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.