Long term tolerance of high dose three-dimensional conformal radiotherapy in patients with localized prostate carcinoma.

BACKGROUND: The current study was undertaken to evaluate the incidence and predictors of late toxicity in patients with localized prostate carcinoma treated with high dose three-dimensional conformal radiotherapy (3D-CRT). METHODS: A total of 743 patients with prostate carcinoma classified as T1c-T3 were treated with 3D-CRT that targeted the prostate and seminal vesicles. A minimum tumor dose of 64.8 gray (Gy) was given to 96 patients (13%), 70.2 Gy to 266 patients (365), 75.6 Gy to 320 patients (43%), and 81.0 Gy to 61 patients (8%). The median follow-up time was 42 months (range, 18-109 months). Late toxicity was graded according to the Radiation Therapy Oncology Group morbidity scoring scale. RESULTS: Late gastrointestinal (GI) and urinary (GU) toxicities were absent or minimal (Grade 0 or 1) in 90% of patients. The 5-year actuarial likelihood of the development of Grade 2 and 3 late GI toxicities was 11% and 0.75%, respectively. A multivariate analysis identified doses > or =75.6 Gy (P<0.001), history of diabetes mellitus (P = 0.01), and the presence of acute GI symptoms during treatment (P = 0.02) as independent predictors of Grade > or =2 late GI toxicity. The 5-year actuarial likelihood of the development of Grade 2 and 3 late GU toxicities was 10% and 3%, respectively. Doses > or =75.6 Gy (P = 0.008) and acute GU symptoms (P<0.001) were independent predictors of Grade > or =2 late GU toxicity. Among 544 patients who were potent before treatment (73% of all patients), 211 (39%) became impotent after 3D-CRT. The 5-year actuarial risk of potency loss was 60%. Doses > or =75.6 Gy (P<0.001) and the use of neoadjuvant androgen deprivation (P = 0.01) were independent predictors of posttreatment erectile dysfunction. CONCLUSIONS: The incidence of severe late complications after high dose 3D-CRT was minimal. Radiation doses > or =75.6 Gy and the presence of acute treatment-related symptoms during 3D-CRT correlated with a higher incidence of Grade > or =2 late GI and GU toxicities. In addition to higher doses, the use of androgen deprivation therapy increased the likelihood of permanent impotence in these patients. Intensity-modulated radiotherapy, which makes it possible to enhance the conformality of the dose distribution, has recently been implemented in an attempt to reduce the incidence of moderate grade toxicities in patients receiving high dose 3D-CRT.     

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.     

Whole pelvic radiotherapy for prostate cancer using 3D conformal and intensity-modulated radiotherapy

PURPOSE: To investigate the correlations between observed clinical morbidity and dosimetric parameters for whole pelvic radiotherapy (WPRT) for prostate cancer using either three-dimensional conformal radiotherapy (3D-CRT) or intensity-modulated radiotherapy (IMRT). METHODS AND MATERIALS: Between December 1996 and January 2002, 27 patients with prostate adenocarcinoma were treated with conformal WPRT as part of their definitive treatment. WPRT was delivered with 3D-CRT in 14 patients and with IMRT in 13 patients. For each of the patients treated with IMRT, optimized conventional two-dimensional (2D) and 3D-CRT plans were retrospectively generated for the whole pelvic phase of the treatment. Dose-volume histograms for the bowel, bladder, and rectum were compared for the three techniques. Acute toxicities were evaluated for all 27 patients, and late toxicities were evaluated for 25 patients with sufficient follow-up. Toxicities were scored according to the Radiation Therapy Oncology Group morbidity grading scales. Median follow-up was 30 months. RESULTS: Three-dimensional-CRT resulted in a 40% relative reduction (p < 0.001) in the volume of bowel receiving 45 Gy compared with 2D, and IMRT provided a further 60% reduction relative to 3D-CRT (p < 0.001). Compared with either 2D or 3D-CRT, IMRT reduced the volume of rectum receiving 45 Gy by 90% (p < 0.001). Overall, 9 patients (33%) experienced acute Grade 2 gastrointestinal (GI) toxicity, and only 1 of these patients was treated with IMRT. Antidiarrhea medication was required for 6 patients (22%). However, 5 of these 6 patients also received chemotherapy, and none were treated with IMRT. No Grade 3 or higher acute or late GI toxicities were observed. No cases of late radiation enteritis were observed. Acute and late genitourinary toxicity did not appear significantly increased by the addition of conformal WPRT. CONCLUSIONS: Compared to conventional 2D planning, conformal planning for WPRT resulted in significant reductions in the doses delivered to the bowel, rectum, and bladder. IMRT was superior to 3D-CRT in limiting the volume of bowel and rectum within high-dose regions. These dosimetric findings correlated with low rates of acute and late GI morbidity.     

Conformal radiotherapy for prostate cancer--longer duration of acute genitourinary toxicity in patients with prior history of invasive urological procedure

The incidence and predictors of acute toxicity were evaluated in patients treated with three-dimensional conformal radiotherapy (3D-CRT) for localized prostate cancer. Between December 1997 and November 1999, 116 patients with T1-T3 prostatic carcinoma were enrolled in the study. Ninety patients were treated with 70 Gy and 26 patients with T3 tumors received 74 Gy. Of the 116 patients 42 (36.2%) had a prior history of invasive urological procedure (IUP) (transurethral resection of the prostate or transvesical prostatectomy for benign prostatic hyperplasia). Acute gastrointestinal (GI) and genitourinary (GU) symptoms were graded according to the EORTC/RTOG scoring system. Toxicity duration after the completion of 3D-CRT was recorded. The majority of patients experienced only mild or no (Grade 1) acute toxicities. Medications for GI and GU symptoms (Grade 2) were required by 28.4% and 12.9% of patients, respectively. Only one case of Grade 3 GI toxicity (0.9%) was observed. Seven patients (6.1%) experienced severe GU toxicity (Grade 3 or 4). No correlation was found between acute toxicity and age, stage, dose (70 Gy vs. 74 Gy), IUP and pelvic lymphadenectomy. A significant relationship was observed between the duration of acute GU toxicity and prior IUP. Symptoms persisted for more than 4 weeks in 51.9% and 26.0% of patients with and without a prior history of IUP, respectively (p = 0.02). The incidence of acute complications, associated with 3D-CRT for prostate cancer, was acceptable in our cohort of patients. A prior history of IUP resulted in a significantly longer duration of acute GU toxicity.     

Significant reduction of acute toxicity following pelvic irradiation with helical tomotherapy in patients with localized prostate cancer.

PURPOSE: To assess and quantify the possible benefit deriving from IMRT with Helical Tomotherapy (HTT) delivery to the pelvic nodal area in patients with prostate cancer in terms of reduction of acute and late toxicities. METHODS AND MATERIALS: Thirty-five patients candidate to radical or postoperative RT on whole pelvis (WPRT) were treated with HTT, while receiving a concomitant boost to the prostate or the prostatic bed (median 74.2 and 72 Gy, respectively) within a moderately hypofractionated (28-33 fractions; median HTT duration 44 days) regimen. Median and mean doses to whole pelvis were 52 and 54 Gy, respectively. One of the major goals of planning optimisation was to minimize the dose received by the intestinal cavity (IC) outside the nodal PTV. RESULTS: HTT resulted to be very efficient in sparing the IC even at dose levels below 30-35 Gy and guaranteed a significant sparing of bladder and rectum even at intermediate-low doses (V20-V40). No acute Grade 3 RTOG toxicity was recorded. Eighteen G1 and two G2 GU acute toxicities, 13 G1 upper GI acute toxicities, 8 G1 and 1 G2 acute proctitis were observed; no patient experienced G2 upper GI toxicity. After a median FU of 11.5 months (>10 in 18 patients) one case of late G3 GU toxicity was reported in one post-prostatectomy treated patient; no G2 late rectal bleeding or other GI toxicity was recorded. CONCLUSIONS: WPRT with HTT resulted in a very low incidence of acute Grade 2 and in the disappearance of acute Grade 3 toxicities.     

Impact of neoadjuvant androgen ablation and other factors on late toxicity after external beam prostate radiotherapy

PURPOSE: To evaluate the late toxicity profile of prostate cancer patients treated with external beam radiotherapy, to investigate the possible risk factors for late toxicity, and to determine whether neoadjuvant androgen ablation (NAA) is a factor. METHODS AND MATERIALS: The study population consisted of 1192 patients with > or =24 months' follow-up. Late GI and GU toxicities were scored with a modified Radiation Therapy Oncology Group/Subjective, Objective, Management, and Analytic scale. All patients were treated with external beam radiotherapy (52.5 Gy in 20 fractions to 72 Gy in 36 fractions), using either conventional or three-dimensional conformal techniques. Of the 1192 patients, 40% received NAA (median 5 months). Risk factors investigated on multivariate analysis were age, past medical history, use of pelvic fields, dose, fractionation, use and duration of neo- and adjuvant androgen ablation, and acute toxicity (Grade 2 or greater). RESULTS: The median follow-up for the group was 49 months (range 24-105). The incidence of late Grade 2-3 GI or GU toxicity was 30% at 5 years (GI 12% and GU 20%). The incidence of late Grade 3 GI or GU toxicity was 8% at 5 years (GI 2.7% and GU 5.5%). No Grade 4 toxicity occurred. The risk factors of significance in relation to the development of late Grade 3 GU toxicity were coexisting GU disease (p = 0.02), prior transurethral resection of the prostate or transurethral resection of bladder tumor (p <0.0001), and presence of acute GU toxicity (p = 0.012). For late Grade 3 GI toxicity, short-term (< or =2 months) NAA (p = 0.0002) and coexisting GI disease (p = 0.017) were risk factors. CONCLUSION: Short-term (< or =2 months) NAA, but not longer durations of NAA, increases the risk of developing Grade 3 GI late toxicity. The possible mechanism of this phenomenon is unclear.     

Predictive factors for late genitourinary and gastrointestinal toxicity in patients with prostate cancer treated with adjuvant or salvage radiotherapy

PURPOSE: To determine the rate and magnitude of late genitourinary (GU) and gastrointestinal (GI) toxicities after salvage or adjuvant radiotherapy (RT) for prostate cancer, and to determine predictive factors for these toxicities. METHODS AND MATERIALS: A large multi-institutional database that included 959 men who received postoperative RT after radical prostatectomy (RP) was analyzed: 19% received adjuvant RT, 81% received salvage RT, 78% were treated to the prostate bed only, and 22% received radiation to the pelvis. RESULTS: The median follow-up time was 55 months. At 5 years, 10% of patients had Grade 2 late GU toxicity and 1% had Grade 3 late GU toxicity, while 4% of patients had Grade 2 late GI toxicity and 0.4% had Grade 3 late GI toxicity. Multivariate analysis demonstrated that adjuvant RT (p = 0.03), androgen deprivation (p < 0.0001), and prostate bed-only RT (p = 0.007) predicted for Grade 2 or higher late GU toxicity. For GI toxicity, although adjuvant RT was significant in the univariate analysis, no significant factors were found in the multivariate analysis. CONCLUSIONS: Overall, the number of high-grade toxicities for postoperative RT was low. Therefore, adjuvant and salvage RT can safely be used in the appropriate settings.     

宫颈癌术后适形调强放疗与三维适形放疗同步化疗的对比研究

背景与目的:适形调强放疗(intensity-modulated radiotherapy,IMRT)是一项很有前景的技术,不仅能提高靶区的照射剂量及适形度,而且减少了周围正常组织受照剂量。本文旨在评估IMRT联合化疗作为宫颈癌术后辅助治疗的局部控制及急性不良反应。方法:2005年7月—2010年11月在我科治疗的61例早期宫颈癌术后高危和中危患者行术后辅助放疗联合化疗,每周顺铂25 mg/m2同步化疗,26例行三维适形放疗(three dimensional conformal radiotherapy,3D-CRT),35例行IMRT,放疗剂量45～50.4 Gy。两组患者的病理类型和FIGO分期差异无统计学意义(P>0.05)。结果:所有患者1、3年的总生存率分别为100%和95.1%。1年的的局控率IMRT与3D-CRT分别为94%和92%(P=0.01),急性消化系统不良反应,IMRT与3D-CRT发生率分别为42.9%和80.9%(P=0.005),泌尿道系统不良反应IMRT与3D-CRT发生率分别为28.6%和57.7%(P=0.034)。在血液系统不良反应的发生率方面,IMRT较3D-CRT有明显的优势(P=0.006)。结论:IMRT与3D-CRT相比,虽然局部控制率相似,但急性不良反应发生率较低。     

Intensity-modulated radiotherapy as primary treatment for prostate cancer: acute toxicity in 114 patients

INTRODUCTION: Dose escalation improves local control in prostate cancer. At Ghent University Hospital, intensity-modulated radiotherapy (IMRT) is used to increase the dose to the prostate and/or seminal vesicles. We report on acute toxicity in 114 patients who received IMRT for prostate cancer. METHODS AND MATERIALS: Intensity-modulated radiotherapy was initiated after approval of our ethics committee. A class solution was used to plan all cases. Three beams (gantry 0 degrees , 116 degrees , and 244 degrees ) and anatomy-based segmentation were used to create an intensity-modulated dose distribution. Maximal rectal dose was set at 2 Gy per fraction. Detailed dose-volume histograms for all relevant structures were present. For all patients, we determined the pretreatment morbidity by a detailed preradiotherapy, in-house developed symptom scale. All patients were treated with 18 MV photons of an Elekta linear accelerator. Patients were seen on a weekly basis during treatment, and 1 month (M1) and 3 months (M3) thereafter. The registration of acute toxicity was standardized by a fixed questionnaire. The Radiation Therapy Oncology Group (RTOG) toxicity scale served as a basis, but additional symptoms, such as rectal blood loss, urgency, and incontinence, were scored as well. RESULTS: All 114 IMRT plans were delivered successfully without any interruption or technical problem. Daily treatment time was always less than 8 min and less than 6 min in 90% of the cases. Grade 1 and Grade 2 gastrointestinal (GI) toxicities were observed in 44% and 29% of the patients, respectively, during the whole period. If only the RTOG scale was used, Grade 1 and Grade 2 GI toxicities were noted in 39% and 27% of the patients, respectively, leaving 34% free of acute RTOG-scaled toxicity. Grade 3 genitourinary (GU) toxicity was seen in 8 patients (7%), all but 1 during treatment. Grade 2 and Grade 1 GU toxicities were seen in 36% and 47% of the patients, respectively, leaving only 10% free of acute GU toxicity. DISCUSSION: Anatomy-based IMRT to treat prostate cancer is incorporated into our daily routine without any problem. Acute toxicity is very low. Most of the recorded symptoms decrease over time, except for GI urgency and incontinence. The incorporation of additional symptoms makes the scoring more detailed.     

Acute toxicity of three-dimensional conformal radiotherapy in prostate cancer patients eligible for implant monotherapy

PURPOSE: To assess the acute toxicity of three-dimensional conformal radiotherapy (3D-CRT) in prostate cancer patients eligible for implant monotherapy. METHODS AND MATERIALS: Between December 1991 and June 1998, 198 prostate cancer patients were treated with 3D-CRT at the University of California Davis Medical Center. Fifty-two of these patients had a prostate-specific antigen (PSA) level /= Grade 3, e.g., hourly nocturia, gross hematuria, diarrhea requiring parenteral support, narcotics for pain control, or catheterization for acute urinary retention, was observed. CONCLUSION: Although relatively high doses of radiation are delivered to prostate cancers with 3D-CRT compared with conventional radiotherapy, 3D-CRT is surprisingly well-tolerated. No patients in the cohort eligible for implant monotherapy experienced acute toxicity >/= Grade 3.     

Treatment outcome of high-dose image-guided intensity-modulated radiotherapy using intra-prostate fiducial markers for localized prostate cancer at a single institute in Japan

ABSTRACT: BACKGROUND: Several studies have confirmed the advantages of delivering high doses of external beam radiotherapy to achieve optimal tumor-control outcomes in patients with localized prostate cancer. We evaluated the medium-term treatment outcome after high-dose, image-guided intensity-modulated radiotherapy (IMRT) using intra-prostate fiducial markers for clinically localized prostate cancer. METHODS: In total, 141 patients with localized prostate cancer treated with image-guided IMRT (76Gy in 13 patients and 80Gy in 128 patients) between 2003 and 2008 were enrolled in this study. The patients were classified according to the National Comprehensive Cancer Networkdefined risk groups. Thirty-six intermediate-risk patients and 105 high-risk patients were included. Androgen-deprivation therapy was performed in 124 patients (88%) for a median of 11months (range: 2-88 months). Prostate-specific antigen (PSA) relapse was defined according to the Phoenix-definition (i.e., an absolute nadir plus 2 ng/ml dated at the call). The 5-year actuarial PSA relapse-free survival, the 5-year distant metastasis-free survival, the 5- year cause-specific survival (CSS), the 5-year overall survival (OS) outcomes and the acute and late toxicities were analyzed. The toxicity data were scored according to the Common Terminology Criteria for Adverse Events, version 4.0. The median follow-up was 60 months. RESULTS: The 5-year PSA relapse-free survival rates were 100% for the intermediate-risk patients and 82.2% for the high-risk patients; the 5-year actuarial distant metastasis-free survival rates were 100% and 95% for the intermediate- and high-risk patients, respectively; the 5-year CSS rates were 100% for both patient subsets; and the 5-year OS rates were 100% and 91.7% for the intermediate- and high-risk patients, respectively. The Gleason score (<8 vs. [greater than or equal to]8) was significant for the 5-year PSA relapse-free survival on multivariate analysis (p=0.044). There was no grade 3 or 4 acute toxicity. The incidence of grade 2 acute gastrointestinal (GI) and genitourinary (GU) toxicities were 1.4% and 8.5%, respectively. The 5-year actuarial likelihood of late grade 2-3 GI and GU toxicities were 6% and 6.3%, respectively. No grade 4 GI or GU late toxicity was observed. CONCLUSIONS: These medium-term results demonstrate a good tolerance of high-dose image-guided IMRT. However, further follow-up is needed to confirm the long-term treatment outcomes.     

Pilot study of conformal intensity modulated radiation therapy for localized prostate cancer]

PURPOSE:- To report our experience on treatment planning and acute toxicity in 16 patients suffering from clinically localized prostate cancer treated with high-dose intensity-modulated radiation therapy (IMRT). PATIENTS AND METHODS: - Between March 2001 and October 2002, 16 patients with clinically localized prostate cancer were treated with IMRT. Treatment planning included an inverse-planning approach, and the desired beam intensity profiles were delivered by dynamic multileaf collimation. All patients received the entire treatment course with IMRT to a prescribed dose of 78 Gy. All IMRT treatment plans were compared with a theoretical conventional three-dimensional conformal radiation therapy (3D-CRT). Acute lower gastro-intestinal (GI) and genito-urinary (GU) toxicity was evaluated in all patients and graded according to the Common Toxicity Criteria for Adverse Events version 3.0 (CTCAE v. 3.0). A relationship between dose volume and clinical toxicity was evaluated. RESULTS: - Ninety-five percent of the PTV2 received more than 76 Gy using IMRT or 3D-CRT with no difference between both methods. The dose-volume histogram mean obtained for the PTV2 was not different between IMRT and 3D-CRT. IMRT improved homogeneity of the delivered dose to the PTV2 as compared with 3D-CRT (7.5 vs 9%, respectively). Ninety-five percent of the PTV1 received 5 Gy more using IMRT with protection of the bladder and the rectum walls. The benefit was considered below 75 and 70 Gy for the wall of the bladder and the rectum, respectively. Grade 2 GI and GU toxicity was observed in four (25%) and five (31%) patients, respectively. No grade 3 toxicity was observed. There was a trend towards a relationship between the mean rectal dose and acute rectal toxicity but without statistical significant difference (P =0.09). CONCLUSION: - Dose escalation with IMRT is feasible with no grade 3 or higher acute GI or GU toxicity. Examination of a larger cohort and longer-term follow-up are warranted in the future.     

Long-term urinary toxicity after 3-dimensional conformal radiotherapy for prostate cancer in patients with prior history of transurethral resection

PURPOSE: To report on the long-term urinary morbidity among prostate cancer patients with a prior history of a transurethral resection of the prostate (TURP) treated with high-dose 3-dimensional conformal radiotherapy (3D-CRT). METHODS AND MATERIALS: Between 1988 and 1997, 1100 patients with clinically localized prostate cancer were treated with 3D-CRT. Of these, 120 patients (8%) were identified as having had a prior TURP and are the subjects of this analysis. The median age was 71 years (range: 49-83 years). The clinical stages of the patients were T1c: 33 (28%); T2a: 38 (32%); T2b: 15 (13%); and T3: 34 (27%). Neoadjuvant androgen ablation therapy was given to 39 (33%). The median radiation dose prescribed to the planning target volume was 75.6 Gy (range: 64.8-81 Gy). The median elapsed time from TURP to initiation of 3D-CRT was 69 months (range: 4-360 months). The median follow-up time was 51 months (range: 18-109 months). RESULTS: Five patients of the 120 with a prior history of TURP (4%) developed a urethral stricture after 3D-CRT which was corrected with dilatation. The 5-year actuarial likelihood of >/= Grade 2 late urinary toxicities was 9%. No Grade 4 urinary toxicities were observed in this group of patients. Among 110 patients who were completely continent of urine prior to 3D-CRT, 10 (9%) developed stress incontinence requiring 1 pad daily for protection or experienced occasional leakage (not requiring pad protection). The 5-year incidence of >/= Grade 1 stress incontinence was 18% in patients who developed acute >/= Grade 2 GU symptoms during the course of 3D-CRT compared to 7% for patients who experienced Grade 1 or no acute urinary symptoms (p = 0.05). The radiation dose (>/=75.6 Gy vs. <75.6 Gy), the number of prior TURP procedures, or the volume of resected tissue at the time of TURP had no significant impact on the long-term urinary morbidity outcome. A multivariate analysis demonstrated that the presence of Grade 2 acute urinary symptoms was the only predictor of >/= Grade 1 stress incontinence after 3D-CRT in this group of patients. CONCLUSIONS: Despite prior TURP, the incidence of >/= Grade 3 urinary toxicities is low. Nevertheless, especially among patients with a prior history of TURP who experience Grade 2 acute urinary symptoms during radiation treatment, a higher risk of stress incontinence is observed.     

Intensity-modulated radiotherapy of pelvic lymph nodes in locally advanced prostate cancer: planning procedures and early experiences

PURPOSE: We present planning and early clinical outcomes of a study of intensity-modulated radiotherapy (IMRT) for locally advanced prostate cancer. METHODS AND MATERIALS: A total of 43 patients initially treated with an IMRT plan delivering 50 Gy to the prostate, seminal vesicles, and pelvic lymph nodes, followed by a conformal radiotherapy (CRT) plan delivering 20 Gy to the prostate and seminal vesicles, were studied. Dose-volume histogram (DVH) data for the added plans were compared with dose-volume histogram data for the sum of two CRT plans for 15 cases. Gastrointestinal (GI) and genitourinary (GU) toxicity, based on the Radiation Therapy Oncology Group scoring system, was recorded weekly throughout treatment as well as 3 to 18 months after treatment and are presented. RESULTS: Treatment with IMRT both reduced normal tissue doses and increased the minimum target doses. Intestine volumes receiving more than 40 and 50 Gy were significantly reduced (e.g., at 50 Gy, from 81 to 19 cm(3); p = 0.026), as were bladder volumes above 40, 50, and 60 Gy, rectum volumes above 30, 50, and 60 Gy, and hip joint muscle volumes above 20, 30, and 40 Gy. During treatment, Grade 2 GI toxicity was reported by 12 of 43 patients (28%), and Grade 2 to 4 GU toxicity was also observed among 12 patients (28%). With 6 to 18 months of follow-up, 2 patients (5%) experienced Grade 2 GI effects and 7 patients (16%) experienced Grade 2 GU effects. CONCLUSIONS: Use of IMRT for pelvic irradiation in prostate cancer reduces normal tissue doses, improves target coverage, and has a promising toxicity profile.     

Late toxicity after intensity modulated and image guided radiation therapy for localized prostate cancer and post-prostatectomy patients

PurposeTo examine late gastrointestinal (GI) and genitourinary (GU) toxicity profiles of patients treated for prostate cancer either definitively or post-prostatectomy with both intensity modulated radiation therapy (IMRT) and image guided radiation therapy (IGRT).Methods and MaterialsA total of 333 patients treated definitively and 104 patients treated postoperatively with IMRT and varying IGRT techniques were retrospectively examined to evaluate GI and GU toxicity profiles > 1 year from treatment. Available dosimetric data were used for correlative analysis.ResultsThe median follow-up time for the definitive patients was 41 months and the median follow-up time for the post-prostatectomy patients was 33 months. No late grade 4 or 5 GI or GU toxicities were observed. For definitive patients, the rates of grade ≥ 2 GI and GU toxicity at 3 years were 4.9% and 4.5%, respectively. In the postoperative cohort the rate of grade > 2 GU toxicity was 11.6%, with no grade ≥ 2 GI toxicity. In the definitive cohort's Cox proportional hazards regression univariate analysis, use of anticoagulation was significantly associated with GI toxicity and age, bladder V50 and IGRT modality were associated with GU toxicity, and only age remained significant in the multivariate model. In univariate analysis for the postoperative cohort, no dosimetric value correlated with GU toxicity, nor did age or time from radical prostatectomy to radiation.ConclusionsIMRT with IGRT achieved low rates of GI and GU toxicity in the definitive and postoperative setting.     

Volume and hormonal effects for acute side effects of rectum and bladder during conformal radiotherapy for prostate cancer

PURPOSE: To identify dosimetric variables predictive of acute gastrointestinal (GI) and genitourinary (GU) toxicity and to determine whether hormonal therapy (HT) is independently associated with acute GI and GU toxicity in prostate cancer patients treated with conformal radiotherapy (RT). METHODS AND MATERIALS: This analysis was performed on 336 patients participating in a multicenter (four hospitals) randomized trial comparing 68 Gy and 78 Gy. The clinical target volume consisted of the prostate with or without the seminal vesicles, depending on the risk of seminal vesicle involvement. The margin from the clinical target volume to the planning target volume was 1 cm. For these patients, the treatment plan for a total dose of 68 Gy was used, because nearly all toxicity appeared before the onset of the 10-Gy boost. Acute toxicity (<120 days) was scored according to the Radiation Therapy Oncology Group criteria. The dosimetric parameters were obtained from the relative and absolute dose-volume/surface histograms derived from the rectal wall (rectal wall volume receiving > or =5-65 Gy) and the bladder surface (bladder surface receiving > or =5-65 Gy). Additionally, relative and absolute dose-length histograms of the rectum were created, and the lengths of rectum receiving more than a certain dose over the whole circumference (rectal length receiving > or =5-65 Gy) were computed. The clinical variables taken into account for GI toxicity were neoadjuvant HT, hospital, and dose-volume group; for GU toxicity, the variables pretreatment GU symptoms, neoadjuvant HT, and transurethral resection of the prostate were analyzed. The variable neoadjuvant HT was divided into three categories: no HT, short-term neoadjuvant HT (started < or =3 months before RT), and long-term neoadjuvant HT (started >3 months before RT). RESULTS: Acute GI toxicity Grade 2 or worse was seen in 46% of the patients. Patients with long-term neoadjuvant HT experienced less Grade 2 or worse toxicity (27%) compared with those receiving short-term neoadjuvant HT (50%) and no HT (50%). The volumes of the prostate and seminal vesicles were significantly smaller in both groups receiving neoadjuvant HT compared with those receiving no HT. In multivariate logistic regression analysis, including the two statistically significant clinical variables neoadjuvant HT and hospital, a volume effect was found for the relative, as well as absolute, rectal wall volumes exposed to intermediate and high doses. Of all the length parameters, the relative rectal length irradiated to doses of > or =5 Gy and > or =30 Gy and absolute lengths receiving > or =5-15 and 30 Gy were significant. Acute GU toxicity Grade 2 or worse was reported in 56% of cases. For patients with pretreatment GU symptoms, the rate was 93%. The use of short-term and long-term neoadjuvant HT resulted in more GU toxicity (73% and 71%) compared with no HT (50%). In multivariate analysis, containing the variables pretreatment symptoms and neoadjuvant HT, only the absolute dose-surface histogram parameters (absolute surface irradiated to > or =40, 45, and 65 Gy) were significantly associated with acute GU toxicity. CONCLUSION: A volume effect was found for acute GI toxicity for relative, as well as absolute, volumes. With regard to acute GU toxicity, an area effect was found, but only for absolute dose-surface histogram parameters. Neoadjuvant HT appeared to be an independent prognostic factor for acute toxicity, resulting in less acute GI toxicity, but more acute GU toxicity. The presence of pretreatment GU symptoms was the most important prognostic factor for GU symptoms during RT.     

Intensity-modulated radiotherapy in treatment of pancreatic and bile duct malignancies: toxicity and clinical outcome

PURPOSE: To assess the efficacy and toxicity of intensity-modulated radiotherapy (IMRT) in pancreatic and bile duct (cholangiocarcinoma) malignancies. METHODS AND MATERIALS: Twenty-five patients with pancreatic and bile duct cancer were treated with IMRT. Twenty-three received concurrent 5-fluoruracil. One patient with a pancreatic primitive neuroectodermal tumor received concurrent etoposide and ifosfamide. Eight patients had resected tumors, and 17 had unresectable primary (n = 14) or recurrent (n = 3) tumors. Six patients underwent treatment planning with conventional three-dimensional four-field techniques for dosimetric comparison with IMRT. RESULTS: Compared with conventional RT, IMRT reduced the mean dose to the liver, kidneys, stomach, and small bowel. IMRT was well tolerated, with 80% experiencing Grade 2 or less acute upper GI toxicity. At a median follow-up of 10.2 months, no resected patients had local failure, and only 1 of 10 assessable patients with unresectable cancer had local progression. The median survival and distant metastasis-free survival of the 24 patients with adenocarcinoma was 13.4 and 7.3 months, respectively. Grade 4 late liver toxicity occurred in 1 patient surviving >5 years. The remainder of the assessable patients experienced no (n = 9) or Grade 1 (n = 4) late toxicity. CONCLUSION: In this hypothesis-generating analysis, the acute and chronic toxicity profile with IMRT in the treatment of pancreatic and bile duct cancer was encouraging. Local control was not compromised, despite efforts to increase conformality and avoid doses to normal structures. Distant failure remains a major obstacle in pancreatic cancer.     

Clinical outcome in posthysterectomy cervical cancer patients treated with concurrent Cisplatin and intensity-modulated pelvic radiotherapy: comparison with conventional radiotherapy

PURPOSE: To assess local control and acute and chronic toxicity with intensity-modulated radiation therapy (IMRT) as adjuvant treatment of cervical cancer. METHODS AND MATERIALS: Between April 2002 and February 2006, 68 patients at high risk of cervical cancer after hysterectomy were treated with adjuvant pelvic radiotherapy and concurrent chemotherapy. Adjuvant chemotherapy consisted of cisplatin (50 mg/m(2)) for six cycles every week. Thirty-three patients received adjuvant radiotherapy by IMRT. Before the IMRT series was initiated, 35 other patients underwent conventional four-field radiotherapy (Box-RT). The two groups did not differ significantly in respect of clinicopathologic and treatment factors. RESULTS: IMRT provided compatible local tumor control compared with Box-RT. The actuarial 1-year locoregional control for patients in the IMRT and Box-RT groups was 93% and 94%, respectively. IMRT was well tolerated, with significant reduction in acute gastrointestinal (GI) and genitourinary (GU) toxicities compared with the Box-RT group (GI 36 vs. 80%, p = 0.00012; GU 30 vs. 60%, p = 0.022). Furthermore, the IMRT group had lower rates of chronic GI and GU toxicities than the Box-RT patients (GI 6 vs. 34%, p = 0.002; GU 9 vs. 23%, p = 0.231). CONCLUSION: Our results suggest that IMRT significantly improved the tolerance to adjuvant chemoradiotherapy with compatible locoregional control compared with conventional Box-RT. However, longer follow-up and more patients are needed to confirm the benefits of IMRT.