Journal «Practical oncology»

Lung cancer (LC) is the most frequent oncological disease worldwide. Treatment
opportunities may significantly depend on the smoking status of the patients. LC in
non-smokers are characterized by elevated frequency of EGFR, ALK, ROS1, RET, MET
and BRAF mutations. There are highly effective inhibitors for each of the mentioned
mutated kinases. Mutations in the above genes are significantly less common in
smoking-induced LCs. However, LCs arising in smokers usually demonstrate high
mutation burden and therefore have increased responsivity to immune checkpoint modulators. LC is the first solid tumor for which molecular diagnosis began to be utilized not only at the start of the
treatment, but also during the course of therapy. Patients with EGFR-mutated LC progressing on gefitinib, erlotinib or afatinib are to be tested for EGFR T790M mutation, with subsequent administration of osimertinib in T790M-positive cases. Liquid biopsy utilizing circulating tumor DNA is being increasingly used for LC monitoring.

Keywords: lung cancer, mutation, smoking, tumor, inhibitor

Discovery of TKI-sensitizing EGFR mutations (EGFR-M+) in non-small cell lung
cancer (NSCLC) is often regarded as the most spectacular event in clinical oncology
during last decades. However, treatment with drugs targeting EGFR (TKIs) almost
never results in complete tumor eradication and inevitably results in the regrowth of
tumor. Inevitably after dramatic primary response to TKI in EGFR mutated NSCLC all patients develop disease progression. Development of resistance to targeted therapies is a major contributor to mortality
in patients with oncogene addicted NSCLC. Since EGFR mutation is an early event in carcinogenesis the absolute majority
of tumor cells harbor activating mutation prior to treatment with TKI. This relative homogeneity underlies high frequency
and depth of primary responses to TKI. Still EGFR driven tumors have genetic instability that influences mutational burden
and sub-clonality though in a lower level than in tumors without activating mutations. Several mechanisms are shown to
drive acquired resistance. Among them EGFR bypass (including MET, HER2, BRAF, etc.) and EGFR ATP pocket alterations
(i.e. T790M, C797S, etc.) as far as phenotypic transformation to small cell lung cancer (EMT). Still the properties and
mechanisms of transitional state from sensitive to resistant status are studied insufficiently. Two actual explanations for
primary insensitivity are described in the literature. First, there are preexisting low-frequency clones that harbor resistance
mechanisms identified at the time of clinical progression. Second, some genetically indistinguishable cells during first
weeks of treatment acquire phenotypical properties (drug tolerant status) that allow them to survive first TKI pressure,
divide and proliferate, and therefore develop resistance mechanisms. While the acquired resistance mechanisms are studied
heavily enough, there are only few identified molecules that probably participate in phenotypical transformation to «drug
tolerant status». Among them Wnt/tankyrase/β – catenin pathway, casein kinase 1a, IGF-1R, STAT3 are shown to make EGFR
mutated cells insensitive to TKI. Identification of the mechanisms underlying incomplete block of tumor cells proliferation
during first period of treatment with either TKI in oncogene addicted NSCLC will help to change primary treatment and
therefore to cure these patients.

Keywords: non-small cell lung cancer, epidermal growth factor receptor, targeted therapy, resistance.

Recent advances in the field of cancer biology have made it possible to identify a set
of molecular changes involved in the development of malignant tumors, which made
it possible to suggest ways of targeting them. To date, a sufficient number of studies
have already been performed in an attempt to dynamically describe the behavior
of malignant cells under the action of targeted drugs by mathematical modeling.
This paper provides an overview of mathematical models in application to targeted
cancer therapy that not only can complement experimental and clinical data, but
also redefine our understanding of the mechanisms of carcinogenesis and form key
questions for future research.

Keywords: cancer, targeted therapy, mathematical modeling, forecasting, new regimens of therapy.

Background. NOSE in LS surgery of colorectal cancer seems to be an option for minimization of surgical trauma and
severity of postoperative period.
Aim. The aim of the study was to analyze our own experience in LS-surgery with NOSE.
Methods. 64 patients with T2-T4 CRC were included in the retrospective study. 2 comparable groups were formed
(32 patient each): LS-surgery of CRC with or without natural orifice extraction of specimen.
Results. In the issue 2 groups were comparable in terms of blood loss (121,5 vs 112 ml), operation time (163 vs
170,4 min) and average number of lymph nodes (22,2 vs 21,8). All resections were with negative margins (R0). Anastomoses
were formed with circular stapler, hand-shewn extracorporally or hand-shewn intracorporally with LS-technique
(NOSE-group only). In terms of postoperative complications both groups were comparable.
The postoperative pain (The Faces Pain Scale-Revised) was less in NOSE group (2,6 vs 4,2, p<0,05).
The cosmetic effect was better in NOSE group (22,2 vs 15,6 points, p<0,05).

Keywords: laparoscopy, colorectal cancer, transluminal surgery, NOTES.

The status of the lymph nodes largely determines the treatment strategy and allow to evaluate the prognosis. In patients
with breast cancer with clinically negative axillary lymph nodes, a biopsy of the signaling lymph nodes (BSLN) should be
used. In elderly patients with breast, cancer with positive axillary lymph nodes carrying out BSLN compared with axillary
lymph node dissection does not impair the long-term survival rates. One of the features of neoadjuvant chemotherapy is
to reduce breast cancer that provides volume reduction surgery, as in breast and in the axillary region. The possibility of
extension of indications of BSLU for patients with cN+ which turned into category cN- after a neoadjuvant chemotherapy
is studied

Keywords: biopsy of signaling lymph nodes, axillary lymphadenectomy, neoadjuvant chemotherapy.

Objective. To show the possibility of repeated (up to 15 times) application of intra-arterial chemotherapy (IACT) for
the recurrence of squamous cell carcinoma of the oral cavity two years after standard chemoradiotherapy (SSRT).
Material and methods. At the patient, male 57 years old, with the cancer of a mucosa of a bottom of an oral cavity
st. II T2N0M0, SSRT was performed: Radiation 2 Gy x 1 times a day, 5 days a week, up to a total dose of 68 Gy; one
induction and two concurrent cycles of systemic chemotherapy (SCT) according to PF scheme (Cisplatin 150 mg in 1 day and
2250 mg of 5-fluorouracil on days 1, 2, 3, 4). A full clinical response was received. After 2 years, a relapse occurred. The use
of SCT (PF, as well as TPF) with palliative purpose did not result. In connection with the rapid progression of the disease,
a decision was made about the use of IACT.
Results. After 2 courses of IACT in both external carotid arteries (Cisplatin 150 mg and 5-fluorourocyl 500 mg), cicatrization
of the tumor ulcer, improvement of the lability of the tongue, complete refusal of analgesics were noted. Re-irradiation
was started up to 42 Gy. Six more cycles of IACT were performed super selectively in both facial arteries (docetaxel 80 mg,
cisplatin 100 mg). Stabilization for 17 months was received. Then with the palliation, another 7 cycles of selective IACT were
performed, which allowed to prolongation the life of the patient for a period of 32 months after the detection of a relapse.
Conclusion. It is possible long-term application of IACT in the recurrence of squamous cell carcinomas after chemoradiotherapy.
The selective IACT allows not only to loco-regional control, but it could be a «bridge» to re-irradiation therapy.
Even after a recurrence, the IACT can be successfully applied with a palliative purpose.

Keywords: squamous cell carcinoma of the head and neck, relapse of oral cavity cancer, chemoradiation treatment, intraarterial chemotherapy.