Combined use of hyperthermia and radiation therapy for treating locally advanced cervical carcinoma.
BACKGROUND
Hyperthermia is a type of cancer treatment in which body tissue is exposed to high temperatures to damage and kill cancer cells. It was introduced into clinical oncology practice several decades ago. Positive clinical results, mostly obtained in single institutions, resulted in clinical implementation albeit in a limited number of cancer centres worldwide. Because large scale randomised clinical trials (RCTs) are lacking, firm conclusions cannot be drawn regarding its definitive role as an adjunct to radiotherapy in the treatment of locally advanced cervical carcinoma (LACC).


OBJECTIVE
To assess whether adding hyperthermia to standard radiotherapy for LACC has an impact on (1) local tumour control, (2) survival and (3) treatment related morbidity.


METHODS
The electronic databases of the Cochrane Central Register of Controlled Trials (CENTRAL), (Issue 1, 2009) and Cochrane Gynaecological Cancer Groups Specialised Register, MEDLINE, EMBASE, online databases for trial registration, handsearching of journals and conference abstracts, reviews, reference lists, and contacts with experts were used to identify potentially eligible trials, published and unpublished until January 2009.


METHODS
RCTs comparing radiotherapy alone (RT) versus combined hyperthermia and radiotherapy (RHT) in patients with LACC.


METHODS
Between 1987 and 2009 the results of six RCTs were published, these were used for the current analysis.


RESULTS
74% of patients had FIGO stage IIIB LACC. Treatment outcome was significantly better for patients receiving the combined treatment (Figures 1 to 3). The pooled data analysis yielded a significantly higher complete response rate (relative risk (RR) 0.56; 95% confidence interval (CI) 0.39 to 0.79; p < 0.001), a significantly reduced local recurrence rate at 3 years (hazard ratio (HR) 0.48; 95% CI 0.37 to 0.63; p < 0.001) and a significanly better overall survival (OS) at three years following the combined treatment with RHT(HR 0.67; 95% CI 0.45 to 0.99; p = 0.05). No significant difference was observed in treatment related acute (RR 0.99; 95% CI 0.30 to 3.31; p = 0.99) or late grade 3 to 4 toxicity (RR 1.01; CI 95% 0.44 to 2.30; p = 0.96) between both treatments.


CONCLUSIONS
The limited number of patients available for analysis, methodological flaws and a significant over-representation of patients with FIGO stage IIIB prohibit drawing definite conclusions regarding the impact of adding hyperthermia to standard radiotherapy. However, available data do suggest that the addition of hyperthermia improves local tumour control and overall survival in patients with locally advanced cervical carcinoma without affecting treatment related grade 3 to 4 acute or late toxicity.
Lutgens
Ludy
L
Radiation Oncology, Maastro Clinic, Dr. Tanslaan 12, 6229 ET Maastricht, Postbus 5800, Maastricht, Netherlands, 6202 AZ.
van der Zee
Jacoba
J
Pijls-Johannesma
Madelon
M
De Haas-Kock
Danielle Fm
DF
Buijsen
Jeroen
J
Mastrigt
Ghislaine Apg van
GA
Lammering
Guido
G
De Ruysscher
Dirk K M
DK
Lambin
Philippe
P
D003131:Combined Modality Therapy / Q000379:methods; D005260:Female; D006801:Humans; D006979:Hyperthermia, Induced / Q000379:methods*; D016032:Randomized Controlled Trials as Topic; D002583:Uterine Cervical Neoplasms / Q000473:pathology / Q000532:radiotherapy / Q000628:therapy*