Modulated Electro-Hyperthermia in Combination With Multimodal Therapy for Locally Advanced Rectal Cancer

Evaluation of the decrease in ypT and ypN staging for patients with locally advanced rectal cancer following the current recommended treatment method, total neoadjuvant therapy (TNT). The ycT and ycN staging will be assessed using MRI within three months post-treatment for patients who do not undergo surgery.

A pCR must include no gross or microscopic tumor identified anywhere within the surgical specimen. This must include:

• No evidence of malignant cells in the primary tumor specimen AND
• No evidence of malignant cells in the lymph nodes.

Using the Dworak Scale, defined as "good tumor shrinkage" with Grade 3 and Grade 4.

OS is defined as time from randomization to the date of death due to any cause.

DFS is defined as the time from randomization to the date of local recurrence, regional recurrence, distant recurrence or death due to all causes whichever comes first. Patients who fail to return for evaluation after beginning therapy will be censored for DFS on the last day of therapy.

LCR is defined as the time from randomization to the date of the first documentation of local recurrence.

DMFS is defined as the time from randomization to the date of the first documentation of distant metastasis.

CFS is defined as being alive without a colostomy, excluding colostomies reversed during follow-up.

Comparison of Surgery Rates is defined as the rate of patients who receive TME between two groups after TNT.

Surgical Techniques to be recorded: Total Mesorectal Excision (TME), local excision or other (specify).

For the optimal treatment, patients in experimental arm receive hyperthermia by using Oncotherm EHY-2030 device, with a planned power output of 60 minutes. The number of treatment where this optimal output could not be reached must be recorded and reported.

Using CTCAE v5.0, scored 0 - 5, with higher scores indicating more severe adverse effects. The items include: radiation dermatitis, anorexia, nausea, vomiting, constipation, diarrhea, dysuria, hematuria, and fatigue. All items are planned to be evaluated at the initiation of treatment (week 1), and subsequently at the week 6, week 9, week 28, week 42, week 48, week 60, week 72, week 84, and week 96 (+/- 3 weeks is permitted).

Recording total white cell counts, absolute neutrophil counts, and absolute lymphocyte counts of all patients. Blood samples are obtained at the initiation of treatment (week 1), and subsequently at the week 6, week 9, week 28, week 42, week 48, week 60, week 72, week 84, and week 96 (+/- 3 weeks is permitted).

Recording hemoglobin levels of all patients. Blood samples are obtained at the initiation of treatment (week 1), and subsequently at the week 6, week 9, week 28, week 42, week 48, week 60, week 72, week 84, and week 96 (+/- 3 weeks is permitted).

Recording platelet counts of all patients. Blood samples are obtained at the initiation of treatment (week 1), and subsequently at the week 6, week 9, week 28, week 42, week 48, week 60, week 72, week 84, and week 96 (+/- 3 weeks is permitted).

Using the LENT/SOMA scoring system, evaluating symptoms such as tenesmus, mucosal loss, sphincter control, stool frequency, pain, bleeding, ulceration, stricture, etc., scored 1 - 4, with higher scores indicating worse outcomes.

Quality of Life (QoL) assessment is mandatory for all eligible patients randomized into the trial. QoL will be evaluated using the total score of the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30). A printed questionnaire will be administered in the clinic by a CRA or study nurse at the following time points:

• Baseline (at the time of randomization, prior to treatment initiation).
• The last week of neoadjuvant CRT with or without mEHT.
• Nine months after the completion of the TNT course (approximately 42 weeks ± 3 weeks post-randomization).

Rectal Cancer Quality of Life (QoL) assessment is mandatory for all eligible patients randomized into the trial. QoL will be evaluated using the total score of the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-CR29). A printed questionnaire will be administered in the clinic by a CRA or study nurse at the following time points:

• Baseline (at the time of randomization, prior to treatment initiation).
• The last week of neoadjuvant CRT with or without mEHT.
• Nine months after the completion of the TNT course (approximately 42 weeks ± 3 weeks post-randomization).

Using the LAR score.

The QoL evaluation focus on functional outcome will be evaluated using LAR score. This assessment is mandatory for all eligible patients randomized into the trial. A printed questionnaire will be administered in the clinic by a CRA or study nurse at the following time points:

• Baseline (at the time of randomization, prior to treatment initiation).
• The last week of neoadjuvant CRT with or without mEHT.
• Nine months after the completion of the TNT course (approximately 42 weeks ± 3 weeks post-randomization).