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. 2015 Jul 15;92(4):837-42.
doi: 10.1016/j.ijrobp.2015.01.036. Epub 2015 Mar 30.

Differences Between Colon Cancer Primaries and Metastases Using a Molecular Assay for Tumor Radiation Sensitivity Suggest Implications for Potential Oligometastatic SBRT Patient Selection

Kamran A Ahmed  1 , William J Fulp  2 , Anders E Berglund  2 , Sarah E Hoffe  1 , Thomas J Dilling  1 , Steven A Eschrich  3 , Ravi Shridhar  1 , Javier F Torres-Roca  4
Affiliations

Differences Between Colon Cancer Primaries and Metastases Using a Molecular Assay for Tumor Radiation Sensitivity Suggest Implications for Potential Oligometastatic SBRT Patient Selection

Kamran A Ahmed et al. Int J Radiat Oncol Biol Phys. .

Abstract

Purpose: We previously developed a multigene expression model of tumor radiation sensitivity index (RSI) with clinical validation in multiple independent cohorts (breast, rectal, esophageal, and head and neck patients). The purpose of this study was to assess differences between RSI scores in primary colon cancer and metastases.

Methods and materials: Patients were identified from our institutional review board-approved prospective observational protocol. A total of 704 metastatic and 1362 primary lesions were obtained from a de-identified metadata pool. RSI was calculated using the previously published rank-based algorithm. An independent cohort of 29 lung or liver colon metastases treated with 60 Gy in 5 fractions stereotactic body radiation therapy (SBRT) was used for validation.

Results: The most common sites of metastases included liver (n=374; 53%), lung (n=116; 17%), and lymph nodes (n=40; 6%). Sixty percent of metastatic tumors, compared with 54% of primaries, were in the RSI radiation-resistant peak, suggesting metastatic tumors may be slightly more radiation resistant than primaries (P=.01). In contrast, when we analyzed metastases based on anatomical site, we uncovered large differences in RSI. The median RSIs for metastases in descending order of radiation resistance were ovary (0.48), abdomen (0.47), liver (0.43), brain (0.42), lung (0.32), and lymph nodes (0.31) (P<.0001). These findings were confirmed when the analysis was restricted to lesions from the same patient (n=139). In our independent cohort of treated lung and liver metastases, lung metastases had an improved local control rate compared to that in patients with liver metastases (2-year local control rate of 100% vs 73.0%, respectively; P=.026).

Conclusions: Assessment of radiation sensitivity between primary and metastatic tissues of colon cancer histology revealed significant differences based on anatomical location of metastases. These initial results warrant validation in a larger clinical cohort.

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Conflict of interest statement

Conflicts of Interest: Steven A. Eschrich PhD and Javier F. Torres-Roca MD report stock and leadership in Cvergenx, Inc. and royalty and patents on RSI

Figures

Figure 1
Figure 1
Differences in RSI between primary and colon cancer metastases, black and red lines represent the 10th, 25th, 50th, 75th, and 90th percentile of RSI values across all samples.
Figure 2
Figure 2
Differences in RSI of colon cancer metastases based on anatomical location, black and red lines represent the 10th, 25th, 50th, 75th, and 90th percentile of RSI values across all samples.
Figure 3
Figure 3
Differences in RSI between primary and metastases from the same patient.
Figure 4
Figure 4
Differences in RSI between primary and metastatic lesions based on anatomical location from the same patient.
Figure 5
Figure 5
Local control rates between lung and liver colon cancer metastases.
See this image and copyright information in PMC

Comment in

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