RADIOTHERAPY
Irradiation of the tumor through the ridge filters in order to reduce the damage of the normal tissues while maintaining the same damage to the neoplastic tissue as with uniform field is used for many decades. In recent years, a positive effect has been demonstrated using synchrotron radiation and beams of accelerated protons with radiation fields diminished to 25-100 micrometers with the same distances between them. Less skin damage achieved while maintaining the required level of large neoplasms eradication in the case of X-ray and gamma irradiation through ridge filters can be partially explained by the features of the physical distribution of the dose over the depth of the irradiated tissue, namely, the “merging” of fields at depth. But the good results from the use of the ‘hills and valleys’ in radiation fields created by the modern radiation sources have attracted attention to radiobiological issues for explaining the principal differences in reaction to spatial fractionation of the absorbed dose between tumor and normal tissues. We are talking about the role of the so-called ‘communal effect/bystander effect’, the effect of radiation on the immunological processes, the differences in damage and restoration of the microvasculature in normal and tumor tissue, etc. Although there is the lot of publications concerning experimental studies of the effectiveness of ‘spatial dose fractionation’, as well as those considering radiobiological mechanisms of the observed expansion of the ‘therapeutic interval’, there is still no clarity in this issue. The purpose of this review is to systematize the available data on the clinical and experimental confirmation of the effectiveness of ‘spatial fractionation’ and the various explanations of its advantages over conventional, uniform dose distribution. Special attention is paid to the issues of combination of spatial fractionation with superhigh dose rate irradiation (FLASH-radiotherapy) on the new radiation facilities, including proton accelerators, which are now in use in this country.
NUCLEAR MEDICINE
Children are not “miniature” adults! Most experts around the world recognize the differences between adult and pediatric thyroid cancer and emphasize the need for specific guidelines for the pediatric population. The American Thyroid Association (ATA) first developed separate Guidelines for the Treatment of Pediatric Thyroid Nodules and Carcinoma (hereafter, ATA Guidelines) in 2015 [1], which has not been revised to date. In September 2022, the European Thyroid Association (ETA) published its Guideline on the Management of Pediatric Thyroid Nodules and Differentiated Thyroid Carcinoma (hereafter, ETA Guidelines) [2]. The aim of our article, in anticipation of the revision of Russian clinical guidelines for the treatment of pediatric thyroid cancer, is to inform specialists in the field of radioiodine therapy (RIT) with the key recommendations of the ETA.
DIAGNOSTIC RADIOLOGY
Purpose: To improve the differential diagnosis of high-grade gliomas and solitary metastases by introducing the diffusion-kurtosis magnetic resonance imaging technique into the MRI scan protocol.
Material and methods: The study included 43 patients who underwent examination and treatment at the N.N. Blokhin National Research Medical Center of Oncology from October 2019 to March 2022, in which, according to magnetic resonance imaging, solitary formations in the brain substance were detected. A total of 43 neoplasms were found in the substance of the brain, of which: 17 glioblastomas in 17 patients (40 %), 25 solitary metastatic tumors of lung, breast, melanoma and kidney cancer (60 %). We evaluated the tumor size, diffusion and kurtosis parameters, such as mean kurtosis (MK), axial kurtosis (AK), radial kurtosis (RK), kurtosis anisotropy (KA), radial diffusion (RD), fractional anisotropy (FA), relative anisotropy (RA), tortuosity of the trajectory (TTD).
Results: Statistically significant differences (р < 0.05) in such parameters of diffusion and kurtosis in the tumor as kurtosis anisotropy (KA), fractional anisotropy (FA) and tortuosity of the trajectory (TT) were revealed. Significant differences between solitary metastases and malignant glial tumors based on diffusion and kurtosis values such as mean kurtosis (MK), axial kurtosis (AK), radial kurtosis (RK), radial diffusion (RD), and relative anisotropy (RA) (criteria where р > 0.05) was not detected.
Background: Cervical cancer occupies one of theleading places in cancer incidence in women. Preservation of residual tumor in patients with cervical cancer after completion of combined chemoradiotherapy is a prognostically unfavorable factor. Detection of an early tumor response to chemoradiation therapy is of great importance for choosing the optimal treatment tactics.
Purpose: To study the possibilities of MRI in assessing the effectiveness of detecting an early tumor response in patients with locally advanced cervical cancer after combined chemoradiotherapy.
Material and methods: The results of magnetic resonance imaging of the pelvic organs, data of laboratory, cytological and postoperative histological studies of 174 patients with locally advanced cervical cancer were analyzed and compared.
MRI of the pelvic organs was performed before the start of treatment to assess the extent of the process (primary study) and 6 weeks after the completion of combined chemoradiotherapy to assess the effectiveness of the treatment and detect residual tumor (control study).
Conclusion: Magnetic resonance imaging of the pelvic organs using a standard research protocol, including obtaining diffusion-weighted images and dynamic contrast studies, is a highly informative method for staging locally advanced cervical cancer and assessing the tumor response to treatment.
COMBINED METHODS OF DIAGNOSTICS AND TREATMENT
Glioblastoma is the most malignant primary brain tumor. For treatment uses a combined regimen that is currently available: surgery, radiation and chemotherapy. However, so far the median survival of patients does not exceed 14 months. In this connection, there is a constant search for effective methods. Improvement in radiation therapy has led to the possibility of its intraoperative, which is a practical and effective method aimed at getting rid of the remaining tumor cells, reducing the spread of the tumor and filling the therapeutic gap between surgery and subsequent chemotherapy and radiation therapy. Intraoperative radiation therapy (IORT) allows you to deliver the required tumoricidal dose exactly to the target, minimally affecting the surrounding healthy tissues.
Goal: Establishment of the safety of intraoperative irradiation of patients with malignant gliomas with the INTRABEAM device (Carl ZEISS, Germany) with a dose of up to 40 Gy on the applicator.
Material and methods: The study involved 15 patients, the average age of which was 51 years, the ratio of men and women was 4:6, the average Karnofsky index before surgery was 97. After surgical removal of the tumor, an express biopsy was performed. Next, intraoperative irradiation was performed with the INTRABEAM device (Carl ZEISS) at a dose of 40 Gy, followed by an assessment of the Karnofsky index, early postoperative and delayed possible complications.
Results: In all patients operated on with intraoperative irradiation and subsequent adjuvant radiochemotherapy, the method was well tolerated, there were no wound healing features or identified complications, there were no cases of wound liquorrhea, wound inflammation.
Conclusion: Intraoperative irradiation after surgical removal of the tumor can be recommended as a safe method for the treatment of malignant gliomas in addition to existing combination therapy.
Relevance: Glial tumors (GTs) amount for about 60 % of all primary CNS tumors. GTs highly express VEGF. Standard approaches to GT treatment do not involve modification of the radiation therapy plan. Adaptive stereotactic radiotherapy (ASRT) allows such correction. The combination of ASRT with bevacizumab (B) or dexamethasone (D) improves the outcomes of patients with GTs, but the effectiveness of therapy varies from patient to patient. B and D are known to have different effects on malignant glioma cells and components of the VEGF system.
Purpose: To reveal specific levels of the VEGF system components in the blood of men with cerebral GTs with different effectiveness of combination ASRT.
Material and methods. One month after radical surgery, men with GTs received ASRT with standard fractionation on the Novalis Tx linear accelerator (Varian): single fraction dose = 2 Gy, total dose = 60 Gy, 30 fractions, using a three-layer stereotaxic mask. ASRT was combined with B (i/v, 5 mg/kg, once every 2 weeks), n = 30, and with D (i/m, 4 mg, twice a day during 45 days), n = 30. Blood levels of VEGFA, sVEGFR1 and sVEGFR2 were measured by IFA before and after ASRT.
Results: Before treatment (ASRT+D), levels of VEGFA were 1.5 times (р < 0.01) higher, and sVEGFR1 was 3.1 times lower in patients with future progression, compared with patients with other responses to treatment; in partial response, sVEGFR was 1.8 times (р < 0.01) higher than in stabilization. After treatment (ASRT+D), sVEGFR1 levels reduced by 1.4 times (р < 0.001) in stabilization and by 2.2 times in partial response, together with VEGFA increase by 3.0 times in stabilization only; in progression, sVEGFR1 increased by 2.3 times. Before treatment (ASRT+B), levels of VEGFA in patients with partial and complete responses were on average 1.4 times (р < 0.01) lower than in stabilization; sVEGFR1 in partial response was 4.4 times lower than in stabilization and 2.2 times lower than in complete response; sVEGFR2 in complete response was 1.3 times (р < 0.02) lower than in partial response. After treatment (ASRT+B), VEGFA levels elevated: in complete and partial responses on average by 14.8 times, in stabilization by 9.7 times.
Conclusions: In men with cerebral GTs, blood levels of the VEGF system components before treatment differed in patients with different future responses to combination ASRT with B or D, which allows prediction of the effectiveness of such therapy even before it is started. This connection is especially obvious for combination ASRT with B.
CLINICAL CASES
Klatskin’s tumor is a rare malignant neoplasm characterized by the absence of specific symptoms, challenges in verification and difficulties in assessing the true extent of the tumor. We present a clinical case of a patient with hilar cholangiocarcinoma. The patient received almost the entire modern complex of radiologic examinations for preoperative staging. However, concominant cholangitis, hard-to-reach anatomical localization and tumor’s creeping-growth distorted the results of instrumental studies. The true volume of the lesion was detected only intraoperatively and resulted in an expansion of liver resection volume.
The study analyzed the clinical observation of the psychological characteristics of a woman diagnosed with breast cancer, who refused part of the proposed therapy, and had no contraindications to start special treatment.
Patient Yu.F., born in 1953, diagnosis: cancer of the right breast T1NxM0 ЭР(95 %), ПР(15 %), Her2neu(0), Ki67 (5 %), refused for personal reasons from the surgical treatment proposed at the 1st stage (a written refusal was taken), in connection with which a course of hormone therapy was prescribed, a course of remote radiation therapy according to a radical program. When assessing the psychological profile of the patient, the data obtained demonstrate the presence of paradoxical hyperprotection in the patient who refused part of the treatment. Her psychological profile is similar to the psychological characteristics of women with breast cancer, whose course of the disease ended in death. In a study conducted in 2021, data were obtained on women with a negative outcome of the disease (death), who were convinced of their own luck and in the ability to control what was happening, used a wide range of coping strategies, were more resilient, are optimistic and had a pronounced internality in comparison with women in whom the disease went into stable remission.
The expression of prostate-specific membrane antigen (PSMA) on the surface of prostate cancer cells is increased with tumor progression, which is the basis for a theranostic approach in the treatment of these patients. The PSMA ligand, labeled with the therapeutic radionuclide lutetium-177 (177Lu), delivers 177Lu beta particle radiation to PSMA-expressing prostate cancer cells. Currently, PSMA-targeted radioligand therapy with the radiopharmaceutical 177Lu-PSMA-617 is approved for the therapy of patients with metastatic castration-resistant prostate cancer (mCRPC). We present a clinical case of successful use of this method of treatment in our center in a patient with mCRPC, progressing after two lines of therapy — hormone therapy with new generation of androgen signal inhibitors (abiraterone, enzalutamide) and chemotherapy with docetaxel.
LETTER TO THE EDITOR
ANNIVERSARY
ISSN 2713-167X (Online)