http://repub.eur.nl/res/aut/16582/ List of Publications en http://repub.eur.nl/static-eur/img/logo.png http://repub.eur.nl http://repub.eur.nl/res/pub/33802/ 2011-11-15T00:00:00Z Purpose: To evaluate the very long-term results of the randomized Post Operative Radiation Therapy in Endometrial Carcinoma (PORTEC)-1 trial for patients with Stage I endometrial carcinoma (EC), focusing on the role of prognostic factors for treatment selection and the long-term risk of second cancers. Patients and Methods: The PORTEC trial (1990-1997) included 714 patients with Stage IC Grade 1-2 or Stage IB Grade 2-3 EC. After surgery, patients were randomly allocated to external-beam pelvic radiotherapy (EBRT) or no additional treatment (NAT). Analysis was by intention to treat. Results: 426 patients were alive at the date of analysis. The median follow-up time was 13.3 years. The 15-year actuarial locoregional recurrence (LRR) rates were 6% for EBRT vs. 15.5% for NAT (p < 0.0001). The 15-year overall survival was 52% vs. 60% (p = 0.14), and the failure-free survival was 50% vs. 54% (p = 0.94). For patients with high-intermediate risk criteria, the 15-year overall survival was 41% vs. 48% (p = 0.51), and the 15-year EC-related death was 14% vs. 13%. Most LRR in the NAT group were vaginal recurrences (11.0% of 15.5%). The 15-year rates of distant metastases were 9% vs. 7% (p = 0.25). Second primary cancers had been diagnosed over 15 years in 19% of all patients, 22% vs. 16% for EBRT vs. NAT (p = 0.10), with observed vs. expected ratios of 1.6 (EBRT) and 1.2 (NAT) compared with a matched population (p = NS). Multivariate analysis confirmed the prognostic significance of Grade 3 for LRR (hazard ratio [HR] 3.4, p = 0.0003) and for EC death (HR 7.3, p < 0.0001), of age >60 (HR 3.9, p = 0.002 for LRR and 2.7, p = 0.01 for EC death) and myometrial invasion >50% (HR 1.9, p = 0.03 and HR 1.9, p = 0.02). Conclusions: The 15-year outcomes of PORTEC-1 confirm the relevance of HIR criteria for treatment selection, and a trend for long-term risk of second cancers. EBRT should be avoided in patients with low- and intermediate-risk EC. http://repub.eur.nl/res/pub/33644/ 2011-08-01T00:00:00Z Only scarce data are available on the utilisation rate of primary radiotherapy (RT) for patients with breast cancer. In this study, we compared the use of primary RT for patients with stages I-III breast cancer in 4 of the 9 Dutch Comprehensive Cancer Centres, focussing specifically on time trends as well as age effects. From the population-based cancer registries, we selected all females diagnosed with breast cancer between 1997 and 2008 (N = 65,966, about 50% of all Dutch breast cancer patients in this period). We observed an overall increase in the use of primary RT for breast cancer patients ranging from 55-61% in 1997 to 58-68% in 2008. This can be explained by a higher rate of breast-conserving surgery (BCS), which was followed by RT in 87-99% of cases, and a reduced rate of total mastectomy (TM) which was followed by RT in 26-47% of cases. Increasing age was associated with a reduced use of RT, especially for those above 75. Finally, we observed a decrease in time of observed regional variances in the use of RT after BCS as well as after TM (for stage III disease). These findings can be attributed to the development and implementation of the Dutch nationwide guidelines for treatment of breast cancer. http://repub.eur.nl/res/pub/34053/ 2011-07-01T00:00:00Z Background: Endometrial cancer (EC) occurs more frequently amongst women over 60 years old, who often also suffer from co-morbidity. Since treatment guidelines are derived from clinical trials that usually exclude such patients, nevertheless these guidelines are also applied for older EC patients. We assessed the independent influence of age and co-morbidity on treatment modalities and survival of patients with stage I EC in everyday clinical practice, thereby also examining the implementation of Dutch guidelines on treatment, since 2000. Methods: All 2099 stage I EC patients diagnosed between 1995 and 2008 in the southern Netherlands were registered in the ECR (Eindhoven Cancer Registry) were included for analysis of the influence of age and co-morbidity on treatment and survival. For co-morbidity we used a modified version of Charlson's list, uniquely recorded in the ECR since 1993. A subgroup analysis was performed of patients who should have received adjuvant radiotherapy based on the risk factors advised in the Dutch guidelines of 2000. We considered five periods (1995-97; 1989-2000; 2001-03; 2004-06; 2007-08). Results: Having two or more co-morbid conditions resulted in a significant reduction of receiving adjuvant radiotherapy (Odds Ratio: 0.6, 95% Confidence Interval (95% CI): 0.3-1.0)) but receiving adjuvant radiotherapy did not appear to improve survival. After adjustment for age, tumour stage, tumour grade, period of diagnosis and treatment, co-morbidity increased the risk of death, especially diabetes (Hazard Ratio (HR) for mortality: 2.9,95% CI: 2.2-4.0), a previous cancer (HR: 2.6, 95%CI: 1.9-3.7) and cardiovascular disease (HR: 2.3, 95%CI: 1.7-3.2). The combination of two or more co-morbid conditions resulted in a HR of 3.0 (95%CI: 2.2-3.9). Conclusion: Co-morbidity decreased the likelihood of receiving adjuvant radiotherapy in patients with stage I EC qualifying to undergo this according to the Dutch guidelines of 2000. Whereas adjuvant radiotherapy did not seem to affect survival in those patients, co-morbidity significantly did. http://repub.eur.nl/res/pub/33687/ 2011-05-01T00:00:00Z Aim: The purpose was to study variations in utilisation rates of external beam radiotherapy (EBRT) and brachytherapy (BT) for prostate cancer patients. Materials and methods: We calculated the proportion and number of EBRT and BT given or planned within 6 months of diagnosis in 4 Dutch regions, according to stage and age in a population-based setting including 47,259 prostate cancer patients diagnosed from 1997 until 2008. Results: During this study period, the overall utilisation rate of EBRT remained stable at around 25%, while the rate of BT for non-metastasized patients increased from 1% (95% CI:0-1%) to 12% (11-13%) in 2006 and slightly decreased towards 10% (9-11%) in 2008. From 2001 on, the overall utilisation rate of EBRT decreased significantly in one region (p < 0.05). In this region, a sharp rise in the utilisation rate of BT for non-metastatic patients was noted to 17% (14-20%) in 2008 after a peak of 24% (21-27%) in 2006. For localised disease, BT was used more often at the expense of EBRT while for locally advanced disease the utilisation rate of EBRT increased. In the multivariate analysis, regional differences in the utilisation rate of EBRT persisted with odds ratios ranging from 0.7 to 0.9 compared to the reference region. Moreover, low rates of EBRT were associated with high BT rates. The regional differences could not be explained by differences in risk profiles. Conclusions: The utilisation rate of EBRT remained stable with limited variation between regions while BT was used increasingly with clear regional differences. To cope with this and in view of the increasing incidence of prostate cancer, adequate resources have to be planned for the optimal care of these patients. http://repub.eur.nl/res/pub/33921/ 2011-05-01T00:00:00Z Purpose: To determine the long-term outcome and health-related quality of life (HRQL) of patients with endometrial carcinoma (EC) treated with or without pelvic radiotherapy in the Post Operative Radiation Therapy in Endometrial Carcinoma 1 (PORTEC-1) trial. Patients and Methods: Between 1990 and 1997, 714 patients with stage IC grade 1 to 2 or IB grade 2 to 3 EC were randomly allocated to pelvic external-beam radiotherapy (EBRT) or no additional treatment (NAT). HRQL was evaluated with the Short Form 36-Item (SF-36) questionnaire; subscales from the European Organisation for Research and Treatment of Cancer (EORTC) PR25 module for bowel and bladder symptoms and the OV28 and CX24 modules for sexual symptoms; and demographic questions. Analysis was by intention-to-treat. Results: Median follow-up was 13.3 years. The 15-year actuarial locoregional recurrence rates were 5.8% for EBRT versus 15.5% for NAT (P < .001), and 15-year overall survival was 52% versus 60% (P = .14). Of the 351 patients confirmed to be alive with correct address, 246 (70%) returned the questionnaire. Patients treated with EBRT reported significant (P < .01) and clinically relevant higher rates of urinary incontinence, diarrhea, and fecal leakage leading to more limitations in daily activities. Increased symptoms were reflected by the frequent use of incontinence materials after EBRT (day and night use, 42.9% v 15.2% for NAT; P < .001). Patients treated with EBRT reported lower scores on the SF-36 scales "physical functioning" (P = .004) and "role-physical" (P = .003). Conclusion: EBRT for endometrial cancer is associated with long-term urinary and bowel symptoms and lower physical and role-physical functioning, even 15 years after treatment. Despite its efficacy in reducing locoregional recurrence, EBRT should be avoided in patients with low- and intermediate-risk EC. http://repub.eur.nl/res/pub/17038/ 2009-11-01T00:00:00Z Objective: This study aims to describe trends and variation in treatment and survival of cervical cancer in two regions in The Netherlands and to relate this to adherence to the treatment recommendations. Study design: Patient characteristics, tumour characteristics, treatment and follow-up data were collected for 1954 cervical cancer cases diagnosed in the period 1989-2004. Results: In FIGO stages IB-IIA 93% of patients were treated according to the recommendations of The Netherlands Working Group Gynaecologic Oncology. Older patients received radiotherapy more often than younger patients: 48% (95%CI 40-57) of patients older than 70 compared to 15% (95%CI 10-20) of patients aged 50-69 and 5% (95%CI 3-7) of patients aged 50 or younger (p < 0.05). In FIGO stages IIB-IVA 76% of patients were treated according to the recommendations of the Working Group. Chemoradiation was given to older patients less often than to younger patients: 2% (95%CI 0.5-5) versus 23% (95%CI 16-29). A decreased risk of death was found for patients receiving chemoradiation (RER 0.6, 95%CI 0.3-0.9) compared to those receiving "radiotherapy only". Conclusion: Far from being always followed, the treatment recommendations were better implemented for treatment of patients with FIGO IB-IIA. Elderly patients received different treatment compared to younger patients in this study and showed an independent increased risk of death in the lower stages, which confirms that the need becomes stronger for paying attention to treatment of elderly patients. http://repub.eur.nl/res/pub/16006/ 2009-06-01T00:00:00Z Purpose: To explore current variations in the use of primary radiotherapy (RT) in a region with two RT departments with adjacent referral areas, one in the eastern and one in the western sector of the southern region of the Netherlands. Methods and Materials: We calculated the proportion of 147,588 patients with newly diagnosed cancer between 1988 and 2006 in the southern Netherlands who received primary RT. Especially for breast and rectal cancer patients we studied primary RT use according to stage (breast cancer) and age and separately for the eastern and western sectors. Results: The number of patients with new diagnoses receiving primary RT increased from 1,668 patients in 1988 to 2,971 patients in 2006, with the proportion of the overall patients receiving RT remaining more or less unchanged (±30%). However, only 20% of elderly patients (75+ years) received primary RT. Over time, more patients with prostate and rectal cancer, fewer patients with lung and bladder cancer or Hodgkin's lymphoma, and, recently, more patients with cervical or endometrial cancer received RT. The proportion of patients with most other tumor types treated with RT remained more or less unchanged. The total RT rate was slightly higher for patients in the eastern sector. Of particular note, patients with breast or rectal cancer in the eastern sector were significantly more likely to receive primary RT than were their counterparts in the western sector (odds ratio = 1.4, 95% confidence interval =1.4-1.5, and odds ratio = 1.4, 95% confidence interval = 1.3-1.6, respectively). Conclusions: Although the number of RT-treated patients increased substantially during 1988 to 2006, the proportion remained essentially unchanged. In addition, large variations were found in referral rates for RT, especially in later years, between the eastern and the western sectors of the region. http://repub.eur.nl/res/pub/16027/ 2009-05-01T00:00:00Z Background and purpose: The suspicion exists that the referral rate for palliative radiotherapy (RT) is too low. RT, especially in a short series, is an essential and established modality within palliative cancer care for localised symptoms. Material and methods: Questionnaires to evaluate the knowledge of palliative RT were sent to the 1100 general practitioners (GP's) in the area of the Comprehensive Cancer Centre South in the Netherlands, covering about 2.6 million inhabitants. Four hundred and ninety-eight questionnaires were evaluated. Results: Forty-six percent of the respondents had cared for patients referred for palliative RT in the last two years. Knowledge about the effects of palliative RT on bone metastases and spinal cord compression was good but about other palliative indications it was moderate to poor. Determinants of the actual referral for palliative RT were mainly patient related. GPs considered their own knowledge to be poor with only 10% reporting previous RT education. Conclusions: It is absolutely necessary to inform GPs about the possibility of short series of palliative irradiation in order to improve their information for symptomatic cancer patients about all possibilities for palliative treatment. http://repub.eur.nl/res/pub/14394/ 2008-01-01T00:00:00Z Objective. The aim of this study was to estimate the effects of age and comorbidity on the choice of treatment modalities and prognosis for patients with cervical cancer. Methods. All patients with cervical cancer newly diagnosed between 1995 and 2004 (n = 775) were selected from the population-based Eindhoven Cancer Registry. Time trends in treatment modalities and differences in treatment between older and younger patients, and those with and without comorbidity were evaluated. Results. Older patients with FIGO Stages IB-IIA, elderly and those with comorbidity underwent less surgery. In multivariate survival analysis, age had independent prognostic value. For patients with FIGO Stages IB2, IIB-IVA, age affected the choice of chemoradiation significantly. According to multivariate survival analysis, comorbidity and FIGO stage were independent prognostic factors. Conclusion. Older patients with cervical cancer and those with comorbidity were treated less aggressively. Because of the ever-increasing role of comorbidity in clinical decision-making for increasingly older patients in the near future, development of age-specific guidelines incorporating levels and management of specific comorbidity seems warranted. http://repub.eur.nl/res/pub/36177/ 2007-10-01T00:00:00Z Aims: To study, in a population-based setting, the use of delayed radiotherapy (RT) in a cohort of 2008 unselected rectal cancer patients diagnosed between 1996 and 2000. Patients and methods: Radiation within 6 months of diagnosis was considered part of the primary treatment (PRT). RT given 6 months or later after diagnosis or after PRT was considered as delayed or secondary RT (SRT). Number, percentage and cumulative proportion of patients receiving SRT were calculated. The odds for receiving SRT (total and for recurrent rectal cancer only) were studied by logistic regression analysis, taking into account age, gender, co-morbidity, socio-economic status, stage, prior PRT and RT department (2 departments, each serving general hospitals only). Results: Forty-six percent of all newly diagnosed patients received RT. Ten percent (n = 203) received at least once SRT, either after PRT or as first RT, of which 96 patients for a relapsed rectal tumour (31 after PRT on the rectal tumour, 65 as a first radiation treatment). In a multivariate analysis of patients with rectal recurrence secondary pelvic irradiation was less often given after primary irradiation (OR: 0.7, 95% CI: 0.4-1.1). Patients with a stage III significantly more often received SRT on a recurrence (OR = 2.5, 95% CI = 1.4-4.5). Generally, patients in the eastern department received more often PRT and less often SRT for recurrence (OR: 0.5, 95% CI: 0.3-0.8). Conclusions: Five percent of all patients with rectal cancer received SRT on a recurrent tumour, with a large variation between the two RT departments in the region. http://repub.eur.nl/res/pub/36027/ 2007-09-01T00:00:00Z Purpose: To compare the health-related quality of life (HRQOL) among 5-10-year survivors of Stage I-II endometrial (adeno-)carcinoma (EC) treated with surgery alone or surgery with external beam adjuvant radiotherapy (EBRT) and an age-matched norm population. Methods and Materials: A population-based, cross-sectional survey was conducted by the Eindhoven Cancer Registry. All patients were included who had been diagnosed with EC between 1994 and 1998 (n = 462). Information from the questionnaires returned was linked to data from the Eindhoven Cancer Registry on patient, tumor, and treatment characteristics. Results: Responses were received from 75% of the patients. The analyses were restricted to women with Stage I-II disease at diagnosis, treated with either surgery alone or surgery with adjuvant EBRT, and without recurrent disease or new primary malignancies (n = 264). The patients who had received adjuvant EBRT (n = 80) had had a significantly higher tumor stage and grade at diagnosis (p < 0.0001) and a longer mean time since diagnosis (p = 0.04). Age, number of comorbid diseases, current marital status, nulliparity, education, and occupation were similar for both treatment groups. On multivariate analyses, adjuvant EBRT was independently and negatively associated with the vitality and physical and social well-being scale scores. The HRQOL scores of both treatment groups, however, were similar to those of an age-matched norm population. Conclusion: In general, the HRQOL of EC survivors is good. EC survivors treated with surgery alone had a better HRQOL than women treated with surgery and adjuvant EBRT, although for both groups, the HRQOL was in the range of the norm population. http://repub.eur.nl/res/pub/35472/ 2007-04-15T00:00:00Z BACKGROUND. The objective of this population-based study was to document the long-term effects (5-15 years postdiagnosis) of non-Hodgkin lymphoma and its treatment on health-related quality of life (HRQL) and social problems. METHODS. The population-based Eindhoven Cancer Registry was used to select all patients who were diagnosed with non-Hodgkin lymphoma from 1989 to 1998. Three hundred sixty patients were invited to complete the 36-item Short Form Health Survey (SF-36) and the Quality of Life-Cancer Survivors questionnaire, and 294 patients (82%) responded. RESULTS. Patients who had received chemotherapy reported significantly worse psychological and social well-being and health-related quality of life (HRQL) than patients who had not received chemotherapy. Radiotherapy and watchful waiting were not associated significantly with HRQL outcomes. Patients who were diagnosed from 10 to 15 years earlier reported better social well-being than patients who were diagnosed from 5 to 9 years earlier. Compared with an age-matched, normative sample from the general population, patients reported significandy worse general health and less vitality, but they reported less bodily pain. Practical problems were reported with work (41%), obtaining health care insurance (6%) and life insurance (15%), and obtaining a home mortgage (22%). CONCLUSIONS. From 5 to 15 years after diagnosis, the general health perceptions and vitality levels of non-Hodgkin lymphoma survivors remained significantly lower than those of their peers in the of general population. In addition, survivors faced practical problems with work and finances that deserve additional attention during the period of rehabilitation. http://repub.eur.nl/res/pub/36151/ 2007-01-01T00:00:00Z Purpose: The use of radiotherapy in patients with advanced Hodgkin's lymphoma (HL) is controversial. The purpose of this study was to describe the role of radiotherapy in patients with advanced HL who were in partial remission (PR) after chemotherapy. Methods: In a prospective randomized trial, patients <70 years old with previously untreated Stage III-IV HL were treated with six to eight cycles of mechlorethamine, vincristine, procarbazine, prednisone/doxorubicin, bleomycine, vinblastine hybrid chemotherapy. Patients in complete remission (CR) after chemotherapy were randomized between no further treatment and involved-field radiotherapy (IF-RT). Those in PR after six cycles received IF-RT (30 Gy to originally involved nodal areas and 18-24 Gy to extranodal sites with or without a boost). Results: Of 739 enrolled patients, 57% were in CR and 33% in PR after chemotherapy. The median follow-up was 7.8 years. Patients in PR had bulky mediastinal involvement significantly more often than did those in CR after chemotherapy. The 8-year event-free survival and overall survival rate for the 227 patients in PR who received IF-RT was 76% and 84%, respectively. These rates were not significantly different from those for CR patients who received IF-RT (73% and 78%) or for those in CR who did not receive IF-RT (77% and 85%). The incidence of second malignancies in patients in PR who were treated with IF-RT was similar to that in nonirradiated patients. Conclusion: Patients in PR after six cycles of mechlorethamine, vincristine, procarbazine, prednisone/doxorubicine, bleomycine, vinblastine treated with IF-RT had 8-year event-free survival and overall survival rates similar to those of patients in CR, suggesting a definite role for RT in these patients.