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M C Hulshof

Publications and source records attributed to M C Hulshof.

17 recordsLinked to original sources
PubMed2001

Effects of hyperbaric oxygen and normobaric carbogen on the radiation response of the rat rhabdomyosarcoma R1H.

PURPOSE: Hypoxic tumor cells are an important factor of radioresistance. Hyperbaric oxygen (HBO) and normobaric carbogen (95% oxygen, 5% carbon dioxide) increase the oxygen delivery to tumors. This study was performed to explore changes of tumor oxygenation during a course of fractionated irradiation and to determine the effectiveness of normobaric carbogen and HBO during the final phase of the radiation treatment. METHODS AND MATERIALS: Experiments were performed on the rhabdomyosarcoma R1H growing on WAG/Rij rats. After 20 X-ray fractions of 2 Gy within 4 weeks, oxygen partial pressure (pO2) was measured using the Eppendorf oxygen electrode under ambient conditions, with normobaric carbogen or HBO at a pressure of 240 kPa. Following the 4-week radiation course, a top-up dose of 10-50 Gy was applied in 2-10 fractions of 5 Gy with or without hyperoxygenation. RESULTS: HBO but not carbogen significantly increased the median pO2 in irradiated tumors. The radiation doses to control 50% of tumors were 38.0 Gy, 29.5 Gy, and 25.0 Gy for air, carbogen, and HBO, respectively. Both high oxygen content gas inspirations led to significantly improved tumor responses with oxygen enhancement ratios (OERs) of 1.3 for normobaric carbogen and 1.5 for HBO (air vs. carbogen: p = 0.044; air vs. HBO: p = 0.02; carbogen vs. HBO: p = 0.048). CONCLUSION: Both normobaric carbogen and HBO significantly improved the radiation response of R1H tumors. HBO appeared to be more effective than normobaric carbogen, both with regard to tumor oxygenation and response to irradiation.

Animals↗
PubMed2001

Prognostic factors in glioblastoma multiforme. 10 years experience of a single institution.

BACKGROUND: To analyze prognostic factors in patients with a glioblastoma multiforme treated in an academic institute over the last 10 years. PATIENTS AND METHOD: From 1988 to 1998, 198 patients with pathologically confirmed glioblastoma multiforme were analyzed. Five radiation schedules were used mainly based on pretreatment selection criteria: 1. 60 Gy in 30 fractions followed by an interstitial iridium-192 (Ir-192) boost for selected patients with a good performance and a small circumscribed tumor, 2. 66 Gy in 33 fractions for good performance patients, 3. 40 Gy in eight fractions or 4. 28 Gy in four fractions for poor prognostic patients and 5. no irradiation. RESULTS: Median survival was 16 months, 7 months, 5.6 months, 6.6 months and 1.8 months for the groups treated with Ir-192, 66 Gy, 40 Gy, 28 Gy and the group without treatment, respectively. No significant improvement in survival was encountered over the last 10 years. At multivariate analysis patients treated with a hypofractionated scheme showed a similar survival probability and duration of palliative effect compared to the conventionally fractionated group. The poor prognostic groups receiving radiotherapy had a highly significant better survival compared to the no-treatment group. Patients treated with an Ir-192 boost had a better median survival compared to a historical group matched on selection criteria but without boost treatment (16 vs 9.7 months, n.s.). However, survival at 2 years was similar. Analysis on pretreatment characteristics at multivariate analysis revealed age, neurological performance, addition of radiotherapy, total resection, tumor size post surgery and deterioration before start of radiotherapy (borderline) as significant prognostic factors for survival. CONCLUSION: Despite technical developments in surgery and radiotherapy over the last 10 years, survival of patients with a glioblastoma multiforme has not improved in our institution. The analysis of prognostic factors corresponded well with data from the literature. A short hypofractionated scheme seems to be a more appropriate treatment for patients with intermediate or poor prognosis as compared to a conventional scheme. The benefit in median survival for patients treated with an interstitial boost is partly explained by patient selection. Since there were no long-term survivors with this boost treatment, its clinical value, if there is one, is still limited.

Actuarial Analysis↗
PubMed2000

Brachytherapy: Results of two different therapy strategies for patients with primary glioblastoma multiforme.

BACKGROUND: In the current study, the authors describe and compare two different strategies of brachytherapy for the treatment of patients with primary glioblastoma multiforme (GBM). METHODS: The study was comprised of 84 patients. Forty-five patients were implanted with permanent or temporary low activity iodine-125 ((125)I) seeds in Cologne and 21 patients were implanted with temporary iridium-192 ((192)Ir) wires in Amsterdam. Both groups received external beam radiation therapy (EBRT); the (125)I group received 10-30 grays (Gy) with the implant in situ and the (192)Ir group received 60 Gy before implantation. In Cologne, implantation was performed after a diagnostic stereotactic biopsy whereas in Amsterdam implantation took place after cytoreductive diagnostic surgery. In addition, 18 patients in Amsterdam served as a control group. This group received only EBRT after cytoreductive surgery. RESULTS: In both groups the mean age of the patients was between 50-55 years, with 80% of the patients age > 45 years. The mean implantation volume encompassed by the referenced isodose was 23 cm(3) for (125)I and 48 cm(3) for (192)Ir. Initial dose rates were 2. 5-2.9 centigrays (cGy)/hour for permanent (125)I, 4.6 cGy/hour for temporary (125)I, and 44-100 cGy/hour (mean, 61 cGy) for (192)Ir. A total dose of 50-60 Gy, 60-80 Gy, and 40 Gy, respectively, was administered at the outer margins of the tumor. The median survival was approximately 16 months for both the (125)I group and the (192)Ir group. This was 6 months longer than the median survival in the control group. Reoperations were performed in 4 patients in the (125)I group (9%) versus 7 patients in the (192)Ir group (33%). No complications or late reactions were reported in the (125)I group, whereas one case of hemorrhage and three cases of delayed stroke were observed in the (192)Ir group. CONCLUSIONS: The equal median survival times in these two brachytherapy groups with such different dose rate radiation schedules support the hypothesis that dose rate does not play a major role in the survival of patients with primary GBM.

Adult↗
PubMed2000

Hypofractionation in glioblastoma multiforme.

PURPOSE: To compare conventional fractionation with hypofractionation in patients with a glioblastoma multiforme. Endpoints of the analysis are overall survival and palliative effect. MATERIALS AND METHODS: From 1988 to 1998, 155 patients with pathologically confirmed glioblastoma multiforme were prospectively analysed. Patients without irradiation and patients receiving an interstitial boost were excluded from this analysis. Three different radiation schemes were used in subsequent periods; 33x2, 8x5 and 4x7 Gy. In the last 5 years a scheme of 4x7 Gy conformal irradiation was given to poor prognosis patients. The more favourable group received the conventionally fractionated scheme up to 66 Gy. RESULTS: Median survival was 7, 5.6 and 6.6 months for the 33x2, 8x5 and 4x7 Gy, respectively. In general, patients in the hypofractionation group had far worse prognostic factors compared with patients treated with the conventional scheme. The period of neurological improvement or stabilisation was similar between the 4x7 and 33x2 Gy group. CONCLUSION: An extreme hypofractionation scheme of 4x7 Gy conformal irradiation in poor prognostic glioblastoma patients is well tolerated, convenient for the patient and provides equal palliation without negative effects on survival compared with conventional fractionation.

Adult↗
PubMed1998

[The relationship between the serum level of prostate specific antigen and bone and CT scans in the staging of the primary carcinoma of the prostate].

OBJECTIVE: To determine the relationship between the serum level of prostate-specific antigen (PSA) and the presence of abnormalities in a skeletal or CT scan in patients with primary carcinoma of the prostate. DESIGN: Retrospective. SETTING: Academic Medical Centre, Amsterdam. PATIENTS AND METHODS: The serum PSA levels were compared with the findings in the skeletal and CT scans of 440 patients with carcinoma of the prostate without clinical signs of metastases, seen in the period from January 1990 to December 1994 in the outpatient clinics for Urology of the Academic Medical Centre (AMC) in Amsterdam, Hospital Gooi-Noord in Blaricum and Hospital De Heel in Zaandam. CT scan data were analysed only from the AMC and Hospital Gooi-Noord. RESULTS: There were 76 patients with a positive bone scan (17.3%) and 31 (out of 337; 9.2%) with a positive CT scan. Higher PSA serum levels went together with increasing risk of abnormalities in bone or CT scan. Of 85 patients with PSA values < 10 micrograms/l, none had a positive bone scan and one (out of 73; 1%) a positive CT scan; of the 180 patients with PSA levels < 20 micrograms/l, 4 (2.2%) had a positive bone scan and 2 (out of 154; 1.3%) a positive CT scan. The T stage, the histological grading and the serum alkaline phosphatase activity appeared not to have any supplementary value. CONCLUSION: In view of the low frequency of abnormalities in a bone or CT scan in patients with low PSA levels, it appears justified no longer to recommend bone or CT scanning for staging of patients for a clinically non-metastasized carcinoma of the prostate and serum PSA levels < 20 micrograms/l.

Aged↗
PubMed1998

Management of benign lymphoepithelial lesions of the parotid gland in human immunodeficiency virus-positive patients.

The diagnosis and radiotherapeutic treatment of these HIV-associated benign lymphoepithelial lesions in the parotid gland are discussed. As an example of these lesions, a case is presented involving a 43-year-old HIV-infected man with a 2-year history of enlargements in both parotid glands. After evaluation by computer tomography and cytology, the diagnosis of benign lymphoepithelial lesions was made. Treatment by low-dose radiotherapy (15 Gy) caused regression of both lesions. The lesion on the left regressed completely, but the one on the right side responded only partially. A second course of high-dose radiotherapy (24 Gy) to the right lesion caused regression to a cosmetically acceptable size.

Adult↗
PubMed1998

Lack of perfusion enhancement after administration of nicotinamide and carbogen in patients with glioblastoma: a 99mTc-HMPAO SPECT study.

BACKGROUND: Nicotinamide (NAM) and carbogen both have been shown to enhance the radiation effect in rodent tumour models and are currently being tested in clinical trials. These agents have demonstrated to act against hypoxia and one of their underlying mechanisms could be an increase of tumour blood perfusion. PURPOSE: To analyse the effect of both agents on normal brain perfusion and tumour perfusion in patients with glioblastoma. MATERIALS AND METHODS: Nineteen patients with glioblastoma were studied with 99mtechnetium-hexamethylpropyleneamine oxime single photon emission computed tomography (99mTc-HMPAO SPECT) before and after administration of carbogen and/or NAM. Another six patients were studied with the same procedure but without any flow modulator and were used as controls. RESULTS: Although the variations between patients were large, no significant enhancement in mean tumour and normal brain perfusion could be demonstrated with NAM or carbogen compared to the control patients. Also no consistent changes in the mean perfusion ratio between tumour and surrounding normal brain were found, suggesting an absence of a selective perfusion effect. CONCLUSIONS: No significant influence of carbogen and/or NAM on tumour perfusion and normal brain perfusion could be detected with SPECT in patients with glioblastoma.

Analysis of Variance↗
PubMed1998

Treatment planning of brain implants using vascular information and a new template technique.

A new template technique has been developed for implanting hyperthermia catheters in the treatment of brain tumors. The technique utilizes an imaging template and a drill template which can be rigidly secured to the head with three skull screws. The anatomic and vascular information needed for hyperthermia treatment planning may be assessed with three-dimensional magnetic resonance (MR) imaging and angiography acquisitions which use a surface coil. In the companioning treatment planning system the catheter positions and lengths and the electrodes in the catheter can be interactively manipulated relative to the anatomy and vasculature. The visualization of the blood vessels relative to the template allows the minimization of the risk on intracranial hemorrhages. This template technique is useful for any brain tumor implants, especially when a large number of catheters are involved. A phantom test has shown that this procedure has an accuracy in the order of 1 mm provided that the MR-related geometry distortions are minimized.

Brain Neoplasms↗
PubMed1997

Hypofractionated radiation induces a decrease in cell proliferation but no histological damage to organotypic multicellular spheroids of human glioblastomas.

The aim of this study was to examine the effect of radiation on glioblastoma, using an organotypic multicellular spheroid (OMS) model. Most glioblastoma cell lines are, in contrast to glioblastomas in vivo, relatively radiosensitive. This limits the value of using cell lines for studying the radiation effect of glioblastomas. The advantage of OMS is maintenance of the characteristics of the original tumour, which is lost in conventional cell cultures. OMS prepared from four glioblastomas were treated with hypofractionated radiation with a radiobiologically equivalent dose to standard radiation treatment for glioblastoma patients. After treatment, the histology as well as the cell proliferation of the OMS was examined. After radiation, a significant decrease in cell proliferation was found, although no histological damage to the OMS was observed. The modest effects of radiation on the OMS are in agreement with the limited therapeutic value of radiotherapy for glioblastoma patients. Therefore, OMS seems to be a good alternative for cell lines to study the radiobiological effect on glioblastomas.

Cell Division↗
PubMed1995

Randomised trial of hyperthermia as adjuvant to radiotherapy for recurrent or metastatic malignant melanoma. European Society for Hyperthermic Oncology.

The value of hyperthermia as an adjuvant to radiotherapy in patients with malignant melanoma was studied in a European multicentre trial. 134 metastatic or recurrent lesions of malignant melanoma in 70 patients were randomly assigned to receive radiotherapy (three fractions of 8 Gy or 9 Gy in 8 days) alone or followed by hyperthermia (43 degrees C for 60 min). Overall, the 2-year actuarial local tumour control was 37 (SE 5)%. Univariate analysis showed a beneficial effect of hyperthermia (radiation alone 28% vs combined treatment 46%, p = 0.008) and radiation dose (24 Gy 25% vs 27 Gy 56%, p = 0.02), but no effect of tumour size (< or = 4 cm 42% vs > 4 cm 29%, p = 0.21). Cox multivariate regression analysis showed the most important prognostic variables to be hyperthermia (odds ratio for 2-year local control 1.73 [95% CI 1.07-2.78], p = 0.023), tumour size (0.91 [0.85-0.99], p = 0.05), and radiation dose (1.17 [1.01-1.36], p = 0.05). Addition of heat did not significantly increase acute or late radiation reactions. Heating was well tolerated, but because of difficulties with equipment only 14% of treatments achieved the protocol objective. The overall 5-year survival rate was 19%, but 38% of the patients for whom all known disease was controlled survived 5 years. Adjuvant hyperthermia significantly improved local tumour control when applied in association with radiation in treatment of malignant melanoma. Successful local treatment of patients with a single or a few metastatic malignant melanoma lesions has significant curative potential.

Adult↗
PubMed1994

Accelerated radiotherapy in glioblastoma multiforme: a dose searching prospective study.

The EORTC Radiotherapy Cooperative Group performed a prospective phase II study in glioblastoma multiforme using accelerated radiotherapy in escalating doses. The aims of the study were to investigate acute and late toxicity as well as tumor response and survival. Only the CT-enhanced tumor zone plus a margin of 2-3 cm were treated (mean volume, 1034 +/- 477 cm3). Radiotherapy was administered with 5-18 MV photons. The radiation schedule consisted of 3 fractions of 2 Gy/day, separated with at least 4 h. The first group of patients was scheduled to receive a total dose of 42 Gy, 21 fractions in 9 days. The total dose was then escalated up to 48 Gy (24 fractions in 10 days), 54 Gy (27 fractions in 11 days) and 60 Gy (30 fractions in 12 days). The numbers of patients entered in each dose-level group were 15, 17, 18 and 16, respectively. Acute toxicity was mild, nausea/vomiting was absent in 91% of the patients. In 80% of the patients the neurological condition improved or remained stable compared with the start of radiotherapy but in 58% of the patients steroids were necessary, either increased in dose or initiated. Acute toxicity did not increase with increasing radiation doses although patients treated with 60 Gy more often required steroids than the other groups. Late toxicity was strongly suspected in 2 patients receiving 52 Gy and 56 Gy, respectively. Within the whole group of 66 patients only one recurrence outside the primary site was found.(ABSTRACT TRUNCATED AT 250 WORDS)

Brain Neoplasms↗
PubMed1993

Feasibility of curative radiotherapy with a concomitant boost technique in 33 patients with non-small cell lung cancer (NSCLC)

Thirty-three patients with an inoperable NSCLC were treated with a dose of 60 Gy/20 fractions/25 days, using a concomitant boost technique. A dose of 40 Gy/2 Gy/25 days was given to the tumor area and a part (15 patients) or the whole (18 patients) mediastinum. During each session a simultaneous boost to the tumor of 1 Gy was administered. Moderate acute oesophageal toxicity was observed in 7/33 patients (22%). One out of 33 patients developed serious late oesophageal toxicity. A correlation between the oesophageal toxicity, absorbed oesophageal dose of irradiation and length of the elective field was observed. Five out of 33 patients developed subacute radiation pneumonitis grade 2 or 3. In selected patients with inoperable NSCLC radiotherapy, with a dose of 60 Gy/20 fractions/25 days, using a concomitant technique is feasible.

Adult↗
PubMed1993

Treatment results in primary intraspinal gliomas.

During the period 1970-1990, 50 patients with primary intraspinal gliomas were treated with either surgery alone or combined surgery and postoperative irradiation. Thirty-four patients had an ependymoma. In this group, 17 patients had a macroscopically total tumor resection; 14 of these patients did not receive further additional treatment. The other 17 patients underwent a partial resection or biopsy; 11 of these patients received postoperative radiation therapy. There were 13 patients with astrocytoma and none of these tumors was radically resected. Twelve patients with astrocytoma received postoperative radiation therapy. Average total dose was 49 Gy for both histological types. The 10-year survival rate in the whole group of patients with ependymomas was 91%. Patients with ependymoma treated with partial tumor resection followed by radiotherapy had a similar survival rate as patients with total resected tumors without postoperative irradiation. The local recurrence rate of ependymomas was 25%, without differences between both treatment modalities. There were 3 major complications due to surgery and no late complications related to radiotherapy. The 10-year survival rate in the group of patients with astrocytoma was 43% and tumor progression was the most important cause of death. Three patients had a spongioblastoma and were treated with radiotherapy following biopsy or partial resection. These patients are alive 6, 11 and 15 years after treatment without evidence of disease. On the basis of our retrospective data and those in the literature we would recommend postoperative radiation therapy in all the intraspinal gliomas where total tumor resection is not possible. The recommended total dose is 50 Gy in 5-6 weeks.

Adolescent↗
PubMedDate not supplied

Hyperthermia as an adjuvant to radiation therapy of recurrent or metastatic malignant melanoma. A multicentre randomized trial by the European Society for Hyperthermic Oncology.

The ESHO protocol 3-85 is a multicentre randomized trial investigating the value of hyperthermia as an adjuvant to radiotherapy in treatment of malignant melanoma. A total of 134 metastatic of recurrent malignant melanoma lesions in 70 patients were randomized to receive radiotherapy alone (3 fractions in 8 days) or each fraction followed by hyperthermia (aimed for 43 degrees C for 60 min). Radiation was given with high voltage photons or electrons. Tumours were stratified according to institution and size (above or below 4 cm) and randomly assigned to a total radiation dose of either 24 or 27 Gy to be given with or without hyperthermia. The endpoint was persistent complete response in the treated area. A number of 128 tumours in 68 patients were evaluable, with an observation time between 3 and 72 months. Sixty-five tumours were randomized to radiation alone and 63 to radiation + heat. Sixty received 24 Gy and 68 tumours received 27 Gy, respectively. Size was < or = 4 cm in 81 and > 4 cm in 47 tumours. Overall the 2-year actuarial local tumour control was 37%. Univariate analysis showed prognostic influence of hyperthermia (rad alone 28% versus rad + heat 46%, p = 0.008) and radiation dose (24 Gy 25% versus 27 Gy 56%, p = 0.02), but not of tumour size (small 42% versus large 29%, p = 0.21). A Cox multivariate regression analysis showed the most important prognostic parameters to be: hyperthermia (odds ratio: 1.73 (1.07-2.78), p = 0.02), tumour size (odds ratio: 0.91 (0.85-0.99), p = 0.05) and radiation dose (odds ratio: 1.17 (1.01-1.36), p = 0.05). Analysis of the heating quality showed a significant relationship between the extent of heating and local tumour response. Addition of heat did not significantly increase the acute or late radiation reactions. The overall 5-year survival rate of the patients was 19%, but 38% in patients if all known disease was controlled, compared to 8% in the patients with persistent active disease.

Adult↗
PubMedDate not supplied

Prognostic value of plasma transforming growth factor-beta in patients with glioblastoma multiforme.

We investigated whether the postoperative concentration of circulating transforming growth factor beta (TGF-beta) yields prognostic value in patients with glioblastoma multiforme (gbm). Blood was collected from 20 healthy volunteers and in 28 patients with mainly glioblastoma multiforme (gbm), both before radiotherapy, during and after 4 weeks of irradiation. Both latent and active TGF-beta were quantified directly in the blood plasma using a bioassay with mink lung epithelial cells transfected with a plasminogen activator inhibitor-1 promotor luciferase construct. The average plasma concentration of TGF-beta before radiotherapy for gbm patients was 26.2 ng/ml, which was significant higher than in normal controls (16.2 ng/ml, p=0.02). No correlation was found between TGF-beta and survival, nor between plasma TGF-beta and the diameter of the postoperative contrast-enhancing lesion. The pattern of plasma TGF-beta during radiotherapy did not correlate with the clinical course of patients, nor with the fractionation scheme. Plasma TGF-beta did not reveal a clinical useful prognostic value for gbm patients, which is partly due to the large variation in TGF-beta plasma levels between individual patients.

Aged↗