Quality assurance guidelines for interstitial hyperthermia.

Quality assurance (QA) guidelines are essential to provide uniform execution of clinical hyperthermia treatments and trials. This document outlines the clinical and technical consequences of the specific properties of interstitial heat delivery and specifies recommendations for hyperthermia administration with interstitial techniques. Interstitial hyperthermia aims at tumor temperatures in the 40-44 °C range as an adjunct to radiation or chemotherapy. The clinical part of this document imparts specific clinical experience of interstitial heat delivery to various tumor sites as well as recommended interstitial hyperthermia workflow and procedures. The second part describes technical requirements for quality assurance of current interstitial heating equipment including electromagnetic (radiative and capacitive) and ultrasound heating techniques. Detailed instructions are provided on characterization and documentation of the performance of interstitial hyperthermia applicators to achieve reproducible hyperthermia treatments of uniform high quality. Output power and consequent temperature rise are the key parameters for characterization of applicator performance in these QA guidelines. These characteristics determine the specific maximum tumor size and depth that can be heated adequately. The guidelines were developed by the ESHO Technical Committee with participation of senior STM members and members of the Atzelsberg Circle.

Hyperthermic chest wall re-irradiation in recurrent breast cancer: a prospective observational study.

PURPOSE: To prospectively investigate the role of re-irradiation (re-RT) combined with hyperthermia (HT) in a contemporary cohort of patients affected by recurrent breast cancer (RBC). METHODS: Within the prospective registry HT03, patients with resected RBC and previous irradiation were included. Re-RT was applied to the recurrence region with doses of 50-50.4 Gy, with a boost up to 60-60.4 Gy to the microscopically or macroscopically positive resection margins (R1/R2) region. Concurrent HT was performed at 40-42 ℃. Primary endpoint was LC. Acute and late toxicity, overall survival, cancer-specific survival (CSS), and progression-free survival (PFS) were also evaluated. RESULTS: 20 patients and 21 RBC were analyzed. Median re-RT dose was 50.4 Gy and a median of 11 HT fractions were applied. Re-RT+HT was well tolerated, with three patients who experienced a grade (G) 3 acute skin toxicity and no cases of ≥G3 late toxicity. With a median follow up of 24.7 months, two local relapses occurred. Ten patients experienced regional and/or distant disease progression. Five patients died, four of them from breast cancer. PFS was favorable in patients treated with re-RT+HT for the first recurrence with doses of 60 Gy. A trend towards better CSS was found in patients with negative or close margins and after doses of 60 Gy. CONCLUSION: Full-dose re-RT+HT for RBC is well tolerated, provides good LC, and seems to be more effective when applied at the time of the first relapse and after doses of 60 Gy. The registry will be continued for validation in a larger cohort and with longer follow-up.

External validation of a rectal cancer outcome prediction model with a cohort of patients treated with preoperative radiochemotherapy and deep regional hyperthermia.

PURPOSE: To validate a nomogram for the prediction of treatment outcomes after preoperative radiochemotherapy and surgery for locally advanced rectal cancer with a cohort of patients treated with additional deep regional hyperthermia. PATIENTS AND METHODS: A total of 86 patients were treated with preoperative radiochemotherapy and deep regional hyperthermia at our institution. For every patient, the 5-year probability for death, distant metastases and local failure based on a previously published nomogram were calculated and patients were divided into three risk groups. RESULTS: Low-lying and clinically lymph node positive tumours were more frequent in the validation cohort. Five-year Kaplan-Meier estimates for overall survival (OS), distant metastases-free survival (DMFS) and local control (LC) were 87.3%, 79.9%, 95.8% (observed) and 75.5%, 71%, 90% (predicted), respectively. Discrimination between low- and high-risk groups was at a significant level for all endpoints. The c-index was 0.81 (OS), 0.67 (DMFS) and 0.92 (LC), respectively. CONCLUSIONS: The nomogram showed reasonable performance when deep regional hyperthermia is incorporated into preoperative therapy. The higher than predicted rates seen for OS and DMFS in particular in the high-risk groups warrant further prospective validation and subsequent investigation of the underlying mechanisms.

Thermoradiotherapy of the chest wall in locally advanced or recurrent breast cancer with marginal resection.

BACKGROUND AND PURPOSE: Evaluation of the efficacy of combined hyperthermia and radiotherapy (TRT) in high-risk breast cancer patients with microscopic involved margins (R1) after mastectomy or with resected locoregional, early recurrence with close margins or R1-resection. Main endpoint was local tumour control (LC); secondary endpoints were overall survival (OS), disease free survival (DFS) and acute toxicity. MATERIAL AND METHODS: Between 1997-2001, 50 patients were treated with TRT. Thirteen patients (group 1) received a post-operative TRT in a high-risk situation (free margin <1 cm or R1, N+), 37 patients (group 2) received TRT after close/R1 resection of a locoregional recurrence. Thirteen out of 37 patients in group 2 already had had two-to-seven recurrences prior to TRT. Median radiation dose was 60 Gy (range: 44-66.4 Gy), the additional local hyperthermia (>41 degrees C, 60 min) was given twice a week. Median follow-up for patients at risk was 28 months. All statistical tests were done using Statistica software. RESULTS: Actuarial OS for all patients at 3 years accounted for 89%, DFS for 68% and LC for 80%. Actuarial OS was 90% for group 1 and 89% for group 2, with four patients having died so far. DFS at 3 years was 64% in group 1 and 69% in group 2, actuarial 3 year LC was 75% and 81%, respectively. For patients with recurrent chest wall disease, there was no difference concerning local control between patients who underwent TRT with or without prior radiation. No prognostic factors could be detected due to the small number of patients investigated. The combined modality treatment was well tolerated. Grade IV toxicity, according to the Common Toxicity Criteria, did not occur. CONCLUSION: The results concerning local tumour control and overall survival in these high-risk patients are promising, especially for TRT for the treatment of local recurrences. A longer follow-up is needed to estimate late toxicity.

Thermoradiotherapy for locally recurrent breast cancer with skin involvement.

PURPOSE: This retrospective analysis investigated the effectiveness and side-effects of combined hyperthermia and radiation therapy in locally recurrent breast cancer after primary modified radical mastectomy. The aim of the thermoradiotherapy was to reduce the substantial risk of symptomatic chest wall disease. MATERIALS AND METHODS: Between May 1995-August 1998, 39 extensively pre-treated women with progressive locoregional chest wall tumours were treated with local radiofrequency hyperthermia, given twice a week immediately before radiotherapy. Sixty-two per cent of the patients had received previous radiotherapy, with a median dose of 50 Gy, 64% had received chemotherapy, 36% hormonal therapy, and 13% local therapy with miltefosin, respectively. Nine patients were treated for microscopic residual disease after local tumour excision (R1-resection) and 30 patients for gross macroscopic nodular recurrences. Twenty-seven patients had two adjacent hyperthermia fields at the ipsilateral chest wall to cover the whole irradiation area. Each field received a median of seven local hyperthermia sessions (range 2-12, average 5.6 sessions) just before radiation therapy, with a median dose of 60 Gy (range 30-68 Gy). The monitored maximum(average) and average(average) epicutaneous temperatures were 42.1 degrees C and 41.0 degrees C, respectively. Maximum(average) and average(average) intratumoural temperatures of 43.0 degrees C and 41.1 degrees C, respectively, were achieved in nine chest wall recurrences with intratumoural temperature probes. Concurrent hormonal therapy was administered in 48%, and concurrent chemotherapy in 10% of patients. RESULTS: Median overall survival time was 28 months (Kaplan Meier), with 71% and 54% of patients living 1 and 2 years after thermoradiotherapy. The median time to local failure has not been reached, local tumour control after 2 years being 53%. Actuarial 1 and 2 year local tumour controls for microscopic residual disease were 89%, and for macroscopic nodular recurrences 71% and 46%, respectively (p = 0.09). Actuarial 1 and 2 year local tumour controls after treatment with a total dose of less than 60 Gy were 51% and 38%, respectively, and, after a total dose greater than 60 Gy, 84% and 60% (p = 0.01), respectively. Actuarial 1 year local tumour control was 92% after complete tumour remission, versus 57% after partial remission (p = 0.002). Three of the 39 patients died of cancer en cuirasse, 13 patients due to distant metastases. Acute thermoradiotherapy related erythema, dry desquamation and moist desquamation were seen in 28.2%, 30.7%, and 30.7% of patients, respectively. Soft tissue necrosis occurred in two patients with previous post-operative delayed wound healing, and in one patient above a silicon implant. CONCLUSION: This study showed that, in extensively pre-treated patients with locally recurrent breast cancer, local tumour control after thermoradiotherapy depended on tumour resectability, response of macroscopic tumour to thermoradiotherapy, and total irradiation dose.

An on-line phase measurement system for quality assurance of the BSD 2000. Part I: technical description of the measurement system.

The hyperthermia system BSD 2000 with the ring applicator Sigma 60 utilizes the principle of a phase controlled group radiation source. The accuracy of the phase relationship between the four receiving HF signals is crucial for the position of the electric field inside the applicator. Therefore, essential significance falls to the phase control of the system. An automatic phase measuring technique has been developed to register immediately the phase position of the four channels of the BSD 2000 with respect to a reference signal. The system improves the insurance of the technical safeguarding. In the first part of this work, the technical realization of the measurement system is described and first measurements with the system are given. In the second part, results with respect to the quality assurance of the BSD 2000 system are presented.

An on-line phase measurement system for quality assurance of the BSD 2000. Part II: results of the phase measurement system.

Phase constancy and accuracy are significant for regional hyperthermia with phased array radiofrequency hyperthermia systems. They are both necessary for a precise target steering in therapy. For the BSD 2000 system (BSD Medical Corp. Salt Lake City, Utah, USA), the phase values of all channels are checked with a self-developed automatic on-line phase measurement system. On different days the phases are measured under identical conditions, where the output paths are cut off with 50 ohm dummy loads to suppress the influence of the radiation conditions of the antennae on the measurement values. The results show how the phase values of the four channels change in the first 30 min and from day to day. During this time interval after the start the phases drop down by up to 15 degrees. For the time later changes are very slight and the differences from day to day are negligible. The phase shift that occurs in the first 30 min is as high as a change of the target point by 1 cm. Earlier switching on of the amplifiers prevents this shift occurring during the treatment. The measurement system provides a good tool for determination of phase accuracy and is easy to realize.

Appendicitis during locoregional thermoradiotherapy of advanced or recurrent rectal and cervical cancer, a report of two cases.

INTRODUCTION: Local tumour control after irradiation alone for advanced, inoperable carcinomas of the bladder and rectum or inoperable recurrent cervical carcinoma is usually disappointing. Both preclinical and clinical studies reported improvements by adding hyperthermia to radiotherapy. Reports for phase II/III trials do not indicate any enhanced side effects. However, two cases of acute suppurating appendicitis were observed in a series of patients treated with deep regional hyperthermia. MATERIALS, METHODS AND RESULTS: Eighty patients with advanced, inoperable, or recurrent rectal or recurrent cervical tumours were treated with deep regional hyperthermia (313 sessions) in addition to radiotherapy between September 1995 and October 1998. The treatment for two of these patients (2.5%) had to be discontinued after the fourth/second hyperthermia treatments at 19.8/10.8 Gy total dose, respectively, for symptoms of pain in the right pelvis and elevated rectal temperature. Both patients underwent laparotomy and were found to have suppurative appendicitis. In addition to the retrocoecal location in both patients, evidence of preexisting chronic appendicitis, and appendiceal faecalith were observed in each patient. CONCLUSION: The development of acute appendicitis in 2.5% of patients during a course of deep regional thermoradiotherapy for pelvic tumour is much higher than the expected incidence of appendicitis in the general population (< 1/1000) (Korner et al. 1997). An enhanced risk of suppurative appendicitis in patients undergoing pelvic thermoradiotherapy cannot be excluded, especially in retrocoecal located appendices with obstructed appendix lumen from preexisting chronic appendicitis or faecalith.

[Emergency rescue in accidents with HDR afterloading units]. / Notfallbergung bei Unfall an HDR-Afterloading-Anlagen.

PROBLEM: HDR brachyradiotherapy has minimized the exposure to radiation of the personnel working in this field. Nonetheless there are periodically reported troubles with afterloading units concerning the retraction of sources that require immediate action for the limitation of possible damage. LEGAL PRINCIPLES ACCORDING TO THE GERMAN REGULATION CONCERNING PROTECTION AGAINST RADIATION (STRAHLENSCHUTZVERORDNUNG = STRLSCHV): If in afterloading brachyradiotherapy the radiation source remains extended through malfunction we deal with an emergency according to the StrlSchV. The rescue personnel should be chosen in accordance with section 50 StrlSchV (Table 1). ORGANIZATION OF THE RESCUE OF THE PATIENT: The quickest possible rescue of a patient in an emergency demands an unequivocal definition of responsibilities. Our recommendations in this instance: the physicist is responsible for the organization of the emergency rescue. The radiation oncologist in charge informs himself about the necessary emergency measures before starting the treatment and carries out the emergency rescue. If the physicist diagnoses a failure in the retraction of the source he tries to remove the failure. If he doesn't succeed in retracting the source the radiation oncologist carries out the rescue of the patient. The organizational structure of the clinic allowing, the emergency physician should invariably be the physician who placed the applicator. In the emergency rescue the radiation oncologist should be protected by a lead barrier (Figure 1, Table 2) and use manipulators (Figure 1). DOSE ASSESSMENT IN PERSONNEL AND PATIENT: The radiation exposure of the rescue personnel is calculated from the photon-equivalence dose HX with the help of the dose-rate constant of 192Ir (Table 3). According to the same procedure there can be evaluated the local radiation exposure of the patient concerned (Table 3). CONCLUSIONS: Generally speaking, all considerations regarding the topic of emergency rescue should always start out from a worst-case scenario. Of all the people involved the patient is the one who is most exposed if the radiation source is located inside his or her body. If an emergency rescue is necessary the radiation exposure of patient and personnel can only be minimized by a quick rescue. This end requires a properly equipped emergency workplace, good training of all the people concerned, and regular exercises of the rescue procedures. A well-practiced emergency management can be of life-saving importance for the patient.