Artificial Intelligence-suggested Predictive Model of Survival in Patients Treated With Stereotactic Radiotherapy for Early Lung Cancer.

BACKGROUND/AIM: Overall survival (OS)-predictive models to clinically stratify patients with stage I Non-Small Cell Lung Cancer (NSCLC) undergoing stereotactic body radiation therapy (SBRT) are still unavailable. The aim of this work was to build a predictive model of OS in this setting. PATIENTS AND METHODS: Clinical variables of patients treated in three Institutions with SBRT for stage I NSCLC were retrospectively collected into a reference cohort A (107 patients) and 2 comparative cohorts B1 (32 patients) and B2 (38 patients). A predictive model was built using Cox regression (CR) and artificial neural networks (ANN) on reference cohort A and then tested on comparative cohorts. RESULTS: Cohort B1 patients were older and with worse chronic obstructive pulmonary disease (COPD) than cohort A. Cohort B2 patients were heavier smokers but had lower Charlson Comorbidity Index (CCI). At CR analysis for cohort A, only ECOG Performance Status 0-1 and absence of previous neoplasms correlated with better OS. The model was enhanced combining ANN and CR findings. The reference cohort was divided into prognostic Group 1 (0-2 score) and Group 2 (3-9 score) to assess model's predictions on OS: grouping was close to statistical significance (p=0.081). One and 2-year OS resulted higher for Group 1, lower for Group 2. In comparative cohorts, the model successfully predicted two groups of patients with divergent OS trends: higher for Group 1 and lower for Group 2. CONCLUSION: The produced model is a relevant tool to clinically stratify SBRT candidates into prognostic groups, even when applied to different cohorts. ANN are a valuable resource, providing useful data to build a prognostic model that deserves to be validated prospectively.

Unresectable stage III non-small cell lung cancer: could durvalumab be safe and effective in real-life clinical scenarios? Results of a single-center experience.

Introduction: The standard of care for patients with unresectable stage III non-small cell lung cancer (NSCLC) is chemoradiotherapy (CRT) followed by consolidation durvalumab as shown in the PACIFIC trial. The purpose of this study is to evaluate clinical outcomes and toxicities regarding the use of durvalumab in a real clinical scenario. Methods: A single-center retrospective study was conducted on patients with a diagnosis of unresectable stage III NSCLC who underwent radical CRT followed or not by durvalumab. Tumor response after CRT, pattern of relapse, overall survival (OS) and progression-free survival (PFS), and toxicity profile were investigated. Results: Eighty-five patients met the inclusion criteria. The median age was 67 years (range 45-82 years). Fifty-two patients (61.2%) started sequential therapy with durvalumab. The main reason for excluding patients from the durvalumab treatment was the expression of PD-L1 < 1%. Only two patients presented a grade 4 or 5 pneumonitis. A median follow-up (FU) of 20 months has been reached. Forty-five patients (52.9%) had disease progression, and 21 (24.7%) had a distant progression. The addition of maintenance immunotherapy confirmed a clinical benefit in terms of OS and PFS. Two-year OS and PFS were respectively 69.4% and 54.4% in the durvalumab group and 47.9% and 24.2% in the no-durvalumab group (p = 0.015, p = 0.007). Conclusion: In this real-world study, patients treated with CRT plus durvalumab showed clinical outcomes and toxicities similar to the PACIFIC results. Maintenance immunotherapy after CRT has been shown to be safe and has increased the survival of patients in clinical practice.

RR Myelo POINT: A Retrospective Single-Center Study Assessing the Role of Radiotherapy in the Management of Multiple Myeloma and Possible Interactions with Concurrent Systemic Treatment.

Background and purpose: Although chemotherapy, biological agents, and radiotherapy (RT) are cornerstones of the treatment of multiple myeloma (MM), the literature regarding the possible interactions of concurrent systemic treatment (CST) and RT is limited, and the optimal RT dose is still unclear. Materials and methods: We retrospectively analyzed the records of patients who underwent RT for MM at our institution from 1 January 2005 to 30 June 2020. The data of 312 patients and 577 lesions (treated in 411 accesses) were retrieved. Results: Most of the treated lesions involved the vertebrae (60%) or extremities (18.9%). Radiotherapy was completed in 96.6% of the accesses and, although biologically effective doses assuming an α/ß ratio of 10 (BED 10) > 38 Gy and CST were significantly associated with higher rates of toxicity, the safety profile was excellent, with side effects grade ≥2 reported only for 4.1% of the accesses; CST and BED 10 had no impact on the toxicity at one and three months. Radiotherapy resulted in significant improvements in performance status and in a pain control rate of 87.4% at the end of treatment, which further increased to 96.9% at three months and remained at 94% at six months. The radiological response rate at six months (data available for 181 lesions) was 79%, with only 4.4% of lesions in progression. Progression was significantly more frequent in the lesions treated without CST or BED 10 < 15 Gy, while concurrent biological therapy resulted in significantly lower rates of progression. Conclusion: Radiotherapy resulted in optimal pain control rates and fair toxicity, regardless of BED 10 and CST; the treatments with higher BED 10 and CST (remarkably biological agents) improved the already excellent radiological disease control.

Stereotactic prostate radiotherapy with or without androgen deprivation therapy, study protocol for a phase III, multi-institutional randomized-controlled trial.

Objective: The therapeutic landscape for localized prostate cancer (PC) is evolving. Stereotactic radiotherapy (SRT) has been reported to be at least not inferior to standard radiotherapy, but the effect of androgen deprivation therapy (ADT) in this setting is still unknown and its use is left to clinical judgment. There is therefore the need to clarify the role of ADT in association with SRT, which is the aim of the present study. Methods: We present a study protocol for a randomized, multi-institutional, Phase III clinical trial, designed to study SRT in unfavorable intermediate and a subclass of high-risk localized PC. Patients (pts) will be randomized 1:1 to SRT + ADT or SRT alone. SRT will consists in 36.25 Gy in 5 fractions, ADT will be a single administration of Triptorelin 22.5 mg concurrent to SRT. Primary end point will be biochemical disease-free survival. Secondary end points will be disease-free survival, freedom from local recurrence, freedom from regional recurrence, freedom from distant metastasis and overall survival (OS); quality of life QoL and patient reported outcomes will be an exploratory end point and will be scored with EPIC-26, EORTC PR 25, IPSS, IIEF questionnaires in SRT + ADT and SRT alone arms. Moreover, clinician reported acute and late toxicity, assessed with CTCAE v. 5.0 scales will be safety end points. Results: Sample size is estimated of 310 pts. For acute toxicity and quality of life results are awaited after 6 months since last patient in, whereas, for efficacy end points and late toxicity mature results will be available 3-5 years after last patient in. Conclusion: Evidence is insufficient to guide decision making concerning ADT administration in the new scenario of prostate ultra-hypofractionation. Hence, the need to investigate the ADT role in SRT specific setting. Advances in knowledge: The stereotactic prostate radiotherapy with or without ADT trial (SPA Trial) has been designed to establish a new standard of care for SRT in localized unfavorable intermediate and a subclass of localized high risk PC.

Skull base osteomyelitis: clinical and radiologic analysis of a rare and multifaceted pathological entity.

Skull base osteomyelitis (SBO) is a potentially life-threatening inflammation of cranial base bony structures of variable origin. Criteria for diagnosis and treatment are still controversial. Demographics, predisposing factors, symptoms, imaging, and clinical, laboratory, histological, and microbiological data of patients managed for SBO at the University Hospital of Brescia (ASST Spedali Civili) between 2002 and 2017 were retrospectively reviewed. Patients were included in different etiological groups. The topographic distribution of magnetic resonance (MR) abnormalities was recorded on a bi-dimensional model of skull base, on which three different patterns of inflammatory changes (edematous, solid, or necrotic) were reported. In patients with a history of radiotherapy, the spatial distribution of SBO was compared with irradiation fields. The association between variables and etiological groups was verified with appropriate statistical tests. A classification tree analysis was performed with the aim of inferring a clinical-radiological diagnostic algorithm for SBO. The study included 47 patients, divided into 5 etiological groups: otogenic (n = 5), radio-induced (n = 16), fungal (n = 14), immune-mediated (n = 6), and idiopathic (n = 6). At MR, five types of topographical distribution were identified (central symmetric, central asymmetric, orbital apex, sinonasal, maxillary). In patients with a history of radiotherapy, the probability to develop SBO was significantly increased in areas receiving the highest radiation dosage. The analysis of patients allowed for design of a classification tree for the diagnosis of SBO. The integration of clinical and radiologic information is an efficient strategy to categorize SBO and potentially guide its complex management.