Adjuvant therapy for gallbladder carcinoma: the Mayo Clinic Experience.

PURPOSE: To analyze the effect of adjuvant chemoradiotherapy on gallbladder carcinoma. METHODS AND MATERIALS: We retrospectively reviewed the records from consecutive patients who underwent R0 resection of gallbladder carcinoma between January 1, 1985, and December 31, 2004. Patients had either Stage I (T1-T2N0M0) or Stage II (T3N0M0 or T1-T3N1M0) disease. Patients undergoing adjuvant therapy received 5-fluorouracil chemotherapy concurrently with radiotherapy (median dosage, 50.4 Gy in 28 fractions). Adverse prognostic factors and the effect of adjuvant treatment on overall survival (OS) were evaluated. RESULTS: A total of 73 patients were included in the analysis; of these, 25 received adjuvant chemoradiotherapy. On univariate analysis, no adverse prognostic factors for OS reached statistical significance, but trends were noted for Stage N1 vs. N0 (p = .06), Nx vs. N0 (p = .09), Stage T3 vs. T1-T2 (p = .06), and histologic findings other than adenocarcinoma (p = .13). The median OS for patients receiving adjuvant chemoradiotherapy vs. surgery alone was 4.8 years and 4.2 years, respectively (log-rank test, p = .56). However, a significantly greater percentage of patients receiving adjuvant chemoradiotherapy had Stage II disease (p <.001). In the multivariate Cox model, increasing T and N category and histologic findings other than adenocarcinoma were significant predictors of decreased OS. Additionally, adjuvant chemoradiotherapy was a significant predictor of improved OS after adjusting for these prognostic factors (hazard ratio for death, 0.3; 95% confidence interval, 0.13-0.69; p = .004). CONCLUSION: After adjusting for the stage parameters and histologic findings, our data suggest that adjuvant chemoradiotherapy might improve OS for patients with gallbladder cancer.

High-dose-rate brachytherapy in the curative treatment of patients with localized prostate cancer.

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.

Systemic lupus erythematosus, radiotherapy, and the risk of acute and chronic toxicity: the Mayo Clinic Experience.

PURPOSE: To determine the acute and chronic toxic effects of radiotherapy in patients with systemic lupus erythematosus (SLE). METHODS AND MATERIALS: Medical records of 21 consecutive patients with SLE, who had received 34 courses of external beam radiotherapy and one low-dose-rate prostate implant, were retrospectively reviewed. Patients with discoid lupus erythematosus were excluded. RESULTS: Median survival was 2.3 years and median follow-up 5.6 years. Eight (42%) of 19 patients evaluable for acute toxicity during radiotherapy experienced acute toxicity of Grade 1 or greater, and 4 (21%) had acute toxicity of Grade 3 or greater. The 5- and 10-year incidence of chronic toxicity of Grade 1 or greater was 45% (95% confidence interval [CI], 22-72%) and 56% (95% CI, 28-81%), respectively. The 5- and 10-year incidence of chronic toxicity of Grade 3 or greater was 28% (95% CI, 18-60%) and 40% (95% CI, 16-72%), respectively. Univariate analysis showed that chronic toxicity of Grade 1 or greater correlated with SLE renal involvement (p < 0.006) and possibly with the presence of five or more American Rheumatism Association criteria (p < 0.053). Chronic toxicity of Grade 3 or greater correlated with an absence of photosensitivity (p < 0.02), absence of arthritis (p < 0.03), and presence of a malar rash (p < 0.04). CONCLUSIONS: The risk of acute and chronic toxicity in patients with SLE who received radiotherapy was moderate but was not prohibitive of the use of radiotherapy. Patients with more advanced SLE may be at increased risk for chronic toxicity.

Chronic toxicity risk after radiotherapy for patients with systemic sclerosis (systemic scleroderma) or systemic lupus erythematosus: association with connective tissue disorder severity.

No method reliably identifies which patients with connective tissue disorders are at greatest risk of radiotherapy-related complications. Building on our prior experience, we postulated that disease severity, as measured by the number of organ systems involved, may predict chronic radiation toxicity risk.

Outcome after combined modality treatment for uterine papillary serous carcinoma: a study by the Rare Cancer Network (RCN).

OBJECTIVES: Uterine papillary serous carcinoma (UPSC) is a rare subtype of endometrial carcinoma, characterized by a poor outcome. We sought to better analyze the effect of surgery and adjuvant therapies on this disease. METHODS: A retrospective analysis was performed on the records of 138 women diagnosed with UPSC between 1986 and 2003 in the framework of the Rare Cancer Network. RESULTS: Median age at diagnosis was 67 years. Pure UPSC was found in 107 patients and mixed histology in 30. Fifty-four patients had stage I, 20 stage II, 41 stage III and 23 stage IV disease. Median follow-up for the surviving patients was 44 months. Surgery was performed in 129 patients, after which 122 were rendered free of gross disease and comprised the adjuvant group. Of these, 23 received platinum-based chemotherapy. Radiotherapy was applied in 52 patients and 28 underwent combined chemo-radiotherapy. At last follow-up, 57 patients were alive free of disease, 10 were alive with disease, 62 died of disease, 8 died of other causes and 1 died due to toxicity. Five-year disease-free survival (DFS), disease-specific survival (DSS) and overall survival for the 122 patients treated with curative intent were 42%, 56% and 54%, respectively. In multivariate analysis, age, stage, histology and adjuvant chemotherapy were significant for DFS; age, stage and histology were significant for DSS. Radiotherapy reduced the pelvic recurrence rate from 29% to 14% (p=0.047). CONCLUSIONS: UPSC harbours a moderate prognosis, with age, stage and histology as significant prognosticators. Conservative surgery followed by adjuvant chemotherapy and pelvic radiotherapy can be suggested as an appropriate treatment approach for patients treated with curative intent.

Radiotherapy for malignancy in patients with scleroderma: The Mayo Clinic experience.

PURPOSE: To determine the frequency of acute and chronic adverse effects in patients with scleroderma who receive radiotherapy for treatment of cancer. METHODS AND MATERIALS: Records were reviewed of 20 patients with scleroderma who received radiotherapy. Acute and chronic toxic effects attributable to radiotherapy were analyzed, and freedom from radiation-related toxicity was calculated. RESULTS: Of the 20 patients, 15 had acute toxic effects, with Grade 3 or higher toxicity for 3 patients. Seven patients had self-limited Grade 1 or 2 radiation dermatitis, and no patient had Grade 3 or higher radiation dermatitis. Thirteen patients had chronic toxic effects, with Grade 3 or higher chronic toxicity for 3 patients. The median estimated time to any grade chronic toxicity was 0.4 years, and the median estimated time to Grade 3 or higher chronic toxicity has not been reached. CONCLUSIONS: The results suggest that although some patients with scleroderma treated with radiation experience considerable toxic effects, the occurrence of Grade 3 or higher toxicity may be less than previously anticipated.

Utility and limitations of abdominal radiotherapy in the management of endometrial carcinomas.

OBJECTIVE: The present review analyzes long-term survival, recurrence sites, and toxicity in women with peritoneal spread of endometrial treated with abdominal radiotherapy, in order to provide therapeutic options as a function of disease spread and histology. METHODS: Retrospective medical record review was performed of 86 patients receiving abdominal radiotherapy for endometrial carcinomas from 1975 to 1995 at the University of Minnesota. RESULTS: FIGO stage distribution was 54 stage IIIA, 2 stage IIIB, 11 stage IIIC, and 19 stage IVB. Disease-free survivals were 55% at 5 years, 46% at 10 years, and 36% at 20 years. Recurrence rates were 16% for stage IIIA with one peritoneal site, 48% for stage IIIA with multiple peritoneal sites or stage IIIB or stage IIIC, and 72% for stage IVB. With univariate analysis, statistical significance was found for stage, gross peritoneal disease, nodal metastases, histology, concurrent chemotherapy, isolated adnexal spread, grade, angiolymphatic invasion, myometrial invasion, and age. Multivariate analysis found only stage, histology, and age to be significant. Most recurrences were pulmonary or peritoneal. Acute toxicity was acceptable. Six percent of patients required surgical intervention for small bowel obstructions. CONCLUSIONS: Abdominal radiotherapy confers an excellent prognosis for women with stage IIIA cancers with one site of peritoneal involvement. Lack of randomized trials makes definitive treatment recommendations difficult to provide. Results are less optimal with multiple peritoneal sites of involvement, gross peritoneal spread, or papillary serous/clear cell pathology but a substantial number of such women can be cured as well.

Second neoplasms after megavoltage radiation for pediatric tumors.

BACKGROUND: Because ionizing radiation is a known carcinogen, diligent long-term follow-up in children exposed to therapeutic radiation is required. The authors updated an earlier study on the nature and risk of second neoplasms (SN) in patients treated with megavoltage radiotherapy as children. METHODS: The authors followed 446 children who were treated for a primary malignancy with megavoltage radiotherapy between January 16, 1954 and December 31, 1980. These children survived a minimum of 5 years. The nature and incidence of SNs were evaluated in this population. Patients with bilateral retinoblastoma or neurofibromatosis were excluded from the study due to their large genetically based predisposition for developing an SN. RESULTS: The Kaplan-Meier actuarial survival rate was 80% (95% confidence interval [CI] 74-85%) at 30 years for all patients. Thirty-seven (8.3%) patients developed SNs, most of which occurred within the original radiation treatment field, 3.8-31.8 years (median, 15.5 years) after radiotherapy. The cumulative risk of developing an SN was 13% (95% CI 9-19%) at 30 years and the standardized incidence ratio for the development of any SN was 5.2 (95% CI 3.4-7.6%). The most common SNs were breast carcinoma (n = 8), skin carcinoma (five basal cell carcinomas, two malignant melanomas, and one dermatosarcoma), and meningiomas (n = 6). All eight breast carcinomas occurred after the treatment of childhood Hodgkin disease. Of the 37 patients with SNs, 12 died of either the SN (n = 10) or of recurrent disease (n = 2). Risk factors associated with developing a SN included initial diagnosis of Hodgkin disease (P = 0.0003), female gender (P = 0.008), and an initial diagnosis of acute lymphoblastic leukemia (P = 0.02). CONCLUSIONS: Patients in the radiation-treated cohort experienced increased mortality, were at an increased risk of developing an SN, and should undergo increased medical surveillance as adults. The cumulative probability of developing an SN has increased substantially at 30 years, largely due to an increase in follow-up time. In addition, the cumulative probability curve does not show evidence of plateau after increased duration of follow-up. Finally, the emergence of secondary breast carcinoma in the current study was not noted in the previous analysis.