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Head and Neck Tumors (HNT)

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Vol 11, No 1 (2021)
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https://doi.org/10.17650/2222-1468-2021-11-1

DIAGNOSIS AND TREATMENT OF HEAD AND NECK TUMORS

12-23 896
Abstract

The study objective is to assess long-term results of treatment for patients with locally advanced external ear skin cancer.

Materials and methods. This research work based on a retrospective and prospective analysis case history for patients with locally advanced external ear skin cancer. These are 45 patients, who received treatment in surgical department of head and neck tumors in Blokhin National Medical Research Center of Oncology between 1994 and 2020. Patient observation time averaged 30.0 ± 32.3 months (from 0.7 to 117.4 months, median 12.0 months). We divided patients into 3 groups depending on treatment methods. Group 1 consisted of patients who received combined or complex treatment (33.3 %, n = 15). Treatment for first group patients involved subtotal, lateral temporal bone resection or incomplete lateral resection and postoperative radiation therapy on the area of primary tumor and regional metastasis zone (total focal dose from 60 Gy). In the case of complex treatment, radiation therapy had carried out against background cisplatin introduction. The second group consisted of patients who received only surgical treatment (40.0 %, n = 18). Temporal bone resections were not performed for patients of the third group (26.7 %, n = 12). Treatment for patients of the third group involved one of the treatment methods: cryodestruction, laser destruction, photodynamic therapy, radiotherapy or chemoradiation treatment.

Results. Five-year survival without signs of progression in a group of patients with locally advanced of the ear skin cancer, who received combined or complex treatment was 73.8 ± 13.1. Median progression-free survival not achieved. In the surgical treatment group 5 year progression-free survival was 40.4 ± 13.0, median was 34.1 months. In a group of patients who did not undergo temporal bone resection (3rd group) median progression-free survival was 4.5 months. Group differences are statistically significant (p <0.05). The most significant adverse prognosis factors that reduce overall survival for patients with locally advanced external ear skin cancer are positive histological margin (p = 0.0001, hazard ratio (HR) = 10.611, 95 % confidence interval (CI) 3.058-36.820), signs of destruction branch of the lower jaw/ zygomatic bone (p = 0.027, HR = 4.65, 95 % CI 1.193-18.116). Facial paralysis is the most unfavorable prognosis factor, reducing tumor-specific survival in patients with locally advanced outer ear skin cancer (p = 0.0001, HR = 19.146, 95 % CI 4.056-90.388).

Conclusion. Combined/complex treatment of patients with locally advanced ear skin cancer (surgery with postoperative radiotherapy/chemoradiotherapy) provides better long-term results compared to other treatment options.

24-33 891
Abstract

Radiation therapy as one of the main specific method of treatment is widely used to treat patients with laryngeal cancer. Currently, the main radiotherapy technique for the treatment of patients with head and neck cancer is linear electron accelerators that can provide individual, complex configurations of radiation volumes. The article presents new modern technologies of radiation therapy in the early and locally-advanced stages of the disease, principles of organ-preservation treatment in laryngeal tumors, indications for pre-and postoperative radiation, methods of prevention of post-therapeutic complications.

34-40 984
Abstract

Background. Anaplastic thyroid cancer (ATC) is one of the most aggressive human tumors. Since median survival of ATC patients is only 4 months, its early diagnosis is very important. Although ATC has specific clinical manifestations, the analysis of expression of different microRNAs can facilitate preoperative diagnostics and help to detect its potential precursors among differentiated cancers and other thyroid malignancies.

The study objective is to identify microRNAs specific for ATC that are different from microRNAs in other thyroid cancers.

Materials and methods. We analyzed the expression of 14 microRNAs in histological specimens of 67 patients with ATC. The control groups included 25 patients with benign nodules, 36 patients with follicular adenomas, 32 patients with follicular cancer, and 152 patients with papillary thyroid cancer. For 7 out of 67 ATC patients, we compared mi-croRNA levels in histological and cytological specimens.

Results. Patients with ATC demonstrated a statistically significant decrease in the expression of miR-145, miR-125b and increase in the expression of miR-155 and miR-21 compared to all control groups. We found two reliable diagnostic markers of ATC: relative miR-21 expression (at a cutoff of 14.9, sensitivity was 0.955 and specificity was 0.837) and the miR-21/miR-145 ratio (at a cutoff of 122, sensitivity was 0.955 and specificity was 0.955). The level of miR-21 expression and miR-21/miR-145 ratio in cytological specimens were accurate in all 7 cases (100 %).

Conclusion. the level of expression of specific microRNAs can be used as a reliable biomarker for ATC. The consistency between the results obtained in cytological and histological specimens enables the use of stained cytological samples for this analysis.

41-50 1102
Abstract

The study objective is to evaluate the results of organ-preserving treatment of locally advanced larynx squamous cell carcinoma.

Materials and methods. Analysis of 28 patients with locally advanced larynx squamous cell carcinoma (stages III-IV) who underwent treatment at the N.N. Blokhin National Medical Research Center of Oncology of the Ministry of Health of Russia between 2017 and 2020 was performed. At the first stage, 2-3 courses of combined inductive polychemotherapy per the DCF scheme with 21-day interval were performed (docetaxel 60 mg/m2, cisplatin 60 mg/m2 intraarterially bolus with detoxication with sodium thiosulfate, 5-fluorouracil 1000 mg/m2/day as 96-hour infusion). The second stage included external beam radiotherapy (60-70 Gy, 2 Gy per day 5 days a week) as monotreatment if complete clinical response after chemotherapy was achieved or with regional administration of cisplatin (60 mg/m2 once per 3 weeks) if after inductive stage full clinical response wasn»t observed.

Results. In 20 (71.5 %) patients, complete clinical response was observed after inductive treatment; in 7 (25 %) patients, partial response was observed. Tumor stabilization was detected in 1 (3.5 %) patient. Two-year overall survival was 95.8 ± 4.1 %, progression-free survival was 90.1 ± 6.8 %.

Conclusion. The proposed strategy of organ-preserving treatment of stage III-IV larynx cancer with substitution of systemic chemotherapy with regional intraarterial chemotherapy prior to radiotherapy is highly effective from the point of view of direct anti-tumor effect and recurrence-free and overall survival.

51-72 1430
Abstract

Squamous cell carcinoma (SCC) is the second most common skin cancer after basal cell carcinoma. Usually, antitumor treatment is sufficiently effective: recovery rate is about 90 %. Primary SCC is characterized by variable growth rate, as well as by involvement of regional lymph nodes (from 1 % for well differentiated tumors to 10 % for poorly differentiated tumors, size >3 cm and /or invasion depth >4 mm). In case of SCC development near post-burn scar, the rate of regional metastasis is 10-30 %. A relatively small possibility of distant metastasis also exists, with overall mortality of 2-3 %. In SCC of the head and neck, both hematogenic and perineural advancement into the CNS are possible. Total rate of local recurrences is 25 %. The main factors of local and regional recurrences are location (head and neck), size (tumor diameter >2 cm), invasion depth (>4 mm), tumor differentiation, perineural involvement, patient's immune status and previous treatment. Tumors in areas that weren»t subjected to solar radiation and tumors in the areas of pervious irradiation, thermal damage, scarring or chronic ulcers are more prone to recurrences and metastasis. Poorly differentiated and anaplastic SCC is more likely to metastasize compared to well differentiated tumors. Medially located SCC is the area of the face mask and lip is more prone to neural invasion. Multidisciplinary approach with involvement of all specialists in antitumor treatment is necessary for development of treatment tactics.

73-77 636
Abstract

Introduction. Skin cancer is the most common type among the cancer statistics. It accounts up to 14.2 % of all types of cancer. Basal cell cancer (BCC) is the most common among the skin cancers. Despite the possibilities of using different types of treatment BCC the long-term results are infavorable-the relapse rates are still high and cosmetic results are unsufficient. Using the local chemotherapy is alternative method of head&neck BCC treatment.

The study objective. Efficency analysis of using «Glycifon» as a local chemotherapy drug for head&neck BCC. Materials and methods. The study included 24 patients with head&neck BCC who underwent local chemotherapy with "Glycifon" drug. 18 (75 %) patients had primary tumors, 6 (25 %) - relapsed tumors. 7 (29.2 %) patients had multicentre BCC. All patients received local chemotherapy by "Glycifon" according to recommended instructions.

Results. 79.2 % of patients had full regress of BCC after "Glycifon" local chemotherapy. Medium follow up time was 11.5 month. 2 patients (8.35) had to interrupt the treatment but for the intensive pain after the drug application. Other patients finished the therapy satisfactorily. No toxic reactions were observed. Inflammatory reactions in application zones were moderate and easily fixed. All patients who finished the therapy (100 %) we satisfied about the cosmetic results.

Conclusion. Usage of "Glycifon" drug for local chemotherapy of head&neck DCC is effective, safe and cosmetic satisfied method. Possibility of using "Glycifon" in ambulatory treatment reduce the total medical & economic costs.

ORIGINAL REPORT

78-85 753
Abstract

The study objective is to analyze the mutation profile of the tall cell variant (TCV) of papillary thyroid carcinoma (PTC).

Materials and methods. The main inclusion criteria according to the WHO classification (2017) was PTC composed of at least 30 % of tall cells. Genetic examination was conducted using the FoundationOne CDx assay (USA) with median depth of coverage of >500x. This study included 5 patients (1 man and 4 women) with a mean age of 52.6 years (range: 48-56 years). The tumor size varied between 0.4 x 0.5 cm and 11.0 x 9.0 cm. All patients have undergone surgical treatment: hemithyroidectomy for patient No. 1 with a small tumor (pT1b); thyroidectomy for patient No. 2 (pT3b); extensive thyroidectomy with the removal of paratracheal tissue for patients No. 3, 4, and 5 (No. 3 - pT3bN0; No. 4 - pT3bN1b; No. 5 - pT3bN1b). Three out of the five patients also had adenomatous goiter. The mean follow-up time was 3.4 to 5.2 years.

Results. Tumors in all patients were characterized by low mutational load (0 to 4 mutations per 1 million nucleotides (megabase)) and no microsatellite instability. All study participants were found to have p.V600E mutation in the BRAF gene; two patients had c.-124C>T mutation in the promoter region of the TERT gene. All patients carried mutations with unknown clinical significance: p.V562I in the EPHB1 gene (in 2 patients); mutations in the genes AR, CREBBP, EP300, ERCC4, FLT1, IKBKE, JAK2, MAF, MLL2, MST1R, MYC, MYCL1, NTRK2, TSC2 (each mutation registered in one patient). One individual with the largest tumor and the most aggressive disease was found to have amplifications of the BTG2, MAP3K1, SMAD2, and TBX3 genes.

Conclusion. In 5 patients analyzed in this study, the mutation profile of TCV PTC was characterized by low mutational load, no microsatellite instability, and presence of p.V600E mutation in the BRAF gene in all cases. Some patients also had c.-124C>T mutation in the TERT gene and p.V562I mutation in the EPHB1 gene.

86-95 650
Abstract

Introduction. Diagnosis verification in patients with malignant tumors developed in the context of chronic inflammation is technically complex with a high percentage of false negative results of histological examination. None of the methods provides sufficiently accurate results necessary for ruling out or confirming a diagnosis.

The study objective is to test a new patented method of pre- and intraoperative differential diagnosis of oncological pathology of the ent-organs using the "InSpektr-M" hardware and software system.

Materials and methods. The study included 30 patients with suspected malignant tumors of the larynx. The study excluded patients with previously verified diagnosis of malignant tumor of the larynx. A diagnostic probe emitting laser light with wavelength 350 nm and radiation power density 25 mW/cm2 was introduced through an additional channel of a fiberscope for a period of time sufficient for excitation of intrinsic tissue fluorescence (from 10-6 to 10-9 ms). Fluorescence intensity in the range of wavelengths between 600 and 650 nm was measured. This intensity was conditionally labelled "epithelial proliferative activity index". Spectrometric analysis of the intact points allowed to evaluate normal values for an individual patient; in the areas with the maximal increase in the index, targeted biopsy was performed.

Results. Values obtained during examination of various types of tumors (epithelial and non-epithelial) are different while tumor location has a negligible effect. In patients with malignant tumors containing non-squamous epithelium, increased protoporphyrin IX and decreased FAD fluorescence were observed in the direction from intact tissues to the center of the suspected tumor; in patients with malignant tumors containing squamous epithelium: increased protoporphyrin IX fluorescence with maximum at 635 nm and dynamic increase in FAD fluorescence in the direction from intact tissues to the tumor center.

Conclusion. Fluorescent spectroscopy can be used for pre- and intraoperative differential diagnosis of squamous and non-squamous cancers of the ENT-organs. Further studies for establishment of reference values of fluorescence intensity in intact and affected tissues are necessary.

REVIEWS

96-100 571
Abstract

Currently accepted standard of surgical treatment of patients with locally advanced stage III and IV laryngeal and laryngopharyngeal cancer is laryngectomy which leads to loss of vocal function. Therefore, vocal rehabilitation is one of the most important tasks of the doctor. It allows to increase quality of life of patients after treatment. Currently used techniques of vocal rehabilitation have their advantages and disadvantages. The article considers various techniques of vocal rehabilitation, primarily, subtotal laryngectomy with laryngotracheal shunt as a promising method of surgical rehabilitation of patients with locally advanced caner of the larynx and laryngopharynx.

101-108 798
Abstract

Glioblastoma multiform^ is one of the most aggressive malignancies, wich standard of treatment not changed over the past decade, and the average life expectancy from diagnosis to death does not exceed two years in the most optimistic trials. The review examines the features of the glioblastoma microenvironment, its genetic heterogeneity, the development of recurrent glioblastoma, the formation of drug resistance, the influence of the blood-brain barrier and the brain lymphatic system on the development of immunotherapy and targeted therapy. Molecular subgroups of glioblastomas with an assumed prognostic value were analyzed. It was determined that numerous relationships between glioblastoma cells and the microenvironment are aimed at ensuring tumor progression, and also cause a state of reduced effector function of T cells. Data on the development of future molecular-targeted therapies for four types of cancer cells based on their different properties and response to therapy are summarized: primary GSC, RISC cells, and proliferating and postmitotic non-GSC fractions. The penetration of blood-brain barrier with chemotherapeutic drugs and antibodies currently remains the main limitation in the treatment of glioblastoma. The resulting analysis of the causes is reduced to the following conclusions. A detailed understanding of the evolutionary dynamics of tumor progression can provide insight into the related molecular and genetic mechanisms underlying glioblastoma recurrence. The most promising methods of treatment for glioblastoma are combined therapy using immune checkpoint inhibitors in combination with new treatment methods -vaccine therapy, CAR-T-cell therapy and viral therapy. A deeper study of the mechanisms of drug resistance and acquisition resistance, biology and subcloning clonal populations of glioblastoma and its microenvironment, with active consideration of combined trips to the treatment will increase the survival rate of patients, and may lead to stable remission of the disease.

CASE REPORT

109-114 577
Abstract

Background. In the structure of malignant neoplasms, basal cell skin cancer (BCC) occupies a leading position. In the initial stages of a malignant neoplasm, the main treatments are local treatment methods, both surgical and radiation. However, in about 1.3 % of cases, BCC can become locally or metastatic in which local treatment methods are limited. With the development of targeted drugs, such as the Hedgehog pathway inhibitor, the possibilities for effective and safe treatment of this category of patients have appeared.

The objective is to present the clinical case of treating a patient with BCC who is receiving systemic therapy with a Hedgehog signaling pathway inhibitor.

Case report. According to the patient, a tumor in the lower eyelid of the left eye appeared in 2000, did not seek medical help. In 2011, he applied to the clinic and was diagnosed with skin cancer of the lower eyelid of the left eye T2bN0M0. The patient refused the proposed treatment. Reapplied only in June 2017 already with a locally distributed process. The case is recognized as unresectable. From June 30, 2017 to September 4, 2017, he underwent a course of a radical program of radiotherapy, with a positive effect. 07/01/2019, he relapsed with a relapse of an orbital tumor on the left. From July 16, 2019, the patient began taking the drug wismodegib 150 mg once a day. Against the background of the treatment, control CT studies on 11/24/2019 and 11/03/2020 compared with CT data from 07/09/2019 reduced the volume of the tumor by 78 and 82 %. The patient currently continues to take wismodegib.

Conclusion. The clinical case demonstrates successful treatment of locally advanced basal cell skin cancer with a Hedgehog signaling pathway inhibitor.

115-121 11853
Abstract

Introduction. Papillary thyroid cancer (PTC) usually metastasizes into the central and lateral lymph nodes (LNs) of the neck. Metastases into the retropharyngeal and parapharyngeal LNs are rare. Their presence attests to aggressive PTC.

The study objective is to describe a rare case of metastases of papillary radioiodine-refractory PTC into the parapharyngeal LN.

Clinical case. In 2015, female patient K., 40 years old, underwent thyroidectomy due to PTC. Histological examination verified papillary PTC with growth through the capsule and ingrowth into the surrounding tissues and muscles. In a separately admitted LN, metastases of the same cancer were observed. One year later, regional metastases in the lateral neck LNs were detected. Radioiodine therapy (activity 131I 4.5 GBq) was performed followed by fascial circular section of the neck tissues on the right per thyroid type. Morphological examination verified presence of papillary PTC metastases in 4 LNs. In January of 2018, positron emission tomography showed metastases in the paratracheal LNs. Central neck lymph node dissection was performed. Per histological conclusion, fat tissue and LN contained multiple metastases of papillary PTC. In October of the same year, repeat radioiodine therapy (activity 131I 3.0 GBq) was performed. Thyroglobulin levels increased. In June of 2020, repeat positron emission tomography showed a single metastasis in the parapharyngeal LN. Due to small size of the metastasis and absence of signs of progression, dynamic follow-up and hormone therapy were suggested to the patient.

Conclusion. Metastatic involvement of parapharyngeal LNs is rare, especially in radioiodine-refractory PTC. They can be detected both during primary diagnosis and after the treatment during dynamic follow-up, as well as a single manifestation of PTC, which should be taken into account during differential diagnosis.

PROBLEMS OF REHABILITATION

122-133 1186
Abstract

Four stages of medical rehabilitation of patients with differentiated thyroid cancer in Russia are described. Specific rehabilitation programs and methods are described for every stage. The pre-rehabilitation program includes psychological and nutritional support, exercise therapy, consultations by the surgeon and anesthesiologist, correction of concomitant disorders, prevention of thromboembolic complications and local hemodynamic abnormalities. At the rehabilitation stage in the ICU antibacterial therapy, patient positioning, percussion massage of the chest, passive mobilization, massage of the extremities are performed. The rehabilitation program at the specialized surgical department includes psychological rehabilitation, adequate pain management, exercise therapy, massage, nutritional support, prevention of thromboembolic complications, treatment of early postoperative complications. The in-hospital rehabilitation at medical facilities additionally includes treatment of delayed and late surgical complications, correction of radioiodine therapy consequences. The outpatient rehabilitation program also involves correction of hypothyroidism and minimization of adverse effects of suppressive hormone therapy, health resort treatment.

JUBILEE



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ISSN 2222-1468 (Print)
ISSN 2411-4634 (Online)