Soft tissue sarcomas in children are a heterogeneous group of malignant diseases. Among these, tumors localized in the head and neck region are especially difficult to treat. While multidisciplinary care has dramatically improved the prognosis of sarcoma patients, their treatment remains uncertain because of demand on radical surgical resection of the tumor. Achieving cure without deforming or mutilating the child remains the primary goal of treatment. This study is the multicenter (nationwide, 11 Polish centers) retrospective analysis of the treatment results in children having soft tissue sarcoma in the head and neck region during the previous decade (from 1991 to 2001). Late effects of the treatment are documented in long-term survivals. Eighty-five children from 1 to 212 months of age were included. Different multimodal treatment protocols were utilized (CWS-91, SIOP-MMT-91, and CWS-96). The median observation time was 25 months. Data on long-term effects were collected in 34 long-term survivals. Complete remission was achieved in 68 (80%) patients. Primary treatment failure occurred in 13 (15.3%) patients, all of whom succumbed in disease progression. Relapse occurred in 21 (30.9%) patients primarily achieving complete remission. Second primary neoplasm occurred in 3 children. The estimated 5-year event-free survival and the 5-year total survival rates for the whole group are 0.38 and 0.55, respectively. The main late effect documented in long-term survivals were cosmetic defects in 12 (35.3%) and visual field deficit or blindness in 8 (26.5%). Despite substantial improvement of the prognosis of pediatric soft tissue sarcomas, the multimodal treatment of head and neck region tumors remains controversial. Improved long-term outcome and focusing on psychosocial difficulties raise the important and difficult problem of functional results and cosmesis. Tumors localized in the orbit carry an excellent prognosis. However, the main late sequela is vision impairment and cosmetic defect due to the therapy given many years earlier. Two other tumor localizations--the parameningeal and nonparameningeal ones--still have bad prognosis. The observations made in this study confirm that main prognostic factors are the size of the primary tumor and the tumor stage. The worst prognosis remains invasive tumor (T2-stage) with a size over 5 cm. Individually adjusted multimodal therapy, which imperatively needs to be radical, though not mutilating, might minimize the late effects. Psychosocial problems in long-term survivors need to be focused on at the national level and better support must be provided in the future, involving a team of different medical and paramedical profiles.
The time-limited efficacy of reversible EGFR-TKIs in patients with advanced non-small cell lung cancer (NSCLC) with EGFR gene activating mutations is associated with development of treatment resistance after some period of therapy. This resistance predominantly results from secondary mutations located in EGFR gene, especially T790M substitution. There is limited information available concerning the prevalence of primary T790M mutations in patients with metastatic NSCLC tumors before treatment with EGFR-TKIs. The aim of work was to assess the prevalence of de novo T790M mutations in EGFR gene in tissue samples from NSCLC metastatases in central nervous system (CNS) in both chemotherapy and EGFR-TKI naive NSCLC patients. We analyzed DNA samples isolated from paraffin-embedded tissue from CNS metastases for T790M mutations using real-time PCR and TaqMan probe against the T790M mutant sequence. The tissue samples were taken during palliative neurosurgery in 143 NSCLC patients. Amplification of the T790M-specific sequence was detected in 25 patients (17.5 %). The quantity of mutated DNA was less than 1 % in all samples with amplification, and in vast majority (20 patients, 14 % of all samples) it was even less that 0.1 %. In 5 patients (3.5 %) quantity of mutated DNA ranged from 0.1 to 1 % and true positive results of T790M mutation presence in these patients were most possible. Amplification of this sequence was not concurrent with common EGFR mutations and was not associated with sex, smoking status and pathological type of cancer. There is a possibility to detect the primary T790M mutation in brain metastases of NSCLC in EGFR-TKIs naïve patients.
The HER2 (ErbB2/neu) protein is a member of the HER (ErbB) receptor family (EGFR, HER2, HER3 and HER4) that expresses tyrosine kinase activity in the intracellular domain. EGFR and HER2 overexpression is observed in numerous types of cancer, nevertheless, the susceptibility of patients with non-small cell lung cancer (NSCLC) to therapy with EGFR and HER2 tyrosine kinase inhibitors (TKIs) depends on mutations present in the respective coding genes (driver mutations). In the present study, PCR and amplified DNA fragment length analysis (FLA) were used along with the multi-temperature single-strand conformation polymorphism (MSSCP) technique in order to identify the 12 base pair insertion in exon 20 of the HER2 gene in 143 patients with NSCLC metastasis to the central nervous system. The prevalence of the HER2 gene mutation was correlated with mutations in the EGFR and BRAF genes. The insertion in exon 20 of the HER2 gene was observed in a single 77-year-old, non-smoking male, with poorly-differentiated adenocarcinoma of the lung (1.5% of adenocarcinoma patients). No other genetic abnormalities were identified in this patient. In the therapy of NSCLC patients with HER2 gene mutations, drugs that inhibit the EGFR and HER2 receptors, for example afatinib, may be effective. The identification of other driving mutations in NSCLC cells appears to be key to the appropriate qualification of molecular targeted therapies.
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