[en] Purpose: To assess morbidity, side effects, and quality of life (QoL) in patients treated for localized prostate cancer with curative aim. Methods and Materials: This descriptive cross-sectional study comprises 154 patients who had undergone definitive radiotherapy (RAD) and 108 patients with radical prostatectomy (PRECT) at the Norwegian Radium Hospital during 1987-1995. At least 1 year after treatment the patients completed several questionnaires assessing quality of life (European Organization for Research and Treatment of Cancer QLQ-C30 instrument [EORTC QLQ-C30]), lower urinary tract symptoms (LUTS): International Prostate Symptom Score (IPSS), or sexuality (selected questions from the Psychosocial Adjustment to Illness Scale [PAIS]). Urinary incontinence and bowel distress were evaluated by ad hoc constructed questionnaires. A control group (OBS) consisted of 38 patients following the watch-and-wait policy. Results: Twenty percent of the patients from the RAD Group had moderate (14%) or severe (6%) LUTS as compared to 12% in the PRECT group. However, 35% of men from the latter group reported moderate to severe urinary incontinence. 'Overall' sexuality was moderately or severely impaired in 71% of the PRECT and 50% of the RAD patients. In the former group high age was correlated with erectile impotency (p < 0.001). In the RAD comorbidity was associated with erectile impotency (p < 0.001). Between 13-38% of the patients recorded moderate or severe bowel distress (blood per rectum: 13%; bowel cramps: 26%; flatulence: 38%), without significant differences comparing patients who had received conventional small 4-field box radiotherapy and patients who had undergone strictly conformal radiotherapy. Despite malignancy and/or treatment-related morbidity, QoL was comparable in both groups with respectively 9% and 6% RAD and PRECT patients, reporting moderately or severely impaired QoL. In the multivariate analysis physical function, emotional function and fatigue were significantly correlated with QoL, whereas sexuality, lower urinary symptoms, and urinary incontinence correlated with QoL only in the univariate analysis. Conclusion: In spite of considerable malignancy and/or treatment-related morbidity QoL was good or only slightly impaired in the majority of patients with localized prostate cancer who presented with stable disease > 1 year after definitive radiotherapy or radical prostatectomy with no difference as compared to the age-matched normal population. Clinicians should be aware of the fact that general QoL dimensions (physical function, emotional function, fatigue) are as a rule of greater significance for QoL than sexuality and lower urinary tract symptoms

[en] Background and purpose: Nausea and vomiting are frequent side effects during adjuvant abdominal radiotherapy in seminoma stage I patients. This study evaluates the efficacy and side effects of prophylactically administered tropisetron in comparison to metoclopramide. Materials and methods: Twenty-three seminona stage I patients who were to undergo adjuvant abdominal radiotherapy (30 Gy) were included in a prospective, randomised, open study. The patients were allocated to receive adjuvant daily tropisetron 5 mg p.o. (TROP group) (11 patients) or metoclopramide 30 mg p.o. (MET group) (12 patients), allowing an eventual dose increase to 60 mg. Evaluation was based on diary cards filled in by the patients during the treatment period. Nausea, vomiting, abdominal pain and bowel motions were assessed. Results: Nausea was significantly lower in the TROP group as compared with the MET group (median: 0.14 vs. 1.32; P = 0.03). Thirty percent of all patients experienced vomiting. In the TROP group one patient had a mean number of emetic events > 0 as compared with 6 patients in the MET group (P = 0.07). Two patients in the TROP group and one in the MET group discontinued therapy due to lacking control of emesis. In two further patients the doubling of the metoclopramide resulted in acceptable control of nausea/vomiting. Both drugs were generally well tolerated. Conclusion: Seminoma stage I patients on tropisetron experienced less nausea and vomiting during abdominal radiotherapy than patients receiving metoclopramide. The costs of the former drug may, however, not justify its use as first choice anti-emetic since few patients in either group experienced severe nausea

[en] This retrospective study describes three clinically different groups of patients with symptomatic androgen-independent prostate cancer (AIPC) referred to palliative radiotherapy (RT): those with a symptomatic pelvic tumour and pelvis-confined disease (M0 P-RT: 35 patients), those with a symptomatic pelvic tumour and distant metastases (M+ P-RT: 97 patients) and those with painful bone metastases (BM-RT: 193 patients). The study emphasises the need of a combined surgical and radiotherapeutic palliation in AIPC patients with symptomatic pelvic tumours. Median overall survival from time of palliative RT was 19, 9 and 8 months for M0 P-RT, M+ P-RT and BM-RT patients, respectively (p<0.001). The significantly prolonged natural course of P-RT patients without distant metastases has to be accounted for in clinical trials of AIPC patients in whom survival represents an endpoint. Furthermore, the optimal palliation regimens for P-RT patients are still to be defined

[en] Late chronic side effects of the rectum constitute one of the principal limiting factors for curative radiation therapy in patients with prostate cancer. The purpose of the study was to determine the impact of immediate androgen deprivation (IAD) prior to conformal radiotherapy on rectal volume exposed to high doses, as compared with a deferred treatment strategy (DAD). Twenty-five patients (13 in the IAD group and 12 in the DAD group) with bulky tumours of the prostate, T3pN1-2M0 from the prospective EORTC trial 30846 were analysed. Three-dimensional conformal radiation treatment plans (3D CRT) using a 4-field box technique were generated based on the digitized computed tomographic or magnetic resonance findings acquired during the first 9 months after inclusion in the EORTC trial. Dose-volume histograms (DVHs) were calculated for the prostate and rectum. In the DAD group, there was no obvious alteration in the mean size of the prostate or other evaluated structures. In the IAD patients, a statistically significant reduction of approximately 40% of the gross tumour volume (GTV) was reached after a 6 months' course of hormonal treatment (p<0.001). High-dose rectal volume was correlated with the volume changes of the GTV (p<0.001). Mean rectal volume receiving 95% or more of the target dose was significantly reduced by 20%. Our study confirms the effect of downsizing of locally advanced prostate tumours following AD treatment and demonstrates the interdependence of the high-dose rectal volume with the volume changes of the GTV. However, the mean beneficial sparing of rectal volume was outweighed in some patients by considerable inter-patient variations

[en] The aim of this study was to examine any relation between DNA ploidy and previously detected TP53 (p53) or p21WAF1/CIP1 expression in 94 patients with muscle-invasive transitional cell carcinoma of the urinary bladder and to associate these factors with survival. DNA ploidy was determined by image cytometry. In a subgroup of patients, the mutational status of the TP53 gene was assessed by temporal temperature gradient electrophoresis (TTGE) or perpendicular denaturant gradient gel electrophoresis (DGGE) and subsequent sequencing. Significantly more aneuploid than euploid tumours showed TP53 accumulation (p = 0.003). Patients with aneuploid tumours lived longer than patients with euploid tumours (p = 0.003). In the euploid, but not in the aneuploid group, TP53 and p21WAF1/CIP1 were associated with cancer-specific survival (p = 0.002 and 0.02, respectively). Patients with > 50% TP53 expression had the longest survival time. Mutation analyses showed acceptable concordance with TP53 expression. We conclude that DNA aneuploidy may confer increased radiosensitivity in bladder cancer patients and that TP53 accumulation may confer increased radiosensitivity, but its effect is detectable only in euploid tumours

[en] The aim of this study was to correlate the expression of cell cycle inhibitors with outcome of patients with muscle-invasive bladder cancer treated with preoperative radiotherapy (46 Gy/4-5 weeks or 20 Gy/1 week) and cystectomy. Patients with pT3b (n=42) or pT0 (n=17) were included in the study. Expression of p16INK4a and p27KIP1 was assessed immunohistochemically in pre-radiotherapy biopsies and cystectomy specimens. Previously reported results of p21CIP1 expression were also included. No difference in pretreatment protein expression was found between patients with pT0 and pT3b. Expression of p21CIP1 and p27KIP1 was lower in cystectomy specimens than in pretreatment biopsies. None of the proteins showed significant impact on survival when analysed separately. However, patients with tumours showing > 50% expression of p16INK4a, p21CIP1, or p27KIP1 displayed poorer cancer-specific survival rates compared with the remaining patients (p=0.025). This effect was more pronounced in patients receiving 46 Gy than in those receiving 20 Gy. In conclusion, low expression of cell cycle inhibitors is related to favourable survival after precystectomy radiotherapy

[en] Purpose. The purpose of this study was to compare late radiation-induced radiological abnormalities of the lung with spirometric observations. Radiological abnormalities were also related to theoretical calculations, in order to predict late effects based on dose-volume histograms. Patients and methods. Sixty-one breast cancer patients who had received postoperative radiotherapy were included. During a follow-up examination 3 years or more after start of radiotherapy, computed tomography (CT) scans and pulmonary function tests were performed. Grading of radiological abnormalities (fibrosis) was performed based on CT images. Based on the dose volume histograms of the lung, effective dose was calculated. Results. There was a positive correlation between the effective radiation dose and the fraction of patients that developed radiation induced fibrosis. No significant association was found between the normalized forced vital capacity (FVC) and the radiological abnormality score or the effective radiation dose. Conclusion. In this study we found no correlation between local radiation-induced changes in the lung tissue and overall lung function. The effective dose was a better predictive factor for radiation induced fibrosis than for overall lung function

[en] Purpose: To compare the efficacy and toxicity of two hypofractionated radiotherapy schedules for the improvement of local symptoms from muscle-invasive bladder cancer. Methods and Materials: A multicenter randomized trial was conducted comparing the efficacy and toxicity of two radiotherapy schedules (35 Gy in 10 fractions and 21 Gy in 3 fractions) for symptomatic improvement in patients considered unsuitable for curative treatment through disease stage or comorbidity. The primary outcome measures were overall symptomatic improvement of bladder-related symptoms at 3 months and changes in bladder- and bowel-related symptoms from pretreatment to end-of-treatment and 3-month assessments. Overall symptomatic improvement was defined prospectively as the improvement in one bladder-related symptom of at least one grade at 3 months, with no deterioration in any other bladder-related symptom. Results: Five hundred patients were recruited, but data on symptomatic improvement at 3 months was only available on 272 patients. Of these, 68% achieved symptomatic improvement (71% for 35 Gy, 64% for 21 Gy), with no evidence of a difference in efficacy or toxicity between the two arms. There was no evidence of a difference in survival between the two schedules (hazard ratio [HR] = 0.99, 95% CI 0.82-1.21, p = 0.933). Conclusion: This is the largest prospective trial to date in the palliative treatment of bladder cancer, and provides baseline data against which other results may be compared. The use of 21 Gy in 3 fractions appears as effective as 35 Gy in 10 fractions, although modest differences in survival, symptomatic improvement rates, and toxicity can not be reliably excluded

[en] Background. The aim of this study was to determine the prevalence and outcome of radiation-induced sarcomas (RISs) among sarcoma patients referred to the Norwegian Radium Hospital (NRH). Material and Methods. Ninety patients were identified from the institutional sarcoma data base. Medical records and histological and cytological material from both primary and secondary tumours were reviewed. Results. RIS represented 3.0 % of the sarcomas in the data base. The median latency time from radiotherapy of the primary tumour to the diagnosis of RIS was 13.6 years (range 2.5-57.8 years). Gynaecological, breast and testicular cancers were the most common primary diagnoses. For the RISs 13 different histological types were identified including 25 malignant fibrous histiocytomas (28% of all) and 22 osteosarcomas (24%). The sarcoma-related 5-year crude survival was 33% (95 % CI 23-43 %). Unfavourable prognostic factors were metastases at presentation, incomplete surgery and presence of tumour necrosis. Conclusion. Radiation-induced sarcoma is rare and harbours an aggressive clinical behaviour. Complete surgical resection is mandatory for cure

[en] Background. Knowledge about female sexual problems after pre- or postoperative (chemo-)radiotherapy and radical resection of rectal cancer is limited. The aim of this study was to compare self-rated sexual functioning in women treated with or without radiotherapy (RT+ vs. RT?), at least two years after surgery for rectal cancer. Methods and materials. Female patients diagnosed from 1993 to 2003 were identified from a national database, the Norwegian Rectal Cancer Registry. Eligible patients were without recurrence or metastases at the time of the study. The Sexual function and Vaginal Changes Questionnaire (SVQ) was used to measure sexual functioning. Results. Questionnaires were returned from 172 of 332 invited and eligible women (52%). The mean age was 65 years (range 42-79) and the time since surgery for rectal cancer was 4.5 years (range 2.6-12.4). Sexual interest was not significantly impaired in RT+ (n=62) compared to RT? (n=110) women. RT+ women reported more vaginal problems in terms of vaginal dryness (50% vs. 24%), dyspareunia (35% vs. 11%) and reduced vaginal dimension (35% vs. 6%) compared with RT? patients; however, they did not have significantly more worries about their sex life. Conclusion. An increased risk of dyspareunia and vaginal dryness was observed in women following surgery combined with (chemo-)radiotherapy compared with women treated with surgery alone. Further research is required to determine the effect of adjuvant therapy on female sexual function