Cryopreservation, semen use and the likelihood of fatherhood in male Hodgkin lymphoma survivors: an EORTC-GELA Lymphoma Group cohort study.

STUDY QUESTION: How does the successful cryopreservation of semen affect the odds of post-treatment fatherhood among Hodgkin lymphoma (HL) survivors? SUMMARY ANSWER: Among 334 survivors who wanted to have children, the availability of cryopreserved semen doubled the odds of post-treatment fatherhood. WHAT IS KNOWN ALREADY: Cryopreservation of semen is the easiest, safest and most accessible way to safeguard fertility in male patients facing cancer treatment. Little is known about what proportion of patients achieve successful semen cryopreservation. To our knowledge, neither the factors which influence the occurrence of semen cryopreservation nor the rates of fatherhood after semen has been cryopreserved have been analysed before. STUDY DESIGN, SIZE, DURATION: This is a cohort study with nested case-control analyses of consecutive Hodgkin survivors treated between 1974 and 2004 in multi-centre randomized controlled trials. A written questionnaire was developed and sent to 1849 male survivors. PARTICIPANTS/MATERIALS, SETTING, METHODS: Nine hundred and two survivors provided analysable answers. The median age at treatment was 31 years. The median follow-up after cryopreservation was 13 years (range 5-36). MAIN RESULTS AND THE ROLE OF CHANCE: Three hundred and sixty-three out of 902 men (40%) cryopreserved semen before the start of potentially gonadotoxic treatment. The likelihood of semen cryopreservation was influenced by age, treatment period, disease stage, treatment modality and education level. Seventy eight of 363 men (21%) used their cryopreserved semen. Men treated between 1994 and 2004 had significantly lower odds of cryopreserved semen use compared with those treated earlier, whereas alkylating or second-line (chemo)therapy significantly increased the odds of use; no other influencing factors were identified. We found an adjusted odds ratio of 2.03 (95% confidence interval 1.11-3.73, P = 0.02) for post-treatment fatherhood if semen cryopreservation was performed. Forty-eight out of 258 men (19%) who had children after HL treatment became a father using cryopreserved semen. LIMITATIONS, REASONS FOR CAUTION: Data came from questionnaires and so this study potentially suffers from response bias. We could not perform an analysis with correction for duration of follow-up or provide an actuarial use rate due to lack of dates of semen utilization. We do not have detailed information on either the techniques used in cryopreserved semen utilization or the number of cycles needed. STUDY FUNDING/COMPETING INTERESTS: Lance Armstrong Foundation, Dutch Cancer Foundation, René Vogels Stichting, no competing interests.

Brachytherapy after external beam radiotherapy and limited surgery preserves bladders for patients with solitary pT1-pT3 bladder tumors.

BACKGROUND: Several French, Belgian and Dutch radiation oncologists have reported good results with the combination of limited surgery after external beam radiotherapy (EBRT) followed by brachytherapy in early-stage muscle-invasive bladder cancer. PATIENTS AND METHODS: Data from 12 of 13 departments which are using this approach have been collected retrospectively, in a multicenter database, resulting in 1040 patients: 811 males and 229 females with a median age of 66 years, range 28-92 years. Results were analyzed according to tumor stage and diameter, histology grade, age and brachytherapy technique, continuous low-dose rate (CLDR) and pulsed dose rate (PDR). RESULTS: At 1, 3 and 5 years, the local recurrence-free probability was 91%, 80% and 75%, metastasis-free probability was 91%, 80% and 74%, disease-free probability was 85%, 68% and 61% and overall survival probability was 91%, 74% and 62%, respectively. The differences in the outcome between the contributing departments were small. After multivariate analysis, the only factor influencing the local control rate was the brachytherapy technique. Toxicity consisted mainly of 24 fistula, 144 ulcers/necroses and 93 other types. CONCLUSIONS: EBRT followed by brachytherapy, combined with limited surgery, offers excellent results in terms of bladder sparing for selected groups of patients suffering from bladder cancer.

Mapping use of radiotherapy for patients with non-small cell lung cancer in the Netherlands between 1997 and 2008.

AIM: After the publication of several reports that the utilisation rate of radiotherapy for patients with non-small cell lung cancer (NSCLC) varies for both medical and non-medical reasons, the utilisation of radiotherapy was studied in four regions in the Netherlands. MATERIALS AND METHODS: Data from 1997-2008 were collected from the population-based cancer registries of four comprehensive cancer centres ('regions'), which represent about half of the Dutch population, resulting in 24 185 non-metastatic patients with NSCLC. Treatment had to be started or planned within 6 months of diagnosis. We evaluated the utilisation of radiotherapy according to age, gender and period for each region. RESULTS: The utilisation of radiotherapy alone decreased over time (from 35 to 19%), whereas the utilisation of radiotherapy in combination with chemotherapy increased (from 5 to 19%). The total utilisation rate remained rather stable at about 40%. The differences between the four regions remained in general no more than 15%. Elderly patients with stage I and II disease had increased odds of receiving radiotherapy (≥75 versus <50 years: odds ratio 2.6, 95% confidence interval 2.0-3.3, whereas this was the opposite for patients with stage III disease: odds ratio 0.5, 95% confidence interval 0.4-0.6). For 17-24% of all patients, especially the elderly, best supportive care was applied. CONCLUSIONS: In the Netherlands, with good accessibility to medical care and well-implemented national guidelines, variation between the four regions is limited for the treatment of non-metastatic NSCLC with radiotherapy.

Use of primary radiotherapy for rectal cancer in the Netherlands between 1997 and 2008: a population-based study.

AIMS: To describe variation in the utilisation rates of primary radiotherapy for patients with rectal cancer in the Netherlands, focusing on time trends and age effects. MATERIALS AND METHODS: Data on primary non-metastatic rectal cancer were derived from the population-based cancer registries of four comprehensive cancer centres (regions) in the Netherlands (1997-2008, n=13,055). RESULTS: An increase in the utilisation rate was noted for the four regions, from 37-46% in 1997 to 66-76% in 2008, for both genders. This increase was found predominately for preoperative radiotherapy (from 13-31% to 58-67%) and (unsurprisingly) was most pronounced for stage T2-3 patients (from 9-27% to 68-80%). The probability of receiving radiotherapy decreased with age: the odds of receiving preoperative radiotherapy was reduced in patients aged 65 years and older, as well as the odds of receiving postoperative radiotherapy in those aged 75 years and older, which remained significant after adjustment for stage, gender and region. Regional differences persisted in multivariable analyses, i.e. the odds of receiving preoperative radiotherapy was reduced in two regions: odds ratio: 0.4 (95% confidence interval: 0.4-0.5) and 0.7 (0.6-0.8). The odds of receiving postoperative radiotherapy was significantly increased in these regions [odds ratio: 2.6 (2.2-3.2) and 1.6 (1.3-1.9), respectively] and reduced in another [odds ratio 0.8 (0.6-0.96)]. CONCLUSIONS: The utilisation rate of radiotherapy for rectal cancer increased significantly over time, particularly for preoperative radiotherapy and was most pronounced for T2-3 patients. Due to national multidisciplinary treatment guidelines, regional differences became limited in recent years after adjustment for age and stage of the disease. A low utilisation rate of radiotherapy was seen in women and elderly patients.

A population-based study on the utilisation rate of primary radiotherapy for prostate cancer in 4 regions in the Netherlands, 1997-2008.

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.

Adherence to national guidelines for treatment and outcome of endometrial cancer stage I in relation to co-morbidity in southern Netherlands 1995-2008.

BACKGROUND: Endometrial cancer (EC) occurs more frequently amongst women over 60years 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.

Comorbidity and age affect treatment policy for cervical cancer: a population-based study in the south of The Netherlands, 1995-2004.

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.

Multicenter cohort study on treatment results and risk factors in stage II endometrial carcinoma.

The aim of this study was to report outcome data and prognostic factors from a large cohort of pathologic stage II endometrioid type endometrial carcinoma. One hundred forty-two stage IIA-B patients were included. A central histopathologic review was performed. Follow-up ranged from 2 to 217 months with a median of 61 months. End points of the study were local and locoregional recurrence rates, distant metastasis-free survival (DMFS), disease-free survival (DFS), and disease-specific survival (DSS). The local failure rate was 5.1% for stage IIA patients and 10.8% for stage IIB patients. Grade was the only significant prognostic factor for local failure. With respect to DMFS, DFS, and DSS, grade 3 showed to be the most prominent prognostic factor in multivariate analyses. Lymphvascular space involvement combined with grades 3 and 2 and myometrial invasion greater than 0.5 also showed to be significant for DMFS and DFS. Our study showed grade 3 to be the most important single independent predictive factor for locoregional and distant recurrences in endometrial carcinoma stage II.

A population-based study of radiotherapy in a cohort of patients with rectal cancer diagnosed between 1996 and 2000.

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.

The morbidity of treatment for patients with Stage I endometrial cancer: results from a randomized trial.

PURPOSE: To compare the treatment complications for patients with Stage I endometrial cancer treated with surgery and pelvic radiotherapy (RT) or surgery alone in a multicenter randomized trial. METHODS AND MATERIALS: The Postoperative Radiation Therapy in Endometrial Carcinoma (PORTEC) trial included patients with endometrial cancer confined to the uterine corpus, either Grade 1 or 2 with more than 50% myometrial invasion, or Grade 2 or 3 with less than 50% myometrial invasion. Surgery consisted of an abdominal hysterectomy and oophorectomy, without lymphadenectomy. After surgery, patients were randomized to receive pelvic RT (46 Gy), or no further treatment. A total of 715 patients were randomized. Treatment complications were graded using the French-Italian glossary. RESULTS: The analysis was done at a median follow-up duration of 60 months. 691 patients were evaluable. Five-year actuarial rates of late complications (Grades 1-4) were 26% in the RT group and 4% in the control group (p < 0.0001). Most were Grade 1 complications, with 5-year rates of 17% in the RT group and 4% in the control group. All severe (Grade 3-4) complications were observed in the RT group (3%). Most complications were of the gastrointestinal tract. The symptoms resolved after some years in 50% of the patients. Grade 1-2 genitourinary complications occurred in 8% of the RT patients, and 4% of the controls. Bone complications occurred in 4 RT patients (1%). Seven patients (2%) discontinued their RT due to acute RT-related symptoms. Patients with acute morbidity had an increased risk of late RT complications (p = 0.001). The 4-field box technique was associated with a lower risk of late complications (p = 0.06). CONCLUSION: Pelvic RT increases the morbidity of treatment in Stage I endometrial cancer. In the PORTEC trial, severe complications occurred in 3% of treated patients, and over 20% experienced mild (mostly Grade 1) symptoms. Patients with acute RT-related morbidity had an increased risk of late complications. As pelvic RT in Stage I endometrial carcinoma was shown to significantly reduce the rate of locoregional recurrence, but without a survival benefit, its use in the adjuvant setting requires careful patient selection (treating those at increased risk of relapse), and the use of treatment schemes with the lowest risk of morbidity.

Surgery and postoperative radiotherapy versus surgery alone for patients with stage-1 endometrial carcinoma: multicentre randomised trial. PORTEC Study Group. Post Operative Radiation Therapy in Endometrial Carcinoma.

BACKGROUND: Postoperative radiotherapy for International Federation of Gynaecology and Obstetrics (FIGO) stage-1 endometrial carcinoma is a subject of controversy due to the low relapse rate and the lack of data from randomised trials. We did a multicentre prospective randomised trial to find whether postoperative pelvic radiotherapy improves locoregional control and survival for patients with stage-1 endometrial carcinoma. METHODS: Patients with stage-1 endometrial carcinoma (grade 1 with deep [> or =50%] myometrial invasion, grade 2 with any invasion, or grade 3 with superficial [<50%] invasion) were enrolled. After total abdominal hysterectomy and bilateral salpingo-oophorectomy, without lymphadenectomy, 715 patients from 19 radiation oncology centres were randomised to pelvic radiotherapy (46 Gy) or no further treatment. The primary study endpoints were locoregional recurrence and death, with treatment-related morbidity and survival after relapse as secondary endpoints. FINDINGS: Analysis was done according to the intention-to-treat principle. Of the 715 patients, 714 could be evaluated. The median duration of follow-up was 52 months. 5-year actuarial locoregional recurrence rates were 4% in the radiotherapy group and 14% in the control group (p<0.001). Actuarial 5-year overall survival rates were similar in the two groups: 81% (radiotherapy) and 85% (controls), p=0.31. Endometrial-cancer-related death rates were 9% in the radiotherapy group and 6% in the control group (p=0.37). Treatment-related complications occurred in 25% of radiotherapy patients, and in 6% of the controls (p<0.0001). Two-thirds of the complications were grade 1. Grade 3-4 complications were seen in eight patients, of which seven were in the radiotherapy group (2%). 2-year survival after vaginal recurrence was 79%, in contrast to 21% after pelvic recurrence or distant metastases. Survival after relapse was significantly (p=0.02) better for patients in the control group. Multivariate analysis showed that for locoregional recurrence, radiotherapy and age below 60 years were significant favourable prognostic factors. INTERPRETATION: Postoperative radiotherapy in stage-1 endometrial carcinoma reduces locoregional recurrence but has no impact on overall survival. Radiotherapy increases treatment-related morbidity. Postoperative radiotherapy is not indicated in patients with stage-1 endometrial carcinoma below 60 years and patients with grade-2 tumours with superficial invasion.

[Pulmonary damage after radiotherapy for breast cancer]. / Longschade na radiotherapie voor mammacarcinoom.

Radiation therapy for breast cancer can cause pulmonary damage. This was diagnosed in two patients aged 75 and 57 years respectively. They had different types of radiation pneumonitis. The first patient presented with a so-called bronchiolitis obliterans organizing pneumonia (BOOP), four months after radiation therapy. Characteristic in BOOP are the bilateral and migrating lung infiltrates that are distributed predominantly in the middle and lower lung zones. The second patient developed a pneumonitis that classically was confined to the area of irradiation four months after radiation therapy. The two types of radiation pneumonitis can be treated successfully with corticosteroids. If symptomatic radiation pneumonitis is diagnosed early it can be treated well and than has a good prognosis.

Postoperative radiotherapy for endometrial carcinoma. Stage I. Wide variation in referral patterns but no effect on long-term survival in a retrospective study in the southeast Netherlands.

The aim of this study was to assess the referral pattern and the impact on long-term survival of postoperative radiotherapy in patients with adenocarcinoma of the endometrium stage I. This was a retrospective study performed in a regional cancer registry which covers a population of approximately 1,000,000 persons. All 724 patients registered between 1975 and 1992 in the Comprehensive Cancer Centre South, Eastern Section, The Netherlands, were analysed. All patients had received surgery as primary treatment which was performed in one of the seven community hospitals of the region. Radiotherapy was given in one regional department. All pathology reports were checked for data on tumour differentiation and myometrial invasion. Almost half the patients (45%) were referred for postoperative radiotherapy. The depth of myometrial invasion and the degree of tumour differentiation were the main factors (P < 0.0001) influencing referral for postoperative radiotherapy. The referral pattern varied between the different hospitals, but became more similar during 1985-1988, to diverge again in recent years. In patients younger than 60 years, the depth of myometrial invasion was significantly (P = 0.01) correlated with survival. In patients older than 60 years, tumour differentiation (P = 0.05) and age (P < 0.001) were correlated with survival, but not the depth of myometrial invasion. After adjustment for known prognostic factors, a survival benefit of postoperative radiotherapy could not be established. The studied group had an excess death rate over the normal Dutch female population. This excess death rate did not decrease during follow-up, as even after 10 years an excess death rate was found. A prospective randomised trial is ongoing in The Netherlands.

Primary gastric non-Hodgkin's lymphoma stage IE and IIE.

The aim of this study was to evaluate retrospectively the different treatment approaches and outcome of patients with stage IE and IIE gastric non-Hodgkin's lymphoma in a cancer registry. Between 1982 and 1992, the Comprehensive Cancer Centre South (CCCS), Eastern Section, The Netherlands, registered, in a population of 1 million people, a total of 81 cases of gastric lymphoma stage IE and IIE (43 men and 38 women). Median age was 69.7 years (range 30.4-88.1). According to the Working Formulation, the malignancy grade was: 9 low, 55 intermediate and 14 high. According to the MALT classification, the malignancy grade was: 38 low and 40 high. Grade was unknown in 3 patients. Patients received the following treatment modalities: surgery alone (n = 22), locoregional radiotherapy without (n = 12) or with (n = 13) surgery; or systemic chemotherapy alone (n = 10) or with radiotherapy and/or surgery (n = 18). No treatment was given or recorded in 6 patients. For stage IE, 5-year actuarial survival and relapse-free survival rates were, respectively, 76 and 64% in 18 patients who received only surgery; 70 and 67% in 17 patients given locoregional treatment (radiotherapy with or without surgery), and 76 and 62% in 13 patients given systemic treatment (chemotherapy alone or with radiotherapy and/or surgery). Radiotherapy as sole treatment seemed to be as effective as other treatment modalities in achieving local and abdominal control. For stage IIE, none of the 4 patients who were treated with surgery alone survived 5 years. The 5-year actuarial survival and relapse-free survival rates of 8 patients who received radiotherapy with or without surgery were, respectively, 25 and 17% and 49 and 33%, for 14 patients given systemic therapy (chemotherapy alone and/or radiotherapy/surgery). In stage IIE, local, abdominal as well as distant relapse were more common, irrespective of treatment modality. In the multivariate analyses, stage (P = 0.002), grade (P = 0.02), age (P = 0.04) and gender (P = 0.04) were significant prognostic factors. This report on a limited number of patients shows that the outcome of patients with stage IIE gastric lymphoma is much worse than for patients with stage IE. Grade, age, gender and particularly stage are much stronger indicators for survival than different modes of treatment. Systemic therapy might improve outcome for stage IIE, but not for stage IE, for which radiotherapy alone seems a good option.

Radiotherapy for T2 and T3 carcinoma of the bladder: the influence of overall treatment time.

The influence of overall treatment time on local control rate was studied on a group of 147 patients with muscle invasive T2 or T3 transitional cell carcinoma of the urinary bladder. All patients received external radiotherapy at the Catharina Hospital, Eindhoven, The Netherlands between January 1974 and December 1984. Patients treated with overall treatment times shorter than 75 days (n = 92) were irradiated during a continuous course; all but one patient, with overall treatment times of 75 days or more (n = 55), received split-course radiotherapy. Actuarial local relapse-free probability at 3 years (LRFP3) was computed from the onset of radiotherapy. LRFP3 proved to be dependent on overall treatment time. For T2 stage, LRFP3 was 80 +/- 18% (n = 5) and 54 +/- 13% (n = 13) for overall times between 15-44 and 45-74 days, respectively, 36 +/- 14% (n = 11) for overall times between 75 and 104 days and 64 +/- 15% (n = 11) for overall times longer than 105 days. For T3 stage, LRFP3 was 33 +/- 19% (n = 6) and 48 +/- 10% (n = 25) for overall times between 15-44 and 45-74 days, respectively, 25 +/- 14% (n = 12) for overall times between 75 and 104 days and 22 +/- 14% (n = 9) for overall times longer than 105 days. The figures between brackets are numbers of patients relapsing within 3 years or at risk of relapse during at least 3 years. Patients who died without local relapse before 3 years were censored. We have reasons to believe that patient selection bias leads to overestimation of LRFP3 for the split-course radiotherapy in retrospective studies where the 'intention to treat' cannot be recalled. This retrospective study suggests that prolonging overall time of radiotherapy has an effect on local control in T2 and T3 transitional cell carcinoma of the urinary bladder. Local control was the worst for patients treated by split-course radiotherapy with a gap of approximately one month. Local control was not further decreased (and seemed even improved) by longer gaps, but this observation is possibly biased as explained in the discussion section. For patients treated by continuous course radiotherapy we could not find a difference in local control rates between patients treated with overall times of 44 days or less and those treated with overall times of 45-74 days.

Adjuvant postoperative radiotherapy for adenocarcinoma of the rectum and rectosigmoid. A retrospective analysis of locoregional control, survival, and prognostic factors on 178 patients.

Results are presented of a retrospective study on 178 patients receiving adjuvant postoperative radiotherapy after curative surgery for adenocarcinoma of the rectum and rectosigmoid. Tumorstages according to Gunderson-Sosin were B2: 67, B3: 5, C1: 9, C2: 94, and C3: 3. Median total dosage was 50 Gy (range: 10-66 Gy), with a median dose per fraction of 2.0 Gy, 5 fractions per week. The censored overall 5-year survival rate was 42%, and 5-year disease-free survival rate was 37%. The respective rates for stage B2 patients (n = 67) were 59% and 53%, and for stage C2 patients (n = 94), 25% and 25%. Recurrences occurred in 89% within 3 years, 8% in the fourth, and 1% in the fifth year of follow-up. Five-year local relapse rates were 27% for the stage B2 tumors and 40% for the stage C2 tumors. For survival, stage (P = .006), grade (P = .02), fixation at surgery (P = .03), and gender (P = .03) were independent prognostic factors. With local relapse-free probability (LRFP) as endpoint, grade (P < .02) was an independent prognostic factor. Dose of radiation was not of prognostic significance, neither for survival (P = .63) nor for LRFP (P = .61). Since improvement should be made in locoregional control, initiatives are taken to start preoperative radiotherapy; furthermore, the key role of surgery is emphasized.

[Adjuvant postoperative radiotherapy in patients with endometrial carcinoma; no effect on length of survival in retrospective study in the Southeastern Netherlands]. / Adjuvante postoperatieve radiotherapie bij patiënten met endometriumcarcinoom; geen effect op overlevingsduur bij retrospectief onderzoek in Zuidoost-Nederland.

OBJECTIVE: To assess the use of postoperative radiotherapy in patients with adenocarcinoma of the endometrium. DESIGN: Retrospective study. SETTING: Catharina Hospital Eindhoven, the Netherlands. METHOD: An assessment was made of referral, survival in relation to patient factors and postoperative radiotherapy treatment, in 422 patients registered in the Eindhoven Cancer Registry between January 1975 and December 1984 with carcinoma of the endometrium. RESULTS: Half the patients (54%) were referred for postoperative radiotherapy, patients over 70 years old less frequently (p = 0.004), patients with deeply infiltrating tumours (p < 0.001) or tumours with poor grade of differentiation (p = 0.03) more frequently. The referral percentages varied between 36% for patients with well differentiated superficial tumours and 83% for patients with poorly differentiated tumours with deep infiltration. Age, postoperative tumour stage and depth of infiltration for patients under 60 showed a statistically significant association with overall survival. A benefit from postoperative radiotherapy with respect to survival could not be established. CONCLUSION: It appears that the variation in referral is also due to differences of opinion concerning appropriate treatment between the referring gynaecologists. This study did not demonstrate a beneficial effect from postoperative radiotherapy. This should be confirmed in a prospective study.

Carcinoma of the urinary bladder: long-term results of interstitial radiotherapy.

Between January 1974 and December 1988, 46 patients with cancer of the urinary bladder, stages T1 or T2, and one patient with stage T3, were treated with an interstitial implant at the radiotherapy department of the Catharina Ziekenhuis at Eindhoven, The Netherlands. Prior to implantation, one patient received no external radiotherapy, all other 46 patients were treated by either a low dose (40 patients: 12 Gy median) or an intermediate dose (six patients: 38-40 Gy) of external radiotherapy. Loco-regional relapse was observed in 14/47 (30%) of the patients (1/14 also had distant metastases). The site of loco-regional relapse was the bladder in 11 patients and the immediate vicinity of the bladder in three patients. Only four patients died due to uncontrolled locoregional disease. A salvage cystectomy was performed in five patients. Distant metastases alone were observed in 3/47 (6.4%) of patients. The intercurrent death corrected actuarial 5 and 10-year survival was 79.5% (72.2% for T1; 85.7% for T2). The difference between T1 and T2 tumors was not significant (P = 0.55). During follow-up, 17/47 (36%) patients died. Cause of death was intercurrent disease in eight patients, bladder cancer in eight patients and unknown cause in one patient. For the whole group, seven patients developed second or third malignancies. Multivariate analyses using survival as the endpoint showed no significant prognostic variables, while using relapse-free survival (RFS) as the endpoint (calculated from the date of interstitial implant and with censoring for death from intercurrent disease) the number of TUR before implant (P = 0.01) and the dose of external radiation before interstitial implant (P = 0.045) were of prognostic significance, both being negatively correlated with RFS. As six patients had received an intermediate dose of interstitial radiotherapy, separate multivariate analyses were performed on the subgroup of 41 patients who had received a high dose of interstitial radiation. Using survival as the endpoint, again no prognostic significant factors were found, but in the analyses using local relapse-free period (LRFP) as the endpoint, dose rate (P = 0.026) and duration of implant (P = 0.021) were inversely correlated with LRFP. The higher the dose rate, the better the LRFP, while a long duration of implantation had a negative impact on the LRFP. Information concerning radiotherapy-related complications was not available in one patient, ulceration of the bladder mucosa was observed in 9/46 (19.6%) and bladder stone formation in 3/46 (6.5%) patients.(ABSTRACT TRUNCATED AT 400 WORDS)

Radiotherapy for locoregional relapses of rectal carcinoma after initial radical surgery: definite but limited influence on relapse-free survival and survival.

A group of 95 patients, treated with irradiation for relapse after radical surgery as only initial treatment modality for a rectal carcinoma was studied. The term locoregional relapse relates to evidence of tumor recurrent in the pelvis or the perineal area. Seventy-six patients presented with locoregional relapse only, and 19 patients presented with locoregional relapse and concomitant distant metastases. All patients were irradiated at the site of locoregional relapse. Total dose of irradiation was resp. 44 Gy median (range 6-66 Gy) and 40 Gy median (range 6-50 Gy). In the group of patients with locoregional relapse only, recurrence-free survival and survival after radiotherapy were, respectively, 23% and 61% at 1 year, and 6% and 13% at 3 years. In the group of patients with concomitant distant metastases, survival after radiotherapy was even worse, 33% at one year, and nihil at 3 years. Recurrences after radiotherapy occurred early during follow-up with 75% of the recurrences being recorded during the first year of follow-up. Recurrent or persistent disease inside the irradiation volume was the most important clinical problem in both groups, being documented in, respectively, 43/76 and 7/19 (7/13 if six patients were excluded with a survival of less than 3 months from onset of therapy). In the group of patients with locoregional relapse only, using recurrence-free survival as the endpoint, dose of irradiation (p = 0.01) was a significant multivariate prognostic factor and using survival as the endpoint, dose of irradiation (p = 0.005) and grade of tumor differentiation (p = 0.002) were significant. Potentials of current radiotherapy regimes are limited. Therefore, maximal initial treatment is warranted. In the event of a relapse after initial radical surgery, one should opt for either more aggressive standard therapy, or either new combined modalities approaches should be studied.

T1 and T2 carcinoma of the urinary bladder: long term results with external, preoperative, or interstitial radiotherapy.

Between January 1974 and December 1984, 273 consecutive patients with cancer of the urinary bladder, Stages T1 or T2, any N, M0, were referred to the radiotherapy department of the Catharina Hospital at Eindhoven, The Netherlands and 265 were treated in a non-randomized fashion according to one of the three following schedules: 137 patients (67 T1, 70 T2) received radiotherapy only; 96 (44 T1, 52 T2) had preoperative radiotherapy followed by cystectomy and diversion according to the Bricker technique in 94/96; 32 patients (13 T1, 19 T2) had low total dose (12 Gy median) external radiotherapy followed by an interstitial cesium implant. The external radiotherapy fields included the pelvic structures. Total dose was 64 Gy median in the radiotherapy-only group and 40 Gy median in the preoperative irradiated group. The median follow-up in survivors was 81 months (range: 15-203). Locoregional relapse was observed in 50% in the group treated by external radiotherapy alone versus 17% in the group treated by preoperative radiation plus surgery and 28% of the patients who received cesium implant. During follow-up, 106/137 (77%), 67/96 (70%) and 13/32 (41%) patients died. In the radiotherapy-alone group, 38 died from intercurrent diseases, 36 from bladder cancer, two from therapy-related complications and cause of death was unknown in 30 patients. In the preoperative radiation group, the figures were 17 for intercurrent deaths, 26 related to progressive bladder cancer, 14 died due to perioperative complications and cause of death was unknown in 10. Cause of death was intercurrent in six and due to bladder cancer in seven patients treated by cesium implant. Probability of survival (calculated from the date of histological diagnosis) for the whole group, with censoring death to intercurrent disease was 53% at 5 years (56% for T1; 51% for T2) and 41% (40% for T1; 43% for T2) at 10 years. No significant difference was observed between T1 and T2 (p = 0.76). Survival in the treatment subgroups was, for patients treated by external radiotherapy only: 50% at 5 years and 33% at 10 years; for patients treated by external radiotherapy and surgery: 49% at 5 years and 42% at 10 years; for patients treated by cesium implant: 76% at 5 years and 76% at 10 years. Survival of patients in the cesium implant group was significantly better than in the other groups (p = 0.0001). Following variables were analyzed using the Cox proportional hazards model: age, gender, T1 or T2 stage, grade, cesium implant or not, and surgery or not.(ABSTRACT TRUNCATED AT 400 WORDS)