New horizons from novel therapies in malignant pleural mesothelioma

Malignant pleural mesothelioma (MPM) is a relatively rare, but highly lethal cancer of the pleural mesothelial cells. Its pathoge-nesis is integrally linked to asbestos exposure. In spite of recent developments providing a more detailed understanding of the pathogenesis, the outcomes continue to be poor. To date, trimodality therapy involving surgery coupled with chemotherapy and/or radiotherapy remains the standard of therapy. The development of resistance of the tumor cells to radiation and several che-motherapeutic agents poses even greater challenges in the management of this cancer. Ionizing radiation damages cancer cell DNA and aids in therapeutic response, but it also activates cell survival signaling pathways that helps the tumor cells to overcome radiation-induced cytotoxicity. A careful evaluation of the biology involved in mesothelioma with an emphasis on the workings of pro-survival signaling pathways might offer some guidance for treatment options. This review focuses on the existing treatment options for MPM, novel treatment approaches based on recent studies combining the use of inhibitors which target different pro-survival pathways, and radiotherapy to optimize treatment

The impact of total neo-adjuvant treatment on nonoperative management in patients with locally advanced rectal cancer: The evaluation of 66 cases

Background: The study aimed to assess if adherence to a total-neoadjuvant-treatment (TNT) protocol followed by observation(watch-and-wait) led to the successful nonoperative-management of low-rectal-cancer

Nowe perspektywy leczenia złośliwego międzybłoniaka opłucnej

Złośliwy międzybłoniak opłucnej to stosunkowo rzadko występująca choroba rozrostowa komórek mezotelialnych opłucnej, cechująca się dużą śmiertelnością. Jej patogeneza nieodłącznie wiąże się z ekspozycją na działanie azbestu. I chociaż coraz więcej wiadomo na ten temat, nadal wiele zagadnień dotyczących mechanizmu powstawania i rozwoju złośliwego międzybłoniaka opłucnej pozostaje niejasnych. Terapia trójmodalna, składająca się z leczenia chirurgicznego skojarzonego z chemioterapią i/lub radioterapią, nadal pozostaje terapią standardową. Rozwój oporności komórek guza na radioterapię oraz niektóre środki chemioterapeutyczne bardzo utrudniają leczenie tego nowotworu. Promieniowanie jonizujące uszkadza DNA komórek nowotworowych i zwiększa odpowiedź na leczenie, lecz uaktywnia także szlaki sygnałowe przeżycia komórki, co pozwala komórkom nowotworowym pokonać cytotoksyczność wywołaną promieniowaniem. Uważna ocena międzybłoniaka na poziomie biologicznym, z naciskiem na mechanizmy działania szlaków sygnałowych prowadzących komórkę na drogę przeżycia, może być pomocna przy wyborze opcji terapeutycznej. Niniejsza praca skupia się na dostępnych metodach leczenia złośliwego międzybłoniaka opłucnej, nowym podejściu terapeutycznym opartym na najnowszych badaniach, wykorzystującym inhibitory ukierunkowane na różne szlaki sprzyjające przeżyciu i radioterapii stosowanej w celu optymalizacji metod leczenia

New Horizons from Novel Therapies in Malignant Pleural Mesothelioma

Malignant pleural mesothelioma (MPM) is a relatively rare, but highly lethal cancer of the pleural mesothelial cells. Its pathoge-nesis is integrally linked to asbestos exposure. In spite of recent developments providing a more detailed understanding of the pathogenesis, the outcomes continue to be poor. To date, trimodality therapy involving surgery coupled with chemotherapy and/or radiotherapy remains the standard of therapy. The development of resistance of the tumor cells to radiation and several che-motherapeutic agents poses even greater challenges in the management of this cancer. Ionizing radiation damages cancer cell DNA and aids in therapeutic response, but it also activates cell survival signaling pathways that helps the tumor cells to overcome radiation-induced cytotoxicity. A careful evaluation of the biology involved in mesothelioma with an emphasis on the workings of pro-survival signaling pathways might offer some guidance for treatment options. This review focuses on the existing treatment options for MPM, novel treatment approaches based on recent studies combining the use of inhibitors which target different pro-survival pathways, and radiotherapy to optimize treatment

Comparison of efficacy and safety of three different chemotherapy regimens delivered with concomitant radiotherapy in inoperable stage III non-small cell lung cancer patients

Concomitant administration of chemotherapy and radiotherapy is currently recognized as the standard of treatment in locally advanced inoperable non-small cell lung cancer (NSCLC). Our study aimed to compare the efficacy and toxicities of three different chemotherapy regimens delivered concurrently with radiotherapy. We retrospectively reviewed the clinical records of patients who received the PE (cisplatin, 50 mg/m(2), on days 1, 8, 29, and 36 plus etoposide, 50 mg/m(2), on days 1 to 5 and 29 to 33), PD (docetaxel, 20 mg/m(2), on day 1 plus cisplatin, 20 mg/m(2), on day 1, every week), and PC (carboplatin, AUC 2 plus paclitaxel, 45 mg/m(2), on day 1, every week) regimens concurrently with radiotherapy. A total of 227 patients were evaluated in the study. Median follow-up time was 13 months (2-101). There were 27 females (11.9 %) and 200 males (88.1 %) with a median age of 61 (38-82) years. The PD group had higher rates of esophagitis, mucositis, and anemia (p < 0.05). The PC group had higher rates of neuropathy (p = 0.000). The progression-free survival (PFS) time was 10 months for patients in the PC group, 15 months for patients in the PD group, and 21 months for the PE group (p = 0.010). Patients in the PC group had a median overall survival time of 23 months, those in the PD group 27 months, and those in the PE group 36 months (p = 0.098). Combination of cisplatin-etoposide with radiotherapy led to a more favorable outcome compared with the other two regimens. It shows generally manageable toxicity profile and compliance to treatment is noticeable

Biological Subtypes and Survival Outcomes in Breast Cancer Patients with Brain Metastases (Study of the Anatolian Society of Medical Oncology)

Background: The aim of this study is to determine the relationship between the survival outcomes and biological subtype in breast cancer patients with brain metastases. Methods: We retrospectively evaluated clinical data from 422 breast cancer patients with brain metastases between 2001 and 2011 from referral centers in Turkey. The study population was divided into four biological subtypes according to their hormone receptor status and HER2 expression. Results: Systemic treatment prolonged median overall survival (OS) after brain metastases in the entire group (14 vs. 3.2 months, p < 0.001). It also prolonged median OS after brain metastases in the triple negative (7.5 vs. 1.6 months, p = 0.010) and luminal A (14.3 vs. 7.1 months, p = 0.003) subgroups. The median OS for untreated patients, chemotherapy and/or hormonal therapy receiving patients, and chemotherapy and/or hormonal therapy plus targeted therapy receivers was 2, 5.8, and 17.7 months, respectively (p < 0.001), in the HER2-overexpressing subgroup. In the luminal B subgroup, it was 3.7, 5.3, and 15.4 months, respectively (p = 0.003). Conclusions: The use of systemic therapy improves OS after brain metastases in all biological subgroups. Targeted therapies also improve OS after brain metastases in HER2-positive patients. The combined use of targeted therapies and lapatinib are superior to single use and trastuzumab, respectively, in these patients. Copyright (C) 2012 S. Karger AG, Base