[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.

[Doege-Potter syndrome with giant malignant solitary fibrous tumour of the pleura]. / Doege­Potter-szindróma a mellhártya óriás malignus szoliter fibrosus tumorával.

Infrequent solitary fibrous tumours of the pleura are associated with hypoglycaemia only in a few percent of the cases; this condition is called Doege-Potter syndrome, named after its first descriptors. Our 63 years old male patient has previously undergone clinical treatment for intrathoracic fluid accumulation on the left side caused by a giant tumour-like mass in the lower left lobe detected by CT scan. In the course of further investigations performed due to increasing load-induced dyspnoea, lung core biopsy verified low grade sarcoma in the tumour. Tumour board suggested surgery. The patient was transferred from the intensive care unit into the operation theater due to increasing dyspnoea and repeated hypoglycaemic periods in rapidly worsening general condition. Pneumonectomy and removal of the tumour was performed on the left side. Histology showed solitary fibrous tumour of the pleura corresponding to Doege-Potter syndrome. The patient was discharged without complications and underwent adjuvant chemotherapy due to pleural dissemination of the tumour observed intraoperatively. One year after surgery the patient underwent surgical removal of a locally recurrent tumour. In spite of repeated chemotherapy local and multiplex contralateral pulmonary progression was observed. Three-year survival was noted from the time of the first surgery. Orv Hetil. 2018; 159(41): 149-153.

[Experience with cabazitaxel therapy for patients with metastatic castrate resistant prostate cancer in Hungary]. / Hazai tapasztalatok kasztrációrezisztens metasztatikus prosztatadaganatos betegek kabazitaxelterápiájával.

Our aim was to assess the efficacy and adverse effects of cabazitaxel (CBZ), a chemotherapeutic agent that can be administered to patients with metastatic castrate resistant prostate cancer (mCRPC) after docetaxel (DOC) therapy. We retrospectively analyzed data of CBZ received by mCRPC patients in 12 Hungarian oncological centers between 01/2016 and 06/2017. CBZ (25 or 20 mg/m2 q3w) was administered after DOC. Physical and laboratory examinations were performed in every cycle, tumor response was evaluated in every third cycle based on PCWG2 criteria. Adverse effects were evaluated based on CTCAE 4.0. Data of 60 patients were analyzed. CBZ was administered in 2nd and 3rd lines in 31.6% and 46.6%, while in 4th and 5th lines in 15% and 6.6% patients, respectively. Its starting dose was 25 mg/m2 and 20 mg/m2 in 65% and 35% of cases, respectively. The median number of cycles was 5. Progression-free survival and overall survival were 5.52 and 15.77 months, respectively. Survival results were similar in case of DOC-CBZ-ART/alfaradin and DOC-ART/alfaradin-CBZ sequences. Adverse effects were detected in 63,3% of patients. The most common adverse effects were neutropenia, anemia, and diarrhea. Our observations suggest that CBZ, with the appropriate support and chemotherapeutic experience, is well-tolerated and effective therapy of mCRPC after DOC.

[Successful sunitinib treatment of a patient with Stauffer's syndrome]. / Stauffer-szindrómában szenvedõ beteg sikeres sunitinibkezelése.

Several potential biomarkers of response to targeted therapies are being evaluated in metastatic renal cell carcinoma (RCC) to improve drug development and to determine which patient may benefit the most from the different treatment options. Stauffer's syndrome is a paraneoplastic syndrome that presents with the elevation of hepatic enzymes without hepatic metastases in patients with renal cell carcinoma. Hereby we report the case of our patient who suffered from multiple peritoneal metastases of renal cell cancer accompanied by Stauffer's syndrome. During his course of disease, the change in the serum gamma-glutamyl transferase (GGT) and alkaline phosphatase (ALP) levels correlated well with the extent of metastatic spread. Hypertension, grade 2 hand-foot syndrome and hypothyreosis also developed in relation to the successful sunitinib treatment. These side effects are predictive biomarkers in patients responding well to sunitinib. As other potential causes of increased GGT and ALP were excluded, the elevation of these enzymes were attributed to Stauffer's syndrome. During treatment, magnetic resonance imaging (MRI) follow-up showed complete regression, while the serum GGT and ALP levels halved. In this case, besides the known biomarkers, changes in serum GGT and ALP levels correlated well with the regression of metastatic renal cell carcinoma. To our knowledge, this is the first case published in the medical literature to show GGT and ALP levels in Stauffer's syndrome as potential biomarkers.

[Rare hereditary tumours]. / Ritka örökletes daganatok.

Almost 5-10% of all tumours are hereditary, which manifest in tumour syndrome or neoplasmic complication of a genetic disease. We present a short introduction of some of these rare diseases through our patients with the aspect of the clinical signs, diversities and challenges. These cases indicate that the incidency of malignancies are increased at genetic diseases, it means even multiple neoplasms in the same patient. The therapy does not differ from the ordinary tumour's therapy and the results are nearly the same as in cases without genetic diseases.

[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.