Radiotherapy and hyperthermia for breast cancer patients at high risk of recurrence.

PURPOSE: To evaluate the long-term efficacy of combined radiotherapy (RT) and hyperthermia (HT) in a large mono-institutional cohort of breast cancer (BC) patients affected by recurrent, newly diagnosed non-resectable or high risk resected tumor. MATERIALS AND METHODS: Records of BC patients treated with RT + HT between 1995 and 2018 were retrospectively analyzed. RT doses of 50-70 Gy concurrent to a twice per week superficial HT were applied. For HT, a temperature between 41 and 42 °C was applied for approximately 1 h. Primary endpoint was local control (LC), secondary endpoints comprised toxicity, overall survival (OS), and progression-free survival (PFS). RESULTS: A total of 191 patients and 196 RT + HT treatments were analyzed. In 154 cases (78.6%) RT + HT was performed for patients with recurrent BC. Among these, 93 (47.4% of the entire cohort) had received RT prior to RT + HT. Median follow up was 12.7 years. LC at 2, 5, and 10 years was 76.4, 72.8, and 69.5%, respectively. OS at 2, 5, and 10 years was 73.5, 52.3, and 35.5%, respectively. PFS at 2, 5, and 10 years was 55.6, 41, and 33.6%, respectively. Predictive factors for LC were tumor stage, distant metastases, estrogen/progesterone receptor expression, resection status and number of HT fractions. At multivariate analysis tumor stage and receptor expression were significant. No acute or late toxicities higher than grade 3 were observed. CONCLUSION: Combined RT + HT offers long-term high LC rates with acceptable toxicity for patients with recurrent, newly diagnosed non-resectable or resected BC at high risk of relapse.

Neoadjuvant Chemoradiation Combined with Regional Hyperthermia in Locally Advanced or Recurrent Rectal Cancer.

BACKGROUND: To prospectively analyze feasibility and pathological complete response (pCR) rates of neoadjuvant chemoradiotherapy combined with regional hyperthermia (RHT) in patients with locally advanced (LARC) or recurrent (LRRC) rectal cancer. METHODS: between 2012 and 2018, 111 patients with UICC stage IIB-IV or any locally recurrent rectal cancer were included (HyRec-Trial, ClinicalTrials.gov Identifier: NCT01716949). Patients received radiotherapy with concurrent 5-Fluororuracil (5-FU)/Capecitabine and Oxaliplatin, and RHT. Stage 1 feasibility analysis evaluated dose-limiting toxicities (DLT) after 19 patients, stage 2 after 59 evaluable patients. Analysis of the pCR rate was based on histopathological reports. RESULTS: the feasibility rates for stages 1 and 2 were 90% (17/19) and 73% (43/59), respectively. In the intention-to-treat population the pCR rate was 19% (20/105; 90% confidence interval (CI) 13.0-26.5). In the per-protocol-analysis, complete tumor regression was seen in 28% (18/64) and 38% (3/8) of the patients with LARC and LRRC, respectively. Complete resection rates (R0) among patients with LARC and LRRC who received surgery were 99% (78/84) and 67% (8/12). CONCLUSIONS: the intensified neoadjuvant and multimodality treatment schedule was feasible and led to comparable early toxicity rates as described by other trials that used the similar chemoradiation protocol. The presented treatment regimen resulted in a very high pCR rate and appears as a promising option for patients with LRRC.

Deep regional hyperthermia with preoperative radiochemotherapy in locally advanced rectal cancer, a prospective phase II trial.

PURPOSE: The goal of the present study was to investigate the effect of deep regional hyperthermia on early and long-term oncological outcomes in the context of preoperative radiochemotherapy in rectal cancer. METHODS: In this prospective phase II trial, patients with locally advanced rectal cancer were treated with 5-fluorouracil based preoperative radiochemotherapy with 50.4 Gy in 28 fractions. Deep regional hyperthermia was scheduled twice weekly. Pathological tumor regression was scored according to the Dworak regression system. The primary endpoint was pathological complete response (pCR). Further endpoints were local control (LC), distant control (DC), disease-free survival (DFS) and overall survival (OS). Hyperthermia was defined as feasible if 70% of patients received at least eight treatments. Quality of life was assessed at follow-up by the EORTC-QLQ-C30 and QLQ-CR29 questionnaires. Time to event data was analyzed according to Kaplan-Meier based on first-events. The study was registered on clinicaltrials.gov (NCT02353858). RESULTS: From 2012 until 2017, 78 patients were recruited. Median follow-up was 54 months. Based on magnetic resonance imaging, the mesorectal fascia was involved or threatened in 60% of the patients. Compliance with radiotherapy was 99%, 91% received both cycles of chemotherapy and 77% had eight or more hyperthermia treatments. Median time from the end of radiotherapy to surgery was 6.7 weeks. A pathological complete response was reported in 14% of the patients, 50% had either Dworak 4 (complete regression) or Dworak 3 regression (scattered tumor cells only). Three year estimates for OS, DFS, LC and DC were 94%, 81%, 96% and 87%. Patients with higher hyperthermia related cumulative temperatures showed stronger tumor regression. Global health status based on EORTC-QLQ-C30 was comparable with data from the general population. CONCLUSION: Deep regional hyperthermia was feasible, did not compromise standard treatments and resulted in promising long-term oncological outcomes and QoL.

A multi-institution study: comparison of the heating patterns of five different MR-guided deep hyperthermia systems using an anthropomorphic phantom.

INTRODUCTION: Within the hyperthermia community, consensus exists that clinical outcome of the treatment radiotherapy and/or chemotherapy plus hyperthermia (i.e. elevating tumor temperature to 40 - 44 °C) is related to the applied thermal dose; hence, treatment quality is crucial for the success of prospective multi-institution clinical trials. Currently, applicator quality assurance (QA) measurements are implemented independently at each institution using basic cylindrical phantoms. A multi-institution comparison of heating quality using magnetic resonance thermometry (MRT) and anatomical representative anthropomorphic phantoms provides a unique opportunity to obtain novel QA insights to facilitate multi-institution trial evaluation. OBJECTIVE: Perform a systematic QA procedure to compare the performance of MR-compatible hyperthermia systems in five institutions. METHODS AND MATERIALS: Anthropomorphic phantoms, including pelvic and spinal bones, were produced. Clinically relevant power of 600 watts was applied for ∼12 min to allow for 8 sequential MR-scans. The 3D-heating distribution, steering capabilities, and presence of off-target heating were analyzed. RESULTS: The evaluated devices show comparable heating profiles for centric and eccentric targets. The differences observed in the 3D-heating profiles are the result of variations in the exact phantom positioning and applicator characteristics, whereby positioning of the phantom followed current ESHO-QA guidelines. CONCLUSION: Anthropomorphic phantoms were used to perform QA-measurements of MR-guided hyperthermia systems operating in MR-scanners of different brands. Comparable heating profiles are shown for the five evaluated institutions. Subcentimeter differences in position substantially affected the results when evaluating the heating patterns. Integration of advanced phantoms and precise positioning in QA-guidelines should be evaluated to guarantee the best quality patient care.

MR Thermometry Data Correlate with Pathological Response for Soft Tissue Sarcoma of the Lower Extremity in a Single Center Analysis of Prospectively Registered Patients.

Background: There is a strong biologic rationale for using locoregional hyperthermia in soft tissue sarcoma and a randomized trial reported significant improvements with hyperthermia. The aim of this study was to describe the opportunities of magnetic resonance (MR)-based thermometry in a cohort of soft tissue sarcoma patients undergoing combined radiotherapy and locoregional hyperthermia. Patients and Methods: For eleven evaluable patients, tumor volume (VTu) and a separate volume for temperature analysis with reliable temperature distribution (Vtherm) were contoured for every hyperthermia treatment (103 therapies). Temperature data were recorded for all tumors and were correlated with clinical features and pathologic response data. Results: Of 48 patients with high-risk soft tissue sarcomas treated with radio(chemo)therapy and locoregional hyperthermia, MR thermometry was possible in 11 (23%) patients. For all patients, the temperature superseded by 90% of VTu (T90(VTu)) and T90 (Vtherm) were in the range of 37-43 °C and 40-45 °C, respectively. Larger tumors tended to reach higher temperatures. For tumors showing a pathologic response in the resection specimen after preoperative treatment, temperature (T90 (Vtherm)) was significantly higher than in tumors without pathologic response. Conclusion: Lower extremity sarcomas undergoing preoperative treatment with locoregional hyperthermia are especially suitable for MR thermometry. MR thermometry is a promising non-invasive way for temperature measurement during locoregional hyperthermia, showing a positive dose-response relationship.

Quantitative, Multi-institutional Evaluation of MR Thermometry Accuracy for Deep-Pelvic MR-Hyperthermia Systems Operating in Multi-vendor MR-systems Using a New Anthropomorphic Phantom.

Clinical outcome of hyperthermia depends on the achieved target temperature, therefore target conformal heating is essential. Currently, invasive temperature probe measurements are the gold standard for temperature monitoring, however, they only provide limited sparse data. In contrast, magnetic resonance thermometry (MRT) provides unique capabilities to non-invasively measure the 3D-temperature. This study investigates MRT accuracy for MR-hyperthermia hybrid systems located at five European institutions while heating a centric or eccentric target in anthropomorphic phantoms with pelvic and spine structures. Scatter plots, root mean square error (RMSE) and Bland-Altman analysis were used to quantify accuracy of MRT compared to high resistance thermistor probe measurements. For all institutions, a linear relation between MRT and thermistor probes measurements was found with R2 (mean ± standard deviation) of 0.97 ± 0.03 and 0.97 ± 0.02, respectively for centric and eccentric heating targets. The RMSE was found to be 0.52 ± 0.31 °C and 0.30 ± 0.20 °C, respectively. The Bland-Altman evaluation showed a mean difference of 0.46 ± 0.20 °C and 0.13 ± 0.08 °C, respectively. This first multi-institutional evaluation of MR-hyperthermia hybrid systems indicates comparable device performance and good agreement between MRT and thermistor probes measurements. This forms the basis to standardize treatments in multi-institution studies of MR-guided hyperthermia and to elucidate thermal dose-effect relations.

Radiotherapy and hyperthermia with curative intent in recurrent high risk soft tissue sarcomas.

PURPOSE: Radiotherapy before or after resection is one of the pillars of treatment for localised high risk soft tissue sarcomas. Treatment intensification has been described with concurrent chemotherapy and hyperthermia. The aim of this study is to assess local control after multimodal treatment, focussing on the treatment of local recurrences after surgery only. PATIENTS AND METHODS: Of 42 patients treated in a prospective protocol with radiotherapy and hyperthermia, nine were treated for isolated local recurrences without metastatic spread. Most patients were treated with trimodal therapy including chemotherapy with ifosfamide and underwent resection whenever possible. Median follow-up was 1.4 years. RESULTS: The treatment was well tolerated. Estimated disease free survival, distant metastases free survival and local control for the whole cohort after 1.5 years were 66, 73 and 88%, respectively. Neoadjuvant vs. adjuvant treatment influenced local control with a trend to statistical significance. Resection status did not influence local control. The cohort of patients treated for local recurrence after surgery alone had a significantly impaired local control compared to multimodal treatment at primary diagnosis (100 vs. 52%, p < 0.001). CONCLUSIONS: With multimodal therapy including radiotherapy and hyperthermia local tumour control is achievable even in locally recurrent tumours. The clear-cut difference of the treatment of local recurrence in contrast to primary diagnosis might either reflect difficulties in diagnosis and treatment of local recurrences or biological aggressiveness of recurrent tumours. However, we recommend to consider multimodal treatment at primary diagnosis of high risk soft tissue sarcomas.

Quality assurance guidelines for superficial hyperthermia clinical trials : II. Technical requirements for heating devices.

Quality assurance (QA) guidelines are essential to provide uniform execution of clinical trials with uniform quality hyperthermia treatments. This document outlines the requirements for appropriate QA of all current superficial heating equipment including electromagnetic (radiative and capacitive), ultrasound, and infrared heating techniques. Detailed instructions are provided how to characterize and document the performance of these hyperthermia applicators in order to apply reproducible hyperthermia treatments of uniform high quality. Earlier documents used specific absorption rate (SAR) to define and characterize applicator performance. In these QA guidelines, temperature rise is the leading parameter for characterization of applicator performance. The intention of this approach is that characterization can be achieved with affordable equipment and easy-to-implement procedures. These characteristics are essential to establish for each individual applicator the specific maximum size and depth of tumors that can be heated adequately. The guidelines in this document are supplemented with a second set of guidelines focusing on the clinical application. Both sets of guidelines were developed by the European Society for Hyperthermic Oncology (ESHO) Technical Committee with participation of senior Society of Thermal Medicine (STM) members and members of the Atzelsberg Circle.

Quality assurance guidelines for superficial hyperthermia clinical trials: I. Clinical requirements.

Quality assurance guidelines are essential to provide uniform execution of clinical trials and treatment in the application of hyperthermia. This document provides definitions for a good hyperthermia treatment and identifies the clinical conditions where a certain hyperthermia system can or cannot adequately heat the tumour volume. It also provides brief description of the characteristics and performance of the current electromagnetic (radiative and capacitive), ultrasound and infra-red heating techniques. This information helps to select the appropriate heating technique for the specific tumour location and size, and appropriate settings of the water bolus and thermometry. Finally, requirements of staff training and documentation are provided. The guidelines in this document focus on the clinical application and are complemented with a second, more technical quality assurance document providing instructions and procedure to determine essential parameters that describe heating properties of the applicator for superficial hyperthermia. Both sets of guidelines were developed by the ESHO Technical Committee with participation of senior STM members and members of the Atzelsberg Circle.

Conservative surgery with combined high dose rate brachytherapy for patients suffering from genitourinary and perianal rhabdomyosarcoma.

BACKGROUND AND PURPOSE: Outcome of patients with genitourinary rhabdomyosarcoma has been improved in the past, but organ preservation rates are too low. Conservative surgery with LDR-brachytherapy has been advocated, but LDR-brachytherapy is often not available. We wanted to establish a novel treatment modality combining HDR-brachytherapy and conservative surgery. MATERIAL AND METHODS: We performed an organ preserving tumor resection with intraoperative placement of brachytherapy tubes. Suitable patients were selected following assessment of response to neoadjuvant chemotherapy where organ preserving surgical resection was deemed feasible. In bladder-prostate rhabdomyosarcoma, only tumors located below the bladder neck could be treated by brachytherapy. After surgery, high dose rate brachytherapy was carried out for 30-36Gy total dose. RESULTS: A total of 11 patients were treated up to now (embryonal histology n=10, alveolar histology n=1) with a median follow-up of 18months [4-80]. All patients were IRS group III. There were no significant side effects. One patient had local relapse and was successfully treated with re-excision. All other patients are in the first complete remission. One patient developed a neurogenic bladder and required creation of a Mitrofanoff stoma. CONCLUSION: Combined conservative surgery and high dose rate brachytherapy is a treatment option for selected rhabdomyosarcoma patients. The paper highlights the essential technical challenges and clearly shows limitations of this treatment approach.

Long-term local control and survival after preoperative radiochemotherapy in combination with deep regional hyperthermia in locally advanced rectal cancer.

PURPOSE: The aim of this study was to evaluate the impact of deep regional hyperthermia on long-term local control and survival in locally advanced non-metastatic rectal cancer. METHODS: In total 103 patients with locally advanced non-metastatic rectal cancer were treated preoperatively with either neoadjuvant radiochemotherapy alone (n = 43) or the same treatment with additional deep regional hyperthermia (n = 60). The two groups were compared with respect to local control, overall survival (OS), disease-free survival (DFS), and distant metastases-free survival (DMFS). RESULTS: Patients receiving additional hyperthermia had excellent long-term local control with a 5-year Kaplan-Meier estimate of 98% compared with 87% in the radiochemotherapy only group (p = 0.09). Five-year rates for OS (88% versus 76%, p = 0.08), DFS (77% versus 73%, p = n.s.) and DMFS (75% versus 77%, p = n.s.) were not statistically different between the two groups. CONCLUSION: Radiochemotherapy combined with hyperthermia results in excellent long-term local control.

Regional hyperthermia and moderately dose-escalated salvage radiotherapy for recurrent prostate cancer. Protocol of a phase II trial.

BACKGROUND: Current studies on salvage radiotherapy (sRT) investigate timing, dose-escalation and anti-hormonal treatment (ADT) for recurrent prostate cancer. These approaches could either be limited by radiation-related susceptibility of the anastomosis or by suspected side-effects of long-term ADT. A phase II protocol was developed to investigate the benefit and tolerability of regional hyperthermia with moderately dose-escalated radiotherapy. METHODS: The study hypothesis is that radio-thermotherapy is a safe and feasible salvage treatment modality. The primary endpoint is safety measured by frequency of grade 3+ genitourinary (GU) and gastrointestinal (GI) adverse events (AE) according to Common Toxicity Criteria (CTC) version 4. Feasibility is defined by number of hyperthermia treatments (n ≥ 7) and feasibility of radiotherapy according to protocol. Target volume delineation is performed according to the EORTC guidelines. Radiation treatment is administered with single doses of 2 Gy 5×/week to a total dose of 70 Gy. Regional hyperthermia is given 2×/week to a total of 10 treatments. RESULTS: European centres participate in the phase II trial using intensity modulated RT (IMRT) or volumetric modulated arc technique (VMAT). The initiating centres were participants of the SAKK 09/10 study, where the same patient criteria and target volume definition (mandatory successful performed dummy run) were applied insuring a high standardisation of the study procedures. CONCLUSIONS: The introduced phase II study implements highly precise image-guided radiotherapy and regional hyperthermia. If the phase II study is found to be safe and feasible, a multicenter phase III study is planned to test whether the addition of regional hyperthermia to dose-intensified sRT improves biochemical control.

Pathological complete response and sphincter-sparing surgery after neoadjuvant radiochemotherapy with regional hyperthermia for locally advanced rectal cancer compared with radiochemotherapy alone.

PURPOSE: To evaluate the influence of regional hyperthermia on rates of complete pathological response (pCR) and sphincter-sparing surgery in the context of an up-to-date radiochemotherapy protocol for locally advanced rectal cancer. METHODS: Between 2007 and 2010, 106 patients with locally advanced cancer of the middle and lower rectum were admitted to neoadjuvant radiochemotherapy either with (n = 61) or without (n = 45) regional hyperthermia. A retrospective comparison was performed between two groups: 45 patients received standard treatment consisting of 5040 cGy in 28 fractions to the pelvis and 5-fluorouracil (RCT group) and 61 patients received the same treatment in combination with regional hyperthermia (HRCT group). Target temperature was 40.5°C for at least 60 min. Total mesorectal excision was performed routinely. RESULTS: pCR was seen in 6.7% of patients in the RCT group and 16.4% in the HRCT group. Patients who received at least four hyperthermia treatments (n = 40) achieved a significantly higher pCR rate (22.5%) than the remaining 66 patients (p = 0.043). Rates of sphincter-sparing surgery were similar in both groups with 64% in the RCT group and 66% in HRCT. When considering only low-lying tumours located within 8 cm of the anal verge prior to treatment, the rate of sphincter-sparing surgery was 57% in the HRCT group compared with 35% in the RCT group (p = 0.077). CONCLUSION: The combination of regional hyperthermia and neoadjuvant radiochemotherapy may lead to an increased pCR rate in locally advanced rectal cancer. Patients with low-lying tumours especially may benefit when additional downsizing allows sphincter-preserving surgery.

Comparison of different adjuvant radiotherapy approaches in childhood bladder/prostate rhabdomyosarcoma treated with conservative surgery.

BACKGROUND AND PURPOSE: Multimodality treatment approaches provide high local control and satisfying overall survival (OS) for children with localized bladder and/or prostate rhabdomyosarcoma (BP-RMS). However, current strategies including surgery and conventional radiotherapy are compromised by high rates of long-term genitourinary adverse effects. Therefore, a planning study combining organ preserving surgery with three different innovative adjuvant radiotherapy approaches was performed. PATIENTS AND METHODS: A case of a 21-month-old boy with BP-RMS treated with polychemotherapy according to the CWS 2002-P protocol, prostatectomy, partial cystectomy, and adjuvant high dose rate brachytherapy (HDR-BT) was used to perform a planning study comparing HDR-BT with intensity-modulated radiotherapy (IMRT) and intensity-modulated proton therapy (IMPT) planning. RESULTS: All modalities provide good coverage of the target volume and spare critical normal tissues. Rectum doses could be reduced by 2/3 using IMPT and by 1/3 using BT compared to IMRT. In terms of sparing the pelvis growth plates, BT and IMPT are also superior to IMRT. CONCLUSION: All modalities provide good sparing of normal tissue. BT and IMPT are superior to IMRT with regard to doses on rectum and growth plates. BT is equivalent to IMPT in adequately selected tumors.

Quality assurance for clinical studies in regional deep hyperthermia.

BACKGROUND: A guideline is provided for the implementation of regional deep hyperthermia treatments under strict rules of quality assurance. The objective is to guarantee a comparable and comprehensible method in the treatment and scientific analysis of hyperthermia. The guideline describes regional deep hyperthermia (RHT) and MR-controlled partial body hyperthermia (PBH) of children, young and adult patients. According to this guideline, hyperthermia treatment is always applied in combination with chemotherapy and/or radiotherapy. METHODS: The guideline is based on practical experience from several hyperthermia centers. The procedure allows applying jointly coordinated standards and quality control in hyperthermia for studies. RESULTS: The guideline contains recommendations for hyperthermia treatments, including indication, preparation, treatment, and standardized analysis.

Experimental thermoradiotherapy in malignant hepatocellular carcinoma.

PURPOSE: The human liver is known to be a relatively radiosensitive organ that develops clinically relevant late radiation hepatitis subsequent to whole liver treatment with total doses above 30 Gy in conventional fractionation. Experimental data, as well as clinical series, have demonstrated that hyperthermia of solid tumors in addition to radiotherapy enhances tumor growth inhibition and tumor control probability. We therefore developed an experimental model for combined radiotherapy and hyperthermia of the liver in transplantable rat Morris hepatoma 3924A. METHODS AND MATERIALS: A cube of approximately 8 mm(3) was implanted subcapsularly into the middle liver lobe of 59 male syngenic ACI rats weighing approximately 180-200 g. On Day 16 after tumor implantation, irradiation of the tumor-bearing liver with either 0 Gy/25 Gy/35 Gy/45 Gy total dose in 10 fractions +/- hyperthermia (target temperature 40-42 degrees C) twice a week was initiated. Energy deposition was monitored by temperature probes in the liver and esophagus of the rats. Determination of tumor volume with magnetic resonance imaging was performed 2 to 5 weeks after the end of therapy. The tumor growth rates could be estimated for 44 rats. If the growth rate was positive (37 rats), the inverse of the growth rate was interpreted as the time to 10-fold tumor volume. Otherwise the maximum observation time was considered as a censored value in a parametric survival analysis. RESULTS: Intrahepatic temperature probes showed a temperature plateau of greater than 40 degrees C after 5 to 8 min subsequent to initiation of hyperthermia. The target temperatures could be maintained for at least 22 min > or =40 degrees C and 10 min > or =41 degrees C, respectively. Median plateau temperature in liver, esophagus, and epicutaneously was 41.2 degrees C (standard deviation [SD] 0.7 degrees C; range 38.2 to 43.3 degrees C), 40.4 degrees C (SD 1.08 degrees C; range 38.9 to 41.8 degrees C), and 40.8 degrees C (SD 0.8 degrees C; range 38.2 to 42.7 degrees C), respectively. Elevation of the temperature in the esophagus correlated with intrahepatic temperatures in the range of 39-42 degrees C, r = 0.957. The increase in time to 10-fold tumor volume for each step of irradiation dosage was by 34% (95% confidence interval [CI] 20% to 49%) without hyperthermia and by 60% (95% CI 47% to 80%) with hyperthermia (p < 0.0001). CONCLUSION: Treatment outcome after experimental percutaneous thermoradiotherapy in intrahepatically implanted Morris hepatoma 3924A was related to total dose of irradiation and concurrently administered regional hyperthermia. An increased radiosensitivity due to hyperthermia (<42 degrees C) has to be assumed.

Hyperfractionated 192Ir brachytherapy for recurrent retroperitoneal sarcoma: a technique for delivery of local tumor boost dose.

BACKGROUND: Radical surgery is the treatment of first choice for retroperitoneal sarcoma. However, locoregional relapse is frequently observed leading to death in the majority of patients. The role of radiotherapy is not well defined in the management of retroperitoneal sarcoma. Yet, there is evidence that adjuvant irradiation does improve local tumor control. MATERIAL AND METHODS: In order to deliver sufficiently high radiation doses to the retroperitoneum, different techniques for application of a local tumor boost dose in addition to external beam treatment have been proposed. We present a technique of hyperfractionated (192)Ir brachytherapy (HFIR) of the tumor bed via intraoperatively implanted plastic catheters. Postoperative CT-based image-guided brachytherapy was performed. In two consecutive patients with recurrent retroperitoneal sarcoma, treatment was delivered twice daily with single doses of 1.5-2.0 Gy in 5-10 mm tissue depth up to a total dose of 18-32.5 Gy. RESULTS: HFIR of the tumor bed was easily accomplished facilitating delivery of high radiation doses to the retroperitoneum. No major late effects of treatment have been observed with a follow-up of 15 and 28 months, respectively. Details of the brachytherapy procedure are presented. CONCLUSION: HFIR via intraoperatively implanted catheters in the retroperitoneum is a technique suitable for application of a local tumor boost dose. Thus, sufficiently high doses of radiation mandatory for long-lasting local tumor control can be delivered in the tumor bed of the retroperitoneum without exceeding normal tissue radiotolerance in this unfavorable disease.

[Physical and technical quality assurance and radiation protection in transperineal interstitial permanent prostate brachytherapy with 125-iodine seeds]. / Physikalisch-technische Qualitätssicherung und Strahlenschutz bei der Monotherapie der Prostata mit Jod-125-Seeds.

BACKGROUND: Early stage prostate cancer can be treated successfully by interstitial brachytherapy with 125-iodine seeds. A quality-assurance programme is presented that was designed for this purpose for internal clinical use. Furthermore the requirements of the new German Ordinance Governing Radiation Protection (StrlSchV) that came into force on August 1, 2001, are taken into account. MATERIAL AND METHODS: For the 125-iodine monotherapy of the prostate we used RAPID STRANDS (Amersham Health, Braunschweig, Germany). According to the guidelines of the new Ordinance Governing Radiation Protection, the determination of the body dose of the staff is made to rely on the new measurement quantities H(p) (10) and H(p) (0.07). The nominal air kerma rate of the seeds is measured with a calibrated well-chamber of the type HDR 1000 Plus and an electrometer of the type MAX 4000 (Standard Imaging Inc., USA). The ultrasound images of the prostate are produced by an ultrasound device of the type Falcon 2101 (B-K Medical, Denmark). For treatment planning the programme VariSeed (Varian, Darmstadt, Germany) was employed. Correct loading of the needles is controlled by autoradiography before implantation. After the implantation radiation-protection measurements in the operating room are carried out. RESULTS: As regards the personnel, for the depth personal dose equivalent Hp(10) and relating to two applications each, measurement values between 0 microSv and 14 microSv resulted. The control of the radiation exposure of the hands revealed superficial personal dose values H(p) (0.07) of up to 1 mSv. The nominal air kerma rates of the RAPID STRANDS were all lying within the 95% confidence interval guaranteed by the producer. The autoradiographs documented -- except for one case -- the correct loading of the needles. The interstitial transperineal prostate implantation of the 125-iodine seeds succeeded as planned with all patients. Until now no contamination of the operating room was detected by the radiation-protection measurements. CONCLUSION: The physical-technical quality assurance programme presented here covers the whole physical-technical range of the internal clinical quality assurance and could be integrated into the course of the treatment without any problems. It has th following advantages: The autoradiographic documentation of the correctly loaded needles serves as proof that the prerequisite for the production of the prescribed physical dose distribution is fulfilled. The internal clinical determination of the nominal air kerma rate is the basis for a correct dose application.

[Physical basics and clinical realization of interstitial brachytherapy of the prostate with iodine 125]. / Physikalische Grundlagen und klinische Durchführung der interstitiellen Brachytherapie der Prostata mit Jod-125.

BACKGROUND: Interstitial brachytherapy with I-125 seeds can be used for successful treatment of early stage prostate cancer. There is presented the technique of permanent transperineal implantation of I-125 seeds with intraoperative treatment planning which is suited for the treatment of prostate cancer up to the clinical stage of T2a. MATERIAL AND METHODS: Some weeks before the implantation of the seeds the prostate volume is determined using transrectal ultrasound (TRUS) so as to estimate the required number of I-125 seeds. At the outset of the treatment the prostate is stabilized by two perineally inserted needles. Subsequently there is carried out an ultrasound guided treatment planning that allows to optimize the distribution of the seeds within the prostate. In interstitial brachytherapy we use RAPID STRANDS((R)), i. e. the I-125 seeds are embedded in vicryl suture at distances of 1 cm. During implantation of the I-125 seeds the transversal placement of the applicator needles is controlled by TRUS and the cranio-caudal placement of the applicator needles is controlled using the fluoroscopic unit as well as TRUS. About 4 weeks after the implantation of the seeds there is carried out a postoperative computation of the dose distribution of the implant using CT imaging. RESULTS: The procedure possesses the advantage that ultrasound imaging, treatment planning and seed implantation are carried out with the prostate remaining in an unaltered position. During implantation the combined imaging of TRUS and fluoroscopy allows a safe placement of the seeds with in the prostate. CONCLUSION: The methods for the calculation of the actually attained dose distribution must still be optimized, because the postoperative examination of the individual results has so far been possible only with difficulties resulting from methodological inconveniences.