By Michael Buckstein, MD, PhD, Icahn School of Medicine at Mount Sinai
The Organ Preservation for Rectal Adenocarcinoma (OPRA) trial is the landmark randomized phase II trial that established chemoradiation followed by chemotherapy (FOLFOX) as the optimal total neoadjuvant (TNT) sequence to achieve potential non-operative management for locally advanced rectal adenocarcinoma. Patients who received upfront chemoradiation followed by chemotherapy had better complete response rates and less tumor regrowth when managed without surgery. While standard of care radiation dosing of 50-50.4 Gy in 25-28 fractions was used in the study, the trial allowed for an optional radiation boost to 54-56 Gy at the discretion of the treating physician. The trial was not stratified for higher radiation doses, and this was not a principal question of the study. The impact of this optional radiation boost has not yet been presented, and this abstract, “Does Radiation Boost Dose Affect Organ Preservation Rates? A Secondary Analysis of the OPRA Trial,” reports for the first time the effect of dose escalation on organ preservation and outcomes.
Out of 303 eligible patients, 210 (64%) received the optional radiation boost. The only statistically significant different pretreatment characteristic of the high dose group vs. standard dosing was the presence of more clinical T3/4 stage in the high dose patients. This subgroup analysis ultimately found no difference in outcomes for high dose vs. standard dosing. With a median follow up of over five years, the five-year organ preservation rates were 52% for standard dosing and 45% for higher dosing, respectively. The rates of endoscopic complete clinical response and near complete response were the same in both groups.
This abstract suggests that despite radiation oncologists having a strong bias toward dose escalation (almost 2/3 chose to boost), dose escalation appears to have no meaningful impact on outcomes in rectal cancer. Higher doses did not improve organ preservation rates or the rate of later tumor regrowth. Believers in dose escalation might argue that the dose escalation was not high enough to have a significant effect on outcomes. They might also say that the higher radiation doses helped with the higher T3/4 disease in those patients than with standard dosing. Conversely, others might argue that tumor biology dictates response, and optimal results are already being achieved with standard dosing. The success of the PROSPECT trial using FOLFOX alone for the neoadjuvant management of rectal cancer suggests that biological sensitivity might be a significant driver in complete response rates and outcomes.
Orly Yariv, MD, the lead author on the study, comments that “this secondary analysis of the OPRA trial addresses a crucial question in rectal cancer treatment: whether increasing the radiation boost dose can enhance organ preservation rates. As non-surgical treatment strategies gain focus, this study holds significant implications for guiding treatment decisions and optimizing therapeutic outcomes. The findings are poised to shape future clinical guidelines, aiming to balance treatment efficacy with the preservation of quality of life for rectal cancer patients.”
In my opinion, this abstract certainly settles a very important question from the OPRA trial and will help direct future studies.
Abstract 302, Does Radiation Boost Dose Affect Organ Preservation Rates? A Secondary Analysis of the OPRA Trial, was presented during the SS 35 - GI 2: Colorectal Cancer: Innovation through Preservation and Observation session of the 66th ASTRO Annual Meeting.
