Focus On Adaptive Treatments For The First Multi-Institutional Online Adaptive Radiation Therapy Trial (SMART) in Pancreas Cancer

Abstract

Early clinical data suggest that Stereotactic MR-guided adaptive radiation therapy (SMART) can safely deliver ablative doses to pancreatic cancer (PCa) patients and potentially improve overall survival in this patient population. A multi-institutional prospective, phase II SMART study for PCa patients has been initiated. This study presents unique quality assurance challenges as each patient will be treated with up to 5 different plans. Of specific concern is that the tumor not be significantly underdosed when adapting to meet normal tissue constraints. We report initial results for the adaptation of PCa patients enrolled in the SMART trial. The 25 reported patients enrolled at 3 institutions had a mean age of 65.4 years. Tumors were mainly located in the pancreatic head or neck (N = 20) rather than the body/tail (N = 5). Gross tumor volume (GTV), duodenum, small bowel, colon, and stomach were delineated on MR simulation images. The planning target volume (PTV) was generated by expanding the GTV by 3mm, and a PTVopt structure was created by subtracting the OARs from the PTV. Mean GTV and PTV volumes were 91.4 cc (36.6 to 174.9 cc) and 148.0 cc (70.4 to 259.8 cc), respectively. Dose was prescribed up to 50 Gy in 5 fractions as limited by protocol-specified OAR constraints. Motion management was required and performed using end exhale (N = 22) or end inhale (N = 3) breath hold. An MRI was acquired daily and used to recontour all OARs within 3cm of the PTV. The original plan was recalculated using the day’s anatomy and estimated over 5 fractions. The plan was adapted if >1cc of any contoured OARs was within the 33Gy isodose or if target coverage was insufficient. Real-time tumor tracking in a sagittal plane was acquired through treatment. Over the 125 fractions treated, 109 (87.2%) required adaptation. Of these, 107 (98.2%) were adapted due to violating OAR constraints. The duodenum was the OAR most often exceeding dose limits (N = 76) where the mean volume >33Gy without adaptation (V33) would have been 4.5cc. Results for the stomach (N = 63, V33 = 5.1cc), small bowel (N = 47, V33 = 4.1cc), and colon (N = 24, V33 = 5.0cc) were similar. Adapted plans achieved V33 of < 0.5cc for all OARs. An average of 15.9cc of the PTV overlapped with OARs leading to a mean D95% of 33.9 Gy for the adapted fractions. However, for the PTVopt structure that excluded overlapping OARs, coverage was maintained at a mean D98% of 41.0Gy. This resulted in a mean CTV D95% of 42.4 Gy (85% of Rx dose). On-line ART was performed using MR-guided treatment devices for an initial set of PCa patients enrolled in the SMART trial. Patients received an escalated SBRT dose regimen while maintaining the isotoxicity of surrounding OARs. Further work will evaluate patient characteristics and optimization parameters that produced the best quality plans as well as toxicity relative to delivered dose.