Contact X-ray Brachytherapy as a Boost Therapy After Neoadjuvant (Chemo)Radiation in High-Risk Locally Advanced Rectal Cancer.

Abstract

Radical surgery following neoadjuvant therapy is the standard of care for locally advanced rectal cancer. A contact x-ray brachytherapy (CXB) boost can alternatively be used to treat residual disease postneoadjuvant (chemo)radiation, especially in patients who are not suitable for or do not wish to have surgery. Its role has mostly been studied to date in low- to intermediate-risk patients. We have now evaluated the utility of CXB boost in high-risk rectal cancers after their tumors have been significantly downstaged by neoadjuvant (chemo)radiation. Oncological outcomes and treatment tolerability were evaluated in 328 patients based on rectal cancer treatment risk stratification: low-/intermediate-risk (cT1-3ab, N0-1, M0, no extramural venous invasion, mesorectal fascia involvement >1 mm) and high-risk (cT3cd-4/N2, M0, mesorectal fascia ≤1 mm, and/or extramural venous invasion positive). With a median follow-up of 33 (IQR, 15-54) months and a median age of 73 (IQR, 62-80) years, no significant differences were found between low/intermediate and high-risk groups in clinical complete response (78% vs. 73%, P = .32), local regrowth (16.6% vs. 22.4%, P = .41), nodal (1.8% vs. 5.8%, P = .051) or regional (1.3% vs. 2.9%, P = .33) relapse, or postradiation toxicities (P = .16). However, the high-risk group had a higher distant relapse rate (21.2% vs. 10.7%, P = .01), with no significant differences in 3-year organ preservation (80% vs. 87%, P = .25), 5-year disease-free survival (62% vs. 64%, P = .46), or overall survival (67% vs. 64%, P = .88). Longer treatment time, treatment gap >24 weeks between therapies, and administration of a higher than standard CXB dose were newly identified factors that negatively impacted outcomes. High-risk patients with rectal cancer treated with CXB boost had more distant relapses, but comparable locoregional tumor control, organ preservation, disease-free survival, and overall survival to lower risk patients, with acceptable toxicities. CXB boost is, therefore, a viable option for selected high-risk patients with rectal cancer. Timely reassessment, prompt referral, and CXB dose optimization are crucial for improving outcomes.