Feasibility of Modulated electro-Hyperthermia in preoperative treatment for locally Advanced Rectal Cancer: Early phase 2 clinical results

Overall Preoperative Treatment Outline

Overall Preoperative Treatment Outline

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Summary

A prospective trial was performed to investigate the feasibility of modulated electro-hyperthermia (mEHT) as a concomitant boost to preoperative chemoradiation in locally advanced rectal cancer. The results showed comparable pathologic treatment outcomes and tolerable toxicity profiles with the addition of mEHT, which may potentially replace part of the radiation dose in neoadjuvant treatment for rectal cancer.

Patients characteristics

60 patients with histologically proven rectal adenocarcinoma had a median age of 59 (range 33–83). Primary tumor located within 15 cm from anal verge, clinical T3–4 or N+ staged by magnetic resonance (MR) and computed tomography (CT) imaging, Eastern Cooperative Oncology Group performance status ≤2, no prior pelvic irradiation, and proper function of the bone marrow, kidney, and liver.

Methodology

Radiation therapy
Preoperative radiation was delivered by the technique of external beam X-ray from a linear accelerator. The beam energy was 6–15 MV. Three- or four-field technique in the supine position was used depending on the location and the extent of the disease. The clinical target volume included the tumor, the mesorectum, the internal iliac nodes, and presacral nodes up to the sacral promontory level.
Modulated electro-hyperthermia
mEHT was performed on a twice-weekly schedule during the radiotherapy period using 13.56 MHz capacitive coupled device (EHY2000, Oncotherm GmbH). All patients were treated in the supine position. A 30 cm diameter sized electrode was applied as an upper pole, whose center was located on the middle of the clinical target volume to cover the tumor and elective pelvic lymph node area. The duration of mEHT treatment was 60 minutes and the radiotherapy of that day followed immediately within one hour. At the beginning of treatment, the power was started at 100 W during the first 20 min, maintained at least at 120 W for the next 20 min, and fixed at 140 W for the last 20 min. From the subsequent treatment session, the power was constantly fixed at 140 W if there were no toxicity problems.

Treatment

A total dose of 40 Gy was delivered via a daily fraction of 2 Gy, with five fractions per week. Either 5-fluorouracil/leucovorin or oral capecitabine was administered concurrently as systemic chemotherapy. 5-fluorouracil/leucovorin was injected intravenously with bolus for 3 days at the 1st and 5th week after initiation of radiotherapy at doses of 400 and 20 mg/m2/day for 5- fluorouracil and leucovorin, respectively. Oral capecitabine was administered at a dose of 825 mg/m2 from the 1st day of radiation during the virtual period of the conventional 28-fraction schedule. In addition to this slightly modified concur-rent chemoradiation course, eight sessions of mEHT were combined twice weekly during scheduled radiation therapy.

Results

Downstaging and tumor regression
After surgery, T-downstaging was observed in 40 patients (66.7%). Regarding the lymph nodes, N-downstaging occurred in 53 patients (88.3%). The proportion of pathologic complete response for T-stage (ypT0) and N-stage (ypN0) was 15.0% (9 patients) and 76.7% (46 patients), respectively. The patient number of minimal, moderate, near total, and total regression grade for primary tumors was 9 (15.0%), 31 (51.7%), 11 (18.3%), and 9 (15.0%), respectively.
Toxicity
Treatment-related toxicities were easily tolerated. Hematologic toxicity of Grade 2 or higher was mainly found as leukopenia in 16 patients (26.7%) and neutropenia in 6 patients (10.0%). In the cases of anemia, Grade 2 or higher was observed in 7 patients (11.7%). Genitourinary toxicity was generally low (only one Grade 2 or higher patient), which presented as non- infective cystitis related symptoms. Nineteen patients (31.7%) experienced Grade 2 or higher gastrointestinal toxicities presenting as pelvic pain, nausea, or diarrhea. There was no Grade 3 or higher non-hematologic toxicity. For heat-related toxicity, the highest was Grade 2 in only one case.

Conclusion

In conclusion, non-inferior primary tumor regression and excellent lymph node response are sufficient to indicate the mEHT boosts as a useful option for rectal cancer treatment. Radiation was shown to be sufficiently supplemented by mEHT, with acceptable toxicity levels and feasibility in multimodality management. Therefore, mEHT can be combined as a boosting method with radiation.

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Scientific article publishing date : 9/18/2019

Immucura identifier BSC21_171EN

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