Prospective phase II trial on ablative stereotactic body radiation therapy (SBRT) for medically inoperable thoracic nodes metastases.

BACKGROUND: Oligometastases in mediastinal nodes are increasingly prevalent, posing challenges for treatment with stereotactic body radiotherapy (SBRT) due to proximity to organs at risk (OARs). We report the results of a single prospective observational phase II trial on ablative SBRT for medically inoperable thoracic nodes metastases (NCT02970955). MATERIAL AND METHODS: Since 2017, patients with < 3 nodal metastases were evaluated by the tumor board and included if deemed inoperable. SBRT was delivered using risk adaptive approach based on number, site and size of metastatic nodes (50 Gy/5fractions, 60 Gy/8fractions, 70 Gy/10 fractions). Planning target volume (PTV) partial underdosage was allowed. The primary end point was local control (LC) at 12 months. Secondary end points were: acute and late toxicities, overall survival (OS), progression free survival (PFS), and time to next systemic therapy (TTNS). RESULTS: Between 03/2017-11/2021, 32 patients (41 nodal metastases) were included. NSCLC (13pts), breast (5pts) and colorectal cancer (4pts) were the most represented primary tumour. In 66 % cases, partial PTV undercoverage was necessary. LC at 1 and 2 years was 93.5 % and 82.3 %, respectively. Treatment was well-tolerated with no acute or late toxicity ≥ G3. Median OS was 59.7 months. OS at 1 and 2 years was 96.9 % and 83.8 % respectively. Median PFS was 12.2 months. PFS at 1 and 2 years was 53.1 % and 31.3 %, respectively. CONCLUSION: This trial supported the feasibility and safety of ablative SBRT for thoracic nodes metastases thanks to risk adaptive approach allowing to delay of new systemic therapies. Larger studies are needed to confirm these observations.

Adjuvant Hypofractionated Whole Breast Irradiation (WBI) vs. Accelerated Partial Breast Irradiation (APBI) in Postmenopausal Women with Early Stage Breast Cancer: 5Years Update of the HYPAB Trial.

Therapeutical strategies in breast cancer are continuously updating. Recent researches assessed the possibility of irradiating only the surgical bed in selected patients (Partial Breast Irradiation, PBI). In 2014 we designed a study to evaluate toxicity and cosmesis of APBI using Volumetric Modulated Arc Therapy-Rapid Arc compared with hypofractionated whole breast irradiation (WBI). We present here the 5-years updated data. HYPAB was a single-institution randomized trial that recruited 172 patients from 2015 to 2018. Patients underwent conserving surgery and were randomized to either adjuvant WBI (40.5Gy/15 fractions with simultaneous boost to 48 Gy to tumoral bed) or APBI (30Gy/5 fractions), both delivered with VMAT-RA technique. Clinical evaluation was performed during the first visit, once a week during radiotherapy and during follow up. Cosmesis was assessed using the Harvard Scale for Breast Cosmesis. At the time of the analysis 161 patients were eligible, 53% in the WBI and 47% in the APBI group, with a median follow-up of 67 months. Most common late skin toxicities were G1 fibrosis (32%) and oedema (28%) and were higher in the WBI group; no G3 toxicities were observed. Cosmesis was rated poor in only 6 cases. 147 patients had no evidence of disease at the last follow-up, and no patients died of the disease. Mature results confirm the safety and efficacy of APBI in selected early stage breast cancer patients. Late toxicity is improved in the APBI arm at the cost of a slight increase in local relapse. Further studies are ongoing to better elucidate the use of APBI as a de-escalation approach.

Oligometastatic sarcoma treated with Curative intent Ablative Radiotherapy (OSCAR): A multicenter study on behalf of AIRO (Italian association of Radiotherapy and clinical Oncology).

BACKGROUND AND PURPOSE: Stereotactic Ablative Radiotherapy (SABR) is emerging as a valid alternative to surgery in the oligometastatic setting in soft tissue sarcomas (STS), although robust data are lacking. The aim of this study is to evaluate toxicity and efficacy of SABR in oligometastatic STS. MATERIALS AND METHODS: This is a retrospective multicenter study including adult patients affected by stage IV STS, treated with SABR for a maximum of 5 cranial or extracranial metastases in up to 3 different organs. SABR was delivered with ablative purposes. Study endpoints were overall survival (OS), local control (LC), distant progression free survival (DPFS), time to polymetastatic progression (TTPP), time to new systemic therapy (TTNS) and toxicity. RESULTS: From 10 Italian RT centers, 138 patients (202 metastases) treated between 2010 and 2022 were enrolled in the study. Treatment was generally well tolerated, no acute or late toxicity ≥ G3 was recorded. Median follow up was 42.5 months. Median OS was 39.7 months. Actuarial OS at 1 and 2 years was 91.5 % and 72.7 %. Actuarial LC at 1 and 2 years was 94.8 % and 88.0 %. Median DPFS was 9.7 months. Actuarial DPFS at 1 and 2 years was 40.8 % and 19.4 %. CONCLUSION: SABR is a safe and effective approach for the treatment of oligometastatic sarcoma. One out of 5 patients is free of progression at 2-years.

Oligometastatic Prostate Cancer Treated with Stereotactic Body Radiation Therapy: The Role of Three-Dimensional Tumour Volume in Patient Survival.

AIMS: The definition of oligometastatic prostate cancer (OPCa) is currently based solely on the maximum number of detectable metastases, as there are no validated biomarkers available. The aim of this study was to identify novel predictive factors for OPCa patients who underwent metastases-directed therapy. MATERIALS AND METHODS: This monocentre, retrospective study included consecutive OPCa patients with a maximum of five metastases in up to two organs, detected with choline- or PSMA-positron emission tomography, who were treated with metastases-directed stereotactic body radiation therapy. Endpoints were overall survival and progression-free survival, assessed with Kaplan-Meier analysis. Univariate and multivariable Cox regression was carried out to evaluate the association between clinical factors and survival outcomes. RESULTS: Between 2009 and 2021, 163 patients and 320 metastases were treated with 226 stereotactic body radiation therapy courses. The median three-dimensional metastatic tumour volume was 4.1 cm3, with a range from 0.01 to 233.4 cm3. In total, 87 (53.4%), 21 (12.9%) and 55 (33.7%) metastases were classified as cN1, cM1a and cM1b, respectively. The median follow-up was 28.5 months. The rates of overall survival at 1, 3 and 5 years were 89.5% (95% confidence interval 83.4-93.4), 74.9% (95% confidence interval 66.1-81.7) and 57.2% (95% confidence interval 45.8-67.1), respectively. Multivariable analysis showed that overall survival reduced with the increase in three-dimensional total tumour volume (hazard ratio 1.93, 95% confidence interval 1.06-3.52; P = 0.030) and confirmed a significant difference between cN1 versus cM1a-b disease (hazard ratio 1.81, 95% confidence interval 1.01-3.25; P = 0.046). The cut-off value of total volume correlated with the highest risk of death was 20 cm3 (hazard ratio 2.37, 95% confidence interval 1.34-4.18; P = 0.003). The median progression-free survival was 17.8 months, with 1-, 3- and 5-year rates of 63.7% (95% confidence interval 55.4-70.9), 31.5% (95% confidence interval 22.8-40.6) and 24.7% (95% confidence interval 16.0-34.3). CONCLUSIONS: This study identified three-dimensional total tumour volume and the site of oligometastases as significant predictors of survival in OPCa patients treated with metastases-directed therapy. These parameters can potentially be used to personalised treatment and improve patient outcome.

Long term results of a phase II trial of hypofractionated adjuvant radiotherapy for early-stage breast cancer with volumetric modulated arc therapy and simultaneous integrated boost.

PURPOSE: to report toxicity and cosmetic outcome with a median follow-up of 6 years of a phase II trial of hypofractionated radiotherapy with volumetric modulated arc therapy (VMAT) and simultaneous integrated boost (SIB) for early-stage breast cancer after conservative surgery. MATERIALS AND METHODS: From August 2010 to September 2014, patients requiring adjuvant radiotherapy for early-stage breast cancer were treated according to a phase I-II protocol with SIB to 40.5 and 48 Gy to the breast and the boost region, respectively, with VMAT technique. The primary endpoint evaluated the treatment feasibility regarding adherence to required dose constraints for target, heart and lungs. Acute and late toxicity, local and distant control were secondary endpoints. RESULTS: 450 patients were included in the trial and analysed after a median follow-up of 6 years. Acute toxicity was already presented in a previous paper. Regarding late toxicity, 93% of patients had no skin alteration at five years, while 5.3% and 1.3% did record G1 and G2 residual toxicity, respectively. Cosmetic outcome was scored good or excellent in almost all cases (97.2%), fair only in 2.3% of patients. Residual tenderness in the irradiated breast was reported by 10% of patients. Cosmesis and breast pain improved during follow-up. Two cases of G2 pneumonitis and two cases of ischemic cardiopathy were registered during follow-up. Five cases presented local recurrence in the homolateral breast, four patients had a new primary cancer in the contralateral breast, while distant metastasis developed in 7 patients. CONCLUSION: After more than six years, hypofractionated VMAT with SIB for adjuvant radiotherapy in early-stage breast cancer patients remains a safe and effective approach. Mature data on skin toxicity and cosmetic outcome are encouraging. However, longer follow-up is required to evaluate local control, cardiac toxicity and secondary carcinogenesis.