A gyomorrák kezelésének aktualitásai

Gastric cancer is the 9th most common malignancy in Hungary, being the 4th most frequent cause of death among all cancers. The traditional treatment approaches did not turn out to be effective against advanced gastric cancer. On the other hand, due to better understanding of the underlying molecular biology of tumors, targeted therapeutics emerge resulting in longer survival times. Dank M. Recent advances in the treatment of gastric cancer

A primer májdaganat gyógyszeres kezelési lehetőségei

Hepatocellular carcinoma is the most common primary malignancy of the liver, with increasing incidence worldwide. Chronic liver diseases, especially liver cirrhosis, are the primary risk factors in the pathogenesis. Curative therapy is usually possible only in early disease, however, most cases are diagnosed at advanced stage. Until recently sorafenib was the only viable option for systemic treatment, however, over the past years many new targeted and immunotherapy drugs proved to be efficient in first and second line as well

Új immunterápias lehetősegek az emlőrák kezelésében

The prognostic value of tumor infiltrating lymphocytes in breast cancer has long been recognized by histopathologists. These observations were reaffirmed by recent immunohistochemistry and gene expression profiling studies that also revealed an association between greater chemotherapy sensitivity and extensive lymphocytic infiltration in early stage breast cancers treated with neoadjuvant chemotherapy. These results suggest that local anti-tumor immune response can at least partially control cancer growth and may mediate the antitumor effects of chemotherapy. However, until recently, there was no direct clinical evidence to demonstrate that enhancing anti-tumor immune response could lead to clinical benefit in breast cancer patients. The recent development of clinically effective immune checkpoint inhibitors made it possible to test the therapeutic impact of augmenting the local anti-tumor immune response. Two Phase I clinical trials using single agent anti-PD-1 (MK-3475, pembrolizumab) and anti-PD-L1 (MPDL3280A, atezolizumab) antibodies demonstrated close to 20% tumor response rates in heavily pretreated, metastatic, triple negative breast cancers. The most remarkable feature of the responses was their long duration. Several patients had disease control close to a year, or longer, which has not previously been seen with chemotherapy regimens in this patient population. A large number of clinical trials are currently underway with these and similar drugs in the neoadjuvant, adjuvant and metastatic settings to define the role of this new treatment modality in breast cancer

Neoadjuvant PF-05280014 (a potential trastuzumab biosimilar) versus trastuzumab for operable HER2+ breast cancer

BACKGROUND: This randomised, double-blind study compared pharmacokinetics, efficacy, safety and immunogenicity of PF-05280014 (potential trastuzumab biosimilar) and trastuzumab reference product (Herceptin) sourced from the European Union (trastuzumab-EU) as neoadjuvant treatment for operable human epidermal growth factor receptor 2 (HER2)-positive breast cancer. METHODS: Patients (N = 226), stratified by primary tumour size and hormone receptor status, were randomised 1:1 to PF-05280014 or trastuzumab-EU (8 mg/kg loading dose; 6 mg/kg thereafter), each with docetaxel and carboplatin, every 3 weeks for six treatment cycles. Primary endpoint was percentage of patients with trough plasma concentration (Ctrough) >20 mug/ml at Cycle 5 (Cycle 6 predose). Efficacy endpoints included pathological complete response and objective response rate. Non-inferiority of PF-05280014 to trastuzumab-EU was declared if the lower limit of the 95% confidence interval for the stratified difference between groups in the percentage of patients with Cycle 5 Ctrough >20 mug/ml was above the prespecified non-inferiority margin of - 12.5%. RESULTS: For PF-05280014 vs trastuzumab-EU patients, respectively, 92.1% vs 93.3% had Cycle 5 Ctrough >20 mug/ml; the lower limit of the 95% confidence interval (- 8.02%, 6.49%) for the stratified difference between groups was above the non-inferiority margin (- 12.5%). Pathological complete response (47.0% vs 50.0%) and central radiology review-assessed objective response (88.1% vs 82.0%) rates were comparable. Incidence of all-causality, grade 3-4 treatment-emergent adverse events was 38.1% vs 45.5%; antidrug antibody rates were 0% vs 0.89%. CONCLUSIONS: PF-05280014 demonstrated non-inferior pharmacokinetics and comparable efficacy, safety and immunogenicity to trastuzumab-EU in patients with operable HER2-positive breast cancer receiving neoadjuvant chemotherapy

Kötődés, korai maladaptív sémák és szubjektív betegségélmény emlőrákkal küzdő nőknél

A legújabb kutatások szerint a kötődésnek kiemelt szerepe lehet a rosszindulatú daganatos megbetegedéssel összefüggő stresszel való megküzdésben. A bizonytalan kötődés kapcsolatban áll a rákos megbetegedés során átélt depresszióval és szorongással, míg a biztonságos kötődés a betegséggel való aktív megküzdéssel társul (Nicholls, Hulbert-Williams és Bramwell, 2014). A vizsgálatok többsége azonban a kategorizációs modellben nem tudott különbséget kimutatni a normatív minták és a rákbetegek között a kötődési típusok arányában. Hiányoznak a betegségélmény és a kötődési mintázat összetevőit komplexebb szinten vizsgáló kutatások. Vizsgálatunkban e hiány egy részének pótlását céloztuk meg. Két kötődésmérő eljárás alkalmazásával térképeztük fel a kötődési mintázatokat és a korai maladaptív kapcsolati sémákat emlőrákos nők (n=38) két életkori csoportjánál. Vizsgáltuk a pszichés tüneteket, valamint a szubjektív betegségélményt és az ezzel való megküzdés összefüggéseit. Eredményeink szerint a szomatizáció és a depresszív tünetek gyakorisága mindkét életkori csoportban magasabb, az ellenségesség pedig jelentősen alacsonyabb volt a magyar egészséges átlaghoz képest. A kötődés Túlzott foglalkozás a kapcsolatokkal skálájának értékei jelentősen magasabbak voltak a fiatalabbak korcsoportjában. A korai maladaptív sémák hasonló mintázatúak voltak a két életkori csoportban. A mélyinterjúk kvalitatív elemzése rávilágított a betegségélmény és a megküzdés egyéni jellemzőire. Ezek alapján felállítottunk egy hipotetikus modellt a kapcsolati mintázatok, a betegségélmény és a megküzdés összefüggéséről, ami támpontul szolgálhat az intervenció tervezéséhez. | According to recent studies attachment may play a crucial role in coping with malignant tumors. Insecure attachment correlates with depression and anxiety while secure attachment correlates with active coping with illness (Nicholls, Hulbert-Williams & Bramwell, 2014). Studies so far have failed to highlight a difference in the distribution of attachment types in the categorical model between normative samples and cancer patients. There is a gap in the literature in studying the interconnections between the attachment patterns and the experience of the illness in a more complex level. In our study we aimed to fill this gap, partially. We assessed attachment patterns and early maladaptive schemas applying two questionnaires in two age groups of women with breast cancer (n = 38). We examined the psychological symptoms, the subjective experience of illness and the way of coping with these experiences. According to our results the frequency of somatization and depressive symptoms in both age groups were higher than the Hungarian healthy average whereas the hostility was much lower. Scores on the Preoccupation with relationships attachment scale was significantly higher in the younger age group. The pattern of early maladaptive schemas were similar in the two age groups. The qualitative anaysis of the interviews shed light on the subjective experiences of the illness and the way of coping with it. Based on these results we have set up a hypothetical model about the interconnections between relationship patterns, subjective experience and coping. This model may prove helpful in planning intervention

Áttétes vesedaganatos betegek everolimusterápiájával szerzett hazai tapasztalatok

Everolimus is indicated for the therapy of adults with advanced renal cell carcinoma after failure of treatment with vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitor (TKI). The aim of the study was a multicenter evaluation of efficiency and toxicity of everolimus in patients with metastatic renal carcinoma who received one line of VEGFR-TKI therapy. Data of one hundred and one patients were analyzed retrospectively. Patients received everolimus therapy between January 2010 and July 2013. Data were collected in 7 different oncology institutes in Hungary. Starting daily dose of everolimus was 10 mg in 28-day cycles. Physical and laboratory examinations were done monthly. Imaging tests were performed every 3 months. Tumor response and toxicity were evaluated according to RECIST 1.0 and NCI CTCAE 3.0, respectively. Statistical analysis was performed with SPPS version 20.0 for Windows. Currently 26 (27%) patients are being treated, 52 (54.1%) patients are alive. Median progression-free survival (PFS) was 5.7 months (95% CI 4.07-7.33). Partial remission, stable disease and progression occurred in 6 (6%), 71 (74%) and 19 (20%) patients, respectively. Median overall survival (OS) was 14.3 months (95% CI 6.99-19.81). PFS and OS results were more favorable in patients with ECOG 0-1. Survival was poorer in case of anemia, while better if PFS was longer than 12 months. In anemic patients with ECOG 0-1 and ECOG 2-3 OS was 30.9 and 7.7 months, respectively (p=0.031). Dose reduction and treatment delay happened in 8 (7.9%) and 12 (11.9%) cases, respectively. The most common side effects were the following: exanthema, edema, stomatitis, pneumonitis, anemia and abnormal kidney-, liver functions, blood sugar and cholesterol levels. According to the Hungarian experience, everolimus can safely be administered. PFS and OS results representing the centers' everyday practice, are similar to the results of the respective subgroups in the registration study

Morphological and pathological response in primary systemic therapy of patients with breast cancer and the prediction of disease free survival

AIM: To identify breast cancer subtypes likely to respond to primary systemic therapy (PST or neoadjuvant therapy) and to assess the accuracy of physical examination (PE) and breast ultrasonography (US) in evaluating and predicting residual size of breast carcinoma following PST. METHODS: 116 patients who received at least two cycles of PST between 1998 and 2009 were selected from a prospectively collected clinical database. Radiological assessment was done by mammography and US. Prior to PST, tumors were subclassified according to core biopsy (NCB) and/or fine-needle aspiration-based immunohistochemical profiles of NCB. Pathological response rates were assessed following the surgeries by using Chevallier classification. Tumor measurements by PE and US were obtained before and after PST. Different clinical measurements were compared with histological findings. Disease-free survival (DFS) was assessed. RESULTS: Pathological complete remission (pCR=Chevallier I/II) was observed in 25 patients (21.5%), 44% of whom had triple negative histology, 28% Her2 positive and 76% had high-grade tumor. Of 116 patients, 24 received taxane-based PST, 48 combined taxane + anthracycline treatment, 8 trastuzumab combinations, 21 anthracycline-based treatments, and 15 other treatments. In the taxane treated group, the pCR rate was 30%, in the taxane + anthracycline group 25%, in the anthracycline group 9.5%, and in trastuzumab group 37.5%. After PST, PE and US were both significantly associated with pathology (P<0.001 and P=0.004, respectively). Concerning OS, significant difference was observed between the Chevallier III and IV group (P=0.031) in favor of Chevallier III group. In the pCR group, fewer events were observed during the follow-up period. CONCLUSIONS: Our results show that even limited, routinely used immunohistochemical profiling of tumors can predict the likelihood of pCR to PST: patients with triple negative and Her2-positive cancers are more likely to achieve pCR to PST. Also, PE is better correlated with pathological findings than US

Az emlőrák szisztémás kezelése: szakmai útmutatás

The article presents the practice guideline of systemic treatment of breast cancer and recommendations of the 3rd Hungarian Breast Cancer Consensus Conference. It reflects the recent international guidelines (ESMO, NCCN, ABC2, St Gallen's) irrespectively of the current financial opportunities. Here we follow the early - locally advanced - locally relapsed - metastatic breast cancer line for didactic considerations and we discuss the different subgroups of breast cancer based on hormone receptor and HER2 receptor status. Diagnosis and treatment options of rare clinical entities are summarised at the end of the paper