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H Bartelink

Publications and source records attributed to H Bartelink.

At least 37 records · Page 2Linked to original sources

From translational research to improved local control and survival: the Gilbert Fletcher Award Lecture, Lugano, March 2000.

Recent clinical trials have shown us that it is possible to improve local control and survival by the concomitant use of radiotherapy and chemotherapy in a large variety of solid tumors, such as head and neck, lung, cervical, and anal cancer. The selection of drugs for this combined treatment, however, has been based on a rather empiric approach. Further research combining the clinical and laboratory expertise now offers the possibility of predicting and improving treatment efficacy for radiotherapy and systemic treatment, given alone or in combination. New methods, such as chromosome and gene expression profiling of individual tumors, are now becoming available with the comparative genomic hybridization assay and microchip DNA arrays. These assays will hopefully be of help in selecting patients for their optimal treatment regimen in the near future. Detailed knowledge of the mechanisms of action of these two treatment modalities will also lead to the development of new and more effective drugs, to be used concomitantly. It is the challenge of translational research to implement its opportunities into daily clinical practice. In analogy to the results obtained with concomitant radiotherapy and chemotherapy, this will lead to improved local control and survival rates in cancer patients.

Antineoplastic Agents, Hormonal↗

Postoperative pelvic radiotherapy with or without elective irradiation of para-aortic nodes and liver in rectal cancer patients. A controlled clinical trial of the EORTC Radiotherapy Group.

OBJECTIVE: The purpose of this randomized multicenter study was to assess the impact on disease free and overall survival of low dose irradiation to para-aortic nodes and liver in patients with a locally advanced resected rectal cancer receiving a 50 Gy postoperative pelvic radiotherapy. PATIENTS AND METHODS: Main inclusion criteria were: a curative resection for a histologically proved carcinoma of the rectum, Gunderson-Sosin stages B2-B3, C1-C3, age <70 years. The patients were randomized between pelvic irradiation (Lim-XRT): 50 Gy in 25 fractions over 5 weeks and extended irradiation (Ext-XRT): same scheme/doses in the pelvis and extended fields on para-aortic nodes and liver, delivering 25 Gy in 19 fractions over 25 days. From 1983 to 1992, 484 patients were enrolled by 18 EORTC institutions and 29 patients were ineligible. The end-points were local and distant relapses, toxicity and survival. RESULTS: Compliance to treatment: 87.2% in Lim-XRT arm and 71.8% in Ext-XRT arm. Moderate acute hematological and hepatic toxicities were significantly increased in Ext-XRT arm. Among 325 patients at risk, 44 suffered a severe intestinal complication requiring surgery in 29. The 5- and 10-year estimates of disease free survival were respectively 42 and 31% in Lim-XRT arm and 47 and 31% in Ext-XRT arm (ns). The corresponding figures for overall survival were respectively 45 and 40% in Lim-XRT arm and 48 and 37% in Ext-arm (ns). The 10 years estimate of intra-pelvic failures was approximately 30% in both arms. Patients in Ext-arm appeared to have a slight shorter interval free of liver metastases (P=0.047). CONCLUSION: Low dose irradiation to the para-aortic nodes and liver did not improve survival for patients with resected adenocarcinoma of the rectum.

Aorta, Abdominal↗

Prognostic factors in transitional cell cancer of the bladder: an emerging role for Bcl-2 and p53.

BACKGROUND AND PURPOSE: In a recent study on patients with transitional cell cancer of the bladder treated with curative radiotherapy following TUR-T, we demonstrated that a low apoptotic index and p53 positivity were associated with poor local control. The purpose of this study was to assess the prognostic significance of additional markers implicated in regulation of cell cycle and apoptosis. PATIENTS AND METHODS: Bcl-2, Bax and p21 positivity were detected immunohistochemically on paraffin-embedded pre-treatment biopsies from 83 patients with invasive transitional cell cancer (TCC) of the bladder, treated with radiotherapy. In addition, markers determined in an earlier analysis, i.e.: p53, apoptotic index, cyclin D1, retinoblastoma protein and Ki-67 were included in the multivariate analysis. A stepwise proportional hazard analysis was performed, adjusting for classic prognostic factors (T-stage, grade, multifocality and macroscopic completeness of the TUR). Positivity was defined as >10% of tumor cells staining positive for Bcl-2, Bax and p21, and >20% for p53. RESULTS: Bcl-2 positivity was found in 63%, Bax was positive in 52% and p21 in 55% of cases. In the PH analysis Bcl-2 positivity was found to be related to poor local control (36 vs. 72% at 3 years; P=0.003), as well as to shorter disease-specific survival (74 vs. 94% at 3 years; P=0.017). Evidence for an adverse effect of p53 positivity was also found (local control: 32 vs. 69% at 3 years;P=0.037, disease-specific survival: 76 vs. 92% at 3 years; P=0.043). In an additional PH analysis, we found poor local control rates for bladder cancers with combined Bcl-2 and p53 positivity (17 vs. 65% at 3 years; P=0.0017), and lower disease specific survival (60 vs. 92%; P=0.0024), disease-free survival (7 vs.35%, P=0.0023) and overall survival (39 vs. 80%; P=0.0018). CONCLUSION: This study provides evidence for a poor outcome in patients treated with radiotherapy for TCC of the bladder expressing both Bcl-2 and p53. This relationship was found for local control and disease-free, disease-specific and overall survival.

Adult↗

Does the combination of radiotherapy and debulking surgery favor survival in paranasal sinus carcinoma?

PURPOSE: To determine the contribution of debulking surgery on local control and survival in paranasal sinus tumors. As most patients present with locally advanced disease, the possibility of radical surgery is limited. Consequently, radiotherapy is often needed as monotherapy or as an adjunct to surgery. METHODS AND MATERIALS: Between 1977 and 1996, 73 patients (50 male: 23 female) with a paranasal sinus carcinoma were treated. The histology distribution was as follows: squamous cell carcinoma, 55%; adenocarcinoma, 19%; adenoid cystic carcinoma, 11%; and undifferentiated carcinoma, 15%. The clinical T classification was (UICC/TNM 1997): T2 14%, T3 27%, and T4 59%. Pathological neck nodes were found in 11% of patients. Treatment consisted of surgery only in 3, chemotherapy only in 1, radiotherapy only in 18, both surgery and radiotherapy in 50 patients. One patient did not receive any treatment at all. Three patients had concurrent chemotherapy. Median follow-up was 66 months (range, 1-213 months). RESULTS: Five-year local control (LC) was 65% with combination of radiotherapy and debulking surgery in comparison with 47% with radiotherapy alone, but this difference was not statistically significant (p = 0.58). However, combination treatment gave significantly better 5-year overall survival (OS) (60% vs. 9%; p = 0.001) and 5-year disease-free survival (DFS) (53% vs. 6%; p < 0. 0001). Cox-regression analysis showed that pathologic N status (p = 0.04), palliative intention of treatment (p = 0.018), clinical orbital invasion (p = 0.003), and orbital wall invasion (p = 0.003) were parameters significantly associated with poor local control. Total radiation dose of greater than 65 Gy (p = 0.05) and treatment consisting of radiotherapy alone (p = 0.002) were associated with worse overall survival; for disease-free survival clinical orbital invasion (p = 0.0005), age of greater than 65 years (p = 0.013) and pathologic T4 classification (p = 0.002) were significant factors for an unfavorable outcome. In 19 of 73 patients, 26 serious (mainly ophthalmological) complications were reported; in the majority of these, the visual tract was (partly) included in the treatment fields because of tumor extension. To analyze on which basis patients were selected for the combination therapy, a logistic regression was performed, concluding that clinical T4 classification (p = 0.05), radiological evidence of skull base invasion (p = 0.005), age of greater than 65 years (p = 0.026), radiological evidence of nasopharynx invasion (p = 0.02), clinical suspicion of palate invasion (p = 0.02), and radiological evidence of skin invasion (p = 0.009) were associated with choosing radiotherapy alone. CONCLUSION: Debulking surgery of paranasal sinus malignancies followed by high-dose radiotherapy to the involved sites was associated with better survival and (although not statistically significant) local control. Patient selection, based on clinical and radiological impression of tumor extension, was the main factor explaining these favorable results. We favor this combination regimen because the surgery gives quick relief of complaints and, at the same time, offers an excellent histologically proven staging method, enabling radiotherapy to be adjusted to the involved sites, thereby decreasing the risk of complications. This can all be achieved with a very low orbital exenteration rate.

Adenocarcinoma↗

Long-term results of a randomized trial comparing breast-conserving therapy with mastectomy: European Organization for Research and Treatment of Cancer 10801 trial.

BACKGROUND: Breast-conserving therapy (BCT) has been shown to be as effective as mastectomy in the treatment of tumors 2 cm or smaller. However, evidence of its efficacy, over the long term, in patients with tumors larger than 2 cm is limited. From May 1980 to May 1986, the European Organization for Research and Treatment of Cancer carried out a randomized, multicenter trial comparing BCT with modified radical mastectomy for patients with tumors up to 5 cm. In this analysis, we investigated whether the treatments resulted in different overall survival, time to distant metastasis, or time to locoregional recurrence. METHODS: Of 868 eligible breast cancer patients randomly assigned to the BCT arm or to the modified radical mastectomy arm, 80% had a tumor of 2.1-5 cm. BCT comprised lumpectomy with an attempted margin of 1 cm of healthy tissue and complete axillary clearance, followed by radiotherapy to the breast and a supplementary dose to the tumor bed. The median follow-up was 13.4 years. All P values are two-sided. RESULTS: At 10 years, there was no difference between the two groups in overall survival (66% for the mastectomy patients and 65% for the BCT patients; P =.11) or in their distant metastasis-free rates (66% for the mastectomy patients and 61% for the BCT patients; P =.24). The rate of locoregional recurrence (occurring before or at the same time as distant metastasis) at 10 years did show a statistically significant difference (12% of the mastectomy and 20% of the BCT patients; P =. 01). CONCLUSIONS: BCT and mastectomy demonstrate similar survival rates in a trial in which the great majority of the patients had stage II breast cancer.

Breast Neoplasms↗

DNA-adduct levels as a predictor of outcome for NSCLC patients receiving daily cisplatin and radiotherapy.

We aimed to investigate whether biological factors related to radiosensitivity and chemosensitivity have prognostic significance in non-small-cell-lung-cancer (NSCLC) patients treated with daily low doses of cisplatin and radiotherapy. We treated 27 NSCLC patients with concomitant daily low-dose cisplatin and radiotherapy between 1993 and 1995. Tumour specimens were analyzed for p53 and bcl-2 expression, and for cell proliferation using antibodies against ki-67. In addition, apoptosis was measured by an end-labeling technique (TUNEL). Finally, cisplatin-induced DNA modification in buccal cells was assessed immunocytochemically using a specific anti-serum. Univariate and multivariate analyses were performed to assess the association between the different variables and survival. The median follow-up was 41 months, and 21 patients (78%) have died. In a univariate analysis, age, tumour stage and cisplatin-DNA-adduct staining were the only factors significantly associated with survival (p < 0.05, log-rank test). p53, bcl-2, Ki-67 and apoptosis showed no relationship with outcome. Multivariate analysis revealed that cisplatin-DNA-adduct staining remained an independent prognostic factor (hazard ratio, 0.10, 95% CI, 0.02-0.49), with shorter survival times for patients with low adduct staining.

Adult↗

Radiotherapy in breast-conserving treatment for ductal carcinoma in situ: first results of the EORTC randomised phase III trial 10853. EORTC Breast Cancer Cooperative Group and EORTC Radiotherapy Group.

BACKGROUND: Ductal carcinoma in situ (DCIS) of the breast is a disorder that has become more common since it may manifest as microcalcifications that can be detected by screening mammography. Since selected women with invasive cancer can be treated safely with breast conservation therapy it is paradoxical that total mastectomy has remained the standard treatment for DCIS. We did a randomised phase III clinical trial to investigate the role of radiotherapy after complete local excision of DCIS. METHODS: Between 1986 and 1996, women with clinically or mammographically detected DCIS measuring less than or equal to 5 cm were treated by complete local excision of the lesion and then randomly assigned to either no further treatment (n=503) or to radiotherapy (n=507; 50 Gy in 5 weeks to the whole breast). The median duration of follow-up was 4.25 years (maximum 12.0 years). All analyses were by intention to treat. FINDINGS: 500 patients were followed up in the no further treatment group and 502 in the radiotherapy group. In the no further treatment group 83 women had local recurrence (44 recurrences of DCIS, and 40 invasive breast cancer). In the radiotherapy group 53 women had local recurrences (29 recurrences of DCIS, and 24 invasive breast cancer). The 4-year local relapse-free was 84% in the group treated with local excision alone compared with 91% in the women treated by local excision plus radiotherapy (log rank p=0.005; hazard ratio 0.62). Similar reductions in the risk of invasive (40%, p=0.04) and non-invasive (35%, p=0.06) local recurrence were seen. CONCLUSIONS: Radiotherapy after local excision for DCIS, as compared with local excision alone, reduced the overall number of both invasive and non-invasive recurrences in the ipsilateral breast at a median follow-up of 4.25 years.

Adult↗

Radiation-induced apoptosis.

Radiation-induced apoptosis has been a topic of intense research during the last decade. Its recognition as a significant component of radiation-induced cell death has initiated several lines of investigation aimed at modulating the apoptotic response and thereby radiosensitivity. These strategies require the integration of both classical radiobiological concepts and the knowledge of the biochemical and molecular biological mechanisms involved in apoptosis induction. This review discusses mechanisms of radiation-induced apoptosis and highlights the radiobiological and radiotherapeutical relevance of this mode of cell death.

Animals↗

The influence of patient, tumor and treatment factors on the cosmetic results after breast-conserving therapy in the EORTC 'boost vs. no boost' trial. EORTC Radiotherapy and Breast Cancer Cooperative Groups.

PURPOSE: To analyze the influence of different patient, tumor, and treatment parameters on the cosmetic outcome after breast-conserving therapy at 3-year follow-up. A subjective and an objective cosmetic scoring method was used and the results of both methods were compared. PATIENTS AND METHODS: In EORTC trial 22881/10882, 5569 early-stage breast cancer patients were treated with tumorectomy and axillary dissection, followed by tangential fields irradiation of the breast to a dose of 50 Gy in 5 weeks, at 2 Gy per fraction. A total of 5318 patients, having a microscopically complete tumorectomy, were randomized between no further treatment and a boost of 16 Gy to the primary tumor bed. The cosmetic result at 3-year follow-up was assessed by a panel for 731 patients, and by digitizer measurements, measuring the displacement of the nipple, for 1141 patients. Univariate and multivariate analyses were used to evaluate the correlation between various patient, tumor, and treatment factors and cosmesis. RESULTS: The factors associated with a worsened cosmesis according to the panel evaluation were: an inferior tumor location, a large excision volume, the presence of postoperative breast complications, and the radiotherapy boost. According to the digitizer measurements, a central/superior tumor location, a large excision volume, an increased pathological tumor size, an increased radiation dose inhomogeneity, and an increased bra cup size resulted in an increased asymmetry in nipple position. It appeared that the evaluation of the nipple position (whether by panel or by digitizer) is only moderately representative of the overall cosmetic outcome. CONCLUSION: To achieve a good cosmesis, it is necessary to excise the tumor with a limited margin, to avoid postoperative complications, to assess the need for a boost in the individual patient, and to give the radiation dose as homogeneously as possible. As far as the method of evaluation is concerned, the panel evaluation is the most appropriate method for giving an overall impression of the cosmetic result after breast-conserving therapy (BCT). The use of the digitizer is recommended for comparing the cosmetic outcome of two different approaches to BCT or for analyzing cosmetic changes over time.

Adult↗

Target volumes in radiotherapy for high-grade malignant glioma of the brain.

Delineation of the clinical target volume (CTV) in radiation treatment planning of high-grade glioma is a controversial issue. The use of computerized tomography (CT) and magnetic resonance imaging (MRI) has greatly improved the accuracy of tumor localization in three-dimensional planning. This review aims at critically analyzing available literature data in which tumor extent of high-grade glioma has been assessed using CT and/or MRI and relating this to postmortem observations. Attention is given to the pattern of tumor spread at initial presentation and to tumor recurrence pattern after external beam irradiation. Special emphasis is given to the site of tumor regrowth after radiation treatment in relation to the boundaries of the CTV. Guidelines for delineating CTV will be inferred from this information, taking data on radiation effects on the normal brain into account.

Brain Neoplasms↗

Telemedicine and its impact on cancer management.

The latest dramatic progress in the technologies of the computer industry is likely to increasingly influence the oncologist's daily routine. Besides well known and established telemedical services such as videoconferencing, the most influential trends are the spread of digital hospital infrastructures with unlimited, secured access to all relevant patient information. This article seeks to summarise the most imminent influences of telemedical developments on the future of the oncologist: the effects of telemedical services and electronic infrastructures on clinical workflow and on medical quality management. In addition, the history of telemedicine, recent technologies and the performance of electronic patient records are described.

Computer Security↗

Toxicity of high-dose radiotherapy combined with daily cisplatin in non-small cell lung cancer: results of the EORTC 08912 phase I/II study. European Organization for Research and Treatment of Cancer.

The purpose of this work was to study the feasibility of concurrent chemoradiation in patients with inoperable non-small cell lung cancer (NSCLC). 40 patients with inoperable NSCLC were treated with escalating doses of radiotherapy and cisplatin (cDDP). The radiation dose was increased step by step from 60.5 to 66 Gy in daily fractions of 2.75 Gy. Chemotherapy was also increased step by step from 20 to 24 daily doses of cDDP 6 mg/m(2) and given concurrently with radiotherapy. A dose of 40 Gy/2 Gy/20 fractions (fx) was given to the EPTV (elective planning target volume) which included the gross tumour volume with a margin of 2 cm and part of or the entire mediastinum. During each session a boost dose of 0.75 Gy was given simultaneously to the BPTV (boost planning target volume), which encompassed the GTV (gross tumour volume) with a margin of 1 cm, for the first 20 fx, so the total dose to the tumour was 55 Gy. Cisplatin 6 mg/m(2) was given 1 h prior to radiotherapy at each fraction. From then on the dose of radiation to the BPTV and the dose of cDDP were increased step by step. In group I the BPTV was irradiated with two extra fractions of 2.75 Gy to a total dose of 60. 5 Gy without cDDP. In group II the same total dose of 60.5 Gy was given but the last two fractions were combined with cDDP. In group III four extra fractions of 2.75 Gy were given to the BPTV to a total dose of 66 Gy, only two of these fractions combined with cDDP. Finally, in group IV a total dose of 66 Gy was given in 24 fractions, all fractions combined with cDDP. All patients were planned by means of a CT-based conformal treatment planning. The maximal length of the oesophagus receiving >/=60.5 Gy was 11 cm. 40 patients were evaluable for acute and late toxicity and for survival. Acute toxicity grade >/=3 (common toxicity criteria, CTC) was rarely observed; nausea/vomiting in 3 patients (8%), leucopenia in 2 patients (5%), thrombocytopenia in 2 patients (5%), whilst 2 patients (5%) suffered from severe weight loss. Late side-effects (European Organization for Research and Treatment of Cancer/Radiation Therapy Oncology Group, EORTC/RTOG) were: oesophageal toxicity >/=grade 3 in 2 patients (5%) and radiation pneumonitis grades 1 (3%) and 2 (3%) in 1 patient each. Overall actuarial 1- and 2-year survival was 53% and 40%, respectively. The 1- and 2-year local disease-free interval was 65% and 58% respectively. Radiotherapy at a dose of 66 Gy/2.75 Gy/24 fx combined with daily cDDP 6 mg/m(2) given over 5 weeks is feasible and results in a good local disease-free interval and a good survival rate. This treatment schedule is at present being tested as one of the two treatment arms of EORTC phase III study protocol 08972/22973.

Adult↗

In vitro differentiation characteristics of human skin fibroblasts: correlations with radiotherapy-induced breast fibrosis in patients.

PURPOSE: To determine whether there is an association between dermal fibroblast differentiation characteristics in vitro and breast fibrosis developing in patients following radiotherapy for breast cancer. MATERIALS AND METHODS: Three hundred and eighty-five patients had been characterized for the degree of breast fibrosis and the level of clinical risk factors for fibrosis as established by logistic regression. Early-passage fibroblasts from 79 patients with a high (HR) or low (LR) level of risk factors were studied in vitro. The percentage differentiated cells (%DC) 7 days after 0 and 8 Gy was scored, and unirradiated colonies were scored for the ratio of early:late fibroblast differentiation stages (E:L ratio). RESULTS: %DC: For the 0 Gy data there was a significant interpatient variation (CoV = 55%, p = 0.0001). HR patients with breast fibrosis had a higher %DC compared with patients without (p = 0.017). E:L ratio: for HR patients there was a significant interpatient variation (82%, p = 0.0030) and a lower E:L ratio for patients with fibrosis compared with those without (p = 0.086), but for LR patients this relationship was reversed (p = 0.079) CONCLUSIONS: There was a true interpatient variation in the in vitro parameters of fibroblast differentiation but insufficient correlation with observed fibrosis after radiotherapy for use as a predictive test.

Adult↗