Journal of Modern Oncology

Biliary tract cancer (BTC) is a group of rare and aggressive types of malignancies that arise from the epithelium of the intra- and extrahepatic bile ducts (cholangiocarcinoma) and gallbladder. The prognosis of unresectable BTC is poor, and less than 5% of patients are alive at 5 years after diagnosis. Radical surgical resection remains the only potentially curative treatment for early stage BTC, and antitumor chemotherapy extends survival rates in patients with unresectable or metastatic BTC. With the emerging of monoclonal antibodies targeting immune checkpoints, the possibility of such therapy in first- and subsequent-line treatment of advanced BTC has been actively studied. The positive high-level results from the TOPAZ-1 Phase III trial showed durvalumab, in combination with standard-of-care chemotherapy (gemcitabine plus cisplatin), statistically improved overall survival versus chemotherapy alone and showed improvements versus chemotherapy alone in prespecified secondary endpoints including progression-free survival and objective response rate. Durvalumab plus chemotherapy was well tolerated, had a similar safety profile versus the comparator arm and did not increase the discontinuation rate due to adverse events compared to chemotherapy alone. The U.S. Food and Drug Administration approved the combination of durvalumab and chemotherapy (gemcitabine plus cisplatin) as the first immunotherapy regimen for patients with locally advanced or metastatic BTC. In July 2022, durvalumab plus chemotherapy (gemcitabine plus cisplatin) was added to the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) as a preferred regimen category 1 in first-line therapy for Unresectable or metastatic BTC based on the data from TOPAZ-1. In addition, the durvalumab plus gemcitabine and cisplatin was recently added to the practical recommendations of the Russian Society of Clinical Oncology (RUSSCO) for the treatment of hepatobiliary cancers as an alternative to standard first-line treatment of BTC.

Aim. To assess the comparative clinical efficacy of Prolgolimab monotherapy versus combination therapy with BRAF/MEK inhibitors (Dabrafenib and Trametinib, Vemurafenib and Cobimetinb) in adult patients with metastatic or unresectable skin melanoma implementing a matching-adjusted indirect comparison (MAIC).

Materials and methods. We conducted a systematic search for randomized clinical trials of Prolgolimab, combinations of Dabrafenib and Trametinib, Cobimetinib and Vemurafenib. Unanchored MAIC was applied due to the absence of common comparator between trials. We determined effect modifiers based on an expert survey. The population from Prolgolimab studies was weighted using defined effect modifiers, followed by the approximation of survival curves.

Results. Systematic literature search revealed 4 RCTs that met the inclusion criteria: MIRACULUM, coBRIM, combi-v and combi-d. To increase the power of prolgolimab comparison, data from the observational study FORA were included in evidence synthesis and combined with data from MIRACULUM. We selected M staging and the proportion of patients with elevated LDH levels as effect modifiers. No significant differences (all p>0.05) were established between Prolgolimab and combination therapy with BRAF/MEK inhibitors for both OS after 1 year and PFS outcomes after 2 years from initiation.

Discussion. Despite the inclusion of observational data and the limitations of adjusted indirect comparison method, the results of this analyses are consistent with both other comparisons of anti-PD1 inhibitors with BRAF/MEK inhibitors, and with real world data. It is necessary to recompare targeted therapy and immunotherapy after five-year follow-up period due to peculiarities of time of onset of their effect with the presence of a primary “failure” with a gradual exit to a long “plateau” on anti-PD1 inhibitor’s therapy.

Conclusion. In these unanchored MAICs, Prolgolimab monotherapy showed comparable efficacy with combinations of BRAF/MEK inhibitors (Dabrafenib + Trametinib, Vemurafenib + Cobimetinib) in first line therapy of patients with metastatic or unresectable melanoma. This analysis may be relevant for clinical decision-making about the choice of the first line therapy for patients with BRAF mutation.

Background. Peripheral nerve sheath malignancies (PNSM) are a rare and aggressive group of sarcomas that can occur sporadically, after radiation therapy, or related to neurofibromatosis type 1. Loss of function of NF1, TP53, and CDKN2A genes is thought to contribute to the progression of benign neurofibroma to PNSM and is a poor prognostic sign. The optimal management of patients with this disease is currently unresolved, and specific prognostic factors have not been established.

Aim. To analyze the results of surgical treatment in patients with PNSM and establish prognostic factors of overall and recurrence-free survival rate.

Materials and methods. The retrospective and prospective studies enrolled adult patients with histologically confirmed PNSM treated between 1998 and 2021 at the N.N. Blokhin National Medical Research Center for Oncology. Surgical intervention was performed on 61 patients, 38 (62%) females and 23 (38%) males. The most common PNSM localization was paravertebral (22 [36%] patients), followed by retroperitoneal (14 [23%] patients), and upper and lower extremities (13 [21%] and 12 [20%] patients, respectively).

Results. For PNSM patients with a history of surgery, the median overall survival (OS) was 46 months (95% confidence interval 26.1–65.9). The 3-year and 5-year OS was 46% and 31%, respectively. The median recurrence-free survival (RFS) was 27 months (8.7–45.3), and 3-year and 5-year RFS was 26% and 13%, respectively. Median OS for grade 1 malignancies was not achieved, while grade 2 and grade 3 malignancy was 53 and 33 months, respectively (p=0.033). The median RFS for grade 1, 2, and 3 tumors was 119, 43, and 15 months, respectively (p=0.078). Patients who underwent radical (R0) surgery had higher RFS (p=0.006) and OS (p<0.0001). After radical (R0) surgery, the median OS was not achieved; after nonradical (R1/R2) surgery, the median was 34 months. The median RFS was 124 months after R0-resection and 48 months after R1/R2.

Conclusion. The most significant prognostic factors in PNSM patients are the radicality of the surgery performed and the malignancy grade. In our study, tumor size and localization did not affect the long-term treatment results.

Background. Uterine myoma is the most common benign tumor of the pelvic organs in women. One of the effective therapies for myomas is uterine artery embolization (UAE), which can be associated with unintended ovarian embolization. However, there is no certainty about the effect of unintended ovarian embolization on fertility and ovarian function since no precise evidence-based ways of identifying unintended embolization have been described.

Aim. To develop a highly accurate method for identifying unintended ovarian embolization during UAE.

Materials and methods. A series of clinical cases of the utilization of combined embolization material based on the paramagnetic contrast agent gadoteridol and saturable HepaSphere microspheres are presented.

Results. On admission, patients underwent magnetic resonance imaging (MRI) of the pelvic organs with contrast enhancement. After UAE with this combined embolization material, another pelvic MRI without contrast enhancement was performed on the in-hospital day 2. In the first clinical case, no hyperintensive zones were detected in the ovarian stroma. However, in the second case, a previously undetected hyperintensive signal up to 6 mm in diameter was seen in the stroma of the left ovary by repeat MRI.

Conclusion. Using this combined material during UAE significantly increases the accuracy of possible unintended ovarian embolization detection as soon as in the early postoperative period.

Anemia in patients with malignancies is a common disorder that has a markedly negative impact on quality of life and overall prognosis. The pathogenesis of anemia is complex and multifactorial, depending on the type and stage of malignancy, nutritional status, renal function, age and gender, cytostatic drug, dose, and chemotherapeutic regimen, with iron deficiency often being the main and potentially treatable factor for anemia. In cancer patients, it can be caused by various concomitant mechanisms, including bleeding (e.g., in malignant gastrointestinal tumors or after surgery), malnutrition, medication, and hepcidin-induced iron sequestration in macrophages, with subsequent iron-deficient erythropoiesis. The variety of clinical manifestations of anemia makes it challenging to establish universal criteria to develop optimal treatments. Current therapy for anemia in malignant tumors includes replacement therapy with an iron supplement, erythropoiesis-stimulating agents (erythropoietins), and blood transfusions. However, blood transfusions should be minimized due to the high risks and costs. Therapy with an iron supplement is an effective approach to correcting the iron deficiency. It can increase the efficacy of erythropoiesis-stimulating drugs and reduce the need for blood transfusions. Published guidelines suggest the wide use of intravenous iron supplements. This article discusses possible approaches to treating iron deficiency in cancer patients in various clinical settings. We build on current guidelines and emphasize the need for further research in this area.

The review is devoted to the analysis of the mechanism of NETosis and the formation of extracellular traps by neutrophils. Neutrophil traps are DNA strands, histones and proteins that are involved in autoimmune diseases, COVID-19, as well as in the pathogenesis of other non-communicable diseases. Based on the literature data, the role of NETosis in the development oncological diseases is analyzed. Two types of neutrophils have been characterized: low-density neutrophils and high-density neutrophils. In particular, the significance of this phenomenon in the progression and metastasis of the cancer. A detailed study of this issue will be useful both from a fundamental standpoint regarding the disclosure of the mechanisms of the metastatic cascade, and from a practical point of view for the development of new immunotherapeutic approaches in the treatment of metastatic tumors.

This publication is the Russian translation of the Plain Language Summary (PLS) of the Cochrane Systematic Review: Adams A, Scheckel B, Habsaoui A, Haque M, Kuhr K, Monsef I, Bohlius J, Skoetz N. Intravenous iron versus oral iron versus no iron with or without erythropoiesis-stimulating agents (ESA) for cancer patients with anaemia: a systematic review and network meta-analysis. Cochrane Database Syst Rev. 2022;6(6):CD012633. DOI:10.1002/14651858.CD012633.pub2