Variables altering the impact of respiratory gated CT simulation on planning target volume in radiotherapy for lung cancer

BackgroundRespiratory gated CT simulation (4D-simulation) has been evolved to estimate the internal body motion. This study aimed to evaluate the impact of tumor volume and location on the planning target volume (PTV) for primary lung tumor when 4D simulation is used.MethodsPatients who underwent CT simulation for primary lung cancer radiotherapy between 2012 and 2016 using a 3D- (free breathing) and 4D- (respiratory gated) technique were reviewed. For each patient, gross tumor volume (GTV) was contoured in a free breathing scan (3D-GTV), and 4D-simulation scans (4D-GTV). Margins were added to account for the clinical target volume (CTV) and internal target motion (ITV) in 3D and 4D simulation scans. Additional margins were added to account for planned target volume (PTV). Univariate and multivariate analyses were performed to test the impact of the volume of the GTV and location of the tumor (relative to the bronchial tree and lung lobes) on PTV changes by more than 10% between the 3D and 4D scans.ResultsA total of 10 patients were identified. 3D-PTV was significantly larger than the 4D-PTV; median volumes were 182.79 vs. 158.21cc, p=0.0068). On multivariate analysis, neither the volume of the GTV (p=0.5027) nor the location of the tumor (peripheral, p=0.5027 or lower location, p=0.5802) had an impact on PTV differences between 3D-simulation and 4D-simluation.ConclusionThe use of 4D-simulation reduces the PTV for the primary tumor in lung cancer cases. Further studies with larger samples are required to confirm the benefit of 4D-simulation in decreasing PTV in lung cancer

Phase I study of a novel glioblastoma radiation therapy schedule exploiting cell-state plasticity

BACKGROUND: Glioblastomas comprise heterogeneous cell populations with dynamic, bidirectional plasticity between treatment-resistant stem-like and treatment-sensitive differentiated states, with treatment influencing this process. However, current treatment protocols do not account for this plasticity. Previously, we generated a mathematical model based on preclinical experiments to describe this process and optimize a radiation therapy fractionation schedule that substantially increased survival relative to standard fractionation in a murine glioblastoma model. METHODS: We developed statistical models to predict the survival benefit of interventions to glioblastoma patients based on the corresponding survival benefit in the mouse model used in our preclinical study. We applied our mathematical model of glioblastoma radiation response to optimize a radiation therapy fractionation schedule for patients undergoing re-irradiation for glioblastoma and developed a first-in-human trial (NCT03557372) to assess the feasibility and safety of administering our schedule. RESULTS: Our statistical modeling predicted that the hazard ratio, when comparing our novel radiation schedule with a standard schedule, would be 0.74. Our mathematical modeling suggested that a practical, near optimal schedule for re-irradiation of recurrent glioblastoma patients was 3.96 Gy x 7 (1 fraction/day) followed by 1.0 Gy x 9 (3 fractions/day). Our optimized schedule was successfully administered to 14/14 (100%) patients. CONCLUSIONS: A novel radiation therapy schedule based on mathematical modeling of cell-state plasticity is feasible and safe to administer to glioblastoma patients

A Prospective Study Assessing the Efficacy and Toxicity of Stereotactic Body Radiation Therapy for Oligometastatic Bone Metastases

Purpose: Stereotactic body radiation therapy (SBRT) is a promising treatment for oligometastatic disease in bone because of its delivery of high dose to target tissue and minimal dose to surrounding tissue. The purpose of this study is to assess the efficacy and toxicity of this treatment in patients with previously unirradiated oligometastatic bony disease. Methods and Materials: In this prospective phase II trial, patients with oligometastatic bone disease, defined as ≤3 active sites of disease, were treated with SBRT at Brigham and Women's Hospital/Dana Farber Cancer Center and Beth Israel Deaconess Medical Center between December 2016 and May 2019. SBRT dose and fractionation regimen were not protocol mandated. Local progression-free survival, progression-free survival, prostatic specific antigen progression, and overall survival were reported. Treatment-related toxicity was also reported. Results: A total of 98 patients and 126 lesions arising from various tumor histologies were included in this study. The median age of patients enrolled was 72.8 years (80.6% male, 19.4% female). Median follow-up was 26.7 months. The most common histology was prostate cancer (68.4%, 67/98). The most common dose prescriptions were 27/30 Gy in 3 fractions (27.0%, 34/126), 30 Gy in 5 fractions (16.7%, 21/126), or 30/35 Gy in 5 fractions (16.7%, 21/126). Multiple doses per treatment regimen reflect dose painting employing the lower dose to the clinical target volume and higher dose to the gross tumor volume. Four patients (4.1%, 4/98) experienced local progression at 1 site for each patient (3.2%, 4/126). Among the entire cohort, 2-year local progression-free survival (including death without local progression) was 84.8%, 2-year progression-free survival (including deaths as well as local, distant, and prostatic specific antigen progression) was 47.5%, and 2-year overall survival was 87.3%. Twenty-six patients (26.5%, 26/98) developed treatment-related toxicities. Conclusions: Our study supports existing literature in showing that SBRT is effective and tolerable in patients with oligometastatic bone disease. Larger phase III trials are necessary and reasonable to determine long-term efficacy and toxicities