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M C C M Hulshof

Publications and source records attributed to M C C M Hulshof.

10 recordsLinked to original sources
PubMed2006

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.

Adenocarcinoma↗
PubMed2006

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 ('DeltaT-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 DeltaT and steady state temperature (SST) was evaluated. RESULTS: There was a strong correlation between the temperature measured in the NT (Ttube) and the temperature measured with a BC (Tballoon): R = 0.88 +/- 0.13. However, Ttube was on average approximately 1 degrees C higher than Tballoon and there was a large variation between the different treatments in the relation between both measurements, rendering Ttube a probably unreliable measure for tumour temperatures. The correlation between the DeltaT measured in the NT (DeltaTtube) and with a BC (DeltaTballoon) was rather weak: R = 0.46 +/- 0.25. The correlation between the initial DeltaT 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, DeltaTballoon has a higher predictive value for the achieved tumour temperatures than DeltaTtube. Both DeltaT 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 (DeltaT) 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.

Brachytherapy↗
PubMed2005

Effects of hyperthermia on the central nervous system: what was learnt from animal studies?

Animal studies show that nervous tissue is sensitive to heat. Although inter-species variations may play a role, the data indicate that the maximum heat dose without obvious complications after localized hyperthermia in regions of the central nervous system (CNS) lies in the range of 40-60 min at 42-42.5 degrees C or 10-30 min at 43 degrees C. Expression of thermotolerance after a 'conditioning' heat dose was clearly observed in the spinal cord of rodents and the thermotolerance ratio's (ratio between heat doses with and without conditioning required to obtain a certain defined effect) were high, approximately 2. The thermotolerant state of CNS is shown to protect also against other types of injury as well: pre-treatment of rats with hyperthermia protected against spinal cord ischemic injury. During the rather long period required for temperature elevation which is inherent to WBH, some degree of thermotolerance may develop. The correlation between thermotolerance and hsp70 induction in CNS is obvious. Heat, at least if applied shortly after X-rays, enhances the response of nervous tissue to radiation. Data on the combined effects of X-ray irradiation and hyperthermia on rodent spinal cord clearly show that the radiation response can be enhanced with a factor of 1.1-1.3. There are no clear experimental data indicating an increase in adverse effects specific to the CNS after localized or whole body hyperthermia as a result of combined treatment with chemotherapy.

Animals↗
PubMed2004

A prospective longitudinal study comparing the impact of external radiation therapy with radical prostatectomy on health related quality of life (HRQOL) in prostate cancer patients.

BACKGROUND: The objective of the present study is to compare the impact on the general and disease-specific health related quality of life (HRQOL) of external radiation therapy (ERT) with radical prostatectomy (RP) in patients with localized prostate cancer, and to explore which factors, and to what extent, contribute to the assessed changes in HRQOL. METHODS: One hundred and thirty eight patients participated in this prospective longitudinal study. They completed before treatment (T0) and after 12 months (T1) a questionnaire constructed of validated instruments, measuring HRQOL and several psychosocial factors (PF). Among other things, multiple regression analyses including all baseline characteristics, HRQOL and PF were executed in order to meet the objectives. RESULTS: RP patients showed significantly more improvement in their emotional function, while they reported more incontinence and a worse sexual function. There was significantly more improvement in the overall HRQOL of ERT patients, while the changes in the gastrointestinal function of these patients were significantly worse. Only the differences with respect to incontinence can be attributed to the treatment itself. Almost all HRQOL change scores are primarily influenced by their own baseline score. The influence of other factors, like age, socioeconomic status, and several PF, is limited. CONCLUSIONS: The impact on HRQOL of ERT is similar to that of RP, except for incontinence. RP patients suffer more from incontinence than ERT patients. Changes in the assessed HRQOL are mainly influenced by the pre-treatment HRQOL scores.

Adaptation, Psychological↗
PubMed2004

Quality of life after brachytherapy in patients with glioblastoma multiforme.

As quality of life (QoL) is perhaps the most important outcome for patients treated for glioblastoma multiforme (GBM), we measured QoL in GBM patients after brachytherapy. QoL was assessed by questionnaires for both patients and partners before brachytherapy and at various times during follow-up in 21 GBM patients by an extension of the Rotterdam Symptom Checklist (e-RSCL), consisting of four subscales. The Karnofsky Performance Scale (KPS) was also measured. Analysis of variance was done to evaluate the direct effect of brachytherapy (visit 1-2, short-term) and during follow up (visit 1-4, longer-term). Significant short-term effects were found for two subscales of the e-RSCL. Longer-term effects were found for all four subscales and for the KPS. A high correlation between partner and patient's QoL assessment was found. QoL in GBM patients after brachytherapy can therefore be carefully monitored with a subjective instrument such as the e-RSCL. Patients and partners experience QoL equally.

Activities of Daily Living↗
PubMed2004

Effects of hyperthermia on the peripheral nervous system: a review.

The present paper overviews the current knowledge about effects of hyperthermia at temperatures used in clinical oncology on the peripheral nervous system. From the experimental studies it may be concluded that the heat sensitivity of the nerve is determined by the sensitivity of the nerve vasculature. These studies show that in order to avoid induction of severe neuropathy, application of heat to the peripheral nerves should not be in excess of doses of 30 min at 44 degrees C or equivalent. Using modern equipment for application of loco-regional hyperthermia the incidence of even mild neurological complications is very low. In hyperthermic isolated limb perfusion (HILP) neurotoxicity is an often-mentioned side effect, this is in spite of the fact that in all studies a relatively mild hyperthermic temperature is used that, based on the experimental studies, should be well tolerated by the nerves and other normal tissues in the limbs. It seems that the neurotoxicity observed after HILP results from thermal enhancement of drug toxicity, very probably combined with effects of a high tourniquet pressure that is used to isolate the blood flow in the leg. Whole body hyperthermia (WBH), using anesthesia and appropriate monitoring to avoid cardiovascular stress is at present considered a safe procedure. Still in the recent past cases of neuropathy after treatment have been described. When chemotherapy, and notably cisplatin, is administered before or during hyperthermia there are several clinical and experimental observations that indicate a limited tolerance of the peripheral nervous tissue in such case. Also previous radiotherapy may limit the tolerance of nerves to hyperthermia, notably when radiation is applied with a large field size. Experimental studies show that combined treatment with radiation and heat leads to enhancement of effects of radiation (enhancement ratio approximately 1.5 at 60 min at 44 degrees C). A clear contraindication for the application of hyperthermia in patients is the presence of a neurodegenerative disease, such as multiple sclerosis. Vigilance is also required in the treatment of diabetic patients with hyperthermia, this based on experimental animal studies, but so far no clear clinical data are available.

Animals↗
PubMed2004

A feasibility study of interstitial hyperthermia plus external beam radiotherapy in glioblastoma multiforme using the Multi ELectrode Current Source (MECS) system.

PURPOSE: Thermoradiotherapy has been shown in several randomized trials to increase local control compared to radiotherapy alone. The first randomized study of interstitial hyperthermia in glioblastoma multiforme showed a survival benefit for hyperthermia, though small. Improvement of the heating technique could lead to improved results. The purpose of this feasibility study is to present the clinical and thermal data of application of an improved interstitial hyperthermia system. METHODS AND MATERIALS: Six patients with a glioblastoma multiforme were treated with interstitial hyperthermia using the Multi Electrode Current Source Interstitial Hyperthermia (MECS-IHT) system. The MECS-IHT system has the capability of spatial monitoring of temperature and individually steering of heating electrodes. Three sessions were given aiming at a steady state temperature of 42 degrees C for 1 h, with an interval of 3-4 days, during an external irradiation scheme of 60 Gy in 6 weeks. Hyperthermia was delivered with a mean of 10 catheters, 18 heating electrodes and 38 thermal probes per patient. RESULTS: Sub-optimal temperatures were encountered in the first two patients leading to adjustments in technique thereafter with subsequent improvement of thermal data. With a catheter spacing of 11-12 mm, measurements yielded a mean T(90), T(50) and T(10) of 39.9, 43.7 and 45.2 degrees C, respectively, over three sessions in the last patient. The power per electrode to reach this temperature distribution varied from 25-100% of full power in each of the last four patients. Thermal data were reproducible over the three sessions. Acute toxicity was minimal. CONCLUSIONS: Despite the spatial steering capabilities of the MECS-IHT system, a large temperature heterogeneity was encountered. The heterogeneity was the reason to limit the catheter spacing to 11-12 mm, thus making only small tumour volumes feasible for interstitial heating.

Aged↗
PubMed2004

A feasibility study in oesophageal carcinoma using deep loco-regional hyperthermia combined with concurrent chemotherapy followed by surgery.

This phase I-II study investigated the feasibility of external deep loco-regional hyperthermia in localized primarily operable carcinoma of the thoracic oesophagus and gastro-oesophageal junction. Toxicity when combining neo-adjuvant hyperthermia with concurrent chemotherapy (CDDP and etoposide) was evaluated. Hyperthermia was given with a four antenna array, operating at 70 MHz arranged around the thorax. Temperatures were monitored rectally, intra-oesophageal at tumour level and intramuscular near the spine. In four steps, a thermal dose escalation was performed from 15-60 min of heating to 41 degrees C with two patients in each step. The combined treatment courses were repeated every 3 weeks for a maximum of four courses. From January 1999-February 2002, 31 patients were included. Pre-treatment tumour stage mainly consisted of T3N1 (stage III) tumours, with a mean length of 6 cm. The maximum tumour temperature failed to reach at least 41 degrees C in five patients during the test session of hyperthermia alone. Combined hyperthermia and chemotherapy was given 55 times in 26 patients. The amplitude was set at a ratio between top:bottom:left:right = 1:3:3:3, with a power range of 800-1000 W. Thermal data showed that is was technically feasible to heat the oesophagus; the median results were T(90) = 39.3 degrees C, T(50) = 40 degrees C, T(10) = 40.7 degrees C and a median T(max) = 41.9 degrees C. In more distally located tumours higher temperatures were reached. In one patient, a transient grade 2 sensory neuropathy was seen. Further toxicity was mainly of haematological origin. Blisters or fat necrosis were not observed. Twenty-two patients underwent oesophageal-cardia resection with gastric tube reconstruction. There was no report of complications in the post-operative phase, which could be contributed to either the prior chemotherapy or the hyperthermia.

Adenocarcinoma↗
PubMed2003

Health-related quality of life and psychosocial factors in patients with prostate cancer scheduled for radical prostatectomy or external radiation therapy.

OBJECTIVE: To assess whether baseline health-related quality of life (HRQOL) and psychosocial profiles differ in patients with prostate cancer scheduled for radical prostatectomy (RP) or external radiation therapy (ERT), as there is evidence that HRQOL is influenced by psychosocial factors (PFs), so that any variation at baseline should be considered when comparing the effect of therapy on HRQOL. PATIENTS AND METHODS: Before receiving therapy, HRQOL and PFs were assessed in 65 patients scheduled for RP and in 73 scheduled for ERT. To measure HRQOL (generic and disease-specific) and PFs, an extended questionnaire was constructed, using validated and standardized instruments. Clinical data were collected from patients' medical records. Comparisons adjusted for age and socio-economic status (SES) were analysed using Student's t-test and univariate analyses of variance and covariance. RESULTS: Patients scheduled for ERT were 7.9 years older and had a lower SES (both P < 0.001), more often had stage T3 and T4 disease, had poorer histopathological differentiation and higher levels of prostate-specific antigen (all P < 0.01). They also reported a worse physical, role, cognitive and social function, more fatigue, more pain, a lower overall HRQOL and worse sexual function than patients scheduled for RP. There were no differences in urinary and bowel function, nor in the PFs assessed. CONCLUSION: The baseline HRQOL profile of patients scheduled for RP is better than in those scheduled for ERT. These results are in line with those from the few other studies on this subject. Knowing the impact of RP and ERT on HRQOL should therefore be based mainly on longitudinal studies including baseline measures, the analyses of which should be adjusted for age and SES. In the present small study, baseline PFs did not differ between the treatments.

Aged↗