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) Gy¹⁰. Two-year LC, DMFS, PFS, and OS were 83%, 46%, 43%, and 49%. BED>75 Gy¹⁰ 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.

Aims: We report the mature toxicity data of a phase II non-randomized trial on the use of SBRT for lung and liver oligometastases. Methods: Oligometastatic patients from breast cancer were treated with SBRT for up to five lung and/or liver lesions. Inclusion criteria were: age > 18 years, ECOG 0–2, diagnosis of breast cancer, less than five lung/liver lesions (with a maximum diameter <5 cm), metastatic disease confined to the lungs and liver or extrapulmonary or extrahepatic disease stable or responding to systemic therapy. Various dose–fractionation schedules were used. Then, a 4D-CT scan and FDG-CTPET were acquired for simulation and fused for target definition. Results: From 2015 to 2021, 64 patients and a total of 90 lesions were irradiated. Treatment was well tolerated, with no G 3–4 toxicities. No grade ≥3 toxicities were registered and the coprimary endpoint of the study was met. Median follow-up was 19.4 months (range 2.6–73.1). Conclusions: The co-primary endpoint of this phase II trial was met, showing excellent tolerability of SBRT for lung and liver oligometastatic in breast cancer patients. Until efficacy data will mature with longer follow-up, SBRT should be regarded as an opportunity for oligometastatic breast cancer patients.

Background: Radiotherapy for thymoma is delivered post-operatively in selected cases. Given the particular location of the thymic bed and the excellent prognosis, late cardiac toxicities may be an issue. The purpose of this retrospective dosimetric study is to investigate whether intensity-modulated proton beam therapy (IMPT) compared to photon therapy could better spare cardiac substructures, given prespecified dose constraints. Methods: We retrospectively selected patients treated with adjuvant radiotherapy for thymoma in our institution. We manually contoured fourteen cardiac substructures (CSs), with the supervision of a team of cardioradiologists. The photon-based plans were re-optimized in adherence to the volumetric modulated arc therapy (VMAT) technique with specific dose constraints for the new contoured structures. The proton-based plans were optimized in adherence to intensity-modulated proton therapy (IMPT) using the beam spot scanning technique. Results: Twenty-nine patients treated with adjuvant radiotherapy with a prescribed dose of 50 Gy in 25 daily fractions for radically resected thymoma were selected. IMPT demonstrated better sparing of most cardiac substructures in terms of Dmax, Dmean and V5Gy. Finally, IMPT plans more easily achieved the proposed dose constraints. Conclusions: Cardiac substructures can be successfully spared with IMPT. Clinical studies are needed to establish a relationship between dose parameters and the development of cardiac events.

Background: This study evaluated the outcome, toxicity and predictive factors in patients unfit for concurrent chemo-radiotherapy (CT-RT) treated with hypofractionated sequential CT-RT or exclusive radiotherapy (RT) for locally advanced non-small cell lung cancer (LA-NSCLC). Methods: We included patients affected by LA-NSCLC (stage IIA-IVA) treated with a total dose of 50–60 Gy in 20 fractions. The primary outcomes were local control (LC), distant metastasis-free survival (DMFS), progression-free survival (PFS) and overall survival (OS). Univariate analysis was used to correlate outcomes with prognostic factors. Results: Between 2011 and 2019, 210 patients were treated, 113 (53.8%) with sequential CT-RT and 97 (46.2%) with exclusive RT. After a median follow-up of 15.3 months, 74 patients (35.2%) had a local progression and 133 (63.3%) had a distant progression. The one-, two- and five-year LC were 73.6%, 55.3% and 47.9%, respectively. At the time of analysis, 167 patients (79.5%) died. The one-, two- and five-year OS were 64.7%, 36% and 20%, respectively. PTV volume correlated with PFS (p = 0.001) and LC (p = 0.005). Acute and late toxicity occurred in 82% and 26% of patients. Conclusions: Albeit with the known limitations of a retrospective and heterogeneous study, our work shows that hypofractionated sequential CT-RT or exclusive RT offer a good local control and toxicity profile and a promising survival rate in LA-NSCLC patients unfit for the concurrent CT-RT scheme.

Few data are available on the role of SBRT re-irradiation for isolated recurrences. We designed a prospective phase I study to evaluate the maximum tolerated dose (MTD) of SBRT for thoracic re-irradiation, for peripheral lung lesions. RT was delivered with a dose escalation design from 30 Gy in five fractions up to 50 Gy in five fractions. The primary end point was the definition of the maximum tolerated dose (MTD) of SBRT for thoracic re-irradiation. The dose-limiting toxicity was pneumonia ≥G3. Fifteen patients were enrolled. No cases of pneumonia ≥G3 occurred in any of our cohorts. Only one patient developed pneumonia G1 during treatment. Three patients developed acute toxicities that included dyspnea G1, cardiac failure G3, and chest wall pain. One patient developed G3 late toxicity with acute coronary syndrome. After a median follow-up of 21 months (range 3.6–29.1 months), six patients (40%) had a local relapse. Distant relapse occurred in five patients (33.3%). At the last follow-up, six patients died, all but two due to progressive disease. SBRT dose escalation for thoracic re-irradiation is an effective and well-tolerated option for patients with inoperable lung lesions after a first thoracic RT with acceptable acute and late toxicities.

Background/Objectives: This multicenter retrospective study aims to evaluate the role of Ablative Radiotherapy (RT) in patients with unresectable pleural mesothelioma (PM) who experienced radiological progression after at least one line of chemotherapy, with a maximum involvement of three pleural or extrapleural sites. Methods: Adult patients (≥18 years) with PM treated with stereotactic radiotherapy between 2011 and 2022, limited to a maximum of three pleural or extrapleural sites, were included in the analysis. Ablative RT was required to be administered with radical intent. Endpoints were time to further systemic therapy (TFST), local control (LC), progression-free survival (PFS), overall survival (OS), and acute and late radiotherapy-related toxicity. Results: A total of 56 patients were identified from six Italian and one Swiss radiotherapy center. Treatment was generally well tolerated. Ten patients experienced grade 1 or 2 acute toxicity, while four patients reported persistent chest pain, with one case reaching grade 3 as late toxicity. The median TFST was 18.6 months, with TFST rates of 61.7% and 46.4% at 12 and 24 months, respectively. The median OS was 37.63 months, with 1- and 2-year OS rates of 85.2% and 65.6%. Local control was favorable (79% at 1 year), but most patients experienced disease recurrence outside the SABR treatment volume. The median disease progression-free survival (DPFS) was 8.17 months, with 1- and 2-year DPFS rates of 36% and 19%, respectively. Smoking history correlated with OS and DPFS in univariate analysis, while statistical significance for OS was maintained in multivariate analysis. Additionally, nodal status and PTV volume were associated with OS. Conclusion: SABR is a safe and effective approach for the treatment of oligorecurrent/oligoprogressive PM. The time to further systemic therapy was extended up to 18 months. At two years, 10% of patients remained disease-free, and more than half were alive at three years, suggesting a potentially indolent biological behavior in oligometastatic PM.