Impact of BRAF and RAS mutations on first-line efficacy of FOLFIRI plus cetuximab versus FOLFIRI plus bevacizumab: analysis of the FIRE-3 (AIO KRK-0306) study.

BACKGROUND: RAS and BRAF mutations have been identified as negative prognostic factors in metastatic colorectal cancer. Efficacy of 5-fluorouracil, leucovorin, irinotecan (FOLFIRI) plus bevacizumab in patients with RAS-mutant tumours needs to be further evaluated. Whether to treat patients with BRAF-mutant tumours with either bevacizumab or anti-epidermal growth factor receptor (EGFR) antibodies remains unclear. METHODS: Patients treated within the FIRE-3 trial were retrospectively tested for BRAF and RAS mutations using formalin fixated paraffin embedded (FFPE) tumour material applying pyrosequencing for KRAS and NRAS exon 2, 3 and 4 mutations as far as for BRAF mutations. Survival analysis was done using Kaplan-Meier estimation and differences were expressed using the log-rank test. Overall response rate (ORR) was compared using Fisher's exact test. Data from a central independent radiological response evaluation were used to calculate early tumour shrinkage (ETS) and depth of response (DpR). RESULTS: Overall, 188 patients with RAS-mutant tumours and 48 with BRAF-mutant tumours were identified. In BRAF-mutant patients, ORR was numerically higher in the cetuximab versus the bevacizumab arm (52% versus 40%), while comparable results were achieved for progression-free survival (PFS; hazard ratio [HR] = 0.84, p = 0.56) and overall survival (OS; HR 0.79, p = 0.45). RAS mutation was associated with a trend towards lower ORR (37% versus 50.5%, p = 0.11) and shorter PFS (7.4 versus 9.7 months; HR 1.25; p = 0.14) in patients receiving FOLFIRI plus cetuximab versus bevacizumab, but OS was comparable (19.1 versus 20.1 months; HR 1.05; p = 0.73), respectively. ETS identified subgroups sensitive to cetuximab-based treatment in both BRAF- (9/17) and RAS-mutant (18/48) patients and was associated with significantly longer OS. DpR was comparable between both treatment arms in RAS- and BRAF-mutant patients, respectively. CONCLUSIONS: In BRAF- and RAS-mutant patients, cetuximab- and bevacizumab-based treatment had comparable survival times. ETS represents an early parameter associated with the benefit from anti-EGFR, while this was not the case with vascular endothelial growth factor A blockade.

Pulmonary arteriovenous malformation: Characterization with time-resolved ultrafast 3D MR angiography.

To avoid potentially deadly consequences from paradoxical emboli, early detection and accurate characterization of pulmonary arteriovenous malformations (AVMs) is highly desirable. We report on a patient with a suspected pulmonary AVM who underwent ultrafast time-resolved 3D MR angiography of the pulmonary arteries. The case documents the suitability of the MRA technique as a noninvasive alternative to computed tomographic angiography and digital subtraction angiography for accurate pre-therapeutic characterization of pulmonary AVMs.

[Hypothenar hammer syndrome: causes, sequelae and diagnostic aspects]. / Das Hypothenar-Hammer-Syndrom--Ursachen, Folgen und diagnostische Aspekte.

PURPOSE: To investigate the reasons and disease course of Hypothenar Hammer Syndrome. INTRODUCTION: Occlusion of the ulnar artery at the level of the hamate bone due to repetitive trauma to the hypothenar eminence is implicated as the cause of the rarely diagnosed hypothenar hammer syndrome (HHS). The thrombotic occlusion and the formation of an aneurysm of the ulnar artery and the superficial palmar arch with possible peripheral embolism of the digital arteries are a direct cause of the chronic damage to the vessel wall. Generally, HHS is diagnosed too late for recanalization to be a viable therapeutic option. METHODS: From 1996 to 1998 the diagnosis of an HHS was made in 8 patients at our hospital. Etiology, clinical settings and disease course were assessed. RESULTS: Our analysis suggests that HHS may be caused by a single severe trauma in addition to repetitive injuries. The pathogenesis of the syndrome is dependent on the vascular anatomy of the individual hand. Interindividual variations in the arterial supply of the affected hand influences the clinical symptomatology with possible masking of arterial occlusions. CONCLUSION: An exact investigation concerning the pathogenesis of HHS is a precondition for treating the disease and may help to establish HHS as an occupational disease. MR-angiography may be a new approach for assessing HHS.