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Biomedical subjects

J D van Dijk

Publications and source records attributed to J D van Dijk.

At least 19 recordsLinked to original sources
PubMed2000

Comparison of radiotherapy alone with radiotherapy plus hyperthermia in locally advanced pelvic tumours: a prospective, randomised, multicentre trial. Dutch Deep Hyperthermia Group.

BACKGROUND: Local-control rates after radiotherapy for locally advanced tumours of the bladder, cervix, and rectum are disappointing. We investigated the effect of adding hyperthermia to standard radiotherapy. METHODS: The study was a prospective, randomised, multicentre trial. 358 patients were enrolled from 1990 to 1996, in cancer centres in the Netherlands, who had bladder cancer stages T2, T3, or T4, NO, MO, cervical cancer stages IIB, IIIB, or IV, or rectal cancer stage M0-1 were assessed. Patients were randomly assigned radiotherapy (median total dose 65 Gy) alone (n=176) or radiotherapy plus hyperthermia (n=182). Our primary endpoints were complete response and duration of local control. We did the analysis by intention to treat. FINDINGS: Complete-response rates were 39% after radiotherapy and 55% after radiotherapy plus hyperthermia (p<0.001). The duration of local control was significantly longer with radiotherapy plus hyperthermia than with radiotherapy alone (p=0.04). Treatment effect did not differ significantly by tumour site, but the addition of hyperthermia seemed to be most important for cervical cancer, for which the complete-response rate with radiotherapy plus hyperthermia was 83% compared with 57% after radiotherapy alone (p=0.003). 3-year overall survival was 27% in the radiotherapy group and 51% in the radiotherapy plus hyperthermia group. For bladder cancer, an initial difference in local control disappeared during follow-up. INTERPRETATION: Hyperthermia in addition to standard radiotherapy may be especially useful in locally advanced cervical tumours. Studies of larger numbers of patients are needed for other pelvic tumour sites before practical recommendations can be made.

Aged↗
PubMed1998

Dose uniformity of ferromagnetic seed implants in tissue with discrete vasculature: a numerical study on the impact of seed characteristics and implantation techniques.

The results from simulations with a new three-dimensional treatment planning system for interstitial hyperthermia with ferromagnetic seeds are presented in this study. The thermal model incorporates discrete vessel structures as well as a heat sink and enhanced thermal conductivity. Both the discrete vessels and the ferroseeds are described parametrically in separate calculation spaces. This parametric description has the advantage of an arbitrary orientation of the structures within the tissue grid, easy manipulation of the structures and independence from the resolution of the tissue voxels (tissue calculation space). The power absorption of the self-regulating seeds is according to empirical data. The thermal effects of an unlimited number of thin layers surrounding the seed (coatings, catheters) can be modelled. The initial calculations have been performed for an array of 12 identical ferromagnetic seeds in a tissue volume with a computer generated artificial vessel network spanning four vessel generations in both the arterial and venous tree. The heterogeneously distributed large isolated vessels impair the temperature distribution significantly, indicating the limited accuracy of continuum models. Simulations with different types of ferromagnetic seeds have confirmed that the efforts of previous studies to optimize the self-regulating temperature control and the implantation techniques of the ferroseeds will improve the homogeneity of the temperature distribution in the target volume. Multifilament seeds implanted in brachytherapy needles and tubular seeds appear to be the most favourable configurations. The division of long seeds into shorter segments with the appropriate Curie temperature will further improve the homogeneity of the temperature distribution without increasing the average temperature in the volume of interest. Given the proper thermal tissue data, the model presented in this study will prove to be a useful tool in making choices for the implant geometry, seed spacing and Curie temperature.

Biophysical Phenomena↗
PubMed1997

Phase II trial of weekly locoregional hyperthermia and cisplatin in patients with a previously irradiated recurrent carcinoma of the uterine cervix.

BACKGROUND: The biologic rationale for combining cisplatin with locoregional hyperthermia (HT) relates to the potentiating effect of HT on cisplatin cytotoxicity. METHODS: Patients with recurrent cervical carcinoma, who had a pelvic recurrence after radiotherapy, were treated with weekly cycles of locoregional HT (using the 70-megahertz, 4 antenna-phased array system for 1 hour and cisplatin, 50 mg/m2 intravenously [i.v.], for a maximum of 12 cycles.) RESULTS: Twenty-three patients were entered in this study. A total of 169 cycles were given. Responses were observed in 12 of 23 patients, a response rate of 52% (95% confidence interval, 31-73%). Salvage surgery became possible in 3 of 12 responding patients, whose tumors were previously considered unresectable. The median duration of response was 9.5+ months, the median overall survival was 8+ months, and the 1-year survival was 42%. No correlation was found between treatment outcome and clinical parameters such as age, weight, performance status, and histology. Thermal parameters such as T20, T50, and T90 were higher in responding patients, but were not significantly different from nonresponding patients. Overall toxicity was moderate. Subcutaneous fatty necrosis due to HT occurred in 10% of the cycles, whereas 2 patients developed skin burns. Squamous cell carcinoma antigen proved to be a valuable tool for the evaluation of response and detection of progression. CONCLUSIONS: Weekly locoregional HT and cisplatin, 50 mg/ m2 i.v., for a maximum of 12 cycles was effective treatment in patients with a previously irradiated recurrent carcinoma of the uterine cervix.

Antigens, Neoplasm↗
PubMed1996

Radiotherapy with or without hyperthermia in the treatment of superficial localized breast cancer: results from five randomized controlled trials. International Collaborative Hyperthermia Group.

PURPOSE: Claims for the value of hyperthermia as an adjunct to radiotherapy in the treatment of cancer have mostly been based on small Phase I or II trials. To test the benefit of this form of treatment, randomized Phase III trials were needed. METHODS AND MATERIALS: Five randomized trials addressing this question were started between 1988 and 1991. In these trials, patients were eligible if they had advanced primary or recurrent breast cancer, and local radiotherapy was indicated in preference to surgery. In addition, heating of the lesions and treatment with a prescribed (re)irradiation schedule had to be feasible and informed consent was obtained. The primary endpoint of all trials was local complete response. Slow recruitment led to a decision to collaborate and combine the trial results in one analysis, and report them simultaneously in one publication. Interim analyses were carried out and the trials were closed to recruitment when a previously agreed statistically significant difference in complete response rate was observed in the two larger trials. RESULTS: We report on pretreatment characteristics, the treatments received, the local response observed, duration of response, time to local failure, distant progression and survival, and treatment toxicity of the 306 patients randomized. The overall CR rate for RT alone was 41% and for the combined treatment arm was 59%, giving, after stratification by trial, an odds ratio of 2.3. Not all trials demonstrated an advantage for the combined treatment, although the 95% confidence intervals of the different trials all contain the pooled odds ratio. The greatest effect was observed in patients with recurrent lesions in previously irradiated areas, where further irradiation was limited to low doses. CONCLUSION: The combined result of the five trials has demonstrated the efficacy of hyperthermia as an adjunct to radiotherapy for treatment of recurrent breast cancer. The implication of these encouraging results is that hyperthermia appears to have an important role in the clinical management of this disease, and there should be no doubt that further studies of the use of hyperthermia are warranted.

Breast Neoplasms↗
PubMed1996

Power absorption and temperature control of multi-filament palladium-nickel thermoseeds for interstitial hyperthermia.

In interstitial hyperthermia using ferromagnetic seeds, multi-filament seeds have gained interest because of a more effective power absorption than solid seeds. Palladium-nickel (PdNi) seeds composed of filaments with diameters in the range from 0.1 to 1.0 mm (maximally 90 filaments) have been investigated to find the conditions for optimal power absorption and temperature control. Magnetic and calorimetric experiments have shown that a decreasing filament radius results in a more effective power absorption. The power absorption approaches a common asymptote for high field intensities at all filament diameters. This asymptotic behaviour can be understood as a consequence of the approach of saturation magnetization of PdNi. The sharpness of the transition at the Curie temperature, which is a measure for the quality of temperature control, improves as the magnetic field strength increases, but it is limited by the asymptote of the power absorption. When the asymptote has been reached the quality of temperature regulation of a seed can only be improved by increasing the amount of PdNi, e.g. by increasing the number of filaments. Calculations of the power absorption, using the generally applied theory based on a linear relation between the magnetization of PdNi and the magnetic field strength, do not correspond quantitatively with experimental results for seeds having an induction number smaller than the 'optimal value' of 2.5. For these seeds the measured heat production is larger than the calculated one.

Calorimetry↗
PubMed1995

The use of a current sheet applicator array for superficial hyperthermia: incoherent versus coherent operation.

There are a number of potential advantages to be gained by using an array of applicators in hyperthermia treatments compared with single applicator systems. These advantages include the possibility of greater spatial control of power deposition and conformability to nonplanar sites. Arrays of applicators can be driven either coherently or incoherently. In the case of coherent operation, an added advantage is the ability to steer power deposition by varying the phases of the antennas. In this study, we investigated the relative merits of the two modes of operation when a 2 x 2 planar array of current sheet applicators is used. The effective field size (EFS) of the array was calculated using a Gaussian beam representation of the applicators on a layered model in which the fat layer had its thickness varied. Good agreement was obtained between the square of the electric field distribution (E2) and quantitative experimental results. It is shown that when the planar array is used with a fat layer greater than about 2 mm present, it should be driven incoherently as this results in a significantly larger EFS than that obtained when the array is driven coherently.

Humans↗
PubMed1995

The development of PdNi thermoseeds for interstitial hyperthermia.

Magnetic induction heating of thermoseed implants can be used to produce highly localized hyperthermia in deep-seated tumors. Automatic temperature control throughout the tumor can be achieved by the self-regulating character of ferromagnetic seeds, which corrects for local variations in heat loss due to blood perfusion. An increased sharpness of the ferromagnetic transition at the Curie temperature, Tc, improves the performance of self-regulating control. This was realized for palladium-nickel alloys by a "cold working" procedure preceded and followed by annealing. Palladium-nickel seeds with a predetermined Tc were produced, showing a sharp decrease at Tc of the magnetic susceptibility and the heat production.

Humans↗
PubMed1991

Results of radiotherapy in patients with stage I orbital non-Hodgkin's lymphoma.

This paper describes the results of radiotherapy in early stage orbital non-Hodgkin's lymphoma. From 1970 to 1985, 33 orbital localizations in 30 patients were treated. The total dose applied ranged from 21 to 57 Gy (2 Gy per fraction), two-thirds of all patients received a dose of 40 Gy. The complete-response rate was 94% and the 10 years actuarial survival was 90%; no significant difference in survival was observed between patients with low grade or intermediate grade lymphoma. No local recurrence was detected during follow up and 20% of the patients developed generalized disease. Two optic nerve neuropathies and three retinopathies were observed in five patients, four of these occurred at a dose level of less than 43 Gy. Keratitis occurred in 58% of the patients treated, a sicca syndrome in 30% and cataract of different grades in 58% of the patients treated. Although local control was excellent, severe complications were observed in 13% of the patients who received a dose of less than 43 Gy.

Dose-Response Relationship, Radiation↗
PubMed1991

Hyperthermia promotes the incidence of tumours following X-irradiation of the rat cervical cord region.

The cervical region of the rat, including the spinal cord (cervical 5-thoracic 2) was irradiated with single doses of 15-32 Gy 250 kV X-rays. Hyperthermia, at temperatures of 42-, 43- and 44 +/- 0.1 degrees C for 30 min was applied to the cervical vertebral column and immediate adjacent tissues for 5-10 min or 7 h after X-irradiation. Over a period of 18-21 months, animals were followed up to monitor neurological complications occurring as a result of damage to the spinal cord (Sminia et al. 1991). We also noted the development of neoplasms either inside or outside the cervical region. The data on tumour incidence were analysed retrospectively using the actuarial method. Although hyperthermia alone was not carcinogenic, it led to a significant increase of radiation-induced tumours. This increase of radiation carcinogenesis was observed both with hyperthermia applied 5-10 min after X-rays and with an interval of 7 h between X-rays and heat. Cancer induction was highest after the lower radiation doses (16 Gy) combined with high heat doses (30 min 44 degrees C). The latent period for induction of tumours by X-rays was 472 +/- 19 days (mean +/- SEM; n = 24). Latency was significantly shortened by hyperthermia to 404 +/- 34 days (n = 22) if applied 5-10 min after X-rays and to 348 +/- 6 days (n = 33) with an interval of 7 h. Histology revealed that 86% (38/44) of the examined tumours found inside the volume treated with hyperthermia and irradiation were sarcomas. The percentage of animals with a tumour outside the treated volume was almost the same for all treatment groups. Most of these tumours were of the mammary gland type.

Animals↗
PubMed1991

Characteristics of a passive RF field probe with fibre-optic link for measurements in liquid hyperthermia phantoms.

An experimental study is described, leading to the design of a near-field electromagnetic radiation probe. A passive field probe with fibre-optic link has been constructed for use in hyperthermia phantoms, i.e. for measurements in lossy media--saline was used in this study as a simulation of biological tissue. The realization of a closed electric circuit on the probe proved to be a major influence on the sensitivity and dynamic range of the probe. The experiments also independently confirmed the dipole length, frequency variations between 5 and 110 MHz and the temperature of the probe as important parameters.

Equipment Design↗
PubMed1989

Carcinoma of the uterine cervix stage IB and IIA: results of postoperative irradiation in patients with microscopic infiltration in the parametrium and/or lymph node metastasis.

One hundred and thirty-two patients received postoperative radiation therapy following radical hysterectomy and pelvic lymphadenectomy for carcinoma of the uterine cervix Stage IB and IIA. In 43 patients with negative lymph node the 5- and 10-year survival rate was 85%. The other 89 patients with positive lymph node had 5- and 10-year survival rates of 60% and 51%, respectively. Multifactorial analysis of prognostic factors in the group of patients with lymph node metastasis disclosed pathology, microscopic infiltration in the parametrium and vascular space invasion as independent prognostic factors, that is, the 5-year survival rates were: 66% for squamous cell carcinomas versus, 25% for adenocarcinomas (p value: 0.001), 76% negative parametrium versus 39% positive parametrium (p value: 0.008), 68% no vascular space invasion versus 43% if invasion was observed (p value: 0.04). Sites of failure in 37 recurrences out of 89 patients with lymph node metastasis were pelvic alone 9, distant metastases alone 15, and combined pelvic plus distant metastasis in 12 patients. In one patient the site of failure was unknown. These data warrant more intensive local and systemic treatment, particularly in patients with poor prognostic factors. In the whole group, severe complications were observed in 11 patients.

Adenocarcinoma↗
PubMed1988

Chestwall recurrences of breast cancer: results of combined treatment with radiation and hyperthermia.

In 35 patients with chestwall recurrences of breast carcinoma, 45 lesions were treated with combined radiation and hyperthermia. The majority of the lesions received 6 fractions of 4 Gy, twice a week during 3 weeks. Hyperthermia was administered within 30 min after irradiation, aiming a tumor temperature of 43 degrees C during one hour. The percentage of complete response (CR) was 57%. In small lesions, the percentage of CR was 80%. The mean duration of the response was 7 months. Response rate increased with increasing temperature. Particularly, mean temperature and isoeffect thermal dose correlated very well with response rate. In nine cases, comparative lesions were treated with either radiation alone or radiation combined with hyperthermia. The response rates were 3/9 and 7/9, respectively. Acute skin reactions were enhanced by the combined treatment. However, late skin reactions were not increased. Although the prognosis of patients with chestwall recurrences is determined by the presence of distant metastases, local control remains an important objective. Combined treatment with radiation and hyperthermia offers the possibility of obtaining a high local control rate particularly in relatively small lesions.

Adult↗
PubMed1986

Combined treatment with radiation and hyperthermia in metastatic malignant melanoma.

In 24 patients with metastatic malignant melanoma, combined treatment with radiation and hyperthermia was administered to 38 localizations, radiation alone to 8 comparative localizations and hyperthermia alone to 3 localizations. Hyperthermia was administered during one hour by using a 433 MHz microwave generator. The heat treatment was given within 30 min following irradiation. Although an intratumoral temperature of 43 degrees C was aimed, considerable variations occurred during one session and from session-to-session. Radiation schedules consisted in either one large fraction (6-8 Gy) once a week in 14-21 days or two fractions (4-5 Gy) twice a week in 21 days. In the group of patients receiving irradiation once a week, three heat treatments were administered. In the twice-a-week radiation schedule, six heat sessions were given. The overall complete response (CR) rate in patients receiving combined treatment was 50%. In the group of patients treated with hyperthermia and irradiation schedules of 8 Gy per fraction, the CR rate was 83%. Irradiation alone achieved 38% CR rate but some of these CR relapsed during follow-up whereas the comparative area treated with radiation and heat remained under control at this time. The lesions treated with heat alone did not show any response to treatment. Enhancement of the acute skin reactions was generally observed. However, because the total doses were relatively low, this enhancement did not constitute a clinical problem. CR appears to occur more frequently in small tumor sizes. The highest and lowest temperature ever registered during any session of hyperthermia did not seem to correlate with the tumor response.

Combined Modality Therapy↗
PubMed1983

Experimental studies on the response of growing bones to X ray and neutron irradiation.

The effects of X ray and 14 MeV neutron irradiation on growing tibia of mice were studied. As reported in the literature, the age of the animal at irradiation was an important factor if the endpoint in analyzing the radiation effect is the absolute shortening, difference in length between unirradiated and irradiated tibia, achieved by the treatment. However, if the growth remaining at the moment of irradiation is taken into account no significant differences in effect were observed with aging, and the dose given appeared to be the overruling factor. This was valid for both X ray and neutron irradiation. Absorbed dose-response curves after X ray irradiation showed a shoulder in the lower range of absorbed doses, which was not the case for neutron irradiation. RBE values for 14 MeV neutrons as compared to 250 kV X rays varied from 3.6 to 2.0 depending on the single absorbed dose level. No differences in RBE were found with aging. A mathematical formula was derived which can predict the absolute shortening when the initial and final length of the tibia are known as well as the absorbed dose of irradiation to be administered.

Animals↗
PubMedDate not supplied

Radiotherapy and hyperthermia.

72 patients with either unresectable or pelvic recurrence of colorectal cancer were treated with combined radiotherapy and locoregional hyperthermia. Radiation doses were 50 Gy or more in patients not previously treated with radiotherapy, and 32 Gy (8 x 4 Gy) in patients who had previously received radiotherapy. Hyperthermia was administered within 30 min of irradiation, and the aim was to give four to six sessions once or twice a week, intending to reach temperatures of at least 41 degrees C over 30 min. The mean of all the minimum (TMIN), maximum (TMAX) and median (TMED) intratumoral temperatures were 39.6, 41.1 and 40.2 degrees C, respectively. Toxicity during hyperthermia treatment consisted mainly of local pain within the heated field (33%) and general discomfort (17%). In 17% of the patients, the hyperthermic treatment was prematurely stopped. Palliation was achieved in 75% of patients with a mean duration of 12 months. The percentage of palliated patients was higher when higher radiation doses were administered. No correlation between palliative effect and thermal parameters was found. A computed tomography scan proved objective remission was obtained in 11 patients (15%). Median survival was 11 months, and 17% of the patients were alive at 3 years. The literature on combined radiotherapy and hyperthermia in colorectal cancer is reviewed. From this review and our own data, it is concluded that thermoradiotherapy is feasible. Acute and late toxicity are not major problems, although pain and general discomfort hamper hyperthermic treatment. The most disappointing fact is that, with the available hyperthermia equipment, the increase in intratumoral temperature does not reach, in general, the therapeutic range.

Colorectal Neoplasms↗
PubMedDate not supplied

Effects of 434 MHz microwave hyperthermia applied to the rat in the region of the cervical spinal cord.

Hyperthermia was applied in the region of the vertebral column between the cervical vertebrae 5 and thoracic 2, using a ring-shaped applicator operating at a microwave frequency of 434 MHz. This region was focally heated, including spinal cord, vertebrae, intervertebral discs and nerve roots. In all experiments temperature was measured at a 'reference' thermocouple probe which was placed against one of the cervical vertebrae 6, 7 or thoracic 1. Temperatures inside the vertebral canal were measured separately and proved to be below the 'reference' temperature: at 42 degrees, 43 degrees, 44 degrees and 45 degrees C (+/- 0.1 degree C) respectively the temperature in the canal was 41.2 degrees, 42.3 degrees, 42.9 degrees and 43.2 degrees C (+/- 0.4 degree C). Temperatures in tissues close to the vertebrae (e.g. within 2 mm lateral to the vertebrae, in the region of the brachial plexus) did not differ significantly from the temperature inside the canal. The temperature inside the intervertebral disc was as high as the 'reference' temperature. Temperatures measured at other sites, e.g. in the oesophagus, rectally and in the cervical muscles 5 or 10 mm lateral from the vertebral column showed that these sites were only slightly heated. The effects of hyperthermia at temperatures inside the spinal canal ranging from 41.2-43.2 degrees C for 30-120 min were investigated. One day after treatment at 41.2 degrees C for 120 min or 42.3 degrees C for 60 min neither neurological symptoms nor deaths were observed. Minor neurological symptoms were observed one day after 75 min at 42.3 degrees C. The incidence and severity of the neurological symptoms (ranging from unco-ordinated use of the forelegs to paralysis) increased with increasing temperature and duration of the hyperthermic treatment. Thermal damage even resulted in lethality: 74 per cent of the rats that died did so between 2 and 42 h after treatment. The LD50 value at 60 days at 43.2 degrees C was 30 min, at 42.9 degrees C, 41 min, and at 42.3 degrees C, 92 min. In most rats with neurological symptoms after treatment, recovery from motor dysfunctions took place within about two weeks. Even severe neurological symptoms which did not lead to lethality recovered completely. At day 60 no neurological symptoms were observed.

Animals↗
PubMedDate not supplied

Quantitative determination of SAR profiles from photographs of the light-emitting diode matrix.

The utility of the light-emitting diode (LED) matrix, i.e. the qualitative localization of maxima and minima in the patterns of the specific absorption rate (SAR), can be extended to quantitative measurements by a method described. With the LED dipoles on the matrix representing light sources of similar characteristics, the minimal field strength necessary to produce light is a criterion which can be easily determined. From the power levels necessary to fulfil this criterion, relative SAR values have been calculated. The attenuation of field strength by the LED matrix has been measured by an additional dipole antenna with fibre-optic read-out, so that the calculated SAR profiles could be corrected for the relatively smaller attenuation near the edges. This technique has been tested for several set-ups in a 'Coaxial TEM applicator' and the resulting SAR profiles along the major axis of the aperture midplane were compared with SAR profiles determined using a single dipole E-field probe. Results show that, from a set of photographs at different power levels, SAR profiles can be constructed with limited accuracy along lines in any direction in the whole aperture midplane and by this the complete two-dimensional SAR pattern can be obtained.

Humans↗