Interstitial high dose rate brachytherapy boost in early-stage breast cancer: deformable image registration for defining target volume

Purpose: optimization of the technique of additional irradiation of the removed tumor bed using high-dose brachytherapy for breast cancer. Material and Methods: the results of treatment of 28 patients diagnosed with breast cancer were analyzed. After surgical treatment and a course of external radiation therapy, all patients underwent additional irradiation of the removed tumor bed using high-dose brachytherapy. The assessment of the operation protocols, the data of the pathomorphological conclusion was carried out, and on the basis of pre- and postoperative CT images, the formation of irradiation fields for high-dose brachytherapy was carried out. Results: After deformable (nonrigid) registration of pre- and postoperative CT images of 28 patients, it was revealed that in 18 women (64.3% of cases) the location of interstitial markers and the primary tumor focus does not match topographically, which can cause incorrect formation of borders irradiation. In 35.7% of cases, radiopaque markers were located on the chest wall (on the pectoralis major muscle) when the primary tumor was located in the breast tissue. In 25% of cases, the markers were located cranial or caudal to the topography of the primary tumor focus. Label migration occurred in 3.6% of cases. In 35.7% of cases, the topography of the primary tumor node and marks completely coincided. Conclusions: The use of deformable (non-rigid) registration of pre- and postoperative CT images is a simpler method to determine the topography of the removed tumor bed, which subsequently leads to a more accurate formation of the clinical volume of irradiation.

Incidence of antiphospholipid antibodies in new patients with non-Hodgkin lymphoma

Non-Hodgkin’s lymphoma (NHL) presents a group of histologically and biologically inhomogeneous B and T cell neoplasms of lymphoid tissue with a completely unidentified etiology. Antiphospholipid antibodies (aPL) are antibodies produced as a result of misinterpretation of platelet membrane phospholipids. It is well known that antiphospholipid antibodies are general risk factors that induce the disorder of the physiological process of hemostasis. Respectively, it is interesting to appreciate the incidence of antiphospholipid antibodies in new non-Hodgkin lymphomas patients depending on age, sex, type of non-Hodgkin’s lymphoma, the peculiarities of the onset of the disease, the degree of disease spread. According to the results of our study, we found a 14.8% incidence of aPL in primary patients with non-Hodgkin’s lymphoma, more frequently in men and people older than 50 years. The positivity of aPL antibodies depended on the immunohistochemical type of malignant lymphoma, the degree of dissemination of the tumor process and independent of the location of the tumor focus (nodal or extranodal) of NHL. The incidence of aPL antibody types was uneven with the obvious predominance of lupus anticoagulant. Th is study allowed the evaluation of the incidence of antiphospholipid antibodies in primary patients with non-Hodgkin’s lymphoma.

The phenomenon of pseudoprogression in cancer immunotherapy: is everything so unambiguous?

When evaluating the effect of therapy for malignant neoplasms with inhibitors of CTLA-4, PD-1 and PD-L1, the phenomenon of pseudoprogression may occur. Pseudoprogression is an increase in the volume of tumor tissue due to immunocompetent cells (lymphocytes, macrophages) mobilized into the tumor focus under the action of immunotherapy. As the antitumor effect of lymphocytes and macrophages is realized, the tumor decreases or disappears over time. Pseudoprogression occurs with varying frequency in various types of cancer. It may also matter which immune checkpoint inhibitors is used to treat a solid tumor or lymphoproliferative disease. Currently, several immune-related response-evaluation criteria have been developed, which can help diagnose the phenomenon of pseudoprogression. But, unfortunately, none of these criteria clearly distinguish pseudoprogression from true tumor progression. In the case of an erroneous judgment about the effect of treatment, immunotherapy ends, and the patient may not get a chance for long-term remission. Using two clinical examples (immunotherapy for metastatic kidney cancer and recurrent Hodgkin lymphoma), the authors discuss the pitfalls of evaluating the effectiveness of treatment with checkpoint inhibitors.

Molecular determinants of recurrences of the human urothelial tumor

Background. Urothelial carcinoma (UTC) is an aggressive disease with a known propensity for frequent recurrence. It is difficult to predict the velocity of the development of UTC recur using modern means of clinical diagnostics. Therefore, the development of the capabilities of histo-morphological study of tumor tissues is of particular relevance.Materials and methods. The materials of publications (PubMed, CrossRef) for 1990-2021, devoted to the choice of biomarkers for the diagnosis of UTC, the analysis of molecular pathways, progression and metastasis, were studied. The search was carried out for the key phrases "urothelial carcinoma", "recurrent UTK", "stem cells", "biomarkers of bladder cancer", "genetic changes in urothelium", "circulating tumor DNA".Results. Cancer stem cells serve as a source of UTC recurrence after removal from the primary focus, localizing in any areas of the urothelium, as well as outside the main tumor focus and are characterized by a common genotype, but different phenotypic manifestations. To predict the recurrence of the tumour is advisable to use gene expression signatures, since the subtypes of UTC are characterized by clear gene expression profiles. A larger sample and independent dataset is needed to confirm the clinical significance of the findings. Combined biomarkers predict UTC behavior, and FGFR3 and TP53 mutations can be components for a panel for predicting UTC recurrence. The use of the liquid biopsy method with the determination of the level of circulating tumor DNA is a promising diagnostic method that needs to evaluate the results of an initiated randomized trial.Conclusion. The accumulation of knowledge base about the molecular patterns of UTC will help bridge the gap between the results of molecular genetic and clinical diagnostics. Molecular changes in the transitional cell UTC demonstrates a high potential for determining the timing of tumor recurrence, assessing disease-free survival of patients and for planning the resource base of the healthcare system.

THE DIAGNOSTIC POTENTIAL OF URINAY AND SERUM CYTOKERATINS FOR URINARY BLADDER CANCER

In our opinion, the obtained results show that the level of UBC cytokeratin determined in urine reflects the destruction of tissue by the tumor to a greater extent with deep invasion and with large tumor sizes. We believe that a decrease in the sensitivity of the UBC test in detecting recurrence in patients after TUR, in comparison with the sensitivity of the UBC test in patients with BC prior to treatment, is associated with an initial level of cytodestruction in the relapse of BC. The level of serum cytokeratin TPA largely reflects the onset of metabolic changes in the tumor focus. It is the combination of UBC + TPA tests that gives rise to true-positive results and a reduction in false-negative results, which increases the sensitivity of the method.

Cancer immunotherapy: current opportunities and perspectives

Cancer immunotherapy is a relatively new and pro­mising method of treating neoplasms. Understanding the antigen-directed cytotoxicity of T-lymphocytes has become one of the central directions in involving the immune system in the fight against cancer. Basic research in this area has led to the invention of checkpoint inhibitors, adoptive T-cell therapy, and cancer vaccines. Cytokines can enhance the action of T-lymphocytes for their ability to directly stimulate effector and stromal cells in tumor focus and enhance recognition of tumor cells by cytotoxic effector cells. They were the first in cancer immunotherapy and remain relevant to this day. Today, immunotherapy is an effective treatment for most malignant tumors, including melanoma, non-small cell lung cancer, liver, stomach, bladder, cervical cancer, some types of breast cancer, lymphoma, etc. However, immunotherapy of some malignant tumors is ineffective, therefore, the development of new and improvement of existing immunotherapy agents is actively underway, and there is a hope that the indications for its use will expand. For this purpose, this review discusses the principles of action of various classes of immunotherapeutic anticancer agents, namely cytokines, immune checkpoint inhibitors, and adaptive T-cell therapy. The work highlights their indications, efficacy and toxicity from the use of each class of drugs, as well as the prospects for the development of immunotherapeutic anticancer drugs.

Wilms Tumor (Nephroblastoma), Version 2.2021, NCCN Clinical Practice Guidelines in Oncology

The NCCN Guidelines for Wilms Tumor focus on the screening, diagnosis, staging, treatment, and management of Wilms tumor (WT, also known as nephroblastoma). WT is the most common primary renal tumor in children. Five-year survival is more than 90% for children with all stages of favorable histology WT who receive appropriate treatment. All patients with WT should be managed by a multidisciplinary team with experience in managing renal tumors; consulting a pediatric oncologist is strongly encouraged. Treatment of WT includes surgery, neoadjuvant or adjuvant chemotherapy, and radiation therapy (RT) if needed. Careful use of available therapies is necessary to maximize cure and minimize long-term toxicities. This article discusses the NCCN Guidelines recommendations for favorable histology WT.

Association of molecular biomarkers heterogeneity and treatment pattern, disease outcomes in multifocal or multicentric breast cancer patients

Purpose To evaluate the rates of estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), and Ki-67 heterogeneity in multifocal or multicentric breast cancer (MMBC) and its association with treatment pattern and disease outcomes. Methods MMBC patients with ER, PR, HER2, and Ki67 results for each tumor focus were retrospectively analyzed and categorized into the Homo group and the Hetero group. Chi-square test were performed to compare the treatment options between the groups. Disease-free survival (DFS) and overall survival (OS) rates were estimated from Kaplan-Meier curves and compared between two groups. Results A total of 330 patients were included and 53 (16.1%) were classified into the Hetero group. Adjuvant endocrine therapy was more frequently assigned for patients in the Hetero group than in the Homo group (84.9% vs. 71.7%, P = 0.046). There was no difference in terms of adjuvant anti-HER2 therapy (28.3% vs. 19.6%, P = 0.196) and chemotherapy (69.9% vs. 69.8%, P = 0.987) usage between two groups. At a median follow-up of 36 months, DFS rates were 81.2% for the Hetero group and 96.5% for the Homo group (HR = 2.81, 95% CI: 1.00-7.88, P = 0.041). The estimated 3-year OS rates for the groups were 95.8% and 99.5%, respectively (HR = 4.31, 95% CI: 0.83–22.46, P = 0.059). Conclusion Heterogeneity of ER, PR, HER2, or Ki67 was present in 16.1% patients with MMBC. Biomarkers heterogeneity influenced adjuvant endocrine therapy usage and was associated with worse disease outcomes, indicating further clinical evaluation.

Pregnancy During Active Surveillance of Papillary Thyroid Microcarcinoma

Introduction: Most patients diagnosed with papillary thyroid microcarcinoma (microPTC) classified as low risk and therefore eligible for active surveillance (AS) are women. Although age is a predictor of tumor progression (more frequent among young people), young adults are “appropriate” candidates for AS. Consequently, a proportion of patients with low-risk microPTC eligible for AS are women of childbearing age and knowledge of the effect of pregnancy on tumor progression is therefore important. In the Japanese population, Ito et al. observed this progression in only 8% of pregnancies. None of the series on the outcomes of AS in western populations has so far reported the behavior of microPTC in women who became pregnant during AS. Methods: We have submitted patients with low-risk microPTC to AS. Our management has been not to interrupt AS, i.e., not to indicate surgery when the patient wishes to become pregnant. We report here the results of five patients who became pregnant during AS and their follow-up up to 6 months after delivery. Results: The patients were 26 to 36 years old (median 29 years) when they became pregnant. None of them had a history of radiation exposure, one had a family history of PTC, one had associated Hashimoto’s thyroiditis, and all of them had only one tumor focus and were considered “appropriate” (but not “ideal”) candidates for AS. In fact, when pregnancy was diagnosed, the patients continued to exhibit the criterion for AS according to our initial protocol (tumor ≤ 1.2 cm, no apparent lymph node metastases [LNM] or extrathyroidal extension [ETE] on ultrasonography [US]). All women were monitored by monthly measurement of TSH and levothyroxine (L-T4) was administered during pregnancy to maintain TSH between 0.1 and 1 mIU/L. US was performed when pregnancy was diagnosed (between 6 and 9 weeks of gestation), around 22 weeks, at the end of pregnancy, and 6 months after delivery. During the evaluations, none of the patients had apparent LNM or ETE on US. None of the patients exhibited tumor growth, defined as an increase in diameter ≥ 3 mm. Tumor growth ≥ 50% was observed in only one patient, with a small reduction after delivery. Conclusions: Our preliminary results suggest that pregnancy is not associated with a high risk of progression of low-risk microPTC and that the desire to get pregnant or pregnancy should not be an exclusion factor for AS. References: Effects of Pregnancy on Papillary Microcarcinomas of the Thyroid Re-Evaluated in the Entire Patient Series at Kuma Hospital. Ito Y, Miyauchi A, Kudo T et al. Thyroid 2016; 26:156-60 AND Active Surveillance in Adults with Low-Risk Papillary Thyroid Microcarcinomas: A Prospective Study. Rosario PW, Mourão GF, Calsolari MR. Horm Metab Res. 2019; 51:703-8.