Vol 25, No 1 (2020)

Ripretinib (DCC-2618) is a novel tyrosine kinase inhibitor designed to broadly inhibit primary and secondary mutations in KIT (exons 9,11, 13, 14,17,18) and PDGFRA (exon 18). Here in our article we describe clinical trials of ripretinib for patient with advanced gastrointestinal stromal tumors (GIST).

The clinical trial INVICTUS-randomized phase III study of ripretinib for patient with advanced GIST in ≥4 lines therapy; it is the most important results, because there are currently no approved drugs for such patients. Median PFS was significantly improved with ripretinib compared with placebo 6,3 и 1 months (p<0,0001) and median OS was significantly improved with ripretinib compared with placebo 15,1 и 6,6 months (p<0,004).

High efficacy of ripretinib was accompanied with favorable profile of toxicity, only 8,2% patients experienced treatment discontinuations due to adverse events.

The purpose of the study: to present an experience of the N. N. Blokhin Russian Cancer Research Center in the treatment of relapses of gestational trophoblastic neoplasias (GTN).

Materials and methods. We performed a retrospective analysis of medical case histories at the N. N. Blokhin Russian Cancer Research Center from 1996 until 2019. 545 patients with GTN were treated. Relapses occurred in 25 (4.6%) patients: 8 (2.1%) patients with low risk of resistance (6 (75%) – early relapses and 2 (25%) – late relapses) and 17 (10%) patients with high risk of resistance (11 (65%) – early relapses and 6 (35%) – late relapses). Treatment of relapses was done by standard chemotherapy regimens (Dactinomycin 500mcg in days 1–5, EMA-CO, EMA-EP). Different surgical interventions and radiosurgery were used in some cases additionally.

Results. Out of 6 patients with early relapses of low-risk GTN, 5 were cured with chemotherapy and one patient by lung resection only. Two patients with late relapses of low-risk GTN were cured with chemotherapy (EMA-CO) and hysterectomy/resection of uterus to achieve complete remission. As a result, all patients with relapses of low-risk GTN were cured, mainly (88%) by chemotherapy. Among 11 patients with early relapses of high-risk GTN, complete remission was achieved in 6 (55%) cases: in 2 patients as a result of EMA-EP chemotherapy, other patients needed combined approaches (chemotherapy + surgery). Three patients with recurrent course continue treatment, two patients died of progression. Of the 6 patients with late relapses of high-risk GTN, 4 (66%) patients were managed mainly through combined treatment (surgery + chemotherapy) and were cured. One patient continues treatment for more than 4 years, and one patient died of progression. In total, out of 17 patients with high-risk relapses, complete remission was achieved in 10 (59%) as a result of combined treatment in the majority of cases (80%).

Conclusion. The optimal method of treatment for patients with relapses of low-risk GTN is chemotherapy; and for high-risk GTN – combined approaches (chemotherapy + surgery)

Objective. To analyze the feasibility of performing plastic surgery in patients with primary skin melanoma (SM).

Material and methods. We studied patients with primary MK treated in our institution in 2013 (n = 333), who were randomized to a group of 2 blind selection methods to the main one (n = 168), in which the tumor removal operation in patients ended with a tissue defect repair and a comparison group ( n = 165) (after removal of the tumor, simple linear suturing of the wound was performed). A statistically significant difference was found in the comparison groups in the occurrence of negative dynamics (ND), progression-free survival (PFS) and overall survival (OS) in patients with MK 0-IIA st during the follow-up period up to 36 months.

Results. It was found that patients with 0-IIA st who underwent plastic surgery to close the defect when removing primary SM have a statistically proven advantage in ND, PFS, and OS compared with patients without plastic surgery for up to 36 months. In general, the use of plastics has a statistical tendency towards the dynamics of an increase in PFS and OS in the early stages of SM.

Discussion. In the early stages (0-IIA) up to 36 months, cases of negative dynamics (4.2%) were observed 2.3 times less frequently than in the comparison group (9.7%) (p = 0.048), and fatal outcomes in the main group (1.8%) were observed 3.7 times less than in the comparison group (6.7%) (p = 0.028). The analysis also shows that in patients who underwent surgery using plastic surgery statistically significantly reduces the risk of distant metastasis by 3 times (p = 0.05), but significantly more often (in every third patient) (p = 0.022) than in the control group (without plastic surgery) met transient metastases. The appearance of ND, as well as an increase in PFS, OS depended on the plastic replacement of the defect after excision of the primary SM in patients with SM 0-IIA st during the observation period up to 36 months.

Conclusion. The use of plastic methods for closing a wound defect reduces the risk of distant metastasis by 3 times compared with linear suturing, provides a reduction in mortality in patients with SM 0 – IIA st for 60 months, prolongs the patient’s life by an average of 10 months and is the operation of choice in this category.

Gestational trophoblastic neoplasia is a rare malignancy. The main treatment approach is chemotherapy. Almost all patients can be cured if the diagnosis is established timely and adequate treatment is provided in specialized centers.

In a small part of patients, the tumor progresses despite the use of all standard chemotherapy regimens. Treatment of such patients is difficult for all oncologists, including ones working in specialized centers for the treatment of gestational trophoblastic neoplasia.

This article presents a clinical case of the successful treatment of a patient with multidrug resistant gestational trophoblastic neoplasia using GEMOX regimen.