Anal carcinoma: impact of TN category of disease on survival, disease relapse, and colostomy failure in US Gastrointestinal Intergroup RTOG 98-11 phase 3 trial.

PURPOSE: The long-term update of US GI Intergroup RTOG 98-11 anal cancer trial found that concurrent chemoradiation (CCRT) with fluorouracil (5-FU) plus mitomycin had a significant impact on disease-free survival (DFS) and overall survival (OS) compared with induction plus concurrent 5-FU plus cisplatin. The intent of the current analysis was to determine the impact of tumor node (TN) category of disease on survival (DFS and OS), colostomy failure (CF), and relapse (local-regional failure [LRF] and distant metastases [DM]) in this patient group. METHODS AND MATERIALS: DFS and OS were estimated univariately by using the Kaplan-Meier method, and 6 TN categories were compared by the log-rank test (T2N0, T3N0, T4N0, T2N1-3, T3N1-3, and T4N1-3). Time to relapse and colostomy were estimated by the cumulative incidence method, and TN categories were compared using Gray's test. RESULTS: Of 682 patients, 620 were analyzable for outcomes by TN category. All endpoints showed statistically significant differences among the TN categories of disease (OS, P<.0001; DFS, P<.0001; LRF, P<.0001; DM, P=.0011; CF, P=.01). Patients with the poorest OS, DFS, and LRF outcomes were those with T3-4N-positive (+) disease. CF was lowest for T2N0 and T2N+ (11%, 11%, respectively) and worst for the T4N0, T3N+, and T4N+ categories (26%, 27%, 24%, respectively). CONCLUSIONS: TN category of disease has a statistically significant impact on OS, DFS, LRF, DM, and CF in patients treated with CCRT and provides excellent prognostic information for outcomes in patients with anal carcinoma. Significant challenges remain for patients with T4N0 and T3-4N+ categories of disease with regard to survival, relapse, and CF and lesser challenges for T2-3N0/T2N+ categories.

Long-term update of US GI intergroup RTOG 98-11 phase III trial for anal carcinoma: survival, relapse, and colostomy failure with concurrent chemoradiation involving fluorouracil/mitomycin versus fluorouracil/cisplatin.

PURPOSE: On initial publication of GI Intergroup Radiation Therapy Oncology Group (RTOG) 98-11 [A Phase III Randomized Study of 5-Fluorouracil (5-FU), Mitomycin, and Radiotherapy Versus 5-Fluorouracil, Cisplatin and Radiotherapy in Carcinoma of the Anal Canal], concurrent chemoradiation (CCR) with fluorouracil (FU) plus mitomycin (MMC) decreased colostomy failure (CF) when compared with induction plus concurrent FU plus cisplatin (CDDP), but did not significantly impact disease-free survival (DFS) or overall survival (OS) for anal canal carcinoma. The intent of the updated analysis was to determine the long-term impact of treatment on survival (DFS, OS, colostomy-free survival [CFS]), CF, and relapse (locoregional failure [LRF], distant metastasis) in this patient group. PATIENTS AND METHODS: Stratification factors included sex, clinical node status, and primary size. DFS and OS were estimated univariately by the Kaplan-Meier method, and treatment arms were compared by log-rank test. Time to relapse and CF were estimated by the cumulative incidence method and treatment arms were compared by using Gray's test. Multivariate analyses used Cox proportional hazard models to test for treatment differences after adjusting for stratification factors. RESULTS: Of 682 patients accrued, 649 were analyzable for outcomes. DFS and OS were statistically better for RT + FU/MMC versus RT + FU/CDDP (5-year DFS, 67.8% v 57.8%; P = .006; 5-year OS, 78.3% v 70.7%; P = .026). There was a trend toward statistical significance for CFS (P = .05), LRF (P = .087), and CF (P = .074). Multivariate analysis was statistically significant for treatment and clinical node status for both DFS and OS, for tumor diameter for DFS, and for sex for OS. CONCLUSION: CCR with FU/MMC has a statistically significant, clinically meaningful impact on DFS and OS versus induction plus concurrent FU/CDDP, and it has borderline significance for CFS, CF, and LRF. Therefore, RT + FU/MMC remains the preferred standard of care.

The importance of urethra visualization for preplanned permanent prostate implants.

PURPOSE: To assess the potential consequences of using a surrogate urethra on urethral dose estimates in preplanned 125I prostate implants. METHODS AND MATERIALS: For n=220 patients, the A-P and L-R extents of prostate and urethra contours were measured in transrectal ultrasound images. Treatment plans were then developed for 6 patients, of which 5 had atypical urethral positions. For each patient, three plan variations were made using the visualized and two different surrogate urethra contours. RESULTS: The urethra typically remains fixed in the L-R direction and extends slightly below midgland, but may veer off-center and can come within 0.5 cm of the posterior surface of the prostate. Use of a surrogate urethra can potentially result in up to 30% of the urethra receiving doses exceeding a planned limit of 1.5 x 145 Gy over a contiguous length of 2.0 cm. CONCLUSIONS: The urethra should be visualized for preplanning purposes, because unintended urethral doses arising from the use of a surrogate urethra can approach levels associated with late urinary morbidity. Visualization is also essential in the postimplant setting for accurate collection of dose-toxicity data.

Dosimetric consequences of increased seed strength for I-125 prostate implants.

Based on the findings of an earlier planning study, we compared post-implant dose distributions for two groups of 20 consecutive patients treated to 145 Gy with 0.414 and 0.526 U I-125 seeds. Dosimetric coverage as measured by the key clinical index D(90) was significantly better for the higher-strength seeds, with no apparent deleterious effects.

Is there a preferred strength for regularly spaced 125I seeds in inverse-planned prostate implants?

PURPOSE: To determine whether a preferred seed strength exists for 125I prostate implants preplanned using a fixed intraneedle seed spacing of 1 cm and an objective needle placement strategy within the planning target volume (PTV), and incorporating explicit dose-volume constraints for the PTV and tissues at risk. METHODS AND MATERIALS: Prostate, urethra, and rectum contours for 10 patients were obtained from transrectal ultrasound studies. The PTV was defined in accordance with Radiation Therapy Oncology Group (RTOG) 0019 protocol. Inverse planning software was used to optimally arrange seeds of strength 0.3-0.8 U to cover the PTV to D(Rx) = 145 Gy, and limit urethra and rectum doses to 150% and 100% of D(Rx), respectively. Isodose distributions and dosimetric indices were calculated: V(200), V(150), V(100), V(90), D(100), D(90) for PTV; V(150) for urethra; and V(100) for rectum. For seeds of strength 0.414 and 0.6 U and three prostate sizes, the sensitivity of V(90) and D(90) to elementary perturbations of the optimal seed arrangement were examined. RESULTS: For our planning scenario, 125I seeds of strength 0.5-0.6 U provided the best possible PTV coverage while maintaining V(200) at approximately 25%. The source arrangement for 0.6-U seeds was only modestly more sensitive to perturbations than that for 0.414-U seeds. These findings may not be applicable to implants planned manually or that involve needle placement outside the PTV. CONCLUSION: Given a particular source arrangement, inverse planning aimed at maximizing dosimetric coverage of the prostate while limiting doses to the urethra and rectum can be used to search for a preferred seed strength. For regularly spaced sources within the PTV, higher strength seeds can provide better dose coverage and better urethral protection than lower strength seeds.