前列腺癌的外照射放疗进展

外照射放疗作为前列腺癌的主要治疗手段之一,随着放疗技术的进步、靶区认识的统一,已进入精确放疗时代.高剂量放疗的准确实施,使前列腺癌的疗效显著提高.而影像引导的放射治疗、质子放疗和低分割放疗则是疗效进一步提高的研究方向.     

前列腺癌放疗方法的剂量学研究

目的分析比较常规、三维适形和调强放疗局限期前列腺癌的最佳处方剂量。方法选取10例C期前列腺癌患者,采用CT定位和瓦里安Eclipse治疗计划系统对其进行3种治疗计划设计和计算,且均分为LFI组和EFI46 Gy LFI组(即不需要和需要盆腔预防照射两种情况)。分析DVH曲线研究下列问题:(1)处方剂量80 Gy时,3种技术25%体积直肠的剂量(D_(25))、30%体积膀胱剂量(D_(30))。(2)同时满足直肠和膀胱最大耐受量时的靶区最大处方剂量。结果(1)处方剂量80 Gy时,LFI组直肠D_(25)分别为77.22、69.18、57.85 Gy,膀胱D_(30)为71.04、60.87、53.02 Gy;EFI46 Gy LFI组直肠D_(25)分别为78.73、75.39、66.80 Gy,膀胱D_(30)为71.05、59.96、52.20 Gy。(2)同时满足直肠D_(25)为70 Gy和膀胱D_(30)为65 Gy耐受剂量时,靶区最大处方剂量LFI组分别为68.26、77.47、90、52 Gy,各组差别均有统计学意义(P<0.05),EFI46 Gy LFI组分别为66.27、69.29、77.39 Gy,调强放疗与另外两组之间差异也有统计学意义(P<0.01)。结论局限期前列腺癌同时满足直肠和膀胱最大耐受量时,LFI组中三维适形和调强放疗可达到根治剂量(77.47 Gy和90.52 Gy),EFI46 Gy LFI组中只有调强放疗可以达到根治剂量(77.39 Gy)。     

Faecal incontinence following radiotherapy for prostate cancer: A systematic review

Background

Faecal incontinence (FI) after radiotherapy is a known phenomenon, but has received little attention to date. This article aimed to review current knowledge on faecal incontinence related to radiotherapy for prostate cancer.

Methods

PubMed was searched for English-language articles published from January 1966 to December 2009 using the primary keywords ‘faecal incontinence’, ‘prostate cancer’ and ‘radiotherapy’. Prospective, retrospective and controlled trials reporting FI as a complication of radiotherapy for prostate cancer were included. The retrieved titles and abstracts were screened permissively and evaluated as to whether they satisfied the predefined inclusion and exclusion criteria.

Results

Nine hundred and ninety four articles were identified from the search. After step-wise review, 213 papers were selected for full article review of which 40 were selected for this review. The incidence of faecal incontinence following radiotherapy for prostate cancer varied from 1.6% to 58%. The mechanism of faecal incontinence was not entirely clear but it is most likely due to injury to the nerve plexus of the rectal muscular layer. Correlation between rectal dose-volume parameters and incidence is equivocal, although some studies suggest parameters confined to the lower rectum and/or anal canal may be of value to predict the extent of the injury and could be used as constraints in the dose planning process.

Conclusions

Interpretation of data is limited due to lack of large cohort studies with data on pre-treatment continence status and because variable instruments have been used to assess the severity of the condition. Well-designed prospective studies are needed to investigate dosimetric parameters focusing on the anal canal and sphincter apparatus. Considering the spatial distribution of radiation to the rectum may identify a more direct linkage between radiation damage and faecal incontinence.     

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.     

Intrafractional prostate motion during online image guided intensity-modulated radiotherapy for prostate cancer

Introduction

Intrafractional motion consists of two components: (1) the movement between the on-line repositioning procedure and the treatment start and (2) the movement during the treatment delivery. The goal of this study is to estimate this intrafractional movement of the prostate during prostate cancer radiotherapy.

Material and methods

Twenty-seven patients with prostate cancer and implanted fiducials underwent a marker match procedure before a five-field IMRT treatment. For all fields, in-treatment images were obtained and then processed to enable automatic marker detection. Combining the subsequent projection images, five positions of each marker were determined using the shortest path approach. The residual set-up error (RSE) after kV-MV based prostate localization, the prostate position as a function of time during a radiotherapy session and the required margins to account for intrafractional motion were determined.

Results

The mean RSE and standard deviation in the antero-posterior, cranio-caudal and left-right direction were 2.3 ± 1.5 mm, 0.2 ± 1.1 mm and −0.1 ± 1.1 mm, respectively. Almost all motions occurred in the posterior direction before the first treatment beam as the percentage of excursions >5 mm was reduced significantly when the RSE was not accounted for. The required margins for intrafractional motion increased with prolongation of the treatment. Application of a repositioning protocol after every beam could decrease the 1 cm margin from CTV to PTV by 2 mm.

Conclusions

The RSE is the main contributor to intrafractional motion. This RSE after on-line prostate localization and patient repositioning in the posterior direction emphasizes the need to speed up the marker match procedure. Also, a prostate IMRT treatment should be administered as fast as possible, to ensure that the pre-treatment repositioning efforts are not erased by intrafractional prostate motion. This warrants an optimized workflow with the use of faster treatment techniques.     

Palliative radiotherapy for locally advanced non-metastatic head and neck cancer: A systematic review

Objectives: The objective of this systematic review was to identify and appraise the existing evidence of role of palliative radiotherapy for locally advanced non-metastatic head and neck cancer. Methods: A systematic search of the literature was conducted using Medline, Embase and Cochrane databases and relevant references were included. Results: Literature search revealed a wide variation in dose fractionation regimens. Reported outcomes showed high efficacy and low rate of significant side effects, except in studies utilising higher doses of radiotherapy where higher grade toxicities were seen. Reported median overall survival was in the range of 3.3–17?months, but most studies reported median survival of around 6?months. Conclusions: The choice of palliative radiotherapy varies significantly. This is in contrast to regimens of curative radiotherapy for locally advanced head and neck cancer, which are well standardised. Given the reported relatively short overall survival of this patient group, an ideal treatment should be of the shortest possible duration whilst ensuring effective palliation and minimal side effects. Future well designed trials are needed to evaluate quality of life and duration of side effects in addition to survival and severity of toxicities in this group of patients.     

前列腺癌放疗的摆位误差分析

目的 探讨前列腺癌仰卧位放疗时左右、头脚、前后方向的摆位误差及各方向的旋转误差。方法 收集2011年10月至2013年6月接受前列腺癌根治性放疗的患者25例,采用仰卧位体模固定,锥形束CT（CBCT）骨配准校位,分析左右、头脚、前后方向的平均摆位误差及各方向的平均旋转误差。结果 全放疗疗程中每例患者校位9次,共计225次。各方向的平均摆位误差：左右（0.19±0.18）cm,头脚（0.36±0.30）cm,前后（0.21±0.16）cm;其中左右方向摆位误差≥5mm占5.8%,头脚占24.3%,前后占8.0%。各方向旋转误差：轴位（1.07±1.03）°,头脚（0.82±0.66）°,水平（0.79±0.68）°。前5次与后4次摆位及旋转误差比较差异无统计学意义（P＞0.05）。结论前列腺癌仰卧位放疗时,头脚摆位误差最大,左右及前后摆位误差相当,旋转误差较小可忽略不计。     

Salvage hypofractionated radiotherapy for biochemically recurrent prostate cancer after radical prostatectomy

PURPOSE: To evaluate whether hypofractionation is well tolerated and to preliminarily assess biochemical control of this regimen in a postprostatectomy, salvage setting. METHODS AND MATERIALS: A retrospective analysis was performed in 50 patients treated between May 2003 and December 2005 with hypofractionated radiotherapy for biochemical recurrence after radical prostatectomy. Radiotherapy was prescribed to the prostatic fossa to 65-70 Gy in 26-28 fractions of 2.5 Gy each, using intensity-modulated radiotherapy with daily image localization. Toxicities were scored using a modified Radiation Therapy Oncology Group scale and the Fox Chase modification of Late Effects Normal Tissue scale. The median follow-up was 18.9 months (range, 5.3-35.9). RESULTS: No Grade 3 or greater acute or late toxicities were observed. Grade 2 toxicities included four acute genitourinary, one acute gastrointestinal, two late genitourinary, and two late gastrointestinal toxicities. Of the 50 patients, 39 demonstrated a continuous biochemical response after salvage therapy, 3 had an initial response before prostate-specific antigen failure, and 7 had prostate-specific antigen progression, 1 of whom died of progressive metastatic disease. Finally, 1 patient discontinued therapy because of the diagnosis of a metachronous pancreatic cancer and died without additional prostate cancer follow-up. All remaining patients were alive at the last follow-up visit. A lower presalvage prostate-specific antigen level was the only significant prognostic factor for improved biochemical control. The estimated actuarial biochemical control rate at 2 years was 72.9%. CONCLUSIONS: The toxicity and early biochemical response rates were consistent with expectations from conventional fractionation. Additional follow-up is required to better document the biochemical control, but these results suggest that hypofractionation is a well-tolerated approach for salvage radiotherapy.     

前列腺癌大分割调强放疗副反应初步分析

目的 分析前列腺癌大分割照射患者的早期和晚期副反应,初步探讨副反应的影响因素.方法 2006-2008年间37例前列腺痛患者接受大分割调强放疗(IMRT).13例临床靶体积(CTV)包括前列腺±精囊或术后瘤床,24例包括前列腺、精囊(或术后瘤床)和盆腔淋巴引流区.分次照射剂量为2.3～2.8 Gy(2.7 Gy占26例).95%PTV处方剂量前列腺精囊为62.5～75.0 Gy,盆腔为50.0 Gy.结果 全组中位随访时间为14个月.早期胃肠反应发生率0级38%,1级2,4%,2级35%,3级3%;直肠V50>27%与V55>20%的≥1级早期直肠反应发生率不同(P<0.05).早期泌尿系统反应发生率0级30%,1级68%,2级0和3级3%;膀胱V60<10%与V60>10%的≥1级泌尿系统反应发生率也不同(X2=6.02,P=0.038).晚期直肠反应发生率0级70%,1级24%,2级5%,无3、4级反应;直肠V65<10%与V65>10%的≥1级晚期胃肠反应发生率不同(X2=5.58,P=0.020).晚期泌尿系统反应发生率0级38%,1级49%,2级11%,3级3%,无4级反应;膀胱平均剂量>40Gy、V40>32%与V50>29%的≥2级晚期泌尿系统反应发生率均不同.结论 前列腺癌大分割IMRT初步研究结果 显示急件和晚期副反应均在可接受范围内.     

Prognostic value of PSA nadir < or =4 ng/mL within 4 months of high-dose radiotherapy for locally advanced prostate cancer

PURPOSE: To investigate early prostate-specific antigen (PSA) kinetics after high radiation doses of 85 Gy on locally advanced prostate cancer. METHODS AND MATERIALS: A total of 201 patients were prospectively and consecutively treated with external beam radiotherapy and a brachytherapy boost. Of the 201 patients, 104 received concomitant hormonal therapy on the decision of the referring urologist and were excluded, yielding a study population of 97 patients. The first posttreatment PSA analysis was performed not earlier than 1 month after treatment completion but within the first 4 months, and then every 4 months. Analysis of PSA kinetics included the PSA nadir (nPSA) at values of < or =4 ng/mL to < or =0.5 ng/mL. The nPSA at < or =4 ng/mL within 4 months (nPSA < or =4/4m) was the variable of interest. RESULTS: We established highly significant associations between an nPSA of < or =1 and < or =0.5 ng/mL and the nPSA < or =4/4m (p <0.0001). A hazard ratio of 0.33 (95% Confidence Interval (CI), 0.12-0.91) underlined the lower risk of recurrence related to nPSA < or =4/4m achievement (p = 0.033). Using time-dependent covariate models for patients who did not reach an nPSA < or =4/4m, an nPSA of < or =1 ng/mL remained without prognostic significance (p = 0.06). However, for patients who reached an nPSA < or =4/4m, an nPSA of < or =1 ng/mL did significantly improve the prognosis (p <0.001), but much later after treatment. The same analysis was repeated for nPSA < or =0.5 ng/mL with similar conclusions as when nPSA < or =4/4m was obtained (p <0.01). CONCLUSION: The nPSA < or =4/4m has been demonstrated to be a significant predictor of biochemical no evidence of disease after high radiation doses of 85 Gy. Its major advantage is that it was available earlier than the other nadirs.     

Fractionation and protraction for radiotherapy of prostate carcinoma

Purpose: To investigate whether current fractionation and brachytherapy protraction schemes for the treatment of prostatic cancer with radiation are optimal, or could be improved.

Methods and Materials: We analyzed two mature data sets on radiotherapeutic tumor control for prostate cancer, one using EBRT and the other permanent seed implants, to extract the sensitivity to changes in fractionation of prostatic tumors. The standard linear-quadratic model was used for the analysis.

Results: Prostatic cancers appear significantly more sensitive to changes in fractionation than most other cancers. The estimated /β value is 1.5 Gy [0.8, 2.2]. This result is not too surprising as there is a documented relationship between cellular proliferative status and sensitivity to changes in fractionation, and prostatic tumors contain exceptionally low proportions of proliferating cells.

Conclusions: High dose rate (HDR) brachytherapy would be a highly appropriate modality for treating prostate cancer. Appropriately designed HDR brachytherapy regimens would be expected to be as efficacious as low dose rate, but with added advantages of logistic convenience and more reliable dose distributions. Similarly, external beam treatments for prostate cancer can be designed using larger doses per fraction; appropriately designed hypofractionation schemes would be expected to maintain current levels of tumor control and late sequelae, but with reduced acute morbidity, together with the logistic and financial advantages of fewer numbers of fractions.     

Target position variability throughout prostate radiotherapy

Purpose: To quantify the variability in prostate and seminal vesicle position during a course of external beam radiotherapy, and to measure the proportion of target variability due to setup error.

Methods and Materials: Forty-four weekly planning computerized tomography (CT) studies were obtained on six patients undergoing radiotherapy for prostate cancer. All patients were scanned in the radiotherapy treatment position, supine with an empty bladder, with no immobilization device. All organs were outlined on 3-mm-thick axial CT images. Anterior and lateral beam’s eye view digitally reconstructed radiographs and multiplanar reformatted images were generated. The position of the prostate and seminal vesicles relative to the isocenter location as set that day was recorded for each CT study. Target position relative to a bony landmark was measured to determine the relative contribution of setup error to the target position variability.

Results: The seminal vesicle and prostate position variability was most significant in the anterior–posterior (AP) direction, followed by cranial–caudal (CC) and mediolateral (ML) directions. Setup error contributed significantly to the total target position variability. Rectal filling was associated with a trend to anterior movement of the prostate, whereas bladder filling was not associated with any trends. Although most deviations from the target position determined at the initial planning CT scan were within 10 mm, deviations as large as 15 mm and 19 mm were seen in the prostate and seminal vesicles respectively. Target position variations were evenly distributed around the initial target position for some patient studies, but unpredictable patterns were also seen. From a simulation based on the observed variability in target position, the AP, CC, and ML planning target volume (PTV) borders around the clinical target volume (CTV) required for target coverage with 95% certainty are 12.4 mm, 10.3 mm, and 5.6 mm respectively for the prostate and 13.8 mm, 8.6 mm, and 3.9 mm respectively for the seminal vesicles.

Conclusion: Target position variability is significant during prostate radiotherapy, requiring large PTV borders around the CTV. This target position variability may be potentially reduced by improving the setup accuracy.     

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.     

Practical approaches to proteomic biomarkers within prostate cancer radiotherapy trials

INTRODUCTION: Proteomic biomarkers may be useful for monitoring therapeutic response and to triage cancer patients to best therapy. OBJECTIVES: In this review, we highlight the importance of specimen acquisition, preparation and analysis in radiotherapy proteomic studies. We also discuss practical approaches for the design and execution of clinical proteomic studies using our recent experience based on specimens accrued during prostate cancer radiation therapy. DISCUSSION AND CONCLUSIONS: Numerous proteomic methods are being employed, including high-throughput mass spectrometry and immunoassays, and using solid tissues, blood and urine for analysis. Given the potential complexity of cytokine and other protein responses, there is a need to assess proteomic signatures within serial samples as longitudinal studies during a course of fractionated radiotherapy (RT).     

Incidence of late rectal and urinary toxicities after three-dimensional conformal radiotherapy and intensity-modulated radiotherapy for localized prostate cancer

PURPOSE: To report the incidence and predictors of treatment-related toxicity at 10 years after three-dimensional conformal radiotherapy (3D-CRT) and intensity-modulated radiotherapy (IMRT) for localized prostate cancer. METHODS AND MATERIALS: Between 1988 and 2000, 1571 patients with stages T1-T3 prostate cancer were treated with 3D-CRT/IMRT with doses ranging from 66 to 81 Gy. The median follow-up was 10 years. Posttreatment toxicities were all graded according to the National Cancer Institute's Common Terminology Criteria for Adverse Events. RESULTS: The actuarial likelihood at 10 years for the development of Grade>or=2 GI toxicities was 9%. The use of IMRT significantly reduced the risk of gastrointestinal (GI) toxicities compared with patients treated with conventional 3D-CRT (13% to 5%; p<0.001). Among patients who experienced acute symptoms the 10-year incidence of late toxicity was 42%, compared with 9% for those who did not experience acute symptoms (p<0.0001). The 10-year incidence of late Grade>or=2 genitourinary (GU) toxicity was 15%. Patients treated with 81 Gy (IMRT) had a 20% incidence of GU symptoms at 10 years, compared with a 12% for patient treated to lower doses (p=0.01). Among patients who had developed acute symptoms during treatment, the incidence of late toxicity at 10 years was 35%, compared with 12% (p<0.001). The incidence of Grade 3 GI and GU toxicities was 1% and 3%, respectively. CONCLUSIONS: Serious late toxicity was unusual despite the delivery of high radiation dose levels in these patients. Higher doses were associated with increased GI and GU Grade 2 toxicities, but the risk of proctitis was significantly reduced with IMRT. Acute symptoms were a precursor of late toxicities in these patients.     

A criterion-based audit of the technical quality of external beam radiotherapy for prostate cancer

Purpose

To evaluate the technical quality of external beam radiotherapy for prostate cancer in Canada.

Methods

This was a multi-institution, retrospective study of a random sample of patients undergoing radiotherapy (RT) for prostate cancer in Canada. Patterns of care were determined by abstracting details of the patients’ management from original records. The quality of patient’s technical care was measured against a previously published, comprehensive suite of quality indicators.

Results

32 of the 37 RT centres participated. The total study population of 810 patients included 25% low-risk, 44% intermediate-risk, and 28% high-risk cases. 649 received external beam RT (EBRT) only, for whom compliance with 12 indicators of the quality of pre-treatment assessment ranged from 56% (sexual function documented) to 96% (staging bone scan obtained in high-risk patients). Compliance with treatment-related indicators ranged from 78% (dose to prostate ?74 Gy in intermediate risk patients not receiving hormone therapy) to 100% (3DCRT or IMRT plan). Compliance varied among centres; no centre demonstrated 100% compliance on all indicators and every centre was 100% compliant on at least some indicators. The number of assessment-related indicators (n = 13) with which a given centre was 100% compliant ranged from 4 to 11 (median 7) and the number of the treatment-specific indicators (n = 8) with which a given centre was 100% compliant ranged from 6 to 8 (median 8). ADT therapy was utilised in most high-risk cases (191, 92.3%).

Conclusions

While patterns of prostate cancer care in Canada vary somewhat, compliance on the majority of quality indicators is very high. However, all centres showed room for improvement on several indicators and few individual patients received care that met target benchmarks on all quality measures. This variation is particularly important for indicators such as delivered dose where impact on disease outcome is known to exist, and suggests that quality improvement programmes have the potential to further improve quality of care.