Local Control Following Stereotactic Body Radiation Therapy for Liver Oligometastases: Lessons from a Quarter Century.

The utilization of stereotactic body radiation therapy for the treatment of liver metastasis has been widely studied and has demonstrated favorable local control outcomes. However, several predictive factors play a crucial role in the efficacy of stereotactic body radiation therapy, such as the number and size (volume) of metastatic liver lesions, the primary tumor site (histology), molecular biomarkers (e.g., KRAS and TP53 mutation), the use of systemic therapy prior to SBRT, the radiation dose, and the use of advanced technology and organ motion management during SBRT. These prognostic factors need to be considered when clinical trials are designed to evaluate the efficacy of SBRT for liver metastases.

Ablative Radiation Therapy in Oligometastatic Pancreatic Cancer to Delay Polyprogression, Limit Chemotherapy, and Improve Outcomes.

PURPOSE: The oligometastatic state is observed in patients across many malignancies, with increased recognition regarding improved outcomes after local therapies. However, there is limited data specifically regarding pancreatic ductal adenocarcinoma. We hypothesized that an oligometastatic pancreatic ductal adenocarcinoma (OPanc) phenotype would benefit from stereotactic ablative radiation therapy (SABR) to all active metastatic sites. Here, we report our institutional experience of SABR-treated OPanc to evaluate the feasibility of the approach. METHODS AND MATERIALS: A retrospective review of patients with synchronous or metachronous OPanc (1 to 5 metastases) who received SABR to all active metastatic sites was performed. We identified a comparable group of patients with similar metastatic burden, range of CA19-9 levels, and no progression for at least 5 months who did not receive SABR. We compared overall survival as the primary outcome, and polyprogression-free survival and time off chemotherapy as the secondary exploratory assessments. A third group presenting with stage IV pancreatic ductal adenocarcinoma and more than 5 distant lesions (polymetastatic) was identified to help define expected outcomes after polyprogression. RESULTS: Our study included 20 patients with OPanc receiving SABR and 21 who did not. SABR was delivered to 38 metastatic tumors. Out of the 20 SABR-treated OPanc patients, 17 (85%) had 6 or more months of time off chemotherapy, compared with 7 patients (33.3%) among the chemotherapy-treated group. Median polyprogression-free survival was 40 and 14 months (hazard ratio = 0.2; 95% confidence interval, 0.07-0.54; P = .0009), and overall survival was 42 and 18 months (hazard ratio = 0.21; 95% confidence interval, 0.08-0.53; P = .0003), for SABR- and chemotherapy-treated cohorts, respectively. CONCLUSIONS: Management of OPanc with SABR as local regional therapy could improve outcomes in a selected population and warrants prospective evaluation.

Simulated dose painting of hypoxic sub-volumes in pancreatic cancer stereotactic body radiotherapy.

Dose painting of hypoxic tumour sub-volumes using positron-emission tomography (PET) has been shown to improve tumour controlin silicoin several sites, predominantly head and neck and lung cancers. Pancreatic cancer presents a more stringent challenge, given its proximity to critical gastro-intestinal organs-at-risk (OARs), anatomic motion, and impediments to reliable PET hypoxia quantification. A radiobiological model was developed to estimate clonogen survival fraction (SF), using18F-fluoroazomycin arabinoside PET (FAZA PET) images from ten patients with unresectable pancreatic ductal adenocarcinoma to quantify oxygen enhancement effects. For each patient, four simulated five-fraction stereotactic body radiotherapy (SBRT) plans were generated: (1) a standard SBRT plan aiming to cover the planning target volume with 40 Gy, (2) dose painting plans delivering escalated doses to a maximum of three FAZA-avid hypoxic sub-volumes, (3) dose painting plans with simulated spacer separating the duodenum and pancreatic head, and (4), plans with integrated boosts to geometric contractions of the gross tumour volume (GTV). All plans saturated at least one OAR dose limit. SF was calculated for each plan and sensitivity of SF to simulated hypoxia quantification errors was evaluated. Dose painting resulted in a 55% reduction in SF as compared to standard SBRT; 78% with spacer. Integrated boosts to hypoxia-blind geometric contractions resulted in a 41% reduction in SF. The reduction in SF for dose-painting plans persisted for all hypoxia quantification parameters studied, including registration and rigid motion errors that resulted in shifts and rotations of the GTV and hypoxic sub-volumes by as much as 1 cm and 10 degrees. Although proximity to OARs ultimately limited dose escalation, with estimated SFs (∼10-5) well above levels required to completely ablate a ∼10 cm3tumour, dose painting robustly reduced clonogen survival when accounting for expected treatment and imaging uncertainties and thus, may improve local response and associated morbidity.