[EGFR protein is a negative prognostic and predictive factor in wild-type RAS colorectal cancer]. / Az EGFR-protein-expresszió negatív prognosztikus és prediktív marker vad RAS típusú vastagbélrákban.

Negative predictive markers of the anti-EGFR antibody therapies are RAS or BRAF mutations, while left sidedness can be considered as a positive predictor. Here we analyzed 97 wild type RAS metastatic colorectal cancers looking for the prognostic and predictive roles of EGFR protein expression. We found that right-sided colorectal cancers are characterized by significantly higher EGFR protein expression as compared to left-sided ones, irrespective of the primary or metastatic tissue analysis. Furthermore, tumors with multiple organ involvement are characterized by significantly higher EGFR protein expression as compared to single organ ones. In the homogenous cetuximab treated cohort (n=90) we have found that lower than the applied EGFR protein expression cut-off was associated with favorable survival. In the multivariate analysis only sidedness proved to be a strong independent predictor, however sidedness is an EGFR-dependent predictor of anti-EGFR therapy.

EGFR Protein Expression in KRAS Wild-Type Metastatic Colorectal Cancer Is Another Negative Predictive Factor of the Cetuximab Therapy.

The selection of colorectal cancer patients for anti-epidermal growth factor receptor (EGFR) antibody therapy is based on the determination of their RAS mutation status-a strongly negative predictive factor-since the protein target, EGFR, is not a reliable predictor of therapeutic response. In this study, we revisited the EGFR protein issue using a cohort of 90 patients with KRAS exon2 wild-type colorectal cancer who have been treated with cetuximab therapy. Twenty-nine of these patients had metastatic tissue available for analysis. The level of EGFR protein expression in the patients was determined by immunohistochemistry and evaluated by H-score (HS) methodology. Progression-free survival (PFS) and overall survival (OS) of the patients were determined according to the EGFR-HS ranges of both the primary and metastatic tissues using Kaplan-Meyer statistics. In the case of primary tumors, EGFR scores lower than HS = 200 were associated with significantly longer OS. In the case of metastatic tissues, all levels lower than the EGFR-HS range chosen were associated with significantly longer OS. These results are explained by the fact that metastatic tissues rarely maintained the expression levels of the primary tumors. On the other hand, high EGFR expression levels in either primary tumors or metastatic tissues were associated with multiple metastatic disease. This suggests a negative prognostic role of EGFR expression. However, in a multivariate analysis, one-sidedness remained a strong independent predictive factor of survival. Previous studies demonstrated that the EGFR expression level depends on sidedness. Therefore, a subgroup analysis of the left- and right-sided cases was performed on both primary and metastatic tissues. In the case of metastic tissues, an analysis confirmed a better OS in low EGFR protein-expressing cases than in high EGFR protein-expressing cases. Collectively, these data suggest that EGFR protein expression is another negative predictive factor of the efficacy of cetuximab therapy of KRAS exon2 wild-type colorectal cancer.

[Treatment of metastatic midgut neuroendocrine tumour associated with carcinoid syndrome]. / Carcinoid szindrómával társuló metasztatikus középbél-eredetu neuroendokrin tumor kezelése.

Although the incidence of neuroendocrine tumours is low, their prevalence is high due to the usually slow course of the disease. Between July 1, 2008 and July 1, 2013 the authors evaluated 56 patients with well-differentiated or moderately differentiated neuroendocrine tumours; 36 patients with metastatic disease underwent treatment while 17 patients who had tumour resection were followed without additional treatment. All patients with metastatic disease received long acting octreotide, and additional therapy was based on the site of origin, grade of differentiation, Ki67 index, and focal labelling of the tumours during somatostatin-receptor or metaiodo-benzyl-guanidine scintigraphy. The authors present a detailed case history of a patient with carcinoid syndrome due to a metastatic midgut neuroendocrine tumour, who received long acting octreotide and peptide receptor radionuclide treatment. In this patient an objective tumour response was reached in addition to the resolution of symptoms of carcinoid syndrome. The authors conclude that the case history confirms previous observations showing that long acting octreotide combined with peptide receptor radionuclide treatment may provide long survival with good quality of life in a patient with metastatic midgut neuroendocrine tumour accompanied with carcinoid syndrome. Orv. Hetil., 2014, 155(5), 194-198.

[Our experience with targeted therapy in glioblastoma multiforme]. / Glioblastoma multiforméban szenvedo betegek célzott terápiás kezelésével szerzett tapasztalataink.

Glioblastoma multiforme (GBM) is the most common and aggressive primary brain tumor in adults. The current standard therapy includes surgical resection or biopsy, followed by a combination of radiation and chemotherapy with temozolomide. After progression or recurrence there is only one recommended effective therapy, bevacizumab. Bevacizumab is a monoclonal VEGF inhibitor antibody, inhibiting the angiogenesis in highly vascularized tumors. Resent studies focused on adjuvant treatment with targeted therapy in newly diagnosed tumors. Our purpose is to evaluate the data from patients treated in our department investigate the clinical response and side effects profile and to compare these data with the international results. The applied protocol was well tolerated and side effects corresponded to the already reported ones. The median PFS and survival data correlate with those in the literature. The AVAglio study demonstrated that the addition of bevacizumab to the adjuvant therapy increased PFS significantly.