Multiple Primary Malignant Neoplasms Research Articles

Endoscopic ultrasound-guided tissue acquisition for focal liver lesions in patients with a history of multiple primary malignant neoplasms.

This study aimed to investigate the usefulness of endoscopic ultrasound-guided tissue acquisition (EUS-TA) for diagnosing focal liver lesions in patients with a history of multiple primary malignant neoplasms. Among patients who underwent EUS-TA for focal liver lesions between 2016 and 2022, those with a history of multiple malignant neoplasms were included. A histologically confirmed malignant tumor within the past 5 years before EUS-TA was defined as a history of malignant neoplasm. The primary outcomes were diagnostic ability and adverse events of EUS-TA. This study included 16 patients (median age, 73 [33-90] years), the median tumor size was 32 (6-51) mm, 14 had a history of double malignant neoplasms, whereas two had triple malignant neoplasms. Malignant neoplasms were detected histologically or cytologically in all cases. Immunohistochemistry was performed in 75% (12/16), and the final diagnosis of EUS-TA was metastatic liver tumor in 12 patients, and primary malignant liver tumor in four patients. The primary site could be identified in 11 of 12 metastatic tumor cases. The diagnostic yield of EUS-TA was 100% (16/16) for differentiating benign and malignant tumors and 94% (15/16) for confirming the histological type including the primary site of metastatic lesions. No adverse events were associated with the procedure. EUS-TA is a useful diagnostic modality for focal liver lesions in patients with a history of multiple malignant neoplasms, allowing for the differential diagnosis of primary and metastatic tumors and identification of the primary site of metastatic lesions.

Treatment of patients with multiple primary malignant neoplasms (solid tumors and malignant diseases of the hematopoietic tissue) using systems for independent prolonged infusion therapy. Clinical observations

Study of the problem of multiple primary malignant neoplasms (MPMNs) becomes more important and significant in modern clinical oncology. MPMN is a varied group of independent tumors of varying origin located in one or several organs. Due to introduction of single-use elastomeric microinfusion pumps into the clinical practice, continuous cyclical drug outpatient and in-hospital treatment of oncological patients with MPMNs can be performed. Significant successes of specific therapy led to increased lifespan of patients with MPMNs. Prolonged administration of drugs using infusion pump with set velocity allows to deliver cytostatics into the patient’s body in strictly controlled amounts. The article presents 2 clinical cases of effective antitumor treatment of patients with MPMNs using infusion pum

Double Synchronous Primary Tumors: Metastatic Melanoma and Advanced Pulmonary Adenocarcinoma in a 32-Year-Old Adult: Case Report and Literature Review

Introduction: The presence of multiple primary malignant neoplasms is an unusual finding during the diagnostic approach of patients with cancer. The coexistence of melanoma with lung adenocarcinoma is extremely rare according to some cohort studies since a prevalence of 0.05% is estimated in this group of patients. The most relevant risk factors for the development of multiple malignant tumors are genetic, environmental exposures to carcinogenic substances, and treatment of a preexistent cancer. Case description: Male, 32 years old who denies family history of malignant neoplasms, drug addiction, chronic degenerative diseases, allergies, surgeries, and hospitalizations. His main symptom was a progressive weakness of the right upper and lower limb which, over a period of days, made it impossible to walk. During his hospitalization, MRI revealed metastatic lesions associated with vasogenic edema. For this reason, an evaluation was requested by the neurosurgery service, who performed a decompressive craniectomy with a biopsy that reported malignant cells consistent with metastatic melanoma. As part of the diagnostic approach, a thoracoabdominal CT with IV contrast was performed, which revealed another tumor at the lung level in the left lower lobe that obliterates the bronchus, not suggestive of metastatic activity, for this reason a lung biopsy was performed, which reported findings of poorly differentiated adenocarcinoma with angiolymphatic invasion present and extensive necrosis. The patient was discharged home with the palliative care measures due to the poor prognosis of both stage IV cancers reported synchronously. Conclusion: The coexistence of 2 primary different cancers in the same patient is an unusual phenomenon which represents a challenge for the multidisciplinary team that treats the patient. Likewise, the coexistence between melanoma and lung adenocarcinoma is exceptionally reported in the literature, which in advanced phases confers a poor prognosis and few therapeutic options.

Optimal tactics of ovarian and metachronous breast cancer treatment in <i>BRCA</i> mutations carriers

Treatment of patients with multiple primary malignant neoplasms caused by genetic mutations requires correct priorities from the clinician in selection of the most effective therapeutic tactics. An important aspect in this case is the identification of the neoplasm determining patient’s survival. The main goal is to achieve maximal treatment effect for this tumor and use therapy methods for control of other synchronous and metachronous tumors.The article presents a clinical case of a patient with BRCA1 mutation-associated recurrent ovarian cancer and de novo breast cancer of negative subtype. Combination multidisciplinary and personalized approach to treatment which led to the maximally effective result is described. Personalized approach to prescription of antitumor drug therapy, timing of surgical intervention and subsequent targeted therapy allowed to realize maximal antitumor effect and increase the patient’s lifespan.

Multiple primary synchronous malignant skin neoplasms (case report and literature review)

The non-melanoma skin cancer is a leader among malignant tumours over last decades. Also, the incidence of multiple primary malignant neoplasms is increasing. We reported the case of a 68-year-old woman with locally advanced multiple primary synchronous malignant skin neoplasms (basal cell carcinoma and sarcomatoid carcinoma of skin) who was successfully treated. Thanks to individualized multimodal treatment, the basis of which is radical surgical intervention, careful follow-up was possible to achieve a complete cure of the patient with a good cosmetic and functional result. Our case report represents the need to increase the level of oncological alertness among primary care specialists and conduct educational work among the population in order to early diagnose tumors.

Detection of a status of microsatellite instability in tumors of patients with endometrioid adenocarcinoma of the ovaries and/or of uterine corpus

Introduction. Multiple primary malignant neoplasms of female reproductive organs are a rare pathology. However, over the past decades, there has been an upsurge of interest in the study of this phenomenon in oncology. This is particularly the case for the diagnosis of synchronous endometrioid adenocarcinoma of the ovaries and uterine corpus, which histogenetically belong to the same germ layer and have similar histological structure. Until recently, clinicians relied only on morphological examination in these cases, but with the development of molecular genetic technologies, new diagnostic possibilities have emerged.Aim. Is the detection of the status of microsatellite instability in tumors of patients with endometrioid adenocarcinoma of the ovaries and/or uterine corpus.Materials and Methods. A pilot retrospective molecular genetic study (n = 48) was conducted to determine the status of microsatellite instability (MSI) in the tumors of the ovaries and/or uterine corpus: it involved 33 patients with solitary endometrioid ovarian cancer and 15 patients with synchronous endometrioid adenocarcinoma of the ovaries and uterine corpus. Microsatellite instability status was detected using PCR method with subsequent fragment analysis performed on ABI PRISM 3500 genetic analyzer (8 capillaries, Applied Biosystems). DNA was isolated from paraffin blocks of surgical specimens using DNAsorb B extraction kit (AmpliSens, Russia), according to the manufacturer’s manual. DNA concentration was estimated fluorometrically using Qubit 2.0 (Life Technologies, USA). The obtained data were analyzed using GeneMapper program (Thermo Fisher, USA). In case of polymorphism of two and more markers high-level microsatellite instability (MSI-H) was observed.Results. The incidence of MSI-H in solitary endometrioid ovarian cancer (n = 33) was 12,1 % (4 cases), while in synchronous ovarian and uterine corpus tumors (n = 15) MSI-H incidence made up 20 % (n = 3). Herewith, there have been only cases of a combination of endometrioid histotypes of ovarian and endometrial cancer with identical status of microsatellite instability. Thus, the incidence of MSI-H in synchronous endometrioid adenocarcinoma of the ovaries and uterine corpus (20 %) is comparable to that in solitary endometrial cancer.Conclusion. Our pilot study became a significant complement to the previously published materials, as it allowed to confirm the clonal origin of tumors in patients with endometrioid adenocarcinoma of the ovaries and uterine corpus, that can affect the stratification of treatment strategy for this category of patients.

Immune thrombocytopenia in the aspect of multiple primary neoplasms

Multiple primary malignant neoplasms (MPMNs) is a complex process in which the development of 2 or more neoplasms simultaneously or after a certain interval is observed. MPMNs develop independently from each other within one or more organs. Many etiopathogenetic factors can cause MPMNs. Numerous studies have been conducted to study the effect of T-cell immunity on the development of this pathology. Today, there is a steady upward trend in the prevalence of mpmns, which, on the one hand, is due to more effective methods of early diagnosis, an increase in patient overall survival, and early antitumor therapy (chemotherapy, radiation therapy), on the other hand, this trend may be associated with pathology of T-regulatory cellular immunity. T-regulatory cells play a strategic role in the development of immune homeostasis, and their function is closely related to the occurrence of a wide range of pathologies, including autoimmune diseases and malignant neoplasms. The article presents a clinical case of a patient with a confirmed diagnosis: mpmn, immune thrombocytopenia (idiopathic thrombocytopenic purpura). On prednisolone therapy, remission was achieved for 2 metachronous tumors and a complete hematological response for immune thrombocytopenia was obtained. there were no signs of hemorrhagic syndrome and complications during prednisone therapy. It is planned to continue monitoring the patient for metachronous tumors by a hematologist, an oncologist at the place of residence, as well as at the center for orphan diseases of the Moscow Regional Research Clinical Institute named after M. F. Vladimirsky with control of platelets and general condition.

The place of multiple primary cancers in urologic oncology

Background. In Russia, statistical record of multiple primary cancers has been implemented only recently, and there are few scientific publications. Multiple primary malignant neoplasms of the urologic locations are described even less in literature. The problem of multiple tumors becomes more pressing with each passing year.Aim. To perform retrospective study of statistical data on urologic multiple primary cancer from one department.Materials and methods. An analysis of retrospective data from medical histories of patients who received treatment between 1997 and 2020 in urologic oncology departments where the authors worked: Omsk Regional Oncological Dispensary (1997–2005), Moscow Oncology Clinical Hospital No. 1 (2003–2005), Moscow City Oncology Hospital No. 62 was performed.Results. During the analyzed period, 23,299 hospitalizations including repeated were registered for 19,040 patients. Year-by-year data analysis showed 1,817 patients with multiple tumors, among them 1,508 patients with multiple primary malignant tumors, one and/or more of which were urologic pathology. The most common diseases were bladder cancer (n = 631), renal cancer (n = 618), prostate cancer (n = 614). A significant number of patients (n = 125; 8.29 %) had multiple tumors in 3 or more urologic locations. Tumors of the upper urinary tract were observed in 78 patients, testicle – in 36, penis – in 22, adrenal gland – in 10, urethra – in 4. Women comprised 28.05 % (n = 423) of the patients, men – almost 72 % (n = 1,085). This patient distribution by sex reflects the fact that urologic oncology includes both tumors of the urinary tract and male sex organs.Conclusion. Currently, the questions of terminology of multiple primary tumors remain open: multiple primary, multilocular, bilateral tumors, and mixed tumors. There is a lack of understanding in definition of the border between implantation metastases and multiple primary tumors in upper tract urothelial carcinoma and bladder cancer, between metastatic or bilateral tumors in bilateral renal cell carcinoma of the same morphology, etc.

Epidemiological review of multiple primary malignant neoplasms of the prostate, kidney, and bladder

Background. In recent years, an increase in the incidence of multiple primary malignancies has been observed. Multiple primary malignancies are an independent occurrence and development of two or more neoplasms of different histological origin in one patient.Aim. To evaluate epidemiological, clinical and morphological aspects of primary multiple malignant neoplasms of the prostate, kidney, and bladder.Materials and methods. Data analysis of the work report of the Saratov region oncological service in 2019, presented by the Regional Clinical Oncological Dispensary, patient case histories in the archive of the medical information system was performed.We performed a comparative analysis of the literature sources and data we obtained based to the following criteria: topographic anatomical combination of tumor locations, distribution of tumor combinations depending on time of occurrence (synchronous, metachronous), dynamics of urogenital multiple primary malignancies diagnosis in 2012-2019, distribution by gender and age, combination of stages of tumor process in both tumors, distribution by combination of histological types.Results. Between 2012 and 2019, 783 cases of multiple primary tumors with lesions in the urogenital system were identified. We studied 186 cases with a combination of two malignant neoplasms in the prostate, kidney, and bladder. Tumors developed synchronously in 36 % of patients, metachronously in 64 %. Mean patient age was 75 years. Half of the cases were in the group of localized stages - 90 (48.4 %), with the most common combination of TI-TII stages observed in 46 (24.7 %) cases. Combinations of acinar adenocarcinoma of the prostate with urothelial carcinoma of the bladder (34.7 %), clear cell renal carcinoma (27.8 %), papillary urothelial carcinoma of the bladder (12.5 %) were the most common according to histological diagnosis of primary multiple tumors of the urogenital system.Conclusion. Over the recent years we can observe a steady growth of diagnosable urogenital multiple primary malignancies. Morphological verification of the tumor and revelation of the most frequent histological types allows to assume the presence of the common mechanisms of development and the influence of tumor microenvironment on the growth of both tumors in a multiple primary malignancies pair.

The role of 18F-FDG PET/CT in patients with synchronous multiple primary malignant neoplasms occurring at the same time.

Synchronous multiple primary malignant neoplasms occurring at the same time (SMPMNS) are not currently uncommon in clinical oncological practice; however, the diagnostic performance of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) for SMPMNS needs further elucidation. This study aimed to evaluate the application of 18F-FDG PET/CT in patients with SMPMNS. The clinical and imaging data of 37 patients with SMPMNS who had undergone 18F-FDG PET/CT from October 2010 to December 2020 were retrospectively analyzed. The kappa consistency test was applied to evaluate the consistency of the diagnostic performance between PET/CT and conventional imaging (CI). The sensitivity, specificity, and accuracy of PET/CT and CI in the detection of metastatic lesions were compared. This retrospective diagnostic study included 74 lesions identified in 37 patients with SMPMNS, with 94.6% of patients having double primary tumors. Of the incidences of SMPMNS, 18.9% occurred in the same organ system, with respiratory tumors being the most common type of neoplasm (43.2%) and the lung being the most common primary site (40.5%). The overall survival of SMPMNS patients without metastases was longer than that of those with metastases (χ 2=12.627, p=0.000). The maximum standardized uptake value (SUVmax), the SUVmax ratio (larger SUVmax/smaller SUVmax), and the difference index of SUVmax (DISUVmax) [(larger SUVmax-smaller SUVmax)/larger SUVmax] of the primary lesions ranged from 0.9 to 41.7 (average=12.3±7.9), from 0.3 to 26.7 (average=4.4±6.9), and from 0.0% to 96.3% (average=50.3%±29.3%), respectively. With regard to diagnostic accuracy, PET/CT and CI showed poor consistency (κ=0.096, p=0.173). For the diagnosis of primary lesions (diagnosed and misdiagnosed), PET/CT and CI also showed poor consistency (κ=0.277, p=0.000), but the diagnostic performance of PET/CT was better than that of CI. In the diagnosis of metastases, the patient-based sensitivity, specificity, and accuracy of PET/CT were 100.0%, 81.8%, and 89.2%, respectively, while those of CI were 73.3%, 100.0%, 89.2%, respectively. The sensitivity and specificity values were significantly different, with PET/CT having higher sensitivity (p=0.02) and CI showing higher specificity (p=0.02). 18F-FDG PET/CT improves the diagnostic performance for SMPMNS and is a good imaging modality for patients with SMPMNS.

The surgical treatment of locally advanced angiosarcoma of the anterior mediastinum. A clinical case

Tumors of the mediastinum is a collective term that includes neoplasms of various degrees of malignancy, different morphogenesis, originating from heterogeneous tissues and combined into one nosological form according to anatomical localization. Angiosarcoma is a rare malignant tumor originating from a vessel wall. In the general structure of sarcomas, its frequency is estimated at 1%. The tumor is characterized by an aggressive course, local recurrence, hematogenous metastasis, poor sensitivity to chemotherapy and radiotherapy. Surgery remains the main treatment for angiosarcomas. The article presents a clinical case. A 55-year-old patient has multiple primary malignant neoplasms: cancer of the body of the uterus pT1aN0M0 IA stage. Surgical treatment from 12.15.2020 panhysterectomy; angiosarcoma of the anterior mediastinum with lesions of the manubrium, body of the sternum and the 1st rib on the left, invasion into the left brachiocephalic vein with the formation of a tumor thrombus in it, growing into the upper lobe of the left lung, T3N0M0, G1. Surgical treatment from 08.12.2021 resection of the manubrium and body of the sternum with resection of the anterior segments I, II, III ribs on both sides, resection of the left brachiocephalic vein, removal of an anterior mediastinal tumor, atypical resection of the upper lobe of the left lung en bloc, reconstruction of the sternum and ribs with an individual titanium 3D prosthesis. The patient was discharged from the hospital in a satisfactory condition.

Management of patients with multiple primary сancer in the practice of a modern oncologist. Case report and literature review

The purpose of the study. Multiple primary malignant neoplasms or polyneoplasia are a phenomenon of tumorigenesis and one of the little-studied categories in modern clinical oncology. The increase in the cancer incidence, as well as the need to make difficult decisions about further treatment strategy, enhance the relevance of studying multiple primary malignant neoplasms. This review discusses the current positions of medicine in relation to this category of malignant neoplasms, and presents a case report of a patient with this disaese. Material and methods. We have analyzed the results of international studies on the management of patients with multiple primary cancer. the search for relevant sources was carried out in the Web of Science, Scopus, Medline systems with a chronological interval of 2016–2021. of the analyzed studies, 60 were used to compile a systematic review with a case report. Results. The analysis showed that timely diagnosis and improvement of cancer screening programs are necessary to improve the control of these tumors. Psychological work with a patient, strengthening of his commitment to therapy and the implementation of medical recommendations are integral parts of improving cancer care for patients with such disease. Conclusion. A comprehensive analysis of multiple primary malignant tumors requires long-term follow-up of a large population, taking into account genetic factors, environmental factors, exposure to smoking and nutrition, and comorbid pathology. Timely diagnosis and improvement of cancer screening programs are necessary to improve the control of multiple primary malignant tumors.

Multiple primary malignant neoplasms of the mouth and oropharynx

Introduction. Probability of development of multiple primary tumors in patients who received treatment due to head and neck cancers varies between 5.6 and 35.9 % per different sources. moreover, treatment capabilities are severely limited by postoperative anatomical changes and previous radiation therapy, and the second tumor frequently causes death in these patients.The study objective is to identify the epidemiological features of the development of synchronous and metachronous primary multiple tumors in the head and neck.Materials and methods. The article analyzes data on 103 patients with multiple primary tumors who received treatment due to tumors of the head and neck between 1991 and 2020 at the N.N. Blokhin National medical Research Center of Oncology and A.S. Loginov Moscow Clinical Scientific Center.Results. During the study, typical locations of metachronous tumors in patients who received treatment due to primary malignant tumors of the head and neck were determined, duration of development of multiple primary tumors, treatment methods and survival rates were analyzed.Conclusion. Due to high risk of multiple primary tumors in patients who received treatment due to malignant tumors of the head and neck in the next 5 plus years, it is expedient to observe these patients during their whole lifetime. Considering typical locations of metachronous tumors, examination during dynamic observation should include instrumental methods such as panendoscopy. Surgical treatment should involve the whole spectrum of minimally invasive interventions including CO2 laser surgery and transoral robot-assisted interventions.

Clinical characteristics and prognostic analysis of multiple primary malignant neoplasms in female patients with breast cancer or genitalia malignancies.

BackgroundAs public awareness of health has increased and diagnostic and treatment options have improved, the survival of patients with malignant tumors has continued to extend, and the population has been aging, the number of multiple primary malignant neoplasms has gradually increased in recent years. There are few reports concerning female patients with multiple primary malignant neoplasms of breast cancer or genitalia malignancies. In this study, we aimed to analyze the clinical characteristics and prognosis of multiple primary malignant neoplasms in female patients with breast cancer or genitalia malignancies, as well as further explore the factors that affect the survival.MethodsWe collected clinical data on 80 female patients diagnosed with multiple primary malignant neoplasms of the breast or genitalia, described their clinical features. Furthermore, we calculated the survival and prognostic factors for 52 participants.ResultsIn our study, the prevalence rate of multiple primary malignant neoplasms was 0.66% (367/55404). Corresponding to female patients with multiple primary malignant neoplasms of breast cancer or genitalia malignancies, it was 1.4% (80/5707). the median age of diagnosis for the first tumor was 48 years, and the median age of diagnosis for the second tumor was 52 years. Regarding the interval, 67.57% (50/74) of patients were within five years. Most tumors were located in the breast (44.68%), followed by the uterus (20.21%), the ovary (17.02%), and the cervix (15.96%). The overall 12-, 36-and 60-month survival rates of the patients were 86.4%, 74.3%, and 69.8%. For the female patients, the stage (III–IV) (P = 0.046), non-radical surgery (P = 0.002), and types of the last tumor (breast cancer or genitalia malignancies) (P = 0.019) were associated with the poor prognosis.ConclusionsFemale patients with breast cancer or genital malignancies should pay attention to screening for the second tumor, especially within 4 years after the first tumor diagnosed. Furthermore, during tumor screening, it may be recommended for these patients to focus on colorectal cancer and lung cancer. Compared with previous studies, in addition to clinical staging and types of surgery, we found whether the last tumor was breast cancer or genitalia malignancies should also be considered a prognostic factor.

Territorial manifestation features of multiple primary malignant neoplasms in carriers of germline mutations in the BRCA 1 gene in Republic of Bashkortostan.

e22523 Background: Recent advances in the diagnostic and therapeutic fields of oncology have increased the life expectancy of cancer patients, and therefore carriers of germline mutations, who are at high risk of developing a malignant neoplasm, also have a higher risk of developing a second synchronous or metachronous malignant tumor. The aim of this work is to study the features of the development of primary multiple malignant neoplasms in patients with germline mutations in the repair genes. Methods: Among all treated in the Republican Clinical Oncological Dispensary patients germline mutations in the repair genes were detected in 225 persons. Mutations were determined by polymerase chain reaction (PCR). The material of the study was a sample of venous blood taken from a patient on an empty stomach. A diagnostic panel was used to detect the most common mutations in Russia in the BRCA1 (5382insC, 4153delA, 300T > G, 185delAG, 2080delA, 3819delGTAAA) and BRCA2 (6174delT) genes. In the absence of a mutation, the study was carried out by the next generation sequencing (NGS) method. Results: After a molecular genetic study from 2014 to 2021, we determined the spectrum of germline mutations in residents of the Republic of Bashkortostan: BRCA 1 - c.5266dupC, c.3143delG, c.5161C > T, c.5382 insC, c.3819delGTAAA, c. 300T > G, c.5136G > A, 185delAG, 4153delA, 2080delA; BRCA 2 - c.6621_6622del, p.39-1_39delGA, c.961_962insAA. Among carriers of germinal mutations, primary multiple cancer was registered in 14.6% (33/225) of patients with mutations in the BRCA 1 genes. The following mutations were identified in patients with primary multiple malignant neoplasms: c.5382 insC and c.3819delGTAAA in the BRCA gene 1. The first primary breast cancer was registered in 10.6% (24/225) of patients, ovarian cancer in 1.8% (4/225), gastric cancer in 0.4% (1/225), primary multiple synchronous breast and ovarian cancer in 1.8% (4/225). In carriers of germinal mutations, manifestations of the first primary cancer were observed at the age of 29 to 60 years. The manifestation of the second primary cancer was registered in 2-18 years after the manifestation of the first primary cancer. Twenty-two patients subsequently developed a second primary breast cancer and 11 patients developed ovarian cancer. Also, 6 patients had a manifestation of the third primary cancer of the breast, ovaries or stomach in 8-26 years after the manifestation of the second primary cancer. Conclusions: Primary multiple cancer in carriers of germline mutations in the Republic of Bashkortostan was observed in 14.6% (33/225) of patients with mutations in the BRCA 1 genes. The period of manifestation of a secondary malignant tumor ranged from 2 to 18 years. This study plays an important role in the process of optimizing screening for multiple primary malignant neoplasms for carriers of germline mutations.

Анализ результатов многолетнего массового скрининга мутаций в генах BRCA1/2 у больных с различными типами злокачественных новообразований

Background: germline mutations in the BRCA1 and BRCA2 genes are associated with a high risk of developing cancer of various localizations. Currently, the determination of BRCA status in such patients is important for choosing surgical tactics and determining indications for the administration of multiple chemotherapy drugs. Aim: to evaluate the results of mass genetic screening for mutations in the BRCA1 and BRCA2 genes in patients with various types of malignant neoplasms (MN). Patients and Methods: the results of genetic screening of 5043 patients who are reviewed in the study. The patients had the following diagnoses: breast cancer (BC, n=4216), ovarian cancer (OC, n=481), multiple primary malignant neoplasms (n=174), pancreatic cancer (n=96) and prostate cancer (n=75). Real-time PCR-based genetic testing for eight recurrent BRCA1/2 gene mutations specific for the Russian population was performed for all patients. The study of the entire coding sequence of the BRCA1/2 genes was carried out in 655 patients with negative screening results for mutations using high-resolution melting curve analysis, Sanger sequencing, and massively parallel sequencing. Results and Discussion: among 5043 cancer patients, the total frequency of BRCA mutations was 8%. In patients with BC the recurrent variants accounted for 6.7%, bilateral BC — 13.5%, OC — 17%, multiple primary malignant neoplasms (MPMN) — 13.1%, pancreatic cancer — 3.1%, while in patients with prostate cancer no mutations were found. The frequency of the c.5266dup mutation in the BRCA1 gene was 5.63%. Forty nine patients (0.97%) were carriers of another mutation — p.C61G, which is specific for the Slavic populations. Other variants were found much less frequently (0.1–0.38%). Thus, screening for common mutations helped to determine the prevalence of each of the variants and proved a high frequency of c.5266dup and p.C61G mutations. The analysis of the coding sequence of the BRCA1/2 genes in 655 patients revealed pathogenic mutations (class 5) in 13% of cases. The prevalence of rare variants in patients with BC was 11.1%, bilateral BC — 26.5%, OC — 14.9%, МPМN — 31%, pancreatic cancer — 2.3%, and prostate cancer — 2.5%. In the BRCA1 gene, 41 unique clinically significant mutations were found, and four of them were repeated in unrelated patients. In the BRCA2 gene, 29 unique clinically significant mutations were found, five of which were repeated. Moreover, 19 missense mutations were detected which, according to the databases, were categorized as variants with unknown clinical significance (class 3). They were analyzed using seven pathogenicity prediction algorithms. As a result, five mutations were interpreted by the most algorithms as likely pathogenic or pathogenic (class 4/5), five mutations were re-assessed as variants with unknown significance, and nine variants were identified as clinically insignificant. Conclusion: thus, the Russian population is characterized by the presence of multiple recurrent mutations, while in patients with different cancer types the prevalence of c.5266dup and p.C61G is significantly higher than the prevalence of other variants. Analysis of recurrent variants in the BRCA1/2 genes enables identification of approx. 80% of carriers of the pathogenic mutations. The use of the panel kit which includes such variants is considered as an inexpensive and sensitive algorithm for the first-step screening of the BRCA1/2 genes. A follow-on investigation of all coding gene regions (sequencing) is feasible for the studied patient groups and can significantly increase the detectability of pathogenic mutations in the BRCA1/2 genes. KEYWORDS: BRCA1 mutations, BRCA2 mutations, breast cancer, ovarian cancer, malignant neoplasms. FOR CITATION: Stroganova A.M., Pospekhova N.I., Golovina D.A. et al. Review of the results of mass screening for the BRCA1/2 gene mutations in patients with different types of malignant neoplasms. Russian Medical Inquiry. 2022;6(6):297–308 (in Russ.). DOI: 10.32364/2587-6821- 2022-6-6-297-308.

Method to Create Multiple Primary Malignant Neoplasms with Stimulation of Tumor Growth under Conditions of Primary Immunodeficiency in Experiment.

The experimental model of synchronous multiple primary malignant tumors (MPMT) was created. B16/F10 melanoma (0.5 ml of suspension diluted 1:20 in saline) and sarcoma 45 (0.5 million tumor cells in 0.5 ml saline) were simultaneously subcutaneously inoculated to male BALB/c nude mice. In the model of synchronous MPMT, the tumors appeared faster by 2.4 times and had greater volumes: melanoma by 2.2 times and sarcoma by 3.2 times; melanoma metastasized into sarcoma in 71.4% cases; the survival of mice with MPMT was lower. The altered dynamics of malignant growth in the MPMT model is based on the mutual influence of tumors, which results in the exchange of "structural information".

Clinical and pathological characteristics of multiple primary malignant neoplasms cases.

To investigate the clinical and pathological features of multiple primary malignant neoplasms (MPMNs) cases. The clinical data of 24105 tumour patients admitted to Jiangsu Cancer Hospital in 2018 were retrospectively reviewed, and 270 patients with MPMNs were selected as the research subjects. Among them, 101 cases of synchronous carcinoma (SC) and 92 cases of metachronous carcinoma (MC) were divided into groups for statistical analysis. Univariate and multivariate cox regression analyses were conducted using SPSS 22.0 software. Among 24105 cases, there was a male-to-female ratio of 1.45:1. Compared with MC cases, SC patients have a higher proportion of male cases. Primary neoplasms in gastric cancer, head and neck cancer, oesophageal cancer and colon cancer occupied most cases in male MPMNs, while primary breast cancer ranked first in female MPMNs. In addition, the leading secondary neoplasms were duodenal carcinoma, lung cancer and male MPMNs and lung cancer in female MPMNs. As for SC MPMNs, primary neoplasms were occupied by lung cancer, gastric cancer and oesophageal cancer, while the secondary neoplasms were mostly consisted of oesophageal cancer and lung cancer. Finally, the MC MPMNs were mostly consisted of breast cancer and gastric cancer as primary neoplasms, while lung cancer and oesophageal cancer as secondary neoplasms. Screening for primary cancer should be strengthened over the age of 50years for male patients with gastric cancer or female patients with breast cancer to reduce or monitor the occurrence of MPMNs.

Propensity score matching analysis of ovarian cancer patients with multiple primary malignant neoplasms using multicenter real-world data.

e17501 Background: Multiple primary malignant neoplasms (MPMNs) in patients with ovarian cancer is rare and has not attracted enough attention. It is unclear how the MPMNs affect the prognosis of ovarian cancer (OC) patients. Methods: This is a multicenter retrospective analysis of 5, 268 ovarian cancer patients from six centers who was diagnosed with ovarian cancer from January 1, 1989 to August 21, 2020. Propensity score matching was used to balance the baseline characteristics between patients with and without MPMNs. Cox regression analysis was utilized to analyze the influence of MPMNs on overall survival (OS). Results: After excluding unqualified medical record, totally 4, 848 patients were analyzed and 240 were concurrent at least one MPMNs other than OC. Ten patients had two MPMNs and one patient had three. The most common concurrent cancer was breast cancer (111/240, 46.25%), followed by endometrial cancer (37/240, 15.42%), and cervical cancer (30/240, 12.50%). Patients with MPMNs were elder than those without MPMNs (52 vs. 51, P = 0.03) when ovarian cancer was diagnosed. And the proportion of early-stage cases was lower in patients with MPMNs (25.8% vs. 27.2%, P < 0.001). Patients with breast cancer had a higher proportion of high-grade serous ovarian cancer (HGSOC) than those without MPMNs. After using the propensity score matching method adjusting age, pathological type, grade, and stage, concurrent MPMNs, including breast cancer, had no effect on OS of ovarian cancer patients. Among 240 patients with MPMNs, patients with breast cancer shared similar age and stage compared with the rest patients, while their proportion of HGSOC was higher than patients with other cancer (68.4% vs. 51.1%, P = 0.028). However, the median OS of those two groups were similar (27.3 m vs.27.1 m, P = 0.744). In addition, 94 patients were diagnosed with breast cancer prior to ovarian cancer, seven diagnosed posteriorly to ovarian cancer, four diagnosed simultaneously, and six had no precise diagnosed dates. There was no remarkable difference in clinical characteristics between the prior and posterior groups, however, the median OS of those seven patients was significantly longer than the prior group (76.0 m vs. 25.4 m, P = 0.002). Conclusions: The MPMNs showed no influence on the overall survival of ovarian cancer patients. The order of diagnosis of ovarian cancer and breast cancer might affect the prognosis.

Clinical characteristics and prognostic outcomes of gynaecological multiple primary malignant neoplasms

Objective: To investigate the clinical characteristics and the prognostic outcomes of patients with gynaecological multiple primary malignant neoplasms (MPMN). Materials and methods: For a period of ten years, from January 2008 to December 2018, patients with gynaecological MPMN were enrolled for this study. The clinical characteristics and survival outcomes were collected and analyzed. Results: A total of 126 patients with gynaecological MPMN were included, comprising 15 synchronous MPMN and 111 metachronous MPMN. The average age of the patients with gynaecological MPMN was 57.6 ± 10.8 years, and the probability of overall survival (OS) at 1, 2, 3, and 5 years was 88.6%, 82.6%, 76.9% and 68.7%, respectively. The OS of patients with gynaecological cancer as the first neoplasm was worse than those with non-gynaecological cancer as the first neoplasm (HR: 2.2, P = 0.049); the OS of patients accompanied by breast cancer was better than those accompanied by other cancers (HR: 0.346, P = 0.033). Univariate regression analysis showed that “age”, “FIGO stage” and “gynaecological cancer as the first neoplasm” were the factors for poor survival; “Accompanied by breast cancer” and “surgery for first or second neoplasm” were the factors for favourable survival. Conclusions: “Gynaecological cancer as the first neoplasm” is a factor for poor survival in patients with gynaecological MPMN, and “FIGO stage” is the independent risk factor (HR: 2.339, P = 0.001). “Accompanied by breast cancer” and “surgery for the neoplasm” are factors for favourable survival. Mostly, “surgery for the second neoplasm” was the independent protective factor (HR: 0.212, P = 0.005) for gynaecological MPMN.