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.

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.

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.

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.

Dose-escalation using intensity-modulated radiotherapy for prostate cancer--evaluation of the dose distribution with and without 18F-choline PET-CT detected simultaneous integrated boost.

BACKGROUND AND PURPOSE: The aim of the study was to evaluate the impact of a dose escalation to an (18)F-choline PET-CT defined simultaneous integrated boost (IB) on the dose distribution and changes of the equivalent uniform dose (EUD). MATERIALS AND METHODS: PET-CT was performed in 12 consecutive patients for treatment planning. An intraprostatic lesion was defined by a tumour-to-background uptake value ratio >2 (GTV(PET)). Dose escalation was focused only on the intraprostatic lesion. Two comparisons were evaluated: whole prostate irradiation to 76 Gy+/-boost to 80 Gy (C1) and whole prostate irradiation to 66.6 Gy+/-boost to 83.25 Gy (C2). RESULTS: PTV/GTV(PET)+margins were covered by a mean EUD of 75.9/76.1 Gy vs. 77.1/80.1 Gy (C1) and 66.5/66.2 Gy vs. 71.1/82.9 Gy (C2) (p<0.01, respectively). Concerning the organs at risk, EUD increased slightly with an additional boost (mean EUD for bladder: C1 53.2 Gy vs. 53.8 Gy; C2 43.0 Gy vs. 45.1 Gy; for rectum: C1 52.0 Gy vs. 52.6 Gy; C2 43.0 Gy vs. 45.4 Gy; p<0.01, respectively). The distance to the organs at risk had a significant impact on the respective maximum doses in the treatment plans with IB. CONCLUSIONS: Treatment planning with IB allows an individually adapted dose escalation. The therapeutic ratio can be improved by a considerable dose escalation to the macroscopic tumour, but only minor EUD changes to the bladder and rectum.

Health-related quality of life after permanent I-125 brachytherapy and conformal external beam radiotherapy for prostate cancer--a matched-pair comparison.

BACKGROUND AND PURPOSE: The aim of the study was to compare quality of life after permanent I-125 brachytherapy (BT) and external beam radiotherapy (EBRT) for prostate cancer. MATERIALS AND METHODS: A group of 104 patients (52 in each group) have been surveyed prospectively before EBRT/BT (time A), at the last day of EBRT (70.2-72.0 Gy) or one month after BT (time B), and a median time of 16 months after EBRT/BT (time C) using a validated questionnaire (Expanded Prostate Cancer Index Composite). Pairs were matched according to the following criteria: age +/-5 years, prostate volume +/-10 cc, use of antiandrogens, and erectile function. RESULTS: Urinary function/bother scores decreased significantly more after BT both at time B and time C. Bowel function/bother scores tended to be higher after BT, with a lower percentage of patients with painful bowel movements (BT: 12%/27%/15%; EBRT: 19%/52%/35% at time A/B/C; p<0.05 for differences at times B/C) and rectal bleeding (BT: 12%/12%/12%; EBRT: 8%/14%/17%). No difference concerning erectile dysfunction was found (67% vs. 61% with preserved erections firm enough for intercourse after BT vs. EBRT at time C). CONCLUSIONS: BT was associated with higher urinary, but lower rectal toxicity. The risk of treatment-associated erectile dysfunction did not differ between these methods.

Image-guided radiotherapy for prostate cancer. Implementation of ultrasound-based prostate localization for the analysis of inter- and intrafraction organ motion.

PURPOSE: To evaluate inter- and intrafraction organ motion with an ultrasound-based prostate localization system (BAT) for patients treated with intensity-modulated radiotherapy for prostate cancer. PATIENTS AND METHODS: After set-up to external skin marks, 260/219 ultrasound-based alignments were performed before/after irradiation in 32 consecutive patients. Image quality was classified as good, satisfactory or poor. Patient- and imaging-related parameters were analyzed to identify predictors for poor image quality. Shifts in relation to the treatment planning computed tomography (CT) were recorded before/after irradiation in the superior-inferior (SI), anterior-posterior (AP) and right-left (RL) directions to determine inter-/intrafraction prostate motion. RESULTS: The thickness of tissue anterior to the bladder and bladder volume during the ultrasound localization as well as an inferior prostate position relative to public symphysis (determined in treatment planning CT) were found to be independent predictors of a poor image quality. Interfraction shifts (mean+/-standard deviation: -0.2+/-4.8 [SI], 2.4+/-6.6 [AP] and 1.9+/-4.6 [RL]) varied much stronger than intrafraction shifts (0.0+/-2.0 [SI], 0.6+/-2.2 [AP] and 0.2+/-1.9 [RL]). A larger pressure of the ultrasound probe (determined as a larger reduction of the distance abdominal skin to prostate between the planning CT and the ultrasound) was applied in case of poor image quality, associated with larger systematic posterior prostate displacements. CONCLUSION: Intrafraction prostate shifts are considerably smaller in comparison to interfraction shifts. Bladder filling and a small pressure on the ultrasound probe are crucial to achieve an adequate image quality without systematic prostate displacements.

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.