Late toxicity after intensity-modulated radiation therapy for localized prostate cancer: an exploration of dose-volume histogram parameters to limit genitourinary and gastrointestinal toxicity.

To characterize the late genitourinary (GU) and gastrointestinal (GI) toxicity for prostate cancer patients treated with intensity-modulated radiation therapy (IMRT) and propose dose-volume histogram (DVH) guidelines to limit late treatment-related toxicity. In this study 296 consecutive men were treated with IMRT for adenocarcinoma of the prostate. Most patients received treatment to the prostate with or without proximal seminal vesicles (90%), to a median dose of 76 Gy. Concurrent androgen deprivation therapy was given to 150 men (51%) for a median of 4 months. Late toxicity was defined by Common Toxicity Criteria version 3.0 as greater than 3 months after radiation therapy completion. Four groupings of DVH parameters were defined, based on the percentage of rectal or bladder tissue receiving 70 Gy (V(70)), 65 Gy (V(65)), and 40 Gy (V(40)). These DVH groupings, as well as clinical and treatment characteristics, were correlated to maximal Grade 2+ GU and GI toxicity. With a median follow-up of 41 months, the 4-year freedom from maximal Grade 2+ late toxicity was 81% and 91% for GU and GI systems, respectively, and by last follow-up, the rates of Grade 2+ GU and GI toxicity were 9% and 5%, respectively. On multivariate analysis, whole-pelvic IMRT was associated with Grade 2+ GU toxicity and age was associated with Grade 2+ GI toxicity. Freedom from Grade 2+ GI toxicity at 4 years was 100% for men with rectal V(70) ≤ 10%, V(65) ≤ 20%, and V(40) ≤ 40%; 92% for men with rectal V(70) ≤ 20%, V(65) ≤ 40%, and V(40) ≤ 80%; and 85% for men exceeding these criteria (p = 0.13). These criteria were more highly associated with GI toxicity in men aged ≥70 years (p = 0.07). No bladder dose-volume relationships were associated with the risk of GU toxicity. IMRT is associated with low rates of severe GU or GI toxicity after treatment for prostate cancer. Rectal dose constraints may help limit late GI morbidity.

Pederson AW ，Fricano J ，Correa D ，Pelizzari CA ，Liauw SL ... -  《-》

Clinical toxicities and dosimetric parameters after whole-pelvis versus prostate-only intensity-modulated radiation therapy for prostate cancer.

To assess whether whole-pelvis (WP) intensity-modulated radiation therapy (IMRT) is associated with increased toxicity compared with prostate-only (PO) IMRT. We retrospectively analyzed all patients with prostate cancer undergoing definitive IMRT to 79.2 Gy with concurrent androgen deprivation at our institution from November 2005 to May 2007 with a minimum follow-up of 12 months. Thirty patients received initial WP IMRT to 45 Gy in 1.8-Gy fractions, and thirty patients received PO IMRT. Study patients underwent computed tomography simulation and treatment planning by use of predefined dose constraints. Bladder and rectal dose-volume histograms, maximum genitourinary (GU) and gastrointestinal (GI) Radiation Therapy Oncology Group toxicity grade, and late Grade 2 or greater toxicity-free survival curves were compared between the two groups by use of the Student t test, Fisher exact test, and Kaplan-Meier curve, respectively. Bladder minimum dose, mean dose, median dose, volume receiving 5 Gy, volume receiving 20 Gy, volume receiving 40 Gy, and volume receiving 45 Gy and rectal minimum dose, median dose, and volume receiving 20 Gy were significantly increased in the WP group (all p values < 0.01). Maximum acute GI toxicity was limited to Grade 2 and was significantly increased in the WP group at 50% vs. 13% the PO group (p = 0.006). With a median follow-up of 24 months (range, 12-35 months), there was no difference in late GI toxicity (p = 0.884) or in acute or late GU toxicity. Despite dosimetric differences in the volume of bowel, bladder, and rectum irradiated in the low-dose and median-dose regions, WP IMRT results only in a clinically significant increase in acute GI toxicity, in comparison to PO IMRT, with no difference in GU or late GI toxicity.

Deville C ，Both S ，Hwang WT ，Tochner Z ，Vapiwala N ... -  《-》

Role of principal component analysis in predicting toxicity in prostate cancer patients treated with hypofractionated intensity-modulated radiation therapy.

To determine if principal component analysis (PCA) and standard parameters of rectal and bladder wall dose-volume histograms (DVHs) of prostate cancer patients treated with hypofractionated image-guided intensity-modulated radiotherapy (hypo-IMRT) can predict acute and late gastrointestinal (GI) toxicity. One hundred twenty-one patients underwent hypo-IMRT at 3 Gy/fraction, 5 days/week to either 60 Gy or 66 Gy, with daily online image guidance. Acute and late GI and genitourinary (GU) toxicity were recorded weekly during treatment and at each follow-up. All Radiation Therapy Oncology Group (RTOG) criteria toxicity scores were dichotomized as <2 and ≥2. Standard dosimetric parameters and the first five to six principal components (PCs) of bladder and rectal wall DVHs were tested for association with the dichotomized toxicity outcomes, using logistic regression. Median follow-up of all patients was 47 months (60 Gy cohort = 52 months; 66 Gy cohort = 31 months). The incidence rates of ≥2 acute GI and GU toxicity were 14% and 29%, respectively, with no Grade ≥3 acute GU toxicity. Late GI and GU toxicity scores ≥2 were 16% and 15%, respectively. There was a significant difference in late GI toxicity ≥2 when comparing the 66 Gy to the 60 Gy cohort (38% vs. 8%, respectively, p = 0.0003). The first PC of the rectal DVH was associated with late GI toxicity (odds ratio [OR], 6.91; p < 0.001), though it was not significantly stronger than standard DVH parameters such as Dmax (OR, 6.9; p < 0.001) or percentage of the organ receiving a 50% dose (V50) (OR, 5.95; p = 0 .001). Hypofractionated treatment with 60 Gy in 3 Gy fractions is well tolerated. There is a steep dose response curve between 60 Gy and 66 Gy for RTOG Grade ≥2 GI effects with the dose constraints employed. Although PCA can predict late GI toxicity for patients treated with hypo-IMRT for prostate cancer, it provides no additional information over using more standard DVH parameters.

Vesprini D ，Sia M ，Lockwood G ，Moseley D ，Rosewall T ，Bayley A ，Bristow R ，Chung P ，Ménard C ，Milosevic M ，Warde P ，Catton C ... -  《-》

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 ... -  《-》

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》