Although preoperative short-term radiotherapy for rectal cancer results in increased local control, there is more long-term bowel dysfunction in irradiated patients than in patients who undergo TME alone. Rectal cancer patients should be informed on late morbidity of both radiotherapy and TME. Future strategies should be aimed at selecting patients for radiotherapy who are at high risk for local failure.
Background: Tumor staging insufficiently discriminates between colon cancer patients with poor and better prognosis. We have evaluated, for the primary tumor, if the carcinoma-percentage (CP), as a derivative from the carcinoma-stromal ratio, can be applied as a candidate marker to identify patients for adjuvant therapy. Methods: In a retrospective study of 63 patients with colon cancer (stage I–III, 1990–2001) the carcinoma-percentage of the primary tumor was estimated on routine H&E stained histological sections. Additionally these findings were validated in a second independent study of 59 patients (stage I–III, 1980–1992). (None of the patients had received preoperative chemo- or radiation therapy nor adjuvant chemotherapy.) Results: Of 122 analyzed patients 33 (27.0%) had a low CP and 89 (73.0%) a high CP. The analysis of mean survival revealed: overall-survival (OS) 2.13 years, disease-free- survival (DFS) 1.51 years for CP-low and OS 7.36 years, DFS 6.89 years for CP-high. Five-year survival rates for CP-low versus CP-high were respectively for OS: 15.2% and 73.0% and for DFS: 12.1% and 67.4%. High levels of significance were found (OS p < 0.0001, DFS p < 0.0001) with hazard ratio’s of 3.73 and 4.18. In a multivariate Cox regression analysis, CP remained an independent variable when adjusted for either stage or for tumor status and lymph-node status (OSp < 0.001, OSp < 0.001). Conclusions: The carcinoma-percentage in primary colon cancer is a factor to discriminate between patients with a poor and a better outcome of disease. This parameter is already available upon routine histological investigation and can, in addition to the TNM classification, be a candidate marker to further stratify into more individual risk groups.
Because accurate electrode placement is pivotal in achieving adequate tumor necrosis, RFA should not be performed percutaneously when electrode placement is impaired. We suggest that lesions >5 cm and lesions located near great vessels or adjacent organs should be treated with open RFA, thus allowing vascular inflow occlusion and complete mobilization of the liver. Lesions that are difficult to reach by electrodes should be approached by an open procedure.
Background: For stage I–II colon cancer a significant number (5–25%) of patients has recurrent disease within 5 years. There is need to identify these high-risk patients as they might benefit from additional treatment.Stroma-tissue surrounding the cancer cells plays an important role in the tumor behavior. The proportion of intra-tumor stroma was evaluated for the identification of high-risk patients. In addition, protein expression of markers involved in pathways related to stroma production and epithelial-to-mesenchymal transition (EMT) was analyzed: β-catenin, TGF-β-R2 and SMAD4.Methods: In a retrospective study of 135 patients with stage I–II colon cancer, the amount of stroma was estimated on routine haematoxylin–eosin stained histological sections. Sections were also immunohistochemically stained for β-catenin, TGF-β-R2 and SMAD4.Results: Of 135 analyzed patients 34 (25.2%) showed a high proportion of stroma (stroma-high) and 101 (74.8%) a low proportion (stroma-low). Significant differences in overall-survival and disease-free-survival were observed between the two groups, with stroma-high patients showing poor survival (OS p < 0.001, HZ 2.73, CI 1.73–4.30; DFS p < 0.001, HZ 2.43, CI 1.55–3.82). A high-risk group was identified with stroma-high and SMAD4 loss (OS p = 0.008, HZ 7.98, CI 4.12–15.44, DFS p = 0.005, HZ 6.57, CI 3.43–12.56); 12 of 14 (85.7%) patients died within 3 years. In a logistic-regression analysis a high proportion of stroma and SMAD4 loss were strongly related (HZ 5.42, CI 2.13–13.82, p < 0.001).Conclusion: Conventional haematoxylin–eosin stained tumor slides contain more prognostic information than previously fathomed. This can be unleashed by assessing the tumor–stroma ratio. The combination of analyzing the tumor–stroma ratio and staining for SMAD4 results in an independent parameter for confident prediction of clinical outcome.
Maintaining high pre-diagnosis physical activity levels and a healthy body weight is associated with better quality of life after breast cancer.
Introduction Nonsteroidal anti-inXammatory drugs (NSAIDs) have been shown to reduce the risk of colorectal cancer in cyclooxygenase-2 (COX-2) overexpressing colorectal cancers. The present study was designed to evaluate the inhibitory eVects of the COX-2 inhibitor celecoxib on the growth of colorectal cancer liver metastases in a syngeneic rat model, CC531. Materials and methods The eVects of celecoxib on cell viability in vitro were evaluated by treatment of CC531 tumor cell cultures with celecoxib. In vivo, Wag/Rij rats were inoculated with CC531 tumor cells at two sites in the liver and treated with celecoxib starting one week before, or directly after tumor inoculation. Control rats were inoculated without treatment. Three weeks after tumor inoculation rats were sacriWced. Tumor size, immune cell inWltration, caspase-3 activity, PGE 2 and celecoxib levels were determined.Results CC531 tumors did not show COX-2 expression. Tumor growth was signiWcantly inhibited by celecoxib treatment in a dose dependent manner. Immune cell inWltration was decreased after celecoxib treatment, indicating that the immune system was not involved in preventing tumor growth. Tumor caspase-3 levels were only signiWcantly increased if treatment was started before tumor inoculation. Celecoxib serum concentration starting at 0.84 g/ml signiWcantly inhibited the outgrowth of CC531 liver tumors. In contrast, in vitro concentrations of celecoxib of at least 12 g/ml were needed to aVect tumor cell viability. Conclusion These results suggest that the inhibitory eVects of celecoxib on tumor growth are not by direct cytotoxicity, but by creating an unfavorable environment for tumor growth.
#4089 Background: Lifestyle habits such as physical activity frequently change after a breast cancer diagnosis and may unfavorably affect quality of life (QoL) as well as breast cancer outcome.
 Patients and Methods: In the Lifestyle side study of the TEAM trial, lifestyle and QoL questionnaires were filled out at approximately one year after starting hormonal therapy (T1) and again one year later (T2). The T1 questionnaire also included a retrospective assessment of pre-diagnosis lifestyle. Level of recreational physical activity was assessed as time engaged in walking, bicycling, gardening, and sports. Intensity values (METs) were assigned to each activity. The overall level of recreational physical activity was calculated by summing the MET-hours/week of all activities. QoL was assessed using the EORTC C30 and BR23 questionnaires, supplemented with FACT-ES questions covering endocrine symptoms.
 Results: A total of 543 breast cancer patients returned the first questionnaire (response 73%), of whom 454 patients also returned the second questionnaire. Relatively high levels of pre-diagnosis recreational physical activity were observed (mean±SD: 10.4±8.0 hours/week), with approximately one hour per day spent on walking or cycling. The level of recreational physical activity decreased to 8.6±7.2 hrs/wk at T1 and was partly restored at T2 (mean±SD; 9.7±7.4 hrs/wk; p<0.01 for pre-diagnosis vs T1 and T1 vs T2).
 Individuals in the lowest quartile of physical activity at T1 had a significantly worse QoL at T1 with respect to the domains of physical functioning, role functioning and sexual functioning, as compared to individuals in highest quartile of physical activity (difference of 9-15 points on a 0-100 scale; p<0.01). Similarly, individuals with a decrease of ≥15 MET-hrs/wk (equivalent to 1 hr/day of moderate-intensity activities on 5 days of the week) from pre-diagnosis to T1 also had a significantly worse QoL at T1 with respect to physical and role functioning, as compared to individuals with stable levels of physical activity (difference of 12-15 points; p<0.01). The least active group and the individuals with a strong decrease in physical activity also scored worse on fatigue (difference of 15 points on a 0-100 scale; p<0.01).
 Overall, no clinically significant changes in QoL were observed from T1 to T2. However, individuals who increased their level of physical activity from T1 to T2 more frequently experienced improved physical functioning (p=0.03) and a decrease in fatigue (p=0.12).
 Conclusions: In this population of relatively active postmenopausal breast cancer patients, being physically active is associated with better QoL. The temporal sequence of changes in both physical activity and QoL needs to be further studied, since physical activity may affect QoL and vice versa. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 4089.
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