Using adaptive magnetic resonance image‐guided radiation therapy for treatment of inoperable pancreatic cancer

Abstract

Background Adaptive magnetic resonance imaging‐guided radiation therapy (MRgRT) can escalate dose to tumors while minimizing dose to normal tissue. We evaluated outcomes of inoperable pancreatic cancer patients treated using MRgRT with and without dose escalation. Methods We reviewed 44 patients with inoperable pancreatic cancer treated with MRgRT. Treatments included conventional fractionation, hypofractionation, and stereotactic body radiation therapy. Patients were stratified into high‐dose (biologically effective dose [BED 10 ] >70) and standard‐dose groups (BED 10 ≤70). Overall survival (OS), freedom from local failure (FFLF) and freedom from distant failure (FFDF) were evaluated using Kaplan‐Meier method. Cox regression was performed to identify predictors of OS. Acute gastrointestinal (GI) toxicity was assessed for 6 weeks after completion of RT. Results Median follow‐up was 17 months. High‐dose patients (n = 24, 55%) had statistically significant improvement in 2‐year OS (49% vs 30%, P = 0.03) and trended towards significance for 2‐year FFLF (77% vs 57%, P = 0.15) compared to standard‐dose patients (n = 20, 45%). FFDF at 18 months in high‐dose vs standard‐dose groups was 24% vs 48%, respectively ( P = 0.92). High‐dose radiation (HR: 0.44; 95% confidence interval [CI]: 0.21‐0.94; P = 0.03) and duration of induction chemotherapy (HR: 0.84; 95% CI: 0.72‐0.98; P = 0.03) were significantly correlated with OS on univariate analysis but neither factor was independently predictive on multivariate analysis. Grade 3+ GI toxicity occurred in three patients in the standard‐dose group and did not occur in the high‐dose group. Conclusions Patients treated with dose‐escalated MRgRT demonstrated improved OS. Prospective evaluation of high‐dose RT regimens with standardized treatment parameters in inoperable pancreatic cancer patients is warranted.

First 500 Fractions Delivered with a Magnetic Resonance-guided Radiotherapy System: Initial Experience

“…Early reports have demonstrated the successful implementation of these systems into a number of clinics world-wide. Today, also a number of retrospective outcome analyses and a smaller number of phase one and phase two prospective clinical trials suggest the clinical value of investing in this technology [5][6][7].…”

Daily dose to organs at risk predicts acute toxicity in pancreatic stereotactic radiotherapy

“…However, long-term follow-up is needed to confirm that these doses aresafe for late toxicity. More intensive dose regimens, delivering higher biological doses, may be of interest to increase response rate [10]: however due to proximity of radiosensitive critical structures, further dose escalation may expose to higher risk of adverse severe events. Moreover, initial experiences of daily imaging with cone-beam CT [22] and more recent trials implementing the use of high-definition imaging such as integrated MRI or helical CT suggest that large inter-fractional variations in shape and position occurs during the treatment course [12,13,23], thus adding further uncertainty in determining the tolerance of OARs to radiation injury, since deformation and movement may allow critical structure to approach higher dose regions [12].…”

“…Results from phase I/II trials [7] reported a cumulative local control rate of 71% at 1 year, and benefit of SBRT is currently evaluated in prospective phase III trials [8]. Moreover, irradiation up to 50 Gy in five fractions to part of the tumor has been correlated with an increase in local control and R0 resection rate, suggesting a potential interest of dose escalation to improve global outcome and disease downstaging in order to achieve surgical resectability [9,10]. However, development of more aggressive treatment schedules is limited by proximity of critical dose-limiting structures (duodenum, stomach, bowel), often resulting in a stringent tradeoff between adequate coverage of the target volume and preservation of dose constraints of the organs at risks (OARs).…”

Three discipline collaborative radiation therapy (3DCRT) special debate: The single most important factor in determining the future of SBRT is immune response

“…A second key to future progress in SBRT is continued advancements in imaging, targeting, and adaptive therapy. These will allow for further dose escalation which has the potential to enhance the radiation therapeutic ratio, as well as enable additional treatment sites to benefit from SBRT . Deeper examination of the modality of radiation used for SBRT delivery (e.g., photon versus proton) continues .…”