Timing of radiotherapy in glioblastoma based on IMRT and STUPP chemo-radiation: may be no need to rush

To investigate the effect of surgery to radiotherapy interval (SRI) on the prognosis of patients with isocitrate dehydrogenase (IDH) wild-type glioblastoma.MethodsRetrospective analysis of the relationship between SRI and prognosis of patients with IDH wild-type glioblastoma who received postoperative intensity modulated radiotherapy (IMRT) in our center from July 2013 to July 2019. The patients were divided into SRI ≤ 42 days (regular group) and SRI > 42 days (delay group). Kaplan–Meier univariate analysis and Cox proportional hazard model were used to analyze whether SRI was an independent factor influencing the prognosis.ResultsA total of 102 IDH wild-type glioblastoma were enrolled. Median follow-up was 35.9 months. The 1-, 2- and 3-year OS of “regular group” were 69.5%, 34.8%, 19.1%, and “delay group” were 69.8%, 26.1% and 13.4% respectively. Multivariate analysis showed that extent of resection (p = 0.041) was an independent prognostic factor for OS. SRI (p = 0.347), gender (p = 0.159), age (p = 0. 921), maximum diameter (p = 0.637) MGMT promoter methylation status (P = 0.630) and ki-67 expression (P = 0.974) had no effect on OS. Univariate analysis (p = 0.483) and multivariate analysis (p = 0.373) also showed that SRI had no effect on OS in glioblastoma who received gross total resection.ConclusionAppropriate extension in SRI has no negative effect on the OS of IDH wild-type glioblastoma. It is suggested that radiotherapy should be started after a good recovery from surgery. This conclusion needs further confirmed by long-term follow-up of a large sample. (AU)

Carcinoma gástrico con estroma linfoide: 3 entidades clínico-patológicas / Gastric carcinoma with lymphoid stroma: 3 clinicopathological entities

Los carcinomas gástricos con estroma linfoide son un grupo heterogéneo de neoplasias mal caracterizadas que históricamente no se han clasificado en entidades clínico-patológicas distintas. Conocer los criterios diagnósticos e identificarlos tiene una importancia relevante tanto clínica como pronóstica. Analizamos 13 casos de pacientes con carcinomas gástricos con estroma linfoide. Con criterios histopatológicos, inmunofenotípicos y moleculares, se definieron 3 subtipos (patrón 1, 2 y 3). Realizamos inmunohistoquímica para caracterizar las poblaciones linfoides (CD3, CD4, CD8 y CD20), para analizar la expresión de virus de Epstein-Barr (VEB) y la expresión de proteínas reparadoras del ADN. El objetivo de este estudio es definir criterios útiles que permitan distinguir estas inusuales lesiones y estudiar el inmunofenotipo de las poblaciones linfoides (AU)

Gastric carcinomas with lymphoid stroma comprise a heterogeneous group of incompletely characterized neoplasms that have not as yet been classified as different clinico-pathological entities. We analysed 13 cases of gastric carcinoma with lymphoid stroma in order to establish diagnostic criteria for their identification. We defined 3 different subtypes (patterns 1, 2 and 3) based on histopathologic, immunophenotypic and molecular criteria. Immunohistochemistry was performed to identify lymphoid populations (CD 3, CD4, CD8 and CD20), the presence of Epstein-Barr Virus (EBV) and the expression of DNA mismatch repair proteins. Our aim is to define criteria that are helpful in the differential diagnosis of these unusual lesions and to clarify the immunophenotype of their lymphoid population (AU)

Prognostic value of ERCC1, RRM1, BRCA1 and SETDB1 in early stage of non-small cell lung cancer

Introduction: Nowadays, 40 % of early-stage NSCLC patients relapse in the 2 years following resection, suggesting a mis-staging in this group of patients who are not receiving adjuvant chemotherapy. Although different biomarkers, such as ERCC1, RRM1 and BRCA1 have been found to present prognostic value in advanced NSCLC patients, in early-stage NSCLC patients its relevance remains unclear. Moreover, SETDB1 has been recently proposed as a bona fide oncogene in lung tumourigenesis and related with metastasis. The aim of the present study was to analyze the prognostic value of ERCC1, RRM1, BRCA1 and SETDB1 expression levels in NSCLC patients at stage I. Patients and methods: ERCC1, RRM1, BRCA1 and SETDB1 expression at mRNA level was analyzed by realtime quantitative RT-PCR in fresh-frozen tumor and normal adjacent lung tissue samples from 64 stage I NSCLC patients. Later, significant association between gene expression levels, clinicopathological characteristics and patient’s disease-free survival was assessed. Results: We did not find any statistically significant correlation between gene expression and gender, age, histological type or smoking status. Univariate followed by multivariate Cox analysis showed that higher levels of BRCA1 and SETDB1 expression were significantly associated with shorter disease-free survival in stage I NSCLC patients. Conclusion: Our study finds that ERCC1 and RRM1 are not independent prognostic factors of recurrence in stage I NSCLC patients. By contrast, BRCA1 and SETDB1 stand out as the most significant prognostic markers in this group of patients, appearing as promising tools to predict tumor recurrence in early-stage NSCLC patients (AU)

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Methylation status of O6-methylguanine-DNA-methyl transferase promoter region in non-small-cell lung cancer patients with brain metastasis

Background. O6-methylguanine-DNA-methyl transferase (MGMT), a DNA repair gene, is a key enzyme for predicting the response to both radiotherapy and temozolomide in glioma patients. Data on the MGMT promoter methylation status in relation to the time to develop intracranial new metastasis or local relapse at the surgical site after brain surgery followed by radiotherapy is limited in non-smallcell lung cancer (NSCLC) patients with a single brain metastasis. Methods. All 55 patients included in this analysis were NSCLC with a single brain metastasis and had undergone brain surgery followed by radiotherapy. Genomic DNA was extracted from the brain tumour. The DNA was treated with bisulphate and a methylation-specific polymerase chain reaction was performed. Survival was compared by the status of promoter region of MGMT. Results. The time to develop intracranial new metastases or local relapse at the surgical site after treatment in patients with methylation of the MGMT promoter region was 4.0 months (N=5), while that of the patients without methylation of the MGMT promoter region was 11.5 months (N=50) (p=0.37). Conclusions. NSCLC patients with brain metastasis treated by brain surgery followed by radiotherapy may have a higher chance of relapse when the tumour has methylation of the MGMT promoter region (AU)

Tumour and serum MGMT promoter methylation and protein expression in glioblastoma patients

INTRODUCTION: Methylation of the promoter of the MGMT gene and MGMT protein expression are recognized as predictive markers for response to alkylating chemotherapy in glioblastoma (GB). MATERIAL AND METHODS: We have assessed MGMT methylation with the methylation-specific polymerase chain reaction (MSP) in tumor samples from 70 GB patients and in serum samples from 37 of these patients. We have also assessed MGMT protein expression by immunohistochemical (IHC) analysis in tissue samples from 63 of these patients. RESULTS: We found concordance between MGMT methylation status in tissue and serum (Cohen's Kappa = 0.586; p<0.0001). MSP for detection of non-methylated MGMT promoter in serum showed a sensitivity of 95.4% and a specificity of 60%, while the IHC methylation test showed a low specificity (8.9%). Patients whose MGMT promoter was methylated in tissue attained longer progression-free and overall survival. In the multivariate analysis, serum MGMT promoter methylation emerged as an independent factor for longer progression-free and overall survival. CONCLUSION: Serum-based MGMT methylation analysis offers a promising alternative to tumor-based MGMT analysis in cases where tissue samples are unavailable (AU)