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H Bartelink

Publications and source records attributed to H Bartelink.

At least 73 records · Page 4Linked to original sources
PubMed1998

Radiation-induced apoptosis--the ceramide-SAPK signaling pathway and clinical aspects.

Apoptosis, or programmed cell death is an important regulatory mechanism that is involved in a variety of homeostatic processes. Decreased cellular sensitivity or inappropriate responses to apoptotic stimuli may be important factors in tumorigenesis and resistance to anticancer treatments. It is generally accepted that all mammalian cells constitutively express the biochemical machinery to execute apoptosis. It is, however, not clear which signal transduction pathways are involved, or to which extent various stimuli activate independent or partially overlapping pathways. In this paper we discuss the involvement of a ceramide-mediated stress-activated protein kinase (SAPK) signaling cascade in radiation-induced apoptosis. Furthermore, examples are presented of pharmacological intervention in specific signal transduction pathways that lead to modulation of the apoptotic response. Finally, data are presented to illustrate the potential clinical relevance of apoptosis.

Apoptosis↗
PubMed1998

Low predictive value of intrinsic fibroblast radiosensitivity for fibrosis development following radiotherapy for breast cancer.

PURPOSE: To test whether the intrinsic radiosensitivity of skin fibroblasts from breast cancer patients correlates with the degree of breast fibrosis after breast conserving therapy. METHODS: In a systematic study design, 79 patients were selected from an earlier study group of 385 patients based on observed fibrosis and seven identified clinical risk factors for fibrosis development. In vitro radiosensitivity of patients' dermal fibroblasts was determined by clonogenic assay of early passage cultures. Survival was determined after irradiation at 0, 2 and 4 Gy, given in two fractions of 2 Gy with a 6 h interval. RESULTS: There was a significant inter-patient variation for SF2 values (coefficient of variation = 40%). The ratio of SF2 values for fibroblasts from patients with breast fibrosis versus those without was 0.80 (95% CI: 0.60-1.07). This was a statistically non-significant trend (p = 0.13). The same ratio for a derived value for SF2 ((SF2 + square root of SF4)/2) was 0.88 (p = 0.19). CONCLUSIONS: A significant variation in intrinsic radiosensitivity of breast cancer patients' dermal fibroblasts was observed. However, the degree of radiosensitivity did not show a significant correlation with fibrosis development. This indicates that the use of fibroblast radiosensitivity will have a limited usefulness for predicting fibrosis following breast irradiation.

Age Factors↗
PubMed1998

Combined Modality Treatment of Anal Carcinoma.

Within the framework of two phase III clinical trials, the superior results of concomitant chemotherapy and radiotherapy in the treatment of patients with locally advanced anal carcinoma were demonstrated. A further phase III clinical trial showed that the role of mitomycin C as part of the concomitant chemotherapy in combination with 5-fluorouracil appeared to be essential in obtaining a higher local control rate. All three of these randomized trials have shown that this improved local control rate results in a reduction of the colostomy rate. The standard treatment for locally advanced anal carcinoma is therefore the concomitant use of chemotherapy and radiotherapy. Future issues to be clarified include a search for the optimal radiation dose and the use of less toxic agents. For smaller tumors, the addition of chemotherapy still has to be assessed.

Journal Article↗
PubMed1997

The potential impact of CT-MRI matching on tumor volume delineation in advanced head and neck cancer.

PURPOSE: To study the potential impact of the combined use of CT and MRI scans on the Gross Tumor Volume (GTV) estimation and interobserver variation. METHODS AND MATERIALS: Four observers outlined the GTV in six patients with advanced head and neck cancer on CT, axial MRI, and coronal or sagittal MRI. The MRI scans were subsequently matched to the CT scan. The interobserver and interscan set variation were assessed in three dimensions. RESULTS: The mean CT derived volume was a factor of 1.3 larger than the mean axial MRI volume. The range in volumes was larger for the CT than for the axial MRI volumes in five of the six cases. The ratio of the scan set common (i.e., the volume common to all GTVs) and the scan set encompassing volume (i.e., the smallest volume encompassing all GTVs) was closer to one in MRI (0.3-0.6) than in CT (0.1-0.5). The rest volumes (i.e., the volume defined by one observer as GTV in one data set but not in the other data set) were never zero for CT vs. MRI nor for MRI vs. CT. In two cases the craniocaudal border was poorly recognized on the axial MRI but could be delineated with a good agreement between the observers in the coronal/sagittal MRI. CONCLUSIONS: MRI-derived GTVs are smaller and have less interobserver variation than CT-derived GTVs. CT and MRI are complementary in delineating the GTV. A coronal or sagittal MRI adds to a better GTV definition in the craniocaudal direction.

Adenocarcinoma↗
PubMed1997

A feasibility study of accelerated fractionation in radiotherapy of carcinoma of the urinary bladder.

PURPOSE: To establish the shortest possible overall treatment time, with respect to acute and late toxicity, in which a radiation dose of 66 Gy in 2 Gy/fraction can be administered to the urinary bladder. METHODS AND MATERIALS: In a stepwise fashion the overall treatment time of our routinely used conventional treatment schedule (66 Gy in 2 Gy/fraction in 6.5 weeks) was reduced to 5 weeks (Step 1) and then 4 weeks (Step 2). Shortening of the overall treatment time was obtained by giving two daily fractions during the last part of the treatment. The interfraction interval was a minimum of 6 h. Toxicity was scored according to a modified scheme of the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer. Fifteen patients received the 5-week schedule and 25 patients received the 4-week schedule. RESULTS: Note that feasibility was very good for the 5-week schedule. No Grade > or = 3 acute bowel or bladder toxicity was seen in these patients. Severe late complications did not occur. In the 4-week schedule, acute bladder toxicity was unaffected but acute bowel toxicity was considerably increased. Of the 25 patients, 16 suffered from Grade 3 toxicity, 3 from Grade 4, and 1 from Grade 5 toxicity. Actuarial analysis at 3 years showed a 31% incidence of Grade 4 late bladder complications. CONCLUSION: It is concluded that the 5-week schedule is well tolerated. In contrast, the 4-week schedule shows unacceptable acute bowel toxicity and an increased incidence of late bladder complications (p = 0.043).

Aged↗
PubMed1997

Quality assurance of the EORTC Trial 22881/10882: boost versus no boost in breast conserving therapy. An overview.

BACKGROUND: The initial quality assurance programme of the EORTC Radiotherapy Cooperative Group in trial 22881/10882 is described. The implications of its results for quality assurance in future trials are discussed. METHODS: In the EORTC trial 22881/10882 patients with stage I or II breast cancer are treated with tumor excision, axillary dissection, 50 Gy whole breast irradiation and then randomized to receive a boost dose of 15 Gy or no boost following complete tumor excision or between 10 Gy or 25 Gy in case of incomplete excision. To avoid or diminish protocol deviations and to quantify inevitable variations an extensive initial quality assurance programme was conducted. The programme consisted of a dummy run procedure an individual case review procedure, in vivo dosimetry studies and phantom dosimetry studies. RESULTS: This combination of quality assurance procedures allows a good estimation of patient to patient and inter-institutional variations, and early detection of (potential) systematic protocol deviations of 3 types: 1. Deviations due to ambiguities in the protocol prescriptions. 2. Deviations not known to the institution, such as mistakes in implementation of treatment planning algorithms resulting in a systematic overdosage or underdosage. 3. Inability of an institution to cope with (precise) protocol prescriptions for technical or logistic reasons. DISCUSSION: The first 2 types of deviations may be corrected or avoided by direct discussions and recommendations. With respect to the third type it is up to the trial coordinator to accept participation or not, depending upon the relative importance of the particular deviation(s) for the trial end points. To be effective, such a quality assurance programme must be implemented as early as possible in the course of a clinical trial.

Breast Neoplasms↗
PubMed1997

Age is not a limiting factor for radical radiotherapy in pelvic malignancies.

BACKGROUND AND PURPOSE: Pelvic radiotherapy (RT) toxicity in the elderly is poorly documented. We developed a study aiming to evaluate whether or not a limit of age could be identified beyond which toxicities in patients receiving pelvic RT were more frequent or more severe. MATERIAL AND METHODS: 1619 patients with pelvic cancers enrolled in nine EORTC trials, RT arms, were retrospectively studied. Patients were split into six age ranges from 50 years to 70 years and over. Survivals and late toxicity occurrence were calculated with the Kaplan-Meier method and comparison between age groups with the logrank test. A trend test was done to examine if chronological age had an impact on acute toxicity occurrence. RESULTS: Survival was comparable in each age group for prostate (P = 0.18), uterus (0.41), anal canal cancer (P = 0.6) and slightly better for the younger group of rectum cancer (P = 0.04). A total of 1722 acute and 514 late grade > or = 1 were recorded. Acute nausea/ vomiting, skin complications and performance status deterioration were significantly more frequent in younger patients. There was no trend toward more aged patients to experience diarrhea (P = 0.149) and after adjustment on RT dose, acute urinary complications were observed equally in each age range (P = 0.32). Eighty percent of patients were free of late complication at 5 years in each age range (P = 0.79). For the grade > 2 late side-effects, a plateau was observed after 1 year at near 9% without any difference (P = 0.06) nor trend (P = 0.13) between age-groups. CONCLUSION: Age per se is not a limiting factor for radical radiotherapy in pelvic malignancies.

Age Factors↗
PubMed1997

The role of radiotherapy in the local management of dermatofibrosarcoma protuberans. Soft Tissue Tumours Working Group.

Dermatofibrosarcoma protuberans (DFSP), a fibrohistiocytic tumour of intermediate malignancy, has a strong tendency to recur locally. Wide local excision is the recommended treatment modality. A retrospective analysis was performed on 38 consecutive DFSP patients presenting to The Netherlands Cancer Institute, to define the role of radiotherapy. Of the 21 patients treated surgically (all with negative resection margins) seven recurred, a local control probability of 67%. Combined modality treatment was given to 17 patients. Prior to radiotherapy, these patients experienced 33 occurrences of DFSP, but after irradiation only three recurrences were seen, a local control probability of 82%. These results are in keeping with the recent literature where increasing value is being given to both adjuvant and curative radiotherapy in the local management of DFSP. We recommend radiotherapy in DFSP patients where repeated surgery may cause mutilation or functional impairment.

Adult↗
PubMed1997

Hormonal therapy prolongs survival in irradiated locally advanced breast cancer: a European Organization for Research and Treatment of Cancer Randomized Phase III Trial.

PURPOSE: To assess the long-term contribution of adjuvant chemotherapy (CT) and hormonal therapy (HT) in patients with locally advanced breast cancer, and to evaluate the impact of time of analysis on the results during accrual and up to 8 years after closure of a randomized phase III trial. MATERIALS AND METHODS: In a trial using a factorial design, 410 patients were randomized between radiotherapy (RT) alone, RT plus CT, RT plus HT, and RT plus HT plus CT. RESULTS: CT and HT each produced a significant prolongation of the time to locoregional tumor recurrence and to distant progression of disease, with the combined treatments providing the greatest therapeutic effect. At the time of trial closure, a significant improvement of survival was observed in patients who received CT (P = .004); however, with a longer follow-up duration, this effect disappeared (P > .05). HT did not initially appear to improve survival (P = .16); however, in the latest analysis with a long-term follow-up duration, a significant improvement of survival was seen (P = .02). A consistent 25% reduction in the death hazards ratio has been seen at all evaluations since trial closure in patients who received HT. The best survival results were observed in patients who received RT, HT, and CT (P = .02), with a reduction of 35% in the death hazards ratio. CONCLUSION: An improvement in survival attributable to HT has been shown in patients with locally advanced breast cancer. The greatest therapeutic effect was seen in the treatment group that received both CT and HT. The improvement obtained with HT became apparent only after long-term follow-up evaluation.

Breast Neoplasms↗
PubMed1997

Concomitant radiotherapy and chemotherapy is superior to radiotherapy alone in the treatment of locally advanced anal cancer: results of a phase III randomized trial of the European Organization for Research and Treatment of Cancer Radiotherapy and Gastrointestinal Cooperative Groups.

PURPOSE: To investigate the potential gain of the concomitant use of radiotherapy and chemotherapy in improving local control and reducing the need for colostomy, a randomized phase III trial was performed in patients with locally advanced anal cancer. MATERIALS AND METHODS: From 1987 to 1994, 110 patients were randomized between radiotherapy alone and a combination of radiotherapy and chemotherapy. The patients had T3-4NO-3 or T1-2N1-3 anal cancer. Radiotherapy consisted of 45 Gy given in 5 weeks, with a daily dose of 1.8 Gy. After a rest period of 6 weeks, a boost of 20 or 15 Gy was given in case of partial or complete response, respectively. Surgical resection as part of the primary treatment was performed if possible in patients who had not responded 6 weeks after 45 Gy or with residual palpable disease after the completion of treatment. Chemotherapy was given during radiotherapy: 750 mg/m2 daily fluorouracil as a continuous infusion on days 1 to 5 and 29 to 33, and a single dose of mitomycin 15 mg/m2 administered on day 1. RESULTS: The addition of chemotherapy to radiotherapy resulted in a significant increase in the complete remission rate from 54% for radiotherapy alone to 80% for radiotherapy and chemotherapy, and from 85% to 96%, respectively, if results are considered after surgical resections. This led to a significant improvement of locoregional control and colostomy-free interval (P = .02 and P = .002, respectively), both in favor of the combined modality treatment. The locoregional control rate improved by 18% at 5 years, while the colostomy-free rate at that time increased by 32% by the addition of chemotherapy to radiotherapy. No significant difference was found when severe side effects were considered, although anal ulcers were more frequently observed in the combined-treatment arm. The survival rate remained similar in both treatment arms. Skin ulceration, nodal involvement, and sex were the most important prognostic factors for both local control and survival. These remained significant after multivariate analysis. The improvement seen in local control by adding chemotherapy to radiotherapy also remained significant after adjusting for prognostic factors in the multivariate analysis. Event-free survival, defined as free of locoregional progression, no colostomy, and no severe side effects or death, showed significant improvement (P = .03) in favor of the combined-treatment modality. The 5-year survival rate was 56% for the whole patient group. CONCLUSION: The concomitant use of radiotherapy and chemotherapy resulted in a significantly improved locoregional control rate and a reduction of the need for colostomy in patients with locally advanced anal cancer without a significant increase in late side effects.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1997

["Second opinion" in online radiology via Internet: report on implementation and analysis of reliability of findings in sectional images].

Numerous medical on-line services have already been established in the world-wide internet. In connection with the Information service TELESCAN, sponsored by the EU, a pilot project has been initiated which offers a radiological "second opinion" via the transmission of radiological findings and images that have been previously rendered anonymous. In addition to a description of the basic implementation, tests of the diagnostic certainty of the transmitted cranial computed tomographs have been performed. The CT images were digitized with a document camera, transmitted over the Internet, and then evaluated on the receiver's monitor. Both the transfer of originally generated digital image files (in ACR-NEMA or DICOM) as well as graphic files after digitization of X-ray films, for example by a document camera, is possible via electronic post (e-mail). Visualization by the receiver requires the use of current proprietary software for special medical image formats, while standard graphic formats such as GIFF or JPEG can be visualized with the usual Internet software. In an ROC analysis, 56 individual images of cranial computed tomographs, half with pathological findings such as space-occupying lesions, infarcts, or brain edema, were tested with regard to the diagnostic certainty after digitization and transmission. In comparison with the original film findings, there was a slight but statistically not significant reduction in diagnostic certainty of the images evaluated on screen after transfer via the Internet. We believe that this result is due to the low local resolution, low dynamic range, the high image noise and of CT arising from the window technique. The same parameters are probably valid for MRI. The result cannot be applied to conventional radiography including mammography because, in comparison to the mentioned image techniques, their local resolution is high and image noise is considerably lower.

Computer Communication Networks↗
PubMed1996

[Internal radiotherapy in prostatic carcinoma; disappointing long-term results of retropubic Iodine-125 implantation].

OBJECTIVE: To evaluate the results of retropubic implantation of 1-125 seeds in patients with carcinoma of the prostate. DESIGN: Retrospective study of records. SETTING: Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital, Amsterdam, the Netherlands. METHOD: A retrospective study of records provided follow-up data on 75 patients treated in the period 1981-1990 with implantation of 1-125 seeds by a retropubic approach, preceded by pelvic lymph node dissection. Criteria for the treatment were: To, T1 or T2 carcinoma of the prostate, prostatic volume < 40 ml, no contraindications to surgery. RESULTS: The median follow-up was 103 (60-157) months. Four patients died of complications (5%). Major postoperative complications occurred in 23% (17/75) of the cases. Residual carcinoma or distant metastasization was encountered in 43 of the 71 patients (61%). Sixteen patients died from the consequences of the prostatic carcinoma. The 5- and 10-year survival rates amounted to 74% and 42%, respectively, the cancer-specific 5- and 10-year survival rates to 85% and 67%, respectively. At the latest check-up, 18 patients were alive with tumour, 16 of them under hormonal treatment, while 21 patients were alive without indications of active prostatic carcinoma. CONCLUSION: Treatment of carcinoma of the prostate with retropubic implantation of 1-125 seeds resulted in a high incidence of local therapeutic failure and numerous postoperative complications. These results are poorer than those of total prostatectomy and external radiotherapy.

Aged↗
PubMed1996

[Good results of bladder-preserving treatment in poorly differentiated and invasive bladder carcinoma using interstitial Iridium-192 radiotherapy].

OBJECTIVE: The analyse the efficacy and safety of conservative treatment for T1G3 and T2-T3a bladder carcinoma. DESIGN: Retrospective. SETTING: National Cancer Institute/Anthoni van Leeuwenhoek Hospital, Amsterdam, the Netherlands. METHODS: Between 1987 and 1994 (7 years) 63 patients with T1G3 or T2-T3a tumours < 5 cm diameter were treated with a combined approach consisting of a transurethral resection, a course of external irradiation (30 Gy in 15 fractions) to the bladder and an Iridium-192 implant procedure. RESULTS: After a mean follow-up of 4.2 years (range 3 months to 7.2 years) 42 patients were alive without tumour. Fourteen patients died from bladder cancer and 4 patients died from intercurrent disease. Three patients were alive with non-curable cancer. Nine patients had an isolated bladder relapse. Seven of these could be salvaged with cystectomy (3 patients) or transurethral resection (4 patients). Eight patients developed distant metastases only and 7 patients distant metastases combined with bladder recurrence. The 5 year actuarial survival was 66%. Acute and late morbidity was limited and mainly related to the surgical procedure. CONCLUSION: Bladder conservation using Iridium-192 implantation is an effective and safe procedure and in selected group of patients with bladder cancer it is a good alternative to radical cystectomy.

Adult↗