Early magnesium reduction in advanced colorectal cancer patients treated with cetuximab plus irinotecan as predictive factor of efficacy and outcome

Introduction: Magnesium plays a role in a large number of cellular metabolic reactions. Cetuximab is able to induce hypomagnesemia by interfering with magnesium (Mg2+) transport in the kidney.We designed this trial to investigate if Mg2+ serum level modifications may be related with clinical response andoutcome in advancedcolorectal cancer patients during treatment with cetuximab plus irinotecan. Experimental Design: Sixty-eight heavily pretreatedmetastatic colorectal cancer patients were evaluatedfor Mg2+ serum levels at the following time points: before; 6 hours; and1, 7, 14, 21, 50, and92 days after the start of treatment. Results: Basal Mg2+ median levels were significantly decreased just 7 days after the first anticancer infusion and progressively decreased from the 7th day onward, reaching the highest significance at the last time point (P < 0.0001).Twenty-five patients showeda reduction in median Mg2+ circulating levels of at least 20% within the 3rdweek after the first infusion. Patients with this reduction showed a response rate of 64.0% versus 25.6% in the nonreduced Mg2+ group. The median time to progression was 6.0 versus 3.6 months in the reduced Mg2+ group andin that without reduction, respectively (P < 0.0001). Overall survival was longer in patients with Mg2+ reduction than in those without (10.7 versus 8.9 months). Conclusions: Our results confirm that cetuximab treatment may induce a reduction of Mg2+ circulating levels andoffer the first evidence that Mg2+ reduction may represent a new predictive factor of efficacy in advanced colorectal cancer patients treated with cetuximab plus irinoteca

Cortical thinning and clinical heterogeneity in amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (ALS) has heterogeneous clinical features that could be translated into specific patterns of brain atrophy. In the current study we have evaluated the relationship between different clinical expressions of classical ALS and measurements of brain cortical thickness. Cortical thickness analysis was conducted from 3D-MRI using FreeSurfer software in 29 ALS patients and 20 healthy controls. We explored three clinical traits of the disease, subdividing the patients into two groups for each of them: the bulbar or spinal onset, the higher or lower upper motor neuron burden, the faster or slower disease progression. We used both a whole brain vertex-wise analysis and a ROI analysis on primary motor areas. ALS patients showed cortical thinning in bilateral precentral gyrus, bilateral middle frontal gyrus, right superior temporal gyrus and right occipital cortex. ALS patients with higher upper motor neuron burden showed a significant cortical thinning in the right precentral gyrus and in other frontal extra-motor areas, compared to healthy controls. ALS patients with spinal onset showed a significant cortical thinning in the right precentral gyrus and paracentral lobule, compared to healthy controls. ALS patients with faster progressive disease showed a significant cortical thinning in widespread bilateral frontal and temporal areas, including the bilateral precentral gyrus, compared to healthy controls. Focusing on the primary motor areas, the ROI analysis revealed that the mean cortical thickness values were significantly reduced in ALS patients with higher upper motor neuron burden, spinal onset and faster disease progression related to healthy controls. In conclusion, the thickness of primary motor cortex could be a useful surrogate marker of upper motor neuron involvement in ALS; also our results suggest that cortical thinning in motor and non motor areas seem to reflect the clinical heterogeneity of the disease. © 2013 Mezzapesa et al

WITHDRAWN: Procalcitonin and mid regional-pro-adrenomedullin promising markers for sepsis diagnosis and prognosis

n/

Phylogenetic analysis of human immunodeficiency virus type 2 group B

Context: Human immunodeficiency virus type 2 (HIV-2) infections are mainly restricted to West Africa; however, in the recent years, the prevalence of HIV-2 is a growing concern in some European countries and the Southwestern region of India. Despite the presence of different HIV-2 groups, only A and B Groups have established human-to-human transmission chains. Aims: This work aimed to evaluate the phylogeographic inference of HIV-2 Group B worldwide to estimate their data of origin and the population dynamics. Materials and Methods: The evolutionary rates, the demographic history for HIV-2 Group B dataset, and the phylogeographic analysis were estimated using a Bayesian approach. The viral gene flow analysis was used to count viral gene out/in flow among different locations. Results: The root of the Bayesian maximum clade credibility tree of HIV-2 Group B dated back to 1957. The demographic history of HIV-2 Group B showed that the epidemic remained constant up to 1970 when started an exponential growth. From 1985 to early 2000s, the epidemic reached a plateau, and then it was characterized by two bottlenecks and a new plateau at the end of 2000s. Phylogeographic reconstruction showed that the most probable location for the root of the tree was Ghana. Regarding the viral gene flow of HIV-2 Group B, the only observed viral gene flow was from Africa to France, Belgium, and Luxembourg. Conclusions: The study gives insights into the origin, history, and phylogeography of HIV-2 Group B epidemic. The growing number of infections of HIV-2 worldwide indicates the need for strengthening surveillance

High-dose-rate Brachytherapy as Adjuvant Local rEirradiation for Salvage Treatment of Recurrent breAst cancer (BALESTRA): a retrospective mono-institutional study

Purpose: To evaluate clinical results of catheter-based interstitial high-dose-rate (HDR) brachytherapy (BT) as adjuvant treatment in previously irradiated recurrent breast cancer. Material and methods: Between January 2011 and September 2015, 31 consecutive patients with histologically confirmed recurrent breast cancer after conservative surgery and conventional whole breast radiotherapy, were retreated with a second conservative surgical resection and reirradiated with adjuvant interstitial HDR-BT. None of the brachytherapy implant was performed during the quadrantectomy procedure. A dose of 34 Gy in 10 fractions, 2 fractions per day, with a minimal interval of 6 hours was delivered. Results: At the time of the implant, the median age of patients was 59.7 years (range, 39.3-74.9 years). The median time from first treatment until BT for local recurrence was 11.9 years (range, 2.5-27.8 years). The median interval between salvage surgery and BT was 3.6 months (range, 1-8.2 months). No acute epidermitis or soft tissue side effects higher than grade 2 were recorded, with good cosmetic results in all patients. Most of the patients presented grade 1-2 late side effects. Only one patient developed grade 3 liponecrosis. After a median follow-up of 73.7 months (range, 28.8-102.4 months), the overall survival and cancer specific survival were 87.1% and 90.3%, respectively; 5-year local control and 5-year progression-free survival rate were 90.3% and 83.9%, respectively. Conclusions: Our preliminary analysis showed that HDR-BT is a feasible treatment for partial breast reirradiation offering very low complications rate and fast procedure. Higher patients' cohort is warranted in order to define the role of this treatment modality in the breast conservative management of local recurrence

Recent advances in radiation oncology

Radiotherapy (RT) is very much a technology-driven treatment modality in the management of cancer. RT techniques have changed significantly over the past few decades, thanks to improvements in engineering and computing. We aim to highlight the recent developments in radiation oncology, focusing on the technological and biological advances. We will present state-of-the-art treatment techniques, employing photon beams, such as intensity-modulated RT, volumetric-modulated arc therapy, stereotactic body RT and adaptive RT, which make possible a highly tailored dose distribution with maximum normal tissue sparing. We will analyse all the steps involved in the treatment: imaging, delineation of the tumour and organs at risk, treatment planning and finally image-guidance for accurate tumour localisation before and during treatment delivery. Particular attention will be given to the crucial role that imaging plays throughout the entire process. In the case of adaptive RT, the precise identification of target volumes as well as the monitoring of tumour response/modification during the course of treatment is mainly based on multimodality imaging that integrates morphological, functional and metabolic information. Moreover, real-time imaging of the tumour is essential in breathing adaptive techniques to compensate for tumour motion due to respiration. Brief reference will be made to the recent spread of particle beam therapy, in particular to the use of protons, but also to the yet limited experience of using heavy particles such as carbon ions. Finally, we will analyse the latest biological advances in tumour targeting. Indeed, the effectiveness of RT has been improved not only by technological developments but also through the integration of radiobiological knowledge to produce more efficient and personalised treatment strategies