Improved toxicity profile following high-dose postprostatectomy salvage radiation therapy with intensity-modulated radiation therapy.

With salvage radiation therapy (SRT) in the postprostatectomy setting, the need to deliver sufficient radiation doses to achieve a high probability of tumor control is balanced with the risk of increased toxicity. Intensity-modulated radiation therapy (IMRT) in the postprostatectomy salvage setting is gaining interest as a treatment strategy. Compare acute and late toxicities in patients treated with IMRT and three-dimensional conformal radiation therapy (3D-CRT) in the postprostatectomy salvage setting. A total of 285 patients who were treated at our institution between 1988 and 2007 with SRT after radical prostatectomy for biochemical recurrence were identified. All medical records were reviewed and toxicity recorded. Median follow-up was 60 mo. All patients were treated with SRT with either 3D-CRT (n=109) or IMRT (n=176). A total of 205 patients (72%) were treated with doses ≥70Gy. Late gastrointestinal (GI) and genitourinary (GU) toxicities were recorded using the Common Terminology Criteria for Adverse Events v. 3.0 definition. The 5-yr actuarial rates of late grade ≥2 GI and GU toxicity were 5.2% and 17.0%, respectively. IMRT was independently associated with a reduction in grade ≥2 GI toxicity compared with 3D-CRT (5-yr IMRT, 1.9%; 5-yr 3D-CRT, 10.2%; p=0.02). IMRT was not associated with a reduction in risk of grade ≥2 GU toxicity (5-yr IMRT, 16.8%; 5-yr 3D-CRT, 15.8%; p=0.86), urinary incontinence (5-yr IMRT, 13.6%; 5-yr 3D-CRT, 7.9%; p=0.25), or grade 3 erectile dysfunction (5-yr IMRT, 26%; 5-yr 3D-CRT, 30%; p=0.82). Of patients who developed late grade ≥2 GI or GU toxicity, 38% and 44%, respectively, experienced resolution of their symptoms prior to the last follow-up. Our experience with high-dose IMRT in the postprostatectomy salvage setting demonstrates that the treatment can be delivered safely with an associated reduction in late GI toxicity.

Goenka A ，Magsanoc JM ，Pei X ，Schechter M ，Kollmeier M ，Cox B ，Scardino PT ，Eastham JA ，Zelefsky MJ ... -  《-》

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

Zelefsky MJ ，Levin EJ ，Hunt M ，Yamada Y ，Shippy AM ，Jackson A ，Amols HI ... -  《INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS》

Comparative toxicity and dosimetric profile of whole-pelvis versus prostate bed-only intensity-modulated radiation therapy after prostatectomy.

To assess whether whole-pelvis (WP) intensity modulated radiation therapy (IMRT) for prostate cancer (PCa) after prostatectomy is associated with increased toxicity compared to prostate-bed only (PB) IMRT. All patients (n = 67) undergoing postprostatectomy IMRT to 70.2 Gy at our institution from January 2006 to January 2009 with minimum 12-month follow-up were divided into WP (n = 36) and PB (n = 31) comparison groups. WP patients received initial pelvic nodal IMRT to 45 Gy. Pretreatment demographics, bladder and rectal dose-volume histograms, and maximum genitourinary (GU) and gastrointestinal (GI) toxicities were compared. Logistic regression models evaluated uni- and multivariate associations between pretreatment demographics and toxicities. Pretreatment demographics including age and comorbidities were similar between groups. WP patients had higher Gleason scores, T stages, and preoperative prostate-specific antigen (PSA) levels, and more WP patients underwent androgen deprivation therapy (ADT). WP minimum (Dmin) and mean bladder doses, bladder volumes receiving more than 5 Gy (V5) and V20, rectal Dmin, and PB bladder and rectal V65 were significantly increased. Maximum acute GI toxicity was Grade 2 and was increased for WP (61%) vs. PB (29%) patients (p = 0.001); there was no significant difference in acute Grade ≥2 GU toxicity (22% WP vs. 10% PB; p = 0.193), late Grade ≥2 GI toxicity (3% WP vs. 0% PB; p = 0.678), or late Grade ≥2 GU toxicity (28% WP vs. 19% PB; p = 0.274) with 25-month median follow-up (range, 12-44 months). On multivariate analysis, long-term ADT use was associated with Grade ≥2 late GU toxicity (p = 0.02). Despite dosimetric differences in irradiated bowel, bladder, and rectum, WP IMRT resulted only in clinically significant increased acute GI toxicity in comparison to that with PB IMRT, with no differences in GU or late GI toxicity.

Deville C ，Vapiwala N ，Hwang WT ，Lin H ，Ad VB ，Tochner Z ，Both S ... -  《-》

High-dose salvage intensity-modulated radiotherapy with or without androgen deprivation after radical prostatectomy for rising or persisting prostate-specific antigen: 5-year results.

Long-term results with salvage radiotherapy (SRT) for a biochemical recurrence after radical prostatectomy (RP) are poor. It has been suggested that radiotherapy doses >70 Gy might result in improved outcome. To report on the late toxicity profile and outcome of patients treated with high-dose salvage intensity-modulated radiotherapy (HD-SIMRT) with or without androgen deprivation (AD). Between 1999 and 2008, 136 patients were referred for HD-SIMRT with or without AD. The median follow-up was 5 yr. Indications for HD-SIMRT were persisting prostate-specific antigen (PSA) or a rising PSA following RP. All patients were irradiated at a single, tertiary, academic centre. AD was initiated on the basis of seminal vesicle invasion, preprostatectomy PSA >20 ng/ml, Gleason score ≥ 4+3 (n=43), or personal preference of the referring urologist (n=54). A median 76-Gy dose was prescribed to the RP bed using intensity-modulated radiotherapy (IMRT) in all patients. AD consisted of a luteinising hormone-releasing hormone analogue for 6 mo. Univariate and multivariate analyses were used to examine the influence of patient- and treatment-related factors on late toxicity, biochemical relapse-free survival (bRFS), and clinical relapse-free survival (cRFS). The 5-yr actuarial bRFS and cRFS were 56% and 86%, respectively. On multivariate analysis, the presence of perineural invasion at RP (hazard ratio [HR]: 6.19, p=0.001) and an increasing pre-SRT PSA (PSA 0.5 ng/ml: HR: 1; PSA 1-1.5 ng/ml: HR: 1.60, p=0.30; and PSA >1 ng/ml: HR: 2.70, p=0.02) were independent factors for a decreased bRFS. The addition of AD improved bRFS (HR: 0.33, p=0.005). On multivariate analysis, none of the variables was a predictor of cRFS. The 5-yr risk of grade 2-3 toxicity was 22% and 8% for genitourinary and gastrointestinal symptoms, respectively. IMRT allows for safe dose escalation to 76Gy with good bRFS.

Ost P ，Lumen N ，Goessaert AS ，Fonteyne V ，De Troyer B ，Jacobs F ，De Meerleer G ... -  《-》

Toxicity analysis of postoperative image-guided intensity-modulated radiotherapy for prostate cancer.

To report on the acute and late gastrointestinal (GI) and genitourinary (GU) toxicity associated with a unique technique of image-guided radiotherapy (IGRT) in patients undergoing postprostatectomy irradiation. Fifty patients were treated with intensity-modulated radiation therapy (IMRT) after radical prostatectomy. Daily image guidance was performed to localize the prostate bed using kilovoltage imaging or cone-beam computed tomography. The median prescription dose was 68 Gy (range, 62-68 Gy). Toxicity was graded every 3 to 6 months according to the Common Terminology Criteria for Adverse Events version 3.0. The median follow-up was 24 months (range, 13-38 months). Grade 2 acute GI and GU events occurred in 4 patients (8%) and 7 patients (14%), respectively. No Grade 3 or higher acute GI or GU toxicities were observed. Late Grade 2 GI and GU events occurred in 1 patient (2%) and 8 patients (16%), respectively. Only a single (2%) Grade 3 or higher late toxicity was observed. Image-guided IMRT in the postprostatectomy setting is associated with a low frequency of acute and late GI/GU toxicity. These results compare more favorably to radiotherapy techniques that do not use in-room image-guidance, suggesting that daily prostate bed localization may reduce the incidence of adverse events in patients undergoing postprostatectomy irradiation.

Nath SK ，Sandhu AP ，Rose BS ，Simpson DR ，Nobiensky PD ，Wang JZ ，Millard F ，Kane CJ ，Parsons JK ，Mundt AJ ... -  《-》