Fractionated Radiotherapy Improves Cancer Surgery Results

Short-course preoperative radiotherapy (RT) combined with delayed surgery reduces the adverse side effects of rectal cancer surgery, according to a new study.

Researchers at Karolinska Institutet, Uppsala University, and other institutions conducted a phase 3 non-inferiority trial involving 840 patients from 18 Swedish hospitals who were randomized to three different RT regimens, with respect to fractionation and time to surgery. All patients suffered from biopsy-proven adenocarcinoma of the rectum, without signs of non-resectability or distant metastases, without severe cardiovascular comorbidity, and with planned abdominal resection.

The participants were randomly assigned with permuted blocks, stratified by participating center, to receive either 5 × 5 Gy radiation dose with surgery within one week (short-course radiotherapy), or after 4–8 weeks (short-course radiotherapy with delay), or 25 × 2 Gy radiation dose with surgery after 4–8 weeks (long-course radiotherapy with delay). The primary endpoint was time to local recurrence, as calculated from the date of randomization to the date of local recurrence.

The results showed that in patients with any local recurrence, median time from date of randomization to local recurrence in the short-course RT comparison was 33.4 months; in the short-course RT group, it was 19.3 months; and in the long-course RT with delay group it was 33.3 months. Postoperative complications were similar between all three arms; however, the risk of postoperative complications was significantly lower after short-course RT with delay. The study was published on February 9, 2017, in The Lancet Oncology.

“The results of the study will give rise to improved therapeutic strategies, fewer complications with a sustained low incidence of local recurrence, and better survival rates for rectal cancer patients,” said senior author Professor Anna Martling, PhD, of the KI department of molecular medicine and surgery. “It also showed that there is no difference between long-course and short-course radiotherapy, other than that the former considerably lengthens the time for treatment.”

When the total dose of radiation is fractionated into several, smaller doses over a period of several days, there are fewer toxic effects on healthy cells. Typical fractionation schemes divide the radiation dose into units delivered every weekday over about six weeks. The logic behind the treatment is that applying greater amounts of radiation works to lower the effects of accelerated tumor growth that typically occurs during the later stages of RT.