As an important result our study shows that even for PSA-values <1.0 ng/ml the detection efficiency of [(11)C]Choline-PET/CT is 36%. Furthermore, the detection rate of [(11)C]Choline-PET/CT shows a positive relationship with serum PSA-levels in patients with biochemical recurrence of prostate cancer after primary therapy. Therefore, in these patients, [(11)C]Choline PET/CT allows not only to diagnose but also to localise recurrent disease with implications on disease management (localised vs systemic therapy).

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. RESULTS: Patterns of care have changed significantly. Contemporary patients received focal treatments such as stereotactic radiosurgery and surgical resection far more frequently. Furthermore, systemic treatment was used more often in contemporary patients, both before and after diagnosis of brain metastasis. Improved survival was observed in the contemporary cohort (P ¼ .03). The 1-year survival rate increased from 15% (95% confidence interval [CI], 7%-25%) to 34% (95% CI, 25%-44%). However, this improvement was largely driven by patients with favorable prognostic features. More than 40% of the patients still belong to unfavorable prognostic groups with limited median survival and little improvement. CONCLUSIONS: Contemporary patients were managed on a much more individualized basis, requiring multidisciplinary case discussion and thorough assessment of prognostic features. Progress has been made, but the overall outcome needs to be improved further. Avoiding overtreatment in patients with poor prognosis is as important as aggressive treatment in patients who might survive for several years. Cancer 2011;117:2505-12.

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Previous studies demonstrated that chemotherapy-induced changes in tumor glucose metabolism measured with 18 F-FDG PET identify patients who benefit from preoperative chemotherapy and those who do not. The prognosis for chemotherapy metabolic nonresponders is poorer than for metabolic responders. Therefore, we initiated this prospective trial to improve the clinical outcome of metabolic nonresponders using a salvage neoadjuvant radiochemotherapy. Methods: Fifty-six patients with locally advanced adenocarcinomas of the esophagogastric junction were included. Tumor glucose uptake was assessed by 18 F-FDG PET before chemotherapy and 14 d after initiation of chemotherapy. PET nonresponders received salvage neoadjuvant radiochemotherapy, whereas metabolic responders received neoadjuvant chemotherapy for 3 mo before surgery. Results: Thirty-three patients were metabolic responders, and 23 were nonresponders. Resection was performed on 54 patients. R0 resection rate was 82% (95% confidence interval [CI], 66%-91%) in metabolic responders and 70% (95% CI, 49%-84%) in metabolic nonresponders (P 5 0.51). Major histologic remissions were observed in 12 metabolic responders (36%; 95% CI, 22%-53%) and 6 nonresponders (26%; 95% CI, 13%-46%). One-year progression-free rate was 74% 6 8% in PET responders and 57% 6 10% in metabolic nonresponders (log rank test, P 5 0.035). One-year overall survival was comparable between the groups (;80%), and 2-y overall survival was estimated to be 71% 6 8% in metabolic responders and 42% 6 11% in PET nonresponders (hazard ratio, 1.9; 95% CI, 0.87-4.24; P 5 0.10). Conclusion: This prospective study showed the feasibility of a PET-guided treatment algorithm.However, by comparing the groups of nonresponding patients in the current trial and the previous published MUNICON (Metabolic response evalUatioN for Individualisation of neoadjuvant Chemotherapy in Esophageal and esophagogastric adeNocarcinoma) I trial, increased histopathologic response was observed after salvage radiochemotherapy, but the primary endpoint of the study to increase the R0 resection rate was not met. The prognosis of the subgroup of PET nonresponders remains poor, indicating their different tumor biology.

Fatigue 2.5 years after RT did not increase above baseline levels before RT in conservatively operated breast cancer patients. Chronic fatigue correlated closely with psychological distress. Patients with pretreatment elevated fatigue, anxiety or depression levels are at risk for chronic fatigue.

Integrin-mediated adhesion to extracellular matrix proteins confers resistance to radiation-or drug-induced genotoxic injury. To analyse the underlying mechanisms specific for b1-integrins, wild-type b1A-integrin-expressing GD25b1A cells were compared to GD25b1B cells, which express signaling-incompetent b1B variants. Cells grown on fibronectin, collagen-III, b1-integrin-IgG or poly-l-lysine were exposed to 0-6 Gy X-rays in presence or depletion of growth factors and phosphatidylinositol-3 kinase (PI3K) inhibitors (LY294002, wortmannin). In order to test the relevance of these findings in tumor cells, human A-172 glioma cells were examined under the same conditions after siRNA-mediated silencing of b1-integrins. We found that b1A-integrin-mediated adhesion to fibronectin, collagen-III or b1-IgG was essential for cell survival after radiation-induced genotoxic injury. Mediated by PI3K, pro-survival b1A-integrin/Akt signaling was critically involved in this process. Additionally, the b1-integrin downstream targets p130Cas and paxillinimpaired survival-regulating PI3K-dependent JNK. In A-172 glioma cells, b1-integrin knockdown and PI3K inhibition confirmed the central role of b1-integrins in Akt-and p130Cas/paxillin-mediated prosurvival signaling. These findings suggest b1-integrins as critical regulators of cell survival after radiation-induced genotoxic injury. Elucidation of the molecular circuitry of prosurvival b1-integrin-mediated signaling in tumor cells may promote the development of innovative moleculartargeted therapeutic antitumor strategies.

FLT-PET did not seem to be a promising method for assessment of tumour response in the studied chemoradiotherapy regimen in patients with rectal cancer.