X-ray-assisted positioning of patients treated by conformal arc radiotherapy for prostate cancer: comparison of setup accuracy using implanted markers versus bony structures

PURPOSE: The aim of this study was to compare setup accuracy of NovalisBody stereoscopic X-ray positioning using implanted markers in the prostate vs. bony structures in patients treated with dynamic conformal arc radiotherapy for prostate cancer. METHODS AND MATERIALS: Random and systematic setup errors (RE and SE) of the isocenter with regard to the center of gravity of three fiducial markers were measured by means of orthogonal verification films in 120 treatment sessions in 12 patients. Positioning was performed using NovalisBody semiautomated marker fusion. The results were compared with a control group of 261 measurements in 15 patients who were positioned with NovalisBody automated bone fusion. In addition, interfraction and intrafraction prostate motion was registered in the patients with implanted markers. RESULTS: Marker-based X-ray positioning resulted in a reduction of RE as well as SE in the anteroposterior, craniocaudal, and left-right directions compared with those in the control group. The interfraction prostate displacements with regard to the bony pelvis that could be avoided by marker positioning ranged between 1.6 and 2.8 mm for RE and between 1.3 and 4.3 mm for SE. Intrafraction random and systematic prostate movements ranged between 1.4 and 2.4 mm and between 0.8 and 1.3 mm, respectively. CONCLUSION: The problem of interfraction prostate motion can be solved by using implanted markers. In addition, the NovalisBody X-ray system performs more accurately with markers compared with bone fusion. Intrafraction organ motion has become the limiting factor for margin reduction around the clinical target volume.     

Combined error of patient positioning variability and prostate motion uncertainty in 3D conformal radiotherapy of localized prostate cancer

: TO measure the patient positioning and prostate motion variability and to estimate its influence on the calculated 3D dose distribution in 3D conformal radiotherapy of patients with localized prostate carcinoma.

: Patient positioning variability was determined retrospectively by comparing weas determined by 107 computed tomography (CT) examinations with a CT simulator in 28 patients during radiotherapy.

: In each observed direction, the patient positioning variability and prostate motion showed a normal distribution. This observation enabled the calculation of a combined error of both components. The standard deviation (1 SD) of the patient positioning error in three directions ranged 3.1 to 5.4 mm; the prostate motion variability was significantly greater in the anterior-posterior direction (1 SD = 2.8 mm) than in the mediolateral direction (1 SD = 1.4 mm). The 1 SD of the estimated combined error was in the anterior-posterior direction 6.1 mm and in mediolateral direction 3.6 mm.

: The range of patient positioning variability and prostate motion statistically predictable under the patient setup cnditions used. Dose-volume histograms demonstrating the influence of the combined error of both components on the calculated dose distribution are presented.     

Clinical use of stereoscopic X-ray positioning of patients treated with conformal radiotherapy for prostate cancer

PURPOSE: To evaluate accuracy and time requirements of a stereoscopic X-ray-based positioning system in patients receiving conformal radiotherapy to the prostate. METHODS AND MATERIALS: Setup errors of the isocenter with regard to the bony pelvis were measured by means of orthogonal verification films and compared to conventional positioning (using skin drawings and lasers) and infrared marker (IR) based positioning in each of 261 treatments. In each direction, the random error represents the standard deviation and the systematic error the absolute value of the mean position. Time measurements were done in 75 treatments. RESULTS: Random errors with the X-ray positioning system in the anteroposterior (AP), lateral, and longitudinal direction were (average +/- 1 standard deviation) 2 +/- 0.6 mm, 1.7 +/- 0.6 mm, and 2.4 +/- 0.7 mm. The corresponding values of conventional as well as IR positioning were significantly higher (p < 0.01). Systematic errors for X-ray positioning were 1.1 +/- 1.2 mm AP, 0.6 +/- 0.5 mm laterally, and 1.5 +/- 1.6 mm longitudinally. Conventional and IR marker-based positioning showed significantly larger systematic errors AP and laterally, but longitudinally, the difference was not significant. Depending on the axis looked at, errors of >or=5 mm occurred in 2%-14% of treatments after X-ray positioning, 13%-29% using IR markers, and 28%-53% with conventional positioning. Total linac time for one treatment session was 14 min 51 s +/- 4 min 18 s, half of which was used for the X-ray-assisted positioning procedure. CONCLUSION: X-ray-assisted patient positioning significantly improves setup accuracy, at the cost of an increased treatment time.     

Late rectal toxicity: dose-volume effects of conformal radiotherapy for prostate cancer

: To identify dosimetric, anatomic, and clinical factors that correlate with late rectal toxicity after three-dimensional conformal radiotherapy (3D-CRT) for prostate cancer.

: We retrospectively analyzed the dose-volume histograms and clinical records of 163 Stage T1b-T3c prostate cancer patients treated between 1992 and 1999 with 3D-CRT, to a total isocenter dose of 74–78 Gy at The University of Texas M. D. Anderson Cancer Center. The median follow-up was 62 months (range 24–102). All late rectal complications were scored using modified Radiation Therapy Oncology Group and Late Effects Normal Tissue Task Force criteria. The 6-year toxicity rate was assessed using Kaplan-Meier analysis and the log-rank test. A univariate proportional hazards regression model was used to test the correlation between Grade 2 or higher toxicity and the dosimetric, anatomic, and clinical factors. In a multivariate regression model, clinical factors were added to the dosimetric and anatomic variables to determine whether they significantly altered the risk of developing late toxicity.

: At 6 years, the rate of developing Grade 2 or higher late rectal toxicity was 25%. A significant volume effect was observed at rectal doses of 60, 70, 75.6, and 78 Gy, and the risk of developing rectal complications increased exponentially as greater volumes were irradiated. Although the percentage of rectal volume treated correlated significantly with the incidence of rectal complications at all dose levels (p <0.0001 for all comparisons), the absolute rectal volume appeared to be a factor only at the higher doses of 70, 75.6, and 78 Gy (p = 0.0514, 0.0016, and 0.0021, respectively). The following variables also correlated with toxicity on the univariate analysis: maximal dose to the clinical target volume, maximal dose to rectum, maximal dose to the rectum as a percentage of the prescribed dose, and maximal dose delivered to 10 cm³ of the rectum. Of the clinical variables tested, only a history of hemorrhoids correlated with rectal toxicity (p = 0.003). Multivariate analysis showed that the addition of hemorrhoids increased the risk of toxicity for each dosimetric variable found to be significant on univariate analysis (p <0.05 for all comparisons).

: Dose-volume histogram analyses clearly indicated a volume effect on the probability of developing late rectal complications. Therefore, dose escalation may be safely achieved by adherence to dose-volume histogram constraints during treatment planning and organ localization at the time of treatment to ensure consistent patient setup.     

Dose escalation for prostate cancer using the three-dimensional conformal dynamic arc technique: analysis of 542 consecutive patients

PURPOSE: To present the results of dose escalation using three-dimensional conformal dynamic arc radiotherapy (3D-ART) for prostate cancer. METHODS AND MATERIALS: Five hundred and forty two T1-T3N0M0 prostate cancer patients were treated with 3D-ART. Dose escalation (from 76 Gy/38 fractions to 80 Gy/40 fractions) was introduced in September 2003; 32% of patients received 80 Gy. In 366 patients, androgen deprivation was added to 3D-ART. Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer criteria and Houston definition (nadir + 2) were used for toxicity and biochemical failure evaluation, respectively. Median follow-up was 25 months. RESULTS: Acute toxicity included rectal (G1-2 28.9%; G3 0.5%) and urinary events (G1-2 57.9%; G3-4 2.4%). Late toxicity included rectal (G1-2 15.8%; G3-4 3.1%) and urinary events (G1-2 26.9%; G3-4 1.6%). Two-year failure-free survival and overall survival rates were 94.1% and 97.9%, respectively. Poor prognostic group (GS, iPSA, T), transurethral prostate resection, and dose >76 Gy showed significant association to high risk of progression in multivariate analysis (p = 0.014, p = 0.045, and p = 0.04, respectively). The negative effect of dose >76 Gy was not observed (p = 0.10), when the analysis was limited to 353 patients treated after September 2003 (when dose escalation was introduced). Higher dose was not associated with higher late toxicity. CONCLUSIONS: Three-dimensional-ART is a feasible modality allowing for dose escalation (no increase in toxicity has been observed with higher doses). However, the dose increase from 76 to 80 Gy was not associated with better tumor outcome. Further investigation is warranted for better understanding of the dose effect for prostate cancer.     

Sexual function after three-dimensional conformal radiotherapy for prostate cancer: results from a dose-escalation trial

PURPOSE: The purpose of this study is to provide information about sexual function (SF) after three-dimensional conformal radiotherapy (3D-CRT) for prostate cancer while taking important factors into account that influence SF. METHODS AND MATERIALS: Between June 1997 and February 2003, a total of 268 patients from a randomized dose-escalation trial comparing 68 Gy and 78 Gy agreed to participate in an additional part of the trial that evaluated SF. RESULTS: At baseline 28% of patients had erectile dysfunction (ED). After 1 year, 27% of the pretreatment potent patients had developed ED. After 2 years this percentage had increased to 36%. After 3 years it almost stabilized at 38%. Satisfaction with sexual life was significantly correlated with ED. After 2 years one third of the pre-treatment potent patients still had considerable to very much sexual desire and found sex (very) important. No significant differences were found between the two dose-arms. Potency aids were used on a regular base by 14% of the patients. CONCLUSION: By taking adjuvant hormonal therapy (HT), HT during follow-up and potency aids into account, we found a lower percentage of ED after 3D-CRT than reported in previous prospective studies. A large group of patients still had sexual desire, considered sex important and 14% used potency aids after 3D-CRT.     

Initial experience with ultrasound localization for positioning prostate cancer patients for external beam radiotherapy

: Transabdominal ultrasound localization of the prostate gland and its immediate surrounding anatomy has been used to guide the positioning of patients for the treatment of prostate cancer. This process was evaluated in terms of (1) the reproducibility of the ultrasound measurement; (2) a comparison of patient position between ultrasound localization and skin marks determined from a CT treatment planning scan; (3) the predictive indicators of patient anatomy not well suited for ultrasound localization; (4) the measurement of prostate organ displacement resulting from ultrasound probe pressure; and (5) quality assurance measures.

: The reproducibility of the ultrasound positioning process was evaluated for same-day repeat positioning by the same ultrasound operator (22 patients) and for measurements made by 2 different operators (38 patients). Differences between conventional patient positioning (CT localization with skin markings) and ultrasound-based positioning were determined for 38 patients. The pelvic anatomy was evaluated for 34 patients with pretreatment CT scans to identify predictors of poor ultrasound image quality. The displacement of the prostate resulting from pressure of the ultrasound probe was measured for 16 patients with duplicate CT scans with and without a simulated probe. Finally, daily, monthly, and semiannual quality assurance tests were evaluated.

: Self-verification tests of ultrasound positioning indicated a shift of <3 mm in approximately 95% of cases. Interoperator tests indicated shifts of <3 mm in approximately 80–90% of cases. The mean difference in patient positioning between conventional and ultrasound localization for lateral shifts was 0.3 mm (SD 2.5): vertical, 1.3 mm (SD 4.7 mm) and longitudinal, 1.0 mm (SD 5.1). However, on a single day, the differences were >10 mm in 1.5% of lateral shifts, 7% of longitudinal shifts, and 7% of vertical shifts. The depth to the isocenter, thickness of tissue overlying the bladder, and position of the prostate relative to the pubic symphysis, but not the bladder volume, were significant predictive indicators of poor ultrasound imaging. The pressure of the ultrasound probe displaced the prostate in 7 of the 16 patients by an average distance of 3.1 mm; 9 patients (56%) showed no displacement. Finally, the quality assurance tests detected ultrasound equipment defects.

: The ultrasound positioning system is reproducible and may indicate the need for significant positioning moves. Factors that predict poor image quality are the depth to the isocenter, thickness of tissue overlying the bladder, and position of the prostate relative to the pubic symphysis. The prostate gland may be displaced a small amount by the pressure of the ultrasound probe. A quality assurance program is necessary to detect ultrasound equipment defects that could result in patient alignment errors.     

Persistently better treatment planning results of intensity-modulated (IMRT) over conformal radiotherapy (3D-CRT) in prostate cancer patients with significant variation of clinical target volume and/or organs-at-risk

PURPOSE: To compare the dose coverage of planning and clinical target volume (PTV, CTV), and organs-at-risk (OAR) between intensity-modulated (3D-IMRT) and conventional conformal radiotherapy (3D-CRT) before and after internal organ variation in prostate cancer. METHODS AND MATERIALS: We selected 10 patients with clinically significant interfraction volume changes. Patients were treated with 3D-IMRT to 80 Gy (minimum PTV dose of 76 Gy, excluding rectum). Fictitious, equivalent 3D-CRT plans (80 Gy at isocenter, with 95% isodose (76 Gy) coverage of PTV, with rectal blocking above 76 Gy) were generated using the same planning CT data set ("CT planning"). The plans were then also applied to a verification CT scan ("CT verify") obtained at a different moment. PTV, CTV, and OAR dose coverage were compared using non-parametric tests statistics for V95, V90 (% of the volume receiving 95 or 90% of the dose) and D50 (dose to 50% of the volume). RESULTS: Mean V95 of the PTV for "CT planning" was 94.3% (range, 88-99) vs 89.1% (range, 84-94.5) for 3D-IMRT and 3D-CRT (p=0.005), respectively. Mean V95 of the CTV for "CT verify" was 97% for both 3D-IMRT and 3D-CRT. Mean D50 of the rectum for "CT planning" was 26.8 Gy (range, 22-35) vs 43.5 Gy (range, 33.5-50.5) for 3D-IMRT and 3D-CRT (p=0.0002), respectively. For "CT verify", this D50 was 31.1 Gy (range, 16.5-44) vs 44.2 Gy (range, 34-55) for 3D-IMRT and 3D-CRT (p=0.006), respectively. V95 of the rectum was 0% for both plans for "CT planning", and 2.3% (3D-IMRT) vs 2.1% (3D-CRT) for "CT verify" (p=non-sig.). CONCLUSION: Dose coverage of the PTV and OAR was better with 3D-IMRT for each patient and remained so after internal volume changes.     

Design and implementation of a system for treating paediatric patients with stereotactically-guided conformal radiotherapy

Background and purpose: Stereotactically-guided conformal radiotherapy (SCRT) allows the delivery of highly conformal dose distributions to localised brain tumours. This is of particular importance for children, whose often excellent long-term prognosis should be accompanied by low toxicity. The commercial immobilisation system in use at our hospital for adults was felt to be too heavy for children, and precluded the use of anaesthesia, which is sometimes required for paediatric patients. This paper therefore describes the design and implementation of a system for treating children with SCRT. This system needed to be well tolerated by patients, with good access for treating typical childhood malignancies.

Materials and methods: A lightweight frame was developed for immobilisation, with a shell-based alternative for patients requiring general anaesthetic. Procedures were set up to introduce the patients to the frame system in order to maximise patient co-operation and comfort. Film measurements were made to assess the impact of the frame on transmission and surface dose. The reproducibility of the systems was assessed using electronic portal images.

Results: Both frame and shell systems are in clinical use. The frame weighs 0.6 kg and is well tolerated. It has a transmission of 92–96%, and fields which pass through it deliver surface doses of 58–82% of the dose at d_max, compared to 18% when no frame is present. However, the frame is constructed to maximise the availability of unobstructed beam directions. Reproducibility measurements for the frame showed a mean random error of 1.0±0.2 mm in two dimensions (2D) and 1.4±0.7 mm in 3D. The mean systematic error in 3D was 2.2 mm, and 90% of all overall 3D errors were less than 3.4 mm. For the shell system, the mean 2D random error was 1.5±0.2 mm.

Conclusions: Two well-tolerated immobilisation devices have been developed for fractionated SCRT treatment of paediatric patients. A lightweight frame system gives a wide range of possible unobstructed beam directions, although beams that intersect the frame are not precluded, provided that output corrections are applied. A shell system allows the use of general anaesthesia. Both systems give reproducible immobilisation to complement the high-precision treatment delivery.     

62例前列腺癌三维适形或调强放疗的临床研究

目的 分析前列腺癌适形调强放射治疗的临床疗效、副反应,分析前列腺癌特异性抗原(PSA)的变化水平和意义.方法 62例前列腺痛患者,60例采用调强放疗,2例采用三维适形放疗.56例放疗前接受内分泌治疗.前列腺+精囊95%计划靶体积的中位处方剂量为78 Gy,盆腔的为48 Gy.放疗前、后测量血液中PSA水平,观察PSA最低点值与预后关系.观察正常组织早、晚期副反应.结果 中位随访时间15.4个月.全组3年无远处转移生存率、无生化复发生存率、总生存率和肿瘤特异生存率分别为77%、87%、90%和92%,5年无远处转移生存率、无生化复发生存率和总生存率分别为55%、69%和83%.放疗后PSA最低点≤2 ng/ml与>2 ng/ml的3年总生存率和无远处转移生存率分别为94%、88%%与56%、11%(χ~2=16.39,P<0.01;χ~2=28.87,P<0.01).1、2级早期泌尿系统副反应发生率分别为32%、0%,1、2级早期直肠副反应发生率分别为19%、3%,1、2级嗍泌尿系统副反应发生率分别为10%、0%,1、2级晚期直肠副反应发生率分别为5%、3%.结论 前列腺癌适形调强放疗疗效好,早、晚期副反应小;放疗后PSA监测利于判断肿瘤预后.     

Acute and late gastrointestinal toxicity after radiotherapy in prostate cancer patients: consequential late damage

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 < or = 0.01). For "stools > or =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.     

Strategy for online correction of rotational organ motion for intensity-modulated radiotherapy of prostate cancer

PURPOSE: To develop and evaluate a correction strategy for prostate rotation using gantry and collimator angle adjustments. METHODS AND MATERIALS: Gantry and collimator angle adjustments were used to correct for prostate rotation without rotating the table. A formula to partially correct for left-right (LR) rotations was derived through geometric analysis of rotation-induced clinical target volume (CTV) beam's-eye-view shape changes. For 10 prostate patients, intensity-modulated radiotherapy (IMRT) plans with different margins were created. Simulating CTV LR rotation and correcting each beam by a collimator rotation, the corrected CTV dose was compared with the original and uncorrected dose. Effects of residual geometric uncertainties were assessed using a Monte Carlo technique. A large number of treatments representative for prostate patients were simulated. Dose probability histograms of the minimum CTV dose (D min) were derived, with and without online correction, resulting in a more realistic margin estimate. RESULTS: Dosimetric analysis of all IMRT plans showed that, with rotational correction and a 2-mm margin, D min was constant to within 3% for LR rotations up to +/-15 degrees . The Monte Carlo dose probability histograms showed that, with correction, a margin of 4 mm ensured that 90% of patients received a D min >or=95% of the prescribed dose. Without correction a margin of 6 mm was required. CONCLUSIONS: We developed and tested a practical method for (online) correction of prostate rotation, allowing safe and straightforward implementation of margin reduction and dose escalation.     

前列腺癌三维适形和调强放疗的初步结果

目的 分析三维适形放疗（3DCRT）和调强放疗（IMRT）前列腺癌的初步疗效和早晚期副反应.方法 36例无远处转移的前列腺癌接受了3DCRT和IMRT,其中35例同时接受内分泌治疗.23例临床靶区包括前列腺或前列腺加精囊,13例先接受盆腔照射然后包括前列腺和精囊.临床靶区的中位剂量为76.0 Gy（52.5～83.0Gy）,盆腔预防性照射中位剂量为45.0Gy（40～50Gy）.结果 3、5年总生存率分别为91%、84%.3、5年癌症相关生存率均为91%.全组早期胃肠道反应≤2级35例,3级1例,无4级反应;早期泌尿系统副反应≤2级34例,3级2例,无4级反应.全组分别有4例1级和3例2级晚期胃肠道反应,无≥3级晚期胃肠道反应;晚期泌尿系统反应发生率低,6例1级,2级1例,3级1例.结论 应用三维适形放疗和调强放疗技术治疗前列腺癌,高剂量放疗是安全的,早期和晚期副反应可接受,未发现严重晚期副反应.