Sensitivity of automated and manual treatment planning approaches to contouring variation in early-breast cancer treatment.

PURPOSE: One of the advantages of integrating automated processes in treatment planning is the reduction of manual planning variability. This study aims to assess whether a deep-learning-based auto-planning solution can also reduce the contouring variation-related impact on the planned dose for early-breast cancer treatment. METHODS: Auto- and manual plans were optimized for 20 patients using both auto- and manual OARs, including both lungs, right breast, heart, and left-anterior-descending (LAD) artery. Differences in terms of recalculated dose (ΔDrcM,ΔDrcA) and reoptimized dose (ΔDroM,ΔDroA) for manual (M) and auto (A)-plans, were evaluated on manual structures. The correlation between several geometric similarities and dose differences was also explored (Spearman's test). RESULTS: Auto-contours were found slightly smaller in size than manual contours for right breast and heart and more than twice larger for LAD. Recalculated dose differences were found negligible for both planning approaches except for heart (ΔDrcM=-0.4 Gy, ΔDrcA=-0.3 Gy) and right breast (ΔDrcM=-1.2 Gy, ΔDrcA=-1.3 Gy) maximum dose. Re-optimized dose differences were considered equivalent to recalculated ones for both lungs and LAD, while they were significantly smaller for heart (ΔDroM=-0.2 Gy, ΔDroA=-0.2 Gy) and right breast (ΔDroM =-0.3 Gy, ΔDroA=-0.9 Gy) maximum dose. Twenty-one correlations were found for ΔDrcM,A (M=8,A=13) that reduced to four for ΔDroM,A (M=3,A=1). CONCLUSIONS: The sensitivity of auto-planning to contouring variation was found not relevant when compared to manual planning, regardless of the method used to calculate the dose differences. Nonetheless, the method employed to define the dose differences strongly affected the correlation analysis resulting highly reduced when dose was reoptimized, regardless of the planning approach.

Clinical implementation of deep learning-based automated left breast simultaneous integrated boost radiotherapy treatment planning.

Background and purpose: Automation in radiotherapy treatment planning aims to improve both the quality and the efficiency of the process. The aim of this study was to report on a clinical implementation of a Deep Learning (DL) auto-planning model for left-sided breast cancer. Materials and methods: The DL model was developed for left-sided breast simultaneous integrated boost treatments under deep-inspiration breath-hold. Eighty manual dose distributions were revised and used for training. Ten patients were used for model validation. The model was then used to design 17 clinical auto-plans. Manual and auto-plans were scored on a list of clinical goals for both targets and organs-at-risk (OARs). For validation, predicted and mimicked dose (PD and MD, respectively) percent error (PE) was calculated with respect to manual dose. Clinical and validation cohorts were compared in terms of MD only. Results: Median values of both PD and MD validation plans fulfilled the evaluation criteria. PE was < 1% for targets for both PD and MD. PD was well aligned to manual dose while MD left lung mean dose was significantly less (median:5.1 Gy vs 6.1 Gy). The left-anterior-descending artery maximum dose was found out of requirements (median values:+5.9 Gy and + 2.9 Gy, for PD and MD respectively) in three validation cases, while it was reduced for clinical cases (median:-1.9 Gy). No other clinically significant differences were observed between clinical and validation cohorts. Conclusion: Small OAR differences observed during the model validation were not found clinically relevant. The clinical implementation outcomes confirmed the robustness of the model.

Stereotactic Radiotherapy Ablation and Atrial Fibrillation: Technical Issues and Clinical Expectations Derived From a Systematic Review.

Aim: The purpose of this study is to collect available evidence on the feasibility and efficacy of stereotactic arrhythmia radio ablation (STAR), including both photon radiotherapy (XRT) and particle beam therapy (PBT), in the treatment of atrial fibrillation (AF), and to provide cardiologists and radiation oncologists with a practical overview on this topic. Methods: Three hundred and thirty-five articles were identified up to November 2021 according to preferred reporting items for systematic reviews and meta-analyses criteria; preclinical and clinical studies were included without data restrictions or language limitations. Selected works were analyzed for comparing target selection, treatment plan details, and the accelerator employed, addressing workup modalities, acute and long-term side-effects, and efficacy, defined either by the presence of scar or by the absence of AF recurrence. Results: Twenty-one works published between 2010 and 2021 were included. Seventeen studies concerned XRT, three PBT, and one involved both. Nine studies (1 in silico and 8 in vivo; doses ranging from 15 to 40 Gy) comprised a total of 59 animals, 12 (8 in silico, 4 in vivo; doses ranging from 16 to 50 Gy) focused on humans, with 9 patients undergoing STAR: average follow-up duration was 5 and 6 months, respectively. Data analysis supported efficacy of the treatment in the preclinical setting, whereas in the context of clinical studies the main favorable finding consisted in the detection of electrical scar in 4/4 patients undergoing specific evaluation; the minimum dose for efficacy was 25 Gy in both humans and animals. No acute complication was recorded; severe side-effects related to the long-term were observed only for very high STAR doses in 2 animals. Significant variability was evidenced among studies in the definition of target volume and doses, and in the management of respiratory and cardiac target motion. Conclusion: STAR is an innovative non-invasive procedure already applied for experimental treatment of ventricular arrhythmias. Particular attention must be paid to safety, rather than efficacy of STAR, given the benign nature of AF. Uncertainties persist, mainly regarding the definition of the treatment plan and the role of the target motion. In this setting, more information about the toxicity profile of this new approach is compulsory before applying STAR to AF in clinical practice.

Ultra-hypofractionated whole breast adjuvant radiotherapy in the real-world setting: single experience with 271 elderly/frail patients treated with 3D and IMRT technique.

PURPOSE: The purpose of the study was to evaluate the toxicity, local control, overall and disease-free survival of elderly breast cancer (BC) patients treated with adjuvant once-weekly ultra-hypofractionated radiotherapy (RT) either with intensity-modulated RT (IMRT) or 3D conformal RT (3DCRT). METHODS: From July 2011 to July 2018, BC patients receiving 5.7 Gy once a week for 5 weeks to the whole breast after breast-conserving surgery were considered for the study. Inclusion criteria were: T1-T3 invasive BC, no or limited axillary involvement, age ≥ 65 years or women with commuting difficulties or disabling diseases. RESULTS: A total of 271 patients were included in the study. Median age was 76 (46-86) years. Most of BC were T1 (77%), while the remaining were T2 (22.2%) and T3 (0.4%). Axillary status was negative in 68.3% of the patients. The only severe acute toxicity (G3) at the end of RT was erythema (0.4%), registered in the 3DCRT group; no G3 edema or epitheliolysis was recorded. With 18 months of median follow-up, severe early-late toxicity (G3) was reported in terms of fibrosis and breast retraction, both with an incidence of 1.4%, mostly in the 3DCRT group. Oncological outcomes at a median follow-up of 2.9 years reported 249/271 (91.9%) patients alive and free from any event and 5 (1.8%) isolated locoregional recurrences. At 3 years, disease-free survival and overall survival were 94.9% and 97.8%, respectively. Breast volume > 500 cm3 was reported as predictive for moderate-severe (≥ G2) acute toxicity. CONCLUSIONS: Weekly ultra-hypofractionated whole breast RT seems feasible and effective. Toxicity was mild, local control was acceptable, and overall survival was 97.8% at 3 years. Rates of severe toxicity were reduced with the IMRT technique.

Stereotactic radioablation for the treatment of ventricular tachycardia: preliminary data and insights from the STRA-MI-VT phase Ib/II study.

PURPOSE: We present the preliminary results of the STRA-MI-VT Study (NCT04066517), a spontaneous, phase Ib/II study, designed to prospectively test the safety and efficacy of stereotactic body radiotherapy (SBRT) in patientswith advanced cardiac disease and intractable ventricular tachycardia (VT). METHODS: Cardiac computed tomography (CT) integrated by electroanatomical mapping was used for substrate identification and merged with dedicated CT scans for treatment plan preparation. A single 25-Gy radioablation dose was delivered by a LINAC-based volumetric modulated arc therapy technique in a non-invasive matter. The primary safety endpoint was treatment-related adverse effects during acute and long-term follow-up (FU), obtained by regular in-hospital controls and implantable cardioverter defibrillator (ICD) remote monitoring. The primary efficacy endpoint was the reduction at 3 and 6 months of VT episodes and ICD shocks. RESULTS: Seven out of eight patients (men; age, 70 ± 7 years; ejection fraction, 27 ± 11%; 3 ischemic, 4 non-ischemic cardiomyopathies) underwent SBRT. At a median 8-month FU, no treatment-related serious adverse event occurred. Three patients died from non-SBRT-related causes. Four patients completed the 6-month FU: the number of VT decreased from 29 ± 33 to 11 ± 9 (p = .05) and 2 ± 2 (p = .08), at 3 and 6 months, respectively; shocks decreased from 11 to 0 and 2, respectively. At 6 months, all patients. showed a significant reduction of VT episodes and no electrical storm recurrence, with the complete regression of iterative VTs in 2/2 patients. CONCLUSION: The STRA-MI-VT Study suggests that SBRT can be considered an alternative option for the treatment of VT in patients with structural heart disease and highlights the need for further clinical investigation addressing safety and efficacy.

Dose-Response of TLD-100 in the Dose Range Useful for Hypofractionated Radiotherapy.

PURPOSE: The aim of the study was to exploit the feasibility of thermoluminescent dosimeters (TLDs) in radiation therapy techniques in which high dose per fraction is involved. METHODS: Dose-response of TLD-100 (LiF: Mg, Ti) was investigated in both 6-MV photon and 6-MeV electron beams. The element correction factor (ECF) generation method was applied to check the variability of the TLDs response. Two batches of 50 TLDs were divided into groups and exposed in the dose range 0 to 30 Gy. Regression analysis was performed with both linear and quadratic models. For each irradiation beam, the calibration curves were obtained in 3 dose range 0 to 8 Gy, 0 to 10 Gy, and 0 to 30 Gy. The best-fitting model was assessed by the Akaike Information Criterion test. RESULTS: The ECF process resulted a useful tool to reduce the coefficients of variation from original values higher than 5% to about 3.5%, for all the batches exposed. The results confirm the linearity of dose-response curve below the dose level of 10 Gy for photon and electron beam and the supralinear trend above. CONCLUSION: The TLDs are suitable dosimeters for dose monitoring and verification in radiation treatment involving dose up to 30 Gy in a single fraction.