François Lemare

High incidence of cetuximab-related infusion reactions in head and neck patients

Background Cetuximab is crucial in the management of squamous cell carcinoma of the head and neck of patients. Grade 3–4 cetuximab-induced infusion reactions (CI-IRs) occur in 2% of patients with colorectal cancer. Despite the 2.7% CI-IR rate in the EXTREME trial, higher rates were reported in small series of patients with head and neck squamous cell carcinoma (HNSCC) (6%–18%). There is an urgent need to better appraise the natural history and the predictive factors for CI-IRs in patients with HNSCC exposed to cetuximab. Methods The medical records from patients with HNSCC (n=428) treated by cetuximab at Gustave Roussy from January 2013 to December 2015 were reviewed. The impact of potential risk factors was analysed. Results Out of 428 patients, 24 patients (5.4%) presented CI-IR, including grade 3–4 (95.7%); about 21% (5/24) requiring intensive care unit referral and quasi all occurred within the first cycle (21/24). In a multivariate analysis, the occurrence of grade 3–4 CI-IR was associated with tobacco and alcohol history (p=8.5e–3) and with prior allergy history (p=2.9e–3). CI-IRs tended to be associated with poor overall survival in patients with recurrent and metastatic HNSCC and with a higher number of further lines of chemotherapy. Conclusion In real life, CI-IRs appear far more common in patients with HNSCC (5.4%) than reported in prospective trials. This is the largest series of patients ever focusing on the risk of CI-IR in patients with HNSCC. Prior allergy history and tobacco history are associated with CI-IR and could be used to better allocate treatment. Further prospective data are required to confirm these findings.

ADAM9 expression promotes an aggressive lung adenocarcinoma phenotype

A disintegrin and metalloproteinase 9 (ADAM9) possesses potent metastasis-inducing capacities and is highly expressed in several cancer cells. Previous work has shown that ADAM9 participates in the adhesive–invasive phenotype in lung cancer cells in vitro. In this study, we evaluated whether ADAM9 expression plays a critical role in metastatic processes in vivo and in angiogenesis. We first found that high ADAM9 expression was correlated with poor lung adenocarcinoma patient prognosis on Prognoscan data base. In vivo model based on intravenous injection in nude mice showed that a stable downregulation of ADAM9 in A549 (TrA549 A9-) cells was associated with a lower number of nodules in the lung, suggesting lower potentials for extravasation and metastasis. On a subcutaneous xenograft we showed that TrA549 A9− produced significantly smaller tumours and exhibited fewer neovessels. In addition, in vitro human umbilical vein endothelial cells exposed to supernatant from TrA549 A9− could reduce the formation of more vessel-like structures. To further understand the mechanism, a human antibody array analysis confirmed that five cytokines were downregulated in TrA549 A9− cells. Interleukin 8 was the most significantly downregulated, and its interaction with CXCR2 was implicated in angiogenesis on an in vitro model. These results emphasize the critical influence of ADAM9 on lung cancer progression and aggressiveness. ADAM9 should at least be a marker of cancer aggressiveness and a potential therapeutic target for cancer treatment.

The cost of molecular-guided therapy in oncology: a prospective cost study alongside the MOSCATO trial

Aim:There is increasing use of molecular technologies to guide cancer treatments, but few cost data are available. Our objective was to assess the costs of molecular-guided therapy for patients with advanced solid tumors alongside the Molecular Screening for Cancer Treatment and Optimization (MOSCATO) trial.Materials and methods:The study population consisted of 529 patients. The molecular diagnosis included seven steps from tumor biopsy to the multidisciplinary molecular tumor board. The cost of a complete molecular diagnosis was assessed by micro-costing. Direct costs incurred from enrollment until progression were assessed from the French National Health Insurance perspective. Results:The patients’ mean age was 54 years (range: 3–82) and the mean follow-up period was 145 days (range: 1–707 days). A complete molecular diagnosis cost [euro ]2,396. There were 220 patients with an actionable target (42%), among whom 105 (20%) actually received a targeted therapy. The cost of molecular-guided therapy per patient was [euro ]31,269. The main cost drivers were anticancer drugs (54%) and hospitalizations (35%).Conclusion:This prospective cost analysis showed that molecular diagnosis accounts for only 6% of the cost of molecular-guided therapy per patient. The costs of drugs and hospitalizations are the main cost drivers.Genet Med advance online publication 01 December 2016

First case report of intrathecal panitumumab for treatment of meningeal carcinomatousis in an EGFR mutant lung adenocarcinoma patient

Intrathecal (IT) chemotherapy has been the mainstay treatment for patients with meningeal carcinomatosis (MC) but the prognosis of MC remains disastrous and most patients expire before 6 months [1]. Recently IT administration of trastuzumab, an IgG1 anti-HER2 monoclonal antibody (mAbs), has been tested with signs of efficacy in HER2 positive breast cancer patients [2–5]. We report here the first case of IT panitumumab, a human recombinant IgG2 kappa mAbs that binds specifically to EGFR, for a patient with MC derived from an EGFR exon 19 mutant lung adenocarcinoma.

Computerized pediatric oncology prescriptions review by pharmacist: A descriptive analysis and associated risk factors

Systematic prescription analyses by clinical pharmacists result in pharmacist interventions (PIs) to reduce prescription errors and improve medication safety. PIs are particularly critical in oncology, because antineoplastic drugs are highly toxic with low therapeutic indexes especially in a pediatric population. The aim of this study is to describe PIs in a pediatric oncology department and to identify potential risk factors associated with prescription errors.

Permeability of expander breast implants: In vitro and in vivo analyses

INTRODUCTION The biocompatibility of the polysiloxane breast implant has been studied moderately. The aging of these implants due to lipid penetration and the release of polymerization impurities, such as Platine or octamethylcyclotetrasiloxane (named D4), has already been documented. Since these studies, manufacturing procedures have been improved; thus, the security of breast implants has also improved. Although polymerization and the choice of monomer influence the shell properties, few studies have compared these together in breast implants. Our study compares the permeability and mechanical resistance of 3 breast expander shells after in vivo and in vitro aging. RESULTS In vitro, all tested shells quickly sorbed linear molecules, such as fatty acids, and released siloxane impurities. The penetration of a molecule with steric hindrance, such as cholesterol, is slower. Allergan shells have the highest rates of molecule sorption and siloxane release. In vivo, after implantation, Allergan shells lost their initial mechanical properties over time. This observation was not found for mentor shells. For all brands, many biological molecules penetrate the shells, among which cholesterol and fatty acids are always present. DISCUSSION The aging of polysiloxane shells depends on the sorption of many biological molecules and the release of siloxane impurities. The siloxanes are impurities and / or degradation products that are due to aging. Moreover, according to our results, the shells act as matrices that separate molecules according to their chemical and physical properties. CONCLUSION Not all polysiloxane expander shells have the same properties during aging. The manufacturing procedures and the choice of siloxane monomers are the two most probative factors that explain the observed differences.