Clinical relevance of KRAS mutation detection in metastatic colorectal cancer treated by Cetuximab plus chemotherapy

The predictive value of KRAS mutation in metastatic colorectal cancer (MCRC) patients treated with cetuximab plus chemotherapy has recently been suggested. In our study, 59 patients with a chemotherapy-refractory MCRC treated with cetuximab plus chemotherapy were included and clinical response was evaluated according to response evaluation criteria in solid tumours (RECIST). Tumours were screened for KRAS mutations using first direct sequencing, then two sensitive methods based on SNaPshot and PCR-ligase chain reaction (LCR) assays. Clinical response was evaluated according to gene mutations using the Fisher exact test. Times to progression (TTP) were calculated using the Kaplan–Meier method and compared with log-rank test. A KRAS mutation was detected in 22 out of 59 tumours and, in six cases, was missed by sequencing analysis but detected using the SNaPshot and PCR-LCR assays. Remarkably, no KRAS mutation was found in the 12 patients with clinical response. KRAS mutation was associated with disease progression (P=0.0005) and TTP was significantly decreased in mutated KRAS patients (3 vs 5.5 months, P=0.015). Our study confirms that KRAS mutation is highly predictive of a non-response to cetuximab plus chemotherapy in MCRC and highlights the need to use sensitive molecular methods, such as SNaPshot or PCR-LCR assays, to ensure an efficient mutation detection

Erythropoiesis-stimulating agents in oncology: a study-level meta-analysis of survival and other safety outcomes

BACKGROUND: Cancer patients often develop the potentially debilitating condition of anaemia. Numerous controlled studies indicate that erythropoiesis-stimulating agents (ESAs) can raise haemoglobin levels and reduce transfusion requirements in anaemic cancer patients receiving chemotherapy. To evaluate recent safety concerns regarding ESAs, we carried out a meta-analysis of controlled ESA oncology trials to examine whether ESA use affects survival, disease progression and risk of venous-thromboembolic events

Critical density for the stability of a 2D magnet array

Confining a given number of magnets with vertically aligned moments on a non-magnetic surface creates a 2D magnet array, self-organized by repulsive forces in a hexagonal crystal-like network. Increasing areal density leads to a dramatic collapse of the structure where magnets finally stick together. We study the origin of this collapse and its critical density both experimentally, by either increasing the number of magnets or reducing the area, and theoretically, by using a dipole model. We suggest the collapse occurs when magnetic forces or torques created by irregularities overcome gravity. Transition from torque-driven to force-induced mechanism is observed when the critical density increases

Is intravenous iron supplementation with erythropoiesis-stimulating agents beneficial in cancer patients with anemia?

Chemotherapy-induced anemia is often an important problem for cancer patients, and this complication can be treated with erythropoiesis-stimulating agents (ESAs). This commentary discusses the findings of a study by Bastit et al., in which 396 patients with nonmyeloid malignancies and chemotherapy-induced anemia were treated with darbepoetin alfa with or without intravenous iron. This phase III trial showed that intravenous iron supplementation increases the hematopoietic response rates to ESAs in cancer patients; however, this study provides no information as to whether all cancer patients with anemia should receive intravenous iron as well as treatment with ESAs. Further data are needed to identify those patients who might benefit from intravenous iron supplementation in addition to ESAs, in order to avoid overtreatment of patients who are unlikely to benefit from the additional iron. As both ESAs and intravenous iron have known short-term and long-term risks, identification of reliable predictors of response that can guide these treatments is necessary before this strategy can be implemented into practice

Flap delineation guidelines in postoperative head and neck radiation therapy for head and neck cancers.

Reconstructive surgery in head and neck cancers frequently involves the use of autologous flaps to improve functional outcomes. However, the literature suggests that postoperative radiotherapy deteriorates functional outcomes due to flap atrophy and fibrosis. Data on patterns of relapse after postoperative radiotherapy with a flap are lacking, resulting in heterogenous delineation of postoperative clinical target volumes (CTV). Flap delineation is unusual in routine practice and there are no guidelines on how to delineate flaps. Therefore, we aim to propose a guideline for flap delineation in head and neck cancers to assess dose-effects more accurately with respect to flaps. Common flaps were selected. They were delineated by radiation oncologists and head and neck surgeons based on operative reports, on contrast-enhanced planning CTs and checked by a radiologist. Each flap was divided into its vascular pedicle and its soft tissue components (fat, fascia/ muscle, skin, bone). Delineation (body and pedicle) of Facial Artery Musculo-Mucosal, pectoralis, radial forearm, anterolateral thigh, fibula and scapula flaps was performed. Based on information provided in operative reports, i.e. tissue components, size and location, flaps can be identified. The various tissue components of each flap can be individualized to facilitate the delineation. This atlas could serve as a guide for the delineation of flaps and may serve to conduct studies evaluating dose-effects, geometric patterns of failure or functional outcomes after reconstructive surgery. Changes in postoperative CTV definitions might be needed to improve risk/benefit ratio in the future based on surgery-induced changes