Long term update on toxicity and survival of a phase II trial of linac-based stereotactic body radiation therapy for low-intermediate risk prostate cancer.

BACKGROUND: In 2016 we published a phase II study exploring safety and efficacy of Stereotactic Body Radiation Therapy (SBRT) delivered with Volumetric Modulated Arc Therapy (VMAT) and Flattening Filter Free (FFF) beams techniques in prostate cancer (PC) patients. We present herein the updated results on late toxicity and long-term survival. METHODS: Patients enrolled in the study had a biopsy-confirmed localized PC and the features of a low- or intermediate-risk disease (National Comprehensive Network Criteria). The radiotherapy (RT) schedule consisted of 35 Gy delivered in five fractions every other day. Toxicities were registered according to the common toxicity adverse events v4.0. Biochemical recurrence was defined as an increase of prostate specific antigen after nadir, confirmed at least once. Local recurrence (LR) and distant metastases were detected either with Choline- or PSMA-PET/CT scans. Kaplan-Meier curves for Biochemical Recurrence-Free Survival (BFS), Local Control (LC), Distant Metastasis Free Survival (DMFS) and Cancer Specific Survival, were calculated by using MedCalc. RESULTS: Ninety patients were submitted to SBRT between February 2012 and March 2015. Fifty-eight patients (64.5%) had a Gleason Score of 6, while 32 (35.5%) had a Gleason Score of 7. A late grade 1 Genito-Urinary toxicity was observed in 54.5% of patients while a grade 2 in 3.3%. A late Gastro-intestinal grade 1 toxicity was reported in 18.9% of patients, while a grade 2 in 2.2%. Erectile dysfunction was reported by 13% of patients No heavier toxicities were observed. At a median follow-up of 102 months, 5- and 8-year BFS were 93.0% and 84.4% respectively, 5- and 8-year LC were 95.2% and 87.0% respectively, 5- and 8-year DMFS were 95.3% and 88.4%, respectively. CONCLUSIONS: This long-term update confirms that SBRT is a valid therapeutic strategy for low-intermediate risk PC. RT with VMAT and FFF warrants optimal results in terms of toxicity and disease control.

Total tumor volume as a predictor of survival in patients with multiple oligometastases treated with stereotactic ablative radiotherapy (SABR).

BACKGROUND: Delivering stereotactic ablative radiotherapy (SABR) in patients with multiple oligometastases represents a challenge for clinical and technical reasons. We aimed to evaluate the outcome of patients affected by multiple oligometastases treated with SABR and the impact of tumor volume on survival. MATERIALS AND METHODS: We included all the patients treated with single course SABR for 3 to 5 extracranial oligometastases. All patients were treated with the volumetric modulated arc therapy (VMAT) technique with ablative intent. End-points of the analysis were overall survival (OS), progression free survival (PFS), local control (LC) and toxicity. RESULTS: 136 patients were treated from 2012 to 2020 on 451 oligometastases. Most common primary tumor was colorectal cancer (44.1%) followed by lung cancer (11.8%). A total of 3, 4 and 5 lesions were simultaneously treated in 102 (75.0%), 26 (19.1%), and 8 (5.9%) patients, respectively. Median total tumor volume (TTV) was 19.1 cc (range 0.6-245.1). With a median follow-up of 25.0 months, OS at 1 and 3 years was 88.4% and 50.2%, respectively. Increasing TTV was independent predictive factor of worse OS (HR 2.37, 95% CI 1.18-4.78, p = 0.014) and PFS (HR 1.63, 95% CI 1.05-2.54; p = 0.028). Median OS was 80.6 months if tumor volume was ≤ 10 cc (1 and 3 years OS rate 93.6% and 77.5%, respectively), and 31.1 months if TTV was higher than 10 cc (1 and 3 years OS rate 86.7% and 42.3%, respectively). Rates of LC at 1 and 3 years were 89.3% and 76.5%. In terms of toxicity, no grade 3 or higher toxicity was reported both in the acute and late settings. CONCLUSION: We demonstrated the impact of tumor volume on survival and disease control of patients affected by multiple oligometastases treated with single course SABR.

Internal Guidelines for Reducing Lymph Node Contour Variability in Total Marrow and Lymph Node Irradiation.

BACKGROUND: The total marrow and lymph node irradiation (TMLI) target includes the bones, spleen, and lymph node chains, with the latter being the most challenging structures to contour. We evaluated the impact of introducing internal contour guidelines to reduce the inter- and intraobserver lymph node delineation variability in TMLI treatments. METHODS: A total of 10 patients were randomly selected from our database of 104 TMLI patients so as to evaluate the guidelines' efficacy. The lymph node clinical target volume (CTV_LN) was recontoured according to the guidelines (CTV_LN_GL_RO1) and compared to the historical guidelines (CTV_LN_Old). Both topological (i.e., Dice similarity coefficient (DSC)) and dosimetric (i.e., V95 (the volume receiving 95% of the prescription dose) metrics were calculated for all paired contours. RESULTS: The mean DSCs were 0.82 ± 0.09, 0.97 ± 0.01, and 0.98 ± 0.02, respectively, for CTV_LN_Old vs. CTV_LN_GL_RO1, and between the inter- and intraobserver contours following the guidelines. Correspondingly, the mean CTV_LN-V95 dose differences were 4.8 ± 4.7%, 0.03 ± 0.5%, and 0.1 ± 0.1%. CONCLUSIONS: The guidelines reduced the CTV_LN contour variability. The high target coverage agreement revealed that historical CTV-to-planning-target-volume margins were safe, even if a relatively low DSC was observed.

Stereotactic radiation therapy for oligometastatic esophagogastric adenocarcinoma: outcome and prognostic factors.

OBJECTIVE: The aim of this study was to evaluate clinical results and prognostic factors in a cohort of patient with oligometastatic esophagogastric adenocarcinoma treated with stereotactic radiation therapy (SRT). METHODS: This retrospective study included patients affected by 1-3 metastases treated with SRT from 2013 to 2021. Local control (LC), overall survival (OS), progression-free survival (PFS), time to polymetastatic dissemination (TTPD) and time to systemic therapy change/initiation (TTS) were evaluated. RESULTS: Between 2013 and 2021, 55 patients were treated with SRT on 80 oligometastatic sites. Median follow-up was 20 months. Nine patients had local progression. 1 and 3 years LC was respectively 92 and 78%. 41 patients experienced further distant disease progression, median PFS was 9.6 months, 1 and 3 years PFS was respectively 40 and 15%. 34 patients died, median OS was 26.6 months, 1 and 3 years OS was respectively 78 and 40%. During follow-up, 24 patients changed or initiated a new systemic therapy; median TTS time was 9 months. 27 patients experienced poliprogression, 44% after 1 year and 52% after 3 years. Median TTPD was 8 months. The best local response (LR), tyming of metastases and PS were related with prolonged PFS on multivariate analysis. LR was correlated with OS at multivariate analysis. CONCLUSION: SRT represents a valid treatment for oligometastatic esophagogastric adenocarcinoma. CR correlated with PFS and OS, while metachronous metastasis and a good PS correlated with a better PFS. ADVANCES IN KNOWLEDGE: In selected gastroesopagheal oligometastatic patients, SRT can prolong OS Local response to SRT, metachronous timing of metastases and better PS improve PFS.Local response correlates with OS.

Predictive value of clinical and radiomic features for radiation therapy response in patients with lymph node-positive head and neck cancer.

BACKGROUND: Prediction of survival and radiation therapy response is challenging in head and neck cancer with metastatic lymph nodes (LNs). Here we developed novel radiomics- and clinical-based predictive models. METHODS: Volumes of interest of LNs were employed for radiomic features extraction. Radiomic and clinical features were investigated for their predictive value relatively to locoregional failure (LRF), progression-free survival (PFS), and overall survival (OS) and used to build multivariate models. RESULTS: Hundred and six subjects were suitable for final analysis. Univariate analysis identified two radiomic features significantly predictive for LRF, and five radiomic features plus two clinical features significantly predictive for both PFS and OS. The area under the curve of receiver operating characteristic curve combining clinical and radiomic predictors for PFS and OS resulted 0.71 (95%CI: 0.60-0.83) and 0.77 (95%CI: 0.64-0.89). CONCLUSIONS: Radiomic and clinical features resulted to be independent predictive factors, but external independent validation is mandatory to support these findings.

Stereotactic Body Radiation Therapy for Lung and Liver Oligometastases from Breast Cancer: Toxicity Data of a Prospective Non-Randomized Phase II Trial.

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.

Treatment outcome and compliance to dose-intensified linac-based SBRT for unfavorable prostate tumors using a novel real-time organ-motion tracking.

PURPOSE/OBJECTIVES: To report preliminary data on treatment outcome and compliance to dose-intensified organ sparing SBRT for prostate cancer using a novel electromagnetic transmitter-based tracking system (RayPilotÒ System) to account for intra-fractional organ motion. MATERIAL/METHODS: Thirteen patients with intermediate unfavorable (9) and selected high-risk (4) prostate cancer underwent dose-escalated SBRT in 4 or 5 fractions (BED1.5 = 279 Gy and 253 Gy, respectively). The VMAT treatment consisted in two 6FFF or 10FFF full arcs optimized to have the 95% isodose covering at least 95% of the PTV (2 mm isotropic expansion of the CTV). Whenever the real-time tracking registered a displacement that exceeded 2 mm during the setup and/or the beam delivery, the treatment was interrupted and the prostate motion was promptly corrected. The incidence of treatment-related genitourinary (GU) and gastrointestinal (GI) toxicity, patient QoL and PSA outcomes were computed from the start of treatment to the last follow-up date. RESULTS: All patients completed the treatment in the expected time (10.2 +/- 4.2 minutes) and their compliance to the procedure was excellent. No clinically significant acute Grade 2 or higher GI (rectal) and GU side effects were observed within 90 days from the treatment completion. The median IPSS increased from 8 at baseline to 12 one-month after treatment and settled to 6 at 3 months. EPIC-26 scores in the urinary domain decreased from a median baseline of 86 pre-treatment to 79 at one-month and returned to baseline at a later timepoint (median score of 85 at 3 months). EPIC-26 scores in the bowel domains did not show significant changes within 3 months following RT. The prostate was found within 1 mm from its initial position in 78% of the beam-on time, between 1 and 2 mm in 20%, and exceeded 2 mm only in 2%, after correction for motion which was performed in 45% of the fractions, either during setup or beam delivery. CONCLUSIONS: Our preliminary findings show that dose intensified SBRT for unfavorable prostate tumors does not come at the cost of an increased toxicity, provided that a reliable technique for real time prostate monitoring is ensured. Fast FFF beams contributed to reduce intra-fractional motion. These observations need to be confirmed on a larger scale and a longer follow up.