Role for postoperative radiation therapy in adenoid cystic carcinoma of the head and neck.

OBJECTIVE: Clarify the role for postoperative radiation for adenoid cystic carcinoma (ACC) of the head and neck as it relates to tumor site, T-stage, and surgical margin status. STUDY DESIGN: Retrospective cohort study at an academic tertiary care hospital. METHODS: A review of 129 patients with biopsy-proven ACC was performed. Previous treatment failures and nonoperative candidates were excluded, with 75 patients considered eligible for further study. Patients were grouped according to treatment modality and Kaplan-Meier estimates of overall survival, locoregional control, and distant control were compared using log-rank tests. Patients were also stratified according to tumor site, T-stage, and surgical margin status, and pair-wise comparisons of treatment outcome within each group were performed using Wald tests from Cox proportional hazards models. RESULTS: Twenty-five patients were treated with surgery alone, and 50 were treated with surgery and postoperative radiation. There was no significant difference in outcome between treatment groups when correlated with tumor site (P =.89). However, postoperative radiation was associated with improved overall survival for advanced T-stage (T4) tumors (P =.019) and greater locoregional control for patients with microscopically positive margins (P =.018). There was no demonstrated benefit of postoperative radiation for patients with microscopically negative margins (P =.93). CONCLUSIONS: The findings of this study suggest that advanced T-stage and positive microscopic margins are important factors in determining the necessity for postoperative radiation therapy for ACC of the head and neck and that radiation therapy may not be necessary for patients with early T-stage tumors and negative surgical margins.

Radical prostatectomy, external beam radiotherapy <72 Gy, external beam radiotherapy > or =72 Gy, permanent seed implantation, or combined seeds/external beam radiotherapy for stage T1-T2 prostate cancer.

PURPOSE: To review the biochemical relapse-free survival (bRFS) rates after treatment with permanent seed implantation (PI), external beam radiotherapy (EBRT) <72 Gy (EBRT <72), EBRT > or =72 Gy (EBRT > or =72), combined seeds and EBRT (COMB), or radical prostatectomy (RP) for clinical Stage T1-T2 localized prostate cancer treated between 1990 and 1998. METHODS AND MATERIALS: The study population comprised 2991 consecutive patients treated at the Cleveland Clinic Foundation or Memorial Sloan Kettering at Mercy Medical Center. All cases had pretreatment prostate-specific antigen (iPSA) levels and biopsy Gleason scores (bGSs). Neoadjuvant androgen deprivation for < or =6 months was given in 622 cases (21%). No adjuvant therapy was given after local therapy. RP was used for 1034 patients (35%), EBRT <72 for 484 (16%), EBRT > or =72 for 301 (10%), PI for 950 (32%), and COMB for 222 patients (7%). The RP, EBRT <72, EBRT > or =72, and 154 PI patients were treated at Cleveland Clinic Foundation. The median radiation doses in EBRT <72 and EBRT > or =72 case was 68.4 and 78.0 Gy, respectively. The median follow-up time for all cases was 56 months (range 12-145). The median follow-up time for RP, EBRT <72, EBRT > or =72, PI, and COMB was 66, 75, 49, 47, and 46 months, respectively. Biochemical relapse was defined as PSA levels >0.2 for RP cases and three consecutive rising PSA levels (American Society for Therapeutic Radiology Oncology consensus definition) for all other cases. A multivariate analysis for factors affecting the bRFS rates was performed using the following variables: clinical T stage, iPSA, bGS, androgen deprivation, year of treatment, and treatment modality. The multivariate analysis was repeated excluding the EBRT <72 cases. RESULTS: The 5-year bRFS rate for RP, EBRT <72, EBRT > or =72, PI, and COMB was 81%, 51%, 81%, 83%, and 77%, respectively (p <0.001). The 7-year bRFS rate for RP, EBRT <72, EBRT > or =72, PI, and COMB was 76%, 48%, 81%, 75%, and 77%, respectively. Multivariate analysis, including all cases, showed iPSA (p <0.001), bGS (p <0.001), year of therapy (p <0.001), and treatment modality (p <0.001) to be independent predictors of relapse. Because EBRT <72 cases had distinctly worse outcomes, the analysis was repeated after excluding these cases to discern any differences among the other modalities. The multivariate analysis excluding the EBRT <72 cases revealed iPSA (p <0.001), bGS (p <0.001), and year of therapy (p = 0.001) to be the only independent predictors of relapse. Treatment modality (p = 0.95), clinical T stage (p = 0.09), and androgen deprivation (p = 0.56) were not independent predictors for failure. CONCLUSION: The biochemical failure rates were similar among PI, high-dose (> or =72 Gy) EBRT, COMB, and RP for localized prostate cancer. The outcomes were significantly worse for low-dose (<72 Gy) EBRT.

Factors associated with improved survival in patients with brain metastases from esophageal cancer: a retrospective review.

There are over 200,000 cases of brain metastases (BrM) every year, but very few are from esophageal cancer primaries. In order to determine predictors for outcome of these patients, the authors conducted a retrospective review of twenty-seven patients with BrM from esophageal carcinoma diagnosed at the Cleveland Clinic Foundation between 1991 and 2001. For the entire cohort, median follow-up and median survival was 3.6 months and 3.6 months, respectively. On univariate analysis, patients with Karnofsky Performance Status (KPS) >/= 70, low recursive partitioning analysis score, single BrM, no systemic disease, and aggressive treatment [surgery, stereotactic radiosurgery (SRS) + whole brain radiation (WBRT), SRS + surgery + WBRT, surgery + WBRT)] had a significantly improved survival. In a multivariate model, patients with higher KPS and aggressive treatment had improved survival. The 1-year survival for the WBRT alone group and the aggressive treatment group was 6%, and 36% respectively. We conclude that based on the data presented here, patients with BrM from esophageal cancer have poor outcome. Aggressive treatment and favorable KPS are associated with longer survival for selected patients. We recommend esophageal cancer patients with BrM be enrolled in clinical trials to better delineate the role of treatment and potentially improve results.

Preliminary observations on biochemical relapse-free survival rates after short-course intensity-modulated radiotherapy (70 Gy at 2.5 Gy/fraction) for localized prostate cancer.

PURPOSE: To compare the preliminary biochemical relapse-free survival rates between short-course intensity-modulated radiotherapy (SCIM-RT) delivering 70 Gy in 28 fractions and three-dimensional conformal radiotherapy (3D-CRT) delivering 78 Gy in 39 fractions. METHODS AND MATERIALS: Between January 1998 and December 1999, 166 patients were treated with SCIM-RT and 116 with 3D-CRT. The SCIM-RT cases were treated to 70 Gy (2.5 Gy/fraction) using 5 intensity-modulated fields using a dynamic multileaf collimator. The BAT transabdominal ultrasound system was used for localization of the prostate gland in all SCIM-RT cases. The 116 3D-CRT cases were treated to 78.0 Gy (2.0 Gy/fraction). The study sample therefore comprised 282 cases; 70 Gy in 28 fractions is equivalent to 78 Gy in 39 fractions for late-reacting tissues, according to the linear-quadratic model. The median follow-up for all cases was 25 months (range 3-42). The median follow-up was 21 months for the SCIM-RT cases (range 3-31) and 32 months for the 3D-CRT cases (range 3-42). The follow-up period was shorter for the SCIM-RT cases, because SCIM-RT was started only in October 1998. Biochemical relapse was defined as 3 consecutive rising prostate-specific antigen levels after reaching a nadir. The analysis was then repeated with a more stringent definition of biochemical control: reaching and maintaining a prostate-specific antigen level of < or =0.5 ng/mL. Radiation Therapy Oncology Group toxicity scores were used to assess complications. RESULTS: For the 282 patients, the biochemical relapse-free survival rate at 30 months was 91% (95% confidence interval 88-95%). The biochemical relapse-free survival rate at 30 months for 3D-CRT vs. SCIM-RT was 88% (95% confidence interval 82-94%) vs. 94% (95% confidence interval 91-98%), respectively. The difference was not statistically significant between the two treatment arms (p = 0.084). The multivariate time-to-failure analysis using the Cox proportional hazards model for clinical parameters showed the pretreatment prostate-specific antigen level (p <0.001) and biopsy Gleason score (p <0.001) to be the only independent predictors of biochemical relapse. Clinical T stage (p = 0.66), age (p = 0.15), race (p = 0.25), and neoadjuvant androgen deprivation (p = 0.66) were not independent predictors of biochemical failure. SCIM-RT showed only a trend toward a better outcome on multivariate analysis (p = 0.058). Late rectal toxicity was limited; the actuarial combined Grade 2 and 3 late rectal toxicity rate at 30 months was 5% for SCIM-RT vs. 12% for 3D-CRT (p = 0.24). Grade 3 late rectal toxicity (rectal bleeding requiring cauterization) occurred in a total of 10 patients. The actuarial Grade 3 late rectal toxicity rate at 30 months was 2% for the SCIM-RT cases and 8% for the 3D-CRT cases (p = 0.059). Late urinary toxicity was rare in both groups. CONCLUSION: With the currently available follow-up period (< or =30 months), the hypofractionated intensity-modulated radiotherapy schedule of 70.0 Gy delivered at 2.5 Gy/fraction had a comparable biochemical relapse profile with the prior 3D-CRT schedule delivering 78.0 at 2.0 Gy/fraction. The late rectal toxicity profile has been extremely favorable. If longer follow-up confirms the favorable biochemical failure and low late toxicity rates, SCIM-RT will be an alternative and more convenient way of providing dose escalation in the treatment of localized prostate cancer.

Dose/volume relationship of late rectal bleeding after external beam radiotherapy for localized prostate cancer: absolute or relative rectal volume?

PURPOSE: The purpose of this study was to analyze predictors of late rectal bleeding after external-beam radiotherapy for localized prostate cancer, with a focus on the volume of rectum irradiated. MATERIALS AND METHODS: One hundred twenty-eight patients were treated with external-beam radiotherapy at the Cleveland Clinic Foundation between January 1998 and June 1999. Conformal radiotherapy (CRT) was used to deliver 78 Gy at 2 Gy per fraction in 76 cases, and short-course intensity-modulated radiotherapy (SCIM-RT) was used to deliver 70 Gy at 2.5 Gy per fraction in 52 cases. All contours were determined by one physician. The rectum was outlined from 1 cm above the target structures to 1 cm below the target structures. The entire volume of the rectum, along with the outer rectal wall, was included. All cases had detailed planning parameters that specifically determined the rectal volume receiving the prescription dose (VrPr), that is, 78 Gy for CRT and 70 Gy for SCIM-RT, and the percent of rectal volume receiving the prescription dose (%VrPr). The RTOG scales were used to evaluate late toxicity. The median follow-up was 24 months for all cases (range, 3-34 months), 21 months for SCIM-RT cases (range, 11-26 months), and 28 months for CRT cases (range, 3-34 months). RESULTS: To date, five patients have had grade 1 late rectal toxicity (one CRT case and four SCIM-RT cases), one patient had grade 2 late rectal toxicity (CRT), and three patients had grade 3 late rectal toxicity (all CRT cases). Because of the low number of events, the analysis was performed with all patients experiencing rectal bleeding grouped together. The actuarial rectal bleeding rates at 18 and 24 months were 6% and 8%, respectively. The actuarial rectal bleeding rates at 24 months were identical (8%) for both SCIM-RT and CRT. A multivariate analysis of the following parameters was performed to determine independent predictors of rectal bleeding: age (continuous variable), race (Caucasian vs African American), coverage of seminal vesicles (yes vs no), adjuvant androgen deprivation (yes vs no), technique (CRT vs SCIM-RT), Radiation Therapy Oncology Group acute rectal toxicity score (continuous variable), VrPr (continuous variable in cubic centimeters), and %VrPr (continuous variable). Only the VrPr (cubic centimeter) was an independent predictor of rectal bleeding; %VrPr was not. With different cut-off levels being used, a VrPr of 15 cm3 was significant on univariate analysis; the actuarial rectal bleeding rates at 24 months for patients with a VrPr < or = 15 cm3 versus a VrPr > 15 cm3 were 5% versus 22%, respectively. CONCLUSION> In our study sample, which included both conformal and intensity-modulated radiotherapy patients, the volume of rectum receiving the prescribed radiation dose (the equivalent of 78 Gy) was an independent predictor of late rectal bleeding. The percent of rectal volume receivingthe full dose was not. Using actual volume rather than percent volume also avoids the dependence on the extent of rectal volume contours. We recommend 15 cm3 as the cut-off of the rectal volume not to exceed the prescription dose. The rectal bleeding rate at 2 years for cases with < 15 cm3 receiving the full dose was only 5%.