ROLE OF TARGETED THERAPY IN THE COMBINATION TREATMENT OF PATIENTS WITH KIDNEY CANCER AND METASTATIC BRAIN INVOLVEMENT

In patients with kidney cancer (KC), the rate of metastatic brain involvement is 2-11%, is steadily growing, and is one of the important reasons for treatment failures in these patients. Surgery and radiotherapy, including radiosurgery, must be considered as optimal treatments for patients with KC and brain metastases. Systemic drug therapy has recently played a more and more increasing role in the treatment of patients with a progressive brain tumor process. At the same time, there are no exact pharmacokinetic data on drugs registered for the treatment of disseminated KC in respect to their concentration in the human central nervous when they are used in therapeutic doses. On the basis of the data of the literature review and the results of the authors’ studies, it may be concluded that while none of the target agents has still shown any significant advantage over others in treating KC patients with brain metastases. All the drugs have demonstrated their ability to achieve a clinical and X-ray verified objective effect (as stabilizations in most cases) in treating brain metastases. The most data are available on the therapeutic efficacy of sunitinib and sorafenib. In case of progressive brain tumor process, drug treatment should be individually discussed in each situation in accordance with standard approaches to treating patients with disseminated KC

СRANIAL AND INTRACRANIAL METASTASES OF THYROID CANCER

Thyroid cancer metastasis to the brain is rare and little-studied pathology. Problems of their diagnosis and treatment remain to be solved. Features of this group is a metastatic lesion of the brain and bones of the cranial vault with extra- and intracranial growth. The paper details the clinical picture, X-ray, morphological diagnosis and treatment of patients with intracranial metastases thyroid cancer

COMBINED CHEMOTHERAPY INCLUDING PROCARBAZINE (NATULAN) IN THE TREATMENT OF ANAPLASTIC OLIGODENDROGLIOMAS

Our investigation has demonstrated the high efficiency of combined chemotherapy (CT) including procarbazine + lomustine or procarbazine + lomustine + vincristine in patients with anaplastic oligodendrogliomas. Postoperative CT has been recently recommended for patients with deletion of chromosomes 1p and 19q, by taking into account the good prognosis of a therapeutic effect, better parameters of time till progression in this patient group, and a risk for cognitive impairments after brain radiotherapy

ХИРУРГИЧЕСКИЙ ЭТАП В КОМПЛЕКСНОМ ЛЕЧЕНИИ ПАЦИЕНТОК С ЦЕРЕБРАЛЬНЫМИ МЕТАСТАЗАМИ РАКА МОЛОЧНОЙ ЖЕЛЕЗЫ

Brain metastases of breast cancer are severe complication of oncological process. Despite the spreading of the process, many patients receive treatment and live for years in contrast to patients with cerebral metastases of other cancers (lung cancer, melanoma, renal cell carcinoma). At different stages of metastatic disease in these patients may be offered different types of treatment: chemotherapy, hormonal therapy, targeted therapy, radiotherapy, radiosurgery, surgical treatment. However, there are no standards that define the indications for surgical treatment of cerebral metastases of breast cancer. This article describes the surgical techniques and defines indications and contraindications for surgical treatment.Церебральные метастазы рака молочной железы являются грозным осложнением онкологического процесса. Несмотря на диссеминацию процесса многие пациентки живут и получают лечение годами, в отличие от пациентов с церебральными метастазами других злокачествен- ных опухолей (рак легкого, меланома, почечноклеточный рак). И на разных этапах метастатической болезни этим пациенткам могут быть предложены различные виды лечения: химиотерапия, гормонотерапия, таргетная терапия, лучевая терапия, радиохирургия, хирургическое лечение. Однако стандартов определяющих показания к хирургическому лечения при церебральных метастазах рака молочной железы в настоящее время нет. В статье описываются хирургические методики, определяются показания и противопоказания к хирургическому лечению

ЛЕКАРСТВЕННАЯ ТЕРАПИЯ БОЛЬНЫХ РАКОМ МОЛОЧНОЙ ЖЕЛЕЗЫ C МЕТАСТАТИЧЕСКИМ ПОРАЖЕНИЕМ ГОЛОВНОГО МОЗГА

The Blokhin RCRC the effectiveness of various schemes of drug therapy in breast cancer patients with brain metastases was evaluated.When using the schemes with anthracyclines (CAF, AC) among 26 patients objective response in the brain (full and partial regression) was registered in 16 (62%) patients (previously untreated patients). Median survival was 12 months. In the group of patients received monotherapy (30 patients), capecitabine was administered at a dose of 2000 mg/m2/day per os the 1 to 14 days every 3 weeks. Partial effect in the brain was registered in 9 patients (30%). Median survival was 15.1 months. In the combination therapy group (capecitabine + radiotherapy) among 30 patients overall effect in the brain was registered in 4 patients (13%), partial response - 18 (60%). Median survival was 22 months. The effectiveness of chemotherapy scheme gemcitabine and cisplatin in 30 breast cancer patients with metastases in the brain, previously treated with I-III line of chemotherapy and radiation therapy in the area of the brain was evaluated. In 4 cases (13.3%) complete regression of metastases in the brain was achieved. In 12 patients (40.0%) a partial regression of metastases in the brain was achieved. Median survival was 10 months. Twenty-three breast cancer patients with overexpression of Her2/neu, and with metastatic brain lesions received capecitabine + lapatinib. Complete response in the brain was achieved in 2 cases (8.7%), partial regression - in 9 cases (39.1%) and stabilization of the disease - in 10 cases (43.5%). Median overall survival was 16 months. Nine patients with breast cancer with overexpression of Her2/neu, and with metastatic brain lesions received therapy with capecitabine + trastuzumab. In 2 cases (22.2%) complete regression of metastases in the brain was achieved, in 4 cases (44.4%) - partial response, in 2 cases (22.2%) - stabilization. The median overall survival was 15.5 months.Thus, the results of this study have shown high efficiency of drug therapy in the treatment of breast cancer patients with metastases in the brain.В РОНЦ им Н. Н. Блохина РАМН изучалась эффективность  различных схем лекарственной  терапии у больных с метастазами рака молочной железы в головном мозге.При применении схем с антрациклинами (CAF, AC) у 26 больных объективный эффект в мозге (полные и частичные регрессии) зарегистрирован  у 16 (62%) пациенток (ранее нелеченые больные). Медиана выживаемости больных составила 12 месяцев. В группе пациентов, получавших монотерапию (30 человек), капецитабин назначался  в дозе 2000 мг/м2/сутки внутрь с 1 по 14 дни, каждые 3 недели.  Частичный эффект в головном мозге зарегистрирован  у 9 пациенток (30%). Медиана выживаемости составила 15,1 месяца. В группе комбинированной  терапии (капецитабин + лучевая терапия) из 30 пациентов полный эффект в головном мозге зарегистрирован у 4 пациенток (13%), частичный эффект — у 18 (60%). Медиана выживаемости составила 22 месяца. Проводилось исследование  по изучению эффективности химиотерапии по схеме гемцитабин + цисплатин у 30 больных раком молочной железы с метастазами в головном мозге,  ранее  получавших I–III линии химиотерапии  и лучевую терапию на область головного мозга. В 4 случаях (13,3%) достигнута полная регрессия  метастазов в головном мозге. У 12 больных (40,0%) достигнута частичная регрессия  метастазов в головном мозге. Медиана общей выживаемости составила 10 мес. 23 больным раком молочной железы с гиперэкспрессией Her-2/neu и c метастатическим поражением головного мозга проводилась терапия по схеме капецитабин + лапатиниб.  В 2 случаях (8,7%) достигнута полная регрессия  в головном мозге, в 9 случаях (39,1%) — частичная регрессия, в 10 случаях (43,5%) — стабилизация болезни. Медиана общей выживаемости составила 16 месяцев. 9 больным раком молочной железы с гиперэкспрессией Her-2/neu и c метастатическим поражением головного мозга проводилась терапия по схеме капецитабин + трастузумаб.  В 2 случаях (22,2%) зарегистрирована  полная регрессия  метастазов в головном мозге, в 4 случаях (44,4%) — частичная регрессия,  в 2 случаях (22,2%) — стабилизация. Медиана общей выживаемости составила 15,5 месяцев.Таким образом,  результаты проведенных исследований показали высокую эффективность лекарственной терапии в лечении больных раком молочной железы с метастазами в головном мозге

Process Mining for Six Sigma

Process mining offers a set of techniques for gaining data-based insights into business processes from event logs. The literature acknowledges the potential benefits of using process mining techniques in Six Sigma-based process improvement initiatives. However, a guideline that is explicitly dedicated on how process mining can be systematically used in Six Sigma initiatives is lacking. To address this gap, the Process Mining for Six Sigma (PMSS) guideline has been developed to support organizations in systematically using process mining techniques aligned with the DMAIC (Define-Measure-Analyze-Improve-Control) model of Six Sigma. Following a design science research methodology, PMSS and its tool support have been developed iteratively in close collaboration with experts in Six Sigma and process mining, and evaluated by means of focus groups, demonstrations and interviews with industry experts. The results of the evaluations indicate that PMSS is useful as a guideline to support Six Sigma-based process improvement activities. It offers a structured guideline for practitioners by extending the DMAIC-based standard operating procedure. PMSS can help increasing the efficiency and effectiveness of Six Sigma-based process improving efforts. This work extends the body of knowledge in the fields of process mining and Six Sigma, and helps closing the gap between them. Hence, it contributes to the broad field of quality management

SURGERY FOR TUMORS OF THE FOURTH VENTRICLE: THE CHARACTERISTICS OF ACCESSES AND THE ROLE OF ENDOSCOPIC TECHNIQUES

The use of current accesses to the tumors of the fourth ventricle, which fill and compress from the outside its cavity, was assessed in 28 patients. Original associated endomicrosurgical techniques were used. Two groups and five topographic types of fourth ventricle tumors are identified. Basic accesses — telovelar and supracerebellar — eliminate the necessity of dissecting the vermis cerebelli. The key endoscopic technique is to provide a simultaneous survey of the lower and upper poles of a tumor during its removal. The technique of trochlear removal of metastatic nodes from the fourth ventricle is shown. The benefits of endoscopic techniques are to early examine the vulnerable vascular and neural structures blocked by a tumor at the access step; to reduce the volume of an access itself and the traction of cerebellar and truncal structures; to completely survey the Sylvian aqueduct without additionally displacing or dissecting the vermis cerebelli; to maintain optical sharpness within sight of differently remote microstructures. Overall, incorporation of the endoscopic method realizes the principle of mini-invasive neurosurgery

Treatment of patients with brain metastases from ovarian cancer: clinical observation

The capacity of drugs to penetrate across the blood-brain barrier (BBB) is primarily traditionally taken into account on choosing chemotherapy (CT) regimens for patients with brain metastatic involvement. P aclitaxel and carboplatin have a low ability to cross the BBB in its normal state. As of now, there is experimental and clinical evidence for BBB dysfunction in brain metastases. The described case serves as another evidence for the successful application of standard approaches to choosing CT regimens for patients with platinum-susceptible recurrent ovarian cancer when the disease recurs and progresses as brain metastatic involvement. The authors also show the effe ctive use of combination treatment: CT in combination with radiation treatments (stereotactic radiosurgery and conventional whole brain radiotherapy) with complete tumor regression being achieved in a patient with ovarian cancer and brain metastatic involvement

Cerebral metastases of endometrial carcinoma. Diagnostic and neurosurgical aspects

Central nervous system (CNS) involvement by endometrial carcinoma is uncommon. Among 1710 patients registered for brain metastases at our institution between 1990 and 2012, 3 (0.18 %) developed brain metastases. All lesions (1 multiple, 2 single) were contrast enhancing on com- puted tomography scans, and were located in the cerebrum (lobus occipitalis) in 2 cases. The CNS was the only site of detectable disease in 1 patient with recurrent disease. One patient received radiotherapy (survival, 3 months) and two underwent surgical resection of solitary metas- tasis followed by radiotherapy (survival = 3 and 5 months and alive to the present). Prognosis of patients with CNS metastases from endometrial carcinoma appears poor; however, in a selected group of patients early diagnosis followed by multimodal treatment may result in a palliation of the disease

Neurosurgical interventions in patients with disseminated solid tumors and poor prognosis

The treatment tactics of patients with cerebral metastases of various solid tumors in the brain currently does not have a accurate determination. This article presents a discussion of the choice of treatment options for patients with cerebral metastases of solid tumors. Discussexistingrecommendations,identifies controversies