Elsevier

The Lancet Oncology

Volume 3, Issue 8, August 2002, Pages 487-497
The Lancet Oncology

Review
Hyperthermia in combined treatment of cancer

https://doi.org/10.1016/S1470-2045(02)00818-5Get rights and content

Summary

Hyperthermia, the procedure of raising the temperature of tumour-loaded tissue to 40–43°C, is applied as an adjunctive therapy with various established cancer treatments such as radiotherapy and chemotherapy. The potential to control power distributions in vivo has been significantly improved lately by the development of planning systems and other modelling tools. This increased understanding has led to the design of multiantenna applicators (including their transforming networks) and implementation of systems for monitoring of E-fields (eg, electro-optical sensors) and temperature (particularly, online magnetic resonance tomography). Several phase III trials comparing radiotherapy alone or with hyperthermia have shown a beneficial effect of hyperthermia (with existing standard equipment) in terms of local control (eg, recurrent breast cancer and malignant melanoma) and survival (eg, head and neck lymph-node metastases, glioblastoma, cervical carcinoma). Therefore, further development of existing technology and elucidation of molecular mechanisms are justified. In recent molecular and biological investigations there have been novel applications such as gene therapy or immunotherapy (vaccination) with temperature acting as an enhancer, to trigger or to switch mechanisms on and off. However, for every particular temperature-dependent interaction exploited for clinical purposes, sophisticated control of temperature, spatially as well as temporally, in deep body regions will further improve the potential.

Section snippets

Methods to increase temperatures

To reach temperatures clearly above the systemic temperature of 37·5°C in a defined target volume is a technical challenge and still under development. The temperature increase is induced by applying a power-density specific absorption rate (SAR; measured in W/kg). Human basal metabolic rate (basal metabolism) is above 1 W/kg. Perfusion counteracts the temperature rise. Perfusion rates in human tumours are around 5–15 mL per 100 g per min, but they vary widely. To reach therapeutic temperatures

Clinical trials on hyperthermia

By searches of the Medline database, we identified 18 comparative, prospective phase III trials on different hyperthermia modalities up to March 2001 (table 1). In ten of these trials, external radiotherapy alone was compared with radiotherapy plus hyperthermia14, 38, 39, 40, 41, 42, 43, 44 or interstitial radiotherapy alone was compared with interstitial radiotherapy plus interstitial hyperthermia.45, 46 Only two studies on locoregional hyperthermia included chemotherapy.47, 48 In three trials

Conclusions

Recent clinical results give new insight into the mechanisms of hyperthermia in multimodal oncological treatments. Hyperthermia is thought to affect tumour sensitivity to other treatments mainly through microenvironmental factors such as pH. One hypothesis is that hypoxic and therefore resistant tumour regions are preferentially eliminated under hyperthermic conditions because associated hypovascularisation results in higher temperatures and higher sensitivity due to hypoxia. This assumption

Search strategy and selection criteria

All the completed randomised studies in this review were identified by searches of Medline. Additional continuing randomised trial are known from recent international conferences of the hyperthermia organisations (in particular the European Society of Hyperthermic Oncology). The phase II studies referenced are a collection personally weighted and known from the German Hyperthermia Organisation, where all German trials are listed, and further from international conferences of the European

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