be managed with curative purpose through salvage radiation therapy (SRT). RT dose escalation, such as stereotactic RT (SSRT), may improve relapse-free survival in this setting. STARR trial (NCT05455736) is a prospective multicenter study including patients affected by macroscopic recurrence within the prostate bed after RP treated with SSRT. Recurrence was detected with a Choline or PSMA CT-PET. In the current analysis, the early biochemical response (BR) rate and toxicity profile after three months of follow-up were assessed. Twenty-five patients were enrolled, and data about BR and toxicity at three months after treatment were available for 19 cases. Overall, BR was detected after three months in 58% of cases. Four G1-G2 adverse events were recorded; no G ≥ 3 adverse events were detected. SSRT appears feasible and safe, with more than half of patients experiencing BR and an encouraging toxicity profile. The STARR trial is one of the few prospective studies aimed at implementing this promising treatment strategy in this scenario.

Introduction: Stereotactic body radiotherapy (SBRT) reported excellent outcomes and a good tolerability profile in case of central lung tumors, as long as risk-adapted schedules were adopted. High grade toxicity was more frequently observed for tumors directly touching or overlapping the trachea, proximal bronchial tree (PBT), and esophagus. We aim to identify prognostic factors associated with survival for Ultra-Central (UC) tumors. Methods: We retrospectively evaluated patients treated with SBRT for primary or metastatic UC lung tumors. SBRT schedules ranged from 45 to 60 Gy. Results: A total number of 126 ultra-central lung tumors were reviewed. The Median follow-up time was 23 months. Median Overall Survival (OS) and Progression Free Survival (PFS) was 29.3 months and 16 months, respectively. Local Control (LC) rates at 1 and 2 were 86% and 78%, respectively. Female gender, age < 70 years, and tumor size < 5 cm were significantly associated with better OS. The group of patients with tumors close to the trachea but further away from the PBT also correlated with better OS. The acute G2 dysphagia, cough, and dyspnea were 11%, 5%, and 3%, respectively. Acute G3 dyspnea was experienced by one patient. Late G3 toxicity was reported in 4% of patients. Conclusion: risk-adaptive SBRT for ultra-central tumors is safe and effective, even if it remains a high-risk clinical scenario.

Introduction: Targeted dose-escalation and reduction of dose to adjacent organs at risk have been the main goal of radiotherapy in the last decade. Prostate cancer benefited the most from this process. In recent years, the development of Intensity Modulated Radiation Therapy (IMRT) and Stereotactic Body Radiotherapy (SBRT) radically changed clinical practice, also thanks to the availability of modern imaging techniques. The aim of this paper is to explore the relationship between diagnostic imaging and prostate cancer radiotherapy techniques., Materials and Methods: Aiming to provide an overview of the integration between modern imaging and radiotherapy techniques, we performed a non-systematic search of papers exploring the predictive value of imaging before treatment, the role of radiomics in predicting treatment outcomes, implementation of novel imaging in RT planning and influence of imaging integration on use of RT in current clinical practice. Three independent authors (GF, IM and ID) performed an independent review focusing on these issues. Key references were derived from a PubMed query. Hand searching and clinicaltrials.gov were also used, and grey literature was searched for further papers of interest. The final choice of papers included was discussed between all co-authors., Results: This paper contains a narrative report and a critical discussion of the role of new modern techniques in predicting outcomes before treatment, in radiotherapy planning and in the integration with systemic therapy in the management of prostate cancer. Also, the role of radiomics in a tailored treatment approach is explored., Conclusions: Integration between diagnostic imaging and radiotherapy is of great importance for the modern treatment of prostate cancer. Future clinical trials should be aimed at exploring the real clinical benefit of complex workflows in clinical practice.

Introduction: Neoadjuvant radiotherapy is currently used mainly in locally advanced rectal cancer and sarcoma and in a subset of non-small cell lung cancer and esophageal cancer, whereas in other diseases it is under investigation. The evaluation of the efficacy of the induction strategy is made possible by performing imaging investigations before and after the neoadjuvant therapy and is usually challenging. In the last decade, texture analysis (TA) has been developed to help the radiologist to quantify and identify the parameters related to tumor heterogeneity, which cannot be appreciated by the naked eye. The aim of this narrative is to review the impact of TA on the prediction of response to neoadjuvant radiotherapy and or chemoradiotherapy., Materials and Methods: Key references were derived from a PubMed query. Hand searching and ClinicalTrials.gov were also used., Results: This paper contains a narrative report and a critical discussion of radiomics approaches in different fields of neoadjuvant radiotherapy, including esophageal cancer, lung cancer, sarcoma, and rectal cancer., Conclusions: Radiomics can shed a light on the setting of neoadjuvant therapies that can be used to tailor subsequent approaches or even to avoid surgery in the future. At the same, these results need to be validated in prospective and multicenter trials.

Background: Stereotactic body radiotherapy (SBRT) in ultra-central (UC) lung tumors, defined in the presence of planning target volume (PTV) overlap or direct tumor abutment to the central bronchial tree or esophagus, may be correlated to a higher incidence of severe adverse events. Outcome and toxicity in oligometastatic (≤3 metastases) non-small-cell lung cancer (NSCLC) patients receiving SBRT for UC tumors were evaluated., Methods: Oligometastatic NSCLC patients treated with SBRT for UC were retrospectively reviewed. Local control (LC), distant metastasis-free survival (DMFS), progression-free survival (PFS) and overall survival (OS) were calculated. Incidence and grade of toxicity were evaluated. Statistical analysis was performed to assess the impact of clinical and treatment-related variables on outcome and toxicity occurrence., Results: Seventy-two patients were treated to a median biologically effective dose (BED) of 105 (75-132) Gy 10 . Two-year LC, DMFS, PFS, and OS were 83%, 46%, 43%, and 49%. BED>75 Gy 10 was correlated to superior LC ( p = 0.02), PFS ( p = 0.036), and OS ( p < 0.001). Grade ≥3 toxicity rate was 7%, including one fatal esophagitis. No variables were correlated to DMFS or to occurrence of overall and grade ≥3 toxicity., Conclusions: SBRT using dose-intensive schedules improves outcome in NSCLC patients. Overall toxicity is acceptable, although rare but potentially fatal toxicities may occur.

Lower pre-surgery Body Mass Index (BMI) and low muscle mass impact negatively long-term survival of non-small cell lung cancer (NSCLC). We investigated their influence on survival after major lung resection for NSCLC., Methods: A retrospective analysis of a prospectively collected database was made on 304 consecutive patients., Results: Underweight, normal, overweight and obese patients represented 7.6%, 51.6%, 28.6%, and 12.6% of the pre-disease population. Weight loss and gain were recorded in 5% and 44.4% of patients, respectively. Low muscle mass was more frequently associated with BMI < 25 kg/m 2 ( p < 0.000001). Overall survival was positively affected by pre-disease ( p = 0.036) and pre-surgery ( p 0.017) BMI > 25 kg/m = , and, even more, in case of BMI > 25 kg/m 2 , and, even more, in case of BMI > 25 kg/m 2 and increasing weight ( p = 0.012). Long-term outcome was negatively influenced by low muscle mass ( p = 0.042) and weight loss ( p = 0.0052) as well as age ( p = 0.017), ASA categories ( p = 0.025), extent of resection ( p = 0.0001), pleural invasion ( p = 0.0012) and higher pathologic stage ( p < 0.0001). Three stepwise multivariable models confirmed the independent favorable prognostic value of higher pre-disease (RR 0.66[0.49-0.89], p = 0.006) and pre-surgery BMI (RR 0.72[0.54-0.98], p = 0.034), and the absence of low muscle mass (RR 0.56[0.37-0.87], p = 0.0091)., Conclusions: Body reserves assessed by simple clinical markers impact survival of surgically treated NSCLC. Strategies improving body fat and muscular mass before surgery should be considered., Competing Interests: The authors declare no conflict of interest.