A Comparison of Oncologic Outcomes and Toxicity with Combined Modality Therapy vs. Carbon Ion Radiotherapy for Locally Recurrent Rectal Cancer in Previously Irradiated Patients

Abstract

<h3>Purpose/Objective(s)</h3> No standard treatment paradigm for previously irradiated, locally recurrent rectal cancer (LRRC) exists. We present comparative oncologic, toxicity, and cost data of previously irradiated patients with LRRC undergoing CIRT versus combined modality therapy (CMT). <h3>Materials/Methods</h3> Patients with LRRC treated between 2006 and 2019 with CIRT alone (n = 85, 70.4 Gy in 16 fractions) at institution A, or CMT (n = 86, photon external beam radiotherapy 30 Gy in 15 fractions with concurrent chemotherapy followed by resection and intraoperative radiotherapy) at institution B were retrospectively compared. Overall survival (OS), pelvic re-recurrence (PR), and distant metastases (DM) were analyzed using the Kaplan-Meier method and competing risk model to report cumulative incidence. Treatment modality was compared using the Cox proportional hazards model. Acute and late toxicities, as well as a 2-year costs were compared. <h3>Results</h3> Median time to follow-up or death was 6.5 years. Median OS in the CIRT and CMT cohorts were 4.5 years and 2.6 years, respectively (HR 0.50 (0.33 – 0.76), <i>P</i> < 0.01). Two- and five-year OS were 83.1% (75.0 – 92.0) and 46.8% (35.2 – 62.3) for CIRT patients and 62.5% (52.5 – 74.4) and 25.7% (17.4 – 38.1) in CMT patients. The five-year cumulative incidence of PR was 53.6% (43.1 – 66.7) for CIRT patients and 36.7% (27.2 – 49.3) in CMT patients (HR 1.40 (0.87 – 2.27), <i>P</i> = 0.17). The five-year cumulative incidence of DM was 61.4% (51.2 – 73.5) for CIRT patients and 50.6% (40.4 – 63.2) in CMT patients (HR 1.20 (0.79 – 1.83), <i>P</i> = 0.39). Acute and late toxicities favored CIRT (Table 1). Costs (over a 2-year period) were higher for CMT than CIRT (median: $96,499 vs. $30,144). <h3>Conclusion</h3> Oncologic outcomes were similar for patients treated with CIRT or CMT, although patient morbidity and cost were lower with CIRT. OS was better with CIRT, potentially attributable to differences in baseline patient health, comorbidities; although, tumor biology cannot be excluded. Prospective comparative studies are needed.