Contact X-ray Brachytherapy (CXB) as a boost therapy after neoadjuvant (chemo)radiation in high-risk locally advanced rectal cancer.

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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 post neoadjuvant (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 tumours 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 invasion (EMVI), mesorectal fascia (MRF) involvement >1mm) and high-risk (cT3cd-4/N2, M0, MRF≤1mm and/or EMVI positive). With median follow-up of 33(IQR:15-54) months and 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=0.32), local regrowth (16.6% vs 22.4%, p=0.41), nodal (1.8% vs 5.8%, p=0.051) or regional (1.3% vs 2.9%, p=0.33) relapse, or post-radiation toxicities (p=0.16). However, the high-risk group had a higher distant relapse rate (21.2% vs 10.7%, p=0.01), with no significant differences in 3-year organ preservation (80% vs 87%, p=0.25), 5-year disease-free (DFS) (62% vs 64%, p=0.46), or overall (OS) survivals (67% vs 64%, p=0.88). 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 rectal cancer patients treated with CXB-boost had more distant relapses, but comparable locoregional tumour control, organ preservation, DFS and OS to lower-risk patients, with acceptable toxicities. CXB-boost is therefore a viable option for selected high-risk rectal cancer patients. Timely reassessment, prompt referral, and CXB dose optimisation are crucial for improving outcomes.