Right-Sided CRC Metastases Call for ‘More Aggressive’ Approach

Colorectal cancer (CRC) metastases from right-sided primary tumors and CRC liver metastases had higher rates of local failure following stereotactic ablative radiotherapy (SABR), a single-institution retrospective study found.

Among 130 patients with oligometastatic CRC, lesions stemming from right-sided CRCs were more than twice as likely to recur locally following SABR, as compared with left-sided tumors (HR 2.328, 95% CI 1.181-4.588, P=0.0146), reported Daniel T. Chang, MD, of Stanford Cancer Center in California, and colleagues.

And this held true across the three metastatic sites analyzed (brain, liver, spin), with right-sided CRC primary tumors significantly or nearly significantly associated with higher local failure, according to the findings in the American Journal of Clinical Oncology.

Local failure following SABR was highest among patients with liver metastases, with 1- and 2-year rates of 26.0% and 38.5%, respectively.

“This paper adds to the body of literature suggesting we need to take a more aggressive local approach to metastatic colorectal cancer, particularly with regard to liver metastases,” agreed Emma Holliday, MD, of the University of Texas MD Anderson Cancer Center in Houston, who was not involved with the study.

She noted that other groups have also suggested that right-sided CRCs have a worse prognosis overall, perhaps because of molecular differences in the cancers themselves. These data corroborate that, Holliday told MedPage Today.

“It is also significant that this study reported worse results when patients received a biologically effective dose less than 70 Gy,” she added. “These data are in line with those published from Massachusetts General Hospital and from other groups that have also shown high rates of local failure after ‘standard’ SABR doses.”

“Although the study has some of the same limitations that all retrospective research is subject to, it supports the long-held belief that colorectal cancer metastases are intrinsically resistant to radiation,” she continued. “In our own multidisciplinary conference discussions, we will often discuss all local treatment options for patients with colorectal cancer liver metastases. If a high dose of stereotactic radiation cannot be delivered safely, we will often favor ablation or other liver-directed therapies if these are safe and feasible.”

Chang and co-authors analyzed 130 patients with pathologically confirmed oligometastatic CRC at the time of treatment, from 2001 to 2016, who had at least one metastatic site treated with SABR in the liver, lung, spine, or brain.

Of the 256 individual metastases included, 129 (50%) were to the brain, 50 (20%) to the liver, 49 (19%) to the spine, and 28 (11%) to the lung. Median gross tumor volumes were 2 mL for brain metastases, 24 mL for liver metastases, 4 mL for spine metastases, and 1 mL for lung metastases. A total of 70 local failures occurred in the total cohort.

Other major findings:

• The overall 1-, 2-, and 3-year cumulative incidences of local failure were 21.6% (95% CI 16.5%-27.1%), 28.2% (95% 22.3%-34.4%), and 31.5% (95% CI 25.2%-38.0%), respectively

• Local failure rates at 1 and 2 years were 25.1% and 31.1%, respectively, for spine metastases, and 20% and 25.2% for brain metastases

• Duration of pre-SABR chemotherapy was also a significant predictor of local failure

Study limitations in addition to the retrospective design, Chang and co-authors said, included the relatively small sample size collected from a single institution.