Acute and late side effects to salivary glands and oral mucosa after head and neck radiotherapy in children and adolescents. Results of the "Registry for the evaluation of side effects after radiotherapy in childhood and adolescence".

BACKGROUND: The registry for the evaluation of side effects after radiotherapy in childhood and adolescence (RiSK) was established to prospectively characterize radiation-associated side effects. The purpose of this analysis was to characterize side effects after radiotherapy to the head and neck in children and adolescents. METHODS: Radiation doses have been collected across Germany since 2001. Acute and late side effects were characterized. RESULTS: Until January 2010, 133 patients (median age, 12.7 years) were recruited who had received radiotherapy to the salivary glands. Toxicity evaluation was available for 114 patients (median follow-up, 2.9 years). Acute and late toxicity significantly depended on the maximum radiation dose to the salivary glands. An increase of the mean value of maximum dose of 1 Gray (Gy) to the submandibular glands resulted in an odds ratio of 1.04 (range, 1.00-1.08; p = .039) for acute toxicities of the salivary glands and 1.08 (range, 1.03-1.13; p = .001) for acute mucosal toxicities. CONCLUSION: These data can be used for an individual risk assessment in pediatric head and neck radiotherapy.

Fat necrosis and parenchymal scarring after breast-conserving surgery and radiotherapy with an intraoperative electron or fractionated, percutaneous boost: a retrospective comparison.

BACKGROUND: The aim of this retrospective analysis was to evaluate mammographic changes such as fat necroses and parenchymal scarring in the breast tissue within the first 3 years after breast-conserving surgery (BCS) and whole-breast irradiation with an additional intraoperative electron boost (IO-B) versus fractionated percutaneous boost (FP-B). METHODS: A total of 53 breast cancer patients (stage I/II) treated between 2006 and 2008 were included. All patients underwent BCS followed by fractionated whole-breast radiotherapy with a total dose and single dose of 50.4 and 1.8 Gy. Twenty patients had 10 Gy IO-B using electrons, and 33 patients were treated with a FP-B with 10.8 Gy. The IO-B was performed using the mobile linear accelerator NOVAC 7. The follow-up mammograms were focused on fat necroses, parenchymal scarring and skin thickening. RESULTS: Fat necroses occurred significantly more frequently in IO-B patients compared to FP-B patients (50.0 vs. 18.2 %). The fat necroses were mammographically detected a median of 17 versus 23 months post-surgery for the IO-B versus FP-B patients. The median size of fat necroses was 24 (14-30) mm for the IO-B group and 14 (4-53) mm for the FP-B group. Parenchymal scarring in the grade 3-4 tumor bed area was seen significantly more frequently in the IO-B patients (55.0 vs. 21.2 %). Skin thickening did not differ significantly. CONCLUSION: The IO-B led to significantly more fat necroses and local restricted parenchymal scarring in our analysis.

N Latex FLC - new monoclonal high-performance assays for the determination of free light chain kappa and lambda.

BACKGROUND: High serum concentrations of monoclonal free light chain (FLC) kappa or lambda are markers of plasma cell dyscrasia. METHODS: We developed new, latex-enhanced, specific nephelometric assays based on monoclonal antibodies for the determination of FLC kappa and lambda in serum, EDTA plasma and Li-heparin plasma for use on the Siemens BN™ systems. RESULTS: Reference ranges were determined from 369 samples: FLC kappa 6.7-22.4 mg/L, FLC lambda 8.3-27.0 mg/L and kappa/lambda ratio 0.31-1.56. Protection from falsely low results due to antigen excess is obtained with a built-in pre-reaction in the assay protocols. Lot-to-lot consistency between three different lots of reagent, calibrators and supplementary reagent lots showed normalized differences <7.5%. The reproducibility of serum samples varied between 4% and 7%. The method comparison with Freelite™ assays showed normalized differences of 19.7%, 32.7% and 21.7%, respectively, for FLC kappa, lambda and ratio, correlations of 0.94, 0.77 and 0.73, and concordance rates of 99.2%, 94.2% and 95%. CONCLUSIONS: N Latex FLC demonstrates high precision, good lot-to-lot consistency and freedom from a high-dose hook effect. The method comparison between Freelite™ and the N Latex FLC assays showed good clinical concordance. Further studies need to reveal the clinical value of the new FLC assays.

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.

Hypothyroidism after head-and-neck radiotherapy in children and adolescents: preliminary results of the "Registry for the Evaluation of Side Effects After Radiotherapy in Childhood and Adolescence" (RiSK).

PURPOSE: The "Registry for the Evaluation of Side Effects After Radiotherapy in Childhood and Adolescence" (RiSK) has been established to prospectively characterize dose-volume effects of radiation in terms of side effects. The aim of this analysis was to characterize the function of the thyroid gland after radiotherapy to the head-and-neck region in children and adolescents. METHODS AND MATERIALS: Detailed information regarding radiation doses to at-risk organs has been collected across Germany since 2001. Thyroid function was evaluated by blood value examinations of thyroid-stimulating hormone, triiodothyronine, and thyroxine. Information regarding thyroid hormone substitution was requested from the treating physicians. RESULTS: Until May 2009, 1,086 patients from 62 centers were recruited, including 404 patients (median age, 10.9 years) who had received radiotherapy to the thyroid gland and/or hypophysis. Follow-up information was available for 264 patients (60.9%; median follow-up, 40 months), with 60 patients (22.7%) showing pathologic values. In comparison to patients treated with prophylactic cranial irradiation (median dose, 12 Gy), patients with radiation doses of 15 to 25 Gy to the thyroid gland had a hazard ratio of 3.072 (p=0.002) for the development of pathologic thyroid blood values. Patients with greater than 25 Gy to the thyroid gland and patients who underwent craniospinal irradiation had hazard ratios of 3.768 (p=0.009) and 5.674 (p<0.001), respectively. The cumulative incidence of thyroid hormone substitution therapy did not differ between defined subgroups. CONCLUSIONS: Radiation-induced thyroid function impairment, including damage to the thyroid gland and/or hypophysis, can frequently be observed after radiotherapy in children. A structured follow-up examination is advised.

Dose-volume analysis of radiation nephropathy in children: preliminary report of the risk consortium.

PURPOSE: To characterize kidney function in children and adolescents who had undergone radiation treatment that included parts of the kidney. METHODS AND MATERIALS: Patients receiving radiotherapy during childhood or adolescence were prospectively registered in Germany's Registry for the Evaluation of Side Effects after Radiation in Childhood and Adolescence (RiSK). Detailed information was recorded regarding radiation doses at the organs at risk since 2001 all over Germany. Toxicity evaluation was performed according to standardized Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer criteria. RESULTS: Up to May 2009, 1086 patients from 62 centers were recruited, including 126 patients (median age, 10.2 years) who underwent radiotherapy to parts of the kidneys. Maximal late toxicity (median follow-up 28.5 months in 74 patients) was characterized as Grade 0 (n = 65), 1 (n = 7) or 2 (n = 2). All patients with late effects had received potentially nephrotoxic chemotherapy. A statistically significant difference between patients with and without Grade 1 toxicity, revealing higher exposed kidney volumes in patients with toxicity, was seen for the kidney volume exposed to 20 Gy (V20; p = 0.031) and 30 Gy (V30; p = 0.003). CONCLUSIONS: Preliminary data indicate that radiation-induced kidney function impairment is rare in current pediatric multimodal treatment approaches. In the future, RiSK will be able to provide further detailed data regarding dose-volume effect relationships of radiation-associated side effects in pediatric oncology patients.

Acute toxicity profile of radiotherapy in 690 children and adolescents: RiSK data.

BACKGROUND AND PURPOSE: The "Registry for the evaluation of side effects after radiation in childhood and adolescence" (risk) was introduced to characterize adverse effects of radiotherapy in childhood and adolescence prospectively. The aim of this analysis was to characterize the pattern of acute side effects. MATERIALS AND METHODS: Since 2001, patients receiving radiotherapy in one of the German pediatric therapy trials have been registered in RiSK with detailed information regarding radiation doses to organs at risk and characterization of acute toxicities. RESULTS: From 2001 to May 2009, 690 patients have been characterized for acute toxicity in primary therapy. Acute toxicity ≥ grade 1 was observed in 506 patients. In patients irradiated in their lung and liver, patients with grade 1 or 2 acute toxicities showed higher organ volumes exposed to radiation doses <20 Gray (Gy) compared to patients without toxicities. For the salivary glands, there was a positive correlation between the acute toxicity grade and the maximum radiation dose to the organ; the lower GI tract showed a similar trend. The impact of different chemotherapy regimens on these acute side effects remains unclear. Age did not have any impact on side effects. CONCLUSION: This analysis gives a comprehensive overview of the acute toxicities of radiotherapy in children and adolescents. With prolongation of follow-up, detailed analyses regarding late toxicities will be possible with the characterization of dose-volume-effect relationships.

Consequential late effects after radiotherapy for prostate cancer - a prospective longitudinal quality of life study.

BACKGROUND: To answer the question if and to which extent acute symptoms at the end and/or several weeks after radiotherapy can predict adverse urinary and gastrointestinal long-term quality of life (QoL). METHODS: A group of 298 patients has been surveyed prospectively before (time A), at the last day (B), two months after (C) and >one year after (D) radiotherapy using a validated questionnaire (Expanded Prostate Cancer Index Composite). A subgroup of 10% with the greatest urinary/bowel bother score decrease at time D was defined as patients with adverse long-term QoL. RESULTS: Subgroup and correlation analyses could demonstrate a strong dependence of urinary/bowel QoL after radiotherapy on urinary/bowel QoL before radiotherapy. In contrast to absolute scores, QoL score changes (relative to baseline scores) did not correlate with pretreatment scores. Long-term changes could be well predicted by acute changes. Patients reporting great/moderate bother with urinary/bowel problems at time C reported to have great/moderate bother at time D in > or = 50%, respectively. In a multivariate analysis of factors for adverse long-term urinary and bowel QoL, score changes at time C were found to be independent predictors, respectively. Additionally, QoL changes at time B were independently predictive for adverse long-term bowel QoL. CONCLUSIONS: Consequential late effects play a major role after radiotherapy for prostate cancer. Patients with greater and particularly longer non-healing acute toxicity are candidates for closer follow-up and possible prophylactic actions to reduce a high probability of long-term problems.

Prostate-specific antigen kinetics following external-beam radiotherapy and temporary (Ir-192) or permanent (I-125) brachytherapy for prostate cancer.

BACKGROUND AND PURPOSE: The aim of the study was the evaluation of PSA kinetics after different radiotherapy methods. MATERIALS AND METHODS: Two-hundred and ninety five patients received external-beam radiotherapy (EBRT; 70.2 Gy; n=135), Ir-192 brachytherapy as a boost to EBRT (HDR-BT; 18 Gy+50.4 Gy; n=66) or I-125 brachytherapy (LDR-BT; 145 Gy; n=94) as monotherapy. "PSA bounce" was defined as a PSA rise of > or = 0.2 ng/ml followed by spontaneous return to prebounce level or lower, biochemical failure as "nadir+2 ng/ml". RESULTS: Patients without biochemical failure reached a lower nadir after brachytherapy (median < or = 0.05 ng/ml after LDR- and HDR-BT without NHT) in comparison to EBRT (0.55 ng/ml without NHT; p<0.01). Not a single patient without NHT and a nadir <0.1 ng/ml failed biochemically (0% vs. 45% with a nadir > or = 0.1 ng/ml; p<0.01). PSA bounces were found predominantly in the LDR-BT group (42% vs. 23%/20% after HDR-BT/EBRT; p<0.01). In a multivariate Cox regression analysis, LDR-BT and HDR-BT were associated with a significantly lower biochemical failure rate in comparison to EBRT. CONCLUSIONS: PSA kinetics differ significantly following different radiotherapy methods. A lower nadir and a higher biochemical control rate suggest a higher radiobiological efficiency of brachytherapy in comparison to EBRT (with a dose of 70.2 Gy).

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.

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.

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.

Neoadjuvant hormonal therapy and external-beam radiotherapy versus external-beam irradiation alone for prostate cancer. A quality-of-life analysis.

PURPOSE: To evaluate the impact of neoadjuvant hormonal therapy (NHT) on quality of life after external-beam radiotherapy (EBRT) for prostate cancer. PATIENTS AND METHODS: A group of 170 patients (85 with and 85 without NHT) has been surveyed prospectively before EBRT (70.2-72 Gy), at the last day of EBRT, a median time of 2 months and 15 months after EBRT using a validated questionnaire (Expanded Prostate Cancer Index Composite). Pairs with and without NHT (median treatment time of 3.5 months before EBRT) were matched according to the respective planning target volume and prostate volume. RESULTS: Before EBRT, significantly lower urinary function/bother, sexual function and hormonal function/bother scores were found for patients with NHT. More than 1 year after EBRT, only sexual function scores remained lower. In a multivariate analysis, NHT and adjuvant hormonal therapy (HT) versus NHT only (hazard ratio 14; 95% confidence interval 2.7-183; p = 0.02) and luteinizing hormone-releasing hormone (LHRH) agonists versus antiandrogens (hazard ratio 3.6; 95% confidence interval 1.1-12; p = 0.04) proved to be independent risk factors for long-term erectile dysfunction (no or very poor ability to have an erection). CONCLUSION: With the exception of sexual function (additional adjuvant HT and application of LHRH analog independently adverse), short-term NHT was not found to decrease quality of life after EBRT for prostate cancer.

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.

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.

Health-related quality of life after adjuvant and salvage postoperative radiotherapy for prostate cancer - a prospective analysis.

BACKGROUND AND PURPOSE: The aim of the study was to analyze health-related quality of life changes after postoperative radiotherapy (RT) for prostate cancer. MATERIALS AND METHODS: A group of 101 patients has been surveyed prospectively before (time A), at the last day (B), two months after (C) and >1 year after (D) RT using a validated questionnaire (Expanded Prostate Cancer Index Composite) with urinary, bowel, sexual and hormonal domains. The prostatic fossa was treated with a four-field box technique up to a total dose of 66.6 Gy. RESULTS: While median urinary scores reached baseline levels already two months after radiotherapy (function/bother scores at time A-B-C-D: 94/89-89/75-94/89-94/89; A vs. B: p<0.01), bowel problems needed a longer time to recover (function/bother scores at time A-B-C-D: 96/100-85/89-88/93-96/100; A vs. B/C: p<0.01). Greater bladder volumes inside specific isodoses were associated with temporary significantly lower urinary bother scores and chronically lower urinary incontinence scores. Only 7% of patients reported of erections firm enough for intercourse before RT, so that RT-associated sexual toxicity played a minor role. CONCLUSIONS: In contrast to bowel symptoms, acute urinary problems recover very soon after the end of postoperative RT. After >1 year, only minor HRQOL changes occurred in comparison to baseline scores.

Toxicity profile with a large prostate volume after external beam radiotherapy for localized prostate cancer.

PURPOSE: To assess the impact of prostate volume on health-related quality of life (HRQOL) before and at different intervals after radiotherapy for prostate cancer. METHODS AND MATERIALS: A group of 204 patients was surveyed prospectively before (Time A), at the last day (Time B), 2 months after (Time C), and 16 months (median) after (Time D) radiotherapy, with a validated questionnaire (Expanded Prostate Cancer Index Composite). The group was divided into subgroups with a small (11-43 cm(3)) and a large (44-151 cm(3)) prostate volume. RESULTS: Patients with large prostates presented with lower urinary bother scores (median 79 vs. 89; p = 0.01) before treatment. Urinary function/bother scores for patients with large prostates decreased significantly compared to patients with small prostates due to irritative/obstructive symptoms only at Time B (pain with urination more than once daily in 48% vs. 18%; p < 0.01). Health-related quality of life did not differ significantly between both patient groups at Times C and D. In contrast to a large prostate, a small initial bladder volume (with associated higher dose-volume load) was predictive for lower urinary bother scores both in the acute and late phase; at Time B it predisposed for pollakiuria but not for pain. Patients with neoadjuvant hormonal therapy reached significantly lower HRQOL scores in several domains (affecting only incontinence in the urinary domain), despite a smaller prostate volume (34 cm(3) vs. 47 cm(3); p < 0.01). CONCLUSIONS: Patients with a large prostate volume have a great risk of irritative/obstructive symptoms (particularly dysuria) in the acute radiotherapy phase. These symptoms recover rapidly and do not influence long-term HRQOL.

Prostate-specific antigen kinetics after brachytherapy or external beam radiotherapy and neoadjuvant hormonal therapy.

OBJECTIVES: To characterize the kinetics of prostate-specific antigen (PSA) after radiotherapy (RT) and neoadjuvant hormonal therapy (NHT) for localized prostate cancer. METHODS: The PSA kinetics of 75 consecutive patients who had undergone RT and NHT (median time 4 months) were followed up for a minimum of 24 months after treatment. RT included a permanent iodine-125 implant (n = 29), a temporary iridium-192 implant as a boost to external beam RT (n = 21), and sole external beam RT (n = 25). A median number of 11 PSA levels per patient were analyzed. RESULTS: After a first nadir (median level 0.1 ng/mL 3 months after RT), rising PSA levels were found in 83% of patients and progressively rising PSA levels until the end of follow-up or salvage hormonal therapy for 21% of patients. The PSA levels dropped again after one (23%), two (21%), or more (17%) consecutive increases up to a median level of 0.6 ng/mL (median time 16 months after RT), so that a nadir of 0.1 ng/mL was reached for a second time (median time 35 months after RT). A first nadir of less than 0.1 ng/mL, a PSA increase of less than 1 ng/mL, and a longer PSA doubling time (median time 10 months) were strongly predictive for long-term biochemical control. CONCLUSIONS: Temporarily rising PSA levels can be expected for most patients after primary RT and NHT following a first nadir. The increasing effects of testosterone owing to NHT withdrawal have a stronger effect than RT in the first months after treatment.

Health-related quality of life after permanent interstitial brachytherapy for prostate cancer: correlation with postimplant CT scan parameters.

PURPOSE: To determine dosimetric risk factors for increased toxicity after permanent interstitial brachytherapy for prostate cancer. PATIENTS AND METHODS: Quality of life questionnaires (Expanded Prostate Cancer Index Composite) of 60 and 56 patients were analyzed after a median posttreatment time of 6 weeks (A-acute) and 16 months (L-late). The corresponding CT scans were performed 30 days after the implant. The prostate, rectal wall, and base of seminal vesicles were contoured. Prostate volume, number of seeds and needles as well as dosimetric parameters were correlated with the morbidity scores. RESULTS: For a prostate volume of 38 +/- 12 cm(3) (mean +/- standard deviation), 54 +/- 7 (125)I sources (Rapid Strands), activity of 22.6 +/- 3.0 MBq [0.61 +/- 0.08 mCi]) were implanted using 20 +/- 6 needles. Improved late urinary function scores resulted from a higher number of sources per cm(3) (> or = 1.35). A prostate D(90) < 170 Gy (A)/< 185 Gy (L) and base of seminal vesicle D(10) < 190 Gy (A and L) were associated with higher urinary function scores. Late rectal function scores were significantly higher for patients with a prostate V(200) < 50% and V(150) < 75%. Patients with a prostate volume < 40 cm(3) reached better sexual function scores (A and L). A higher number of needles per cm(3) (> or = 0.5) resulted in improved late urinary, bowel and sexual function scores. CONCLUSION: Quality of life after a permanent implant can be improved by using an adequate amount of sources and needles. With an increasing number of seeds per cm(3), dose homogeneity is improving. A prostate D(90) < 170 Gy and a base of seminal vesicle D(10) < 190 Gy (as an indicator of the dose to the bladder neck and urethral sphincter) can be recommended to maintain a satisfactory urinary function.

Association of neoadjuvant hormonal therapy with adverse health-related quality of life after permanent iodine-125 brachytherapy for localized prostate cancer.

OBJECTIVES: To characterize the influence of neoadjuvant hormonal therapy (NHT) on health-related quality of life after permanent iodine-125 brachytherapy (BT) for prostate cancer. METHODS: A cross-sectional survey using the Expanded Prostate Cancer Index Composite health-related quality-of-life instrument was administered to 134 consecutive patients a median of 29 months after BT. A separate group of 111 patients with comparable demographic characteristics without any prior treatment for prostate cancer rendered the baseline information (control group). The scores and symptom rates were compared. The effect of NHT was tested for independence in a multivariate analysis. RESULTS: In contrast to patients who received NHT, prostatic edema was hardly detectable 30 days after implantation in patients who received BT alone (comparing median preimplant and postimplant volumes), resulting in a greater dose to the prostate and anterior rectal wall. However, compared with the control group and the patients who received BT alone, the addition of NHT to BT led to lower health-related quality-of-life scores in all domains. Score differences of more than 10 points with a statistical significance were found for the urinary bother, sexual function/bother, and hormonal function/bother domains. Apart from the sexual function scores (patient age shown to be the crucial factor), the influence of NHT remained independent on multivariate analysis. CONCLUSIONS: The results stress the need for well-considered administration of NHT before BT and the need for reporting the use of NHT in studies dealing with BT-related toxicity.