DIAGNOSIS AND TREATMENT OF HEAD AND NECK TUMORS
Introduction. Incidence of brain metastases rises in recent years. Local control after surgical resection of brain metastases is a priority for patients with limited intracranial disease and controlled primary tumor. Surgery should be combined with other methods because of the high risk of local recurrences.
Aim. To analyze the overall survival (OS) and influencing factors for patients with brain metastasis after combined therapy. Materials and methods. The retrospective study included 196 patients with stable systemic cancer or available systemic therapy in cases of progressive disease. All patients had from 1 to 3 brain metastasis. Overall survival and influencing factors after surgical and combined therapy were analysed.
Results. Median OS for the entire cohort was 16.9 months. The highest levels of OS were achieved for patients with renal cancer (median OS 32.5 months). For patients with non-small cell lung cancer, breast cancer, melanoma and other cancers OS were 18.8; 19.9; 11.0 and 15.3 months, appropriately. Age, continuation of local therapy in brain (surgical intervention, stereotactic radiosurgery), using of the cisplatin for patients with non-small lung cancer brain metastasis were independent factors that have influenced OS.
Conclusion. Application of combined therapy for brain metastasis can provide reasonable OS for patients with controlled systemic disease. Using of the cisplatin as a part of combined therapy provide statistically meaningful rise in OS for patients with non-small lung cancer brain metastasis.
Intrоduction. Sinonasal papilloma is a benign tumor. The standard treatment for sinonasal inverted papilloma (SIP) is surgical intervention. The tumor is located primarily in the maxillary sinus (50.9 %). Sinonasal inverted papilloma originated from the maxillary sinus has aggressive characteristics and can dislodge local anatomical structures, infraorbital canal in particular.
Aim. To present a descriptive characteristic of structural changes in the infraorbital canal during SIP growth and determine the optimal volume of canal dissection.
Materials and methods. A retrospective study of patients with SIP was performed. From the total cohort (n = 37), 15 patients with primary localization of sinonasal inverted papilloma in the maxillary sinus were selected. In all cases, the same diagnostic algorithm was used. Separately, evaluation of infraorbital canal anatomy based on preoperative analysis of computed tomography of the paranasal sinuses and intraoperative endoscopic exam was performed. Surgical strategy used in all cases consisted of endoscopic SIP tissue removal, total resection of the mucoperiosteum and subperiosteal dissection of all walls of the maxillary sinus using a bur. During surgery material was collected for control histological examination.
Results. In 20 % of cases, changes in the walls of the infraorbital canal in the form of hyperostosis, erosion and dehiscence were observed. In 13.3 % of cases, growth of sinonasal inverted papilloma caused distortions in the structure of infraorbital canal walls. In all cases, computed tomography data showed the same results as intraoperative endoscopic visualization. For removal of the lesion and pathologically changed walls of the infraorbital canal, transnasal endoscopic partial maxillectomies (type 3 or 4) were performed. Follow-up duration varied between 1 and 5 years, mean follow-up duration was 3 years. SIP resection was effective in all patients, no recurrences were observed.
Conclusion. For SIPs growing in the maxillary sinus, condition of the infraorbital canal must be of special interest. The study showed the effectiveness and flexibility of the surgical strategy consisting of the combination of total mucoperiosteum resection with subperiosteal dissection of all walls of the maxillary sinus.
Introduction. Measurement of thyroglobulin (Tg) in a washout after fine-needle aspiration (FNA) is recommended for the diagnosis of metastases of differentiated thyroid cancer (DTC), but the method is not standardized and there is no recommended threshold value of Tg washout, which makes it difficult to interpret the results.
Aim. To analyze Tg in the washout after FNA of lesions of different origin on the neck and to determine its optimal cutoff for the diagnosis of DTC metastases.
Materials and methods. Ultrasound-guided FNA was performed in 1258 neck masses from 591 patients, 566 of them with confirmed DTC. In 1023 lesions, FNA was performed after thyroidectomy, 22 – after lobectomy, 213 – with preserved thyroid gland. The needle after FNA was washed in 1 ml of saline, in which the concentration of Tg was then examined. The level of Tg in the washout was compared with the histological (n = 522) or cytological diagnosis if no surgery was performed. The cut-off for Tg washout was determined by ROC analysis.
Results. DTC lymph node metastases detected in 577 specimens. Nine specimens were obtained from metastases of thyroid cancer (TC) that does not express Tg (anaplastic TC, poorly differentiated TC, columnar-cell variant DTC), 22 – from neck metastases of other malignancy (lung cancer, mucinous soft tissues tumor, ovarian cancer, esophageal cancer, melanoma, neuroendocrine tumor), 6 – from other tumors of the neck (lymphoma, parathyroid adenoma, neurinoma). In 26 cases, the specimen was regarded as normal thyroid tissue left after thyroidectomy, 37 – postoperative seroma or granuloma, 1 – cyst of the neck, 578 – lymph node hyperplasia, 2 – sarcoidosis. The level of Tg washout from DTC metastasis and thyroid remnant significantly differed from that of non-thyroidal origin (p <0.0001). At the cut-off of 7.8 ng/ml, the sensitivity and specificity of Tg washout in the diagnosis of DTC metastases is 94 and 95 %, and at the cut-off of 20 ng/ml, 90 and 98 %, respectively. False-negative results were obtained from DTC with squamous metaplasia or sparse tumor cells in a specimen. False-positive results were obtained more often from lesions of level VI and IV compared with other localizations (8 % versus 4 %; p = 0.04). There were no differences in false positive rate in patients before and after thyroidectomy (p = 0.17), but in patients after thyroidectomy with a serum Tg >200 ng/ml, the false positive rate of Tg washout was significantly higher than that with a lower level of serum Tg (28 % versus 3 %; p = 0.0004). When comparing diagnostic performance of cytology and Tg washout, the advantage of the latter is in the diagnosis of cystic metastases, and the former is in the diagnosis of micrometastases and tumors that do not express Tg. Thyroglobulin in the washout increased the sensitivity of the cytology by 8 %. The combined use of these methods detected DTC metastases in 100 % of patients.
Conclusion. Measurement of Tg in the washout is a useful addition to the cytology, increasing the diagnostic performance of the latter, mainly due to better detection of cystic metastases of DTC. The optimal suggested cut-off for Tg washout is 20 ng/mL, at which there are fewer false positives.
Introduction. Squamous cell carcinoma of the oral mucosa advances into the mandible in locally advanced tumors in 13–38 % of cases. Frequently, this situation requires inclusion of segmental resection of the mandible into the surgical plan. This approach requires adequate reconstruction for preservation of satisfactory functional and esthetic treatment results. Selection of reconstruction method remains an important clinical problem in everyday practice of a head and neck cancer specialist.
Aim. To analyze clinical materials on the use of reconstruction plates in oncological practice, evaluate esthetic and functional results of their use in patients who underwent single-stage reconstruction after segmental resection of the mandible.
Materials and methods. The results of treatment of 103 patients after segmental resection of the mandible with defect reconstruction using only a reconstruction plate or a reconstruction plate with a distant or free flap who were treated at the Loginov Moscow Clinical Scientific Center and N.N. Blokhin Scientific Medical Research Center of Oncology between 1998 and 2019 were analyzed.
Results. Complications at various times (between 2 months and 3 years) were observed in 15 (14.6 %) patients. The most frequent complications were plate cutting through the skin and mucosa (6 (5.8 %) cases) and osteomyelitis of fragments of the mandible (7 (6.7 %) cases). In 2 (1.9 %) cases, plate fracture was observed. It is necessary to note that during anti-inflammatory treatment in 4 (3.9 %) patients, osteomyelitis was managed while 11 (10.7 %) patients required removal of the reconstruction plate. Per the data analysis, in patents with surgical defect in the anterior area (defects ТТ, АТТ, САТ per the J.S. Brown classification, 2016) complications are significantly more common (in 11 (23.9 %) of 46 cases) than in patients with limited defects of the body and condyle (defects АТ, АС) (in 4 (7.0 %) of 57 cases). The rate of complications is also significantly affected by radiation dose.
Conclusion. Therefore, use of a plate for reconstruction of mandible defect is aesthetically and functionally acceptable reconstruction technique. Severe complications leading to plate removal are rare and were observed in 11 (10.7 %) patients.
Introduction. Glioblastoma is the most common primary malignant glial tumor of the brain in adult patients. Median overall survival for this pathology varies between 3 and 12 months, and only 5 % of patients live for more than 5 years. Current treatment methods allow to slightly increase lifespan of the patients with glioblastoma but not in all cases.
Aim – to determine the utility of full exome sequencing of biopsy materials of patients with glioblastoma using expanded gene panel for prescription of new targeted therapy.
Materials and methods. The study included 28 patients with glioblastoma multiforme. Foundation One CDx assay was performed using DNA extraction from a paraffin block and next-generation sequencing. In total, 4 classes of genomic changes in 324 genes, introns of 34 genes taking part in rearrangements, as well as microsatellite instability and tumor mutation load were evaluated. For every tumor profile, individual therapy options were identified in accordance with the current knowledge, references for the relevant scientific studies were included. From some patients, feedback was received allowing to evaluate the dynamics of their condition and changes in therapy after the performed study.
Results. Genes in which mutations are the most common were identified: EGFR – in 11 patients, CDKN2A – in 13, TP53 – in 9, TERT (frequent mutations in TERT gene promoters с.-124C>T and c.-146C>T) – in 15, MTAP – in 10. Mean mutation level was 4.5 mutations/ MB and tumors did not have microsatellite instability. For 6 patients, appropriate targeted therapy was identified.
Conclusion. Sequencing using an extended gene panel is justified and recommended for patients with glioblastoma multiforme for selection of new targeted therapy.
ORIGINAL REPORT
Introduction. Thyroid cancer has a favorable prognosis but in long term patients are observed to be in psychological distress manifesting through elevated anxiety and depression which disrupt social adaptation. Studies have shown that 2–4 years after diagnosis and treatment of this malignant tumor, the majority of patients report dissatisfaction with family relationships and difficulties in performing everyday activities. These data demonstrate the necessity of rehabilitation aimed at patient adaptation to everyday life after therapy completion. Psychological help is an important aspect of rehabilitation.
Aim. To evaluate the effectiveness of psychological help in patients with thyroid cancer.
Materials and methods. The study included 42 women with thyroid cancer, stages I–III, Т1–3N0–1М0. Mean patient age was 44.5 ± 1.1 years. The patients were randomly divided into 2 groups matched by age, disease stage and type of surgical intervention: treatment and control groups. The treatment group (n = 24) included patients who underwent psychological training in the postoperative period, the control group (n = 18) included patients who did not receive psychological help. Mental state was evaluated using the Hospital Anxiety and Depression Scale (HADS). The patients’ mental state was evaluated dynamically: 1st testing was performed after surgery, 2nd testing 12 months after surgery. Psychological training was performed in the postoperative period and included 5 individual classes teaching self-regulation skills.
Results. After the surgery, HADS scale showed insignificant increase in anxiety in both groups. Analysis of repeat testing showed decreased anxiety levels in patients in the treatment group from 7.7 ± 0.2 to 6.3 ± 0.2, i. e. to normal level. In the control group, anxiety significantly increased from 7.8 ± 0.2 to 9.2 ± 0.2 (Student’s t-test = 5.17; p = 0.000168). Additionally, 12 months after surgical treatment statistically significant differences in anxiety levels between groups were observed: 6.3 ± 0.2 and 9.0 ± 0.2, respectively (Student’s t-test = 9.55; р <0.05). Primary examination showed subthreshold depression in patients of both groups: 7.9 ± 0.1 and 8.1 ± 0.2, respectively. No statistically significant differences between the groups were observed (Student’s t-test = 0.89; р >0.05). Repeat examination showed decreased depression level (in treatment group from 7.9 ± 0.1 to 7.4 ± 0.2, in the control group from 8.1 ± 0.2 to 7.7 ± 0.1), however it remained in the range of mean values. No statistically significant differences between the groups were observed (Student’s t-test = 1.34; р >0.05).
Conclusion. Psychological training using self-regulation techniques performed in the early postoperative period normalizes anxiety level and prevents its elevation in long term in patients with thyroid cancer.
Introduction. Cutaneous melanoma is one of the most aggressive malignant tumors, and its nodular form with vertical growth is characterized by unfavorable prognosis. However, in the recent years due to advances in basic oncology, a breakthrough in drug therapy of this pathology was made. To a great extent, it is linked to implementation of new therapy with checkpoint inhibitors. The best and longest response rates of cutaneous melanoma to this treatment were achieved compared to other oncological diseases. This fact can be explained by immunogenicity of cutaneous melanoma, high mutational load, as well as features of its tumor microenvironment, where in most cases high infiltration by immunocompetent cell is observed. However, immune cells vary by their composition and functions. Some of them can even promote tumor growth. Therefore, study of cell composition, degree and distribution of immune infiltration in the tumor can help identify potential factors of favorable and unfavorable prognosis for cutaneous melanoma which is important in clinical practice.
Aim. To determine the frequency of CD3+-, CD4+-, CD8+-T-lymphocytes, CD163, BCL6 and SOX10 expression in patients with primary nodular cutaneous melanoma, as well as correlation of these markers with each other and standard morphological parameters for this non-epithelial malignant tumor.
Materials and methods. In the study, the expression frequency of CD3+-, CD4+-, CD8+-T-lymphocytes, CD163, BCL6 and SOX10 in the postoperative material of 20 patients with true primary nodular cutaneous melanoma was measured using immunohistological analysis. The correlation of these markers with each other and standard morphological parameters was determined.
Results. In most cases of nodular cutaneous melanoma, moderate and marked lymphocytic (immune) infiltration (grade II–III) was observed with no correlation with Breslow tumor thickness. Study of the ratio between CD4-positive T helpers and CD8-positive cytotoxic T lymphocytes in the tumor microenvironment showed that the number of the latter increased the higher was the degree of immune infiltrate. Markedness of macrophage infiltration directly correlated with markedness of lymphocytic infiltration. BCL6 expression in lymphocytes was observed in all cases of infiltration.
Conclusion. Immune infiltrate in nodular cutaneous melanoma is a multicomponent, dynamic microenvironment containing both antitumor and tumor-promoting components with balance shifting to one or other side. Their qualitative, quantitative and, possibly, topographic ratios in the primary lesion of cutaneous melanoma affect the effectiveness of drugs and disease prognosis. Knowledge on the predominance of components negatively affecting tumor growth in the primary lesion can help an oncologist in selection of correct treatment tactics and disease observation.
Introduction. Oncological and palliative patients undergo treatment causing adverse events including mental and cognitive disorders leading to their inability to express their wishes in the legal sense. This affects the possibility of preparation of documents on disposal of property: wills, donation or sale and purchase agreements, letters of authorization.
Aim. To consider problems arising when an oncological or palliative patient decides to dispose of their property and to suggest solutions to these problems.
Materials and methods. An analysis of the current normative legal acts and legal precedents in the Russian Federation in the context of property disposal by severely ill patients was performed. Clinical guidelines on treatment of chronic pain in oncological and palliative patients, as well as Russian and international approaches to this therapy were considered.
Results. Legal solutions for the considered problem appear to lack effectiveness. Use of tafalgin in treatment of severely ill patients can decrease risks and ease the process of preparation of documents on property disposal. This medication is indicated for chronic pain syndrome and unlike other pharmaceuticals is not an opioid analgesic and does not have severe side effects. Administration of tafalgin allows patients to retain mental clarity and avoid the risk of physical and psychological addiction.
Conclusion. It is necessary to continue the search for new therapeutic approaches to chronic pain treatment taking into account needs and special aspects of oncological and palliative patients which would allow them to preserve full legal competency and dispose of their property without legal risks.
REVIEW
Thyroid cancer is the most common cancer of the endocrine system. The diagnosis of thyroid cancer has taken a step forward due to the introduction of fine-needle biopsy of the thyroid gland with subsequent evaluation of cytological material using the Bethesda system. One category of this classification traditionally remains a gray area of diagnosis. The detection of a follicular tumor in the cytological material (category IV according to Bethesda) does not allow one to reliably classify the neoplasia as benign or malignant and requires surgical intervention. The traditional informative and widely used method for diagnosing thyroid tumors is ultrasound. However, the sensitivity and specificity of the method varies over a wide range. This review analyzes the literature on the possibilities of ultrasound diagnostics in assessing the malignant potential of follicular tumors of the thyroid gland.
Timeliness of accurate dynamic observation and a clear understanding of the treatment response guarantees health of patients with differentiated thyroid cancer. Multidimensional approach to evaluation of thyroid-stimulating hormone, tumor markers, ultrasound picture, as well as results of molecular imaging with radioactive iodine is clearly defined in international clinical guidelines. At the A.F. Tsyb Medical Radiological Research Center – branch of the National Medical Research Radiological Center for more than 15 years tactics of control exam 6 months after radioactive iodine ablation has been implemented. The aim of the current article is to consider the sequence of diagnostic search for different responses to treatment of differentiated thyroid cancer.
More than 90 % of newly diagnosed cases of endocrine cancer occur in the thyroid gland. Introduction of fine needle puncture of the thyroid gland, with the classification of cytological material according to the Bethesda system, has become the cornerstone of the diagnosis of malignant neoplasms of the thyroid gland. However, traditionally in this classification there remains a weak link called a follicular tumor (category IV). The detection of a follicular tumor in the cytological material does not allow one to reliably classify the mass as benign or malignant and requires surgical intervention with morphological verification. In recent years, the possibilities of molecular genetic testing have improved markedly. Follicular tumors tend to accumulate mutations, which over time can lead to malignant transformation, but can also be used as a method of timely diagnosis. This review analyzes the literature on the possibilities of molecular genetic testing in assessing the malignant potential of follicular formations of the thyroid gland.
CASE REPORT
A rare clinical observation of advanced myeloid sarcoma developed through blast transformation of post-polycythemia vera myelofibrosis as extramedullary manifestation of acute myeloid leukemia affecting larynx, laryngopharynx, trachea, soft tissues of the neck, pleura, and skeletal bones is presented.
Continuous development of oncology as a science in the last decades and years led to noticeable improvement in treatment outcomes for patients with various malignant tumors. Diagnostics, surgery, radiotherapy significantly contributed to this improvement, however they cannot be compared to the progress achieved through advancements in our knowledge of genetic structure of tumors and subsequent advancements in pharmacology which allowed to achieve qualitatively better survival in oncological patients. These advancements did not leave out such a serious and highly lethal, though fortunately rare, disease as anaplastic thyroid cancer. This article is dedicated to the possibilities of using checkpoint inhibitors in treatment of this pathology to increase expected life span of the patients.
JUBILEE
INFORMATION FOR THE AUTHORS
ISSN 2411-4634 (Online)