High dose proton and photon-based radiation therapy for 213 liver lesions: a multi-institutional dosimetric comparison with a clinical perspective.

BACKGROUND: Stereotactic radiotherapy (SRT) and Proton therapy (PT) are both options in the management of liver lesions. Limited clinical-dosimetric comparison are available. Moreover, dose-constraint routinely used in liver PT and SRT considers only the liver spared, while optimization strategies to limit the liver damaged are poorly reported. METHODS: Primary endpoint was to assess and compare liver sparing of four contemporary RT techniques. Secondary endpoints were freedom from local recurrence (FFLR), overall survival (OS), acute and late toxicity. We hypothesize that Focal Liver Reaction (FLR) is determined by a similar biologic dose. FLR was delineated on follow-up MRI. Mean C.I. was computed for all the schedules used. A so-called Fall-off Volume (FOV) was defined as the area of healthy liver (liver-PTV) receiving more than the isotoxic dose. Fall-off Volume Ratio (FOVR) was defined as ratio between FOV and PTV. RESULTS: 213 lesions were identified. Mean best fitting isodose (isotoxic doses) for FLR were 18Gy, 21.5 Gy and 28.5 Gy for 3, 5 and 15 fractions. Among photons, an advantage in terms of healthy liver sparing was found for Vmat FFF with 5mm jaws (p = 0.013) and Cyberknife (p = 0.03). FOV and FOVR resulted lower for PT (p < 0.001). Three years FFLR resulted 83%. Classic Radiation induced liver disease (RILD, any grade) affected 2 patients. CONCLUSIONS: Cyberknife and V-MAT FFF with 5mm jaws spare more liver than V-MAT FF with 10 mm jaws. PT spare more liver compared to photons. FOV and FOVR allows a quantitative analysis of healthy tissue sparing performance showing also the quality of plan in terms of dose fall-off.

Stereotactic Body Radiation Therapy for Oligoprogressive Pleural Mesothelioma: Fine-Tuning the Optimal Doses.

There is growing evidence of a role of stereotactic body radiation therapy (SBRT) in the treatment of patients with oligoprogressive pleural mesothelioma (PM). The objective of this study was to investigate the optimal radiation therapy doses and schedules in this setting. The records of patients treated with SBRT (>5 Gy per fraction) for oligoprogression of PM at 2 institutions from June 2014 to September 2022 were reviewed. Patients were divided into 2 groups: "intermediate-dose" SBRT (i-SBRT; total dose, 30-36 Gy in 5-6 fractions) and "high-dose" SBRT (h-SBRT; total dose, 45-50 Gy in 4-8 fractions). The comparison between the 2 groups in terms of local control (LC) and toxicity was the primary endpoint of the study. Overall, 23 patients were treated for 25 pleural lesions. All had received upfront chemotherapy with platinum/pemetrexed. Fifteen patients were treated with i-SBRT and 8 patients with h-SBRT. The median equivalent dose was 40 Gy (range, 40-49.6) in the i-SBRT group and 74.46 Gy (range, 64-88) in the h-SBRT group. Six-month, 1-year, and 2-year LC were 100%, 100%, and 80% in the i-SBRT group and 100%, 100%, and 67% in the h-SBRT group, respectively (p =.94). Only 2 patients (1 for each dose group) had a recurrence in the radiation therapy field, both after experiencing a distant relapse. No severe acute and late toxicities were observed in the i-SBRT group, whereas in the h-SBRT group, 2 patients experienced G2 acute and late thoracic pain and 1 patient experienced G2 acute and G3 chronic thoracic pain. In our experience, SBRT is a safe and effective option for selected patients with oligoprogressive PM. Use of intermediate total doses keeping the dose per fraction high seems to offer an excellent LC, avoiding the risk of severe toxicity.

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.

Prevention and management of acute esophageal toxicity during concomitant chemoradiotherapy for locally advanced lung cancer.

BACKGROUND: Standard treatment for locally advanced non-small cell lung cancer (LA-NSCLC) is concomitant chemoradiotherapy. The survival benefit of combined treatment is partially counterbalanced by an increased rate of acute esophageal toxicity. Several pharmaceutical products are available for prevention and management of esophagitis, including Faringel Plus. AIM: To assess the incidence and the grade, identify the correlations with clinical, dosimetric, and therapeutic variables, and analyse the role of Faringel Plus as a pharmaceutical preventive measure against acute esophageal toxicity. METHODS: Patients with LA-NSCLC treated with concomitant radiochemotherapy were retrospectively reviewed. Acute esophagitis and dysphagia were graded according to Common Terminology Criteria for Adverse Events version 5.0. Clinical, dosimetric, and therapeutic correlations were investigated using χ2 test. RESULTS: Among the 23 analysed patients, 18 (78.3%) and 1 (4.3%) developed G2 and G3 esophagitis, respectively; G1-2 dysphagia were reported in 11 cases (47.8%). No statistically significant correlation between the variables considered and acute esophageal toxicity was identified. In the group of patients who received Faringel Plus as preventive treatment (10 subjects, 43.5%), dysphagia presentation time was significantly longer (p = 0.038); esophagitis onset time was longer and symptoms duration was shorter. Faringel Plus allowed a reduction in the use of analgesic drugs. CONCLUSIONS: Acute mild esophageal toxicity was confirmed to be a common side effect in this setting. No clinical-dosimetric parameter has been demonstrated to be effective in predicting acute esophageal toxicity. The use of Faringel Plus appears effective as a therapeutic and prophylactic tool to manage acute esophageal toxicity.

A Systematic Review on Intensity Modulated Radiation Therapy for Mediastinal Hodgkin's Lymphoma.

BACKGROUND: Secondary malignant neoplasms (SMNs) and cardiovascular diseases induced by chemotherapy and radiotherapy represent the main cause of excess mortality for early-stage Hodgkin lymphoma patients, especially when the mediastinum is involved. Conformal radiotherapy techniques such as Intensity-Modulated Radiation Therapy (IMRT) could allow a reduction of the dose to the organs-at-risk (OARs) and therefore limit long-term toxicity. METHODS: We performed a systematic review of the current literature regarding comparisons between IMRT and conventional photon beam radiotherapy, or between different IMRT techniques, for the treatment of mediastinal lymphoma. RESULTS AND CONCLUSIONS: IMRT allows a substantial reduction of the volumes of OARs exposed to high doses, reducing the risk of long-term toxicity. This benefit is conterbalanced by the increase of volumes receiving low doses, that could potentially increase the risk of SMNs. Treatment planning should be personalized on patient and disease characteristics. Dedicated techniques such as "butterfly" VMAT often provide the best trade-off.

Thoracic re-irradiation with 3D-conformal or more advanced techniques: A systematic review of treatment safety by the Re-irradiation Study Group of the Italian Association of Radiation and Oncology AIRO.

Re-irradiation (re-RT) is a treatment modality that has been actively investigated in recurrent lung cancer or in lung metastases appeared in previously irradiated areas. A literature search, according PRISMA recommendations and a meta-analysis technique were performed with the aims to identify possible factors related to the toxicity incidence and severity of ≥ G3 acute toxicity. 1243 patients and 36 studies, met inclusion criteria. Our results, showed that there was no difference in ≥ G3 acute (10,5%) toxicity rate with respect to different radiation techniques, cumulative dose and re-irradiation total dose and fractionation. Factors eventually related to severe toxicity were described. The frequent lack of a sufficient description of the treatment's intent, the heterogeneity in technique and radiotherapy regimen, makes balancing risk and benefit of re-RT based on published data even more difficult.

The NIPRO Study: An Observational, Retrospective, Multicenter Study on the Safety of the Radiotherapy and Immunotherapy Combination for Advanced-Stage NSCLC.

INTRODUCTION: In this observational, retrospective, multicenter study, we aimed to assess the safety of the combination of local metastasis-directed radiotherapy (RT) and immunotherapy (IT) in a cohort of advanced non-small-cell lung cancer (aNSCLC) patients. MATERIAL AND METHODS: We collected clinical data of aNSCLC patients who received concomitant RT and anti-PD-1/PD-L1 inhibitors in seven Italian centers from September 2015 to June 2019. Concomitant RT was defined as delivered ≤4 weeks before or after the first or last administration of immunotherapy, or within two consecutive cycles of ICI. All adverse events apparently related to RT and/or IT were graded according to the Common Terminology Criteria for Adverse Events, version 4.0, and reported in terms of incidence and severity as immune related or RT related, or combined. RESULTS: We analyzed the clinical charts of 187 patients. Median follow-up time was 23 months, and median overall survival was 16.5 months (range, 3-162). Thirteen patients developed pure RT-related side effects, and 43 patients (23.9%) developed immune-related side effects. No additive toxic effects were observed. A case of grade 5 pulmonary toxicity was recorded as a possible consequence of a combined effect. CONCLUSION: This analysis suggests that the combination of concomitant RT and anti-PD-1/PD-L1 agents is safe, and the two toxicity profiles are independent.

A single-center retrospective safety analysis of cyclin-dependent kinase 4/6 inhibitors concurrent with radiation therapy in metastatic breast cancer patients.

Cyclin dependent kinases 4/6 (CDK4/6) inhibitors gained an essential role in the treatment of metastatic breast cancer. Nevertheless, data regarding their use in combination with radiotherapy are still scarce. We performed a retrospective preliminary analysis of breast cancer patients treated at our Center with palliative radiation therapy and concurrent CDK4/6 inhibitors. Toxicities were measured according to CTCAE 4.0, local response according to RECIST 1.1 or PERCIST 1.0 and pain control using verbal numeric scale. 18 patients (32 treated sites) were identified; 50% received palbociclib, 33.3% ribociclib and 16.7% abemacliclib. Acute non-hematologic toxicity was fair, with the only exception of a patient who developed G3 ileitis. During 3 months following RT, 61.1% of patients developed G 3-4 neutropenia; nevertheless no patient required permanent suspension of treatment. Pain control was complete in 88.2% of patients three months after radiotherapy; 94.4% of patients achieved and maintained local control of disease. Radiotherapy concomitant to CDK4/6 inhibitors is feasible and characterized by a fair toxicity profile, with isolated episodes of high-grade reversible intestinal toxicity. Rate of G 3-4 neutropenia was comparable with that measured for CDK4/6 inhibitors alone. Promising results were reported in terms of pain relief and local control of disease.

Two months of radiation oncology in the heart of Italian "red zone" during COVID-19 pandemic: paving a safe path over thin ice.

BACKGROUND: Coronavirus Disease 2019 (COVID-19) pandemic had an overwhelming impact on healthcare worldwide. Outstandingly, the aftermath on neoplastic patients is still largely unknown, and only isolated cases of COVID-19 during radiotherapy have been published. We will report the two-months experience of our Department, set in Lombardy "red-zone". METHODS: Data of 402 cancer patients undergoing active treatment from February 24 to April 24, 2020 were retrospectively reviewed; several indicators of the Department functioning were also analyzed. RESULTS: Dedicated measures allowed an overall limited reduction of the workload. Decrease of radiotherapy treatment number reached 17%, while the number of administration of systemic treatment and follow up evaluations kept constant. Conversely, new treatment planning faced substantial decline. Considering the patients, infection rate was 3.23% (13/402) and mortality 1.24% (5/402). Median age of COVID-19 patients was 69.7 years, the large majority were male and smokers (84.6%); lung cancer was the most common tumor type (61.5%), 84.6% of subjects were stage III-IV and 92.3% had comorbidities. Remarkably, 92.3% of the cases were detected before March 24. Globally, only 2.5% of ongoing treatments were suspended due to suspect or confirmed COVID-19 and 46.2% of positive patients carried on radiotherapy without interruption. Considering only the last month, infection rate among patients undergoing treatment precipitated to 0.43% (1/232) and no new contagions were reported within our staff. CONCLUSIONS: Although mortality rate in COVID-19 cancer patients is elevated, our results support the feasibility and safety of continuing anticancer treatment during SARS-Cov-2 pandemic by endorsing consistent preventive measures.