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Combined hyperthermia and radiation therapy

Hee Chul Park, M.D., Ph.D.

The standard treatment of unresectable liver metastasis in gastrointestinal tract cancer is chemotherapy, but considerable portion of the patients progressed and most of the liver is converted to metastatic tumor lesions. Significant quality of life decrement was detected in those patients, especially in patients suffered severe symptoms Several studies reported that whole liver RT (WLRT) can be used effectively to control severe symptoms from unresectable liver metastasis in gastrointestinal tract cancer patients. However, it is well known fact that the liver is a very sensitive to RT. Despite symptom palliation is obtained after 20 to 30 Gy RT but only in small subset of patients get local control. In this aspect, the combined with radiosensitizer with WLRT is considered to enhance RT effect to palliate symptom and control local tumor progression, and increase the quality of life ultimately.

It is reported that hyperthermia is considered as the most valuable radiosensitizer in cancer treatment, theoretically. Based on those studies, we start this prospective study to investigate the effect of combination treatment of WLRT and hyperthermia on quality of life in the patients with unresectable chemoresistant liver metastasis from gastrointestinal tract cancer.

1.1 gastrointestinal tract cancer liver metastasis Most mortality of the gastrointestinal tract cancer patients is related with distant metastasis, especially liver is the main site. It has been estimated that 25% of colorectal cancer patients have hepatic metastases at diagnosis, and another 50% will have their tumor recurrence in the liver within 5 years.

Selected patients who had oligo (usually 2 to 3) or isolated liver metastases resected curatively and have yielded 5-year survival rates of 50% to 60%, showing that local therapy has the potential to cure. It is only possible in less than 25% of all patients with hepatic metastasis because of medical and/or surgical reasons, furthermore two-thirds of resected patients showed ultimately liver recurrence within 2 years.

The standard treatment of unresectable liver metastasis in gastrointestinal tract cancer is chemotherapy, but considerable portion of the patients progressed and most of the liver is converted to metastatic tumor lesions. Significant quality of life decrement was detected in those patients, especially in patients suffered severe symptoms

1.2 Radiation therapy (RT) for liver metastasis Several studies reported that whole liver RT (WLRT) can be used effectively to control severe symptoms from unresectable liver metastasis in colorectal cancer patients. However, it is well known fact that the liver is a very sensitive to RT. The radiation induced liver disease (RILD), dreadful complication without special treatment method and subset of patients could be dead, can be developed as low as 30 gray (Gy). Despite symptom palliation is obtained after 20 to 30 Gy RT but only in small subset of patients get local control. In this aspect, the combined with radiosensitizer with WLRT is considered to enhance RT effect to palliate symptom and control local tumor progression, and increase the quality of life ultimately.

1.3 Hyperthermia It is reported that hyperthermia is effective in S phase, Low oxygen partial pressure (pO2), low hydrogen ion concentration (pH), and low perfusion site which are known as radio-resistant. Because of these characteristics, it considered as the most valuable radiosensitizer in cancer treatment, theoretically. Furthermore, mild hyperthermia (41 to 41.5 ºC) can promote tumor reoxygenation.

1.4 Purpose of this study Based on those studies, we start this prospective study to investigate the effect of combination treatment of WLRT and hyperthermia on quality of life in the patients with unresectable chemoresistant liver metastasis from gastrointestinal tract cancer.

Effectiveness of the Combined WLI and Hyperthermia for GI Cancer Liver Metastasis

Effectiveness of the Combined Whole Liver Irradiation (WLI) and Hyperthermia for Unresectable Chemoresistant Multiple Liver Metastasis From Gastrointestinal Tract Cancer: Prospective Phase II Trial

Local progression will be defined as more than 20% size increase of metastatic lesions or new metastatic lesion in liver. Time to local tumor progression will be measured from the date of RT start to the date of local progression or last follow-up visit.

To measure the quality of life, European Organisation for Research and Treatment of Cancer (EORTC)- quality of life questionnaire (QLQ) 30 and Functional Assessment of Cancer Therapy-Hepatobiliary will be used. (grade 1 to 4, 1; not at all, 2; a little, 3; quite a bit, 4; very much)

Local progression will be defined as more than 20% size increase of metastatic lesions or new metastatic lesion in liver. Local progression free survival will be measured from the date of RT start to the date of local progression or last follow-up visit.

All grade III or higher toxicities (repeated measure)

Overall survival will be measured from the date of RT start to the date of death or last follow-up visit.

Samsung Medical Center

Combined Hypertermia and RT

Combination treatment with transarterial chemoembolization, radiotherapy, and hyperthermia

CERT

Age, Categorical

Age, Continuous

Sex: Female, Male

South Korea

Region of Enrollment

Child Pugh Class A

Child Pugh Class B

Child Pugh Class A; score 5 to 6 Child Pugh Class B; score 7 to 10 Child Pugh Class Cl score 11 to 18

Total range of score is 5 to 18 with higher scores/increased scores indicate greater severity of poor liver function.

Child Pugh Class

HCC patients who will receive combination treatment with transarterial chemoembolization, radiotherapy, and hyperthermia

Professor

Patients who underwent combined hyperthermia and radiation therapy

Time to Local Tumor Progression After Combined Hyperthermia and RT

Objective Response Rate of Combined Hyperthermia and RT

European Organisation for Research and Treatment of Cancer (EORTC)- quality of life questionnaire (QLQ) 30 and Functional Assessment of Cancer Therapy-Hepatobiliary will be used from grade 1 to 4.

Spots Global Cancer Trial Database for combined hyperthermia and radiation therapy