Does Radiation Boost Dose Affect Organ Preservation Rates? A Secondary Analysis of the Organ Preservation in Patients...

The Organ Preservation in Patients with Rectal Adenocarcinoma trial was a randomized clinical trial investigating the optimal sequencing of total neoadjuvant therapy for patients with rectal cancer desiring organ preservation (OP). An optional higher-dose radiation boost was allowed on this trial. We aimed to determine whether a higher radiation boost dose was associated with the probability of clinical complete response and OP.

Patients with clinical stage II/III rectal adenocarcinoma were randomized to induction chemotherapy followed by chemoradiation or chemoradiation followed by consolidation chemotherapy. Radiation therapy was delivered to the primary tumor and involved nodes to 4500 cGy with concurrent chemotherapy. The standard boost dose to the primary tumor was 500 to 540 cGy, but the treating physician was allowed to give an optional higher-dose boost of 900 to 1100 cGy. Post-total neoadjuvant therapy restaging assessment with flexible sigmoidoscopy and magnetic resonance imaging stratified patients into 3 tiers of clinical response. Patients with a clinical complete or near-complete response were offered OP, whereas those with an incomplete clinical response were recommended for total mesorectal excision. In a post hoc analysis, OP rates by radiation boost dose (standard-dose [SD] vs high-dose [HD] boost) were estimated using the Kaplan-Meier method and tested for statistical significance using the log-rank test. Tumor clinical response rates were estimated using proportions and tested for statistical significance using the Fisher exact test.

Of the 324 patients randomized in the Organ Preservation in Patients with Rectal Adenocarcinoma trial, 303 patients were eligible for the present analysis, including 93 patients in the SD boost group (median total dose, 5000 cGy) and 210 in the HD boost group (median total dose, 5400 cGy). Clinical T3/T4 stage at presentation was more common among HD patients (83% and 10%, respectively) compared with SD patients (62% and 18%, respectively) (P < .001); otherwise, the 2 groups were comparable in all other measured aspects. Rates of restaging endoscopic clinical complete response and near-complete response were similar among SD patients (41% and 44%, respectively) and HD patients (44% and 39%, respectively) (P = .5). The median follow-up for patients with OP was 5.14 (IQR, 3.75-5.67) years. The 3- and 5- year probability of OP were both 52% (95% CI, 43-64) for SD patients, and 47% (95% CI, 41-54) and 45% (95% CI, 38-52) for HD patients, respectively.

In the prospective phase 2 Organ Preservation in Patients with Rectal Adenocarcinoma trial of total neoadjuvant therapy for locally advanced rectal cancer, a higher radiation boost dose was not significantly associated with the probability of achieving a clinical complete response or the durability of OP.