№76. Critical view on the development of oncology in the last 20 years

Early diagnostic algorithms for prostate cancer has been dramatically changed
for the last 20 years: from massive screening to individual risk-adapted strategy for
well-informed patients in high risk group with estimated life expectancy 10–15 years.
Utilization of modern PSA isoforms, new biological markers and mpMRI help to
avoid unnecessary biopsies, overdiagnosis of clinically insignificant PCa and adverse
outcomes of unreasonable treatment.

Keywords: prostate cancer, screening, prostate-specific antigen (PSA), prostate health index, multiparameter magnetic-resonance tomography (mpMRI), biomarkers (Select MDX, HOXX6, DLX1), genetic mutations (BRCA1/2, HOXB13).

Adjuvant chemotherapy is currently one of the most important «tools» in the treatment of many malignant tumors. However, if in the treatment of certain diseases its role and effectiveness is clear and understandable (breast cancer, colorectal cancer, melanoma, sarcomas), then for other pathologies, such as soft tissue sarcomas, its effectiveness and appropriateness is unproven. Currently, there is an active study and improvement of the regimens for the use of adjuvant chemotherapy for certain tumors, as well as the decision of the question of whether it should be used in others.

Keywords: adjuvant chemotherapy, breast cancer, colorectal cancer, melanoma, sarcoma.

This article critically reviews twenty years’ experience of targeted therapy use for the treatment of solid tumors. Resistance mechanisms, predictive biomarkers and inter-tumor differences in targeted therapy efficacy are discussed. Data for pros and cons of the use of modern multigene panels in routine practice to personify therapy are critically
reviewed.

Keywords: targeted therapy, precision medicine, tyrosine kinase inhibitor, biomarker, oncology; review.

Bevacizumab was the first antiangiogenic targeted drug, which was approved in 2004 in metastatic colorectal cancer patients. During the next 14 years antiangiogenic therapy became the integral part of the routine clinical practice for the treatment of several cancers. However, for these years the conception of the anticancer activity of antiangiogenic drugs was changed, a lot of study with negative result was published as for metastatic cancer and adjuvant settings. Several mechanisms of resistance for antiangiogenic therapy were discovered. All these data demand of detailed critical investigation for determination of genuine opportunities and perspectives of antiangiogenic therapy in oncology.

Keywords: antiangiogenic therapy, bevacizumab, resistance, biomarkers.

The emergence of novel immunotherapeutic approaches for the treatment of
cancer produced a revolution in oncology during past decade. Check-point inhibitors
were shown to be active against the wide range of malignancies and most significantly
to be able to generate long-lasting responses and probably cure in some patients with advanced disease. These data inspired hope in cancer patients and physicians for the victory in the war against cancer in
the near future. However it appeared clear that immunotherapy is not a panacea and is active only in a subset of cancer patients. Moreover in some settings immunotherapy shows inferior results compared to standard chemotherapy and possibly can even make harm. In this paper the positive and negative features of immunotherapeutic approaches for cancer treatment are overviewed. Also hypothetical limits of immunotherapy effectiveness in the future and the current place in cancer treatment practice
are discussed.

Keywords: cancer immunotherapy, effectiveness, toxicity, hyperprogression, predictive biomarkers.

Surgical pathology is the most important practical and scientific tool that
solves the diagnostic problems of many specialists. The rules for surgical pathology
diagnostic are regulated. Implementation of traditional histopathology examinaton
is a criterion of the quality of medical care. The use of modern diagnostic criteria and
molecular markers has shown that histotypes of tumors can demonstrate a spectrum
of morphological variations. The discovery of new information on the variations of
DNA, RNA, proteins, and the epigenome characteristics of many types of tumors has led to the creation of new molecular classifications. Molecular diagnostics no longer represents a single test performed
during a primary examination. Modern therapy involves monitoring the characteristics of tumor clones throughout all stages of medical care. Integration of genetics with classical morphology led to the emergence of a new discipline – molecular pathology.

Keywords: molecular pathology, molecular diagnostic, pathology

This article presents the immediate results of neoadjuvant systemic cytotoxic therapy in patients with hereditary breast cancer

Material and methods. In our study, a comparative analysis of the efficacy of non-adjuvant polychemotherapy in
accordance with the molecular biological characteristics of 266 patients with locally advanced breast cancer T2-3N1-2M0
was performed in 45 of which the tumor was associated with a mutation in the BRCA1, CHEK2 or BLM genes.
Results. The complete pathological response in the group of hereditary breast cancer was achieved more often than in the control group in a comparative evaluation of the immediate results of neoadjuvant chemotherapy, 17,8% vs 8,6% (p=0,04). The complete pathological response was recorded with presence of germinal mutations of BRCA1 genes at 34,1%, BLM с. 1642С>T (Q548X) in 20% and did not occur in patients with CHEK2 1100delC. The incidence of complete pathological response in the group of triple negative breast cancer with the «founder mutation» was higher in comparison with the control group – 26,1% vs 7,8% (p=0,01). Among patients with BRCA1 5382insC-associated triple negative breast cancer the greatest efficacy was observed after anthracyclinecontaining neoadjuvant chemotherapy compared with taxane-containing chemotherapy (pCR=57,1% vs 9,1% (p=0,04)). A high incidence of the general objective response (OR) to neoadjuvant endocrine therapy with aromatase inhibitors in comparison with cytotoxic therapy was identified in patients with luminal A breast cancer (80% vs 40,6% (p=0,001)). The magnitude of the overall objective response (OR) after neoadjuvant chemotherapy was higher in patients with BRCA1/ CHECK2/ BLM-associated luminal A breast cancer compared with sporadic breast cancer – 58,8% vs 34% (p=0,048).
Conclusions. Hereditary breast cancer is overwhelmingly associated with BRCA1 5382insC mutation. The predictive value for neoadjuvant chemotherapy of triplе negative and luminal A breast cancer had mutations in the BRCA1 gene. A marker of high sensitivity to anthracyclinecontaining neoadjuvant chemotherapy in comparison with taxanecontaining regimens in patients with triple negative breast cancer is the mutation BRCA1 5382insC.

Keywords: breast cancer, triple negative breast cancer, hereditary breast cancer

Aim. This article reflects the results of a retrospective study conducted with the purpose of expert evaluation of medical errors in malignant trophoblastic tumors, their prediction and prevention.
Material and methods. The work is based on a retrospective analysis of the clinical data of 115 patients with malignant trophoblastic tumors who underwent diagnostic and treatment stages in medical institutions in the regions of Russia between 1993 and 2014. The study included a study of the frequency, structure, as well as the causes of diagnostic and therapeutic – tactical errors committed by doctors of non-specialized regional clinics.
Results. The result of erroneous diagnostics and tactics became: the frequency of metastasis – 49 (43%) of observations, which is 2,3 times higher than metastasis with timely diagnosis; frequency of lethality – 16 (14%) of observations, which is 7 times higher than the lethality in a specialized clinic; tumor resistance to chemotherapy – 71 (62%) observation, which is 5 times higher than the resistance in standard treatment; the frequency of hysterectomies – 55 (48%), which is 16 times higher than the frequency of hysterectomies in a specialized clinic.
Conclusion. The results demonstrate the relevance of the study and give grounds to believe that this disease continues to be a problem for all parts of practical health care and needs to optimize diagnosis and treatment in medical institutions
in the regions.

Keywords: trophoblastic, tumors, choriocarcinoma, bladder skeleton, chorionic gonadotropin, chemotherapy.

Pancreatic cancer is not a common disease: there are approximately 330000 cases a year worldwide. However, it is highly lethal, with nearly equal numbers of new cases and deaths. Surgery is the only potentially curative modality for patients with clinically localized and operable pancreatic cancer. Combined modality therapy compared to surgery alone has shown an advantage in terms of overall survival and should be considered for adjuvant treatment of resectable cancer patients. An improvement of surgical resectability and in overall survival has been shown for patients with unresectable tumor treated with neoadjuvant chemo-radiotherapy and surgical resection (median survival: 16–32 months).

Keywords: pancreas cancer, adjuvant treatment, neoadjuvant treatment, radical operation, pancreatoduodenal resection

Background. A significant shortcoming of percutaneous cryoablation (PC) is its low efficiency of the treatment of malignant liver tumors adjacent to large (more than 3 mm) blood vessels. The transfer of heat from the blood to the tumor does not allow the creation of lethal hypothermia near the wall of a large vessel. This leads to incomplete necrosis of pathological tissue or the formation of an insufficient minimal ablation margin (less than 5 mm), fraught with local progression. In this regard, the feasibility of performing the PC of primary and metastatic liver tumors adjacent to large
vessels is being questioned.
Aim. To demonstrate the case of a technically successful PC of colorectal liver metastasis adjacent to the large (d=10mm) vessel using an additional cryoprobe which temporarily blocks the blood flow in this vessel (blocking cryoprobe).

Case presentation. The patient M 73 years old hospitalized in our clinic for the treatment of newly diagnosed metachronous solitary unresectable (in connection with concomitant diseases) colorectal liver metastasis 25 mm in diameter, localized in the IVA segment and closely adjacent to a large vessel – the middle hepatic vein (MHV) 10 mm in diameter. The multidisciplinary team was decided to carry out the PC of this metastasis under the local anesthesia. For the temporary cessation of blood flow over the MHV (in order to exclude heat transfer to the tumor) during the PC, it was decided to positioning an additional cryoprobe in the immediate vicinity of the MHV (blocking cryoprobe) under the US and FDCT during hepatic arteriography. The insertion of blocking cryoprobe allowed to create «ice ball» in the lumen of the MHV and completely block the blood flow in this vessel during PC. Due to this, the effect of heat return to the tumor
was excluded and an ablation zone of the required volume was created. As a result, the procedure of PC was technicallyeffective. After PC a complete recovery of blood flow through the MHV and its branches was noted, with no complications
after the intervention.
Conclusion. The use of one or more blocking cryoprobes can increase the technical efficiency of PC of liver tumors
closely adjacent to the large blood vessels, improve the long-term results of treatment of such tumors, and extend the
indications for the PC of liver tumors in the future.

Keywords: percutaneous cryoablation, blocking cryoprobe, flat-detector computed tomography, capillary phase of hepatic arteriography, peritumoral ring enhancement, FDCT.

The amount of digital information is recently quickly growing. It is ahead of the increasing of computers upgrading. It was named Big data by journal «Nature» in 2008. The EMC corporation predicts that increasing of digital data will be larger than 40 zettabytes to 2020, that is larger than the sand grains across all the beaches of the world. The most difficult is not only data storage, but data processing. Artificial intelligence (AI) is a technology for creating smart programs and machines that can solve the necessary tasks and generate new information based on the existing. In fact, AI models the human intellectual activity. In accordance with well-known expert opinions, one of the most perspective applications of AI is medicine. The article presents a review of the basis and algorithms of AI, shows the opportunity of AI system application in the lung cancer diagnostic.

Keywords: artifitial intelligence, mashine learning, lung cancer, diagnostic, computed tomography, neural network.

The purpose of this review is to describe the history of the biopsy technique of the signaling lymph node in head and neck cancer. Biopsy of the signaling lymph node is a minimally invasive procedure that allows selection of those patients who need to be treated for metastatic lesions of the lymph nodes of the neck. Despite the fact that this procedure was recently approved for early oral cancer, the first studies on the visualization of cervical lymph vessels were published in the 1960s. In the 1980s, studies began on mapping lymphatic outflow from specific localization of the head and neck. Biopsy of the signaling lymph node was further developed in the 1990s and after validation in this century is routinely used in several centers dealing with head and neck tumors. New technologies can further improve the biopsy accuracy of the signaling lymph node, especially in complex tumor localizations, for example,the bottom of the oral cavity.

Keywords: head and neck tumors, oral cavity cancer, biopsy of the signaling lymph nodes.