Vol 19, No 2 (2017)


The treatment of patients with advanced lung cancer associated with EGFR mutation

Bolotina L.V.


In this article we produce present practice in treatment of advanced stages of non-small cell lung cancer with activating mutations in EGFR genes. Describe opportunities of effective using of target agents in these cases. There are notions about mechanisms of resistance for target therapy, and demonstrate different approach in this field.
Journal of Modern Oncology. 2017;19(2):5-9
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PARP inhibitors in female reproductive system cancers

Pokataev I.A., Tyulyandin S.A.


PARP-1 and PARP-2 enzymes are one of six known DNA damage repair systems - nitrogenous base excision repair. PARP inhibitor disrupts excision repair and under the conditions of the absence of another pathway of DNA damage repair (homologous recombination) can cause apoptosis in tumor cells. One of the most frequent causes of defects in homologous recombination is the loss of BRCA1 or BRCA2 function by means of inactivated mutations. It makes PARP-inhibitors the most effective in the treatment of tumors associated with BRCA germline and somatic mutations. This paper discusses the differences of PARP inhibitors (olaparib, niraparib, veliparib, rucaparib and talazoparib), the results of their clinical trials for female reproductive system cancers, toxicity of PARP inhibitors as monotherapy or in combination with cytotoxic drugs, as well as the registration of these products in Russia and in other countries.
Journal of Modern Oncology. 2017;19(2):10-15
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Experience of the usage intraoperative radiation therapy after neoadjuvant systemic drug treatment and sentinel lymph node biopsy in breast cancer patients with clinical stage T2N0M0

Manikhas A.G., Grinev I.A., Oganesian A.S., Chikrizov S.I., Manikhas G.M.


Relevance. Breast cancer is the leading oncological disease among female population. In some cases, clinical stage T2N0M0 is contraindication to breast-concerving surgery due to a big size of the primary tumor. Mastectomy is an optimal surgery in this situation. However, removal of the breast is a serious psychological trauma for the patient, causing quality of life decrease. Attempting to perform breast-conserving surgery is quite logical. Due to this we investigated a method of complex treatment of breast cancer using intraoperative radiation therapy, sentinel lymph node biopsy and neoadjuvant systemic drug therapy. Goal: the main goal is to improve the results of early breast cancer treatment, through the introduction into clinical practice of the original method of complex treatment. Materials and methods. 101 patients treated in the State clinical oncology department of St. Petersburg in the period from 2014 to 2016 were included in the study. The main inclusion criteria was a clinical stage T2N0M0. All the patients are not the candidates for breast - conserving surgery. In the experience group were patients (n=51) who received treatment on the method studied. 50 patients were randomized to the control group, where the mastectomy was performed. In the experience group late toxicity was evaluated after radiosurgery using modified LENT-SOMA scale. Quality of life was assessed by questionnaire QLQ-C30 in both groups. Results. 49 (96%) patients of the experience group were treated by breast-conserving surgery (lumpectomy with intraoperative radiation) due to clinical and radiological tumor response to neoadjuvant therapy. After systemic therapy 10 (20%) women were performed axillary lymph node dissection. Quality of life in the experience group was significantly higher. Late toxicity was not significant after application of intraoperative and whole breast radiotherapy. Conclusion. The investigated method of a complex treatment of early breast cancer is safe and effective and is able to provide the same control of locoregional recurrence as modified radical mastectomy. However, the proposed method provides a statistically significant better quality of life.
Journal of Modern Oncology. 2017;19(2):16-21
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Internal mammary nodes metastases for breast cancer: whether the morphological verification is necessary?

Trigolosov A.V., Uimanov V.A., Chernikh M.V., Petrovskiy A.V., Nikitina E.A., Nechushkin M.I.


Background. Metastatic involvement of the internal mammary chain lymph nodes (IMN) is associated with poor prognosis for breast cancer (BC) patients. However, parasternal radiation therapy is still a subject for debate. Methods. Results of 1144 consecutively treated patients with primary BC, who underwent one-stage videothoracoscopic (VATS) parasternal lymphadenectomy from 1998 to 2009, were retrospectively studied. Results. Surgical complications associated with thoracoscopic procedure did not exceed 2%. IMN metastases were detected in 211 (18.4%) patients, 6.0% of these cases did not have axillary invasion. In a wide analysis, the frequency of metastasis was statistically more influenced by: tumor localization (different from external quadrants), primary tumor size (T), level of involved axillary lymph nodes (N) and lymphovascular invasion. Patients with IMN metastases showed significantly poorer long-term outcomes: 5-year overall - OS and disease-free survival - DFS (OS 79.0±3.1% vs 91.4±1.0%, p<0.001; DFS 69.0±3.4% vs 86.0±1.2%, p<0.001, respectively) both in the whole group and in the subgroups with and without axillary lymph node metastases. IMN metastases along with tumor size and axillary nodes showed a negative independent prognostic influence on the DFS and OS (hazard ratio 2.24 [1.45-3.46]; 2.50 [1.41-4.43], respectively). Conclusions. IMN status is an important criterion which may influence on the prognosis and adjuvant treatment strategy in BC. Our study is in favor of conducting randomized clinical studies supporting the impact of radiotherapy treatment for involved IMN.
Journal of Modern Oncology. 2017;19(2):22-27
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Perspectives of pharmacogenetics approach to personalized tamoxifen therapy

Savelyeva M.I., Ignatova A.K., Panchenko Y.S., Urvantseva I.A., Poddubnaya I.V.


Tamoxifen is a selective modulator of estrogen receptors and is widely used in receptor-a-positive breast cancer treatment. Adjuvant tamoxifen treatment substantially reduces breast cancer relapse and mortality rates. However, high interindividual variability in response is observed. One of the causes of this variability may be genetic polymorphisms of the cytochrome P450 (CYP) enzymes, which are responsible for the formation of tamoxifen active metabolites. Polymorphisms of genes encoding the enzymes with decreased or absent activity could be associated with lower tamoxifen active metabolites concentration in serum and consequently reduce the effectiveness of treatment. Pharmacogenetic approach is a promising tool of personalized medicine and may help personolize pharmacotherapy of breast cancer in the future. Throughout this review we analyze the up-to-date information on the influence of the gene CYP2C19 polymorphisms that they have on pharmacokinetic and pharmacodynamic of tamoxifen.
Journal of Modern Oncology. 2017;19(2):28-32
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Brachytherapy with ultrasound assistance in patients with cervical cancer

Kizhaev Y.E., Razumova E.L., Bessolova O.V.


Main risk factors of uterine perforation during tandem placement are demonstrated in patients with cervical cancer after EBRT in our study. We show tendency to co-existence of more than one of risk factors. Real-time ultrasound assistance of tandem placement allowed us to avoid injury in all cases.
Journal of Modern Oncology. 2017;19(2):33-36
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Clinico-morphological predictors and treatment outcomes in cervical stump cancer

Usmanova L.S., Kuznetsov V.V., Mustafina E.A., Barinov V.V., Bokin I.I., Knyazev R.I., Akhmedova M.D.


The aim of the study is to analyze the characteristics of cervical stump cancer (CSC), identify the clinical and morphological factors influencing prognosis of the disease. Another aim is to study the results of CSC treatment according to the predictive factors. Materials and methods. We have analyzed the treatment results of 150 patients with FIGO stage 0-IIIB metastatic CSC (mCSC). Patients were treated in N.N.Blokhin Russian Cancer Research Center, over the period from 1977 to 2010. Results. We showed that statistically significant predictive factors of mCSC were regional lymph node metastases, stromal invasion greater than 1 cm in depth, stage of disease, the mixed form of tumor growth and the presence of lymph vessel tumor emboli. We also identified that the survival of the patients with histologically verified adenocarcinoma and with the spread of the tumor to the cervical stump was poor. Conclusion. We showed that the risk factors in case of mCSC were the same as in case of cervical cancer.
Journal of Modern Oncology. 2017;19(2):37-41
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Using of multi-kinase inhibitor regorafenib for metastatic colorectal cancer

Kit O.I., Vladimirova L.Y., Abramova N.A., Storozhakova A.E., Popova I.L., Tikhanovskaya N.M., Lyaynova A.A., Ryadinskaya L.A.


The data of the efficacy and safety regorafenib in the treatment of 7 patients with metastatic colorectal cancer (mCRC) refractory to treatment with cytostatics and monoclonal antibodies - blockers EGFR and VEGF were analyzed. The maximum anti-tumor effect in 1 patient had partial remission, in 6 - stabilization. The duration of progression-free period from start of treatment regorafenib ranged from 1.5 to 6 months. 3 patients continued antitumor therapy after progression, 3 - had the symptomatic therapy after progression, 1 - had stabilization within 4 months and continued therapy of regorafenib. Toxic effects of therapy were nausea, vomiting, diarrhea, complications of the skin, temperature reaction, increased blood pressure, dysphonia. The most clinically significant adverse events were changes in laboratory parameters in 3 patients (increase of ALT, AST and bilirubin), that resulted an interruption in the treatment and correction of the dose. The use of regorafenib in mCRC ensure adequate tumor control, and is characterized by mild toxicity that is relevant for pretreated patients resistant to other forms of anticancer therapy.
Journal of Modern Oncology. 2017;19(2):42-46
pages 42-46 views

Hyperthermia is an additional option in the treatment of squamous cell cancer of the anal canal

Glebovskaya V.V., Tkachev S.I., Ivanov S.M., Nazarenko A.V., Rasulov A.O., Gordeev S.S., Bulychkin P.V., Besova N.S., Barsukov U.A., Trofimova O.P., Borisova T.N., Timoshkina E.V.


Purpose: to estimate the rate of locoregional recurrence and distant metastases, and the grade of chemoradiotherapy toxicity when in combination with local hyperthermia for treating squamous cell anal canal cancer T1-4N0,1-3M0-1. Materials and methods. 112 patients with squamous cell anal canal cancer were treated between 2011 and 2015 with chemotherapy, radiation therapy based on 3D CRT, intensity-modulated radiation therapy (IMRT) and volumetric intensity modulated arc therapy (VMAT), and local hypothermia. Staging was based on TNM (7th edition): I - 4 (3.6%) patients, II - 39 (34.8%) patients; IIIA - 33 (29.5%) patients, IIIB - 34 (30.3%) patients and IV - 2 (1.8%) patients. The median of mean follow-up was 32 months (range, 3-63 months). Local hyperthermia was performed in 81 (72.3%) patients. Results. 2-year local control was 73.2%. All recurrences, no matter which chemotherapy was performed, were in patients with advanced disease (IIIA/IIIB stages), from which 22.2% relapses were in group without local hyperthermia vs. 4.7% in group with radiomodification, p=0.038. Distant metastases were found in 9.4% patients with hyperthermia and in 11.1% patients without radiomodification, p=1. Usage of local hyperthermia is associated with increase II grade of dermatological toxicity (p=0.056). Conclusion. The combination of local hyperthermia and modern technologies of conformal radiation therapy has influenced the decrease of locoregional recurrences, but it is associated with lack of influence on distant metastases appearance regardless on chemotherapy regimen.
Journal of Modern Oncology. 2017;19(2):48-52
pages 48-52 views

Targeted therapy in pediatric malignancies treatment: Pediatric Oncology and Haematology Research Institute experience

Valiev T.T., Levashov A.S., Batmanova N.A., Senzhapova E.R., Turupaev K.A., Tomchik U.V., Aleskerova G.A.


Actually targeted drugs became a therapeutic component for adult patients with malignancies and merge into clinical therapeutic recommendations. Targeted drugs in pediatric oncology had been using for 10-15 years and this experience under systematization and analysis. In the current issue 12-year experience of targeted therapy of Pediatric Oncology and Haematology Research Institute of N.N.Blokhin National Cancer Research Center is presented. Authors estimated efficacy and toxicity of rituximab, bortezomib, sorafenib and everolimus in 108 patients with advanced stages of mature B-cell non-Hodgkins lymphomas (B-NHL), relapsed/refractory acute lymphoblastic leukemia (ALL) and refractory osteosarcoma. Rituximab plus standard chemotherapy of advanced stages of B-NHL increased 10-years event-free survival up to 93.8±3%. Bortezomib plus anti-relapsed chemotherapy protocol (COG AALL07P1) reached minimal residual disease - negative status in 64.3% patients, but relapse-free survival was 24.5±19.4% (median 28±3.3 months). Sorafenib and everolimus were used for refractory osteosarcoma treatment, response rate was 100%, progression-free survival more than 6 months was 46% (median follow up 7±1.2 months). Toxicity profile was acceptable.Our data demonstrate a fact of significant improvement of advanced stages B-NHL treatment results by rituximab use, but relapsed/refractory ALL and osteosarcoma need treatment improvement.
Journal of Modern Oncology. 2017;19(2):54-60
pages 54-60 views

Interferon α (IFN-α) vs. the combination IFN-α and octreotide LAR in the treatment of patients with well differentiated neuroendocrine tumors (NET) of various localizations

Yemelyanova G.S., Kuzminov A.E., Orel N.F., Markovich A.A., Kuznetsova A.A., Gorbunova V.A.


It is still unknown whether the combination of IFN-α with octreotide has benefit compared with IFN-α alone. We compared efficacy and toxicyty of IFN-α and IFN-α plus octreotide in first line of therapy of patients with NETs. There was trend to longer TTP in lung NETs pts comparing with GEP NETs pts treated with IFN-α. IFN-α may be a therapy of choice in pts with well differentiated lung NETs as first line treatment. IFN-α have a similar toxicity profile comparing with IFN-α combined with octreotide.
Journal of Modern Oncology. 2017;19(2):61-65
pages 61-65 views

The application of oral transmucosal fentanyl for the treatment of breakthrough pain in cancer patients

Nevzorova D.V., Kunyaeva T.A., Ibragimov A.N.


This review focuses on the modern treatment of breakthrough pain in cancer patients with the application of transmucosal fentanyl. Pain is one of the most common and severe problem that is significantly worse the quality of life of cancer patients. The prevalence of pain in this population is estimated to be high and increases with disease progression. For about 80% of cancer patients experience chronic pain. The separate problem of the cancer pain treatment is so-called treatment of breakthrough pain.
Journal of Modern Oncology. 2017;19(2):66-71
pages 66-71 views

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