Jörg Kleef and colleagues systematically reviewed studies on neoadjuvant therapy and tumor response, toxicity, resection, and survival percentages in pancreatic cancer and suggest that patients with locally nonresectable tumors should be included in neoadjuvant protocols.

Assessment of histological tumor regression after preoperative chemotherapy in GC provides objective and highly valuable prognostic information in addition to posttherapeutic lymph node status. A standardized tumor regression grading system should be implemented in pathological reports of these tumors.

Purpose: To evaluate 3 ¶-deoxy-3 ¶-[18 F]fluorothymidine-positron emission tomography (FLT-PET) for early monitoring response of high-grade non-Hodgkin's lymphoma to treatment with cyclophosphamide-adriamycin-vincristine-prednisone chemotherapy with or without rituximab immunotherapy (R-CHOP/CHOP). Experimental Design: Twenty-two patients with histologically proven high-grade nonHodgkin's lymphoma scheduled to undergo first line treatment with R-CHOP/CHOP were included. All patients received baseline imaging before therapy with FLT-PET. For noninvasive assessment of treatment response, FLT-PET was repeated at following time points: group 1 (n = 6), 1and 6 weeks after R-CHOP/CHOP; group 2 (n = 16), 2 days after rituximab and 2 days after CHOP application. Emission images were acquired 45 min after injection of 300 to 370 MBq of FLT. FLT uptake was quantified by region-of-interest technique on a lesion basis. Maximum standardized uptake values (SUV) for FLT were calculated using circular region of interest (diameter, 1.5 cm). Results: In all patients, morphologically proven lesions showed initially high FLT uptake (mean SUV, 8.1 F 3.9). In group 1, mean FLT SUV decreased 7 days after R-CHOP/CHOP by 77% (P < 0.001), the reduction in FLT SUV from baseline was 85% after 40 days (P = 0.003). In group 2, FLTuptake in patients without dexamethasone pretreatment revealed no significant reduction after rituximab (P = 0.3) but significantly decreased 2 days after CHOP to 32% compared with the baseline value (P = 0.004). Conclusions: Administration of R-CHOP/CHOP is associated with an early decrease in lymphoma FLT uptake. Interestingly, there was no reduction of FLT uptake after rituximab alone, indicating no early antiproliferative effect of immunotherapy. FLT-PET seems to be promising for early evaluation of drug effects in lymphoma.The standard therapy for high-grade non-Hodgkin's lymphoma is cyclophosphamide-adriamycin-vincristine-prednisone (CHOP) or CHOP-like regimens. The introduction of the chimeric monoclonal anti-CD20 antibody rituximab to standard chemotherapy has been shown to significantly improve both event-free as well as overall survival (1, 2). In contrast to its role in combination therapies, rituximab itself does not reveal a major cytotoxic effect as a single agent on high-grade non-Hodgkin's lymphoma (3).To evaluate antitumor efficacy and possible mechanisms of action in vivo, therapy monitoring plays a major role for evaluation of new therapeutic approaches. For the last decades, helical computed tomography (CT) has represented the gold standard for staging and restaging of non-Hodgkin's lymphoma. However, definition of response criteria based on conventional radiographic characteristics remains difficult because patients treated with chemotherapy often present with residual masses of uncertain significance. Especially differentiation between fibrotic tissue and viable tumor by CT is only of limited accuracy (4 -10).Positron emission tomography using the glucose analogue 2-[18 F]fluoro-2-deox...

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.

NF-kappaB (Rel) transcription factors control physiological and pathological immune cell function. The scaffold proteins Bcl-10 and MALT1 couple antigen-receptor signals to the canonical NF-kappaB pathway and are pivotal in lymphomagenesis. Here we found that Bcl-10 and MALT1 differentially regulated B cell receptor-induced activation of RelA and c-Rel. Bcl-10 was essential for recruitment of the kinase IKK into lipid rafts for the activation of RelA and c-Rel, for blocking apoptosis and for inducing division after B cell receptor ligation. In contrast, MALT1 participated in survival signaling but was not involved in IKK recruitment or activation and was dispensable for RelA induction and proliferation. MALT1 selectively activated c-Rel to control a distinct subprogram. Our results provide mechanistic insights into B cell receptor-induced survival and proliferation signals and demonstrate the selective control of c-Rel in the canonical NF-kappaB pathway.

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AEG is more likely to respond to preoperative chemotherapy than GC, a finding that might help identify patients who would benefit from preoperative chemotherapy.

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