David Correa

Late Toxicity After Intensity-Modulated Radiation Therapy for Localized Prostate Cancer: An Exploration of Dose–Volume Histogram Parameters to Limit Genitourinary and Gastrointestinal Toxicity

PURPOSE 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. METHODS AND MATERIALS 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. RESULTS 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. CONCLUSIONS 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.

The use of anticoagulants improves biochemical control of localized prostate cancer treated with radiotherapy

Substantial experimental evidence suggests that anticoagulants (ACs) may inhibit cancer growth and metastasis, although the limited data from clinical trials have been inconsistent. The potential antineoplastic effect of ACs was investigated in patients who received radiotherapy for localized prostate cancer.

Biochemical Control and Toxicity after Intensity-Modulated Radiation Therapy for Prostate Cancer:

Intensity modulated radiation therapy (IMRT) has achieved widespread use for prostate cancer; however, in relation to this use, outcomes studies are still relatively sparse. We report a single-institutional experience in outcomes analysis with the use of IMRT for the primary management of prostate cancer. One hundred thirty consecutive patients with adenocarcinoma of the prostate were treated at a single institution using IMRT with curative intent. Thirty-six (28%) patients were classified as low-risk, 69 (53%) as intermediate-risk, and 25 (19%) as high-risk. The median dose prescription was 76 Gy to the planning target volume. Sixty-five (50%) patients received androgen deprivation therapy (ADT) for a median 4 months, starting 2 months prior to IMRT. Biochemical failure was defined as PSA > post-treatment nadir+2. Gastrointestinal (GI) and Genitourinary (GU) toxicity were defined by RTOG criteria. Median follow-up was 53 months. By NCCN risk category, 4-year biochemical control was 97%, 94%, and 87% for low, intermediate, and high-risk patients, respectively. Among disease factors, multivariable analysis demonstrated the strongest association between biochemical control and Gleason score ≤6 (p=0.0371). Therapy was well tolerated with no Grade 4 toxicity and limited grade 3 GI or GU toxicity. Acute Grade 3+ GI and GU toxicity rates were 0% and 2%, and maximal late Grade 3+ GI and GU toxicity rates were 5% and 6%, respectively. Late rectal toxicity was associated with higher volumes of RT to the rectum. By last follow-up late Grade 3+ toxicity was 2% for both GI and GU systems. In conclusion, patients treated with IMRT for prostate cancer have excellent rates of biochemical control and low rates of severe toxicity of treatment.

Influence of intensity-modulated radiotherapy on acute genitourinary and gastrointestinal toxicity in the treatment of localized prostate cancer.

The objective of this investigation is to compare acute genitourinary (GU) and gastrointestinal (GI) toxicity results of radiotherapy to localized fields delivered using intensity-modulated radiotherapy (IMRT) versus conventional radiotherapy (ConvRT). The records of 481 consecutive prostate cancer patients receiving RT to localized fields at a single institution were reviewed; 108 received IMRT and 373 received ConvRT. Acute GU and GI toxicity, as defined by the Radiation Therapy Oncology Group (RTOG) grading system, were compared using the chi-square test. Ordered logit regression analyses were performed using all major disease and treatment factors as covariates. Acute GU grade 0, 1, 2, 3, and 4 toxicity rates were 23%, 40%, 34%, 3%, and 0%, respectively, in the IMRT cohort and 31%, 37%, 30%, 1%, and 1%, respectively, in the ConvRT cohort - these rates were not significantly different (p=0.118). Acute GI grade 0, 1, 2, 3, and 4 toxicity rates were 42%, 37%, 22%, 0%, and 0%, respectively, in the IMRT cohort and 33%, 32%, 35%, 0%, and 0%, respectively, in the ConvRT cohort - this lower toxicity in the IMRT group was significant (p=0.013). The regression analyses showed that only IMRT use (p=0.046) predicted reduction in acute GI toxicity but no factors correlated with acute GU toxicity rate. In conclusion, in our retrospective single-institution analysis, IMRT was not associated with reduction of acute GU toxicity but was associated with a reduction of acute GI toxicity over ConvRT in the treatment of prostate cancer to localized fields.

Dose-Escalated Radiotherapy for High-Risk Prostate Cancer: Outcomes in Modern Era With Short-Term Androgen Deprivation Therapy

PURPOSE Randomized data have supported the use of long-term androgen deprivation therapy (ADT) combined with radiotherapy (RT) for men with high-risk prostate cancer. The present study reviewed the outcomes of intermediate- and high-risk men treated with RT and short-term ADT. MATERIALS AND METHODS A total of 184 men with any single risk factor of prostate-specific antigen >or=10 ng/mL, clinical Stage T2b or greater, or Gleason score >or=7 were treated with primary external beam RT for nonmetastatic adenocarcinoma of the prostate. The median radiation dose was 74 Gy; 55% were treated with intensity-modulated RT. All patients received ADT for 1 to 6 months (median, 4), consisting of a gonadotropin-releasing hormone analog. Univariate and multivariable analyses were performed for risk factors, including T stage, Gleason score, radiation dose, and prostate-specific antigen level. RESULTS With a median follow-up of 51 months, the 4-year freedom from biochemical failure (FFBF) using the nadir plus 2 ng/mL definition was 83% for all patients. Clinical Stage T3 disease was the only variable tested associated with FFBF on univariate (4-year FFBF rate, 46% vs. 87% for Stage T1-T2c disease; p = .0303) and multivariable analysis (hazard ratio, 3.9; p = .0016). On a subset analysis of high-risk patients (National Comprehensive Cancer Network criteria), those with clinical Stage T3 disease (4-year FFBF rate, 46% vs. 80%; p = .0303) and a radiation dose <74 Gy (4-year FFBF rate, 64% vs. 80%) had a poorer outcome on univariate analysis. However, clinical Stage T3 disease and radiation dose were not significant on multivariable analysis, although a statistical multivariable trend was seen for both (p = .0650 and p = .0597, respectively). CONCLUSION Short-term ADT and RT might be acceptable for men with intermediate- and high-risk prostate cancer, especially for clinically localized disease treated with doses of >or=74 Gy.

Dose-escalated radiation therapy for intermediate-risk prostate cancer: patient selection for androgen deprivation therapy using percentage of positive cores.

Randomized trials supported the use of androgen deprivation therapy (ADT) with radiation therapy (RT) for intermediate‐risk prostate cancer. However, the value of concurrent ADT was less certain with dose‐escalated RT. Better methods of stratifying patients in this risk group may help select patients who are most likely to benefit.