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Objectives: To evaluate the dosimetry, clinical outcomes, and toxicity of patients treated with stereotactic body radiotherapy (SBRT) for adrenal metastases., Materials and Methods: From February 2009 to February 2011, a total of 13 patients were treated with SBRT for metastases to the adrenal glands. Median age was 71 years (range, 60.8 to 83.2). Primary sites included lung (n=6), kidney (n=2), skin (n=2), bladder (n=1), colon (n=1), and liver (n=1). Nine patients had metastases to the left adrenal gland and 4 to the right. The median prescribed total dose was 45 Gy (range, 33.75 to 60 Gy), all in 5 fractions., Results: Median follow-up for living patients was 12.3 months (range, 3.1 to 18 mo). Twelve of the 13 patients (92.3%) were evaluable for local control (LC). The crude LC rate was 100%, with no cases of local or marginal failure. Two patients had a complete response to treatment, 9 patients had a partial response, and 1 patient displayed stable disease. One-year overall survival and distant control were 62.9% and 55%, respectively. Median OS was 7.2 months (range, 2 to 18 mo). Grade 2 nausea was noted in 2 patients., Conclusions: SBRT seems to be a safe and effective measure to achieve LC for adrenal metastases.

Purpose: Gastrointestinal injury occurs rarely with agents that affect the vascular endothelial growth factor receptor and with abdominal stereotactic body radiation therapy (SBRT). We explored the incidence of serious bowel injury (SBI) in patients treated with SBRT with or without vascular endothelial growth factor inhibitor (VEGFI) therapy., Methods and Materials: Seventy-six patients with 84 primary or metastatic intra-abdominal lesions underwent SBRT (median dose, 50 Gy in 5 fractions). Of the patients, 20 (26%) received VEGFI within 2 years after SBRT (bevacizumab, n=14; sorafenib, n=4; pazopanib, n=1; sunitinib, n=1). The incidence of SBI (Common Terminology Criteria for Adverse Events, version 4.0, grade 3-5 ulceration or perforation) after SBRT was obtained, and the relationship between SBI and VEGFI was examined., Results: In the combined population, 7 patients (9%) had SBI at a median of 4.6 months (range, 3-17 months) from SBRT. All 7 had received VEGFI before SBI and within 13 months of completing SBRT, and 5 received VEGFI within 3 months of SBRT. The 6-month estimate of SBI in the 26 patients receiving VEGFI within 3 months of SBRT was 38%. No SBIs were noted in the 63 patients not receiving VEGFI. The log-rank test showed a significant correlation between SBI and VEGFI within 3 months of SBRT (P=.0006) but not between SBI and radiation therapy bowel dose (P=.20)., Conclusions: The combination of SBRT and VEGFI results in a higher risk of SBI than would be expected with either treatment independently. Local therapies other than SBRT may be considered if a patient is likely to receive a VEGFI in the near future., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Purpose/objectives: To present clinical outcomes, early toxicity, and dosimetric constraints for patients undergoing stereotactic body radiation therapy (SBRT) for abdominal or pelvic tumors., Materials and Methods: From May 2008 to February 2010, 47 patients with 50 lesions in proximity to hollow viscous organs at risk, including stomach, duodenum, small bowel, and colon, underwent SBRT at Mayo Clinic. Treated sites included liver (21), lymph node (14), adrenal gland (6), intramuscular (4), pancreas (3), and spleen (2). Treatment planning was performed with full body immobilization and 4-dimensional computed tomography (CT)-based planning with daily cone-beam CT or stereoscopic kV imaging for pretreatment image guidance. SBRT was delivered in 1 to 5 consecutive daily fractions in a single week. The most commonly prescribed dose was 50 Gy in 5 fractions (median 45 Gy, range: 20 to 60 Gy). Toxicities were scored by CTCAE v.3. Local failure was defined as per the Response Evaluation Criteria in Solid Tumors., Results: Median follow-up was 12 months (range: 2 to 28 mo). Tumor responses of the 48 target lesions evaluable by Response Evaluation Criteria in Solid Tumor were complete response in 18 lesions (36%), partial response in 12 lesions (24%), stable disease in 12 lesions (24%), and progressive disease in 6 lesions (12%). Kaplan-Meier estimates of local control, overall survival, and freedom from metastasis at 6 and 12 months were 98%, 90%, and 63%, and 87%, 62%, 37%, respectively. Treatment was well-tolerated acutely without reported grade ≥3 toxicity. Five grade 3 late toxicities were reported, and 1 patient died of complications from duodenal perforation 11 months after SBRT. No dose correlation with toxicity could be established., Conclusions: SBRT is a practical treatment option for patients with abdominopelvic tumors. Relapse typically occurs outside treatment fields, and most patients achieve a favorable response. The dose constraints used in this cohort of patients was associated with acceptable early treatment-related toxicity.

Purpose: The management of patients diagnosed with thymoma remains unclear. This report attempts to identify the impact of adjuvant radiotherapy on overall survival (OS) and cause-specific survival (CSS) in patients diagnosed with thymoma., Methods and Materials: Patients diagnosed with thymic malignancy between 1973 and 2003 were retrospectively identified from centers participating in the Surveillance, Epidemiology, and End Results (SEER) program. Those patients classified as having thymic carcinoma were excluded from this analysis. OS and CSS were estimated by the Kaplan-Meier method. Outcomes for patients treated with and without radiation therapy were compared using the log-rank test. Multivariate analysis was performed with the Cox proportional hazards model to analyze factors predictive of OS and CSS., Results: A total of 1,464 patients were identified as having thymic malignancy, and of these, 1,254 patients were identified as having malignant thymoma. The median follow-up time was 41 months (range, 4-337 months). Among patients who did not receive radiotherapy (RT), the 10-year rate of OS was 41% compared to 42% for those who did receive RT (p = 0.06). The median OS for the patients who did not receive RT was 80 months compared to 97 months for those who did receive RT. In patients with Masaoka stage II-III malignancy, OS was significantly improved with RT (p = 0.002), and a trend in improved CSS was observed (p = 0.1). Patients were also analyzed based on resection status. For those patients who had an incomplete excision, the 10-year OS was 63% with RT and 46% without RT (p = 0.38). On multivariate analysis, factors predictive of OS included age, extent of surgery, stage, and number of lymph nodes examined., Conclusions: This study reports treatment results of a large cohort of patients who were diagnosed with malignant thymoma. This study demonstrates that the use of RT following resection for thymoma significantly improves OS for those with regional disease and marginally improves CSS., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Purpose: To quantify the dosimetric deviations that would arise from delivering subsequent prostate high-dose-rate fractions with only needle readjustment and no replanning after the first fraction., Methods and Materials: Patients were treated with either two implant sessions (two 9.5-Gy fractions per session) separated by 2-4 weeks or with one implant session and external beam radiotherapy. After needle placement, needle positions were adjusted under CT guidance, after which dosimetric planning was performed before each fraction. To evaluate the consequence of not replanning before the second fraction, we analyzed the dosimetric parameters of 45 consecutive implants (26 patients). Needles with optimized dwell positions from the first fraction were transferred to the needle positions in the second fraction. Needle displacement between fractions was assessed as well as changes in plan metrics., Results: After adjustment, the mean interfractional needle displacement was 3.5 mm. If replanned, the probability of planning target volume D90% ≥ 95% is 100%, prostate V100% ≥ 95% is 87%, and urethra V115% ≤10% is 78%. If treated without replanning, the probability of planning target volume D90% ≥ 95% is 82%, prostate V100% ≥ 95% is 53%, and urethra V115% ≤ 10% is 69%. Even for implants with minimal needle displacement (<3 mm) and minimal prostate volume change (<3 cc), the dosimetric consequence of not replanning the second fraction would result in 46% of cases with a prostate V100% < 95%., Conclusion: The dosimetric consequences of not replanning the second fraction for prostate high-dose-rate implants results in significantly inferior plan metrics., (Copyright © 2012 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.)

Purpose: The benefit of adjuvant radiotherapy (RT) after surgical resection for extrahepatic cholangiocarcinoma has not been clearly established. We analyzed survival outcomes of patients with resected extrahepatic cholangiocarcinoma and examined the effect of adjuvant RT., Methods and Materials: Data were obtained from the Surveillance, Epidemiology, and End Results (SEER) program between 1973 and 2003. The primary endpoint was the overall survival time. Cox regression analysis was used to perform univariate and multivariate analyses of the following clinical variables: age, year of diagnosis, histologic grade, localized (Stage T1-T2) vs. regional (Stage T3 or greater and/or node positive) stage, gender, race, and the use of adjuvant RT after surgical resection., Results: The records for 2,332 patients were obtained. Patients with previous malignancy, distant disease, incomplete or conflicting records, atypical histologic features, and those treated with preoperative/intraoperative RT were excluded. Of the remaining 1,491 patients eligible for analysis, 473 (32%) had undergone adjuvant RT. After a median follow-up of 27 months (among surviving patients), the median overall survival time for the entire cohort was 20 months. Patients with localized and regional disease had a median survival time of 33 and 18 months, respectively (p<.001). The addition of adjuvant RT was not associated with an improvement in overall or cause-specific survival for patients with local or regional disease., Conclusion: Patients with localized disease had significantly better overall survival than those with regional disease. Adjuvant RT was not associated with an improvement in long-term overall survival in patients with resected extrahepatic bile duct cancer. Key data, including margin status and the use of combined chemotherapy, was not available through the SEER database., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Background and Purpose: Identify the incidence of early pulmonary toxicity in a cohort of patients treated with lung stereotactic body radiation therapy (SBRT) on consecutive treatment days., Material and Methods: A total of 88 lesions in 84 patients were treated with SBRT in consecutive daily fractions (Fx) for medically inoperable non-small cell lung cancer or metastasis. The incidence of pneumonitis was evaluated and graded according to the NCI CTCAE v3.0., Results: With a median follow-up of 15.8 months (range 2.5-28.6), the median age at SBRT was 71.8 years (range 23.8-87.8). 47 lesions were centrally located and 41 were peripheral. Most central lesions were treated with 48Gy in 4 Fx, and most peripheral lesions with 54Gy in 3 Fx. The incidence of grade ≥ 2 pneumonitis was 12.5% in all patients treated, and 14.3% among the subset of patients treated with 54Gy in 3 Fx. A total of two grade 3 toxicities were seen as one grade 5 toxicity in a patient treated for recurrence after pneumonectomy., Conclusions: Treating both central and peripheral lung lesions with SBRT in consecutive daily fractions in this cohort was well tolerated and did not cause excessive early pulmonary toxicity., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Purpose: Proton radiotherapy (PT) and stereotactic body radiotherapy (SBRT) have the capacity to optimize the therapeutic ratio. We analyzed the dosimetric differences between PT and SBRT in treating primary peripheral early-stage non-small-cell lung cancer., Methods and Materials: Eight patients were simulated, planned, and treated with SBRT according to accepted techniques. SBRT treatments were retrospectively planned using heterogeneity corrections. PT treatment plans were generated using single-, two-, and three-field passively scattered and actively scanned proton beams. Calculated dose characteristics were compared., Results: Comparable planning target volume (PTV) median minimum and maximum doses were observed between PT and SBRT plans. Higher median maximum doses 2 cm from the PTV were observed for PT, but higher median PTV doses were observed for SBRT. The total lung mean and V5 doses were significantly lower with actively scanned PT. The lung V13 and V20 were comparable. The dose to normal tissues was lower with PT except to skin and ribs. Although the maximum doses to skin and ribs were similar or higher with PT, the median doses to these structures were higher with SBRT. Passively scattered plans, compared with actively scanned plans, typically demonstrated higher doses to the PTV, lung, and organs at risk., Conclusions: Single-, two-, or three-field passively or actively scanned proton therapy delivered comparable PTV dose with generally less dose to normal tissues in these hypothetic treatments. Actively scanned beam plans typically had more favorable dose characteristics to the target, lung, and other soft tissues compared with the passively scanned plans. The clinical significance of these findings remains to be determined.

Objective: Lymph node (LN) metastasis portends a poor outcome in women with carcinoma of the uterine cervix. We queried a large database to analyze the importance of number of positive LN and histology in relation to survival after radical hysterectomy and lymphadenectomy., Methods: Data were collected from the Surveillance, Epidemiology, and End Results Program on women who had primary surgery for the years 1988 to 2003 (n = 4559). Statistical analyses were performed using conventional methods., Results: The median number of LNs examined per patient has significantly declined in recent years (P = 0.003). The 5-year rates of cause specific and overall survival were 94% and 91%, 76% and 69%, 62% and 58%, and 41% and 35%, for 0, 1 to 2, 3 to 9 and > or =10 positive LNs, respectively. Pathologic LN involvement was associated with higher grade, higher stage, larger tumor size, and squamous cell histology. Predictors for both cause specific and overall survival on multivariate analysis included number of involved LN, histology, tumor grade, tumor size, disease stage, and pelvis or paraaortic lymphatic involvement., Conclusions: Adenocarcinoma histology independently predicted for a more aggressive phenotype, particularly in women with LN involvement. The number of LNs examined did not independently predict for survival when adjusted for patient and disease characteristics, providing context for the investigation of sentinel node biopsy or other sampling methods. LN positive disease in carcinoma of the cervix predicts a prognosis that is inversely related to the number of involved nodes. Tumor grade, size, and FIGO stage were associated with increasing risk for lymph node metastases.

Background: Prophylactic cranial irradiation has been used in patients with small cell lung cancer to reduce the incidence of brain metastasis after primary therapy. The purpose of this study was to evaluate the effects of prophylactic cranial irradiation (PCI) on overall survival and cause-specific survival., Methods: A total of 7995 patients with limited stage small cell lung cancer diagnosed between 1988 and 1997 were retrospectively identified from centers participating in the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) Program. Of them, 670 were identified as having received PCI as a component of their first course of therapy. Overall survival and cause-specific survival were estimated by the Kaplan-Meier method, comparing patients treated with or without prophylactic whole-brain radiotherapy. The Cox proportional hazards model was used in the multivariate analysis to evaluate potential prognostic factors., Results: The median follow-up time was 13 months (range, 1 month to 180 months). Overall survival at 2 years, 5 years, and 10 years was 23%, 11%, and 6%, respectively, in patients who did not receive PCI. In patients who received PCI, the 2-year, 5-year, and 10-year overall survival rates were 42%, 19%, and 9%, respectively (P =or <.001). The cause-specific survival rate at 2 years, 5 years, and 10 years was 28%, 15%, 11%, respectively, in patients who did not receive PCI and 45%, 24%, 17%, respectively, in patients who did receive PCI (P =or <.001). On multivariate analysis of cause-specific and overall survival, age at diagnosis, sex, grade, extent of primary disease, size of disease, extent of lymph node involvement, and PCI were found to be significant (P = or<.001). The hazards ratios for disease-specific and all cause mortality were 1.13 and 1.11, respectively, for those not receiving PCI., Conclusions: Significantly improved overall and cause-specific survival was observed in patients treated with prophylactic cranial irradiation on unadjusted and adjusted analyses. This study concurs with the previously published European experience. Prophylactic cranial irradiation should be considered for patients with limited stage small cell lung cancer., ((c) 2008 American Cancer Society.)

High-dose-rate brachytherapy is a relatively new radiotherapeutic intervention that is used as a curative treatment for patients with many types of cancer. Advances in mechanical systems and computer applications result in a sophisticated treatment technique that reliably delivers a high-quality radiation dose distribution to the intended target. Patients with localized prostate cancer may benefit from high-dose-rate brachytherapy, which may be used alone in certain circumstances or in combination with external-beam radiotherapy in other settings. The authors comprehensively searched the MEDLINE database for clinical studies published from January 1, 2002, through December 31, 2007, using the key terms brachytherapy, high-dose-rate, and prostatic neoplasms. Criteria for study review were study design, English language, relevance to clinicians, and validity based on design and appropriateness of conclusions. The abstract proceedings of meetings sponsored by the American Brachytherapy Society and the American Society for Therapeutic Radiology and Oncology were reviewed to identify additional relevant material. These sources provided the basis for a concise review of the rationale and advantages of high-dose-rate brachytherapy in the management of localized prostate cancer, as well as the details of the clinical use and therapeutic outcomes of this treatment as observed in a contemporaneous time frame.

Objective: To compare the incidence, mortality, and presentation of small cell carcinoma of the cervix with other histologies., Methods: From 1977 to 2003, 290 women with small cell carcinoma of the cervix uteri were identified from the Surveillance, Epidemiology, and End Results database. Also, 27,527 patients with squamous cell carcinoma of the cervix and 5,231 patients with adenocarcinoma of the cervix were identified for comparison. The annual incidence was calculated and examined for trend. Patient and disease characteristics were compared among histologies. Univariable analyses were conducted using the log-rank test. Multivariable analysis was performed using Cox regression., Results: The mean annual incidence for small cell carcinoma was 0.06 per 100,000 women, compared with 6.6 and 1.2 for squamous cell carcinoma and adenocarcinoma, respectively. There were significant differences at presentation between small cell carcinoma compared with squamous cell carcinoma and adenocarcinoma for race, treatment, International Federation of Gynecology and Obstetrics stage, and lymph node involvement (P<.05). A trend for improved survival was identified for adenocarcinoma (P=.036) and squamous cell carcinoma (P<.001) but not for small cell carcinoma (P=.672). Five-year survival for small cell carcinoma (35.7%) was worse compared with squamous cell carcinoma (60.5%, hazard ratio 0.55; 95% confidence interval (CI) 0.43-0.69) and adenocarcinoma (69.7%, hazard ratio 0.48; 95% CI 0.37-0.61). On multivariable analysis, age, stage, and race were prognostic for survival in women with small cell carcinoma (P<.05)., Conclusion: Small cell carcinoma is a rare histology of cervical cancer associated with a worse prognosis and a predilection for nodal and distant metastasis. The decrease in survival was marked in early-stage and node-negative patients. Because of the high rates of nodal involvement even with early-stage disease, multimodality treatment with radiotherapy and chemotherapy should be considered., Level of Evidence: II.

Background: The role of radiotherapy (RT) for rising PSA after radical prostatectomy (RP) is debatable. We analyzed a large database of men to evaluate for predictors of prostate-specific antigen (PSA) failure after salvage RT., Methods: Data from the Cancer of the Prostate Strategic Urologic Research Endeavor database (CaPSURE) identified 4,563 men with RP between 1989 and 2004; 194 underwent salvage RT > or = 6 months after RP. PSA failure following RT was defined as a PSA >0.2 ng/ml. The association between clinical and pathologic characteristics and PSA failure was examined using a chi-square metric. A multivariable analysis of predictors for time to PSA failure was performed using a Cox proportional hazard regression model., Results: After a median follow-up of 66 months, 121 (62%) men experienced PSA failure at a median 20 months. Significant associations for PSA failure were found for the clinical T category (P < .01), race/ethnicity (P = 0.04), pT3 disease (P < 0.01), seminal vesicle invasion (P < 0.01), and pre-RT PSA level (P < 0.01). The pre-RT PSA level (P = 0.07) was the only factor to approach significance as an independent predictor of PSA failure on multivariable analysis. Pre-RT PSA doubling time was calculated for 131 men but did not predict for PSA failure on univariate (P = 0.38) or multivariate analyses (P = 0.13) for < or = 12 vs. >12 months., Conclusions: Salvage RT provided the greatest benefit in PSA control in men with the lowest pre-RT PSA levels. Post-RP PSA doubling time >12 months trended toward predicting for PSA failure but was not significant likely owing to limited sample size. Together, these findings would suggest that salvage RT is optimal at low pre-RT PSA and long doubling times with favorable pathologic features.

Background: Although endometrial cancer remains the most common gynecologic malignancy in the United States, differing approaches to adjuvant radiotherapy treatment for early disease exist within the medical community because of the lack of a national consensus., Methods: The authors studied patterns of adjuvant care for stage I and II endometrial adenocarcinoma using a large United States population database. A retrospective analysis was conducted from the Surveillance, Epidemiology, and End Results (SEER) Program of the U.S. National Cancer Institute from 1988 to 2002, and 26,923 women with American Joint Committee on Cancer stage I and II endometrial adenocarcinoma were selected. The following prognostic factors were analyzed: age, race, stage, grade, year of diagnosis, SEER registry location, and use and type of postoperative radiotherapy (RT). Adjuvant RT was coded as none, external-beam RT (EBRT), brachytherapy (BR), or a combination of the 2 (EBRT + BR)., Results: Higher tumor grade and stage led to greater use of RT. The odds ratio (OR) for adjuvant RT was 3.4 for stage IB versus stage IA and 51.8 for stage IC/II versus stage IA. The effect of grade depended on stage: for stages IA and IB, the OR was 2.9 for grade 2 versus grade 1 and 11.7 for grade 3/4 versus grade 1; whereas, for stage IC/II, the OR was 1.5 for grade 2 versus grade 1 and 2.0 for grade 3/4 versus grade 1. Within stage I, increasing substage and grade increased the odds of EBRT with or without BR compared with BR alone. Race did not effect the choice of therapy (all P > .1). Geographic location had a significant effect on overall RT use and therapy choice., Conclusions: To the authors' knowledge, this was the largest patterns of care analysis to date of adjuvant RT in patients with stage I and II endometrial adenocarcinoma. The current study revealed that there is significant diversity in the use of adjuvant RT across the United States, and the results reflected the absence of a national consensus on adjuvant treatment for early-stage disease.

Objectives: To analyze an observational database of prostate cancer, assessing for patterns of use and predictors of prostate-specific antigen (PSA) recurrence after adjuvant radiotherapy (RT)., Methods: From the Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE), 5336 men underwent prostatectomy from 1989 to 2004. Of these 5336 men, 96 men (1.8%) underwent adjuvant RT. These 96 men were classified as having low (Stage T1c-T2a and PSA level of 10 ng/mL or less and Gleason score of 6 or less), intermediate (Stage T2b or PSA level greater than 10 ng/mL and 20 ng/mL or less or Gleason score 7), or high (Stage T2c or higher or PSA level greater 20 ng/mL or Gleason score of 8 or greater) risk of PSA recurrence. PSA recurrence was defined as two consecutive PSA levels greater than 0.2 ng/mL. Differences between patients who experienced failure were assessed by chi-square tests or analysis of variance. Univariate and multivariate analyses were performed using a Cox proportional hazard regression model., Results: Of the 96 men, 27 (28%) experienced PSA failure and 20 (21%) received additional treatment, with a median of 60 months of follow-up. The clinical risk group (P <0.01), PSA level at diagnosis (P <0.01), Gleason score (P <0.01), and seminal vesicle invasion (P <0.01) all significantly associated with PSA recurrence. The clinical risk group was the sole predictor of PSA recurrence-free survival on multivariate analysis (hazard ratio 2.4, 95% confidence interval 1.7 to 8.3, P = 0.007)., Conclusions: Adjuvant RT was not frequently used in men enrolled in CaPSURE. PSA recurrence was observed more frequently in men with high-risk disease, suggesting that adjuvant RT is not adequate therapy and that these men might benefit from the combined use of hormonal therapy and RT.

Purpose: The utility of serial simulations in vaginal vault irradiation is controversial. Our primary endpoint was to assess the significance of simulation in women who received adjuvant intracavitary high-dose-rate brachytherapy (HDR-BT) for early-stage endometrial adenocarcinoma. Secondary endpoints included assessment of acute and late treatment toxicity, medication requirements, and charges related to the HDR-BT simulation and procedure., Methods and Materials: Twenty-four consecutive women with early-stage endometrial cancer treated with adjuvant HDR-BT were evaluated. Descriptive statistical analyses were performed on the ratio of calculated to prescription BT dose at predefined dosimetric points. Data on acute and late toxicities, medication usage, and simulation charges were evaluated and compared., Results: The intravaginal cylinder was placed three times over 10-14 days (median 6.5Gy prescribed to 5mm). No substantial deviation in the means of the calculated ratios was observed except at the bladder point (mean 0.77+/-0.23). Early toxicity was found to be no greater than Grade 1 (n=5). Serious late toxicities were uncommon; one woman developed a Grade 3 gastrointestinal toxicity. Half of the women required prescription medication incident to simulation. The average simulation charge was $1252.80., Conclusions: Despite the broad range of doses calculated at the bladder point, genitourinary toxicity was minimal. Simulation proved useful in recording dose and represented a small, yet important portion of the total treatment charge but did not alter treatment in this series. The necessity of simulation for intracavitary high-dose-rate vaginal brachytherapy remains unclear.

Objectives: To analyze the prostate-specific antigen (PSA) outcome after low-dose adjuvant RT at a single institution, because the role and optimal dose of external beam radiotherapy (RT) after radical prostatectomy for prostate cancer remain controversial., Methods: We retrospectively identified 65 men who had received low-dose adjuvant RT (median 50 Gy) for microscopically positive margins with an undetectable postoperative PSA from 1990 to 2004. Biochemical failure-free survival was the primary endpoint. Biochemical failure was defined as two consecutive PSA increases to greater than 0.2 ng/mL., Results: At a median follow-up of 5 years, 2 men had developed distant metastasis, 2 had local recurrence, and 2 had died (neither attributable to prostate cancer). Biochemical failure had occurred in 7 men (11%). The 5 and 8-year rate of biochemical failure-free survival was 87%. A greater Gleason score (P = 0.04) and seminal vesicle invasion (P = 0.04) predicted significantly for increased biochemical failure on univariate analysis. No single factor was significant on multivariate analysis. Men with a Gleason score of 7 or less had a 5-year biochemical failure-free survival rate of more than 90%. In contrast, those with a Gleason score of 8 or more had a 50% risk of biochemical failure at 5 years. Acute bowel or bladder toxicity (all grade 2 or less) developed in 25%. Two men developed chronic urethral stricture requiring dilation, and 34 (51%) developed surgery-related toxicity that persisted throughout and after RT., Conclusions: Low-dose RT is well tolerated and can potentially provide PSA control in men with Gleason score 7 or less disease with positive surgical margins after radical prostatectomy.

Objective: The role of post-operative radiotherapy (RT) in women with early-stage, low to intermediate risk cancer of the uterine corpus remains controversial. The primary objective of this analysis was to evaluate the survival outcomes of women with early-stage endometrial cancer treated with surgery alone or surgery followed by RT., Methods: Data from two institutions were collected from 1990 to 2003. The 608 eligible women had FIGO stage IA to IIA endometrial cancer and underwent primary surgery +/-RT. Univariate and multivariate analyses of pertinent variables were performed for the end points of disease-free survival (DFS) and overall survival (OS)., Results: The median age for all women was 64 years. RT was delivered to 133 women (22%). Unfavorable histologic grade (P < 0.0001) and stage (P < 0.0001) were significantly more prevalent in the adjuvant RT group. At a median follow-up of 5.2 years, 26 pelvic (11 vaginal) and 16 distant failures occurred along with 110 deaths (with no significant differences between women undergoing surgery alone or followed by RT). Adjuvant RT, younger age, and lower stage predicted for improved DFS and OS on multivariate analysis. Stratified analysis revealed that adjuvant RT conferred a survival benefit in women with stage IC or IIA disease., Conclusions: Adjuvant RT was associated with improved disease-free and overall survival in women with higher risk disease. Despite significantly worse disease characteristics among women in the adjuvant RT group, the analyzed end points were equivalent among the two groups. These findings suggest that adjuvant radiotherapy has a significant benefit in reducing mortality and disease progression in early-stage carcinoma of the uterine corpus.

Background: Malignant phyllodes tumor is a rare and potentially aggressive breast neoplasm. Little information is available regarding the optimal management of these lesions and rarer still are data regarding survival. The current study used a large population database to determine prognostic factors that predict cause-specific survival (CSS)., Methods: Data were obtained from the Surveillance, Epidemiology, and End Results Program (SEER) for the years 1983-2002. Women receiving resection for primary nonmetastatic malignant phyllodes tumor of the breast were included (n = 821). Analyses of patient, pathologic, and treatment characteristics were performed using univariate and multivariate Cox regression analyses for the CSS endpoint., Results: With a median follow-up of 5.7 years, CSS was 91%, 89%, and 89%, at 5, 10, and 15 years, respectively. Mastectomy was performed in 428 women (52%) and wide excision or lumpectomy in 393 (48%). Women undergoing mastectomy were significantly older (P = .004) and had larger tumors (P = .009). Wide excision was associated with equivalent or improved CSS relative to mastectomy on univariate and multivariate analyses. Older age predicted for cause-specific mortality on multivariate analysis. Adjuvant radiotherapy (RT) predicted for worse CSS when implemented compared with surgery alone., Conclusions: Mastectomy was not found to provide a benefit in CSS compared with wide excision in malignant phyllodes tumor of the breast. Women undergoing wide excision had at the minimum similar cancer-specific mortality compared with those who received mastectomy. The role of adjuvant RT is uncertain and requires further investigation., ((c) 2006 American Cancer Society.)

Purpose: This study was performed to evaluate the results and prognostic factors associated with radiotherapy for a detectable serum prostate specific antigen level after radical prostatectomy., Materials and Methods: From July 1987 through July 2003, 368 patients received radiotherapy for a detectable prostate specific antigen level (biochemical relapse) as the sole evidence of recurrence after radical prostatectomy for node negative prostate cancer. Estimated survival and relapse-free probabilities were obtained via Kaplan-Meier estimation. Associations of patient factors with survival and biochemical relapse were investigated using Cox proportional hazards models., Results: With a median followup of 5 years the 5 and 8-year freedom from biochemical relapse were an estimated 46% (95% CI 41%-53%) and 35% (95% CI 29%-43%) while survival was 92% (95% CI 89%-95%) and 80% (95% CI 74%-87%), respectively. Patient and treatment variables showing evidence of association with biochemical relapse on multivariate analysis included pathological stage T3a or less vs T3b (seminal vesicle involvement, p = 0.029), pathological Gleason score 7 or less vs 8 or greater (p <0.001) and pre-radiotherapy prostate specific antigen (p <0.001). Four biochemical failure risk groups were created by assigning seminal vesicle involvement, Gleason score and pre-radiotherapy prostate specific antigen each a score of 0 to 2. These individual scores were summed. The freedom from biochemical failure at 5 years for each risk group was 0 to 1-69%, 2-53%, 3-26% and 4 to 5-6%., Conclusions: The presence of seminal vesicle involvement and high Gleason score in the radical prostatectomy specimen are inherent predictors of adverse outcome. Early referral for salvage radiotherapy can decrease subsequent biochemical relapse.

Context: The benefit of adjuvant radiation therapy (RT) in stage I endometrial adenocarcinoma remains controversial despite several phase 3 trials., Objective: To evaluate the frequency and effect of adjuvant RT on overall and relative survival within a large US population database., Design, Setting, and Population: A retrospective analysis that used data from the Surveillance, Epidemiology, and End Results program of the US National Cancer Institute from January 1, 1988, to December 31, 2001. A total of 21,249 patients with American Joint Committee on Cancer stage IA-C node-negative endometrial adenocarcinoma comprised the study population., Main Outcome Measures: Overall survival curves were constructed using Kaplan-Meier method and compared via stratified log-rank test within T stage/grade combinations, adjusted for age. Relative survival was performed to assess the effects of age, race, stage, grade, whether nodes were examined, and whether adjuvant RT was administered., Results: Of 21,249 women, 4080 received adjuvant RT (19.2%) and 17,169 did not receive adjuvant RT (80.8%). The mean age at diagnosis was 63.2 years (range, 14-99 years). Adjuvant RT significantly improved overall survival for patients with stage IC/grade 1 (P<.001) and stage IC/grades 3 and 4 (P<.001). Cox proportional hazards regression analysis revealed a statistically detectable association of adjuvant RT with improved relative survival in patients with stage IC/grade 1 and stage IC/grades 3 and 4 (hazard ratio [HR], 0.44; 95% confidence interval [CI], 0.31-0.63; P<.001; and HR, 0.72; 95% CI, 0.57-0.92; P = .009; respectively). A separate analysis of those patients with a surgical lymph node examination at the time of total abdominal hysterectomy and bilateral salpingo-oophorectomy revealed similar estimates (HR, 0.59; 95% CI, 0.39-0.90; P = .01; and HR, 0.73; 95% CI, 0.55-0.96; P = .02; respectively)., Conclusions: As the largest reported population analysis to date of adjuvant RT in early stage endometrial adenocarcinoma, our study reveals a statistically significant association between improved overall and relative survival and adjuvant RT in stage IC disease (grades 1 and 3-4). Future work is needed to continue to delineate clinical and biological factors, which can guide treatment decisions and account for disparities in outcome between varied subsets of patients.

Objective: To evaluate treatment outcomes in women with early-stage endometrial cancer (FIGO IA, IB, IC, or IIA) surgically managed by a general gynecologist (GYN) or a gynecologic oncologist (GYO)., Methods and Results: 349 women treated from 1990-2003 were studied. Median follow-up was 3.7 years. Ninety-five were classified as high-intermediate risk (HIR: stages IB grade III, IC grade II or III, any stage IIA). 110 women received adjuvant radiotherapy. The GYO group had more unfavorable tumor characteristics based on stage and grade (P<0.0001), shorter follow-up (median 3.1 vs. 5.1 years, P=0.0002), and an absolute 12% less likelihood of receiving adjuvant radiotherapy (P=0.04). Local and distant failures were not significantly different. Overall survival favored GYN patients (P=0.02) with no difference in disease-specific survival (P=0.38). Multivariate analysis for disease-free survival revealed HIR disease (P=0.04) and GYO treatment (P=0.049) to be significant, with a trend for age

Objectives: To compare, in a retrospective analysis, the outcome of salvage external beam radiotherapy (EBRT) for isolated prostate-specific antigen (PSA) elevation or palpable local recurrence after radical prostatectomy (RP)., Methods: We evaluated 102 men who underwent EBRT from 1993 to 1999, 60 for a rising PSA level alone and 42 for palpable local disease after RP. Biochemical disease-free survival and overall survival were calculated. Prognostic factors were evaluated to determine associations with biochemical disease-free survival., Results: The 5-year rate of biochemical disease-free survival, local control, freedom from distant metastasis, and overall survival for all 102 patients was 38%, 94%, 87%, and 88%, respectively. All palpable disease resolved completely after salvage EBRT. The greatest 5-year rate of biochemical control (69%) was obtained in patients with a pre-EBRT PSA level of 0.5 ng/mL or less. The 5-year overall survival rate was significantly better for those who underwent salvage EBRT for a rising PSA level than for those with palpable recurrence (96% versus 78%, P = 0.02). A low pre-EBRT PSA level and a less than 2-year interval from RP to EBRT were independent predictors of biochemical failure. Five patients (5%) experienced chronic grade 3 or 4 RT-related toxicity., Conclusions: Salvage EBRT provides excellent local control of recurrent disease after RP. Salvage EBRT before the development of palpable local disease may confer a survival benefit and decrease the risk of metastasis, and durable biochemical control was achieved best in those whose pre-EBRT PSA level was 0.5 ng/mL or less. Early referral and careful patient selection is vital for salvage EBRT to be of optimal benefit.

Purpose: A retrospective study to evaluate the outcome of salvage radiotherapy (RT) for clinically apparent, palpable prostate cancer recurrence after radical prostatectomy (RP)., Methods and Materials: Forty-two patients underwent RT for clinically apparent recurrent prostate cancer after RP between 1993 and 1999. The end points and treatment variables of biochemical disease-free survival were evaluated statistically., Results: The median follow-up was 4.3 years. All 42 patients experienced resolution of clinically detectable recurrence within 1 year after RT. The 5-year biochemical disease-free survival, local control, freedom from distant metastases, and overall survival rate was 27%, 94%, 82%, and 78%, respectively. The initial pathologic stage (T3 or T4; p = 0.04) and interval (<2 years from RP to RT; p = 0.01) were independent predictors of biochemical failure, and RT simulation without contrast (p = 0.05) was nearly significant on multivariate analysis. Three patients (7%) experienced chronic Grade 3 or 4 RT-related toxicity., Conclusion: Salvage prostate bed RT for clinically apparent locally recurrent prostate cancer after RP provides effective local tumor control with modest durable biochemical control. Patients irradiated with a better simulation technique were found to have a more favorable outcome. A consensus on a definition of biochemical disease-free survival after salvage RT is critical for meaningful comparison of the available data and to future progress in treating this disease process.

Controversy exists regarding the management of recurrent disease, heralded by a rising prostate specific antigen (PSA), in men who have undergone primary treatment of prostate cancer by radical prostatectomy. Although retrospective in nature, the use of salvage radiation therapy (RT) after prostatectomy has been extensively investigated and reported. Salvage RT alone is likely not optimal for every man presenting with recurrent disease after RP. Those with palpable recurrent disease or unfavorable disease characteristics are less likely to benefit from salvage RT alone and may respond better to a combined modality approach. However, early referral and proper patient selection maximizes the potential for durable biochemical control after salvage RT in men with rising PSA alone.

Purpose: In this retrospective study we determined the results of salvage external beam radiation therapy (RT) to the prostate bed for isolated increase of serum prostate specific antigen (PSA) after radical prostatectomy., Materials and Methods: A total of 60 patients underwent RT for PSA failure after radical prostatectomy from 1993 to 1999. Median followup was 51 months. Biochemical disease-free survival (bDFS) with a serum PSA of 0.3 ng/ml or less was estimated using the Kaplan-Meier method. Potential prognostic factors were evaluated for significant associations with bDFS., Results: Median PSA before RT was 0.69 ng/ml. Median radiation dose was 64.8 Gy. The 5-year actuarial bDFS was 45%. There were 32 patients with a minimum followup of 4 years (median 73 months) who experienced a 5-year bDFS rate of 43%. PSA before RT (p = 0.016), RT dose (p = 0.026), surgical margin involvement (p = 0.017) and Gleason score (p = 0.018) were identified as prognostic factors for bDFS. A significant association with bDFS was present at 5 years of 65%, 34% and 0% for PSA before RT less than 0.6, 0.6 to 1.2, and greater than 1.2 ng/ml, respectively (p = 0.036). Patients with PSA before RT less than 0.6 ng/ml and total RT dose greater than 64.8 Gy had improved bDFS at 5 years compared to all others (77% vs 32%, p = 0.04). Of 60 patients 3 (5%) experienced chronic grade 3 toxicity., Conclusions: Optimal benefit from salvage RT was achieved in patients with a PSA less than 0.6 ng/ml and doses of RT greater than 64.8 Gy. Early treatment with a sufficiently high dose of RT maximizes the potential for salvage.

Local failure is the primary limitation for cure in patients with BTC. whether or not they have been resected. The use of radiotherapy with or without chemotherapy in the postoperative setting is controversial, but some studies have reported improvement in 5-year survival. In patients with unresectable BTC, EBRT offers effective palliation of symptomatic disease and has resulted in improved median and long-term survival in a small number of patients in most studies. Novel approaches, including neoadjuvant chemoradiotherapy combined with OLT, and escalated conformal irradiation, seem to be promising and warrant further investigation.