# Neoadjuvant Radiochemotherapy Combined with Locoregional Hyperthermia in Locally Advanced Rectal Cancer: Feasibility and Tolerance of Short-Course Versus Long-Course Radiotherapy Schedules

## TL;DR

This study shows that adding deep hyperthermia to standard pre-surgery treatments for rectal cancer is safe and well-tolerated for most patients.

## Contribution

The study is the first in Spain to demonstrate the feasibility of integrating deep hyperthermia with both short- and long-course radiotherapy for rectal cancer.

## Key findings

- Deep hyperthermia was completed in 100% of short-course and 63.6% of long-course radiotherapy patients.
- No serious hyperthermia-related side effects were observed, with most symptoms being mild and temporary.
- All patients received their planned radiotherapy and surgery on schedule.

## Abstract

Rectal cancer is a common and serious disease that often requires treatment before surgery to improve the chances of removing the tumor completely. This pre-surgery treatment usually includes radiotherapy and chemotherapy. In our hospital, we tested adding a technique called deep hyperthermia, which gently warms the tumor area using a special device. Warming the tumor can make cancer cells more sensitive to other treatments. We applied this approach to 67 patients with rectal cancer before surgery. Some patients received a short, one-week course of radiotherapy, and others received a longer, five-week course. Alongside these treatments, patients had either two or ten heating sessions, depending on the schedule. Most patients completed the planned sessions, and the treatment was generally well tolerated. The most common effects were mild and temporary discomfort, such as local pain, and no serious problems were caused by hyperthermia. All patients received their radiotherapy and surgery on time. These results show that deep hyperthermia can be safely and smoothly combined with standard pre-surgery treatment for rectal cancer. This approach could improve the way this disease is treated, and further research will help to understand its benefits for long-term recovery.

Background: Integrating deep regional hyperthermia (HT) with neoadjuvant chemoradiotherapy (CRT) may enhance treatment efficacy in locally advanced rectal cancer (LARC), yet feasibility and tolerance data remain scarce for both short-course (SCRT) and long-course (LCRT) radiotherapy (RT) regimens. Methods: In this single-center prospective observational study, 67 LARC patients received neoadjuvant RT and chemotherapy (CT) combined with deep radiative HT using a phased-array system (ALBA 4D). Patients treated with SCRT (5 × 5 Gy) were prescribed two HT sessions; those treated with LCRT (25 × 2 Gy) were prescribed ten. HT planning was guided by dedicated software, and real-time thermometry ensured precise thermal delivery. Feasibility was defined as completion of ≥50% of prescribed sessions. Tolerance and toxicity were assessed with standardized clinical scales (QMHT, UMC, CTCAE v4.03). Results: HT was feasible in both groups: 100% of SCRT and 63.6% of LCRT patients completed ≥50% of prescribed sessions. In total, 243 sessions were delivered. Most symptoms were mild and transient, predominantly localized pain. No grade ≥3 HT-related toxicities occurred. All scheduled RT and surgery proceeded without delay. Median T50 was 40.3 °C (SCRT) and 40.4 °C (LCRT); the median RT-to-HT interval was 42 min in both groups. Conclusion: This first Spanish experience shows that deep radiative HT can be seamlessly integrated into both SCRT and LCRT neoadjuvant protocols for rectal cancer. High adherence, favorable tolerance, and reliable thermal control support clinical implementation. Any between-schedule observations are descriptive only; no formal comparative testing was performed. The study was not designed or powered to establish comparative effectiveness between SCRT and LCRT, and the sample size was insufficient to detect rare HT-specific adverse events.