Radiation Dose Escalation to the Tumor-Arterial Interface of Locally Advanced and Borderline Resectable Pancreatic Cancer

Martin C. Tom, MD, Eugene J. Koay, MD, PhD, Priya Bhosale, MD, Prajnan Das, MD, MPH, Matthew H. Katz, MD, Jason B. Fleming, MD, Jeffrey E. Lee, MD, Gauri R. Varadhachary, MD, Robert A. Wolff, MD, and Christopher H. Crane, MD
Published: Saturday, Jul 09, 2016
Martin C. Tom, MD

About the lead author:

Martin C. Tom, MD
Houston Methodist
Houston, TX 77030

Eugene J. Koay, MD, PhD
Eugene J. Koay, MD, PhD
Department of Radiation Oncology
The University of Texas MD Anderson Cancer Center
Houston, TX 77030

Expert’s Perspective:

Sarah Hoffe, MD
Sarah Hoffe, MD
lack Department of Radiation Oncology
Moffitt Cancer Center

Why is this article contemporary?

Although homogeneous dose prescriptions have been the standard in radiation therapy delivery, advanced technology integration now creates the potential for dose painting (DP). With the article by Crane et al in this issue, differential dose deposition is explored in those pancreatic cancer patients with extensive vascular involvement on the basis that higher biologically effective doses may be needed to facilitate conversion to negative margin resection. The incorporation of intensity-modulated radiation therapy and motion management allow the highly precise delivery of 63 Gy to that portion of the tumor at higher risk for residual disease, should resection become feasible.

Contextually, this data invites consideration of novel dose painting strategies, suggesting that the future may invite innovative heterogeneous dose escalation. Recent data from radiomic studies have reported that intra-tumoral heterogeneity is present with marked molecular differences between cells in the core of the tumor vs the tumor edge.1 Analysis of metastatic liver tumor deposits from colorectal cancer has shown that those tumors with higher intra-individual genetic heterogeneity have worse 3-year survival.2 With the improved imaging techniques now available, the near future may herald the capacity for the prospective imaging delineation of clinically relevant microhabitats to guide molecularly targeted radiation therapy.

This article therefore sets the stage for new dose exploration in the setting of patients with unresectable pancreatic cancer. The authors report their experience with this technique, raising the question of how radiation oncologists can best maximize a DP approach to improve outcomes. Improved correlation of imaging data with intra-tumoral molecular phenotypes has the future potential to significantly accelerate a new dosimetric paradigm.

1. Gillies RJ, Kinahan PE, Hricak H. Radiomics: images are more than pictures, they are data. Radiology. 2016;278(2):563-577. doi: 10.1148/radiol.2015151169.

2. Sveen A, Loes IM, Alagaratnam S, et al. Intra-individual genetic heterogeneity among liver metastases in metastatic colorectal cancer. ASCO Meeting Abstracts. 2016;34(4_suppl):555.

Abstract

Objective

There is substantial interest in the use of escalated doses of radiation to improve tumor resectability in pancreatic cancer, but true radiographic downstaging does not frequently occur. We reviewed our experience integrating a radiation boost to the tumor-arterial interface in borderline resectable and locally advanced pancreatic cancer with the objective of downstaging.

Materials and Methods

Twenty-three patients with borderline resectable (n = 14) or locally advanced disease (n = 9) received chemoradiation with an integrated radiation boost to the tumor-arterial interface (median dose: 63 Gy in 28 fractions). We recorded patient outcomes and compared CT scans before and after radiotherapy to evaluate response.

Results

There was no downstaging in 21 of 23 patients. The 2 patients who achieved downstaging of their primary tumor had early distant metastasis (DM) that precluded surgery. Three patients with borderline resectable disease underwent margin-negative resection. Many patients developed DM soon after chemoradiation as median distant metastasis-free survival (DMFS) was 8 months. The median local progression-free survival (LPFS) was 23 months and median overall survival (OS) was 16 months.

Conclusion

An integrated boost with conventional fractionation to the tumor-arterial interface is unlikely to lead to downstaging in borderline resectable and locally advanced pancreatic cancer.

Introduction

Surgical resection remains the only potentially curative treatment for pancreatic cancer. However, fewer than 20% of patients present with potentially resectable disease.1 Consequently, outcomes remain poor with an estimated 5-year relative survival rate of 6%.2 For those patients who proceed to surgical resection, negative margins (R0) have been established as crucial in attaining long-term survival.3 Pancreatic cancer has a tendency to spread along the vasculature of the retroperitoneal border, and the most common site of microscopically positive resection is the superior mesenteric artery (SMA) margin.4,5 Thus, in the absence of distant metastasis (DM), the primary determinant of resectability in pancreatic cancer is the extent of vascular involvement.


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Online CME Activities
TitleExpiration DateCME Credits
Oncology Briefings™: Integrating Novel Targeted Treatment Strategies to Advance Pancreatic Cancer CareNov 30, 20181.0
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