Joanne F. Chou

PURPOSE: The risk of breast cancer is high in women treated for a childhood cancer with chest irradiation. We sought to examine variations in risk resulting from irradiation field and radiation dose. PATIENTS AND METHODS: We evaluated cumulative breast cancer risk in 1,230 female childhood cancer survivors treated with chest irradiation who were participants in the CCSS (Childhood Cancer Survivor Study). RESULTS: Childhood cancer survivors treated with lower delivered doses of radiation (median, 14 Gy; range, 2 to 20 Gy) to a large volume (whole-lung field) had a high risk of breast cancer (standardized incidence ratio [SIR], 43.6; 95% CI, 27.2 to 70.3), as did survivors treated with high doses of delivered radiation (median, 40 Gy) to the mantle field (SIR, 24.2; 95% CI, 20.7 to 28.3). The cumulative incidence of breast cancer by age 50 years was 30% (95% CI, 25 to 34), with a 35% incidence among Hodgkin lymphoma survivors (95% CI, 29 to 40). Breast cancer-specific mortality at 5 and 10 years was 12% (95% CI, 8 to 18) and 19% (95% CI, 13 to 25), respectively. CONCLUSION: Among women treated for childhood cancer with chest radiation therapy, those treated with whole-lung irradiation have a greater risk of breast cancer than previously recognized, demonstrating the importance of radiation volume. Importantly, mortality associated with breast cancer after childhood cancer is substantial.

BACKGROUND: Preoperative chemoradiation is the standard treatment for locally advanced rectal cancer. However, it is uncertain whether pretreatment clinical stage, degree of response to neoadjuvant treatment, or pathologic stage is the most reliable predictor of outcome. This study compared various staging elements and treatment-related variables to identify which factors or combination of factors reliably prognosticates disease-free survival in rectal cancer patients receiving neoadjuvant combined modality therapy. METHODS: From a prospectively maintained single institution database, 342 consecutive patients with locally advanced rectal cancer staged by endorectal ultrasound were identified. Patients underwent rectal resection 4 to 8 weeks after a 5.5-week course of pelvic radiotherapy/concurrent chemotherapy. The degree of tumor regression was histologically graded on each resected specimen using a previously reported response scale of 0% to 100%. Predictive models of disease-free survival were created utilizing available pretherapy and postoperative staging elements in addition to the degree of tumor regression noted histologically. Model accuracy was measured and compared by concordance index, with 95% confidence interval (CI). RESULTS: Stratifying patients by degree of tumor regression predicted outcome with a concordance index of 0.65 (95% CI, 0.59-0.71), which was significantly better than models using preoperative stage elements (concordance index of 0.54; 95% CI, 0.50-0.58). However, the model found to be most predictive of disease-free survival stratified patients by final pathologic T classification and N classification elements, with a concordance index of 0.75 (95% CI, 0.70-0.80). CONCLUSIONS: Tumor response to preoperative therapy is a strong predictor of disease-free survival. However, outcome is most accurately estimated by final pathologic stage, which is influenced by both preoperative stage and response to therapy.

PURPOSE: Adjuvant therapy for Stage II colon cancer remains controversial but may be considered for patients with high-risk features. The purpose of this study was to assess the prognostic significance of commonly reported clinicopathologic features of Stage II colon cancer to identify high-risk patients. METHODS: We analyzed a prospectively maintained database of patients with colon cancer who underwent surgical treatment from 1990 to 2001 at a single specialty center. We identified 448 patients with Stage II colon cancer who had been treated by curative resection alone, without postoperative chemotherapy. RESULTS: With median follow-up of 53 months, 5-year disease-specific survival for this cohort was 91 percent. Univariate and multivariate analyses identified three independent features that significantly affected disease-specific survival: tumor Stage T4 (hazard ratio (HR), 2.7; 95 percent confidence interval (CI), 1.1-6.2; P = 0.02), preoperative carcinoembryonic antigen > 5 ng/ml (HR, 2.1; 95 percent CI, 1.1-4.1; P = 0.02), and presence of lymphovascular or perineural invasion (HR, 2.1; 95 percent CI, 1-4.4; P = 0.04). Five-year disease-specific survival for patients without any of the above poor prognostic features was 95 percent; five-year disease-specific survival for patients with one of these poor prognostic features was 85 percent; and five-year disease-specific survival for patients with > or = 2 poor prognostic features was 57 percent. CONCLUSIONS: Patients with Stage II colon cancer generally have an excellent prognosis. However, the presence of multiple adverse prognostic factors identifies a high-risk subgroup. Use of commonly reported clinicopathologic features accurately stratifies Stage II colon cancer by disease-specific survival. Those identified as high-risk patients can be considered for adjuvant chemotherapy and/or enrollment in investigational trials.