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Purpose: To analyze the correlation between dose-volume parameters of the corpora cavernosa and erectile dysfunction (ED) after external beam radiotherapy (EBRT) for prostate cancer. Methods and Materials: Between June 1997 and February 2003, a randomized dose–escalation trial comparing 68 Gy and 78 Gy was conducted. Patients at our institute were asked to participate in an additional part of the trial evaluating sexual function. After exclusion of patients with less than 2 years of follow-up, ED at baseline, or treatment with hormonal therapy, 96 patients were eligible. The proximal corpora cavernosa (crura), the superiormost 1-cm segment of the crura, and the penile bulb were contoured on the planning computed tomography scan and dose–volume parameters were calculated. Results: Two years after EBRT, 35 of the 96 patients had developed ED. No statistically significant correlations between ED 2 years after EBRT and dose–volume parameters of the crura, the superiormost 1-cm segment of the crura, or the penile bulb were found. The few patients using potency aids typically indicated to have ED. Conclusion: No correlation was found between ED after EBRT for prostate cancer and radiation dose to the crura or penile bulb. The present study is the largest study evaluating the correlation between ED and radiation dose to the corpora cavernosa after EBRT for prostate cancer. Until there is clear evidence that sparing the penile bulb or crura will reduce ED after EBRT, we advise to be careful in sparing these structures, especially when this involves reducing treatment margins. [Copyright &y& Elsevier]

Purpose: To quantify the anatomic changes caused by external beam radiotherapy in head-and-neck cancer patients in full three dimensions and to relate the local anatomic changes to the planned mean dose. Methods and Materials: A nonrigid registration method was adapted for RT image registration. The method was applied in 10 head-and-neck cancer patients, who each underwent a planning and a repeat computed tomography scan. Contoured structures (parotid, submandibular glands, and tumor) were registered in a nonrigid manner. The accuracy of the transformation was determined. The transformation results were used to summarize the anatomic changes on a local scale for the irradiated and spared glands. The volume reduction of the glands was related to the planned mean dose. Results: Transformation was accurate with a mean error of 0.6 ± 0.5 mm. The volume of all glands and the primary tumor decreased. The lateral regions of the irradiated parotid glands moved inward (average, 3 mm), and the medial regions tended to remain in the same position. The irradiated submandibular glands shrank and moved upward. The spared glands showed only a small deformation (∼1 mm in most regions). Overall, the primary tumors shrank. The volume loss of the parotid glands correlated significantly with the planned mean dose (p <0.001). Conclusion: General shrinkage and deformation of irradiated glands was seen. The spared glands showed few changes. These changes were assessed by a nonrigid registration method, which effectively described the local changes occurring in the head-and-neck region after external beam radiotherapy. [Copyright &y& Elsevier]

Purpose: To quantify intrafraction patient motion and its time dependence in immobilized intracranial and extracranial patients. The data can be used to optimize the intrafraction imaging frequency and consequent patient setup correction with an image guidance and tracking system, and to establish the required safety margins in the absence of such a system. Method and Materials: The intrafraction motion of 32 intracranial patients, immobilized with a thermoplastic mask, and 11 supine- and 14 prone-treated extracranial spine patients, immobilized with a vacuum bag, were analyzed. The motion was recorded by an X-ray, stereoscopic, image-guidance system. For each group, we calculated separately the systematic (overall mean and SD) and the random displacement as a function of elapsed intrafraction time. Results: The SD of the systematic intrafraction displacements increased linearly over time for all three patient groups. For intracranial-, supine-, and prone-treated patients, the SD increased to 0.8, 1.2, and 2.2 mm, respectively, in a period of 15 min. The random displacements for the prone-treated patients were significantly higher than for the other groups, namely 1.6 mm (1 SD), probably caused by respiratory motion. Conclusions: Despite the applied immobilization devices, patients drift away from their initial position during a treatment fraction. These drifts are in general small if compared with conventional treatment margins, but will significantly contribute to the margin for high-precision radiation treatments with treatment times of 15 min or longer. [Copyright &y& Elsevier]

Purpose: To determine the planning target volume (PTV) margin for an adaptive radiotherapy procedure that uses five computed tomography (CT) scans to calculate an average prostate position and rectum shape. To evaluate alternative methods to determine an average rectum based on a single delineation. Methods and Materials: Repeat CT scans (8-13) of 19 patients were used. The contoured prostates of the first four scans were matched on the planning CT (pCT) prostate contours. With the resulting translations and rotations the average prostate position was determined. An average rectum was obtained by either averaging the coordinates of corresponding points on the rectal walls or by selecting the "best" rectum or transforming the pCT rectum. Dose distributions were calculated for various expanded average prostates. The remaining CT scans were used to determine the dose received by prostate and rectum during treatment. Results: For the prostate of the pCT scan and a 10-mm margin, all patients received more than 95% of the prescribed dose to 95% of the prostate. For the average prostate, a margin of 7 mm was needed to obtain a similar result (average PTV reduction 30%). The average rectum overestimated the mean dose to the rectum by 0.4 +/- 1.6 Gy, which was better than the pCT rectum (2.1 +/- 3.0 Gy) and the alternative average rectums (1.0 +/- 2.6 Gy and 1.4 +/- 3.2 Gy). Conclusions: Our adaptive procedure allows for reduction of the PTV margin to 7 mm without decreasing prostate coverage during treatment. For accurate estimation of the rectum dose, rectums need to be delineated and averaged over multiple scans. [ABSTRACT FROM AUTHOR]

Purpose: To investigate whether a large rectum filling visible on the planning CT scan was associated with a decrease in freedom from any failure (FFF) and freedom from clinical failure (FFCF) for prostate cancer patients. Methods and Materials: Patients from the Dutch trial (78 Gy vs. 68 Gy) with available acute toxicity data were analyzed (n = 549). A 10-mm margin was applied for the first 68 Gy and 0-5 mm for the 10-Gy boost. The dose in the seminal vesicles (SVs) was prescribed within four treatment groups according to the estimated risk of SV involvement. Two potential risk factors (RFs) for a geometric miss were defined: (1) an anorectal volume > or = 90 cm(3) and > or = 25% of treatment-time diarrhea (RF1); and (2) the mean cross-sectional area of the anorectum (RF2). We tested whether these were significant predictors for FFF and FFCF within each treatment group. Results: Significant results were observed only for patients with a risk of SV involvement > 25% (dose of 68-78 Gy to the SVs, n = 349). We found a decrease in FFF (p = 0.001) and FFCF (p = 0.01) for the 87 patients with RF1 (for RF2, p = 0.02 and p = 0.01, respectively). The estimated decrease in the FFCF rate at 5 years was 15%. Conclusion: Tumor control was significantly decreased in patients with a risk of SV involvement > 25% and at risk of geometric miss. Current image guidance techniques offer several solutions to geometrically optimize the treatment. Additional research is needed to evaluate whether geometric misses can be prevented using these techniques. [ABSTRACT FROM AUTHOR]

Purpose: To analyze whether inclusion of predisposing clinical features in the Lyman-Kutcher-Burman (LKB) normal tissue complication probability (NTCP) model improves the estimation of late gastrointestinal toxicity. Methods and Materials: This study includes 468 prostate cancer patients participating in a randomized trial comparing 68 with 78 Gy. We fitted the probability of developing late toxicity within 3 years (rectal bleeding, high stool frequency, and fecal incontinence) with the original, and a modified LKB model, in which a clinical feature (e.g., history of abdominal surgery) was taken into account by fitting subset specific TD50s. The ratio of these TD50s is the dose-modifying factor for that clinical feature. Dose distributions of anorectal (bleeding and frequency) and anal wall (fecal incontinence) were used. Results: The modified LKB model gave significantly better fits than the original LKB model. Patients with a history of abdominal surgery had a lower tolerance to radiation than did patients without previous surgery, with a dose-modifying factor of 1.1 for bleeding and of 2.5 for fecal incontinence. The dose–response curve for bleeding was approximately two times steeper than that for frequency and three times steeper than that for fecal incontinence. Conclusions: Inclusion of predisposing clinical features significantly improved the estimation of the NTCP. For patients with a history of abdominal surgery, more severe dose constraints should therefore be used during treatment plan optimization. [Copyright &y& Elsevier]

: PurposeTo identify dose–volume parameters related to late rectal bleeding after radiotherapy for prostate cancer.: Materials and methodsClinical complication data from a randomized trial were collected and linked to the individual dose–volume data. In this trial, patients with prostate cancer were treated with either conventional (with rectangular fields) or three-dimensional conformal radiotherapy to a dose of 66 Gy. Patient complaints, including rectal blood loss, were collected for 199 patients, using questionnaires. Absolute and relative dose–volume histograms (DVHs) of the rectal wall (with and without the anal region) were calculated with and without rectal filling. A proportional hazard regression (PHR) model was applied to estimate the probability of any rectal blood loss within 3 years, as a function of several DVH parameters. In a multivariable analysis, dose–volume parameters were tested together with patient- and treatment-related parameters (age, smoking, diabetes, cardiovascular disease, tumor stage, neo-adjuvant androgen deprivation, conformal vs. conventional and rectal bleeding during treatment).: ResultsThe estimated incidence of any and moderate/severe rectal bleeding at 3 years was 33% and 8%, respectively. Differences between the conventional and conformal technique were small and not significant. The analysis of relative DVHs of the rectal wall (with and without the anal region), showed significant (p < 0.01) relations between the irradiated volume and the probability of rectal blood loss within 3 years for dose levels between 25 Gy and 60 Gy. This relationship was shown in subgroups defined by dose–volume cutoff points as well as in the PHR model, in which a continuously rising risk was seen with increasing volumes. For absolute DVHs and DVHs of the rectum including filling, less or no significant results were observed. The most significant volume-effect relation (p = 0.002) was found at 60 Gy for the rectum wall excluding the anal region. The probability of rectal bleeding increased from 10% to 63% when the irradiated rectum volume at 60 Gy increased from 25% to 100%. Other factors. including age, smoking, diabetes, cardiovascular disease, tumor stage, neo-adjuvant androgen deprivation, conformal vs. conventional, rectal bleeding during treatment, rectum length. and whole rectum volume. did not have a significant effect in the multivariable analysis. When controlling for the volumes at 60 Gy, the volumes at lower dose levels (25–55 Gy) were no longer significant (p = 0.5).: ConclusionsFor any rectal bleeding within 3 years, an overall incidence of 33% was observed for patients treated to 66 Gy. For this endpoint, a volume-effect relation was found for DVH parameters of the relative rectal wall volume. This relationship appeared to be most significant for the rectum without the anal region and for the higher dose levels (50–60 Gy). [Copyright &y& Elsevier]

Purpose: To quantify the residual geometric uncertainties after on-line corrections with intraprostatic fiducial markers, this study analyzed the deformation of the prostate and, in particular, the seminal vesicles relative to such markers. Patients and Methods: A planning computed tomography (CT) scan and three repeat CT scans were obtained for 21 prostate cancer patients who had had three to four cylindrical gold markers placed. The prostate and whole seminal vesicles (clinical target volume [CTV]) were delineated on each scan at a slice thickness of 1.5 mm. Rigid body transformations (translation and rotation) mapping the markers onto the planning scan positions were obtained. The translation only (Tonly) or both translation and rotation were applied to the delineated CTVs. Next, the residue CTV surface displacements were determined using nonrigid registration of the delineated contours. For translation and rotation of the CTV, the residues represented deformation; for Tonly, the residues stemmed from deformation and rotation. Tonly represented the residues for most currently applied on-line protocols. The patient and population statistics of the CTV surface displacements were calculated. The intraobserver delineation variation was similarly quantified using repeat delineations for all patients and corrected for. Results: The largest CTV deformations were observed at the anterior and posterior side of the seminal vesicles (population average standard deviation ≤3 mm). Prostate deformation was small (standard deviation ≤1 mm). The increase in these deviations when neglecting rotation (Tonly) was small. Conclusion: Although prostate deformation with respect to implanted fiducial markers was small, the corresponding deformation of the seminal vesicles was considerable. Adding marker-based rotational corrections to on-line translation corrections provided a limited reduction in the estimated planning margins. [Copyright &y& Elsevier]

Purpose: Late gastrointestinal (GI) toxicity after radiotherapy can be partly explained by late effects of acute toxicity (consequential late damage). We studied whether there is a direct relationship between acute and late GI toxicity. Patients and Methods: A total of 553 evaluable patients from the Dutch dose escalation trial (68 Gy vs. 78 Gy) were included. We defined three outcomes for acute reactions: 1) maximum Radiation Therapy Oncology Group acute toxicity, 2) maximum acute mucous discharge (AMD), and 3) maximum acute proctitis. Within a multivariable model, late endpoints (overall toxicity and five toxicity indicators) were studied as a function of acute toxicity, pretreatment symptoms, and relevant dose parameters. Results: At multivariable analysis, AMD and acute proctitis were strong predictors for overall toxicity, “intermittent bleeding,” and “incontinence pads” (p ≤ 0.01). For “stools ≥6/day” all three were strong predictors. No significant associations were found for “severe bleeding” and “use of steroids.” The predictive power of the dose parameters remained at the same level or became weaker for most late endpoints. Conclusions: Acute GI toxicity is an independent significant predictor of late GI toxicity. This suggests a significant consequential component in the development of late GI toxicity. [Copyright &y& Elsevier]