Reliability of temperature and SAR measurements at oesophageal tumour locations

Introduction: For treatment of oesophageal cancer, neo-adjuvant locoregional hyperthermia (HT) has been applied in combination with chemotherapy (ChT)?±?radiotherapy (RT) at the institute. Until now, 26 patients were treated within a completed phase I study combining HT with ChT and 29 patients within an ongoing phase II study combining HT with ChT?+?RT.

Methods: HT was given with the 70?MHz AMC-4 waveguide system. Initially, oesophageal temperatures were measured using multi-sensor thermocouple probes (TCs) inside a nasogastric tube (NT), but the question arose whether these measurements were reliable enough to quantify the achieved tumour temperatures accurately. Presently, TCs are mounted on the outside of an inflatable balloon catheter (BC) for better intra-luminal fixation and better contact with the tumour. During 14 treatment sessions in four patients TCs inside a NT and mounted on a BC were used simultaneously. Data from these 14 treatment sessions were used to compare temperature and Specific Absorption Rate (SAR) measurements (‘ΔT-measurements’) using NTs or BCs. To determine the predictive value of the local SAR for the tumour temperatures achieved during treatment, the relation between the initial ΔT and steady state temperature (SST) was evaluated.

Results: There was a strong correlation between the temperature measured in the NT (T_tube) and the temperature measured with a BC (T_balloon): R?=?0.88?±?0.13. However, T_tube was on average ～1°C higher than T_balloon and there was a large variation between the different treatments in the relation between both measurements, rendering T_tube a probably unreliable measure for tumour temperatures. The correlation between the ΔT measured in the NT (ΔT_tube) and with a BC (ΔT_balloon) was rather weak: R?=?0.46?±?0.25. The correlation between the initial ΔT and the SST was much stronger for the BC measurements, R?=?0.78?±?0.19, than for the NT measurements, R?=?0.61?±?0.23. Thus, ΔT_balloon has a higher predictive value for the achieved tumour temperatures than ΔT_tube. Both ΔT and SST were generally higher for the NT measurements than for the BC measurements, suggesting an over-estimation of tumour temperatures. Averaged over all treatments in the phase I trial using a NT (20 treatments) or a BC (45 treatments), T₉₀ was significantly higher when measured with a NT.

Conclusion: Oesophageal temperature and SAR (ΔT) measurements inside a NT are less reliable than BC measurements. These artefacts are due to bad thermal contact with the tumour tissue and are, therefore, not specific for thermocouple thermometry. For reliable temperature or SAR measurements inside lumina or cavities good thermal contact must be assured, e.g. by using a balloon catheter.     

On verification of hyperthermia treatment planning for cervical carcinoma patients.

PURPOSE: The aim of this study was to verify hyperthermia treatment planning calculations by means of measurements performed during hyperthermia treatments. The calculated specific absorption rate (SAR(calc)) was compared with clinically measured SAR values, during 11 treatments in seven cervical carcinoma patients. METHODS: Hyperthermia treatments were performed using the 70 MHz AMC-4 waveguide system. Temperatures were measured using multisensor thermocouple probes. One invasive thermometry catheter in the cervical tumour and two non-invasive catheters in the vagina were used. For optimal tissue contact and fixation of the catheters, a gynaecological tampon was inserted, moisturized with distilled water (4 treatments), or saline (6 treatments) for better thermal contact. During one treatment no tampon was used. At the start of treatment the temperature rise (DeltaT(meas)) after a short power pulse was measured, which is proportional to SAR(meas). The SAR(calc) along the catheter tracks was extracted from the calculated SAR distribution and compared with the DeltaT(meas)-profiles. RESULTS: The correlation between DeltaT(meas) and SAR(calc) was on average R = 0.56 +/- 0.28, but appeared highly dependent on the wetness of the tampon (preferably with saline) and the tissue contact of the catheters. Correlations were strong (R approximately 0.85-0.93) when thermal contact was good, but much weaker (R approximately 0.14-0.48) for cases with poor thermal contact. CONCLUSION: Good correlations between measurements and calculations were found when tissue contact of the catheters was good. The main difficulties for accurate verification were of clinical nature, arising from improper use of the gynaecological tampon. Poor thermal contact between thermocouples and tissue caused measurement artefacts that were difficult to correlate with calculations.     

Prospective treatment planning to improve locoregional hyperthermia for oesophageal cancer.

BACKGROUND: In the Academic Medical Center (AMC) Amsterdam, locoregional hyperthermia for oesophageal tumours is applied using the 70 MHz AMC-4 phased array system. Due to the occurrence of treatment-limiting hot spots in normal tissue and systemic stress at high power, the thermal dose achieved in the tumour can be sub-optimal. The large number of degrees of freedom of the heating device, i.e. the amplitudes and phases of the antennae, makes it difficult to avoid treatment-limiting hot spots by intuitive amplitude/phase steering. AIM: Prospective hyperthermia treatment planning combined with high resolution temperature-based optimization was applied to improve hyperthermia treatment of patients with oesophageal cancer. METHODS: All hyperthermia treatments were performed with 'standard' clinical settings. Temperatures were measured systemically, at the location of the tumour and near the spinal cord, which is an organ at risk. For 16 patients numerically optimized settings were obtained from treatment planning with temperature-based optimization. Steady state tumour temperatures were maximized, subject to constraints to normal tissue temperatures. At the start of 48 hyperthermia treatments in these 16 patients temperature rise (DeltaT) measurements were performed by applying a short power pulse with the numerically optimized amplitude/phase settings, with the clinical settings and with mixed settings, i.e. numerically optimized amplitudes combined with clinical phases. The heating efficiency of the three settings was determined by the measured DeltaT values and the DeltaT-ratio between the DeltaT in the tumour (DeltaToes) and near the spinal cord (DeltaTcord). For a single patient the steady state temperature distribution was computed retrospectively for all three settings, since the temperature distributions may be quite different. To illustrate that the choice of the optimization strategy is decisive for the obtained settings, a numerical optimization on DeltaT-ratio was performed for this patient and the steady state temperature distribution for the obtained settings was computed. RESULTS: A higher DeltaToes was measured with the mixed settings compared to the calculated and clinical settings; DeltaTcord was higher with the mixed settings compared to the clinical settings. The DeltaT-ratio was approximately 1.5 for all three settings. These results indicate that the most effective tumour heating can be achieved with the mixed settings. DeltaT is proportional to the Specific Absorption Rate (SAR) and a higher SAR results in a higher steady state temperature, which implies that mixed settings are likely to provide the most effective heating at steady state as well. The steady state temperature distributions for the clinical and mixed settings, computed for the single patient, showed some locations where temperatures exceeded the normal tissue constraints used in the optimization. This demonstrates that the numerical optimization did not prescribe the mixed settings, because it had to comply with the constraints set to the normal tissue temperatures. However, the predicted hot spots are not necessarily clinically relevant. Numerical optimization on DeltaT-ratio for this patient yielded a very high DeltaT-ratio ( approximately 380), albeit at the cost of excessive heating of normal tissue and lower steady state tumour temperatures compared to the conventional optimization. CONCLUSION: Treatment planning can be valuable to improve hyperthermia treatments. A thorough discussion on clinically relevant objectives and constraints is essential.     

Temperature data and specific absorption rates in pelvic tumours: predictive factors and correlations.

The system BSD 2000 has been in clinical use for regional hyperthermia for more than 10 years. Several technical details of this hyperthermia system, as well as the results of clinical studies employing this system have been investigated. The intention of this paper is to investigate the correlation between technical efficiency or feasibility of hyperthermia with the BSD 2000, in terms of power densities and temperatures depending upon parameters such as tumour histology, tumour location, patient age, patient sex, and patient cross section. The possible conclusions of predictive factors derived from the above correlations were closely scrutinized. Data acquired from 772 treatment sessions of 190 patients with pelvic tumours, mainly sarcomas and carcinomas of the rectum, cervix, prostate and anus, have been evaluated. For every session, index temperatures T90 (temperature attained at 90% of tumour related measurement points), cumulative minutes for T90 > Tref, tumour related power density (SAR: specific absorption rate, in W/kg) and the effective perfusion Weff (in ml/100 g min) were calculated. Temperatures were measured either invasively or endoluminally. The statistics software SPSS was employed subsequently for univariate, as well as multivariate analyses. The results exhibit that index temperatures mainly depend on the power density SAR and the hyperthermia induced effective perfusion. The total power P (in 100 W) and, complementarily, the relative power density absolute value(SAR) (= SAR/P) seem to have lesser influence. Clear differences between the tumour entities were established regarding their index temperatures and temperature distributions. SAR, Weff and P were correlated with several anatomical, biological and clinical factors. Sessions rendering low index temperatures and SAR values also revealed decreased individual tolerance to the treatment. This clearly displays that power-induced side effects define the limits of the efficiency of regional hyperthermia. Equivalent relationships and correlations are derived from intratumoural and endoluminal thermometry. Individual limitations of regional hyperthermia caused by anatomical, biological and clinical factors are liable to be difficult to overcome with the rather restricted potentials of the BSD 2000 system to control the SAR distribution.     

Clinical integration of software tool VEDO for adaptive and quantitative application of phased array hyperthermia in the head and neck

Abstract

Background and purpose: In Rotterdam, patient-specific hyperthermia (HT) treatment planning (HTP) is applied for all deep head and neck (H&N) HT treatments. In this paper we introduce VEDO (the Visualisation Tool for Electromagnetic Dosimetry and Optimisation), the software tool required, and demonstrate its value for HTP-guided online complaint-adaptive (CA) steering based on specific absorption rate (SAR) optimisation during a H&N HT treatment.

Materials and methods: VEDO integrates CA steering, visualisation of the SAR patterns and mean tumour SAR (SAR_target) optimisation in a single screen. The pre-calculated electromagnetic fields are loaded into VEDO. During treatment, VEDO shows the SAR pattern, overlaid on the patients’ CT-scan, corresponding to the actually applied power settings and it can (re-)optimise the SAR pattern to minimise SAR at regions where the patient senses discomfort while maintaining a high SAR_target.

Results: The potential of the quantitative SAR steering approach using VEDO is demonstrated by analysis of the first treatment in which VEDO was used for two patients using the HYPERcollar.

These cases show that VEDO allows response to power-related complaints of the patient and to quantify the change in absolute SAR: increasing either SAR_target from 96 to 178?W/kg (case 1); or show that the first SAR distribution was already optimum (case 2).

Conclusion: This analysis shows that VEDO facilitates a quantitative treatment strategy allowing standardised application of HT by technicians of different HT centres, which will potentially lead to improved treatment quality and the possibility of tracking the effectiveness of different treatment strategies.     

Clinical experience with a multi-element ultrasonic hyperthermia system: Analysis of treatment temperatures

A summary of tumour temperature data obtained from 31 patients who underwent 147 hyperthermia treatments with the Sonotherm 1000 ultrasonic system is presented. The treatment goal was to achieve a minimum of 42.0°C in tumour for 60 min duration with normal tissues remaining below 43.0°C. In 83% of treatments at least one measured tumour temperature reached or exceeded 42.0°C at some time during the treatment. Nineteen per cent of these treatments had a time-and spatial-averaged temperature (measured in tumour) ≥ 42.0°C. A variety of anatomical sites were treated and these were grouped into four categories: groin/trunk, axilla, breast/chest wall and head/neck. Measured temperatures in tumours located in the groin and trunk sites were significantly higher (22% ≥ 42°C) than other locations. The head and neck treatment temperatures were significantly lower (8% of measured points ≥ 42°C).     

Temperature data and specific absorption rates in pelvic tumours: predictive factors and correlations

The system BSD 2000 has been in clinical use for regional hyperthermia for more than 10 years. Several technical details of this hyperthermia system, as well as the results of clinical studies employing this system have been investigated. The intention of this paper is to investigate the correlation between technical efficiency or feasibility of hyperthermia with the BSD 2000, in terms of power densities and temperatures depending upon parameters such as tumour histology, tumour location, patient age, patient sex, and patient cross section. The possible conclusions of predictive factors derived from the above correlations were closely scrutinized. Data acquired from 772 treatment sessions of 190 patients with pelvic tumours, mainly sarcomas and carcinomas of the rectum, cervix, prostate and anus, have been evaluated. For every session, index temperatures T ₉₀ (temperature attained at 90% of tumour related measurement points), cumulative minutes for T₉₀ > T_ref, tumour related power density (SAR: specific absorption rate, in W/kg) and the effective perfusion W_eff (inml/100gmin) were calculated. Temperatures were measured either invasively or endoluminally. The statistics software SPSS was employed subsequently for univariate, as well as multivariate analyses. The results exhibit that index temperatures mainly depend on the power density SAR and the hyperthermia induced effective perfusion. The total power P (in 100W) and, complementarily, the relative power density ||SAR|| (= SAR/P) seem to have lesser influence. Clear differences between the tumour entities were established regarding their index temperatures and temperature distributions. SAR, W_eff and P were correlated with several anatomical, biological and clinical factors. Sessions rendering low index temperatures and SAR values also revealed decreased individual tolerance to the treatment. This clearly displays that powerinduced side effects define the limits of the efficiency of regional hyperthermia. Equivalent relationships and correlations are derived from intratumoural and endoluminal thermometry. Individual limitations of regional hyperthermia caused by anatomical, biological and clinical factors are liable to be difficult to overcome with the rather restricted potentials of the BSD 2000 system to control the SAR distribution.     

Evolving connections between molecular chaperones and neuronal function

Background: In the Academic Medical Center (AMC) Amsterdam, locoregional hyperthermia for oesophageal tumours is applied using the 70?MHz AMC-4 phased array system. Due to the occurrence of treatment-limiting hot spots in normal tissue and systemic stress at high power, the thermal dose achieved in the tumour can be sub-optimal. The large number of degrees of freedom of the heating device, i.e. the amplitudes and phases of the antennae, makes it difficult to avoid treatment-limiting hot spots by intuitive amplitude/phase steering.

Aim: Prospective hyperthermia treatment planning combined with high resolution temperature-based optimization was applied to improve hyperthermia treatment of patients with oesophageal cancer.

Methods: All hyperthermia treatments were performed with ‘standard’ clinical settings. Temperatures were measured systemically, at the location of the tumour and near the spinal cord, which is an organ at risk. For 16 patients numerically optimized settings were obtained from treatment planning with temperature-based optimization. Steady state tumour temperatures were maximized, subject to constraints to normal tissue temperatures. At the start of 48 hyperthermia treatments in these 16 patients temperature rise (ΔT) measurements were performed by applying a short power pulse with the numerically optimized amplitude/phase settings, with the clinical settings and with mixed settings, i.e. numerically optimized amplitudes combined with clinical phases. The heating efficiency of the three settings was determined by the measured ΔT values and the ΔT-ratio between the ΔT in the tumour (ΔT_oes) and near the spinal cord (ΔT_cord). For a single patient the steady state temperature distribution was computed retrospectively for all three settings, since the temperature distributions may be quite different. To illustrate that the choice of the optimization strategy is decisive for the obtained settings, a numerical optimization on ΔT-ratio was performed for this patient and the steady state temperature distribution for the obtained settings was computed.

Results: A higher ΔT_oes was measured with the mixed settings compared to the calculated and clinical settings; ΔT_cord was higher with the mixed settings compared to the clinical settings. The ΔT-ratio was ～1.5 for all three settings. These results indicate that the most effective tumour heating can be achieved with the mixed settings. ΔT is proportional to the Specific Absorption Rate (SAR) and a higher SAR results in a higher steady state temperature, which implies that mixed settings are likely to provide the most effective heating at steady state as well. The steady state temperature distributions for the clinical and mixed settings, computed for the single patient, showed some locations where temperatures exceeded the normal tissue constraints used in the optimization. This demonstrates that the numerical optimization did not prescribe the mixed settings, because it had to comply with the constraints set to the normal tissue temperatures. However, the predicted hot spots are not necessarily clinically relevant. Numerical optimization on ΔT-ratio for this patient yielded a very high ΔT-ratio (～380), albeit at the cost of excessive heating of normal tissue and lower steady state tumour temperatures compared to the conventional optimization.

Conclusion: Treatment planning can be valuable to improve hyperthermia treatments. A thorough discussion on clinically relevant objectives and constraints is essential.     

Temperature distributions during clinical scanned, focused ultrasound hyperthermia treatments

In this study a scanned focused ultrasound (SFUS) system was used to heat 66 tumours at various anatomical locations in 52 patients. A total of 160 treatments were given. On average, temperatures were measured in 14 or 15 locations in the scanned volume. The time-averaged temperatures over the 30 min treatment period in the best treatment of each tumour were 44.0 +/- 2.4 degrees C (mean +/- SD) and 39.6 +/- 1.5 degrees C at the location of the highest and lowest sensor, respectively. On average, 39% of the sensors were above 42.5 degrees C. When only the cases that were judged to be good candidates for the hyperthermia device were analysed, 64% of the sensors reached a temperature over 42.5 degrees C with the highest temperature achieved being 45.9 +/- 2.3 degrees C and the lowest 40.7 +/- 1.4 degrees C. Although the system tested has many technical limitations (for example, fixed frequency, beam geometry and power during the scan cycle), the results demonstrate that therapeutic temperatures can be achieved in many tumours. Significantly better temperatures are expected when all of the theoretical potential of scanned focused ultrasound systems has been used.     

Clinical experience with a multi-element ultrasonic hyperthermia system: analysis of treatment temperatures

A summary of tumour temperature data obtained from 31 patients who underwent 147 hyperthermia treatments with the Sonotherm 1000 ultrasonic system is presented. The treatment goal was to achieve a minimum of 42.0 degrees C in tumour for 60 min duration with normal tissues remaining below 43.0 degrees C. In 83% of treatments at least one measured tumour temperature reached or exceeded 42.0 degrees C at some time during the treatment. Nineteen per cent of these treatments had a time- and spatial-averaged temperature (measured in tumour) greater than or equal to 42.0 degrees C. A variety of anatomical sites were treated and these were grouped into four categories: groin/trunk, axilla, breast/chest wall and head/neck. Measured temperatures in tumours located in the groin and trunk sites were significantly higher (22% greater than or equal to 42 degrees C) than other locations. The head and neck treatment temperatures were significantly lower (8% of measured points greater than or equal to 42 degrees C.     

Specific absorption rate and tissue temperature in local hyperthermia

Specific absorption rate (SAR) and tissue temperature were measured for a total of 83 treatments in 33 patients who received local hyperthermia treatment for cancer. The patients were grouped into three categories according to tumor size. Hyperthermia was induced by 13.56 MHz electromagnetic energy applied using capacitive coupling. A method is described for evaluating SAR from the tissue temperature traces at any time in the treatment when a step change is made in applied power. The method is possible only if the temperature traces are free from interference and the total power delivered to the patient is monitored. Mean values of SAR ranged from 4.6 to 89 W kg-1 depending on the treatment site. Satisfactory heating was achieved for superficial tumors, with temperatures greater than 42 degrees C being recorded in 69% of treatments. For axillary nodes only 4% of treatments exceeded 42 degrees C. For cervix tumors an idealized tumor model was used to estimate tumor temperature from the temperature and SAR measured in the adjacent normal tissue. From the model it appears necessary either to raise the systemic temperature to 40 degrees C or to increase the SAR by at least a factor of 4 to obtain a temperature of 42 degrees C in a typical tumor. Measurements of SAR and temperature are essential for feedback control of computer models which, in principle, could provide a complete distribution of temperature during a hyperthermia treatment. Furthermore, measured SAR provides a direct comparison of the power deposition from different treatment machines in a clinical environment. The data presented form a basis for comparison with the clinical use of other heating systems.     

Use of the vasodilator sodium nitroprusside to increase tumour temperature during loco-regional hyperthermia with a capacitive ring applicator in a rat tumour model.

The influence of sodium nitroprusside (SNP) induced hypotension (to a mean arterial pressure of 60 mmHg) on tumour and normal tissue temperature during hyperthermia (HT) was examined. Loco-regional HT was given to the calf of BD IX rats by external radiofrequency heating from a capacitive ring applicator. In experiments in rats with subcutaneous BT(4)An tumours, the mean tumour temperature increased by 0.49 degrees C from 42.36 to 42.85 degrees C, on average, during SNP-hypotension. This represented 58% of the increase in tumour temperature found in the same rats when the tumour circulation was stopped completely by sacrificing the rats. SNP-hypotension resulted in a decrease in mean muscle temperature from 41.73 to 41.23 degrees C. The temperature difference between the tumour and the underlying muscle thereby increased by approximately 1 degrees C, indicating that SNP can increase tumour temperature during HT without increasing the risk of heat-related damage to skeletal muscle. Experiments in rats without tumours were also done to further examine the effect of SNP-hypotension on muscle temperature under different treatment conditions (variation of radiofrequency energy deposition and water bolus temperature). It was found that SNP decreased the muscle temperature during HT in two experiments where the average muscle temperature was 42.1 and 42.6 degrees C, respectively. In an experiment where the muscle temperature was 43.0 degrees C, on average, before SNP infusion, the muscle temperature increased during SNP-hypotension. This finding indicates that SNP-hypotension during HT may increase the risk of skeletal muscle necrosis with muscle temperatures at this level.     

Use of the vasodilator sodium nitroprusside to increase tumour temperature during loco-regional hyperthermia with a capacitive ring applicator in a rat tumour model

The influence of sodium nitroprusside (SNP) induced hypotension (to a mean arterial pressure of 60mmHg) on tumour and normal tissue temperature during hyperthermia (HT) was examined. Loco-regional HT was given to the calf of BD IX rats by external radiofrequency heating from a capacitive ring applicator. In experiments in rats with subcutaneous BT 4 An tumours, the mean tumour temperature increased by 0.49°C from 42.36 to 42.85°C, on average, during SNP-hypotension. This represented 58% of the increase in tumour temperature found in the same rats when the tumour circulation was stopped completely by sacrificing the rats. SNP-hypotension resulted in a decrease in mean muscle temperature from 41.73 to 41.23°C. The temperature difference between the tumour and the underlying muscle thereby increased by ~1°C, indicating that SNP can increase tumour temperature during HT without increasing the risk of heat-related damage to skeletal muscle. Experiments in rats without tumours were also done to further examine the effect of SNP-hypotension on muscle temperature under different treatment conditions (variation of radiofrequency energy deposition and water bolus temperature). It was found that SNP decreased the muscle temperature during HT in two experiments where the average muscle temperature was 42.1 and 42.6°C, respectively. In an experiment where the muscle temperature was 43.0°C, on average, before SNP infusion, the muscle temperature increased during SNP-hypotension. This finding indicates that SNP-hypotension during HT may increase the risk of skeletal muscle necrosis with muscle temperatures at this level.     

Correlation of thermal parameters with outcome in combined radiation therapy-hyperthermia trials.

Many studies utilizing combined hyperthermia (HT) and radiation therapy (XRT) in the treatment of advanced or recurrent malignancies have reported a correlation between some measure of the minimum temperature achieved and outcome. Previous reported studies at Stanford have demonstrated a statistically significant correlation between the duration of local control and Tmin, the mean over treatments of the minima of (a) measured intratumoral temperatures in fields which contained diffuse or nodular tumours, or (b) measured interstitial temperatures in fields treated for microscopic residual disease. Recently, T90, the mean of the temperatures above which 90% of all measured intratumoral temperatures fall, has been proposed as an alternative characterization of the efficacy of the HT treatment that reportedly has a superior correlation with outcome. To test this hypothesis, T90 was computed by two different methods for three groups of patients treated at Stanford with XRT-HT for superficially located tumor recurrences. Tmin was found to be strongly correlated with T90 calculated by both methods. All three thermal parameters correlated with complete response at 3 weeks and with local control, although Tmin usually demonstrated the strongest correlation.     

MicroCT image-generated tumour geometry and SAR distribution for tumour temperature elevation simulations in magnetic nanoparticle hyperthermia

Abstract

Objectives: The objective of this study was to develop and test computer algorithms to export micro computed tomography (microCT) images and to generate tumour geometry and specific absorption rate (SAR) distribution for heat transfer simulation in magnetic nanoparticle hyperthermia. Methods: Computer algorithms were written to analyse and export microCT images of 3D tumours containing magnetic nanoparticles. MATLAB® and ProE® programs were used to generate a prototype of the tumour geometry. The enhancements in the microCT pixel index number due to presence of nanoparticles in the tumours were first converted into corresponding SAR values. The SAR data were then averaged over three-dimensional clusters of pixels using the SAS® program. This greatly decreased the size of the SAR file, while in the meantime it ensured that the amount of total energy deposited in the tumour was conserved. Both the tumour geometry and the SAR file were then imported into the COMSOL® software package to simulate temperature elevations in the tumour and their surrounding tissue region during magnetic nanoparticle hyperthermia. Results: A linear relationship was obtained to relate individual pixel index numbers in the microCT images to the SAR values under a specific magnetic field. The generated prototype of the tumour geometry based on only 30 slices of microCT images resembled the original tumour shape and size. The tumour geometry and the simplified SAR data set were successfully accepted by the COMSOL software for heat transfer simulation. Up to 20?°C temperature elevations from its baseline temperature were found inside the tumours, implying possible thermal damage to the tumour during magnetic nanoparticle hyperthermia.     

DCE-MRI parameters have potential to predict response of locally advanced breast cancer patients to neoadjuvant chemotherapy and hyperthermia: A pilot study

Combined therapies represent a staple of modern medicine. For women treated with neoadjuvant chemotherapy (NA ChT) for locally advanced breast cancer (LABC), early determination of whether the patient will fail to respond can enable the use of alternative, more beneficial therapies. This is even more desirable when the combined therapy includes hyperthermia (HT), an efficient way to improve drug delivery, however, more costly and time consuming. There is data showing that this goal can be achieved using magnetic resonance imaging (MRI) with contrast agent (CA) enhancement. This work for the first time proposes combining the information extracted from pre-treatment MR imaging into a morpho-physiological tumour score (MPTS) with the hypothesis that this score will increase the prognostic efficacy, compared to each of its MR-derived components: morphological (derived from the shape of the tumour enhancement) and physiological (derived from the CA enhancement variance dynamics parameters). The MPTS was correlated with response as determined by both pathologic residual tumour and MRI imaging, and was shown to have potential to predict response. The MPTS was extracted from pre-treatment MRI parameters, so independent of the combined therapy used.

Purpose: To use a novel morpho-physiological tumour score (MPTS) generated from dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) to predict response to treatment.

Materials and methods: A protocol was designed to acquire DCE-MRI images of 20 locally advanced breast cancer (LABC) patients treated with neoadjuvant chemotherapy (NA ChT) and hyperthermia (HT). Imaging was done over 30 min following bolus injection of gadopentetate-based contrast agent. Parametric maps were generated by fitting the signal intensity to a double exponential curve and were used to derive a morphological characterisation of the lesions. Enhancement-variance dynamics parameters, wash-in and wash-out parameters (WiP, WoP), were extracted. The morphological characterisation and the WiP and WoP were combined into a MPTS with the intent of achieving better prognostic efficacy. The MPTS was correlated with response to NA therapy as determined by pathological residual tumour and MRI imaging.

Results: The contrast agent in all tumours typically peaked in the first 1–4 min. The tumours’ WiP and WoP varied considerably. The MPTS was highly correlated with whether the patients had a pathological response. This scoring system has a specificity of 78% and a sensitivity of 91% for predicting response to NA chemotherapy. The kappa was 0.69 with a 95% confidence interval of [0.38, 1] and a p-value of 0.002.

Conclusions: This pilot study shows that the MPTS derived using pre-treatment MRI images has the potential to predict response to NA ChT and HT in LABC patients. Further prospective studies are needed to confirm the validity of these results.     

Hyperthermia treatment planning guided applicator selection for sub-superficial head and neck tumors heating

Purpose: In this study, we investigated the differences in hyperthermia treatment (HT) quality between treatments applied with different hyperthermia systems for sub-superficial tumours in the head and neck (H&;N) region.

Materials and methods: In 24 patients, with a clinical target volume (CTV) extending up to 6?cm from the surface, we retrospectively analysed the predicted HT quality achievable by two planar applicator arrays or one phased-array hyperthermia system. Hereto, we calculated and compared the specific absorption rate (SAR) and temperature distribution coverage of the CTV and gross tumour volume (GTV) for the Lucite cone applicator (LCA: planar), current sheet applicator (CSA: planar) and the HYPERcollar (phased-array).

Results: The HYPERcollar provides better SAR coverage than planar applicators if the target region is fully enclosed by its applicator frame. For targets extending outside the HYPERcollar frame, sufficient SAR coverage (25% target coverage, i.e. TC25?≥?75%) can still be achieved using the LCA when the target is fully under the LCA aperture and not deeper than 50?mm from the patient surface.

Conclusion: Simulations predict that the HYPERcollar (hence also its successor the HYPERcollar3D) is to be preferred over planar applicators such as LCA and current sheet applicator in sub-superficial tumours in the H&;N region when used within specifications.     

A comparison of temperatures in canine solid tumours during local and whole-body hyperthermia administered alone and simultaneously

Temperature measurements were made in canine solid tumours during whole-body hyperthermia (WBH) alone, local hyperthermia alone and local hyperthermia given simultaneously with WBH. During the plateau phase of WBH alone, mean intratumoral temperature ranged from 41.3 +/- 0.2 degrees C to 41.7 +/- 0.1 degrees C and was statistically lower (P = 0.0028) and more variable than rectal temperature, which ranged from 42.0 +/- 0.02 degrees C to 42.1 +/- 0.03 degrees C. The temperature distribution in solid tumours during WBH is more uniform than during local hyperthermia. The simultaneous administration of whole-body and local hyperthermia in five dogs resulted in increased tumour temperatures in comparison to WBH and in more uniformly increased tumour temperatures in comparison to local hyperthermia alone. Median intratumoral temperatures (+/- 95% confidence intervals) resulting from local hyperthermia alone and local hyperthermia given simultaneously with WBH were 39.9 degrees C (39.7-40.1) and 42.9 degrees C (42.6-43.1), respectively, and were statistically different (P = 0.0012). Local applied power requirements to meet predetermined intratumoral temperature limits were decreased by 50% (P = 0.011) in dogs undergoing combined local/whole-body hyperthermia versus local hyperthermia alone. Dogs tolerated the combination of local and WBH without complication.     

Thermal enhancement of low dose rate irradiation in a murine tumour system

The effects of localized hyperthermia (HT) in combination with low dose rate irradiation (brachytherapy) have been investigated in vivo using a murine mammary adenocarcinoma. Flank tumours were grown to 0.45-0.70 cm3 in volume, at which time their treatment course was initiated. Tumours were locally heated in a water bath for 15 min at either 44 or 45 degrees C. For tumour irradiations a non-invasive cap was devised to permanently house three iodine-125 sealed sources located at 120 degree intervals around the circumference of the hemispherical cap. During treatment, mice were secured in a modified syringe tube allowing mobility while restricting access to the cap which was placed over the tumour. Calculated dose rates ranged from 15 to 40 cGy/h. Brachytherapy (BT) was delivered for 48 or 72 h to obtain a dose range of 830-2378 cGy. Mice were randomized into one of 10 treatment protocols: BT alone, HT-BT, BT-HT, HT-BT-HT, 1/2BT-HT-1/2BT, four control groups of HT alone and a sham treatment group. Normalized tumour doubling volume growth delays (GDDv) were used to calculate the thermal enhancement ratios (TER). In the 44 degrees C experiments, HT before BT (TER = 1.33 +/- 0.071) was more efficacious than HT after BT (TER = 1.07 +/- 0.042). Two HT treatments, one given before and one after BT (TER = 1.38 +/- 0.152), were not different from a single HT treatment given before BT. However, a single HT treatment given in the middle of an interrupted course of BT resulted in the greatest thermal enhancement (TER = 1.64 +/- 0.072) compared to any other treatment sequence. These data suggest that potentiation of low dose rate irradiation by a single heat treatment may be maximized if the HT is given either in the middle of, or simultaneously with, the BT.