Proximally located presacral recurrences of rectal carcinomas are known to be difficult to heat d... more Proximally located presacral recurrences of rectal carcinomas are known to be difficult to heat due to the complex anatomy of the pelvis, which reflect, shield and diffract the power. This study is to clarify whether a change of position of the Sigma-Eye applicator in this region can improve the heating. Finite element (FE) planning calculations were made for a phantom model with a proximal presacral tumour using a fixed 100 MHz radiofrequency radiation. Shifts of the applicator were simulated in 1 cm steps in x-(lateral), y-(posterior) and z-(longitudinal) direction. Computations also considered the network effects of the Sigma-Eye applicator. Optimisation of the phases and amplitudes for all positions were performed after solving the bioheat-transfer-equation. The parameters T90, T50, sensitivity, hot spot volume and total deposited power have been sampled for every applicator position with optimised plans and a standard plan. The ability to heat a presacral tumour clearly depends on the applicator position, for standard antenna adjustment and also for optimised steering of the Sigma-Eye applicator. The gamma-direction (anterior-posterior) is very sensitive. Using optimised steering for each position, in z-direction (longitudinal), we found an unexpected additional optimum at 8 cm cranial from the middle position of the phantom. The x-direction (lateral) is in a clinical setting less important and shows only smaller changes of T90 with an expected optimum in the central position. A positioning of the applicator in the axial and anterior position of the mid-pubic symphysis should be avoided for treatment of the presacral region, regardless of the used adjustment. Use of amplitude and phase optimisation yields better T90 values than plans optimised only by phases, but they are much more sensitive for small variations of phases and amplitudes during a treatment, and the total power of the Sigma-Eye applicator can be restricted by the treatment software. Complex geometry of the human pelvis seems to be the reason for the difficulties to warm up the proximal presacral region. The assumption that every position can be balanced by a proper phase adaption, is true only in a small range. A centring of the applicator on the mid-pubic symphysis to heat this region should be avoided. From the practical point of view improved warming should be performed by optimisation of phases only.
International Journal of Radiation Oncology Biology Physics, 1998
Purpose: Invasive thermometry for regional hyperthermia is time-consuming, uncomfortable, and ris... more Purpose: Invasive thermometry for regional hyperthermia is time-consuming, uncomfortable, and risky for the patient. We tried to estimate the benefit/cost ratio of invasive thermometry in regional hyperthermia using the radiofrequency system BSD-2000.Methods and Materials: We evaluated 182 patients with locally advanced pelvic tumors that underwent regional hyperthermia. In every patient a tumor-related temperature measurement point was obtained either by invasive
A measurement device for noninvasive and simultaneous control of antennas during regional radiofr... more A measurement device for noninvasive and simultaneous control of antennas during regional radiofrequency (rf) hyperthermia and, subsequently, the estimation of the power distribution in the interior of patients are essential preconditions for further technological progress. Aiming at this, the feasibility of an electro-optical electric field sensor was investigated during clinical rf hyperthermia. The electro-optical electric field (E-field) sensor is based on lithiumniobate crystals and the Mach-Zehnder interferometer structure, and was tested in an earlier phantom study. For this study, a mechanical scanning device was developed allowing the registration of the E-field during clinical application. Data were recorded along a curve in the water bolus of the SIGMA 60 applicator of the annular phased-array system BSD-2000 (BSD Medical Corp., Salt Lake City, UT) close to the base points of the flat biconical dipole antennas. The results were compared with modeling calculations using the finite-difference time-domain (FDTD) method. For the latter, different antenna models were assumed. For systematic registration of the E-field curves in amplitude and phase, we employed an elliptical lamp phantom with fat-equivalent ring (filled with saline solution) and an elliptical polyacrylamide phantom with acrylic glass wall. Further measurements were carried out during the treatment of 5 patients with 20 hyperthermia treatments. Data of both phantom and patient measurements can be satisfactorily described by the FDTD method, if the antenna model is refined by taking into account the conical form of the dipoles and the special dielectric environment of the feeding point. Phase deviations can be entered ex posteriori for correction in the calculation algorithm. A comparison of amplifier power measurement (forward and backward power) and bolus E-field scans near the antenna base points demonstrates that E-field measurements between antennas and patient are a necessity for the appropriate characterization of antenna radiation properties. These measurements are sensitive to variations of the lossy medium in position and shape, and can be correctly predicted with current models. However, the differences between different patients are moderate and unspecific in both calculations and measurements, with fluctuations at maximum of 30 degrees in phases and 40% in amplitudes. The measurement method presented here turned out to be a practical tool for online registration of E-fields in phases and amplitudes along arbitrary curves in a water bolus or phantom. It can be utilized to evaluate antenna design and modeling calculations and leads, thus, to a better understanding of complicated multiantenna systems. In clinical routine, it can be employed as input for patient-specific hyperthermia planning and, finally, for the realization of online control with subsequent optimization of the power distribution in the patient.
ABSTRACT Die Hyperthermie (Wärmetherapie) hat bisher keinen Eingang in die onkologische Standardt... more ABSTRACT Die Hyperthermie (Wärmetherapie) hat bisher keinen Eingang in die onkologische Standardtherapie gefunden. Sie bietet jedoch große onkologische Potenziale, da sie gut verträglich ist und sowohl die Radiotherapie als auch die Chemotherapie bei vielen Ausbreitungsstadien verstärken kann. Für das lokal fortgeschrittene Zervixkarzinom (im Stadium ≥FIGO IIB) wurden mehrere randomisierte Studien durchgeführt, in denen die höhere lokale Wirksamkeit der hyperthermen Radiotherapie im Vergleich zur Standardradiotherapie belegt werden konnte. Der Einfluss der Hyperthermie auf die Radiochemotherapie wird nun in einer internationalen prospektiven Studie geprüft. Auch die präoperative trimodale Anwendung wurde in einer Phase-II-Studie evaluiert. Darüber hinaus gibt es neuere technologische Entwicklungen in der Hyperthermie (Hybridhyperthermie, Nanotherapie und Teilkörperhyperthermie), die insbesondere eine Anwendung in der Behandlung des rezidivierenden Zervixkarzinoms ermöglichen (Beckenwandrezidiv und/oder peritoneale Ausbreitung).
Hyperthermia, one of the oldest forms of cancer treatment involves selective heating of tumor tis... more Hyperthermia, one of the oldest forms of cancer treatment involves selective heating of tumor tissues to temperatures ranging between 39 and 45°C. Recent developments based on the thermoradiobiological rationale of hyperthermia indicate it to be a potent radio- and chemosensitizer. This has been further corroborated through positive clinical outcomes in various tumor sites using thermoradiotherapy or thermoradiochemotherapy approaches. Moreover, being devoid of any additional significant toxicity, hyperthermia has been safely used with low or moderate doses of reirradiation for retreatment of previously treated and recurrent tumors, resulting in significant tumor regression. Recent in vitro and in vivo studies also indicate a unique immunomodulating prospect of hyperthermia, especially when combined with radiotherapy. In addition, the technological advances over the last decade both in hardware and software have led to potent and even safer loco-regional hyperthermia treatment deliv...
Cancer Management in Man: Chemotherapy, Biological Therapy, Hyperthermia and Supporting Measures, 2010
Page 1. Chapter 21 Induced Hyperthermia in the Treatment of Cancer Bert Hildebrandt,Johanna Gelle... more Page 1. Chapter 21 Induced Hyperthermia in the Treatment of Cancer Bert Hildebrandt,Johanna Gellermann, Hanno Riess, and Peter Wust 21.1 Basic Principles of Clinical Hyperthermia 21.1.1 Classification of Hyperthermia Techniques ...
The synergistic effects of hyperthermia (raising temperatures to 40 degrees C and above) when com... more The synergistic effects of hyperthermia (raising temperatures to 40 degrees C and above) when combined with radiotherapy and cytotoxic drugs and a modulation of immunological phenomena have been demonstrated in the laboratory. Pre-clinical data relating to hyperthermia are summed up, along with their implications for clinical application. Controlled studies of local and regional hyperthermia have been performed during recent years, and these show us that the adjunction of hyperthermia provides at least an improvement of local control compared with radiotherapy alone. Current clinical results are summarized. Therapy systems based on radiowave irradiation have been commercially available for regional hyperthermia of the pelvis since the mid 1980s. This technology allows us to perform sufficiently tolerable and effective regional hyperthermia on rectal carcinomas. Used as part of curative preoperative and postoperative multimodal therapeutic strategies, hyperthermia can lead to improvement in local control (resectability, down-staging, progression-free time, recurrence rate), at least for certain risk groups. The preoperative radio-chemo-thermotherapy of advanced primary and recurring rectal carcinoma, uT3/4, was tested in a phase-I/II study of 20 patients. Therapy procedure, acute toxicity, thermal parameters, and response are described and discussed for this patient group. The regimen proved to be sufficiently tolerable, and complications did not occur. Tumor resection was performed on 14 of the 20 patients; 13 of the procedures were R0-resections and one was an R2 resection. In 64% of the resected rectal carcinomas, histopathological down-staging of the pretherapeutic endosonographical stadium was achieved; in three of the patients, despite continued non-resectability, local control has now been maintained for more than 12 months. In two patients with nonresectable rectal carcinomas, local progress was seen during the neoadjuvant combination therapy.
Magnetic Resonance Materials in Physics, Biology and Medicine, 2014
To develop and test in a clinical setting a double-echo segmented echo planar imaging (DEPI) puls... more To develop and test in a clinical setting a double-echo segmented echo planar imaging (DEPI) pulse sequence for proton resonance frequency (PRF)-based temperature monitoring that is faster than conventional PRF thermometry pulse sequences and not affected by thermal changes in tissue conductivity. Four tumor patients underwent between one and nine magnetic resonance (MR)-guided regional hyperthermia treatments. During treatment, the DEPI sequence and a FLASH PRF sequence were run in an interleaved manner to compare the results from both sequences in the same patients and same settings. Temperature maps were calculated based on the phase data of both sequences. Temperature measurements of both techniques were compared using Passing and Bablok regression and the Bland-Altman method. The temperature results from the DEPI and FLASH sequences, on average, do not differ by more than ΔT = 1 °C. DEPI images showed typically more artifacts and approximately a twofold lower signal-to-noise ratio (SNR), but a sufficient temperature precision of 0.5°, which would theoretically allow for a fivefold higher frame rate. The results indicate that DEPI can replace slower temperature measurement techniques for PRF-based temperature monitoring during thermal treatments. The higher acquisition speed can be exploited for hot spot localization during regional hyperthermia as well as for temperature monitoring during fast thermal therapies.
The method to acquire MR-temperature datasets by the proton-resonance-shift method is outlined an... more The method to acquire MR-temperature datasets by the proton-resonance-shift method is outlined and verified in phantoms and patients. An online adaptation process has been developed to achieve agreement between planning calculations and MR-temperature measurements. This is used as a basis to optimize the pattern by a control loop. This procedure is successful after the second iteration step in phantoms. In patients an increase of SAR (specific absorption rate) in the tumor relative to the surroundings has been demonstrated for the MR-temperature increase as optimization variable. The optimization results are even improved under clinical conditions, if perfusion and thermal conduction are considered during the optimization procedure. The mathematical background is presented.
International Journal of Radiation Oncology*Biology*Physics, 2003
The main aim is to prove the clinical practicability of the hyperthermia treatment planning syste... more The main aim is to prove the clinical practicability of the hyperthermia treatment planning system HyperPlan on a beta-test level. Data and observations obtained from clinical hyperthermia are compared with the numeric methods FE (finite element) and FDTD (finite difference time domain), respectively. The planning system HyperPlan is built on top of the modular, object-oriented platform for visualization and model generation AMIRA. This system already contains powerful algorithms for image processing, geometric modeling, and three-dimensional graphics display. A number of hyperthermia-specific modules are provided, enabling the creation of three-dimensional tetrahedral patient models suitable for treatment planning. Two numeric methods, FE and FDTD, are implemented in HyperPlan for solving Maxwell's equations. Both methods base their calculations on segmented (contour based) CT or MR image data. A tetrahedral grid is generated from the segmented tissue boundaries, consisting of approximately 80,000 tetrahedrons per patient. The FE method necessitates, primarily, this tetrahedral grid for the calculation of the E-field. The FDTD method, on the other hand, calculates the E-field on a cubical grid, but also requires a tetrahedral grid for correction at electrical interfaces. In both methods, temperature distributions are calculated on the tetrahedral grid by solving the bioheat transfer equation with the FE method. Segmentation, grid generation, E-field, and temperature calculation can be carried out in clinical practice at an acceptable time expenditure of about 1-2 days. All 30 patients we analyzed with cervical, rectal, and prostate carcinoma exhibit a good correlation between the model calculations and the attained clinical data regarding acute toxicity (hot spots), prediction of easy-to-heat or difficult-to-heat patients, and the dependency on various other individual parameters. We could show sufficient agreement between the calculations and measurements for power density (specific absorption rate) within the range of assessed precision. Tumor temperatures can only be estimated, because of the rather variable perfusion conditions. The results of the FE and FDTD methods are comparable, although slight differences exist resulting from the differences in the underlying models. There are also statistically provable differences among the tumor entities regarding the attained specific absorption rate, temperatures, and volume loads in normal tissue. However, gross fluctuations exist from patient to patient. The hyperthermia planning system HyperPlan could be validated for a number of the 30 patients. Further improvements in the implemented models, FE and FDTD, are required. Even at its present state of development, hyperthermia planning for regional hyperthermia delivers valuable information, not only for clinical practice, but also for further technologic improvements.
Peritoneal carcinomatosis is a stage of gynecological and gastrointestinal malignancies with poor... more Peritoneal carcinomatosis is a stage of gynecological and gastrointestinal malignancies with poor prognosis. Options for enhancing the effect of standard chemotherapy, such as aggressive surgery and intraperitoneal chemotherapy, have limitations. In this phase I/II study, we evaluated regional hyperthermia of the pelvis and abdomen using the annular-phased-array technique as an adjunct to chemotherapy. Forty-five patients with peritoneal carcinomatosis (with or without liver metastases) in colorectal cancer (CRC) (n = 16), ovarian cancer (OC) (n = 17), or gastric/pancreatic/biliary cancer (n = 12) underwent standard chemotherapy and regional hyperthermia. Most CRC patients received second-line chemotherapy. All OC patients were platinum resistant. Regional hyperthermia was applied using a SIGMA-60 applicator (OC), a SIGMA-Eye/MR applicator (CRC), or various ring applicators (gastric/pancreatic/biliary cancer). Abdominal regional hyperthermia was well tolerated, with acceptable acute discomfort and no long-term morbidity. The SIGMA-Eye/MR applicator achieved higher systemic temperatures (associated with higher systemic stress) and more effective heating of the upper abdomen; the SIGMA-60 applicator achieved higher temperatures (and power densities) in the pelvis. Three-year overall survival was encouraging for patients with CRC (22%) and OC (29%) but not gastric/pancreatic/biliary cancer. For the SIGMA-60 applicator (patients with OC), higher measured temperatures at the vaginal stump correlated with better outcome. CONCLUSIONS. The SIGMA-60 and SIGMA-Eye/MR applicators are feasible for abdominal heating and have low toxicity. The SIGMA-60 applicator is specifically suitable for malignancies with high pelvic burden; the SIGMA-Eye/MR applicator better heats the upper abdomen, including the liver. Further randomized investigations are warranted.
Proximally located presacral recurrences of rectal carcinomas are known to be difficult to heat d... more Proximally located presacral recurrences of rectal carcinomas are known to be difficult to heat due to the complex anatomy of the pelvis, which reflect, shield and diffract the power. This study is to clarify whether a change of position of the Sigma-Eye applicator in this region can improve the heating. Finite element (FE) planning calculations were made for a phantom model with a proximal presacral tumour using a fixed 100 MHz radiofrequency radiation. Shifts of the applicator were simulated in 1 cm steps in x-(lateral), y-(posterior) and z-(longitudinal) direction. Computations also considered the network effects of the Sigma-Eye applicator. Optimisation of the phases and amplitudes for all positions were performed after solving the bioheat-transfer-equation. The parameters T90, T50, sensitivity, hot spot volume and total deposited power have been sampled for every applicator position with optimised plans and a standard plan. The ability to heat a presacral tumour clearly depends on the applicator position, for standard antenna adjustment and also for optimised steering of the Sigma-Eye applicator. The gamma-direction (anterior-posterior) is very sensitive. Using optimised steering for each position, in z-direction (longitudinal), we found an unexpected additional optimum at 8 cm cranial from the middle position of the phantom. The x-direction (lateral) is in a clinical setting less important and shows only smaller changes of T90 with an expected optimum in the central position. A positioning of the applicator in the axial and anterior position of the mid-pubic symphysis should be avoided for treatment of the presacral region, regardless of the used adjustment. Use of amplitude and phase optimisation yields better T90 values than plans optimised only by phases, but they are much more sensitive for small variations of phases and amplitudes during a treatment, and the total power of the Sigma-Eye applicator can be restricted by the treatment software. Complex geometry of the human pelvis seems to be the reason for the difficulties to warm up the proximal presacral region. The assumption that every position can be balanced by a proper phase adaption, is true only in a small range. A centring of the applicator on the mid-pubic symphysis to heat this region should be avoided. From the practical point of view improved warming should be performed by optimisation of phases only.
International Journal of Radiation Oncology Biology Physics, 1998
Purpose: Invasive thermometry for regional hyperthermia is time-consuming, uncomfortable, and ris... more Purpose: Invasive thermometry for regional hyperthermia is time-consuming, uncomfortable, and risky for the patient. We tried to estimate the benefit/cost ratio of invasive thermometry in regional hyperthermia using the radiofrequency system BSD-2000.Methods and Materials: We evaluated 182 patients with locally advanced pelvic tumors that underwent regional hyperthermia. In every patient a tumor-related temperature measurement point was obtained either by invasive
A measurement device for noninvasive and simultaneous control of antennas during regional radiofr... more A measurement device for noninvasive and simultaneous control of antennas during regional radiofrequency (rf) hyperthermia and, subsequently, the estimation of the power distribution in the interior of patients are essential preconditions for further technological progress. Aiming at this, the feasibility of an electro-optical electric field sensor was investigated during clinical rf hyperthermia. The electro-optical electric field (E-field) sensor is based on lithiumniobate crystals and the Mach-Zehnder interferometer structure, and was tested in an earlier phantom study. For this study, a mechanical scanning device was developed allowing the registration of the E-field during clinical application. Data were recorded along a curve in the water bolus of the SIGMA 60 applicator of the annular phased-array system BSD-2000 (BSD Medical Corp., Salt Lake City, UT) close to the base points of the flat biconical dipole antennas. The results were compared with modeling calculations using the finite-difference time-domain (FDTD) method. For the latter, different antenna models were assumed. For systematic registration of the E-field curves in amplitude and phase, we employed an elliptical lamp phantom with fat-equivalent ring (filled with saline solution) and an elliptical polyacrylamide phantom with acrylic glass wall. Further measurements were carried out during the treatment of 5 patients with 20 hyperthermia treatments. Data of both phantom and patient measurements can be satisfactorily described by the FDTD method, if the antenna model is refined by taking into account the conical form of the dipoles and the special dielectric environment of the feeding point. Phase deviations can be entered ex posteriori for correction in the calculation algorithm. A comparison of amplifier power measurement (forward and backward power) and bolus E-field scans near the antenna base points demonstrates that E-field measurements between antennas and patient are a necessity for the appropriate characterization of antenna radiation properties. These measurements are sensitive to variations of the lossy medium in position and shape, and can be correctly predicted with current models. However, the differences between different patients are moderate and unspecific in both calculations and measurements, with fluctuations at maximum of 30 degrees in phases and 40% in amplitudes. The measurement method presented here turned out to be a practical tool for online registration of E-fields in phases and amplitudes along arbitrary curves in a water bolus or phantom. It can be utilized to evaluate antenna design and modeling calculations and leads, thus, to a better understanding of complicated multiantenna systems. In clinical routine, it can be employed as input for patient-specific hyperthermia planning and, finally, for the realization of online control with subsequent optimization of the power distribution in the patient.
ABSTRACT Die Hyperthermie (Wärmetherapie) hat bisher keinen Eingang in die onkologische Standardt... more ABSTRACT Die Hyperthermie (Wärmetherapie) hat bisher keinen Eingang in die onkologische Standardtherapie gefunden. Sie bietet jedoch große onkologische Potenziale, da sie gut verträglich ist und sowohl die Radiotherapie als auch die Chemotherapie bei vielen Ausbreitungsstadien verstärken kann. Für das lokal fortgeschrittene Zervixkarzinom (im Stadium ≥FIGO IIB) wurden mehrere randomisierte Studien durchgeführt, in denen die höhere lokale Wirksamkeit der hyperthermen Radiotherapie im Vergleich zur Standardradiotherapie belegt werden konnte. Der Einfluss der Hyperthermie auf die Radiochemotherapie wird nun in einer internationalen prospektiven Studie geprüft. Auch die präoperative trimodale Anwendung wurde in einer Phase-II-Studie evaluiert. Darüber hinaus gibt es neuere technologische Entwicklungen in der Hyperthermie (Hybridhyperthermie, Nanotherapie und Teilkörperhyperthermie), die insbesondere eine Anwendung in der Behandlung des rezidivierenden Zervixkarzinoms ermöglichen (Beckenwandrezidiv und/oder peritoneale Ausbreitung).
Hyperthermia, one of the oldest forms of cancer treatment involves selective heating of tumor tis... more Hyperthermia, one of the oldest forms of cancer treatment involves selective heating of tumor tissues to temperatures ranging between 39 and 45°C. Recent developments based on the thermoradiobiological rationale of hyperthermia indicate it to be a potent radio- and chemosensitizer. This has been further corroborated through positive clinical outcomes in various tumor sites using thermoradiotherapy or thermoradiochemotherapy approaches. Moreover, being devoid of any additional significant toxicity, hyperthermia has been safely used with low or moderate doses of reirradiation for retreatment of previously treated and recurrent tumors, resulting in significant tumor regression. Recent in vitro and in vivo studies also indicate a unique immunomodulating prospect of hyperthermia, especially when combined with radiotherapy. In addition, the technological advances over the last decade both in hardware and software have led to potent and even safer loco-regional hyperthermia treatment deliv...
Cancer Management in Man: Chemotherapy, Biological Therapy, Hyperthermia and Supporting Measures, 2010
Page 1. Chapter 21 Induced Hyperthermia in the Treatment of Cancer Bert Hildebrandt,Johanna Gelle... more Page 1. Chapter 21 Induced Hyperthermia in the Treatment of Cancer Bert Hildebrandt,Johanna Gellermann, Hanno Riess, and Peter Wust 21.1 Basic Principles of Clinical Hyperthermia 21.1.1 Classification of Hyperthermia Techniques ...
The synergistic effects of hyperthermia (raising temperatures to 40 degrees C and above) when com... more The synergistic effects of hyperthermia (raising temperatures to 40 degrees C and above) when combined with radiotherapy and cytotoxic drugs and a modulation of immunological phenomena have been demonstrated in the laboratory. Pre-clinical data relating to hyperthermia are summed up, along with their implications for clinical application. Controlled studies of local and regional hyperthermia have been performed during recent years, and these show us that the adjunction of hyperthermia provides at least an improvement of local control compared with radiotherapy alone. Current clinical results are summarized. Therapy systems based on radiowave irradiation have been commercially available for regional hyperthermia of the pelvis since the mid 1980s. This technology allows us to perform sufficiently tolerable and effective regional hyperthermia on rectal carcinomas. Used as part of curative preoperative and postoperative multimodal therapeutic strategies, hyperthermia can lead to improvement in local control (resectability, down-staging, progression-free time, recurrence rate), at least for certain risk groups. The preoperative radio-chemo-thermotherapy of advanced primary and recurring rectal carcinoma, uT3/4, was tested in a phase-I/II study of 20 patients. Therapy procedure, acute toxicity, thermal parameters, and response are described and discussed for this patient group. The regimen proved to be sufficiently tolerable, and complications did not occur. Tumor resection was performed on 14 of the 20 patients; 13 of the procedures were R0-resections and one was an R2 resection. In 64% of the resected rectal carcinomas, histopathological down-staging of the pretherapeutic endosonographical stadium was achieved; in three of the patients, despite continued non-resectability, local control has now been maintained for more than 12 months. In two patients with nonresectable rectal carcinomas, local progress was seen during the neoadjuvant combination therapy.
Magnetic Resonance Materials in Physics, Biology and Medicine, 2014
To develop and test in a clinical setting a double-echo segmented echo planar imaging (DEPI) puls... more To develop and test in a clinical setting a double-echo segmented echo planar imaging (DEPI) pulse sequence for proton resonance frequency (PRF)-based temperature monitoring that is faster than conventional PRF thermometry pulse sequences and not affected by thermal changes in tissue conductivity. Four tumor patients underwent between one and nine magnetic resonance (MR)-guided regional hyperthermia treatments. During treatment, the DEPI sequence and a FLASH PRF sequence were run in an interleaved manner to compare the results from both sequences in the same patients and same settings. Temperature maps were calculated based on the phase data of both sequences. Temperature measurements of both techniques were compared using Passing and Bablok regression and the Bland-Altman method. The temperature results from the DEPI and FLASH sequences, on average, do not differ by more than ΔT = 1 °C. DEPI images showed typically more artifacts and approximately a twofold lower signal-to-noise ratio (SNR), but a sufficient temperature precision of 0.5°, which would theoretically allow for a fivefold higher frame rate. The results indicate that DEPI can replace slower temperature measurement techniques for PRF-based temperature monitoring during thermal treatments. The higher acquisition speed can be exploited for hot spot localization during regional hyperthermia as well as for temperature monitoring during fast thermal therapies.
The method to acquire MR-temperature datasets by the proton-resonance-shift method is outlined an... more The method to acquire MR-temperature datasets by the proton-resonance-shift method is outlined and verified in phantoms and patients. An online adaptation process has been developed to achieve agreement between planning calculations and MR-temperature measurements. This is used as a basis to optimize the pattern by a control loop. This procedure is successful after the second iteration step in phantoms. In patients an increase of SAR (specific absorption rate) in the tumor relative to the surroundings has been demonstrated for the MR-temperature increase as optimization variable. The optimization results are even improved under clinical conditions, if perfusion and thermal conduction are considered during the optimization procedure. The mathematical background is presented.
International Journal of Radiation Oncology*Biology*Physics, 2003
The main aim is to prove the clinical practicability of the hyperthermia treatment planning syste... more The main aim is to prove the clinical practicability of the hyperthermia treatment planning system HyperPlan on a beta-test level. Data and observations obtained from clinical hyperthermia are compared with the numeric methods FE (finite element) and FDTD (finite difference time domain), respectively. The planning system HyperPlan is built on top of the modular, object-oriented platform for visualization and model generation AMIRA. This system already contains powerful algorithms for image processing, geometric modeling, and three-dimensional graphics display. A number of hyperthermia-specific modules are provided, enabling the creation of three-dimensional tetrahedral patient models suitable for treatment planning. Two numeric methods, FE and FDTD, are implemented in HyperPlan for solving Maxwell's equations. Both methods base their calculations on segmented (contour based) CT or MR image data. A tetrahedral grid is generated from the segmented tissue boundaries, consisting of approximately 80,000 tetrahedrons per patient. The FE method necessitates, primarily, this tetrahedral grid for the calculation of the E-field. The FDTD method, on the other hand, calculates the E-field on a cubical grid, but also requires a tetrahedral grid for correction at electrical interfaces. In both methods, temperature distributions are calculated on the tetrahedral grid by solving the bioheat transfer equation with the FE method. Segmentation, grid generation, E-field, and temperature calculation can be carried out in clinical practice at an acceptable time expenditure of about 1-2 days. All 30 patients we analyzed with cervical, rectal, and prostate carcinoma exhibit a good correlation between the model calculations and the attained clinical data regarding acute toxicity (hot spots), prediction of easy-to-heat or difficult-to-heat patients, and the dependency on various other individual parameters. We could show sufficient agreement between the calculations and measurements for power density (specific absorption rate) within the range of assessed precision. Tumor temperatures can only be estimated, because of the rather variable perfusion conditions. The results of the FE and FDTD methods are comparable, although slight differences exist resulting from the differences in the underlying models. There are also statistically provable differences among the tumor entities regarding the attained specific absorption rate, temperatures, and volume loads in normal tissue. However, gross fluctuations exist from patient to patient. The hyperthermia planning system HyperPlan could be validated for a number of the 30 patients. Further improvements in the implemented models, FE and FDTD, are required. Even at its present state of development, hyperthermia planning for regional hyperthermia delivers valuable information, not only for clinical practice, but also for further technologic improvements.
Peritoneal carcinomatosis is a stage of gynecological and gastrointestinal malignancies with poor... more Peritoneal carcinomatosis is a stage of gynecological and gastrointestinal malignancies with poor prognosis. Options for enhancing the effect of standard chemotherapy, such as aggressive surgery and intraperitoneal chemotherapy, have limitations. In this phase I/II study, we evaluated regional hyperthermia of the pelvis and abdomen using the annular-phased-array technique as an adjunct to chemotherapy. Forty-five patients with peritoneal carcinomatosis (with or without liver metastases) in colorectal cancer (CRC) (n = 16), ovarian cancer (OC) (n = 17), or gastric/pancreatic/biliary cancer (n = 12) underwent standard chemotherapy and regional hyperthermia. Most CRC patients received second-line chemotherapy. All OC patients were platinum resistant. Regional hyperthermia was applied using a SIGMA-60 applicator (OC), a SIGMA-Eye/MR applicator (CRC), or various ring applicators (gastric/pancreatic/biliary cancer). Abdominal regional hyperthermia was well tolerated, with acceptable acute discomfort and no long-term morbidity. The SIGMA-Eye/MR applicator achieved higher systemic temperatures (associated with higher systemic stress) and more effective heating of the upper abdomen; the SIGMA-60 applicator achieved higher temperatures (and power densities) in the pelvis. Three-year overall survival was encouraging for patients with CRC (22%) and OC (29%) but not gastric/pancreatic/biliary cancer. For the SIGMA-60 applicator (patients with OC), higher measured temperatures at the vaginal stump correlated with better outcome. CONCLUSIONS. The SIGMA-60 and SIGMA-Eye/MR applicators are feasible for abdominal heating and have low toxicity. The SIGMA-60 applicator is specifically suitable for malignancies with high pelvic burden; the SIGMA-Eye/MR applicator better heats the upper abdomen, including the liver. Further randomized investigations are warranted.
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Papers by J. Gellermann