Hyperthermia and radiotherapy with or without chemotherapy in locally advanced cervical cancer: a systematic review with conventional and network meta-analyses.
Topic: Hyperthermia

A systematic review with conventional and network meta-analyses (NMA) was conducted to examine the outcomes of loco-regional hyperthermia (HT) with radiotherapy (RT) and/or chemotherapy (CT) in locally advanced cervix cancer, IIB-IVA (LACC).

PICO
Population: Patients with locally advanced cervix cancer, IIB-IVA (LACC)
Intervention: Loco-regional hyperthermia (HT) with radiotherapy (RT) and/or chemotherapy (CT)
Comparison: Radiotherapy (RT) and/or chemotherapy (CT) alone
Outcomes: Outcomes of treatment efficacy and safety in locally advanced cervix cancer

Included studies:
title: First results of triple-modality treatment combining radiotherapy, chemotherapy, and hyperthermia for the treatment of patients with stage IIB, III, and IVA cervical carcinoma.
abstract: Patients with advanced cervical carcinoma are treated routinely with radiotherapy and cisplatin-containing chemotherapy. It has been shown that hyperthermia can improve the results of both radiotherapy and cisplatin. In the current study, the feasibility and efficacy of the combination of all three modalities was studied in previously untreated patients with cervical carcinoma.
title: Effects of physical activity on risk factors for coronary heart disease in previously sedentary women: a five-year longitudinal study.
abstract: Fitness, weight, blood-pressure, and lipids were measured in 290 women joining a fitness programme. Five years later, 110 (38%) had remained active, and the others had become sedentary again. The net effect of being active was to increase fitness by 18% and to reduce weight by 1.9 kg, diastolic blood pressure by 3 mmHg, and triglycerides by 0.15 mmol/L-1. After controlling for age, weight and fitness, physical activity accounted for 1% and 3% of the variance of changes in systolic and diastolic blood pressure respectively, and was not associated with changes in lipids. Change in fitness accounted for only 1% of change in diastolic blood pressure. More 'active' women gave up smoking than 'inactive' (70% versus 10%). Hypertensive women were more sensitive to changes in weight and fitness than normotensive women. It was concluded that physical activity and change in fitness were only weakly related to changes in blood pressure and were unrelated to changes in lipids.
title: A randomized clinical trial of radiation therapy versus thermoradiotherapy in stage IIIB cervical carcinoma.
abstract: To clarify the role of thermoradiotherapy for FIGO Stage IIIB cervical carcinomas, both the clinical response and survival of patients treated with radio- or thermoradiotherapy were investigated. Forty patients with Stage IIIB uterine cervix carcinoma were treated with external beam irradiation to the pelvis, combined with iridium 192 high-dose-rate intracavitary brachytherapy. All patients were divided randomly into the following two groups: the radiotherapy (RT) group of 20 patients, who underwent radiotherapy alone; and the thermoradiotherapy (TRT) group of 20 patients, who underwent three sessions of hyperthermia in addition to radiotherapy. The primary endpoint of this study was local complete response and survival. A complete response was achieved in 50% (10 of 20) in the RT group versus 80% (16 of 20) in the TRT group (p = 0.048). The 3-year overall survival and disease-free survival of the patients who were treated with TRT (58.2 and 63.6%) were better than those of the patients treated with RT (48.1 and 45%), but these differences were not significant. The 3-year local relapse-free survival of the patients who were treated with TRT (79.7%) was significantly better than that of the patients treated with RT (48.5%) (p = 0.048). TRT, as delivered in this trial, was well tolerated and did not significantly add to either the relevant clinical acute or long-term toxicity over radiation alone. TRT resulted in a better treatment response and 3-year local relapse-free survival rate than RT for patients with FIGO Stage IIIB cervical carcinoma.
title: Side-effects of local hyperthermia: results of a prospectively randomized clinical study.
abstract: In 1986, 25 patients with stage II and III carcinoma of the cervix were treated by a combination of radiation and local hyperthermia using an endotract intravaginal applicator. Another 25 patients were treated with radiation alone. Both groups were followed up for a minimum period of 18 months. The acute and long-term toxicity of local hyperthermia was closely monitored. Our study shows that whereas local hyperthermia adds significantly to the local control achieved with radiation alone, it is not in any way associated with any significant short- or long-term toxicity, and does not enhance the radiation reactions.
title: Long-term improvement in treatment outcome after radiotherapy and hyperthermia in locoregionally advanced cervix cancer: an update of the Dutch Deep Hyperthermia Trial.
abstract: The local failure rate in patients with locoregionally advanced cervical cancer is 41-72% after radiotherapy (RT) alone, whereas local control is a prerequisite for cure. The Dutch Deep Hyperthermia Trial showed that combining RT with hyperthermia (HT) improved 3-year local control rates of 41-61%, as we reported earlier. In this study, we evaluate long-term results of the Dutch Deep Hyperthermia Trial after 12 years of follow-up.
title: Does pretreatment human papillomavirus (HPV) titers predict radiation response and survival outcomes in cancer cervix?--a pilot study.
abstract: To evaluate if pretreatment HPV titers in cancer cervix could predict radiation response and survival outcomes.
title: HDR brachytherapy combined with interstitial hyperthermia in locally advanced cervical cancer patients initially treated with concomitant radiochemotherapy: a phase I study.
abstract: The aim of this study was to investigate whether hyperthermia (HT) combined with interstitial brachytherapy (ISBT) has any influence on acute and late side effects in patients with advanced cervical cancer. Local control (LC) and disease-free survival (DFS) were also analysed.
title: Radiation therapy combined with hyperthermia versus cisplatin for locally advanced cervical cancer: Results of the randomized RADCHOC trial.
abstract: Chemoradiation (RT-CT) is standard treatment for locally advanced cervical cancer (LACC). This study tried to establish if radiotherapy combined with hyperthermia (RT-HT) should be preferred in bulky and/or FIGO-stage ⩾III.
title: Long-term survival data of triple modality treatment of stage IIB-III-IVA cervical cancer with the combination of radiotherapy, chemotherapy and hyperthermia - an update.
abstract: Advanced cervical cancer is routinely treated with radiotherapy and cisplatin-containing chemotherapy. Hyperthermia has been shown to improve the results of both radiotherapy and cisplatin. The feasibility of the combination of all three modalities was demonstrated and reported in a study of 68 previously untreated cervical cancer patients in 2005. Long-term follow-up is presented here.
title: Regional hyperthermia combined with radiotherapy for uterine cervical cancers: a multi-institutional prospective randomized trial of the international atomic energy agency.
abstract: Hyperthermia can be used to enhance the effects of radiation, and a combined treatment may, in some circumstances, be an advantage. Uterine cervical cancer is very common in developing countries. The control of locally advanced pelvic tumors is difficult with conventional treatment modalities. Based upon the biologic rationale and in view of the recent advances in heating and thermometry techniques, radiotherapy in combination with hyperthermia was investigated in a multi-institutional prospective randomized trial sponsored by the International Atomic Energy Agency. The primary purpose was to clarify whether the combination of hyperthermia and radiotherapy improves the rate of local control, compared with radiotherapy alone.
title: The Cervix Cancer Research Network: A Global Outreach Effort on Behalf of the Gynecologic Cancer InterGroup.
title: HDR brachytherapy combined with interstitial hyperthermia in locally advanced cervical cancer patients initially treated with concomitant radiochemotherapy--a phase III study.
abstract: The aim of this randomised trial was to investigate whether hyperthermia (HT) combined with interstitial brachytherapy (ISBT) has any influence on local control (LC), disease-free survival (DFS), or acute and late side effects in patients with advanced cervical cancer.
title: Hyperthermia adds to chemotherapy.
abstract: The hallmarks of hyperthermia and its pleotropic effects are in favour of its combined use with chemotherapy. Preclinical research reveals that for heat killing and synergistic effects the thermal dose is most critical. Thermal enhancement of drug cytotoxicity is accompanied by cellular death and necrosis without increasing its oncogenic potential. The induction of genetically defined stress responses can deliver danger signals to activate the host's immune system. The positive results of randomised trials have definitely established hyperthermia in combination with chemotherapy as a novel clinical modality for the treatment of cancer. Hyperthermia targets the action of chemotherapy within the heated tumour region without affecting systemic toxicity. In specific clinical settings regional hyperthermia (RHT) or hyperthermic perfusion has proved its value and deserve a greater focus and investigation in other malignancies. In Europe, more specialised centres should be created and maintained as network of excellence for hyperthermia in the field of oncology.
title: Radiotherapy and hyperthermia for treatment of primary locally advanced cervix cancer: results in 378 patients.
abstract: To report response rate, pelvic tumor control, survival, and late toxicity after treatment with combined radiotherapy and hyperthermia (RHT) for patients with locally advanced cervical carcinoma (LACC) and compare the results with other published series.