A randomized, phase III trial of capecitabine plus bevacizumab (Cape-Bev) versus capecitabine plus irinotecan plus bevacizumab (CAPIRI-Bev) in first-line treatment of metastatic colorectal cancer: The AIO KRK 0110 Trial/ML22011 Trial

<p>Abstract</p> <p>Background</p> <p>Several randomized trials have indicated that combination chemotherapy applied in metastatic colorectal cancer (mCRC) does not significantly improve overall survival when compared to the sequential use of cytotoxic agents (CAIRO, MRC Focus, FFCD 2000-05). The present study investigates the question whether this statement holds true also for bevacizumab-based first-line treatment including escalation- and de-escalation strategies.</p> <p>Methods/Design</p> <p>The AIO KRK 0110/ML22011 trial is a two-arm, multicenter, open-label randomized phase III trial comparing the efficacy and safety of capecitabine plus bevacizumab (Cape-Bev) versus capecitabine plus irinotecan plus bevacizumab (CAPIRI-Bev) in the first-line treatment of metastatic colorectal cancer. Patients with unresectable metastatic colorectal cancer, Eastern Cooperative Oncology Group (ECOG) performance status 0-1, will be assigned in a 1:1 ratio to receive either capecitabine 1250 mg/m²bid for 14d (d1-14) plus bevacizumab 7.5 mg/kg (d1) q3w (Arm A) or capecitabine 800 mg/m²BID for 14d (d1-14), irinotecan 200 mg/m²(d1) and bevacizumab 7.5 mg/kg (d1) q3w (Arm B). Patients included into this trial are required to consent to the analysis of tumour tissue and blood for translational investigations. In Arm A, treatment escalation from Cape-Bev to CAPIRI-Bev is recommended in case of progressive disease (PD). In Arm B, de-escalation from CAPIRI-Bev to Cape-Bev is possible after 6 months of treatment or in case of irinotecan-associated toxicity. Re-escalation to CAPIRI-Bev after PD is possible. The primary endpoint is time to failure of strategy (TFS). Secondary endpoints are overall response rate (ORR), overall survival, progression-free survival, safety and quality of life.</p> <p>Conclusion</p> <p>The AIO KRK 0110 trial is designed for patients with disseminated, but asymptomatic mCRC who are not potential candidates for surgical resection of metastasis. Two bevacizumab-based strategies are compared: one starting as single-agent chemotherapy (Cape-Bev) allowing escalation to CAPIRI-Bev and another starting with combination chemotherapy (CAPIRI-Bev) and allowing de-escalation to Cape-Bev and subsequent re-escalation if necessary.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov Identifier <a href="http://www.clinicaltrials.gov/ct2/show/NCT01249638">NCT01249638</a></p> <p>EudraCT-No.: 2009-013099-38</p

Combined cytomorphologic and immunophenotypic analysis in the diagnostic workup of lymphomatous effusions

OBJECTIVE: To analyze the results of cytomorphology and immunophenotyping in 54 patients with lymphomatous effusions. STUDY DESIGN: We report the results of cytomorphology and immunophenotyping in 54 patients with lymphomatous effusions. Twenty-three of the 54 had a previous diagnosis of NHL. In the remaining 31 patients, lymphomatous involvement was clinically suspected. RESULTS: Thirty-three lymphomatous effusions were positive for involvement by NHL. Twenty-one of these 33 patients (64%) had a previous diagnosis of NHL. Of the remaining 12 patients with newly diagnosed NHL, 11 had high grade lymphoma, and one had follicular center lymphoma. Twenty effusions were considered to be reactive; only two of these patients had NHL. One effusion revealed involvement by a previously unknown carcinoma. We observed seven false negative results if only one of both methods was considered. A high grade NHL was not diagnosed by immunophenotyping in one case, and six cases of low grade NHL could not be detected by cytomorphology. The combined strategy of cytomorphology and immunophenotyping had a sensitivity of 100% and specificity of 100% in our study, confirmed by follow-up studies. CONCLUSION: Both methods have shown difficulties in the examination of lymphomatous effusions. Cytomorphology has problems distinguishing reactive effusions from low grade NHL. The detection of high grade NHL by immunophenotyping is difficult. However, both methods together offer the advantage of dual staining ability and are most helpful in distinguishing clonal lymphomatous from reactive effusions

Fine needle aspiration cytology in extramedullary plasmacytoma

Extramedullary plasmacytoma is a rare plasma cell neoplasm. It can occur as the sole manifestation of plasma cell neoplasm, as a metastasis from another extramedullary plasmacytoma, as a solitary plasmacytoma of the bone or as a consequence of multiple myeloma. These plasma cell tumors can occur anywhere and have to be differentiated from other neoplasms, infectious processes and chloroma. STUDY DESIGN: We report the findings of fine needle aspiration cytology (FNAC) in 18 patients with extramedullary plasmacytoma. In six patients extramedullary plasmacytoma was the initial presentation of plasma cell neoplasm. In the remaining 12 patients the tumors occurred under or after treatment of plasma cell disease. RESULTS: Eleven lesions were located in the skin, seven in the lymph nodes, one in the liver and another in the spleen. Two patients with known diagnoses of plasma cell disease were thought, before FNAC, to have an infection, and two had a histologic diagnosis of non-Hodgkin#s lymphoma. In 13 of 18 patients, cytologic smears showed anaplastic plasma cells. CONCLUSION: FNAC is a front-line investigative procedure in diagnosing extramedullary plasmacytoma

Mediastinal masses diagnosed as thymus hyperplasia by fine needle aspiration cytology

Thymic hyperplasia in the anterior mediastinum can occur in healthy children as idiopathic thymic hyperplasia or as a rebound effect after administration of chemotherapy in patients with malignancies. Thymic hyperplasia after chemotherapy is a well-documented phenomenon, particularly in children and less frequently in adults. Both forms of thymic hyperplasia are a diagnostic challenge, and most patients undergo surgical exploration. Fine needle aspiration cytology (FNAC) has supposed to be inadequate to diagnose benign thymic hyperplasia and to seperate it from malignant disease. STUDY DESIGN: We report the cytologic findings on eight patients presenting with a mass in the anterior mediastinum that was diagnosed as thymic hyperplasia on FNAC. In five patients the masses developed after chemotherapy. The remaining three patients were healthy children. Three patients underwent ultrasound-guided aspiration; in five cases the procedure was performed under computerized guidance. RESULTS: In all eight patients the cytologic smears showed a mixed population of lymphoid cells. Cytologic diagnosis of thymic hyperplasia was confirmed by immunophenotyping in three patients and by follow-up studies in all of them (median, 68 months; range, 8-113). CONCLUSION: In contrast to previous reports, this study demonstrated the utility of FNAC as a front-line investigative procedure in diagnosing thymic hyperplasia

Assessment of Potential for Ion Driven Fast Ignition

Critical issues and ion beam requirements are explored for fast ignition using ion beams to provide fuel compression using indirect drive and to provide separate short pulse ignition heating using direct drive. Several ion species with different hohlraum geometries are considered for both accelerator-produced and laser-produced ion ignition beams. Ion-driven fast ignition targets are projected to have modestly higher gains than with conventional heavy-ion fusion, and may offer some other advantages for target fabrication and for use of advanced fuels. However, much more analysis and experiments are needed before conclusions can be drawn regarding the feasibility for meeting the ion beam transverse and longitudinal emittances, focal spots, pulse lengths, and target standoff distances required for ion-driven fast ignition