Radiation improves outcomes for right-sided metastatic colorectal tumors

The addition of selective internal radiation therapy to first-line chemotherapy significantly prolonged OS in patients with liver metastases from right-sided primary colorectal tumors, according to study results presented at the European Society for Medical Oncology World Congress on Gastrointestinal Cancer.

Patients with left-sided primary tumors did not experience a significant benefit with selective internal radiation therapy, results showed.

“These findings are good news for patients with right-sided primary tumors, who have a much worse prognosis and fewer treatment options than patients with left-sided tumors,” Guy van Hazel, MD, clinical professor of medicine in the School of Medicine and Pharmacology at University of Western Australia in Perth, Australia, said in a press release. “We are excited because hitherto no treatment apart from the addition of bevacizumab [Avastin, Genentech] to chemotherapy has improved the dismal outcome of liver metastases coming from right-sided primary tumors.”

Although right-sided primary tumors are known to have an inferior prognosis and response, the impact of primary tumor location on outcomes from selective internal radiation therapy in patients with liver metastases from colorectal cancer had not been evaluated.

van Hazel and colleagues evaluated data from SIRFLOX and FOXFIRE-Global trial cohorts to determine whether primary tumor location impacted OS and PFS.

In those studies, researchers randomly assigned patients with previously untreated liver-only or liver-dominant metastatic colorectal cancer to receive modified FOLFOX6 chemotherapy — which consists of oxaliplatin, leucovorin and 5-fluorouracil — alone or with a single administration of selective internal radiation therapy using yttrium-90 resin microspheres (SIR-Spheres, Sirtex). Patients also could receive bevacizumab at investigator discretion.

Researchers defined right-sided primary tumors as those located proximal to the splenic feature, and left-sided primary tumors included those at the splenic feature, the more distal colon and the rectum.

The analysis included 739 patients — 530 from SIRFLOX and 209 from FOXFIRE-Global — the majority of whom had a left-sided primary tumor (n = 540, 73.1%). Another 179 patients (24.2%) had a right-sided primary tumor, and 3% of patients had primary tumors on both sides of the colon or an unknown primary site.

Among all patients, the addition of selective internal radiation therapy to modified FOLFOX6 chemotherapy did not impact median PFS (11.1 months vs. 10.6 months) or median OS (24.3 months vs. 24.6 months).

However, patients with right-sided tumors demonstrated a significant OS benefit (median, 22 months vs. 17.1 months; HR = 0.64; 95% CI, 0.46-0.89) and a trend toward a PFS benefit (median, 10.8 months vs. 8.7 months; HR = 0.73; 95% CI, 0.53-1.01) with the addition of selective internal radiation therapy.

This finding did not persist for patients with left-sided primary tumors in terms of OS (24.6 months vs. 25.6 months; HR = 1.12; 95% CI, 0.92-1.36) and PFS (11.4 months vs. 10.8 months; HR = 0.93; 95% CI, 0.78-1.11).

For OS, researchers reported a highly significantly treatment interaction by tumor location (Chi-square, 9.49; P = .002; HR = 0.54; 95% CI, 0.37-0.8).

Grade 3 or worse adverse events did not differ by tumor location. Patients who received the addition of selective internal radiation therapy had more adverse events than those who received chemotherapy alone, but van Hazel considered these “predictable and manageable.”

“It remains to be confirmed whether these results mean that right-sided tumors are more sensitive to this kind of radiotherapy, or whether this is simply related to the fact that the molecular characteristics of right-sided tumors allow less treatment options, because they have more mutations,” Dirk Arnold, MD, from Instituto CUF de Oncologia in Lisbon, Portugal, and Eric Van Cutsem, MD, PhD, of University Hospitals Leuven in Belgium, both of whom are ESMO spokespersons who were not involved with the study, said in the press release. “Additionally, the well-known worse prognosis of right-sided tumors increased the relative importance of a nonsystemic treatment option. More data on the molecular features determining these results are warranted.” – by Alexandra Todak

Reference:

van Hazel G, et al. Abstract LBA-006. Presented at: European Society for Medical Oncology World Congress on Gastrointestinal Cancer; June 28-July 1, 2017; Barcelona.

Disclosure: HemOnc Today could not confirm the researchers’ relevant financial disclosures at the time of reporting.