Purpose: to summarize available data on the diagnostic value of various circulating biomarkers for the detection of glioblastoma recurrence. Material and Methods. A literature search was conducted using PubMED ExoCarta and SILVA databases. Results. Glioblastoma multiforme (GBM) is the most common glioma in adults with an unfavorable prognosis. Treatment of tumor recurrence can improve the survival of patients. Neuroimaging is the standard method of diagnosing brain tumor recurrence. However, a neuroimaging method to clearly distinguish between pseudo progression and tumor progression has not been found to date. Current molecular tumor profling relies heavily on tissue resection or biopsy. Tissue profling has several disadvantages in the central nervous system’s tumors, including the challenge associated with invasive biopsy, the heterogeneous nature of many malignancies where a small biopsy can under represent the mutational profle. Liquid biopsy is a promising method in diagnosing malignant tumors. Blood collection is a simple, minimally invasive procedure, but cerebrospinal fuid allows tumor markers to be detected more confdently. However, collection of cerebrospinal fuid is a complex and invasive procedure that can be accompanied by serious complications. Conclusion. Biological fuid markers such as circulating tumor cells, extracellular vesicles, cell-free DNA and cell-free RNA allow for the detection of GMB, determination of molecular genetic features of cancer during response to therapy, and early detection of GBM recurrence.
Circulating small extracellular vesicles (sEVs) are emerging as potential biomarkers for glioblastoma progression. This study aimed to compare the levels of matrix metalloproteinases (MMP2 and MMP9), terminal complement complex (C5b-9), and VEGF-A in circulating sEVs in glioblastoma patients (GBMPs) with and without tumor recurrence. Using differential ultracentrifugation, sEVs were isolated from blood samples of GBMPs with no tumor recurrence for over one year (n = 6) and after first relapse (n = 14). The vesicles were characterized and quantified using flow cytometry. In both groups, C5b-9 was predominantly detected on tumor-specific circulating sEVs (glial fibrillary acidic protein (GFAP)-positive sEVs) with high VEGF-A expression, while C5b-9 was significantly less frequent on sEVs with low VEGF-A expression (p < 0.05). GFAP+VEGF+dimMMP2-C5b-9+ vesicles were rarely detected in GBMPs without relapse, suggesting their potential utility as biomarkers for a favorable relapse-free prognosis. In recurrent GBMPs, a positive correlation was observed between GFAP+VEGF+bright MMP2+C5b-9+ sEVs and MGMT gene promoter methylation levels (r = 0.543, p < 0.05). Additionally, a trend toward a negative correlation was found between GFAP+VEGF+bright MMP2+C5b-9- sEVs and mutant p53 expression in primary tumor tissue (r = −0.44, p = 0.114). These findings suggest that sEV profiles may serve as valuable prognostic markers for glioblastoma recurrence and treatment responses.
Glioblastoma is the most frequent and aggressive primary brain tumor. The patient can be alive with this pathology using the modern standard of intensive combined treatment less than 2 years. Between December 2013 and August 2017, 30 patients with newly diagnosed supratentorial glioblastoma had received concomitant chemoradiotherapy with transcranial radiofrequency hyperthermia. The gross total or the subtotal resection of the tumor was made previously in all cases. The median follow-up time after operation achieved 12 months (95% confidence interval (CI): 8.5–23 months) in this study. The median disease-free survival time was 9.6 months (95% CI: 7.2–19.0 months). The median overall survival time of patients included in the study was 23.4 months. No increase in the systemic side effects of chemotherapy was found compared with the frequency described in the population. Preliminary results had shown that the usage of concomitant thermochemoradiotherapy with transcranial radiofrequency hyperthermia improves progression-free survival rates. Overall survival rates also tended to increase. Given the absence of severe complications, it is necessary to continue research to achieve statistically significant results.
Surgical treatment is leading in the treatment of malignant tumors of the salivary glands. The complexity of the anatomical areas, the severity of the tumor process, the close location of the facial nerve branches lead to frequent complications in the postoperative period. The technique of elimination of paresis of mimic muscles with the use of a complex of therapeutic measures, including a course of physiotherapy with the appointment of a magnetolaser and SCENAR therapy developed at the Cancer Research Institute, Tomsk National Research Medical Center of the RAS and the prospect of its use in this pathology. The clinical case of application of this material is described.
В НИИ онкологии Томского НИМЦ разработана методика проведения химиолучевой терапии на фоне локальной электромагнитной гипертермии в составе комбинированного лечения пациентов с впервые выявленными глиобластомами головного мозга. В соответствии с разработанной методикой комбинированное лечение получили 20 пациентов, которым одновременно с проведением химиолучевой терапии с темозоломидом два раза в неделю выполнялась локальная гипертермия (10 сеансов на курс лечения) на системе для глубокой гипертермии Celsius TCS. Все пациенты перенесли лечение удовлетворительно. При оценке профиля токсичности термохимиолучевой терапии с темозоломидом была выявлена высокая частота гематологической и неврологической токсичности. Необходимо отметить, что в рандомизированных исследованиях безопасности проведения химиолучевой терапии с темодалом неврологической токсичности обнаружено не было. Если более высокая частота гематологической токсичности может быть связана с небольшой выборкой пациентов в исследовании, появление неврологической токсичности, вероятно, отражает большее токсическое воздействие химиопрепарата на головной мозг при проведении локальной гипертермии, однако причин возникновения неврологической токсичности во время курсов адъювантной терапии в настоящий момент мы объяснить не можем. Непосредственные результаты термохимиолучевой терапии показали объективный ответ в 70 % случаев, однако частота прогрессирования увеличилась в процессе курсов адъювантной химиотерапии. Одногодичная безрецидивная выживаемость составила 53,3 ± 13,3 %, медиана до прогрессирования – 10,5 мес. Одногодичная общая выживаемость составила 91,7 ± 8 % при медиане наблюдения 9 мес, медиана общей выживаемости не достигнута. Небольшие сроки наблюдения за пациентами в исследовании не позволяют сделать достоверных выводов о влиянии локальной гипертермии на выживаемость пациентов, однако отмечается тенденция к увеличению безрецидивной и общей выживаемости.
22 February 2024 in Russian Journal of Preventive Medicine
Tomsk region is one of the areas with low population density, and the low level of transport accessibility of a number of settlements makes it difficult to organize oncological care. The analysis of posthumously recorded cases of registration of tumors of the central nervous system (CNS) and the search for reserves to reduce this indicator are of interest. Objective. To study the structure of the cohort of posthumously registered patients with primary tumors of the CNS and to evaluate the dynamics in 2011—2021 years. Material and methods. The analysis of cases of posthumously registered neuro-oncological pathology was performed using data from the population-based cancer registry of the Tomsk region for 2011—2021 yrs. and «BARS» medical information system. Results. A comparative analysis of morbidity and mortality in the Tomsk region and the Russian Federation revealed the absence of statistically significant dynamics. The increase of mortality rate from malignant neoplasms (MN) of the central nervous system in the Tomsk region against the background of a decline in this indicator in Russia as a whole, and a high rate of postmortem registration of neuro-oncological pathology compared to the MN of all localizations in the Tomsk region have been noted. There has been a growth in the proportion of postmortem registration of MN of the CNS with increasing age, thus more than a half of cases of neuro-oncological pathology in the 80 years and older age group were registered posthumously. The cerebral tumor caused sudden death in only one third of cases, with one in three patients diagnosed with CNS tumor during lifetime (organizational failure). In the remaining cases, the clinical symptoms and the anamnesis data allowed to suspect of the cerebral tumor before fatal outcome. Conclusion. There is a decrease in the proportion of posthumously recorded cases of malignant neoplasms of the central nervous system in the Tomsk region in the dynamics. In two thirds of cases, postmortem registration of malignant neoplasms of the central nervous system in the population-based cancer registry of the Tomsk Region is due to the lack of adequate routing of patients with tumors of the central nervous system and low neuro-oncological alertness of the general health network’s doctors.