Purpose This study evaluates the use of the mCycle automated planning system integrated into the Monaco Treatment Planning System (TPS) for step-and-shoot intensity-modulated radiotherapy (IMRT) and volumetric modulated arc therapy (VMAT) in whole breast irradiation (WBI). The aim is to assess whether automation can standardize plan quality across a diverse patient cohort and compare dosimetric outcomes and robustness of the two techniques against setup errors and anatomical variations. Materials and Methods A total of 65 breast cancer patients who underwent postoperative WBI were selected for the study. Treatment plans were generated using mCycle, which employs multicriteria optimization (MCO) with no manual intervention. Two automated planning techniques—IMRT and VMAT—were implemented and evaluated based on dosimetric outcomes, physician review, planning time, and plan robustness. The plan deliverability was verified through γ index and point dose measurements. Results The mCycle system produced clinically acceptable plans for both IMRT and VMAT across all patient cohorts. VMAT showed superior target coverage (V95%= 97.9%) and better sparing of ipsilateral organs at risk (OARs), while IMRT demonstrated enhanced sparing of contralateral OARs and greater robustness to anatomical changes such as breast swelling. Planning times were reduced with VMAT due to complete automation. Plan deliverability was confirmed with high γ passing rates and acceptable point dose deviations. Conclusions The use of mCycle in WBI planning successfully standardized plan quality and improved workflow efficiency. VMAT provided superior target coverage and ipsilateral OAR sparing but was more sensitive to anatomical changes. IMRT showed better contralateral OAR sparing and robustness. Both techniques are viable, with advantages depending on clinical scenarios.

PURPOSE:To implement and commission a rotational Total Skin Electron Therapy (TSET) technique using high-dose-rate electron (HDRE) beams on an Elekta VersaHD linac and a custom-made flattening filter (FF), with the aim of improving delivery efficiency and dose uniformity. METHODS:Two HDRE beams (6 and 8 MeV) were characterized at an extended source-to-skin distance (SSD = 490 cm) using EBT3 film dosimetry. A customized FF was designed to optimize field uniformity in both vertical and horizontal directions. Percentage depth dose (PDD) and profile measurements were acquired in static and rotational setups. Monte Carlo simulations with EGSnrc/BEAMnrc and DOSXYZnrc were used to model the linac head and validated against measurements. Output ratios (ORs) were measured on a phantom to estimate the monitor units needed for rotational delivery. End-to-end (E2E) testing with an Alderson-Rando phantom and in vivo dosimetry on the first 50 patients were performed to assess dose uniformity and reproducibility. RESULTS:The custom FF significantly improved field flatness. Measured surface doses per 1000 MU were 82 cGy (HDRE1) and 106 cGy (HDRE2), with ORs of 0.52 and 0.56, respectively. The rotational technique allowed dose rates of 12.8-17.9 cGy/min and treatment times of 6-8 min. PDDs from Monte Carlo simulations matched measurements. E2E and in vivo dosimetry confirmed high uniformity and <1 % variability. In vivo dosimetry confirmed adequate surface dose coverage and intra-patient consistency. CONCLUSIONS:The rotational TSET technique using HDRE beams on a VersaHD linac with a custom FF is feasible, reproducible, and dosimetrically robust, representing a valid alternative to conventional dual-field approaches.

Purpose: This study evaluates the use of the mCycle automated planning system integrated into the Monaco Treatment Planning System for step-and-shoot intensity modulated radiation therapy (IMRT) and volumetric modulated arc therapy (VMAT) in whole breast irradiation (WBI). The aim was to assess whether automation can standardize plan quality across a diverse patient cohort and compare dosimetric outcomes and robustness of the 2 techniques against setup errors and anatomical variations. Methods and Materials: A total of 65 patients with breast cancer who underwent postoperative WBI were selected for the study. Treatment plans were generated using mCycle, which employs multicriteria optimization with no manual intervention. Two automated planning techniques—IMRT and VMAT—were implemented and evaluated based on dosimetric outcomes, physician review, planning time, and plan robustness. The plan deliverability was verified through γ index and point dose measurements. Results: The mCycle system produced clinically acceptable plans for both IMRT and VMAT across all patient cohorts. VMAT showed superior target coverage (V95% = 97.9%) and better sparing of ipsilateral organs at risks (OARs), whereas IMRT demonstrated enhanced sparing of contralateral OARs and greater robustness to anatomical changes such as breast swelling. Planning times were reduced with VMAT because of complete automation. Plan deliverability was confirmed with high γ passing rates and acceptable point dose deviations. Conclusions: The use of mCycle in WBI planning successfully standardized plan quality and improved workflow efficiency. VMAT provided superior target coverage and ipsilateral OAR sparing but was more sensitive to anatomical changes. IMRT showed better contralateral OAR sparing and robustness. Both techniques are viable, with advantages depending on clinical scenarios.

The mechanisms governing the abscopal effects of local radiotherapy in cancer patients remain an open conundrum. Here, we show that off-target intestinal low-dose irradiation (ILDR) increases the clinical benefits of immune checkpoint inhibitors or chemotherapy in eight retrospective cohorts of cancer patients and in tumor-bearing mice. The abscopal effects of ILDR depend on dosimetry (≥1 and ≤3 Gy) and on the metabolic and immune host-microbiota interaction at baseline allowing CD8+ T cell activation without exhaustion. Various strains of Christensenella minuta selectively boost the anti-cancer efficacy of ILDR and PD-L1 blockade, allowing emigration of intestinal PD-L1-expressing dendritic cells to tumor-draining lymph nodes. An interventional phase 2 study provides the proof-of-concept that ILDR can circumvent resistance to first- or second-line immunotherapy in cancer patients. Prospective clinical trials are warranted to define optimal dosimetry and indications for ILDR to maximize its therapeutic potential.

This study, derived from the phase 3 SAFE trial (ClinicalTrials.gov identifier: NCT2236806), explores subclinical cardiac damage in breast cancer patients receiving anthracycline-based chemotherapy and left-sided breast radiation therapy (RT). Eligible patients were randomized to a cardioprotective pharmacological therapy (bisoprolol, ramipril, or both) or placebo, with cardiac surveillance at multiple time-point using standard and 3-dimensional echocardiography. Dosimetric parameters were analysed, including mean heart dose (MHD) and various metrics for heart substructures, employing advanced contouring techniques and auto-contouring software. In the analysis of left-sided breast RT patients, the study encompassed 39 out of 46 irradiated individuals, focusing on GLS and 3D-LVEF outcomes with ≥ 10

Purpose/Objective(s) Management of locally advanced Soft Tissue Sarcoma (STS) is based on surgery and external beam radiation therapy (EBRT). Theoretical benefits of neoadjuvant EBRT include reduced volume and dose requirements and possible tumor shrinkage, particularly in association with concurrent chemotherapy (CT), that may facilitate clear margin resection, although at the price of increased wound complications rate in up to 35% of patients. The aim of this study is to evaluate outcome and toxicity results of neoadjuvant radiotherapy in STS patients candidate to surgical excision and to assess prognostic-related features to guide treatment personalization. Materials/Methods Clinical and treatment related data were retrospectively retrieved from a consecutive cohort of non-metastatic STS patients treated at our Institution with neoadjuvant RT followed by surgery from 1991 to 2023. CT consisted of an Epirubicin-Ifosfamide regimen for 3 cycles during EBRT delivery in selected candidates. Overall survival (OS), Distant-metastasis free survival (DMFS), Local control (LC) data were extrapolated using Kaplan-Meier method. Chi-square, log-rank test and Cox model were performed to identify factors related with outcome and toxicity. Results 156 patients were included in our study. Median age was 55 years. Tumors were mostly located in the limbs (94%). Disease stage was T≥3 in 71% of cases. Most represented histologic subtypes were liposarcoma (LPS) (34%), undifferentiated pleomorphic sarcoma (UPS) (24%) and synovial sarcoma (5%). Neoadjuvant EBRT was administered to a dose of 50 Gy in 25 daily fractions concurrently with CT in 82 % patients. IMRT was used in 34% of case. R0 and R1 resection were obtained in 93% and 7% of patients respectively. Wound complications were observed in 16% of patients. Grade (G) 3 disease was found in 70% patients. After a median follow-up of 32 months, 5-year OS, DMFS and LC rates were 72%, 57% and 82%, respectively. At multivariate analysis only R1 resection was significantly associated to worse LC rates (p = 0.0214), while G3 disease was correlated with impaired DMFS (p = 0.0029). UPS (p = 0.0028), G3 (p = 0.004) and R1 (p = 0.05) correlated with poorer OS rates. None of the examined variables, particularly use of IMRT and CT, were associated with higher occurrence of wound complications. Conclusion In this large STS cohort, neoadjuvant RT resulted in excellent RO rate and favorable outcomes. Wound complications rate was inferior to historical data from landmark trials. R1 resection and G3 disease correlated respectively with impaired LC and DMFS. Both factors were associated with poorer OS, as well as UPS subtype, suggesting an unmet need for treatment intensification in selected patients. Use of IMRT and concurrent CT were not correlated with wound complications occurrence.

Background This study aimed to evaluate an a-priori multicriteria plan optimization algorithm (mCycle) for locally advanced breast cancer radiation therapy (RT) by comparing automatically generated VMAT (Volumetric Modulated Arc Therapy) plans (AP-VMAT) with manual clinical Helical Tomotherapy (HT) plans. Methods The study included 25 patients who received postoperative RT using HT. The patient cohort had diverse target selections, including both left and right breast/chest wall (CW) and III-IV node, with or without internal mammary node (IMN) and Simultaneous Integrated Boost (SIB). The Planning Target Volume (PTV) was obtained by applying a 5 mm isotropic expansion to the CTV (Clinical Target Volume), with a 5 mm clip from the skin. Comparisons of dosimetric parameters and delivery/planning times were conducted. Dosimetric verification of the AP-VMAT plans was performed. Results The study showed statistically significant improvements in AP-VMAT plans compared to HT for OARs (Organs At Risk) mean dose, except for the heart and ipsilateral lung. No significant differences in V 95% were observed for PTV breast/CW and PTV III-IV, while increased coverage (higher V 95% ) was seen for PTV IMN in AP-VMAT plans. HT plans exhibited smaller values of PTV V 105% for breast/CW and III-IV, with no differences in PTV IMN and boost. HT had an average (± standard deviation) delivery time of (17 ± 8) minutes, while AP-VMAT took (3 ± 1) minutes. The average γ passing rate for AP-VMAT plans was 97%±1%. Planning times reduced from an average of 6 h for HT to about 2 min for AP-VMAT. Conclusions Comparing AP-VMAT plans with clinical HT plans showed similar or improved quality. The implementation of mCycle demonstrated successful automation of the planning process for VMAT treatment of locally advanced breast cancer, significantly reducing workload.