Regional deep hyperthermia: quantitative evaluation of predicted and direct measured temperature distributions in patients with high-risk extremity soft-tissue sarcoma.

BACKGROUND: Temperature distributions resulting from hyperthermia treatment of patients with high-risk soft-tissue sarcoma (STS) were quantitatively evaluated and globally compared with thermal simulations performed by a treatment planning system. The aim was to test whether the treatment planning system was able to predict correct temperature distributions. METHODS: Five patients underwent computed tomography (CT) fluoroscopy-guided placement of tumor catheters used for the interstitial temperature measurements. For the simulations, five 3 D patient models were reconstructed by segmenting the patient CT datasets into different tissues. The measured and simulated data were evaluated by calculating the temperature change ( ΔT ), T90, T50, T20, Tmean, Tmin and Tmax, as well as the 90th percentile thermal dose (CEM43T90). In order to measure the agreement between both methods quantitatively, the Bland-Altman analysis was applied. RESULTS: The absolute difference between measured and simulated temperatures were found to be 2°, 6°, 1°, 4°, 5° and 4 °C on average for Tmin, Tmax, T90, T50, T20 and Tmean, respectively. Furthermore, the thermal simulations exhibited relatively higher thermal dose compared to those that were measured. Finally, the results of the Bland-Altman analysis showed that the mean difference between both methods was above 2 °C which is considered to be clinically unacceptable. CONCLUSION: Given the current practical limitations on resolution of calculation grid, tissue properties, and perfusion information, the software SigmaHyperPlan™ is incapable to produce thermal simulations with sufficient correlation to typically heterogeneous tissue temperatures to be useful for clinical treatment planning.

MR-imaging changes of musculoskeletal soft-tissue sarcomas associated with neoadjuvant chemotherapy and hyperthermia.

PURPOSE: To evaluate early changes in musculoskeletal soft-tissue sarcomas under neoadjuvant chemotherapy combined with regional hyperthermia (RHT). PATIENTS AND METHODS: Nineteen consecutive patients with high-grade soft-tissue sarcomas of the musculoskeletal system were treated with neoadjuvant chemotherapy combined with RHT. Patients were imaged, using a high field MR-scanner, before onset of therapy, immediately after one and after four cycles of therapy. The images were evaluated for volume reduction and development of tumour necrosis. In addition, side effects such as surrounding soft-tissue oedema, bleeding and muscle or bone marrow necrosis were analysed. RESULTS: Tumour volume reduction was significant after the completion of neoadjuvant therapy (mean 49%, range 5-91%; (p < 0.001). Extent of tumour necrosis was also significantly different before (mean 22%) and after therapy (mean 58%, p < 0.001). Three patients showed strong tumour necrosis already after one cycle of treatment. Tumour volume reduction was not associated with the extent of pre-existing necrosis or necrosis development. The extent of tumour volume before start of therapy did not affect volume reduction or necrosis induction after therapy. Reduction of tumour oedema was significant after therapy (p < 0.001). No side effects were observed during thermochemotherapy. CONCLUSION: Neoadjuvant chemotherapy combined with RHT resulted in significant tumour volume reduction and induction of tumour necrosis, which can be detected early and monitored closely with MRI.

Treatment of primary, recurrent or inadequately resected high-risk soft-tissue sarcomas (STS) of adults: results of a phase II pilot study (RHT-95) of neoadjuvant chemotherapy combined with regional hyperthermia.

The efficacy of thermochemotherapy in adult patients with primary, recurrent or inadequately resected non-metastatic high-risk soft-tissue sarcomas (STS) was assessed. 54 patients were prospectively treated with four cycles of etoposide, ifosfamide and doxorubicin (EIA) combined with regional hyperthermia (RHT) followed by surgery, another four cycles of EIA without RHT and external beam radiation. The objective response rate was 16% and at a median follow-up time of 57 months, the 4-year estimated rates of local failure-free survival (LFFS), distant metastasis-free survival (DMFS), event-free survival (EFS) and overall survival (OS) were 59% (95% confidence interval (CI) 45-73%), 59% (95% CI 44-73%), 26% (95% CI 14-38%) and 40% (95% CI 27-53%), respectively. OS was in favour of patients responding to neoadjuvant treatment (P=0.073). In comparison to a preceding phase II study including pre- and postsurgical thermochemotherapy (RHT-91), at a 4-year follow-up the RHT-95 study cohort showed an inferior LFFS rate (P=0.027), but this did not affect DMFS (P=0.558) or OS (P=0.126). Hence, postsurgical thermochemotherapy seems critical for local tumour control without affecting survival.

[MRI-controlled regional hyperthermia]. / MRT-gesteuerte regionale Tiefenhyperthermie.

PURPOSE: Regional hyperthermia in combination with chemotherapy or/and radiotherapy is a promising treatment concept for locally advanced, deep-seated tumors. The purpose of the project is the optimization of the therapy using non-invasive, three-dimensional imaging of tissue changes or of the temperature distribution during regional hyperthermia. METHODS: MRI offers methods suitable in principle for tissue characterization and MR thermometry. A new MRI-hyperthermia hybrid system has been developed based on an innovative hyperthermia applicator and an open MRI system. RESULTS: After successful testing of the new MRI-hyperthermia hybrid system simultaneous MRI and regional hyperthermia in patients could be accomplished for the first time. At present the T1 relaxation time seems to be a promising parameter for MR thermometry. CONCLUSION: The first clinical application of the MRI-hyperthermia hybrid system can be regarded as an important step towards the development of regional hyperthermia. This new hybrid system and the MR thermometry methods have to be investigated prospectively in clinical studies.