Comparison of Radiotherapy Alone With Radiotherapy First Results of Triple-Modality Treatment

Comparison of Radiotherapy Alone With Radiotherapy
Plus Hyperthermia in Locally Advanced Pelvic Tumors:
A Prospective, Randomized, Multicentre Trial
Jacoba van der Zee, Dionisio González, Gerard van Rhoon, Jan van Dijk, Wim van
Putten and Augustinus Hart, for the Dutch Deep Hyperthermia Group
BACKGROUND: Local-control rates after radiotherapy for locally advanced
tumours of the bladder, cervix, and rectum are disappointing. We investigated
the effect of adding hyperthermia to standard radiotherapy.
METHODS: The study was a prospective, randomised, multicentre trial. 358
patients were enrolled from 1990 to 1996, in cancer centres in the Netherlands,
who had bladder cancer stages T2, T3, or T4, N0, M0, cervical cancer stages IIB,
IIIB, or IV, or rectal cancer stage M0–1 were assessed. Patients were randomly
assigned radiotherapy (median total dose 65 Gy) alone (n=176) or radiotherapy
plus hyperthermia (n=182). Our primary endpoints were complete response and
duration of local control. We did the analysis by intention to treat.
FINDINGS: Complete-response rates were 39% after radiotherapy and 55% after
radiotherapy plus hyperthermia. The duration of local control was significantly
longer with radiotherapy plus hyperthermia than with radiotherapy alone.
Treatment effect did not differ significantly by tumour site, but the addition of
hyperthermia seemed to be most important for cervical cancer, for which the
complete-response rate with radiotherapy plus hyperthermia was 83% compared
with 57% after radiotherapy alone. 3-year overall survival was 27% in the radiotherapy group and 51% in the radiotherapy plus hyperthermia group. For bladder
cancer, an initial difference in local control
disappeared during follow-up.
INTERPRETATION: Hyperthermia in addition
to standard radiotherapy may be especially
useful in locally advanced cervical tumors.
Studies of larger numbers of patients are
needed for other pelvic tumor sites before
practical recommendations can be made.
Live your life.
First Results of Triple-Modality Treatment
Combining Radiotherapy, Chemotherapy, and
Hyperthermia for the Treatment of Patients with
Stage IIB, III, and IVA Cervical Carcinoma
Anneke M. Westermann, M.D., Ph.D., Ellen L. Jones, M.D., Baard-Christian Schem, M.D.,
Elzbieta M. van der Steen-Banasik, M.D., Peter Koper, M.D., Olav Mella, M.D., Apollonia L. J.
Uitterhoeve, M.D., Ronald de Wit, M.D., Ph.D., Jacobus van der Velden, M.D., Ph.D., Curt
Burger, M.D., Ph.D., Clasina L. van der Wilt, M.Sc., Olav Dahl, M.D., Ph.D., Leonard R. Prosnitz,
M.D., Jacoba van der Zee, M.D., Ph.D.
BACKGROUND: 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.
METHODS: Patients with advanced cervical carcinoma were registered prospectively in the U.S., Norway, and the Netherlands. External-beam radiotherapy and
brachytherapy were administered for a biologically effective dose 86.7 gray. At
least 4 courses of weekly cisplatin (40 mg/m2) and 4 sessions of weekly locoregional hyperthermia were added to radiotherapy.
RESULTS: Sixty-eight patients with a median age of 45
years were enrolled. Fulldose
radiotherapy was delivered
“Complete remission was achieved
to all patients according to
by 61 patients (90%). After a median
follow-up of 538 days, 74% of
plan. At least 4 courses of
patients remained alive without
signs of recurrence, and the overall
chemotherapy were received
survival rate was 84%.”
Complete Remission Rate 90%
by 97% of patients, and at
least 4 courses of hyperthermia treatment were received by 93% of patients. Toxicity was fully comparable to
that described for chemoradiotherapy alone, and the median total treatment
time was 45 days. Complete remission was achieved by 61 patients (90%). After
a median follow-up of 538 days, 74% of patients remained alive without signs of
recurrence, and the overall survival rate was 84%.
68 Patients, Stages IIB, IIIA, IVA Cervical Cancer
CANCER, August 15, 2005/Volume 104/ Number 4
CONCLUSIONS: The combination of full-dose radiotherapy, chemotherapy, and
hyperthermia was feasible and effective in a multicenter international setting
among patients with advanced cervical carcinoma. A Phase III study comparing
this novel triplet with standard chemoradiation, designed to show at least a 15%
improvement in overall survival, has been launched. Cancer 2005;104:763–70.
© 2005 American Cancer Society.
MRI Thermometry
Intensity Modulated Conformal Thermal Therapy
The BSD 2000 3D MR Hyperthermia System
Not For Sale In The U.S.
Noninvasive Magnetic Resonance Thermography of Recurrent Rectal Carcinoma in a 1.5 Tesla Hybrid System
Johanna Gellermann, Waldemar Wlodarczyk, Bert Hildebrandt, Hildegard Ganter, Anett Nicolau, Beate Rau, Wolfgang Tilly, Horst Fahling, Jacek Nadobny,
Roland Felix, and Peter Wust Clinic for Radiation Medicine, Clinic for Medicine, Hematology, and Medical Onkology, and Clinic for Surgery and Surgical
Oncology, Charite´ Medical School, Berlin, Germany
To implement noninvasive thermometry, we installed a hybrid system consisting of a radiofrequency multiantenna applicator (SIGMA-Eye) for deep hyperthermia (BSD-2000/3D) integrated into the gantry of a 1.5 Tesla magnetic resonance (MR) tomograph Symphony. This system can record MR data during radiofrequency heating and is suitable for application and evaluation of methods for MR thermography. In 15 patients with preirradiated pelvic rectal recurrences, we
acquired phase data sets (25 slices) every 10 to 15 minutes over the treatment time (60-90 minutes) using gradient echo sequences (echo time = 20 ms),
transformed the phase differences to MR temperatures, and fused the color-coded MR-temperature distributions with anatomic T1-weighted MR data sets.
We could generate one complete series of MR data sets per patient with satisfactory quality
for further analysis. In fat, muscle, water bolus, prostate, bladder, and tumor, we delineated
regions of interest (ROI), used the fat ROI for drift correction by transforming these regions
to a phase shift zero, and evaluated the MR-temperature frequency distributions. Mean MR
temperatures (TMR), maximum TMR, full width half maximum (FWHM), and other descriptors
of tumors and normal tissues were noninvasively derived and their dependencies outlined.
In 8 of 15 patients, direct temperature measurements in reference points were available. We
correlated the tumor MR temperatures with direct measurements, clinical response, and
tumor features (volume and location), and found reasonable trends and correlations.
Therefore, the mean TMR of the tumor might be useful as a variable to evaluate the quality
and effectivity of heat treatments, and consequently as optimization variable.Feasibility of
noninvasive MR thermography for regional hyperthermia has been shown and should be further investigated. (Cancer Res 2005; 65(13): 1-9)
Live your life.
2188 West 2200 South
Salt Lake City, Utah 84119
Tel 801 972 5555
Fax 801 972 5930
Email [email protected]
Schatzbogen 86
D-81829 Munich
+49 89 542143-0
Email [email protected]