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.

Definitive results of a prospective non-randomized phase 2 study on stereotactic body radiation therapy (sbrt) for medically inoperable lung and liver oligometastases from breast cancer.

BACKGROUND AND PURPOSE: To report mature results for local control and survival in oligometastatic (OM) breast cancer patients treated with stereotactic body radiotherapy (SBRT) on lung and/or liver lesions in a phase II trial. METHODS: This is a prospective non-randomized phase II trial (NCT02581670) which enrolled patients from 2015 to 2021. Eligibility criteria included: age > 18 years, ECOG 0-2, diagnosis of breast cancer, maximum of 4 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. The primary end-points were local control (LC) and treatment-related toxicities. The secondary end-points included overall survival (OS), distant metastasis-free survival (DMFS), time to next systemic therapy (TTNS), poly-progression free survival (PPFS). RESULTS: The study included 64 patients with a total of 90 lesions treated with SBRT. LC at 1 and 2 years was 94.9 %, 91 % at 3 years. Median local control was not reached. Median OS was 16.5 months, OS at 1, 2 and 3 years was 87.5 %, 60.9 % and 51.9 %, respectively. Median DMFS was 8.3 months, DMFS at 1, 2 and 3 years was 38.1 %, 20.6 % and 16 % respectively. At univariate analysis, local response to SBRT was found to be statistically linked with better OS, DMFS and STFS. CONCLUSION: SBRT is a safe and valid option in oligometastatic breast cancer patients, with very high rates of local control. An optimal selection of patients is likely needed to improve survival outcomes and reduce the rate of distant progression.

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.

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.

Adjuvant radiotherapy treatment for soft tissue sarcoma of extremities and trunk. A retrospective mono-institutional analysis.

Soft tissue sarcomas (STS) are uncommon, heterogeneous malignant tumors of mesodermal origin. Other than conservative surgery (CS), neoadjuvant or adjuvant radiotherapy (RT) is recommended when the risk of local recurrence is high. The aim of this study is to present our Institutional experience in adjuvant RT for treatment of STS of extremities and trunk (with either brachytherapy (BRT), external beam RT (EBRT), or both) and to provide an insight of toxicity and oncological outcomes for each RT modality. According to the RT treatment approach, patients were divided into three categories: 1) BRT alone; 2) EBRT alone; 3) combined BRT+EBRT. Differences among the three groups were assessed by the Chi-squared test. Patients' follow-up was performed every 6 months for the first two years after the end of RT and then once a year. Data from 90 patients were analyzed. The overall 3-year distant relapse-free survival (DRFS), progression-free survival (PFS), and overall survival (OS) were 84%, 80%, and 97%, respectively. Acute erythema was the most frequent side effect, although severe grade 3 toxicity was present in 5 patients. Chronic toxicity of any grade was reported in 14 patients. The incidence of chronic toxicity did not show any association with treatment modality. Multivariate analysis suggested a significant correlation between acute toxicity and tumor size, RT modality, and RT dose. In conclusion, good local control and toxicity profile were observed, despite negative patients' selection at baseline. Further investigation on wider series is warranted in order to define the optimal combination with systemic therapy.

Radiation-induced acute dysphagia : Prospective observational study on 42 head and neck cancer patients.

PURPOSE: Acute toxicity in head and neck (H&N) cancer patients treated with definitive radiotherapy (RT) has a crucial role in compliance to treatments. The aim of this study was to correlate doses to swallowing-associated structures and acute dysphagia. METHODS: We prospectively analyzed 42 H&N cancer patients treated with RT. Dysphagia (grade ≥ 3) and indication for percutaneous endoscopic gastrostomy (PEG) insertion were classified as acute toxicity. Ten swallowing-related structures were considered for the dosimetric analysis. The correlation between clinical information and the dose absorbed by the contoured structures was analyzed. Multivariate logistic regression method using resampling methods (bootstrapping) was applied to select model order and parameters for normal tissue complication probability (NTCP) modelling. RESULTS: A strong multiple correlation between dosimetric parameters was found. A two-variable model was suggested as the optimal order by bootstrap method. The optimal model (Rs = 0.452, p < 0.001) includes V45 of the cervical esophagus (odds ratio [OR] = 1.016) and Dmean of the cricopharyngeal muscle (OR = 1.057). The model area under the curve was 0.82 (95% confidence interval 0.69-0.95). CONCLUSION: Our results suggested that the absorbed dose to the cricopharyngeal muscle and cervical esophagus might play a relevant role in the development of acute RT-related dysphagia.