Long-Term Outcome in a Phase II Study of Regional Hyperthermia Added to Preoperative Radiochemotherapy in Locally Advanced and Recurrent Rectal Adenocarcinomas

Abstract

Hyperthermia was added to standard preoperative chemoradiation for rectal adenocarcinomas in a phase II study. Patients with T3-4 N0-2 M0 rectal cancer or local recurrences were included. Radiation dose was 54 Gy combined with capecitabine 825 mg/m2 × 2 daily and once weekly oxaliplatin 55 mg/m2. Regional hyperthermia aimed at 41.5–42.5 °C for 60 min combined with oxaliplatin infusion. Radical surgery with total or extended TME technique, was scheduled at 6–8 weeks after radiation. From April 2003 to April 2008, a total of 49 eligible patients were recruited. Median number of hyperthermia sessions were 5.4. A total of 47 out of 49 patients (96%) had the scheduled surgery, which was clinically radical in 44 patients. Complete tumour regression occurred in 29.8% of the patients who also exhibited statistically significantly better RFS and CSS. Rate of local recurrence alone at 10 years was 9.1%, distant metastases alone occurred in 25.6%, including local recurrences 40.4%. RFS for all patients was 54.8% after 5 years and CSS was 73.5%. Patients with T50 temperatures in tumours above median 39.9 °C had better RFS, 66.7% vs. 31.3%, p = 0.047, indicating a role of hyperthermia. Toxicity was acceptable.

Oncologic Thermoradiotherapy: Need for Evidence, Harmonisation, and Innovation

“…In this special issue new evidence is presented. In a long term retrospective study of preoperative chemoradiation plus deep hyperthermia Schemm et al [1]. reports an encouraging level in five-year survival with better RFS for patients reaching T50 temperatures above 39.9 • C. The impact of a high thermal dose was also found in the retrospective study on RT+HT for prostate cancer by Nakahare et al [2]: CEM43T90 > 7 min.…”

“…The various contributions provide numerous suggestions to innovate thermotherapy, aiming at improved efficiency of combined thermoradiotherapy. The papers by Schemm et al [1] and Nakahara et al [2] are new support of the existence of a thermal dose effect relationship and is another confirmation for the need to always strive for the highest quality assurance and control for optimal treatment outcome. As reported by various papers improved efficiency can be achieved by innovating the heating and improved patient selection to fit with the correct level (complexity) of technology (Kroesen et al [11], Poni et al [12], Androulakis et al [13]) enhanced understanding of the biological principles, either by experimental or clinical research (Dewhirst et al [6], Sengedorj et al [7]) or through building new more advanced biological models (Scheidegger et al [14]) and supported by adequate computer modelling to predict the temperature distribution in the tissue (Kok et al [15]).…”

“…For instance, the review by Datta et al [8] discusses the potential role of hyperthermia as a potential gamechanger in the management of cancer in low-middle-income group countries. It reflects on different hyperthermia technologies that are available including annular-phased array systems for regional hyperthermia as well as capacitive hyperthermia systems without and with the use of amplitude modulation [1][2][3][4]. As each technology involves advantages and disadvantages, it is most important to consciously use it for appropriate clinical indications, preferably within prospective clinical trials.…”

Avoiding Pitfalls in Thermal Dose Effect Relationship Studies: A Review and Guide Forward

“…Ohguri, 2018 [71] Relationships between thermal dose parameters and the efficacy of definitive chemoradiotherapy plus regional hyperthermia in the treatment of locally advanced cervical cancer: data from a multicentre randomised clinical trial Kroesen, 2019 [72] The effect of the time interval between radiation and hyperthermia on clinical outcome in 400 locally advanced cervical carcinoma patients Datta, 2021 [13] Quantification of thermal dose in moderate clinical hyperthermia with radiotherapy: a relook using temperature-time area under the curve (AUC) Nakahara, 2022 [73] Intensity-modulated radiotherapy with regional hyperthermia for high-risk localized prostate carcinoma Schem, 2022 [74] Long-term outcome in a phase ii study of regional hyperthermia added to preoperative radiochemotherapy in locally advanced and recurrent rectal adenocarcinomas…”

“…Cancers 2022, 14, x 7 of 25 Yahara, 2015 [70] Definitive radiotherapy plus regional hyperthermia for high-risk and very high-risk prostate carcinoma: Thermal parameters correlated with biochemical relapse-free survival Ohguri, 2018 [71] Relationships between thermal dose parameters and the efficacy of definitive chemoradiotherapy plus regional hyperthermia in the treatment of locally advanced cervical cancer: data from a multicentre randomised clinical trial Kroesen, 2019 [72] The effect of the time interval between radiation and hyperthermia on clinical outcome in 400 locally advanced cervical carcinoma patients Datta, 2021 [13] Quantification of thermal dose in moderate clinical hyperthermia with radiotherapy: a relook using temperature-time area under the curve (AUC) Nakahara, 2022 [73] Intensity-modulated radiotherapy with regional hyperthermia for high-risk localized prostate carcinoma Schem, 2022 [74] Long-term outcome in a phase ii study of regional hyperthermia added to preoperative radiochemotherapy in locally advanced and recurrent rectal adenocarcinomas All included articles analysed the ability of different temperature and thermal dose parameters to predict treatment outcome or toxicity. Treatment outcome was the investigated endpoint in 90% (44/48) of the articles, while toxicity was investigated in 50% (24/48) of the articles.…”