Risk of Heart Failure With Preserved Ejection Fraction in Older Women After Contemporary Radiotherapy for Breast Cancer.

BACKGROUND: Cardiomyocytes are resistant to radiation. However, cardiac radiation exposure causes coronary microvascular endothelial inflammation, a perturbation implicated in the pathogenesis of heart failure (HF) and particularly HF with preserved ejection fraction (HFpEF). Radiotherapy for breast cancer results in variable cardiac radiation exposure and may increase the risk of HF. METHODS: We conducted a population-based case-control study of incident HF in 170 female residents of Olmsted County, Minnesota (59 cases and 111 controls), who underwent contemporary (1998-2013) radiotherapy for breast cancer with computed tomography-assisted radiotherapy planning. Controls were matched to cases for age, tumor side, chemotherapy use, diabetes mellitus, and hypertension. Mean cardiac radiation dose (MCRD) in each patient was calculated from the patient's computed tomography images and radiotherapy plan. RESULTS: Mean age at radiotherapy was 69±9 years. Of HF cases, 38 (64%) had EF≥50% (HFpEF), 18 (31%) had EF<50% (HF with reduced EF), and 3 (5%) did not have EF measured. The EF was ≥40% in 50 of the 56 HF cases (89%) with an EF measurement. The mean interval from radiotherapy to HF was 5.8±3.4 years. The odds of HF was higher in patients with a history of ischemic heart disease or atrial fibrillation. The MCRD was 2.5 Gy (range, 0.2-13.1 Gy) and higher in cases (3.3±2.7 Gy) than controls (2.1±2.0 Gy; P=0.004). The odds ratio (95% confidence interval) for HF per log MCRD was 9.1 (3.4-24.4) for any HF, 16.9 (3.9-73.7) for HFpEF, and 3.17 (0.8-13.0) for HF with reduced EF. The increased odds of any HF or HFpEF with increasing MCRD remained significant after adjustment for HF risk factors and in sensitivity analyses matching by cancer stage rather than tumor side. Only 18.6% of patients experienced new or recurrent ischemic events between radiotherapy and the onset of HF. CONCLUSIONS: The relative risk of HFpEF increases with increasing cardiac radiation exposure during contemporary conformal breast cancer radiotherapy. These data emphasize the importance of radiotherapy techniques that limit MCRD during breast cancer treatment. Moreover, these data provide further support for the importance of coronary microvascular compromise in the pathophysiology of HFpEF.

Spatially Fractionated Radiation Therapy in Sarcomas: A Large Single-Institution Experience.

Purpose: Spatially fractionated radiation therapy (SFRT) is a recognized technique for enhancing tumor response in radioresistant and bulky tumors. We analyzed clinical and treatment outcomes in patients with bone and soft tissue sarcomas treated with modern SFRT techniques. Methods and Materials: Patients with metastatic or unresectable sarcoma treated with brass collimator, volumetric modulated arc therapy lattice, or proton SFRT from December 2019 to June 2022 were retrospectively reviewed. Consolidative external beam radiation therapy (EBRT) was delivered at the physician's discretion. Patient and treatment characteristics, treatment response (symptom improvement, local control, and imaging response), and toxicity data were collected. Results: The cohort consisted of 53 patients treated with 61 SFRT treatments. Median age at treatment was 60.0 years. The primary location was soft tissue in 46 courses (75%) and bone in 15 (25%). Fifty-three courses (87%) were treated for symptom relief. The most used SFRT technique was volumetric modulated arc therapy lattice (n = 52, 85%) to a dose of 20 Gy (n = 48, 79%; range, 16-20 Gy). EBRT was delivered post-SFRT in 55 (90%) treatment courses with a median time interval from SFRT to EBRT of 5 days (range, 0-14 days). Median physical EBRT dose and fractionation was 40 Gy (range, 9-73.5 Gy) and 10 fractions (range, 3-33 fractions). Median follow up was 7.4 months (range, 0.2-30 months). One-year overall survival and local control rates were 53% and 82%. Symptom relief was documented with 32 treatment courses (60%). Stable or partial response was observed with 47 treatment courses (90%). Four grade 3 to 4 acute and subacute toxicities were attributable to SFRT (8%). Conclusions: The current series is the largest to date documenting outcomes for SFRT in sarcomas. Our results suggest combined SFRT with EBRT is associated with a favorable toxicity profile and high rates of symptomatic and radiographic responses for metastatic or unresectable sarcomas.

Automated target placement for VMAT lattice radiation therapy: enhancing efficiency and consistency.

Objective. An algorithm was developed for automated positioning of lattice points within volumetric modulated arc lattice radiation therapy (VMAT LRT) planning. These points are strategically placed within the gross tumor volume (GTV) to receive high doses, adhering to specific separation rules from adjacent organs at risk (OARs). The study goals included enhancing planning safety, consistency, and efficiency while emulating human performance.Approach. A Monte Carlo-based algorithm was designed to optimize the number and arrangement of lattice points within the GTV while considering placement constraints and objectives. These constraints encompassed minimum spacing between points, distance from OARs, and longitudinal separation along thez-axis. Additionally, the algorithm included an objective to permit, at the user's discretion, solutions with more centrally placed lattice points within the GTV. To validate its effectiveness, the automated approach was compared with manually planned treatments for 24 previous patients. Prior to clinical implementation, a failure mode and effects analysis (FMEA) was conducted to identify potential shortcomings.Main results.The automated program successfully met all placement constraints with an average execution time (over 24 plans) of 0.29 ±0.07 min per lattice point. The average lattice point density (# points per 100 c.c. of GTV) was similar for automated (0.725) compared to manual placement (0.704). The dosimetric differences between the automated and manual plans were minimal, with statistically significant differences in certain metrics like minimum dose (1.9% versus 1.4%), D5% (52.8% versus 49.4%), D95% (7.1% versus 6.2%), and Body-GTV V30% (20.7 c.c. versus 19.7 c.c.).Significance.This study underscores the feasibility of employing a straightforward Monte Carlo-based algorithm to automate the creation of spherical target structures for VMAT LRT planning. The automated method yields similar dose metrics, enhances inter-planner consistency for larger targets, and requires fewer resources and less time compared to manual placement. This approach holds promise for standardizing treatment planning in prospective patient trials and facilitating its adoption across centers seeking to implement VMAT LRT techniques.

Clinical aspects of spatially fractionated radiation therapy treatments.

PURPOSE: To provide clinical guidance for centers wishing to implement photon spatially fractionated radiation therapy (SFRT) treatments using either a brass grid or volumetric modulated arc therapy (VMAT) lattice approach. METHODS: We describe in detail processes which have been developed over the course of a 3-year period during which our institution treated over 240 SFRT cases. The importance of patient selection, along with aspects of simulation, treatment planning, quality assurance, and treatment delivery are discussed. Illustrative examples involving clinical cases are shown, and we discuss safety implications relevant to the heterogeneous dose distributions. RESULTS: SFRT can be an effective modality for tumors which are otherwise challenging to manage with conventional radiation therapy techniques or for patients who have limited treatment options. However, SFRT has several aspects which differ drastically from conventional radiation therapy treatments. Therefore, the successful implementation of an SFRT treatment program requires the multidisciplinary expertise and collaboration of physicians, physicists, dosimetrists, and radiation therapists. CONCLUSIONS: We have described methods for patient selection, simulation, treatment planning, quality assurance and delivery of clinical SFRT treatments which were built upon our experience treating a large patient population with both a brass grid and VMAT lattice approach. Preclinical research and patient trials aimed at understanding the mechanism of action are needed to elucidate which patients may benefit most from SFRT, and ultimately expand its use.

VMAT Grid Therapy: A Widely Applicable Planning Approach.

PURPOSE: To describe a novel and practical volumetric modulated arc therapy (VMAT) planning approach for grid therapy. METHODS AND MATERIALS: Dose is prescribed to 1.5-cm diameter spherical contours placed throughout the gross tumor volume (GTV). Placement of spheres is variable, but they must maintain at least a 3-cm (center to center) separation, and the edge of any sphere must be at least 1 cm from any organ at risk (OAR). Three concentric ring structures are used during optimization to confine the highest doses to the center of the spheres and maximize dose sparing between them. The end result is alternating regions of high and low dose throughout the GTV and minimal dose to OARs. High-intensity flattening filter-free (FFF) modes are used to efficiently deliver the plans, and entire treatments typically take only 15 to 20 minutes. RESULTS: The approach is illustrated with 2 examples treated at our institution. Patient #1 had a 1703-cm3 mediastinal mass and was prescribed 20 Gray (Gy) to 24 spherical regions within the GTV. Patient #2 had a 3680-cm3 abdominal tumor and was prescribed 18 Gy to 32 spherical regions within the GTV. Both patients received additional consolidative radiation approximately 1 week after the initial VMAT grid treatment. Each patient experienced marked reduction in tumor size and symptomatic relief without treatment-related complications. CONCLUSIONS: We have described in detail a planning approach for VMAT grid therapy treatments that can typically be delivered in a clinically practical time span. The VMAT approach is especially useful for tumors that are surrounded by sensitive critical structures. As many centers offer VMAT treatments, the approach is widely accessible and can be readily implemented once appropriate patient selection and delivery processes are established.

Dosimetric comparison between volumetric-modulated arc therapy and a hybrid volumetric-modulated arc therapy and segmented field-in-field technique for postmastectomy chest wall and regional lymph node irradiation.

Decreasing radiotoxicity to the heart, lungs, and contralateral breast has proven to lower the risk of secondary malignancy and improve overall outcomes when treating chest wall (CW) and regional lymph nodes in postmastectomy breast cancer patients. In this retrospective study, 11 postmastectomy patients were selected and planned with a novel hybrid treatment method and a traditional volumetric arc therapy (VMAT) approach for comparison. This hybrid technique was able to optimize tangential beams to minimize heart dose and the VMAT contribution to improve dose conformity around the planning target volume (PTV). Overall, this hybrid technique produced more homogenous target dose coverage and demonstrated a decrease of integral dose to organs at risk (OAR), while the VMAT technique demonstrated a higher affinity for maintaining dose conformity. Further observation of dose distributions also revealed that the hybrid plans were more effective in sparing low-dose spread to healthy tissue in both right- and left-sided cases. This observation was made evident by the reduction in heart V5 and Dmean, decreases in all parameters regarding the contralateral lung, as well as all values other than the V20 of the ipsilateral lung. This unique hybrid planning technique could present an alternative to standard intensity-modulated radiation therapy (IMRT) planning when treating postmastectomy CW and regional lymph nodes, as it has shown the capacity to decrease cardiac, lung, and contralateral breast toxicity while maintaining quality PTV coverage.

Multi-isocenter hybrid electron and rapid arc photon treatment for reirradiation of extensive recurrent inflammatory breast cancer.

Delivering an adequate and homogenous dose to a large volume of recurrent cutaneous disease can be challenging even with modern techniques. Here, the authors describe a 3-isocenter hybrid electron and rapid arc photon radiation treatment plan to provide optimal tumor coverage to an extensive recurrence of inflammatory breast carcinoma. This approach allowed for homogeneous treatment of a large volume while effectively modulating dose to previously irradiated tissue and minimizing dose to the underlying heart, lungs and brachial plexus.