MAMMOLOGY. ORIGINAL REPORTS
Background. Dual anti-HER2-targeted therapy in breast cancer (BC) significantly increased the rate of pathological complete response (pCR) compared to single blockade when added to chemotherapy. However, limited data exist on the long-term impact on survival of the additional increase in pCR.
Aim. To improve recommendations regarding HER2-targeted agents and chemotherapy in the neoadjuvant treatment of BC.
Materials and methods. N.N. Petrov National Medical Research Oncology Center, Ministry of Health of Russia took participation in some clinical trials of neoadjuvant treatment of HER2-positive breast cancer, including NeoSphere and NeoALTTO. In multicenter, open-label, phase 2 randomised NeoSphere trial, patients with locally advanced, inflammatory, or early-stage HER2-positive BC were randomly assigned to receive four neoadjuvant cycles of trastuzumab (8 mg/kg loading dose, followed by 6 mg/kg every 3 weeks) plus docetaxel (75 mg/m2 from every 3 weeks, increasing to 100 mg/m2 from cycle 2 if tolerated) (group A), pertuzumab (420 mg every 3 weeks) and trastuzumab plus docetaxel (group B), pertuzumab and trastuzumab (group C), or pertuzumab and docetaxel (group D). After surgery, patients received three cycles of FEC. Рatients in group C received four cycles of docetaxel prior to FEC, and trastuzumab 6 mg/kg every 3 weeks to complete 1 years treatment. In NeoALTTO trial from 455 patients 154 patients received lapatinib, 149 – trastuzumab, 152 – combination of lapatinib and trastuzumab.
Results. Between 2007, and 2009, 417 patients were randomly assigned to group A (107 patients), group B (n = 107), group C (n = 107), or group D (n = 96). At clinical cutoff, 87 patients had disease progression or died. 5-year progressionfree survival rates were 81 % (95 % confidence interval (CI) 71–87) for group A, 86 % (95 % CI 72–91) for group B, 73 % for group C, and 73 % for group D (95 % CI 0.34–1.40). Disease-free survival rates were consistent with progressionfree survival rates and were 81 % (95 % CI 72–88) for group A, 84 % (95 % CI 72–91) for group B, 80 % (95 % CI 70–86) for group C, and 75 % (95 % CI 64–83) for group D. In NeoALTTO trial patients who achieved pCR had longer progressionfree survival (85 % (95 % CI 76–91)) compared with patients who did not achieve pCR (76 % (95 % CI 71–81)).
Conclusion. High levels of progression-free survival and disease-free survival at 5–10-years follow-up show large and overlapping CI, but support the primary endpoint (pCR) and suggest that neoadjuvant pertuzumab is beneficial when combined with trastuzumab and docetaxel. Additionally, they suggest that pCR could be an early indicator of long-term outcome in early-stage HER2-positive BC.
Background. Breast cancer (BC) stands as one of the most prevalent malignancies affecting women, posing a significant threat to health and life. Timely diagnosis and treatment of BC play a pivotal role in enhancing patient survival rates.
Aim. To explore such a method of visualization of BC as mammography and the correlation of its results with the data of histological and immunohistochemical studies, and their significance in planning organ-conserving operations.
Materials and methods. The study involved 217 patients diagnosed with nodular BC (T1-2N1M0). AH patients underwent digital mammography, histological examination of biopsy and surgical specimens, and immunohistochemical analysis of tumor tissue (determination of the expression of sex hormone receptors (estrogen and progesterone), HER2/neu status and the status of the Ki-67 marker, reflecting the proliferative activity of tumor cells).
Results. Comparison of mammographic and histological/immunohistochemical findings revealed significant differences in tumor visualization among major molecular subtypes of BC. A statistically significant association (p <0.001) was established between carcinoma in situ and radiological features such as spiculated margins and calcifications on mammography.
Conclusion. Mammography emerges as an objective and accessible visualization method for BC, enabling assessment of tumor size and peritumoral region. However, for planning breast-conserving surgery for luminal and HER2-positive BC subtypes, a multimodal diagnostic approach is recommended to assess tumor spread, incorporating ultrasound and contrast-enhanced magnetic resonance imaging.
MAMMOLOGY. REVIEWS
Combined methods of treatment of oligometastatic breast cancer (OMBC) based on systemic drug treatment and local treatment methods - stereotactic radiation therapy (SRT) or surgical treatment - are not included in current clinical guidelines. The European Society of Medical Oncology (ESMO) recommends the use of local control methods for patients with breast cancer without taking into account the biological subtype of the tumor. This review presents a modern understanding of the oligometastatic biological subtype based on data from clinical studies on this topic, which could contribute to decision-making in real clinical practice.
The aim of the review is analysis of the effectiveness of combined treatment methods: systemic drug therapy and local treatment methods (SRT) or surgical treatment of breast cancer of various molecular genetic subtypes.
To assess the clinical effectiveness of various approaches to the treatment of breast cancer, depending on the biological subtype, a search was conducted for scientific publications in the Medline bibliographic database. Prospective and retrospective studies demonstrate an increase in the effectiveness of treatment through a combination of systemic therapy and local control methods (surgical treatment or SRT) OMBC depending on the biological subtypes. In hormonepositive breast cancer with bone damage, SRT is most preferable, whereas in visceral oligometastases, surgical treatment is recommended. For immunocompetent tumors of triple-negative and HER2-positive biological subtypes of breast cancer, surgical treatment of OMBC is not recommended, except in cases where the positive status of HER2 is combined with a high level of expression of hormonal receptors or metastatic bone damage.
The results of current prospective studies focusing on certain biological subtypes of breast cancer will help further determine the role of this strategy in the treatment of this cohort of patients. Understanding the characteristics of the tumor process in breast cancer will allow you to personalize the treatment of patients with this disease.
We analyzed literature data on the peculiarities of the clinical manifestation and therapeutic approaches ofB RCA-associated ovarian carcinomas. The ESMO-ESGO consensus emphasised the importance of determining BRCA1/2 status in ovarian cancer patients for planning the entire treatment strategy. BRCA-associated carcinomas differ significantly from sporadic forms in terms of clinical course, response to systemic therapy, spectrum of drugs which are used for treatment, mechanisms of chemoresistance development, and prognosis. This category of patients needs new therapeutic approaches, including the development of tactics to overcome chemoresistance and modification of the entire combined treatment programme.
GYNECOLOGY. ORIGINAL REPORTS
Background. The non-declining cervical cancer incidence in the Siberian Federal District 16.30/0000 (in Russia - 13.80 /0000) necessitate preventive vaccination against the human papillomavirus (HPV).
Aim. To evaluate the cost-effectiveness of HPV vaccination in girls aged 9-14 years in the Siberian Federal District as a whole and in the context of subjects with a 60, 80, 90 percent target cohort.
Materials and methods. We studied the size of the female population aged 9-14 years in the constituent entities of the Siberian Federal District for 2022, the average total cost of the vaccine, information on the gross regional product per capita, form C51 “Distribution of deaths by gender, age groups and causes of death” of Tomsk region, 2022. Age-standardized rate per 100,000 population of morbidity and detection (in percentages) of pre-invasive cervix cancer (carcinoma in situ) in the Siberian Federal District were calculated per 100 newly diagnosed malignant cervix neoplasms in 2022.
Results. In the Irkutsk, Tomsk regions, Altai and Krasnoyarsk territories age-standardized rate (16.6; 17.8; 16.3; 18.90 /0000, respectively), the detection rate of pre-invasive cancer was 48.0-82.4 %, which indicates on the effectiveness of measures for early cervical cancer diagnosis. In the Republics of Tyva, Altai, Khakassia, age-standardized rate (26.4; 20.1; 19.30 /0000, respectively), cancer in situ was diagnosed in 8.2-23.6 % of cases, which indicates an insufficient level and defects in the organization preventive examinations in medical institutions. In the first year of vaccination against HPV with 60 % coverage of a girls cohort 9-14 years old (n = 404,943), 9.3 billion rubles will be required, with 80 % coverage (539,924 girls) - more than 12.4 billion rubles, with 90 % coverage (607,415 girls) - more than 13.9 billion rubles for primary vaccination against HPV. In subsequent years, more than 2.5-2.8 billion rubles will be required annually. Over 5 years, with 90 % coverage of the population, the financial costs of vaccination will be (817.8 million rubles), and the subsequent 4 annual investments (163.6 million rubles per year). The economic damage caused by mortality from cervical cancer in the Tomsk region over five years (2018-2022) amounted to 3,166.4 million rubles.
Conclusion. Using the example of the Tomsk region, it was noted that when comparing financial resources, the costs of vaccinating girls against HPV are 2.2 times less than the economic damage from cervical cancer mortality. Regional budget funding for girls vaccination in administrative territories is relevant before its integration into the national calendar of preventive vaccinations.
Aim. To analyze the dynamics of cervical intraepithelial neoplasia according to cytology and morphology data on the example of women’s consultations in Yekaterinburg.
Materials and methods. A descriptive epidemiological study was conducted. The authors analyzed data from reports on the work of the cervical pathology office on the basis of two women’s consultations in Yekaterinburg: the women’s consultation No. 1 of Central City Clinical Hospital No. 6 and the women’s consultation No. 2 of Central City Clinical Hospital No. 6 for the period from the 1st quarter of 2022 to the 2nd quarter of 2023.
Results. The number of results on the absence of pathological changes in the cytological examination of the cervix (negative for intraepithelial lesion or malignancy, NILM) increased quarterly in both the city’s women’s consultations during the analyzed time period. Low-grade squamous intraepithelial lesion (LSIL) has the highest proportion in the structure of abnormal cytological results. The observation group in the women’s consultation No. 1 is almost 2 times larger than in the women’s consultation No. 2 (р = 0.0048). Statistically significant differences are observed only in the frequency of ASC-US (р = 0.049). The authors did not reveal statistically significant differences in the findings of histological studies of cervical tissue.
Conclusion. After Order No. 521p entered into force in Yekaterinburg, a larger number of patients were covered by cytological screening. The number of normal results increased due to healthy women, but the frequency of abnormal cytology results remains at the same level. This may be due to increased accessibility and improved quality of medical care. In patients who have undergone cervical screening, secondary prevention of cervical cancer can be effectively carried out.
Background. Endometrial cancer (EC) treatment outcomes need to be improved. Immunotargeted therapy lead to long-term and delayed effects compared to chemotherapy. Estimation of long-term efficacy and quality of life are crucial when we are talking about efficacy in whole.
Aim. To evaluate the long-term clinical efficacy of lenvatinib plus pembrolizumab therapy in patients with EC.
Materials and methods. The study included 43 patients with stages I-IV EC with mismatch repair-proficient tumors and treatment duration of more than 9 months. We evaluated median progression-free survival, objective response, duration of treatment depending on the line of therapy, prevalence and type of adverse events, and correction regimens. Results. Lenvatinib plus pembrolizumab treatment was safe and efficacious in recurrent EC. Median of progression-free survival (patients with response or stabilization more than 9 months) is 10.2 months (95 % confidence interval 9.1-13.0), median of follow up is 9.7 (1.4-33.8) months. There were no complete responses, partial response was in 12 (28 %) patients, disease stabilization was in 31 (72 %) patients. Regarding safety, the overall rate of any-grade adverse events was 56.3 %. The most common treatment-related adverse events were fatigue (32.6 %), hypertension (23.3 %), and hypothyroidism (18.6 %). Dose reduction was performed in 22 (51.2 %) patients.
Conclusion. The combination of lenvatinib plus pembrolizumab has long-term efficacy and manageable profile of safety. The presence of a significant pool of patients with durable response allows improving the survival rate of such patients in Russia.
Background. Currently, genital endometriosis is considered as one of the most severe conditions in women of reproductive age, which has detrimental consequences for social, professional and psychological functioning. It ranks third in the structure of gynecological diseases after inflammatory diseases of the female reproductive system and uterine fibroids. Because of this, it acquires a more pronounced social significance and ceases to be only a medical problem. Aim. To study the results of surgical treatment of patients with severe forms of genital endometriosis using the da Vinci surgical robotic complex.
Materials and methods. A retrospective analysis of the treatment results of 51 patients operated on at the N.I. Pirogov National Medical and Surgical Center for the period from January 2015 to July 2024, who underwent robot-assisted (da Vinci) operations for deep endometriosis involving neighboring organs. The duration of surgery and hospital stay, the amount of blood loss, the frequency of intra- and postoperative complications, the clinical course of the disease in the long-term postoperative period, the frequency of detection of residual infiltration in the postoperative period, and the implementation of reproductive plans were analyzed.
Results. The duration of the surgical intervention was 220.8 ± 21.87 minutes. The postoperative bed-day was 6.9 ± 1.5 bed days. The average blood loss was 160.2 ± 67.58 ml. There were no intraoperative complications. Postoperative complications accounted for 7.8 %. Residual infiltration occurred in 11.7 % of cases. 94.1 % of the patients had no clinical symptoms of endometriosis in the long-term postoperative period. The pregnancy rate was 31.9 %.
Conclusion. Surgical treatment of deep endometriosis using da Vinci surgical robotic complex in the amount of radical removal of endometrioid infiltrate has a positive effect on both the clinical course of the disease and the reproductive potential of a woman. Real-time fluorescence navigation has demonstrated additional imaging capabilities in robotic surgery for deep endometriosis, potentially increasing the radicalism of surgical treatment of infiltrating endometriosis and may lead to a reduction in recurrence rates.
GYNECOLOGY. REVIEWS
The article presents a systematic analysis of studies evaluating the impact of surgical treatment of benign ovarian tumors on reproductive health, taking into account the criteria stated by the International Classification of Functioning, Disability and Health. To identify articles, foreign and domestic scientific databases were used (PubMed, Cochrane, eLibrary). After the initial identification of 704 scientific publications, 46 articles were selected using inclusion and exclusion criteria.
The conducted systemic analysis allows us to formulate the conclusion that surgical interventions performed for benign ovarian tumors contribute to damage to ovarian tissue, and as a result, a decrease in the ovarian reserve of patients, which is associated with impaired fertility. A number of authors have demonstrated some recovery of anti-Mullerian hormone (AMH) levels 3-12 months after surgery. A significant portion of the studies have demonstrated a more pronounced postoperative decrease in AMH rates in patients with endometriomas compared with women operated on for non-endometrioid ovarian tumors. Lower AMH rates were noted in women with bilateral surgeries for bilateral ovarian tumors compared to patients who had unilateral surgeries. The performed systemic analysis showed higher postoperative AMH rates in patients with intraoperative suture hemostasis in comparison with the use of bipolar energy; in addition, there is a relationship between the number of coagulations and the severity of the decrease in AMH rates. In a few studies, it was noted that patients who underwent surgical treatment of ovarian tumors experienced an earlier onset of menopause. In connection with these possible functional disorders, further clinical studies of a high level of evidence are needed, aimed at developing effective strategies for preserving the functioning of the reproductive system after surgical treatment of benign ovarian tumors.
GYNECOLOGY. CLINICAL CASE
In most cases, ovarian cancer is diagnosed at advanced stages, leading to a poor prognosis. Currently, there is no effective screening for ovarian cancer, so detecting it in the early stages is a fairly successful case.
Iatrogenic ureteral injury is the most frequent trauma during pelvic surgery. Due to the peculiarities of this topographic region, assessment of ureteral wall perfusion is critical for prevention of ischemic complications.
In modern surgical practice, assessing local ureteral perfusion is often based on the surgeon’s subjective opinion. Intraoperative angiography with indocyanine green (indocyanine green, ICG) has been shown to be an adequate reflection of tissue perfusion and potentially influence the outcome of surgery.
Currently, there are insufficient data regarding the use of ICG in iatrogenic ureteral injury. In this article, we describe a successful ICG fluorescence-guided middle third ureteroplasty in a 92-year-old patient with uterine cancer who underwent a simple hysterectomy. We also review the literature on this topic. The literature search for the review was performed using the PubMed database.
Based on currently available data, the use of ICG for defect detection and control during ureteral resection is feasible and safe. However, the significance of this procedure should be evaluated in further studies.
ISSN 1999-8627 (Online)