Asessment of the effect of different parameters of radiotherapy on treatment outcomes of infiltrative low-grade glioma (GRADE II)

The purpose of the study was to develop more effective fractionation regimens and radiation therapy programs in the treatment of infiltrative low-grade gliomas (WHO grade II). Material and methods. The study included 53 patients with morphologically verified supratentorial infiltrative low-grade gliomas (WHO grade II). Diffuse astrocytoma was diagnosed in 35 (66 %) patients, oligoastrocytoma in 7 (13 %) patients and oligodendroglioma in 11 (21 %) patients. Results. The overall survival (OS) was influenced by fractionated radiotherapy regimens (conventionally fractionated versus hypofractionated radiotherapy) (p=0.000) and type of radiotherapy (3D conformal versus 2D radiotherapy) (p=0.023). Multivariate analysis showed a statistically significant difference between the equivalent total dose (LQ-model) and OS (p=0.068). Risk factors proposed by the Association of Russian oncologists (p=0.947) and the extent of surgical excision (p=0.423) had no significant impact on the overall survival. Conclusion. Conventionally fractionated radiation therapy (2 Gy per fraction daily) significantly improved the OS compared to hypofractionated radiotherapy (3 Gy per fraction daily). The value of α/β ratio=6.8 Gy can be used to calculate the total dose using a linear-quadratic model

Comparison of matrix proteinase mRNA expression in morphologically normal, neoplastic, andmetastatic colon tissue and colon biopsies from healthy donors

Matrix metalloproteinases (MMPs) responsible for the extracellular matrix remodeling, the activation of various growth factors, and angiogenesis play an important role in the colorectal cancer (CRC) development. In the present work the comparative analysis of MMP-7, -8, -9, and -11 mRNA as well mRNA of the Ki-67 proliferation marker in tissue samples obtained from CRC patients and healthy individuals. Employing the real time PCR method the expression levels of several MMPs (MMP-7, -8, -9, and -11) and cell proliferation marker, Ki-67, were simultaneously measured in 256 tissue samples obtained from 112 patients with CRC: 112 samples of the primary tumor (CRC), 112 samples of the most distant border of morphologically normal colonic mucosa (MNT), 16 samples of liver metastases) and from 16 healthy volunteers who underwent colonoscopy and biopsy. The expression of both MMPs studied and Ki-67 was found to be elevated in CRC primary tumors and liver metastases compared with the normal mucosa. CRC tumor and metastatic cells exhibited similar proliferative activity. The metastases are characterized by the highest cross-correlation of MMPs among tissue types tested. For the first time it was shown that normal mucosa from healthy individuals and CRC patients varied in the MMP-8 expression level. They also had dissimilar MMP correlation patterns thus suggesting that epithelial cells adjusted to CRC tumor differ from mucosal epithelial cells of healthy individuals. © 2018 Russian Academy of Medical Sciences. All rights reserved

Comparison of matrix proteinase mRNA expression in morphologically normal, neoplastic, andmetastatic colon tissue and colon biopsies from healthy donors

Matrix metalloproteinases (MMPs) responsible for the extracellular matrix remodeling, the activation of various growth factors, and angiogenesis play an important role in the colorectal cancer (CRC) development. In the present work the comparative analysis of MMP-7, -8, -9, and -11 mRNA as well mRNA of the Ki-67 proliferation marker in tissue samples obtained from CRC patients and healthy individuals. Employing the real time PCR method the expression levels of several MMPs (MMP-7, -8, -9, and -11) and cell proliferation marker, Ki-67, were simultaneously measured in 256 tissue samples obtained from 112 patients with CRC: 112 samples of the primary tumor (CRC), 112 samples of the most distant border of morphologically normal colonic mucosa (MNT), 16 samples of liver metastases) and from 16 healthy volunteers who underwent colonoscopy and biopsy. The expression of both MMPs studied and Ki-67 was found to be elevated in CRC primary tumors and liver metastases compared with the normal mucosa. CRC tumor and metastatic cells exhibited similar proliferative activity. The metastases are characterized by the highest cross-correlation of MMPs among tissue types tested. For the first time it was shown that normal mucosa from healthy individuals and CRC patients varied in the MMP-8 expression level. They also had dissimilar MMP correlation patterns thus suggesting that epithelial cells adjusted to CRC tumor differ from mucosal epithelial cells of healthy individuals. © 2018 Russian Academy of Medical Sciences. All rights reserved

Влияние объема хирургического вмешательства на результаты лечения инфильтративных глиом низкой степени злокачественности WHO Grade II в зависимости от ряда прогностических факторов

Objectives. Study and analysis of the influence of the degree of primary tumor resection on the results of treatment of infiltrating low-grade gliomas WHO Grade II, depending on various prognostic factors Materials and methods. In total, 107 patients with morphologically verified infiltrative glioma of low grade WHO Grade II were included in the study. Morphological examination revealed 14 patients (13%) with oligoastrocytoma, 36 patients (34%) - with oligodendroglioma, and 57 patients (53%) - with diffuse astrocytoma. The average age of patients was 38.5 years. Non- progressive survival (progression-free survival, PFS) was under study. Results. In patients under 30 years old, radical surgery significantly improved PFS compared to non-radical surgery (test Log Rank p=0.058; test Breslow p=0,036; test Tarone-Ware p=0.037). Radical surgery did not differ by the indices of PFS in patients with diffuse astrocytoma and oligodendroglial tumors (test Log Rank p=0,964; test Breslow p=0,444; test Tarone-Ware p=0,653). Differences between the groups according the NCCN (National Comprehensive Cancer Network) prognostic criteria were significant (test Breslow p=0,015; test Tarone-Ware p=0,036). Conclusion. Within individual prognostic categories, the degree of surgical intervention affects PFS. The NCCN criteria have a high prognostic value for clinical practice.Цель исследования. Изучение и анализ значимости влияния степени хирургической резекции первичной опухоли на результаты лечения у пациентов с супратенториальными инфильтративными глиомами низкой степени злокачественности WHO Grade II в зависимости от различных прогностических факторов. Материалы и методы. В данное исследование включены 107 пациентов с морфологически верифицированной инфильтративной глиомой низкой степени злокачественности WHO Grade II. При проведении морфологического исследования у 14 пациентов (13%) была выявлена олигоастроцитома, у 36 больных (34%) - олигодендроглиома, и у 57 (53%) - диффузная астроцитома. Средний возраст пациентов составил 38,5 лет. Оценка результатов исследования проводилась по показателям беспрогрессивной выживаемости (БПВ). Результаты. У пациентов младше 30 лет радикальное удаление опухоли значимо улучшает показатели БПВ по сравнению с нерадикальным удалением (тест Log Rank р=0,058; тест Breslow р=0,036; тест Tarone-Ware р=0,037). При радикальном хирургическом вмешательстве не было выявлено статистически значимых различий между показателями БПВ пациентов с диффузной астроцитомой и олигодендроглиальными опухолями (тест Log Rank р=0,964; тест Breslow р=0,444; тест Tarone-Ware р=0,653). Различия между группами прогноза NCCN (National Comprehensive Cancer Network / Национальное общество всесторонних исследований рака) были значимыми (тест Breslow р=0,015; тест Tarone-Ware р=0,036). Выводы. Радикальность хирургического вмешательства значимо влияет на показатели БПВ у пациентов отдельных прогностических категорий. Группы прогноза NCCN имеют высокое прогностическое значение для клинической практики

Asessment of the effect of different parameters of radiotherapy on treatment outcomes of infiltrative low-grade glioma (GRADE II)

The purpose of the study was to develop more effective fractionation regimens and radiation therapy programs in the treatment of infiltrative low-grade gliomas (WHO grade II). Material and methods. The study included 53 patients with morphologically verified supratentorial infiltrative low-grade gliomas (WHO grade II). Diffuse astrocytoma was diagnosed in 35 (66 %) patients, oligoastrocytoma in 7 (13 %) patients and oligodendroglioma in 11 (21 %) patients. Results. The overall survival (OS) was influenced by fractionated radiotherapy regimens (conventionally fractionated versus hypofractionated radiotherapy) (p=0.000) and type of radiotherapy (3D conformal versus 2D radiotherapy) (p=0.023). Multivariate analysis showed a statistically significant difference between the equivalent total dose (LQ-model) and OS (p=0.068). Risk factors proposed by the Association of Russian oncologists (p=0.947) and the extent of surgical excision (p=0.423) had no significant impact on the overall survival. Conclusion. Conventionally fractionated radiation therapy (2 Gy per fraction daily) significantly improved the OS compared to hypofractionated radiotherapy (3 Gy per fraction daily). The value of α/β ratio=6.8 Gy can be used to calculate the total dose using a linear-quadratic model

Влияние объема хирургического вмешательства на результаты лечения инфильтративных глиом низкой степени злокачественности WHO Grade II в зависимости от ряда прогностических факторов

Objectives. Study and analysis of the influence of the degree of primary tumor resection on the results of treatment of infiltrating low-grade gliomas WHO Grade II, depending on various prognostic factors Materials and methods. In total, 107 patients with morphologically verified infiltrative glioma of low grade WHO Grade II were included in the study. Morphological examination revealed 14 patients (13%) with oligoastrocytoma, 36 patients (34%) - with oligodendroglioma, and 57 patients (53%) - with diffuse astrocytoma. The average age of patients was 38.5 years. Non- progressive survival (progression-free survival, PFS) was under study. Results. In patients under 30 years old, radical surgery significantly improved PFS compared to non-radical surgery (test Log Rank p=0.058; test Breslow p=0,036; test Tarone-Ware p=0.037). Radical surgery did not differ by the indices of PFS in patients with diffuse astrocytoma and oligodendroglial tumors (test Log Rank p=0,964; test Breslow p=0,444; test Tarone-Ware p=0,653). Differences between the groups according the NCCN (National Comprehensive Cancer Network) prognostic criteria were significant (test Breslow p=0,015; test Tarone-Ware p=0,036). Conclusion. Within individual prognostic categories, the degree of surgical intervention affects PFS. The NCCN criteria have a high prognostic value for clinical practice.Цель исследования. Изучение и анализ значимости влияния степени хирургической резекции первичной опухоли на результаты лечения у пациентов с супратенториальными инфильтративными глиомами низкой степени злокачественности WHO Grade II в зависимости от различных прогностических факторов. Материалы и методы. В данное исследование включены 107 пациентов с морфологически верифицированной инфильтративной глиомой низкой степени злокачественности WHO Grade II. При проведении морфологического исследования у 14 пациентов (13%) была выявлена олигоастроцитома, у 36 больных (34%) - олигодендроглиома, и у 57 (53%) - диффузная астроцитома. Средний возраст пациентов составил 38,5 лет. Оценка результатов исследования проводилась по показателям беспрогрессивной выживаемости (БПВ). Результаты. У пациентов младше 30 лет радикальное удаление опухоли значимо улучшает показатели БПВ по сравнению с нерадикальным удалением (тест Log Rank р=0,058; тест Breslow р=0,036; тест Tarone-Ware р=0,037). При радикальном хирургическом вмешательстве не было выявлено статистически значимых различий между показателями БПВ пациентов с диффузной астроцитомой и олигодендроглиальными опухолями (тест Log Rank р=0,964; тест Breslow р=0,444; тест Tarone-Ware р=0,653). Различия между группами прогноза NCCN (National Comprehensive Cancer Network / Национальное общество всесторонних исследований рака) были значимыми (тест Breslow р=0,015; тест Tarone-Ware р=0,036). Выводы. Радикальность хирургического вмешательства значимо влияет на показатели БПВ у пациентов отдельных прогностических категорий. Группы прогноза NCCN имеют высокое прогностическое значение для клинической практики

СОПОСТАВИТЕЛЬНЫЙ АНАЛИЗ МОЛЕКУЛЯРНО-ГЕНЕТИЧЕСКИХ ХАРАКТЕРИСТИК ПЕРВИЧНОГО ОПУХОЛЕВОГО ОЧАГА И МЕТАСТАТИЧЕСКИХ ЛИМФАТИЧЕСКИХ УЗЛОВ ПРИ РАКЕ МОЛОЧНОЙ ЖЕЛЕЗЫ

The purpose of systemic treatment in patients with breast cancer is based largely on the molecular characteristics of the primary tumor, but many clinical recommendations suggest also the study of metastatic nodes with an assessment of their receptor status (estrogen receptor ER, progesterone receptor RP, human epidermal growth factor receptor 2 Her2/neu). This is due to the fact that according to numerous studies, the discrepancy between the status of the primary tumor and the secondary nodes can reach high rates: 3-54 % for ER, 5-78 % for RP, and 0-34 % for Her2/neu. At the same time, more and more data actively demonstrate the imperfection of immunohistochemical analysis and the need to study additional parameters to improve the quality of diagnosis of patients with breast cancer. Material and methods. A morphological and immunohistochemical study of the tumor tissue of the primary node and axillary lymph nodes was performed in 199 patients with breast cancer (T1-3N0-3M0) using standard methods, and RT-PCR was also studied with the expression of 24 genes. Results. The incidence of differences between the molecular phenotypes of the main tumor and metastatic axillary lymph nodes was 26 (26 %) of 99 cases. Most often, differences were noted in cases of breast cancer with luminal A type - 13 cases (50 %). According to the results of a comparative PCR analysis of tissue samples from the primary tumor and metastatic regional lymph nodes, only the expression of the CD68, ERSR1, GRB7 and MMD11 receptors was statistically significant. Conclusion. The results indicate the need for an integrated approach and additional methods for the diagnosis of breast cancer, which will undoubtedly improve the quality of planning and the effectiveness of systemic treatment in patients with breast cancer.Назначение системного лечения у больных раком молочной железы (РМЖ) основано в большей степени на молекулярных характеристиках первичной опухоли, однако многие клинические рекомендации предлагают исследование также метастатических очагов с оценкой их рецепторного статуса (рецепторов эстрогена (РЭ), рецепторов прогестерона (РП), рецепторов эпидермального фактора роста человека Her2/neu). Это обусловлено тем, что по данным многочисленных исследований несоответствие статуса первичной опухоли и вторичных узлов может достигать высоких показателей: 3-54 % для РЭ, 5-78 % для РП и 0-34 % для Her2/neu. В то же время все больше данных свидетельствуют о несовершенстве иммуногистохимического анализа и необходимости изучения дополнительных параметров для повышения качества диагностики больных РМЖ. Материал и методы. Выполнялось морфологическое и иммуногистохимическое изучение опухолевой ткани первичного узла и аксиллярных лимфатических узлов у 199 больных РМЖ (T1-3N0-3M0) по стандартным методикам, также проводилось исследование методом ПЦР с обратной транскрипцией с выявлением экспрессии 24 генов. Результаты. Частота различий молекулярных фенотипов основного опухолевого и пораженных аксиллярных лимфатических узлов составила 26 (26 %) из 99 случаев. Наиболее часто различия отмечались в случаях РМЖ с люминальным типом А - 13 случаев (50 %). По результатам сравнительного ПЦР-анализа опухолевой ткани основного опухолевого узла и пораженных регионарных лимфатических узлов статистически значимыми являлась лишь экспрессия рецепторов CD68, ERSR1, GRB7 и MMD11. Заключение. Полученные результаты свидетельствуют о необходимости комплексного подхода и проведения дополнительных методов диагностики РМЖ, что, несомненно, повысит качество планирования и эффективность системного лечения у больных РМЖ