Treatment planning facilitates clinical decision making for hyperthermia treatments.

Background: Treatment quality is important in clinical hyperthermia. Guideline-based treatment protocols are used to determine system settings and treatment strategies to ensure effective tumor heating and prevent unwanted treatment-limiting normal tissue hot spots. Realizing both these goals can prove challenging using generic guideline-based and operator-dependent treatment strategies. Hyperthermia treatment planning (HTP) can be very useful to support treatment strategies. Although HTP is increasingly integrated into the standard clinical workflow, active clinical application is still limited to a small number of hyperthermia centers and should be further stimulated.Purpose: This paper aims to serve as a practical guide, demonstrating how HTP can be applied in clinical decision making for both superficial and locoregional hyperthermia treatments.HTP in clinical decision making: Seven problems that occur in daily clinical practice are described and we show how HTP can enhance insight to formulate an adequate treatment strategy. Examples use representative commercially available hyperthermia devices and cover all stages during the clinical workflow. Problems include selecting adequate phase settings, heating ability analysis, hot spot suppression, applicator selection, evaluation of target coverage and heating depth, and predicting possible thermal toxicity in case of an implant. Since we aim to promote a general use of HTP in daily practice, basic simulation strategies are used in these problems, avoiding a need for the application of dedicated advanced optimization routines that are not generally available.Conclusion: Even fairly basic HTP can facilitate clinical decision making, providing a meaningful and clinically relevant contribution to maintaining and improving treatment quality.

Current state of the art of regional hyperthermia treatment planning: a review.

Locoregional hyperthermia, i.e. increasing the tumor temperature to 40-45 °C using an external heating device, is a very effective radio and chemosensitizer, which significantly improves clinical outcome. There is a clear thermal dose-effect relation, but the pursued optimal thermal dose of 43 °C for 1 h can often not be realized due to treatment limiting hot spots in normal tissue. Modern heating devices have a large number of independent antennas, which provides flexible power steering to optimize tumor heating and minimize hot spots, but manual selection of optimal settings is difficult. Treatment planning is a very valuable tool to improve locoregional heating. This paper reviews the developments in treatment planning software for tissue segmentation, electromagnetic field calculations, thermal modeling and optimization techniques. Over the last decade, simulation tools have become more advanced. On-line use has become possible by implementing algorithms on the graphical processing unit, which allows real-time computations. The number of applications using treatment planning is increasing rapidly and moving on from retrospective analyses towards assisting prospective clinical treatment strategies. Some clinically relevant applications will be discussed.

Intensity-modulated and image-guided radiotherapy in patients with locally advanced inoperable pancreatic cancer after preradiation chemotherapy.

BACKGROUND: Radiotherapy (RT) in patients with pancreatic cancer is still a controversial subject and its benefit in inoperable stages of locally advanced pancreatic cancer (LAPC), even after induction chemotherapy, remains unclear. Modern radiation techniques such as image-guided radiotherapy (IGRT) and intensity-modulated radiotherapy (IMRT) may improve effectiveness and reduce radiotherapy-related toxicities. METHODS: Patients with LAPC who underwent radiotherapy after chemotherapy between 09/2004 and 05/2013 were retrospectively analyzed with regard to preradiation chemotherapy (PRCT), modalities of radiotherapy, and toxicities. Progression-free (PFS) and overall survival (OS) were estimated by Kaplan-Meier curves. RESULTS: 15 (68%) women and 7 men (median age 64 years; range 40-77) were identified. Median duration of PRCT was 11.1 months (range 4.3-33.0). Six patients (27%) underwent conventional RT and 16 patients (73%) advanced IMRT and IGRT; median dosage was 50.4 (range 9-54) Gray. No grade III or IV toxicities occurred. Median PFS (estimated from the beginning of RT) was 5.8 months, 2.6 months in the conventional RT group (conv-RT), and 7.1 months in the IMRT/IGRT group (P = 0.029); median OS was 11.0 months, 4.2 months (conv-RT), and 14.0 months (IMRT/IGRT); P = 0.141. Median RT-specific PFS for patients with prolonged PRCT > 9 months was 8.5 months compared to 5.6 months for PRCT < 9 months (P = 0.293). This effect was translated into a significantly better median RT-specific overall survival of patients in the PRCT > 9 months group, with 19.0 months compared to 8.5 months in the PRCT < 9 months group (P = 0.049). CONCLUSIONS: IGRT and IMRT after PRCT are feasible and effective options for patients with LAPC after prolonged preradiation chemotherapy.

Unresectable colorectal liver metastases: percutaneous ablation using CT-guided high-dose-rate brachytherapy (CT-HDBRT).

PURPOSE: To evaluate the clinical outcome of CT-guided high-dose-rate brachytherapy (CT-HDRBT) of unresectable colorectal liver metastases (CRLMs). MATERIALS AND METHODS: Retrospective analysis of all consecutive patients with unresectable CRLMs treated with CT-HDRBT between January 2008 and November 2012. Treatment was performed by CT-guided catheter placement and high-dose-rate brachytherapy with an iridium-192 source. MRI follow-up was performed after 6 weeks and then every 3 months post-intervention. The primary endpoint was local tumor control (LTC); secondary endpoints included time to progression (TTP) and overall survival (OS). RESULTS: 80 heavily pretreated patients with 179 metastases were available for MRI evaluation for a mean follow-up time of 16.9 months. The mean tumor diameter was 28.5 mm (range: 8 - 107 mm). No major complications were observed. A total of 23 (12.9 %) local tumor progressions were observed. Lesions ≥ 4 cm in diameter showed significantly more local progression than smaller lesions (< 4 cm). 50 patients (62.5 %) experienced systemic tumor progression. The median TTP was 6 months. 28 (43 %) patients died during the follow-up period. The median OS after ablation was 18 months. CONCLUSION: CT-HDRBT is an effective technique for the treatment of unresectable CRLMs and warrants promising LTC rates compared to thermal ablative techniques. A combination with other local and systemic therapies should be evaluated in patients with lesions > 4 cm in diameter, in which higher progression rates are expected. KEY POINTS: • CT-HDRBT enables a highly cytotoxic irradiation of colorectal liver metastases with simultaneous conservation of important neighboring structures (eg liver parenchyma, bile ducts and bowel)• The local tumor control rates obtained by CT-HDRBT in patients with colorectal liver metastases are promising, also compared to the local tumor control rates after RFA• Metastases with a diameter of 4 cm or abow, display a higher local progression rate after CT-HDRBT, therefor a combination therapy with other locoregional or systemic treatments should be investigated in prospective studies.

Intrafraction variations in linac-based image-guided radiosurgery of intracranial lesions.

PURPOSE: This study investigated image-guided patient positioning during frameless, mask-based, single-fraction stereotactic radiosurgery of intracranial lesions and intrafractional translational and rotational variations in patient positions. PATIENTS AND METHODS: A non-invasive head and neck thermoplastic mask was used for immobilization. The Exactrac/Novalis Body system (BrainLAB AG, Germany) was used for kV X-ray imaging guided positioning. Intrafraction displacement data, obtained by imaging after each new table position, were evaluated. RESULTS: There were 269 radiosurgery treatments performed on 190 patients and a total of 967 setups within different angles. The first measured error after each table rotation (mean 2.6) was evaluated (698 measurements). Intrafraction translational errors were (1 standard deviation [SD]) on average 0.8, 0.8, and 0.7mm for the left-right, superior-inferior, and anterior-posterior directions, respectively, with a mean 3D-vector of 1.0mm (SD 0.9mm) and a range from -5mm to +5mm. On average, 12%, 3%, and 1% of the translational deviations exceeded 1, 2, and 3mm, respectively, in the three directions. CONCLUSION: The range of intrafraction patient motion in frameless image-guided stereotactic radiosurgery is often not fully mapped by pre- and post-treatment imaging. In the current study, intrafraction motion was assessed by performing measurements at several time points during the course of stereotactic radiosurgery. It was determined that 12% of the intrafraction values in the three dimensions are above 1mm, the usual safety margin applied in stereotactic radiosurgery.

Percutaneous ablation of lymph node metastases using CT-guided high-dose-rate brachytherapy.

OBJECTIVE: To assess the technical feasibility, safety and clinical outcome of CT-guided high-dose-rate brachytherapy (CT-HDRBT) for achieving local tumour control (LTC) in isolated lymph node metastases. METHODS: From January 2008 to December 2011, 10 patients (six males and four females) with isolated nodal metastases were treated with CT-HDRBT. Five lymph node metastases were para-aortic, three were at the liver hilum, one at the coeliac trunk and one was a left iliac nodal metastasis. The mean lesion diameter was 36.5 mm (range 12.0-67.0 mm). Patients were followed up by either contrast-enhanced CT or MRI 6 weeks and then every 3 months after the end of treatment. The primary end point was LTC. Secondary end points included primary technical effectiveness rate, adverse events and progression-free survival. RESULTS: The first follow-up examination after 6 weeks revealed complete coverage of all nodal metastases treated. There was no peri-interventional mortality or major complications. The mean follow-up period was 13.2 months (range 4-20 months). 2 out of 10 patients (20%) showed local tumour progression 9 and 10 months after ablation. 5 out of 10 patients (50%) showed systemic tumour progression. The mean progression-free interval was 9.2 months (range 2-20 months). CONCLUSION: CT-HDRBT is a safe and effective technique for minimally invasive ablation of nodal metastases. ADVANCES IN KNOWLEDGE: CT-HDRBT of lymph node metastases is feasible and safe. CT-HDRBT might be a viable therapeutic alternative to obtain LTC in selected patients with isolated lymph node metastases.

[Radiation therapy in patients with cardiac pacemakers or implantable cardioverter defibrillators. Interdisciplinary safety recommendations]. / Strahlentherapie bei Patienten mit Herzschrittmachern oder implantierbaren Kardioverter-Defibrillatoren. Interdisziplinäre Sicherheitsempfehlungen.

BACKGROUND: With increasing numbers of implanted pacemakers and implantable cardioverter defibrillators (ICD) and a rising incidence of malignant tumors, there is a growing probability of radiation-mediated device dysfunction. The only guidelines for the management of patients with cardiac pacemakers in the case of radiation therapy were published in 1994 and have not been updated since then. Based on the current evidence and modern device technology, the present paper aims to develop contemporary and interdisciplinary safety recommendations for the minimization of patient risk. METHODS AND RESULTS: A systematic literature research was carried out including the most relevant medical electronic databases. The search yielded 147 articles published between 1994 and 2012 of which 45 met the selection criteria and of these studies 34 presented primary data (9 in vitro and 25 in vivo studies). The impact of ionizing radiation varied significantly between implanted devices and ranged from no functional changes to complete loss of function. Important device dysfunctions included changes in sensing capability, altered pacing pulses or rate, changed or disabled tachyarrhythmia ICD therapies, early battery depletion and loss of telemetry. Modern pacemakers and ICDs are more sensitive to radiation than older models. Potentially life-threatening complications were observed after exposure of the pulse generator to comparatively low radiation doses (0.11 Gy). CONCLUSIONS: Practical recommendations for patient management and safety are presented that can be readily adopted by any institution carrying out radiation therapy.

[Percutaneous CT-guided high-dose brachytherapy (CT-HDRBT) ablation of primary and metastatic lung tumors in nonsurgical candidates]. / Perkutane CT-gesteuerte Hochdosis-Brachytherapie (CT-HDRBT) von primären und metastatischen Lungentumoren in nicht chirurgischen Kandidaten.

PURPOSE: To evaluate the safety and efficacy of CT-guided high-dose brachytherapy (CT-HDRBT) ablation of primary and metastatic lung tumors. MATERIALS AND METHODS: Between November 2007 and May 2010, all consecutive patients with primary or metastatic lung tumors, unsuitable for surgery, were treated with CT-HDRBT. Imaging follow-up after treatment was performed with contrast-enhanced CT at 6 weeks, 3 months and every 6 months after the procedure. The endpoints of the study were local tumor control and time to progression. The Kaplan-Meier method was used to estimate survival functions and local tumor progression rates. RESULTS: 34 procedures were carried out on 33 lesions in 22 patients. The mean diameter of the tumors was 33.3 mm (SD = 20.4). The first contrast-enhanced CT showed that complete ablation was achieved in all lesions. The mean minimal tumor enclosing dose was 18.9 Gy (SD = 2). Three patients developed a pneumothorax after the procedure. The mean follow-up time was 13.7 (3 - 29) months. 2 of 32 lesions (6.25 %) developed a local tumor progression. 8 patients (36.3 %) developed a distant tumor progression. After 17.7 months, 13 patients were alive and 9 patients had died. CONCLUSION: CT-HDRBT ablation is a safe and attractive treatment option for patients with lung malignancies and allows targeted destruction of tumor tissue with simultaneous preservation of important lung structures. Furthermore, CT-HDRBT is independent of the size of the lesion and its location within the lung parenchyma.

A literature survey on indicators for characterisation and optimisation of SAR distributions in deep hyperthermia, a plea for standardisation.

PURPOSE: To evaluate the predictive value of SAR indicators by assessing the correlation of a SAR indicator with the corresponding predicted temperature. Ultimately, this should lead to a number of verified SAR indicators for characterization and optimization of a predicted SAR distribution. METHODS: A literature survey is followed by an evaluation of the SAR indicators on their functionality, using a set of heuristic classification criteria. To obtain an objective assessment of the predictive value for SAR characterisation, all SAR indicators are evaluated by correlating the value of the SAR indicator to the predicted target temperature when heated with the BSD2000 Sigma 60 applicator. Two methods were followed. First, the specificity of the SAR indicator to target temperature was assessed for each of the 36 patient-specific models, using 30 randomly chosen phase and amplitude settings. Secondly, each SAR indicator was used as a goal function to assess its suitability for optimisation purposes. RESULTS: Only a selected number of SAR indicators correlate well with tumour/target-temperature. Hence, for target-related properties, an adequate set of SAR indicators is found in the literature. For hotspots, modifications are desirable. For optimisation purposes, improved objective functions have been defined. CONCLUSIONS: From the correlation of the SAR indicators with tumour temperature, a preferred set of SAR indicators is derived: For target heating, 'average SAR ratio', 'Hotspot-target SAR ratio', and 'homogeneity coefficient' provide suitable objective criteria, while for hotspot reduction, 'Hotspot-target SAR ratio' is considered the most useful indicator. For optimisation procedures, 'Hotspot-target SAR ratio' is currently the most suitable objective function.

Use of H(2) (15)O-PET for investigating perfusion changes in pelvic tumors due to regional hyperthermia.

PURPOSE: An increase in tumor oxygenation and perfusion due to hyperthermia has been reported for experimental tumors. The present study was performed to investigate this hypothesis in patients who underwent regional hyperthermia. METHODS: Twenty-seven patients with primary or recurrent pelvic tumors were included in this study. Prior to and up to 1 h after regional hyperthermia, perfusion and partition coefficient were quantitatively determined by utilizing H(2) (15)O-PET. First pass PET images were fused with the segmented common iliac artery from separately acquired CT scan. The arterial input function was extracted from the common iliac arteries using the dynamic PET images and the fused CT. The fused images were also used to extract tumor activity-time curves. Perfusion was calculated from the total tumor curves with correction for arterial spill-over. Changes in perfusion and partition coefficient were analyzed and correlated with various treatment parameters. RESULTS: Heating under hyperthermia conditions significantly increased the partition coefficient for pelvic tumors (P = 0.005). The increase correlated with the duration of hyperthermia and was found in patients treated for more than 1 h and persisted for more than 1 h after the end. Significant changes in perfusion were not observed. Perfusion had recurred to initial values 20 min after heating. CONCLUSIONS: The increase in partition coefficient reflects an increased diffusion distance of radio-labeled water. Therefore water diffusion is increased due to hyperthermia. Analogous to water diffusion, the diffusion of inert gases is also facilitated, improving the oxygenation of hypoxic tumor cells. Our results suggest that tumor oxygenation can probably be enhanced by regional hyperthermia for a period of more than 1 h after heating, provided hyperthermia is applied for at least 60 min. The effect was observed to be reversible within one week.

[Influence of time-dose-relationships in therapeutic nuclear medicine applications on biological effectiveness of irradiation: consequences for dosimetry]. / Einfluss der Dosisleistung nuklearmedizinischer Therapie auf die biologische Strahlenwirkung. Konsequenzen für die Dosimetrie.

AIM: The biological effectiveness of irradiation is influenced not only by the total dose but also the rate at which this dose is administered. Tolerance dose estimates from external radiation therapy with a conventional fractionation protocol require adaptation for application in targeted radionuclide therapy. METHODS: The linear-quadratic model allows for calculation of the biologically effective dose (BED) and takes into consideration tissue specific factors (recovery capacity) as well as dose rate effects (recovery kinetics). It can be applied in radionuclide therapy as well. For relevant therapeutic radionuclides (e. g. (188)Re, (90)Y, (177)Lu, and (131)I), the effect of different physical decay times and variable biological half-lives on BED was calculated for several organs. RESULTS: BED is markedly increased using (188)Re compared to longer-lived radionuclides. The effect is dose-dependent and tissue-specific, resulting, for example, in higher effects on the kidneys compared to bone marrow. Therefore, in unfavourable conditions (e. g. reduced recovery capacity due to concomitant diseases or previous therapy), the BED may exceed organ dose tolerance. CONCLUSION: Time-dose-relationships have to be taken into consideration by the calculation of BED for internal radionuclide therapy. The biological effectiveness depends on dose- and tissue-specific factors and is much more pronounced in (188)Re than in (90)Y and other longer living radionuclides. Determination of organ tolerance dose values should take into account these radiobiological differences, since it is currently not considered in dosimetry programs.

Regional hyperthermia of the abdomen in conjunction with chemotherapy for peritoneal carcinomatosis: evaluation of two annular-phased-array applicators.

BACKGROUND: 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. METHODS: 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). RESULTS: 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.

Image artifacts during MRT hybrid hyperthermia--causes and elimination.

PURPOSE: Online MR-thermometry during hyperthermia can improve treatment control. It needs excellent image quality during hyperthermia treatment to get information from subtracted images. MATERIALS AND METHODS: For hybrid hyperthermia two high-frequency devices were used in combination working with different frequencies. The imaging was performed on a 1.5 T MR tomograph (Siemens Symphony, Quantum Gradienten, Maestro Class, Firma Siemens, Erlangen, Germany) at 64 MHz whereas hyperthermia was administered with a BSD 2000 3D unit utilizing a Sigma Eye applicator and a 12 channel DODECK transistor amplifier (BSD 2000, BSD-MC, Salt Lake City, Utah, USA) operating at 100 MHz. For analysing image artifacts a spectrum analyser (Hewlett Packard HP8591E) was used. RESULTS: Two different image artifacts, occurring during the use of this hybrid system, are described. The artifacts result from introduction of additional frequencies into the imager. Here we demonstrated the detection and elimination of these spurious frequencies in the context of two case studies. CONCLUSION: Hybrid hyperthermia requires excellent imaging for optimal operation. Additional frequencies causing image artifacts can be identified by use of a spectrum analyser. Once identified, these interfering frequencies can be eliminated with appropriate RF filters. With MRI quality control for hyperthermia systems with different treatment frequencies is possible.

The biologic rationale of hyperthermia.

The clinical efficacy of various of hyperthermia approaches has been demonstrated in the scope of various randomised trials. In addition, a large body of preclinical data on alterations of cellular and molecular pathways under the circumstance of elevated temperatures is available. However, there is still uncertainty about the mechanisms which are acutally responsible for the beneficial effect of clinical hyperthermia when applied as an adjunt to radiotherapy, chemotherapy, or radiochemotherapy. This chapter gives a clinically orientated overview on the cytotoxic effect of heat alone and in conjunction with radiation and drugs, heat-induced alterations of the tumour microenvironment, and the immunological targets of hyperthermia.

Interactions between hyperthermia and cytotoxic drugs.

Pioneering studies of the 1970s and 1980s demonstrated that heat application induces cell death at temperatures of more than 43 degrees C in cell cultures and animal experiments, and sensitises tumour cells to radiation and certain cytotoxic drugs in the temperature range of 39 degrees C - 43 degrees C. Further research revealed further details of the complex interactions of heat and drugs in the living organism. In this chapter, we discuss the fundamentals of heat-drug interactions, their variations between certain classes of cytotoxic agents, induction and reversal of drug resistance under hyperthermic conditions, and pharmacological aspects of drug administration during hyperthermia.

Morbidity and quality of life during thermotherapy using magnetic nanoparticles in locally recurrent prostate cancer: results of a prospective phase I trial.

PURPOSE: To investigate the treatment-related morbidity and quality of life (QoL) during thermotherapy using superparamagnetic nanoparticles in patients with locally recurrent prostate cancer. MATERIALS AND METHODS: Ten patients with biopsy-proven locally recurrent prostate cancer following primary therapy with curative intent and no detectable metastases were entered on a prospective phase I trial. Endpoints were feasibility, toxicity and QoL. Following intraprostatic injection of a nanoparticle dispersion, six thermal therapy sessions of 60 min duration were delivered at weekly intervals using an alternating magnetic field. National Cancer Institute (NCI) common toxicity criteria (CTC) and the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 and QLQ-PR25 questionnaires were used to evaluate toxicity and QoL, respectively. In addition, prostate specific antigen (PSA) measurements were carried out. RESULTS: Maximum temperatures up to 55 degrees C were achieved in the prostates at 25-30% of the available magnetic field strength. Nanoparticle deposits were detectable in the prostates one year after thermal therapy. At a median follow-up of 17.5 months (3-24), no systemic toxicity was observed. Acute urinary retention occurred in four patients with previous history of urethral stricture. Treatment-related morbidity was moderate and QoL was only temporarily impaired. Prostate-specific antigen (PSA) declines were observed in eight patients. CONCLUSIONS: Interstitial heating using magnetic nanoparticles was feasible and well tolerated in patients with locally recurrent prostate cancer. Deposition of nanoparticles in the prostate was highly durable. Further refinement of the technique is necessary to allow application of higher magnetic field strengths.

123I-IMT SPECT for evaluation of the response to radiation therapy in high grade gliomas: a feasibility study.

Assessing response to radiation therapy in patients with high grade gliomas is needed upon making decisions toward further therapy strategies. Currently used standard imaging tools such as CT and MRI are not sensitive enough to detect early therapy effects. We prospectively investigated if single photon emission computed tomography (SPECT) using radiolabelled amino acid derivate (123)I-methyltyrosine (IMT) would be useful for this aim. 10 patients with histologically proven high grade gliomas, who were candidates for radiation therapy, were enrolled in this investigation. All patients were examined by IMT SPECT before radiation therapy and 4 weeks after the initiation of the hypofractionated application of 40 Gy. Patients were followed up for 39 months; the tumours to background ratios (T/B) for IMT under/before radiation therapy were correlated to survival times. Initially, SPECT depicted an abnormal intratumoural IMT uptake in all patients (mean T/B ratios 1.37-1.87). In four out of 10 patients, the mean T/B ratios decreased by more than 10% under radiation therapy. In six other patients, the BQ decreased by less than 10% or increased. There were no significant correlations between the degree of changes in T/B and survival (r = -0.1, p = 0.973). Serial IMT SPECT measurements allow detection of changes in amino acid accumulation in high-grade gliomas under radiation therapy. However, these changes seem to possess no prognostic value in respect to survival prediction.