Deep Hyperthermia Research Articles

Deep electro-hyperthermia (EHY) with or without thermo-active agents in patients with advanced hepatic cell carcinoma: Phase II study

15168 Background: Advanced HCC has no standard chemotherapy , all pts would be valuabled in clinical trials. We evaluated effectiveness and toxicity of capacitatively coupled low-frequency 13.56 MHz deep hyperthermia (Oncotherm-EHY 2000) treatment on chemo- refractory malignant primary liver cancer which underwent all other possible treatment. Methods: From February 2005 to July 2006, we enrolled 22 pts with advanced HCC. ECOG PS was 1 or O. Viral hepatic infection status was 7 HBV+, 8 HCV+, 1 HCV/HBV+. Median age was 67,5 y (range 63 -78), male/female 20/2 . 15 pts were uneligible for liver surgery, 3 pts received TACE, 1 PEI, 1 a lot of therapy. 7 pts were pre-treated with surgery, 2 also received TACE, 1 PEI and 1 a lot of therapy. 75% of pts were in stage C of BCLC classification. 2 pts had also distant metastases, 70% of pts had portal vein thromboses. 8 pts underwent only to EHY without CT. Schedule : EHY was achieved by arrangements of capacitative electrodes with a radiofrequency field of 13.56 Mhz (RF-DHT) at 80- 130 W equivalent to 41 °- 47° C for 60 minutes, 2 times/w for 5 weeks in combination with thermo-active agents . EHY was applied over 2 time a week over 1 hour as mono - combined therapy . Concomitant chemotherapy was oxaliplatin 50 mgr at fixed dose on D 1and D 15 . One cycle is 10 treatments of EHY ; 4 pts underwent 2 cycles and 2 pts to 3 cycles and 1 pt to 4 cycles . Median number of cycles was 1,5 (range 1–4), total EHY applications were 365. Results: EHY plus thermo-active drug is beneficial on clinical conditions off treated pts with an excellent compliance on out- patients. We observed 1 CR ( pt has only one bone metastases after 6 months without liver relapse), no PR, 25% of SD. Median survival time was 20’5 weeks (5 - 81+) We noted that 11 pts (50%) presented evidence of increasing well-being. Toxicity : 4 pts had skin reaction after application of EHY. In 3 pts we observed cutaneous hyperemia on the area of treatment and mild burn on the skin ; all symptoms disappeared after local steroid therapy , treatment was interrupted until resolution . Conclusions: Low toxicity and clinical benefit will be confirmed in further clinical studies. Capacitively coupled low-frequency 13.56 deep-hyperthermia is feasible for chemo-refractory HCC. No significant financial relationships to disclose.

Numerical model for RF capacitive regional deep hyperthermia in pelvic tumors

A numerical model based on Finite Element Method (FEM) for the prediction of power density distribution and temperature during RF-capacitive hyperthermia treatment has been presented in the paper and the results are discussed. In particular the models are related to the treatment of pelvic tumors where it is more difficult to localize and focus heat in deep regions. The geometrical and physical model of the patient is reconstructed with a segmentation procedure by means of dedicated software. The geometrical meshed model has been used as input for the solution of coupled electromagnetic and thermal problems. A deep analysis of different configurations derived from specific scientific literature of the last years has been presented in the paper and discussed. The results obtained by FEM analyses have demonstrated the suitability of this method for the prediction of power and temperature distribution during RF capacitive hyperthermia and that the calculation procedure is an efficient mean to evaluate the efficacy of the heating system.

RF-power and temperature data analysis of 444 patients with primary cervical cancer: Deep hyperthermia using the Sigma-60 applicator is reproducible

Treatment reproducibility is important to guarantee reproducible treatment-outcome, a low-complication rate and efficient treatment procedures. This study evaluated the performance of loco-regional deep hyperthermia with four BSD-2000 configurations during 1990–2005 using the direct available parameters, i.e., temperature and power. Primary cervical cancer patients (n = 444) were all treated within the Sigma-60. Patients were grouped in three weight-groups: <61 kg, 61–70 kg, >70 kg. Different temperature and power indices were extensively analyzed per BSD configuration, per weight-group, and over the time-period. No substantial variations were found for temperature/power indices over the four BSD configurations or for the temperature doses in similar weight-groups. The ‘bare’ power indices were increased with weight; however, the derivative power-related (W/kg, W/cm2) and temperature indices decreased. Large variations were found in the power-related parameters during 1991–1996 (1st time-period), whereas they were much smaller during 1997–2005 (2nd time-period). The most relevant change noted was the adaptation of the treatment strategy with respect to power modulation. The average frequency of switched-off was 3.4 and 8.9 times/treatment session for the 1st and 2nd time-period, respectively, while the average duration of each switched-off time was 78.2 vs. 38.3 s. The yearly average of vagina T50 was in the range of 39.3–40.2°C (1st time-period) and 40.0–40.5°C (2nd time-period). In 40% of the patients, a positive correlation was found between normalized net integrated power per pelvic area and vagina T50. Good reproducible heating is achieved with the BSD-2000 Sigma-60 irrespective of the regular technological upgrades of the system and variation of trained staff-members.

Ovarian small cell carcinoma of the hypercalcemic type in children and adolescents

Ovarian small cell carcinoma of the hypercalcemic type is a rare neoplasm that is associated with a poor prognosis. The objective of the current study was to investigate the clinicopathologic features of this tumor and to develop preliminary diagnostic and therapeutic guidelines. Between 1994 and 2005, 11 girls (ages 9-22 years) who were registered on the German Maligne Keimzelltumoren studies and the Kiel Pediatric Tumor Registry were analyzed. Prior to histopathologic review, 8 patients had been misdiagnosed with either germ cell tumor or juvenile granulosa cell tumor. According to the International Federation of Gynecologic Oncology, 4 patients had Stage IA disease, 3 patients had Stage IC disease, and 4 patients had Stage III disease. After resection, 4 patients were followed without additional therapy, and all 4 patients developed recurrent disease after 3 to 11 months. Seven patients received adjuvant chemotherapy during first-line treatment. One patient with Stage III disease received additional regional deep hyperthermia. During first-line treatment, high-dose chemotherapy was received by 4 patients who achieved a complete response (CR) after conventional chemotherapy. All 4 of those patients remained in CR for 7 to 73 months, whereas the other 3 patients developed recurrent disease. Salvage treatment after recurrence or tumor progression consisted of surgery and chemotherapy. One patient received high-dose chemotherapy in 2nd CR and remained in 2nd CR. In total, 5 patients remained alive with no evidence of disease. Patients with ovarian small cell carcinoma of the hypercalcemic type require multiagent chemotherapy during first-line treatment. High-dose chemotherapy may be used to consolidate the therapeutic success.

Temperature data analysis for 22 patients with advanced cervical carcinoma treated in Rotterdam using radiotherapy, hyperthermia and chemotherapy: A reference point is needed

Introduction: The growing interest and participation in multi-institutional trials involving deep hyperthermia treatment is an important step towards the further consolidation of hyperthermia as an oncological treatment modality. However, the differences in the clinical procedures of hyperthermia application also raises questions as how to compare the reported temperatures data obtained by the different institutes. In this study our recent developed approach, RHyThM (Rotterdam Hyperthermia Thermal Modulator), has been used for thermal data analysis to investigate the temperature dynamics behaviour of a series of deep hyperthermia treatments.Patients and methods: All 22 patients (104 hyperthermia treatments) with locally advanced cervical carcinoma who participated in a feasibility study for treatment with a three-modality therapy were selected. The patients received mega-voltage external beam radiotherapy to the pelvis in daily fractions of 2 Gy five times a week to a total dose of 46 Gy and additional brachytherapy, at least four courses of weekly cisplatin (40 mg m−2) and five sessions of weekly loco regional deep hyperthermia treatments with the BSD2000-3D with the Sigma 60 or the Sigma-eye applicators at frequencies 70–120 MHz. Using RHyThM tissue type was defined along the insertion length, based on the CT scan information in radiotherapy position, for each single treatment. A step change in the slope of the profile of the first temperature map was identified to verify the insertion length of the thermometry catheter and precise location of the transition between in- and outside the body. Data analysis was performed based on the temperature readout provided by RHyThM.Results: The temperature and RF-power data of 97 treatments could be analysed. The intra-vaginal temperature indices were slightly lower than those for bladder and rectum. The average T50 (median temperature) in all lumens, i.e. bladder, vagina and rectum, was 40.4 ± 0.6°C. The average vagina all lumen T50 was 40.0 ± 0.8°C. The average bladder and rectum all lumen T50 was 40.6 ± 0.7°C and 40.5 ± 0.6, respectively. When the analysis was restricted to the deepest 5 cm of the vagina lumen, the average T50 was 39.8 ± 0.9°C. Good correlation exists between the various temperature indices like T20, T50 and T90, for all lumen measurements in bladder, vagina and rectum. No correlation was found between temperature indices and treatment number. For the complete patient population, no relationship was found between T50 and net integrated RF-power applied. In an explorative analysis on individual patients a positive correlation coefficient or trend was found in 14 patients between normalized net integrated RF-power and vagina T50.Conclusion: Average all lumen T50 for bladder, vagina and rectum differ less than 1°C, indicating that a large volume was heated relatively homogeneously. The vagina T50 value depends on how many measurement points are included for the analysis. In this group of patients the vagina T50 of the first treatment is not a good measure to discriminate between patients with ‘heatable’ and ‘non-heatable’ tumours. In order to compare temperature data reported by different institutes dealing with the same group of patients, one needs a strict and clear agreement on which temperature measurements or reference point(s) that should be included in the analysis.

Intra-luminal thermometry: Is tissue type assignment a necessity for thermal analysis?

Introduction: Tissue type assignment, i.e. differentiation tumour from normal tissue, is a normal procedure for interstitial thermometry. In our department, thermometry in patients with a tumour in the lower pelvis is usually restricted to the intra-luminal tracks. It is unknown whether discrimination between normal and tumour tissue is relevant for deep regional hyperthermia thermal dosimetry using only intra-luminal tumour contact and tumour adjacent thermometry. This study has analysed the acquired temperature data in order to answer this question.Patients and methods: Seventy-five patients with locally advanced cervical carcinoma were selected randomly. Patients were treated with a two or three modality combination, i.e. radiotherapy +hyperthermia or radiotherapy + hyperthermia + chemotherapy from October 1997 to September 2003. The first 100 hyperthermia treatments fulfilling the only selection criterion: no displacement of the thermometry catheter along the insertion length during the treatment, were included in the study, resulting in 43 patients with one-to-five treatments/patient (median 2). Using RHyThM (Rotterdam Hyperthermia Thermal Modulator), for each single treatment tissue type, was defined on the basis of information given by a CT scan in radiotherapy position. A step change in the slope of the profile of the first temperature map was identified to verify the insertion length of the catheter.Results: The average T50 (median temperature) in bladder tumour indicative, vagina tumour contact and rectum tumour indicative was 40.9 ± 0.9°C, 39.7 ± 0.9°C and 40.6 ± 0.8°C, respectively. The average normal tissue T50 in bladder, vagina and rectum was 40.8 ± 0.9°C, 40.1 ± 0.9°C and 40.7 ± 0.8°C, respectively. The differences between bladder tumour indicative T50 and bladder normal tissue T50 and also between vagina tumour contact T50 and vagina normal tissue T50 were significant ( p = 0.0001). No statistical difference was found between rectum tumour indicative T50 and rectum normal tissue T50.Conclusion: At present the cause of the temperature difference is not known. However, as the difference between tumour (indicative/contact) and normal tissue is very small and considering also the inaccuracy in the tissue type assignment it can be stated that this study does not provide sufficient evidence to conclude that the statistical difference has clinical relevance. Therefore, it was concluded that at this time there is no need to differentiate between normal and tumour tissue in intra-luminal thermometry.

Avascular osteonecrosis after hyperthermia in children and adolescents with pelvic malignancies: A retrospective analysis of potential risk factors

Purpose: In children with locally advanced or recurrent malignant tumours, prognosis can be improved by regional deep hyperthermia (RHT) in combination with platin-based chemotherapy. However, because of the increasing number of patients that achieve long-time remission with this therapy, it is necessary to evaluate long-term sequelae of thermochemotherapy. During the years 1993–2004 one has observed avascular osteonecrosis (AON) of the femoral head after RHT in seven children with pelvic germ cell tumours or rhabdomyosarcomas.Methods: Although AON may develop in patients with malignancies treated with chemo- or radiotherapy alone, RHT might nevertheless contribute to the occurrence of AON. In order to determine potential risk factors for AON after RHT, this study analysed the relationship of AON to the patient's age, medical history and treatment parameters such as thermal dose equivalent and power output.Results and conclusions: In the present study AON was associated with young age as well as intensity of hyperthermia indicated by high power levels that exceed 20 W per kg body weight and/or application of eight or more heat sessions as well as additional radiotherapy. Based on this observation, it was assumed that an optimized three dimensional thermal field modelling may be helpful to avoid hazardous temperatures in the femoral heads during RHT treatment and to reduce AON of the femoral heads.

Cervical cancer: Radiotherapy and hyperthermia

Background: For many years, the standard treatment of advanced cervical cancer has been radiotherapy (RT), including brachytherapy. The achievement of locoregional tumour control is essential for cure. Results of RT in early stages are reasonably satisfactory, but locoregional failure rates for stage IIIb and IVa are high. In several randomized trials, the addition of hyperthermia (HT) to RT has been investigated.Randomized trials: The Dutch Deep Hyperthermia Trial was completed in 1996. In this trial a beneficial effect of additional hyperthermia was clearly demonstrated. Three-year locoregional control and overall survival rates were significantly higher in the RT + HT group than in the RT alone group, while radiation toxicity was not affected. Cost-per-life-year-gained was less than 4000 Euros. The results of this trial have led to the acceptance of RT plus HT as standard treatment for advanced cervical cancer in the Netherlands. Five trials conducted in Asia have been published, of which three showed significant better complete response, locoregional tumour control and/or disease-free survival rates. One trial showed a trend of better locoregional tumour control and one did not show any benefit.Conclusion: Hyperthermia added to standard radiotherapy of locally advanced cervical tumours results in considerable therapeutic gain and is cost-effective. For a beneficial effect, the use of an adequate heating technique is an important requirement.

Noninvasive Magnetic Resonance Thermography of Recurrent Rectal Carcinoma in a 1.5 Tesla Hybrid System

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 (T(MR)), maximum T(MR), 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 T(MR) 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.

Leg coverage with towels during regional deep hyperthermia treatment and its effect on pelvic temperature and temperature distribution

Introduction: The feasibility and its effects on pelvic temperature distribution of covering the legs with towels during the second half of the deep hyperthermia treatment (DHT) is evaluated.Patients and methods: Patients treated with DHT and radiotherapy were randomized to an alternating treatment schedule: 2nd and 4th treatment or 3rd and 5th treatment with the legs covered with towels in the second half of the treatment. Intra-luminal temperatures (vesical, vaginal and rectal) classified as tumour indicative (TI) or tumour contact (TC), oral temperature, applied maximum power and power at the end of the treatment were measured and compared between the two treatment schedules.Results: Fourteen female patients receiving a total of 51 treatments, 24 with and 27 without towels, were included for analysis. The mean intra-luminal, TI and TC temperatures, standard deviation and range for each site were calculated. The applied power was documented. There were no significant differences in any of the measured temperatures. There were no significant differences in the applied power. In only three treatments, the towels were removed preliminarily.Conclusion: In the authors’ experience, covering the legs with towels during the second half of DHT does not result in significantly higher or more homogeneous pelvic temperatures. There is no indication that the TC and TI temperatures are higher compared to all pelvic temperatures when towels are applied. Regarding the used power, there is no significant decrease with towels placed on the legs. Coverage of the legs does not increase the systemic temperature. Isolating the legs with a water-perfused heater is considered.

Waterbath versus ultrasound hyperthermia in vivo: Implications for clinical hyperthermia

Ultrasound is utilized clinically for both superficial and deep hyperthermia. In contrast, in vivo experimentation has primarily utilized waterbath limb immersion. We determined the response of xenotransplants to waterbath immersion versus focal ultrasound hyperthermia using immunhistochemistry, histopathology, and tumor growth delay assays. We also assessed thermal dosimetry of ultrasound hyperthemia and compared the local, regional, and systemic temperature changes.

Trombo pedunculado ao nível da transição entre a aorta ascendente e o arco aórtico

A 52-year-old male alcoholic patient with hypertension and a prior history of brain ischemia was admitted to the neurosurgery department with signs and symptoms of ischemic stroke. A transesophageal echocardiogram and computed tomography suggested a possible pedunculated thrombus at the transition of the ascending aorta to the aortic arch. The therapeutic option was surgical treatment using cardiopulmonary bypass, deep hyperthermia and total cardiac arrest. The procedure involved resection of the aortic wall together with the thrombus to avoid recurrence. There were no adverse consequences and the patient was released from hospital with the use of oral anticoagulant drugs.

Characterization of the SAR-distribution of the Sigma-60 applicator for regional hyperthermia using a Schottky diode sheet

Introduction: Characterization of the performance of an hyperthermia applicator by phantom experiments is an essential aspect of quality assurance in hyperthermia. The objective of this study was to quantitatively characterize the energy distribution of the Sigma-60 applicator of the BSD2000 phased array system operated within the normal frequency range of 70–120 MHz. Additionally, the accuracy of the flexible Schottky diode sheet to measure E-field distributions was assessed.Material and methods: The flexible Schottky diode sheet (SDS) consists of 64 diodes mounted on a flexible 125 µm thick polyester foil. The diodes are connected through high resistive wires to the electronic readout system. With the SDS E-field distributions were measured with a resolution of 2.5 × 2.5 cm in a cylindrical phantom, diameter of 26 cm and filled with saline water (2 g/l). The phantom was positioned symmetrically in the Sigma-60 applicator. RF-power was applied to the 4-channel applicator with increasing steps from 25 W to a total output of 400 W.Results: The complete system to measure the E-field distribution worked fine and reliably within the Sigma-60 applicator. The E-field distributions measured showed that the longitudinal length of the E-field distribution is more or less constant, e.g. 21–19 cm, over the frequency range of 70–120 MHz, respectively. As expected, the radial E-field distributions show a better focusing towards the centre of the phantom for higher frequencies, e.g. from 15.3–8.7 cm diameter for 70–120 MHz, respectively. The focusing target could be moved accurately from the left to the right side of the phantom. Further it was found that the sensitivity variation of nine diodes located at the centre of the phantom was very small, e.g. <3% over the whole frequency range.Conclusion: The SAR distributions of the Sigma-60 applicator are in good agreement with theoretically expected values. The flexible Schottky diode sheet proves to be an excellent tool to make accurate, quantitative measurements of E-field distributions at low (25 W) and medium (400 W) power levels. An important feature of the SDS is that it enables one to significantly improve quantitative quality assurance procedures and to start quantitative comparisons of the performance of the different deep hyperthermia systems used by the various hyperthermia groups.

Efficacy of irradiation and external hyperthermia in locally advanced, hormone-refractory or radiation recurrent prostate cancer: A preliminary report

Purpose To present a preliminary report on the feasibility, efficacy, and toxicity of irradiation (RT) and hyperthermia (HT) in patients with locally advanced, hormone-refractory prostate cancer (LAHRPC) who may or may not have received prior RT. Methods and materials Between 1997 and 2002, 13 consecutive patients with LAHRPC or RT-recurrent prostate cancer were treated with RT and HT on a Phase I–II protocol. Eight patients had RT-recurrent LAHRPC (Group A) and 5 had LAHRPC without prior RT (Group B). All patients had large and clinically symptomatic tumors. The median RT dose was 39.6 Gy and 66.6 Gy in Groups A and B, respectively. External deep HT was delivered using a BSD-2000 Sigma-60 applicator. The median number of HT treatments was 8 in group A and 10 in group B. Results The median follow-up was 14 and 13 months for Groups A and B, respectively. All patients achieved a complete or partial response (CR/PR) and complete palliation of symptoms. Eleven patients had follow-up CT scans that demonstrated a CR in six and a PR in five. Two patients, who died of metastasis, did not have CT scans and had a PR on digital rectal examination. Two patients demonstrated a biochemical CR. The median duration of the CR/PR among Group A patients was 12 months after therapy. Three patients in Group A developed tumor recurrence at 9, 17, and 27 months after repeat RT to doses of 39.6, 36, and 50 Gy, respectively. At last follow-up, no Group B patient developed local recurrence. Grade 1-2 rectal bleeding was noted in 3 patients. RT and HT were generally well tolerated by all patients who had not previously undergone RT. Of the 8 patients who had, 6 (75%) tolerated retreatment well with minimal or no complications. Two patients in the repeat RT group had severe complications. One patient with lymphoma and factor XI deficiency developed Grade 4 hemorrhagic cystitis. Another previously irradiated patient developed a rectovesical fistula 4 months after retreatment, after disappearance of a large, invasive, and necrotic tumor. Conclusion This preliminary report demonstrates the feasibility and efficacy of RT and HT in patients with LAHRPC, who may or may not have received prior RT. Presently, such patients who have undergone previous RT have no effective treatment options. RT and HT were generally well tolerated by patients who were not previously undergone RT. Of those who had been, most (6 of 8) tolerated retreatment well with minimal or no complications. The high-risk factors for treatment- and tumor regression-related side effects include the presence of large necrotic tumors, previous RT with a large dose/fraction, and the presence of bleeding disorders. Despite the size of these large tumors, RT and HT resulted in significant tumor shrinkage, rapid serum prostate-specific antigen decline, durable treatment responses, and durable palliation of symptoms. Additional clinical studies are warranted.

338 Regional deep hyperthermia and pei-chemotherapy in children and adoles-cents with unresectable malignant germ cell tumors: an approach for cure

338 Regional deep hyperthermia and pei-chemotherapy in children and adoles-cents with unresectable malignant germ cell tumors: an approach for cure

Edge-element based finite element analysis of microwave hyperthermia treatments for superficial tumours on the chest wall

Several three-dimensional hyperthermia treatment planning systems for deep regional hyperthermia have been successfully utilized for improving the performance of applicators such as the BSD Sigma 60. Treatment planning systems for superficial heating in contrast have been less utilized. This paper presents a study of the applicability of the finite element method that has been developed for modelling hyperthermia treatments of recurrent chest wall cancer using a patient geometry. The patient model was created by reconstructing the tissue geometry of a patient using a series of axial CT scans. Tetrahedral grids were generated from this geometry for use in finite element simulations of the SAR profile using edge-elements and in finite element simulations of the steady-state temperature profile using scalar elements. The predicted temperature profile was well correlated with thermometry readings taken after 30 min of heating during a hyperthermia treatment. The model predicted the presence of hot-spots in regions that were not monitored. Simulations also showed that the hot-spots can be manipulated by rotating the applicator by 90°. This study demonstrates the ability of the model to provide detailed and accurate heating profiles in a patient specific model for superficial microwave hyperthermia of the chest wall.

高効率発熱を有する微小インプラントの開発

高効率発熱を有する微小インプラントの開発

727 Poster Progress in total quality control for deep hyperthermia: implications of tissue segmentation variations in regional hyperthermia treatment planning

727 Poster Progress in total quality control for deep hyperthermia: implications of tissue segmentation variations in regional hyperthermia treatment planning

COUNTERPOINT: Test the value of hyperthermia in patients with carcinoma of the cervix being treated with concurrent chemotherapy and radiation

Major advances in the treatment of locally advanced cervical carcinoma were reported in 1999-2000 in five studies from the Gynecologic Oncology Group, Radiation Therapy Oncology Group and Southwestern Oncology Group. Collectively these trials reported a decrease in the risk of recurrence or death from cervical cancer ranging from 30-50% with the use of concurrent chemoradiation, as compared with radiation alone. On the basis of these trials the National Cancer Institute in 1999 issued a clinical alert concluding 'Strong consideration should be given to the incorporation of concurrent cisplatin-based chemotherapy with radiation therapy in women who require radiation therapy for treatment of cervical cancer.' Concurrently with these publications there appeared the publication in the Lancet in 2000 of the Dutch Deep Hyperthermia Group trial of radiotherapy alone versus combined radiation and hyperthermia for locally advanced pelvic tumors including carcinoma of the cervix. This multi-center phase III trial demonstrated an approximate doubling of the three year survival from 27 to 51% for the addition of hyperthermia to radiotherapy in patients with locally advanced cervical carcinoma. Additional trials to test the value of hyperthermia in patients with cervical carcinoma treated with concurrent chemotherapy and radiation are imperative and take precedence over a trial to investigate the value of chemotherapy in patients treated with hyperthermia and radiation.

The Dutch Deep Hyperthermia Trial: results in cervical cancer

Background : Radiotherapy plus hyperthermia was compared to radiotherapy alone in the Dutch Deep Hyperthermia Trial, in patients with advanced bladder, cervical, and rectal tumours. The overall results, published elsewhere, demonstrate that addition of hyperthermia to radiotherapy improves both pelvic control and overall survival rates. The therapeutic gain appeared especially worthwhile in locally advanced cervical tumours. Here, the results in patients with cervical cancer are summarized and discussed, and further details provided. Methods : From 1990-1996, 114 patients with cervical cancer were entered into this prospective randomized trial. RT was applied to a median total dose of 68 Gy. HT was given once weekly. The median follow-up time was 43 months. All randomized patients were included in the statistical analysis, which was done by intention to treat . The primary end points of the trial were complete response (CR) and duration of pelvic control (PC), secondary end points were overall survival (OS) and toxicity. Besides, an economic evaluation was performed. Results : CR rates were 57% following RT and 83% following RT + HT( p = 0.003). The difference in PC was maintained during follow-up, with 3-year LC rates of 41% following RT and 61% following RT + HT. The 3-year OS rates were 27% and 51% following RT and RT + HT, respectively ( p = 0.009). When the patients were divided into two subgroups by whether or not the planned RT was completed, a beneficial effect of hyperthermia was observed in both subgroups. Radiation toxicity was not enhanced by HT. Additional hyperthermia proved to be cost-effective, with maximum discounted cost-per-life-year gained of about Euro 4000. Conclusion : Hyperthermia in addition to standard radiotherapy of locally advanced cervical tumours results in therapeutic gain and is cost-effective.