Francesca Negri

Expression of HER2/neu is uncommon in human neuroblastic tumors and is unrelated to tumor progression.

Abstract. Neuroblastic tumors (NT) are the most frequently occurring extracranial solid tumors during childhood. The overall 5-year survival is approximately 20% for patients with metastatic disease. Novel treatments are therefore intensively sought and tumor-targeted immuno- and chemotherapy appear promising. The HER2/neu oncogene, which is highly homologous to the EGF receptor, was initially isolated from rat neuroblastoma cells. HER2/neu over-expression is frequently detected in breast tumors and constitutes an important unfavorable prognostic factor. HER2/neu is a suitable target for antibody-based immunotherapy, as demonstrated by the clinical efficacy of the Herceptin monoclonal antibody (mAb), which reacts with its extracellular domain. Expression of HER2/neu has also been reported to be a negative prognostic factor in a small survey of NT tumors. Here, we have investigated HER2/neu expression in 14 human and 2 murine neuroblastoma (NB) cell lines by flow cytometric analysis and in 93 NT by means of a certified immunohistochemical system. HER2/neu over-expression was found in 2 human cell lines and 11 tumors (14% for both types of samples). No significant association was found between HER2/neu expression and stage, age, sex, ploidy, histological type or subtype. Moreover, log rank test indicated that overall and event-free survival was not significantly different in HER2/neu positive and negative patients. These data suggest that HER2/neu should not be considered as a relevant prognostic factor in NT, and that HER2/neu-based immunotherapy may be feasible only in a minority of NT patients.

Chromosomal imbalances in pediatric Burkitt-like lymphoma and review of the literature in relation to other germinal center derived B-cell tumors

This study reports on the cytogenetic features of a novel case of pediatric Burkitt-like lymphoma (BLL), that adds to the three published. Four groups of cytogenetic abnormalities were detected in the present case: (1) imbalances shared by most germinal center (GC) derived B-cell tumors including BLL (+1q, −6q, −8p, +8q24 and +11); (2) imbalances already reported in adult but not in pediatric BLL cases and shared with most GC B-cell tumors (+7, −9p, −9q, +12q, −13q, +17, +19, −3 and −4); (3) imbalances already reported in pediatric but not in adult BLL cases and shared with some GC B-cell tumors (−2q); and (4) imbalances never described before in pediatric or adult BLL, but present in different GC B-cell tumors (−6p, −1p and −18q). In view of the paucity of pediatric BLL cases published, this report adds novel, relevant information on the molecular cytogenetic features of this rare tumor.

Urea-Based Cream to Prevent Sorafenib-Induced Hand-and-Foot Skin Reaction: Which Evidence?

TO THE EDITOR: Sorafenib tosylate is one of oldest commercially available multikinase inhibitors. It was first approved for the treatment of advanced kidney cancer in 2005 and then hepatocellular carcinoma (HCC) in 2007. More recently, in 2013, it was also approved for use in the treatment of metastatic differentiated thyroid cancer. From the beginning, it was clear that, among the peculiar adverse events (AEs) induced by this agent, hand-and-foot skin reaction (HFSR) and diarrhea were the most troublesome for our patients. These frequently affected our ability to administer a correct dosage intensity of oncologic treatment. It was also clear then that any attempt to prevent HFSR was key to guaranteeing the best treatment possible and to maintaining the highest quality of life. Therefore, practical use of urea-based creams (UBCs) to prevent and/or treat HFSR was implemented from almost the first time sorafenib and other similar multikinase inhibitors were clinically used. This practical approach was recently validated by the results of a large, randomized controlled trial performed in the People’s Republic of China involving more than 850 patients with HCC and reported in the article by Ren et al. Although results of this study provide the highest level of evidence and the highest grade of recommendation regarding the prophylactic use of UBC for sorafenib-induced HFSR, potentially useful information is still missing, and relevant doubts remain unsolved. First, because UBCs are commonly used, given the advice of many authors starting in 2009, what practical relevance should we give to this trial? That is, UBC was compared with nothing. Beyond the lack of a placebo, the most important issue with this trial is: what was the true control arm? It was not best supportive care (BSC). Careful reading of the article by Ren et al reveals that BSC was scheduled, per protocol, just to manage AEs other than HFSR. This suggests that no other preventive measures were applied to prevent HFSR beyond the application of the UBC itself. If so, this is a huge bias because it is well established that a number of preventive measures—which should be regarded as part of an adequate BSC—should be applied in patients who are treated with drugs that can potentially induce HFSR, such as sorafenib. A few other questions remain. Are there possible differences between patients with HCC and patients who have other solid tumors, such as kidney and thyroid cancer, for which sorafenib is used? What is the ideal concentration of urea? Finally, should we regard UBC as the present standard of care for the prevention of HFSR? The first question is all but trivial because cirrhosis, irrespective of its cause, is often associated with skin manifestations. This, once again, makes the typical patient with HCC quite different from any other patient with cancer. The most appropriate concentration of urea is still unknown; 10% and 12.5% have been empirically suggested. Finally, last year, data from a phase II randomized trial of a limited number of patients with renal cancer suggested that a hydrocolloid dressing containing ceramide could prevent sorafenib-induced HFSR more effectively than a 10% UBC. Ren et al should be applauded for their effort as well as for providing us with a high level of evidence for the use of UBC to prevent HFSR. Still, many unanswered questions remain regarding how to deal with this distressing and difficult to manage AE.

517PFOLFOXIRI PLUS BEVACIZUMAB (BEV) AS FIRST-LINE TREATMENT OF RAS WILD-TYPE (WT) METASTATIC COLORECTAL CANCER (MCRC) PATIENTS (PTS)

ABSTRACT Aim: Phase III TRIBE trial demonstrated that FOLFOXIRI plus bev provides a significant advantage in PFS, response rate and OS as compared to FOLFIRI plus bev. No interaction between RAS mutational status and treatment effect was reported. The aim of the present analysis is to describe the clinical outcome of RAS wt pts treated with the triplet plus bev. Methods: Patients not bearing KRAS or NRAS codon 12, 13 and 61 mutations were defined as RAS wt. Best response according to RECIST, early response and deepness of response (DoR) were analysed. Patients achieving a >20% reduction in the sum of longest diameters of RECIST target lesions at week 8 compared to baseline were defined as early responders. A further analysis was performed in the RAS and BRAF wt subgroup. Results: Seventy-eight RAS wt patients received first-line FOLFOXIRI plus bev. BRAF mutation was detected in 14 (18%) RAS wt patients. Fifty-one (65%) out of 78 pts achieved RECIST response and 21 (27%) reported a disease stabilization for an overall disease control rate of 92%. Early response was reported in 44 (63%) out of 70 evaluable pts. The median DoR was 43.5% (range 100%/-38.2%). Twenty-three patients (29%) underwent a secondary resection with curative intent (R0/R1/R2) and a R0 resection was performed in 14 patients (18%). Median PFS and OS were 12.8 and 36.0 months, respectively. Out of 64 RAS and BRAF wt pts, RECIST response rate was 69% and median PFS and OS were 13.3 and 41.7 months, respectively. Conclusions: RAS wt pts treated with the triplet plus bev in the TRIBE trial achieved notable results in terms of RECIST response, PFS and OS. Though acknowledging limitations of cross-trial comparisons, these results compare favourably with those reported in phase III trials with first-line doublets plus an anti-EGFR monoclonal antibody, in particular for PFS. Disclosure: A. Falcone: Consultant, honoraria and research funding for Roche, Merck and Amgen. Consultant and honoraria fro Sanofi-Aventis, Bayer and Celgene.All other authors have declared no conflicts of interest.