Differences Between Colon Cancer Primaries and Metastases Utilizing a Molecular Assay for Tumor Radiosensitivity Suggest Implications for Potential Oligometastatic SBRT Patient Selection

Abstract

Purpose/Objectives-We have previously developed a multigene expression model of tumor radiosensitivity (RSI) with clinical validation in multiple independent cohorts (breast, rectal, esophageal, and head and neck). The purpose of this study was to assess differences in RSI scores between primary colon cancer and metastases.Methods and Materials-Patients were identified from our institutional IRB approved prospective observational protocol. A total of 704 metastatic and 1,362 primary lesions were obtained from a de-identified meta-data pool. RSI was calculated using the previously published ranked based algorithm. An independent cohort of 29 lung or liver colon metastases treated with 60 Gy in 5 fractions stereotactic body radiotherapy (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-radioresistant (RSI-RR) peak, suggesting that, metastatic tumors may be slightly more radioresistant than primaries (p=0.01). In contrast, when we analyzed metastases based on anatomical site, we uncovered large differences in RSI. The median RSIs for metastases Corresponding Author: Javier F. Torres-Roca MD, H. Lee Moffitt Cancer Center and Research Institute, Department of Radiation Oncology, 12902 Magnolia Dr., Tampa, FL 33612 USA, Telephone: 00-1-813-745-3568, Fax: 00-1-813-745-7231, javier.torresroca@moffitt.org. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Conflicts of HHS Public Access Author Manuscript Author ManuscriptAuthor ManuscriptAuthor Manuscript in descending order of radioresistance were ovary (0.48), abdomen (0.47), liver (0.43), brain (0.42), lung (0.32), and lymph nodes (0.31), p<0.0001. 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 (LC) rate over patients with liver metastases (2 yr LC 100% vs. 73.0%, p=0.026).Conclusions-Assessment of radiosensitivity between primary and metastatic tissues of colon cancer histology, reveals significant differences based on anatomical location of metastases. These initial results warrant validation in a larger clinical cohort.

Stereotactic Body Radiotherapy in the Management of Oligometastatic Disease

“…62 In another study, we assessed RSI differences between primary and metastatic colon cancers. 63 As suggested by the clinical experience of other groups using SBRT, we found significant differences in RSI based on the anatomical location of metastases. 63 We found that colon cancer metastasized to sites such as the ovary, abdomen, and liver and were more radioresistant than when tumors metastasized to sites such as the lung and lymph nodes (P < .0001).…”

“…63 As suggested by the clinical experience of other groups using SBRT, we found significant differences in RSI based on the anatomical location of metastases. 63 We found that colon cancer metastasized to sites such as the ovary, abdomen, and liver and were more radioresistant than when tumors metastasized to sites such as the lung and lymph nodes (P < .0001). 63 These results were confirmed when we restricted our analysis to lesions from the same study patient.…”

“…63 These results were confirmed when we restricted our analysis to lesions from the same study patient. 63 Our clinical practice has been to treat both lung and liver metastases regardless of primary histology to 60 Gy in 5 fractions of SBRT. Assessing our own institutional experience with the management of lung and liver metastases with primary colon cancer, we have found significant differences in local control outcomes, with lung metastases fairing better than liver metastases.…”

“…63 We found that colon cancer metastasized to sites such as the ovary, abdomen, and liver and were more radioresistant than when tumors metastasized to sites such as the lung and lymph nodes (P < .0001). 63 These results were confirmed when we restricted our analysis to lesions from the same study patient. 63 Our clinical practice has been to treat both lung and liver metastases regardless of primary histology to 60 Gy in 5 fractions of SBRT.…”

“…This correlates well to our RSI analysis, which revealed liver metastases of primary colon cancer to be more radioresistant than those of lung metastases. 63 Thus, we propose that RSI could be used as a model to select dose and fractionation schedules for various anatomical sites and various histologies, possibly setting the stage for use in future clinical trials.…”