Early hematologic changes during prostate cancer radiotherapy predictive for late urinary and bowel toxicity.

BACKGROUND: The primary objective of the study was to identify early hematologic changes predictive for radiotherapy (RT)-associated genitourinary and gastrointestinal toxicity. METHODS: In a group of 91 prostate cancer patients presenting for primary (n = 51) or postoperative (n = 40) curative RT, blood samples (blood count, acute phase proteins, and cytokines) were analyzed before (T1), three times during (T2-T4), and 6-8 weeks after (T5) radiotherapy. Before RT (baseline), on the last day (acute toxicity), a median of 2 months and 16 months (late toxicity) after RT, patients responded to a validated questionnaire (Expanded Prostate Cancer Index Composite). Acute score changes > 20 points and late changes > 10 points were considered clinically relevant. RESULTS: Radiotherapy resulted in significant changes of hematologic parameters, with the largest effect on lymphocytes (mean decrease of 31-45 %) and significant dependence on target volume. C-reactive protein (CRP) elevation > 5 mg/l and hemoglobin level decrease ≥ 5 G/1 at T2 were found to be independently predictive for acute urinary toxicity (p < 0.01, respectively). CRP elevation was predominantly detected in primary prostate RT (p = 0.02). Early lymphocyte level elevation ≥ 0.3G/l at T2 was protective against late urinary and bowel toxicity (p = 0.02, respectively). Other significant predictive factors for late bowel toxicity were decreasing hemoglobin levels (cut-off ≥ 5 G/l) at T2 (p = 0.04); changes of TNF-α (tumor necrosis factor; p = 0.03) and ferritin levels (p = 0.02) at T5. All patients with late bowel toxicity had interleukin (IL)-6 levels < 1.5 ng/l at T2 (63 % without; p = 0.01). CONCLUSION: Early hematologic changes during prostate cancer radiotherapy are predictive for late urinary and bowel toxicity.

Hematologic changes during prostate cancer radiation therapy are dependent on the treatment volume.

AIM: To assess hematologic changes of modern prostate radiation therapy (RT) comparing different target volumes. PATIENTS & METHODS: Blood samples were evaluated before (T1), during (T2-T4) and 6-8 weeks after (T5) RT in a group of 113 patients. Whole-pelvic RT up to 46 Gy was applied in 27 cases. The total dose to the prostatic fossa (n = 46)/prostate (n = 67) was 66/76 Gy. RESULTS: Erythrocyte, leukocyte and platelet levels decreased significantly relative to baseline levels at T2-T5. Neoadjuvant hormonal therapy had an impact on hemoglobin levels before and during RT. The cumulative incidence of grade 2 leukopenia was 15 versus 2% (p = 0.02) and grade 2 anemia 8 versus 0% (p = 0.03) with versus without whole-pelvic RT, respectively. Lymphocyte decrease was larger at times T2-T5 (36 vs 3% grade 3 toxicity; p < 0.01). CONCLUSION: Prostate RT has a small but significant and longer effect on the blood count. Lower lymphocyte levels need to be considered when larger volumes are treated.

Transurethral resection of the prostate after radiotherapy for prostate cancer: impact on quality of life.

OBJECTIVES: To evaluate the impact of transurethral resection of the prostate on quality of life after radiotherapy for prostate cancer. METHODS: A group of 49 consecutive patients with and 487 without prior transurethral resection of the prostate responded to the Expanded Prostate Cancer Index Composite questionnaire before, on the last day, and a median time of 2 months and 16 months after external beam radiotherapy (70-78 Gy). A matched-pair analysis was used to avoid the influence of treatment-associated confounding factors, including dose, treatment volume and hormonal therapy. RESULTS: Significantly smaller acute urinary score changes relative to baseline levels resulted with versus without prior transurethral resection of the prostate (mean function/bother score decrease of 3/6 vs 18/21 points at the end of radiotherapy; P < 0.01), affecting urinary incontinence (pads to control urinary leakage in 4% vs 24%; P = 0.03) and irritative/obstructive symptoms (big/moderate problem with weak urinary stream in 11% vs 37%; P = 0.02). As opposed to acute changes, transurethral resection of the prostate was a significant predisposing factor for a long-term urinary function score decrease >10 points (20% vs 6% of patients with vs without prior resection; P = 0.04). Urinary incontinence risk was higher for patients with a longer time from resection to radiotherapy. CONCLUSIONS: Transurethral resection of the prostate significantly affects acute (considerably fewer symptoms) and long-term (relevant toxicity in some cases) urinary quality of life after radiotherapy for prostate cancer.

Combination of dose escalation with technological advances (intensity-modulated and image-guided radiotherapy) is not associated with increased morbidity for patients with prostate cancer.

PURPOSE: The aim was to evaluate treatment-related morbidity after intensity-modulated (IMRT) and image-guided (IGRT) radiotherapy with a total dose of 76 Gy in comparison to conventional conformal radiotherapy (3DCRT) up to 70.2-72 Gy for patients with prostate cancer. PATIENTS AND METHODS: All patients were prospectively surveyed prior to, on the last day, as well as after a median time of 2 and 16 months after RT using a validated questionnaire (Expanded Prostate Cancer Index Composite). Criteria for the 78 matched pairs after IMRT vs. 3DCRT were patient age, use of antiandrogens, treatment volume (± whole pelvis), prognostic risk group, and urinary/bowel/sexual quality of life (QoL) before treatment. RESULTS: QoL changes after dose-escalated IMRT were found to be similar to QoL changes after 3DCRT in all domains. Only sexual function scores more than 1 year after RT decreased slightly more after 3DCRT in comparison to IMRT (mean 9 vs. 6 points; p = 0.04), with erections firm enough for intercourse in 14% vs. 30% (p = 0.03). Painful bowel movements were reported more frequently after 3DCRT vs. IMRT 2 months after treatment (≥ once a day in 10% vs. 1%; p = 0.03), but a tendency for higher rectal bleeding rates was found after IMRT vs. 3DCRT more than 1 year after RT (≥ rarely in 20% vs. 9%; p = 0.06). CONCLUSION: Combination of dose escalation with technological advances (IMRT and IGRT) is not associated with increased morbidity for patients with prostate cancer.

Intensity-modulated radiotherapy for prostate cancer implementing molecular imaging with 18F-choline PET-CT to define a simultaneous integrated boost.

PURPOSE: To report the own experience with 66 patients who received 18F-choline PET-CT (positron emission tomography-computed tomography) for treatment planning. PATIENTS AND METHODS: Image acquisition followed 1 h after injection of 178-355 MBq (18)F-choline. An intraprostatic lesion (GTV(PET) [gross tumor volume]) was defined by a tumor-to-background SUV (standard uptake value) ratio > 2. A dose of 76 Gy was prescribed to the prostate in 2-Gy fractions, with a simultaneous integrated boost up to 80 Gy. RESULTS: A boost volume could not be defined for a single patient. One, two and three or more lesions were found for 36 (55%), 22 (33%) and seven patients (11%). The lobe(s) with a positive biopsy correlated with a GTV(PET) in the same lobe in 63 cases (97%). GTV(PET) was additionally defined in 33 of 41 prostate lobes (80%) with only negative biopsies. GTV(PET), SUV(mean) and SUV(max) were found to be dependent on well-known prognostic risk factors, particularly T-stage and Gleason Score. In multivariate analysis, Gleason Score > 7 resulted as an independent factor for GTV(PET) > 8 cm(3) (hazard ratio 5.5; p = 0.02) and SUV(max) > 5 (hazard ratio 4.4; p = 0.04). Neoadjuvant hormonal treatment (NHT) did not affect SUV levels. The mean EUDs (equivalent uniform doses) to the rectum and bladder (55.9 Gy and 54.8 Gy) were comparable to patients (n = 18) who were treated in the same period without a boost (54.3 Gy and 55.6 Gy). CONCLUSION: Treatment planning with (18)F-choline PET-CT allows the definition of an integrated boost in nearly all prostate cancer patients - including patients after NHT - without considerably affecting EUDs for the organs at risk. GTV(PET) and SUV levels were found to be dependent on prognostic risk factors, particularly Gleason Score.

Impact of the target volume (prostate alone vs. prostate with seminal vesicles) and fraction dose (1.8 Gy vs. 2.0 Gy) on quality of life changes after external-beam radiotherapy for prostate cancer.

PURPOSE: To evaluate the impact of the clinical target volume (CTV) and fraction dose on quality of life (QoL) after external-beam radiotherapy (EBRT) for prostate cancer. PATIENTS AND METHODS: A group of 283 patients has been surveyed prospectively before, at the last day, at a median time of 2 months and 15 months after EBRT (70.2-72 Gy) using a validated questionnaire (Expanded Prostate Cancer Index Composite). EBRT of prostate alone (P, n = 70) versus prostate with seminal vesicles (PS, n = 213) was compared. Differences of fraction doses (1.8 Gy, n = 80, vs. 2.0 Gy, n = 69) have been evaluated in the patient group receiving a total dose of 72 Gy. RESULTS: Significantly higher bladder and rectum volumes were found at all dose levels for the patients with PS versus P within the CTV (p < 0.001). Similar volumes resulted in the groups with different fraction doses. Paradoxically, bowel function scores decreased significantly less 2 and 15 months after EBRT of PS versus P. 2 months after EBRT, patients with a fraction dose of 2.0 Gy versus 1.8 Gy reported pain with urination (> or = once a day in 12% vs. 3%; p = 0.04) and painful bowel movements (> or = rarely in 46% vs. 29%; p = 0.05) more frequently. No long-term differences were found. CONCLUSION: The risk of adverse QoL changes after EBRT for prostate cancer cannot be derived from the dose-volume histogram alone. Seminal vesicles can be included in the CTV up to a moderate total dose without adverse effects on QoL. Apart from a longer recovery period, higher fraction doses were not associated with higher toxicity.

Impact of age and comorbidities on health-related quality of life for patients with prostate cancer: evaluation before a curative treatment.

BACKGROUND: Interpretation of comparative health-related quality of life (HRQOL) studies following different prostate cancer treatments is often difficult due to differing patient ages. Furthermore, age-related changes can hardly be discriminated from therapy-related changes. The evaluation of age-and comorbidity-related changes was in focus of this study. METHODS: HRQOL of 528 prostate cancer patients was analysed using a validated questionnaire (Expanded Prostate Cancer Index Composite) before a curative treatment. Patients were divided into age groups 75 years. The impact of specific comorbidities and the Charlson Comorbidity Index (CCI) were evaluated. The questionnaire comprises 50 items concerning the urinary, bowel, sexual and hormonal domains for function and bother. For assessment of sexual and hormonal domains, only patients without prior hormonal treatment were included (n = 336). RESULTS: Urinary incontinence was observed increasingly with higher age (mean function scores of 92/88/85/87 for patients 75 years) complete urinary control in 78%/72%/64%/58% (p < 0.01). Sexual function scores decreased particularly (48/43/35/30), with erections sufficient for intercourse in 68%/50%/36%/32% (p < 0.01) a decrease of more than a third comparing patients 75 years; p < 0.05). A multivariate analysis revealed an independent influence of both age and comorbidities on urinary incontinence, specifically diabetes on urinary bother, and both age and diabetes on sexual function/bother. Rectal domain scores were not significantly influenced by age or comorbidities. A CCI>5 particularly predisposed for lower urinary and sexual HRQOL scores. CONCLUSION: Urinary continence and sexual function are the crucial HRQOL domains with age-related and independently comorbidity-related decreasing scores. The results need to be considered for the interpretation of comparative studies or longitudinal changes after a curative treatment.

Platelet and plasma BDNF in lower respiratory tract infections of the adult.

Enhanced bronchial responsiveness during and following lower respiratory tract infections is a major clinical problem, but its pathogenesis is poorly understood. Brain-derived neurotrophic factor (BDNF), which can be released by platelets and leukocytes, has been identified as a mediator of bronchial hyperresponsiveness. It is unknown whether the release of BDNF is altered during lower respiratory tract infections of the adult. In this clinical pilot study, 16 patients (35-80 years old) with the diagnosis of an acute bacterial lower respiratory tract infection and elevated serum concentrations of c-reactive protein (>100 microg/ml) and procalcitonin (>0.1 ng/ml) were examined on admission to the hospital and 1 week after antibiotic treatment. Sixteen age- and sex-matched controls were examined in the same time period. BDNF concentrations in serum and platelets, but not in plasma, were markedly reduced in patients on the day of admission (median <25% of the controls). Analysis of the platelet marker serotonin (5-HT) suggested that the decrease of platelet BDNF is part of a non-specific release of platelet-derived mediators in this condition. Clinical improvement was accompanied by a restoration of serum and platelet BDNF concentrations which returned to control levels after 1 week of treatment. Cell culture experiments revealed that bacterial lipopolysaccharide (LPS) enhanced the release of BDNF by peripheral blood mononuclear cells of the patients at both time points. In conclusion, these data suggest that lower respiratory tract infections might be associated with an augmented release of BDNF by platelets and mononuclear cells.

Spacer stability and prostate position variability during radiotherapy for prostate cancer applying a hydrogel to protect the rectal wall.

BACKGROUND AND PURPOSE: The aim was to evaluate the spacer dimensions and prostate position variability during the course of radiotherapy for prostate cancer. MATERIALS AND METHODS: CT scans were performed in a group of 15 patients (G1) after the 10 ml injection of a hydrogel spacer (SpaceOAR™) and 30 patients without a spacer (G2) before the beginning of treatment (CT1) and in the last treatment week, 10-12 weeks following spacer implantation (CT2). Spacer dimensions and displacements were determined and prostate displacements compared. RESULTS: Mean volume of the hydrogel increased slightly (17%; p<0.01), in 4 of 15 patients >2 cm(3). The average displacement of the hydrogel center of mass was 0.6mm (87%≤ 2.2mm), -0.6mm (100% ≤ 2.2mm) and 1.4mm (87% ≤ 4.3mm) in the x-, y- and z-axes (not significant). The average distance between prostate and anterior rectal wall before/at the end of radiotherapy was 1.6 cm/1.5 cm, 1.2 cm/1.3 cm and 1.0 cm/1.1cm at the level of the base, middle and apex (G1). Prostate position variations were similar comparing G1 and G2, but significant systematic posterior displacements were only found in G2. CONCLUSIONS: A stable distance between the prostate and anterior rectal wall results during the radiotherapy course after injection of the spacer before treatment planning. Larger posterior prostate displacements could be reduced.

Learning curve in the application of a hydrogel spacer to protect the rectal wall during radiotherapy of localized prostate cancer.

OBJECTIVE: To evaluate the effect of increasing experience on hydrogel dimensions, rectal dose, and acute toxicity, and to discuss important technical issues gained from this experience. METHODS: Sixty-four consecutive patients with prostate cancer were included in this analysis (G1/G2 corresponding to first/second 32 patients) after injection of 10 mL spacer gel. All patients were treated with a 5-field intensity-modulated radiotherapy technique to 76-78 Gy. Treatment toxicity was evaluated with a validated quality of life questionnaire (expanded prostate cancer index composite) before and after radiotherapy. RESULTS: Rectum volume could be entirely excluded from the planning target volume in 31% in G1 vs 56% in G2 (P = .04). Increasing symmetry was detected comparing the first 15 patients to the subsequent rest, with mean differences between right and left of 0.6 cm vs 0.3 cm at the midgland (P = .03). Mean distance between prostate and anterior rectal wall increased from 0.8 cm/1.1 cm/0.8 cm (G1) at the base/middle/apex to 1.3 cm/1.5 cm/1.2 cm (G2), respectively, so that the dose to the rectum decreased significantly (6% vs 2% of the volume inside the 70 Gy isodose; P <.01). Bowel function and bother score changes were smaller comparing baseline with last day of radiotherapy levels (mean 16/18 in G1 vs 9/12 in G2). CONCLUSION: A learning curve could be demonstrated in our patient population, respecting improved and more symmetrical spacer placement, improved treatment planning, and less treatment-related acute toxicity. Several important technical aspects need to be considered.

Local prostate cancer radiotherapy after prostate-specific antigen progression during primary hormonal therapy.

BACKGROUND: The outcome of patients after radiotherapy (RT) for localized prostate cancer in case of prostate-specific antigen (PSA) progression during primary hormonal therapy (HT) is not well known. METHODS: A group of 27 patients presenting with PSA progression during primary HT for local prostate cancer RT was identified among patients who were treated in the years 2000-2004 either using external-beam RT (EBRT; 70.2 Gy; n=261) or Ir-192 brachytherapy as a boost to EBRT (HDR-BT; 18 Gy + 50.4 Gy; n=71). The median follow-up period after RT was 68 months. RESULTS: Median biochemical recurrence free (BRFS), disease specific (DSS) and overall survival (OS) for patients with PSA progression during primary HT was found to be only 21, 54 and 53 months, respectively, with a 6-year BRFS, DSS and OS of 19%, 41% and 26%. There were no significant differences between different RT concepts (6-year OS of 27% after EBRT and 20% after EBRT with HDR-BT).Considering all 332 patients in multivariate Cox regression analysis, PSA progression during initial HT, Gleason score>6 and patient age were found to be predictive for lower OS (p<0.001). The highest hazard ratio resulted for PSA progression during initial HT (7.2 in comparison to patients without PSA progression during primary HT). PSA progression and a nadir >0.5 ng/ml during initial HT were both significant risk factors for biochemical recurrence. CONCLUSIONS: An unfavourable prognosis after PSA progression during initial HT needs to be considered in the decision process before local prostate radiotherapy. Results from other centres are needed to validate our findings.

Urinary morbidity after permanent prostate brachytherapy - impact of dose to the urethra vs. sources placed in close vicinity to the urethra.

BACKGROUND AND PURPOSE: The impact of the dose to the urethra and sources placed close to the urethra on urinary morbidity after permanent prostate brachytherapy (PPB) is not well known. MATERIALS AND METHODS: Fifty-nine patients were surveyed prospectively before treatment (A), 1 month after (B) and > 1 year after PPB (C) using a validated questionnaire (Expanded Prostate Cancer Index Composite). Computed tomography (CT) postimplant scans were performed at days 1 (Foley catheter in situ) and 30 after PPB and sources within 5mm of the urethra at day 1 were identified. RESULTS: As opposed to the urethral dose-volume histogram, a larger number of sources within 5mm of the urethra at day 1 predicted significantly larger urinary bother score changes at times B and C - with an impact on incontinence and frequency (e.g. moderate/big problem with leaking urine in 25% vs. 3%, p = 0.02; moderate/big problem with frequent urination in 33% vs. 7%, p < 0.01, at time C with vs. without ≥ 3 sources in a single strand placed close to the urethra). CONCLUSIONS: Placement of sources with a minimum distance of a few mm to the urethra should be a major aim to avoid urinary morbidity irrespective of the urethral dose-volume histogram.

Dose-escalation using intensity-modulated radiotherapy for prostate cancer - evaluation of quality of life with and without (18)F-choline PET-CT detected simultaneous integrated boost.

BACKGROUND: In comparison to the conventional whole-prostate dose escalation, an integrated boost to the macroscopic malignant lesion might potentially improve tumor control rates without increasing toxicity. Quality of life after radiotherapy (RT) with vs. without (18)F-choline PET-CT detected simultaneous integrated boost (SIB) was prospectively evaluated in this study. METHODS: Whole body image acquisition in supine patient position followed 1 h after injection of 178-355MBq (18)F-choline. SIB was defined by a tumor-to-background uptake value ratio > 2 (GTV(PET)). A dose of 76Gy was prescribed to the prostate (PTV(prostate)) in 2Gy fractions, with or without SIB up to 80Gy. Patients treated with (n = 46) vs. without (n = 21) SIB were surveyed prospectively before (A), at the last day of RT (B) and a median time of two (C) and 19 month (D) after RT to compare QoL changes applying a validated questionnaire (EPIC - expanded prostate cancer index composite). RESULTS: With a median cut-off standard uptake value (SUV) of 3, a median GTV(PET) of 4.0 cm(3) and PTV(boost) (GTV(PET) with margins) of 17.3 cm(3) was defined. No significant differences were found for patients treated with vs. without SIB regarding urinary and bowel QoL changes at times B, C and D (mean differences ≤3 points for all comparisons). Significantly decreasing acute urinary and bowel score changes (mean changes > 5 points in comparison to baseline level at time A) were found for patients with and without SIB. However, long-term urinary and bowel QoL (time D) did not differ relative to baseline levels - with mean urinary and bowel function score changes < 3 points in both groups (median changes = 0 points). Only sexual function scores decreased significantly (> 5 points) at time D. CONCLUSIONS: Treatment planning with (18)F-choline PET-CT allows a dose escalation to a macroscopic intraprostatic lesion without significantly increasing toxicity.

Quality of life after whole pelvic versus prostate-only external beam radiotherapy for prostate cancer: a matched-pair comparison.

PURPOSE: Comparison of health-related quality of life after whole pelvic (WPRT) and prostate-only (PORT) external beam radiotherapy for prostate cancer. METHODS AND MATERIALS: A group of 120 patients (60 in each group) was surveyed prospectively before radiation therapy (RT) (time A), at the last day of RT (time B), at a median time of 2 months (time C) and >1 year after RT (time D) using a validated questionnaire (Expanded Prostate Cancer Index Composite). All patients were treated with 1.8- to 2.0-Gy fractions up to 70.2 to 72.0 Gy with or without WPRT up to 45 to 46 Gy. Pairs were matched according to the following criteria: age±5 years, planning target volume±10 cc (considering planning target volume without pelvic nodes for WPRT patients), urinary/bowel/sexual function score before RT±10, and use of antiandrogens. RESULTS: With the exception of prognostic risk factors, both groups were well balanced with respect to baseline characteristics. No significant differences were found with regard to urinary and sexual score changes. Mean bladder function scores reached baseline levels in both patient subgroups after RT. However, bowel function scores decreased significantly more for patients after WPRT than in those receiving PORT at all times (p<0.01, respectively). Significant differences were found for most items in the bowel domain in the acute phase. At time D, patients after WPRT reported rectal urgency (>once a day in 15% vs. 3%; p=0.03), bloody stools (≥half the time in 7% vs. 0%; p=0.04) and frequent bowel movements (>two on a typical day in 32% vs. 7%; p<0.01) more often than did patients after PORT. CONCLUSION: In comparison to PORT, WPRT (larger bladder and rectum volumes in medium dose levels, but similar volumes in high dose levels) was associated with decreased bowel quality of life in the acute and chronic phases after treatment but remained without adverse long-term urinary effects.

Prognostic value of early [18F]fluoroethyltyrosine positron emission tomography after radiochemotherapy in glioblastoma multiforme.

PURPOSE: Early detection of treatment response in glioma patients after radiochemotherapy (RCX) is uncertain because treatment-related contrast enhancement in magnetic resonance imaging can mimic tumor progression. Positron emission tomography (PET) using the amino acid tracer [(18)F]fluoroethyltyrosine (FET) seems to be a promising tool for treatment monitoring. The aim of this prospective study was to evaluate the prognostic value of early changes of FET uptake after postoperative RCX in glioblastomas. METHODS AND MATERIALS: Twenty-two patients with glioblastoma were treated by surgery and subsequent RCX (whole dose 60-72 Gy). The FET-PET studies were performed before RCX, 7-10 days and 6-8 weeks after completion of RCX. Early treatment response in PET was defined as a decrease of the maximal tumor-to-brain ratio (TBR(max)) of FET uptake after RCX of more than 10%. The prognostic value of early changes of FET uptake after RCX was evaluated using Kaplan-Maier estimates for median disease-free survival and overall survival. RESULTS: The median overall and disease-free survival of the patients was 14.8 and 7.8 months. There were 16 early responders in FET-PET (72.7%) and 6 nonresponders (27.3%). Early PET responders had a significantly longer median disease-free survival (10.3 vs. 5.8 months; p < 0.01) and overall survival ("not reached" vs. 9.3 months; p < 0.001). No statistically significant differences between the patient subgroups were found concerning the defined prognostic parameters. CONCLUSIONS: FET-PET is a sensitive tool to predict treatment response in patients with glioblastomas at an early stage after RCX.

Rectal morbidity after permanent interstitial brachytherapy for prostate cancer--impact of day 1 vs. day 30 computed tomography-based postimplant dosimetry.

PURPOSE: The aim of the study was to evaluate bowel quality-of-life changes after prostate brachytherapy and the impact of Day 1 vs. Day 30 postimplant dosimetry. METHODS AND MATERIALS: In 61 patients, computed tomography (CT) scans were performed at Days 1 and 30 after (125)I brachytherapy. The patients have been surveyed prospectively before (time A), 1 month (time B), and >1 year after treatment (time C) using a validated questionnaire (Expanded Prostate Cancer Index Composite). Different parameters were tested for their predictive value on bowel quality-of-life changes (bowel bother score decrease >20 points at time B=BB20; bowel bother score decrease >10 points at time C=BC10), including seed displacements. RESULTS: Mean bowel function/bother score decreased 13/13 points at time B (p<0.01) and 1/4 points at time C (change not significant). BB20 and BC10 were found in 25% and 20% of patients, respectively. Bowel bother score declines at time B correlated well with declines at time C (r=0.53; p<0.01). Prostate volume before implantation and the number of seeds per cubic centimeters were found to be predictive for BB20 and BC10. Smaller rectal wall volumes covered by the 60-100% isodoses at Day 1 were (paradoxically) found to be significantly predictive for BC10. Larger posterior seed displacements between Days 1 and 30 were significantly associated with BB20. CONCLUSIONS: Quality-of-life scores have not been found to change significantly >1 year after brachytherapy. Larger rectal wall volumes within higher isodoses at Day 1 or 30 were not found to be predisposing for adverse quality-of-life changes.

Erectile dysfunction after external beam radiotherapy for prostate cancer.

BACKGROUND: There is a lack of prospective studies focusing on the sexual quality of life of prostate cancer patients after conformal radiotherapy (RT). OBJECTIVE: To evaluate the incidence, progression, and predictive factors for erectile dysfunction (ED). DESIGN, SETTING AND PARTICIPANTS: Patients who responded to the sexual domain of the Expanded Prostate Cancer Index Composite (EPIC) questionnaire before and more than 1 yr after RT and never received an antiandrogen treatment were included (n=123). INTERVENTION: RT dose was 70.2-72 Gy. Eleven patients used a phosphodiesterase-5 (PDE-5) inhibitor. MEASUREMENTS: Patients responded to the EPIC questionnaire before (time A), at the last day (B), a median time of 2 mo after (C), and 16 mo after (D) RT. In a multivariate analysis, risk factors (patient age, prostate volume, planning target volume, use of PDE-5 inhibitor, comorbidities) were tested for their independent effects on ED before and after RT. RESULTS AND LIMITATIONS: Sexual function and bother scores had already decreased by the end of RT (median function and bother scores at times A/B/C/D: 41/30/32/24 and 75/50/50/50). Initial function scores correlated well with late function scores (r=0.7; p<0.001). The ability to have an erection was reported by 81%/72%/74%/60% (preserved erectile ability in 70% at time D), erections firm enough for sexual intercourse by 44%/33%/35%/27% (preserved erections sufficient for intercourse in 53% at time D) of patients. A higher patient age and diabetes were predictive of both a pre-existing ED and a post-RT acquired ED. Nightly erections before treatment proved prognostically favourable (at least weekly vs. < weekly-hazard ratio of 5.9 for preserved erections sufficient for intercourse; p=0.01). Higher rates of ED can be expected with longer follow-up. CONCLUSIONS: The incidence of ED progressively increases after RT. Patient age and diabetes are risk factors for both pre-treatment and RT-associated ED. Nightly erections before RT proved prognostically favourable.

Self-assessed bowel toxicity after external beam radiotherapy for prostate cancer--predictive factors on irritative symptoms, incontinence and rectal bleeding.

BACKGROUND: The aim of the study was to evaluate self-assessed bowel toxicity after radiotherapy (RT) for prostate cancer. In contrast to rectal bleeding, information concerning irritative symptoms (rectal urgency, pain) and incontinence after RT has not been adequately documented and reported in the past. METHODS: Patients (n = 286) have been surveyed prospectively before (A), at the last day (70.2-72.0 Gy; B), a median time of two (C) and 16 months after RT (D) using a validated questionnaire (Expanded Prostate Cancer Index Composite). Bowel domain score changes were analyzed and patient-/dose-volume-related factors tested for a predictive value on three separate factors (subscales): irritative symptoms, incontinence and rectal bleeding. RESULTS: Irritative symptoms were most strongly affected in the acute phase, but the scores of all subscales remained slightly lower at time D in comparison to baseline scores. Good correlations (correlation indices >0.4; p < 0.001 for all) were found between irritative and incontinence function/bother scores at times B-D, suggesting the presence of an urge incontinence for the majority of patients who reported uncontrolled leakage of stool. Planning target volume (PTV), haemorrhoids and stroke in past history were found to be independent predictive factors for rectal bleeding at time D. Chronic renal failure predisposed for lower irritative scores at time D. Paradoxically, patients with greater rectum volumes inside higher isodose levels presented with higher quality of life scores in the irritative and incontinence subscales. CONCLUSION: PTV and specific comorbidities are important predictive factors on adverse bowel quality of life changes after RT for prostate cancer. However, greater rectum volumes inside high isodose levels have not been found to be associated with lower quality of life scores.

Rectal dosimetry following prostate brachytherapy with stranded seeds--comparison of transrectal ultrasound intra-operative planning (day 0) and computed tomography-postplanning (day 1 vs. day 30) with special focus on sources placed close to the rectal wall.

BACKGROUND AND PURPOSE: The aim of the study was to compare intra-operative and postplanning at different intervals with special focus on sources placed close to the rectal wall. MATERIALS AND METHODS: In 61 consecutive patients, CT scans were performed on day 1 and day 30 after an I-125 implant with stranded seeds. The number of sources < or =7 mm to the rectal wall was determined, and displacements were analyzed. The angulation of strands relative to rectal wall was compared between intra-operative transrectal ultrasound (TRUS) and both postplanning CT scans. RESULTS: Sources close to the rectum on day 1 (n=204) have been the most apical in a strand in 98.5% (n=201). By comparing day 1 and day 30 data, significant inferior source displacements (mean 3.6 mm; p=0.02) relative to pelvic bones and a decreasing distance to the rectal wall (mean 1.2 mm; p<0.01)--consequentially increasing rectal dose--were determined only for sources initially > or =3 mm to the rectum. In contrast to an almost parallel arrangement of the needle track and the rectal wall in TRUS, strands and rectal wall converged towards the apex in the postplanning CT scans (mean >30 degrees). CONCLUSIONS: Posterior preplanning margins around the prostate should be particularly limited at the level of the prostate apex.