Temperature and thermal dose during radiotherapy and hyperthermia for recurrent breast cancer are related to clinical outcome and thermal toxicity: a systematic review.

Objective: Hyperthermia therapy (HT), heating tumors to 40-45 °C, is a known radiotherapy (RT) and chemotherapy sensitizer. The additional benefit of HT to RT for recurrent breast cancer has been proven in multiple randomized trials. However, published outcome after RT + HT varies widely. We performed a systematic review to investigate whether there is a relationship between achieved HT dose and clinical outcome and thermal toxicity for patients with recurrent breast cancer treated with RT + HT. Method: Four databases, EMBASE, PubMed, Cochrane library and clinicaltrials.gov, were searched with the terms breast, radiotherapy, hyperthermia therapy and their synonyms. Final search was performed on 3 April 2019. Twenty-two articles were included in the systematic review, reporting on 2330 patients with breast cancer treated with RT + HT. Results: Thirty-two HT parameters were tested for a relationship with clinical outcome. In studies reporting a relationship, the relationship was significant for complete response in 10/15 studies, in 10/13 studies for duration of local control, in 2/2 studies for overall survival and in 7/11 studies for thermal toxicity. Patients who received high thermal dose had on average 34% (range 27%-53%) more complete responses than patients who received low thermal dose. Patients who achieved higher HT parameters had increased odds/probability on improved clinical outcome and on thermal toxicity. Conclusion: Temperature and thermal dose during HT had significant influence on complete response, duration of local control, overall survival and thermal toxicity of patients with recurrent breast cancer treated with RT + HT. Higher temperature and thermal dose improved outcome, while higher maximum temperature increased incidence of thermal toxicity.

Implementation of treatment planning in the routine clinical procedure of regional hyperthermia treatment of cervical cancer: an overview and the Rotterdam experience.

PURPOSE: This manuscript provides an overview in the field of hyperthermia treatment planning (HTP) in cervical cancer. Treatment planning techniques: The workflow of an HTP assisted treatment generally consists of patient imaging, tissue segmentation, model generation, electromagnetic (EM) and thermal calculations, optimisation, and clinical implementation. A main role in HTP is played by numerical simulations, for which currently a number of software packages are available in hyperthermia. To implement these simulations, accurate applicator models and accurate knowledge of dielectric and thermal parameters is mandatory. Model validation is necessary to check if this is implemented well. In the translation from HTP models to the clinic, the main aspect is accurate representation of the actual treatment situation in the HTP models. Accurate patient positioning and organ-specific segmentation can be helpful in minimising the differences between model and clinic. STEERING STRATEGIES: In the clinic, different approaches are possible: simple, i.e. target centre point (TCP) steering, often called 'target steering', or only pretreatment planning versus advanced, i.e. active HTP guided steering or image guided hyperthermia by non-invasive thermometry (NIT). The Rotterdam experience: To illustrate the implementation of HTP guided steering, the Rotterdam approach of complaint adaptive steering is elaborated, in which optimisation is adapted with increased constraints on tissues with heat-induced discomfort. CONCLUSIONS: Many publications on HTP show that HTP can be considered a feasible method to optimise and control a hyperthermia treatment, with the objective to enhance treatment quality and documentation. Ultimately, after overcoming the various uncertainties, this may lead to dose prescription.

The tolerance of reirradiation and hyperthermia in breast cancer patients with reconstructions.

BACKGROUND: Breast cancer recurrences in previously irradiated areas are treated with reirradiation (reRT) and hyperthermia (HT). The aim of this retrospective study is to quantify the toxicity of HT in breast cancer patients with reconstruction. METHODS: Between 1992 and 2009, 36 patients were treated with reRT with a scheme of 8 fractions of 4.0 Gy in 4 weeks, and HT on a total of 37 tissue reconstructions. The types of reconstructions were: split-thickness skin graft (15), transverse rectus abdominis myocutaneous flap (1), latissimus dorsi flap (14), rhomboid flap (1) or a combination of grafts and flaps (6). Toxicities were graded according to the Common Terminology Criteria for Adverse Events (CTCAE), version 3.0. Patient, tumour, and treatment characteristics predictive for the endpoints were identified in univariate and multivariate analyses. The primary endpoint was HT toxicity. Secondary endpoints were acute and late radiotherapy (RT) toxicity, complete response (CR), local control (LC) and overall survival (OS). RESULTS: The median follow-up time was 64 months. Grade 2 HT toxicity occurred in four patients and grade 3 in three. The three patients with grade 3 HT toxicity required reoperation. None of the evaluated parameters showed a significant relationship with HT toxicity. The CR rate in 15 patients with macroscopic disease was 80%. The 3 and 5 year LC rates were 74% and 69%; the median OS was 55 months. CONCLUSIONS: Combined reRT and HT in breast cancer patients with reconstruction is safe and effective.

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.

BACKGROUND: 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. METHODS: Sixty-eight patients with advanced cervical cancer were prospectively registered in the USA, Norway and the Netherlands, and treated with a combination of radiotherapy (external beam radiotherapy and brachytherapy for a biologically effective dose of at least 86.7 Gy), chemotherapy (at least four courses of weekly cisplatin (40 mg/m(2))) and locoregional hyperthermia (four weekly sessions). Long-term follow-up was gathered and recurrence-free survival (RFS) and overall survival (OS) curves and survival estimates were obtained. RESULTS: Median follow-up was 81 months. Tumours in 28 patients have recurred, 21 of whom have died. Five-year RFS from the day of registration in the study is 57.5% (95%CI: 46.6-71.0) and five-year OS is 66.1% (95%CI: 55.1-79.3). Differences between countries can be explained by patient characteristics. CONCLUSION: The long-term survival results of the combination of full-dose radiotherapy, chemotherapy and hyperthermia fall well within previous reports for this patient group in randomised trials. The small trial size and lack of randomisation do not permit further interpretation.

Procedure for creating a three-dimensional (3D) model for superficial hyperthermia treatment planning.

PURPOSE: To make a patient- and treatment-specific computed tomography (CT) scan and to create a three-dimensional (3D) patient model for superficial hyperthermia treatment planning (SHTP). PATIENTS, MATERIALS, AND METHODS: Patients with recurrent breast adenocarcinoma in previously irradiated areas referred for radiotherapy (RT) and hyperthermia (HT) treatment and giving informed consent were included. After insertion of the thermometry catheters in the treatment area, a CT scan in the treatment position was made. RESULTS: A total of 26 patients have been, thus far, included in the study. During the study period, five types of adjustments were made to the procedure: (1) marking the RT field with radioopaque markers, (2) making the CT scan after the first HT treatment instead of before, (3) using an air- and foam-filled (dummy) water bolus, (4) a change to radiolucent catheters for which radioopaque markers were needed, and (5) marking the visible/palpable extent of the tumor with radioopaque markers, if necessary. With these adjustments, all necessary information is visible on the CT scan. Each CT slice was automatically segmented into muscle, fat, bone, and air. RT field, catheters, applicators, and tumor lesions, if indicated, were outlined manually using the segmentation program iSeg. Next the model was imported into SEMCAD X, a 3D electromagnetic field simulator. CONCLUSION: Using the final procedure to obtain a patient- and treatment-specific CT scan, it is possible to create a 3D model for SHTP.

Intra-patient comparison between two annular phased array applicators, Sigma-60 and Sigma-Eye: Applied RF powers and intraluminally measured temperatures.

PURPOSE: To investigate whether one can replace the Sigma-60 with the Sigma-Eye applicator (or vice versa) during a deep hyperthermia treatment series without a loss in quality of the treatment. PATIENTS AND METHODS: Hyperthermia data of all 48 patients with locally advanced cervical cancer who were treated with both applicators were analysed. In this study no use was made of the longitudinal SAR steering option of the Sigma-Eye. Hence, the Sigma-Eye was used as a Sigma-60 with a modified shape and water bolus. Power and intraluminal temperature were analysed. Sub-group analyses were performed for six groups, categorised according to the reasons for switching between the applicators. RESULTS: The 'all patient' analysis showed a significant difference for radio frequency (RF) power indices as applied to the two applicators, but for temperatures no difference between applicators was found. Sub-group analyses showed a consistent difference for RF power indices, i.e. the RF power for the Sigma-Eye was 8-29% higher than that for Sigma-60. In contrast, in about 90% of patients the number of switch-offs was 8-62% lower when the Sigma-Eye was applied. Similarly, in 73% of patients total switch-off time was 18-150% lower for the Sigma-Eye than for the Sigma-60. For the largest sub-group (n = 23), patients treated with the Sigma-Eye all had temperature indices slightly lower (ΔT = 0.2-0.5°C) than those for the Sigma-60 (p < 0.028). For the other five sub-groups no relevant difference was found between temperatures obtained by the two applicators. CONCLUSION: In the case of severe patient discomfort with the Sigma-60 or Sigma-Eye applicator, or if achieved temperatures are not satisfactory, one can freely switch between both applicators without loss of hyperthermia treatment quality.

Quality control of superficial hyperthermia by treatment evaluation.

Steering of multi-element heating arrays for superficial hyperthermia (SHT) can be a challenge in the clinic. This is because the technician has to deal with a multiple-input multiple-output system, varying tissue dynamics, and often sparse tissue temperature data. In addition, patient feedback needs to be taken into account. Effective management of the steering task determines the quality of heating. Systematic evaluation is an effective tool to control the quality of treatments. The purpose of this manuscript is to report on a treatment evaluation flow developed for SHT at the Erasmus MC. This flow is used to secure the quality of steering as well as to stimulate general quality awareness in the hyperthermia team. All treatments are evaluated in a multidisciplinary discussion. Tools and methods were developed to enable effective and efficient evaluations. The treatment evaluation sheet is a compact and intuitive representation of power and temperature data. Trend lines and a temperature-depth plot allow a quick analysis of the steering parameters and the heating profile within the target volume. In addition, the principal statistics of applicator power, water bolus and tissue temperature values are given. Power steering data includes the number of switch-off events, interruption time and the number of steering actions. A list of basic checks and reference values for clinical data support further the treatment evaluation. These tools and the systematic treatment evaluations they facilitate, ultimately lead to consistent performance and fine tuning of the set-up and steering strategy for each individual patient.

Evaluation of CEM43 degrees CT90 thermal dose in superficial hyperthermia: a retrospective analysis.

BACKGROUND AND PURPOSE: Prospective use of the CEM43 degrees CT90 thermal dose parameter has been proposed for hyperthermia treatments. This study evaluates the CEM43 degrees CT90 parameter by means of a retrospective analysis of recurrent breast cancer patients receiving reirradiation plus hyperthermia. MATERIAL AND METHODS: CEM43 degrees CT90 was calculated for 72 patients who received 8 x 4 Gy reirradiation plus 8 x 1 h hyperthermia for adenocarcinoma recurrences at the chest wall. Associations of prognostic factors CEM43 degrees CT90 and tumor maximum diameter with endpoints complete response (CR), duration of local control (DLC), and overall survival (OS) were determined. RESULTS: A highly significant inverse association between CEM43 degrees CT90 and tumor maximum diameter (rho = -0.7, p < 1e-6) was found. The association between CR and CEM43 degrees CT90 was not significant (p > or = 0.7). CEM43 degrees CT90 was associated with DLC. Both CEM43 degrees CT90 and tumor maximum diameter had a significant association with survival (p < or = 0.01). The association with thermal dose, when adjusted for tumor maximum diameter, was not significant for either CR, DLC, or OS (p > 0.2). CONCLUSION: In this retrospective study, no clear CEM43 degrees CT90 thermal dose targets or associations with clinical endpoints could be established.

Use of combined radiation and hyperthermia for gynecological cancer.

PURPOSE OF REVIEW: We reviewed all literature on the clinical use of combined radiation and hyperthermia for gynecologic malignancies. RECENT FINDINGS: Combined radiation and hyperthermia should be considered an alternative to chemoradiation for patients with locally advanced cervix cancer and be the first treatment of choice for these patients when radiation cannot be combined with chemotherapy. Several randomized trials have shown an improvement by adding hyperthermia to radiation that is comparable to the improvement found with the addition of chemotherapy to radiation. Hyperthermia does not seem to add to treatment-induced toxicity and the results of hyperthermia are consistent even at 12 years follow-up and could be reproduced in a large, unselected group of cervix cancer patients. A novel indication for combined radiotherapy and hyperthermia is vaginal cancer. Recently, a cohort study showed that the addition of hyperthermia to radiation seems to improve overall survival for patients with vaginal cancer International Federation of Gynecology and Obstetrics stage III. SUMMARY: Combined radiation and hyperthermia should be considered for patients with locally advanced cervix cancer (International Federation of Gynecology and Obstetrics stage IIb and upwards) as an alternative to chemoradiation for patients with a contraindication for chemotherapy. For other patients, the optimal treatment combination is the subject of randomized trials. For vaginal cancer, a prospective registration study is currently ongoing.

Clinical implementation of hyperthermia treatment planning guided steering: A cross over trial to assess its current contribution to treatment quality.

PURPOSE: To assess the current feasibility of online hyperthermia treatment planning guided steering (HGS) and its current contribution to treatment quality in deep hyperthermia for locally advanced cervical cancer. MATERIALS AND METHODS: 36 patients were randomized to receive either their second and fourth (arm A) or their third and fifth (arm B) hyperthermia treatment of the series with the aid of HGS. The other treatments were conducted according to the Rotterdam Empirical Steering Guidelines (RESG). RESULTS: During period I (second and third treatment of the series) similar results were found for HGS and RESG with a slight, non-significant difference found in favour of HGS. The average temperature T50 was 40.3 degrees C for both (p = 0.409) and the dose parameter CEM43T90 was 0.64 for RESG and 0.63 for HGS (p = 0.154). However, during period II (fourth and fifth treatment of the series) HGS performed less well, with significant lower thermal dose parameters, minimum, mean and maximum intraluminal temperatures, tolerance measures and net integrated power. T50 was 40.4 degrees C after RESG and 40 degrees C after HGS (p = 0.001) and CEM43T90 0.57 and 0.38 (p = 0.01) respectively. CONCLUSION: We found that the procedure of online treatment planning guided steering is feasible. For maximal exploitation of its possibilities, however, better control and understanding of several patient, tumour and technical parameters is required. This study has been very helpful in identifying some of the challenges and flaws that warrant further investigation in the near future, such as patient positioning and the prevention of hotspot-related complaints.

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). OBJECTIVES: 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. SEARCH STRATEGY: 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. SELECTION CRITERIA: RCTs comparing radiotherapy alone (RT) versus combined hyperthermia and radiotherapy (RHT) in patients with LACC. DATA COLLECTION AND ANALYSIS: Between 1987 and 2009 the results of six RCTs were published, these were used for the current analysis. MAIN 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. AUTHORS' 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.

Combined use of hyperthermia and radiation therapy for treating locally advanced cervix 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 cervix carcinoma (LACC). OBJECTIVES: 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. SEARCH STRATEGY: 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. SELECTION CRITERIA: RCTs comparing radiotherapy alone (RT) versus combined hyperthermia and radiotherapy (RHT) in patients with LACC. DATA COLLECTION AND ANALYSIS: Between 1987 and 2009 the results of six RCTs were published, these were used for the current analysis. MAIN RESULTS: 74% of patients had FIGO stage IIIB LACC. Treatment outcome was significantly better for patients receiving the combined treatment (Figures 4 to 6). 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 (hazard ratio (HR) 0.48; 95% CI 0.37 to 0.63; p < 0.001) and a significantly better overall survival (OS) 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. AUTHORS' 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 cervix carcinoma without affecting treatment related grade 3 to 4 acute or late toxicity.

Concomitant hyperthermia and radiation therapy for treating locally advanced rectal cancer.

BACKGROUND: Surgery has been the treatment of choice for patients with rectal cancer. For locally advanced cancer results were poor, with high rates of locoregional recurrences and poor overall survival data. Adding (chemo)radiotherapy upfront improved results mainly in locoregional control. Adding hyperthermia to radiotherapy preoperatively might have an equivalent beneficial effect. OBJECTIVES: To quantify the potential beneficial effect of thermo radiation compared to chemo-radiation with respect to pathological complete responses, overall survival and toxicity in rectal cancer therapy. SEARCH STRATEGY: We identified the relevant phase II and III randomised controlled trials in any language trough electronic searches May 2007 of the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 1, 2007), the Cochrane Colorectal Cancer Groups Specialised Register, MEDLINE (from 1966), EMBASE (from 1974), CINAHL (from 1982). Furthermore, various trial databases were searched for the identification of recent completed and ongoing trials (metaRegister of Controlled Trials, Cancer Research UK, Cancer.gov, The Eastern Cooperative Oncology Group Trials Database). All studies identified until May 2007 were considered for inclusion in the present study. SELECTION CRITERIA: Only phase II and III randomised controlled clinical trials were included in the analysis. DATA COLLECTION AND ANALYSIS: All identified studies were assessed by two independent reviewers. A weighted estimate of the treatment effect was computed for 2, 3, 4 and 5-year survival, for local tumour recurrence, severe acute and late toxicity and complete tumour response (CR). CR was defined either clinically by disappearance of all pretreatment signs of local tumour or pathologically by microscopically free margins. The risk ratio (RR) and hazard ratio (HR) were used. Analyses were performed with the Reference Manager (RevMan). MAIN RESULTS: Six RCTs published between 1990 and 2007 were identified. A total number of 520 patients was treated, 258 in the radiotherapy only arm (RT) and 262 in the radiotherapy-hyperthermia arm (RHT). Four studies (424 patients) reported overall survival (OS) rates. After 2 years, OS was significantly better in the RHT group (HR 2.06; 95% CI 1.33-3.17; p=.001), but this difference disappeared after a longer period (3, 4 and 5 year OS). All but one studies reported CR rates. A significant higher CR rate was observed in the RHT group (RR 2.81; 95% CI 1.22-6.45; p=.01). Only 2 studies reported on acute toxicity. In these 2 studies no significant differences were observed between the RT and the RHT group. Late toxicity data were not reported. AUTHORS' CONCLUSIONS: Further studies are needed to compare chemoradiation versus thermoradiation versus chemoradiation plus hyperthermia in well selected/conducted and quality controlled randomised trials.

Long-term improvement in treatment outcome after radiotherapy and hyperthermia in locoregionally advanced cervix cancer: an update of the Dutch Deep Hyperthermia Trial.

PURPOSE: 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. METHODS AND MATERIALS: From 1990 to 1996, a total of 114 women with locoregionally advanced cervical carcinoma were randomly assigned to RT or RT+HT. The RT was applied to a median total dose of 68 Gy. The HT was given once weekly. The primary end point was local control. Secondary end points were overall survival and late toxicity. RESULTS: At the 12-year follow-up, local control remained better in the RT+HT group (37% vs. 56%; p=0.01). Survival was persistently better after 12 years: 20% (RT) and 37% (RT+HT; p=0.03). World Health Organization (WHO) performance status was a significant prognostic factor for local control. The WHO performance status, International Federation of Gynaecology and Obstetrics (FIGO) stage, and tumor diameter were significant for survival. The benefit of HT remained significant after correction for these factors. European Organization for Research and Treatment of Cancer Grade 3 or higher radiation-induced late toxicities were similar in both groups. CONCLUSIONS: For locoregionally advanced cervical cancer, the addition of HT to RT resulted in long-term major improvement in local control and survival without increasing late toxicity. This combined treatment should be considered for patients who are unfit to receive chemotherapy. For other patients, the optimal treatment strategy is the subject of ongoing research.

Steering in locoregional deep hyperthermia: evaluation of common practice with 3D-planning.

PURPOSE: In Rotterdam, fifteen years of clinical experience with deep hyperthermia has sublimated in empirical treatment guidelines. In this paper, a hyperthermia treatment planning system (HTPS) is employed to investigate the effect of these guidelines on global power distribution, their effectiveness and the rationale behind each guideline. MATERIALS AND METHODS: Four guidelines were investigated. The first two prescribe steering actions for balancing intraluminal temperatures and alleviating complaints of deep-seated pain or pressure. The third guideline handles superficial complaints of pain or heat sensation. The last guideline states that frequency should be increased from 77 MHz upwards in case of multiple, opposite, painful regions uncontrollable by the previous steering actions. For all steering actions it is assumed that input power is increased until complaints occur. Sigma Hyperplan was used to calculate specific absorption rate (SAR) distributions for five patient models with locally advanced cervical cancer. Absorbed power ratios of different regions of interest were evaluated to illustrate steering efficacy and complaint reduction. RESULTS AND CONCLUSIONS: Phase steering is effective in shifting the central power distribution to the periphery, and is an appropriate method to balance temperatures or to handle deep-seated complaints. Reduction of amplitude is the proper action to alleviate superficial complaints of heat or pressure. Compression of the SAR distribution, mainly in the lateral direction, is predicted with increasing frequency. Hence, for complaints in the lower back or on the sides, a frequency increase should be considered. We conclude that the results of the HTPS are in close agreement with the empirical steering guidelines.

Concomitant radiotherapy and hyperthermia for primary carcinoma of the vagina: a cohort study.

OBJECTIVE: To evaluate the supplementary value of adding hyperthermia to radiotherapy in patients with primary vaginal cancer. STUDY DESIGN: Cohort of 44 patients diagnosed with primary vaginal cancer between 1990 and 2002 was assessed. Survival rates and median survival of patients with primary vaginal cancer undergoing radiotherapy with and without hyperthermia were compared. Hyperthermia was solely added to radiotherapy in case of a tumor size >4 cm in diameter for FIGO stage III disease. RESULTS: The calculated overall 5-year survival of primary vaginal cancer was 63%. In comparison to histologic high grade tumors, higher survival rates for histologic low grade tumors were calculated. For FIGO stage III of disease, the addition of hyperthermia to radiotherapy for tumors >4 cm in diameter resulted similar survival rates and median survival when compared to those achieved by radiotherapy as monotherapy in tumors of <4 cm in diameter. CONCLUSIONS: The addition of hyperthermia to radiotherapy might result in better survival rates in primary vaginal cancer for tumors >4 cm in diameter. The supplementary effect of hyperthermia to radiotherapy may be a feasible and beneficial approach in the treatment of vaginal cancer.

Radiation therapy combined with hyperthermia versus cisplatin for locally advanced cervical cancer: Results of the randomized RADCHOC trial.

BACKGROUND: 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. METHODS: In this open-label, multicenter randomized trial, patients with LACC were randomly assigned by a computer-generated, biased coin minimization technique to RT-CT or RT-HT. Central randomization was done with stratification by FIGO-stage, tumour diameter and nodal status. Primary endpoint was event free survival (EFS). Secondary endpoints were pelvic recurrence free survival (PRFS), overall survival (OS) and treatment related toxicity. Analysis was done by intention to treat. RESULTS: The trial was closed prematurely (87 of 376 planned patients enrolled: 43 RT-CT; 44 RT-HT). Median follow-up time was 7.1 years. The cumulative incidence of an event was 33% in the RT-CT group and 35% in the RT-HT group. The corresponding hazard rate (HR) for EFS was 1.15 (CI: 0.56-2.36, p=0.7). Also the hazards for PRFS (0.94; CI 0.36-2.44) and OS (1.04; CI 0.48-2.23) at 5 years were comparable between both treatment arms as was grade ⩾3 radiation related late toxicity (6 RT-CT and 5 RT-HT patients). CONCLUSION: After 25% of intended accrual, data suggest comparable outcome for RT-CT and RT-HT.

Local control rate after the combination of re-irradiation and hyperthermia for irresectable recurrent breast cancer: Results in 248 patients.

BACKGROUND AND PURPOSE: Randomized studies have shown that adding hyperthermia (HT) to re-irradiation (re-RT) improves treatment outcome for patients with breast cancer recurrences. We evaluated the efficacy and side effects in patients treated with re-RT and HT for irresectable locoregional breast cancer recurrences. MATERIAL AND METHODS: From September 1996 to December 2011, 248 patients with a macroscopic breast cancer recurrence were treated with re-RT and HT. Radiotherapy (RT) was applied to a dose of 32 Gy in 4 Gy fractions, twice weekly. HT was prescribed once weekly after RT. Primary endpoints for this analysis were complete response (CR) and local control (LC). Secondary endpoints were overall survival (OS), and toxicity. Patient-, tumor-, and treatment-related characteristics predictive for the endpoints were identified in univariate and multivariate analyses. RESULTS: The median follow-up period was 32 months. The CR rate was 70%. At 1, 3, and 5 years LC was 53%, 40% and 39%, and OS was 66%, 32%, and 18%, respectively. OS after 10 years was 10%. Thermal burns developed in 23% patients, healing with conservative measures. The incidence of 5 years late grade 3 toxicity was 1%. A few patients survived more than 10 years without evidence of disease. CONCLUSIONS: The combination of re-RT and HT results in a high rate of long-term LC with acceptable late toxicity, and many patients remained locally controlled for the rest of their survival period.

Long-term results of a double perfusion schedule using high dose hyperthermia and melphalan sequentially in extensive melanoma of the lower limb.

The aim of this study was to assess the results of an isolated limb perfusion (ILP) schedule with high dose hyperthermia (42-43 degrees C) and melphalan, applied sequentially in patients with advanced melanoma of the limbs. Seventeen patients with extensive recurrent or bulky melanoma of a limb were treated with hyperthermic femoral ILP (42-43 degrees C) without drugs followed by normothermic (37-38 degrees C) ILP with melphalan. Eleven patients (65%) had a complete response. Three patients (27%) had limb recurrences after 5, 6 and 18 months, respectively. The 5 year limb recurrence-free interval for patients with a complete response was 63%. Limb toxicity was mild; pressure-related blistering and transient sensory disturbances occurred after the hyperthermic ILP, and 88% of the patients had a grade II reaction (mild erythema and oedema) after the second ILP. This sequential ILP schedule resulted in a high complete response rate and a low limb-recurrence rate in patients with extensive, recurrent melanoma of the limbs at the cost of only mild toxicity. This regimen could be an alternative to ILP with tumour necrosis factor-alpha and melphalan.