Comparative analysis of the efficiency different chemomodification schemes of radiotherapy in patients with local cancer heads and neck

В роботі представлено результати проведеного дослідження щодо ефективності та токсичності різних схем хіміомодифікації променевої терапії у хворих на плоскоклітинний рак голови та шиї. Доказано, що безпосередні результати лікування та показники виживаності вище в групах з застосуванням цисплатину та 5-фторурацилу ніж при використанні самостійної променевої терапії. Проте, розроблений метод хрономодульованої радіохіміотерапії в режимі гіпофракціонування дози опромінення з 5-фторурацилом проявляє меншу токсичність у порівнянні з застосуванням схеми променева терапія+цисплатин і тому може бути рекомендований хворим похилого віку та пацієнтам з низьким соматичним статусом.В работе представлены результаты проведенного исследования по эффективности и токсичности различных схем химиомодификации лучевой терапии у больных с плоскоклеточным раком головы и шеи. Доказано, что результаты лечения и показатели выживаемости выше в группах с применением цисплатина и 5-фторурацила, чем при использовании самостоятельной лучевой терапии. Однако, разработанный метод хрономодулированной радиохимиотерапии в режиме гипофракционирования дозы облучения с 5-фторурацилом показывает меньшую токсичность по сравнению с применением схемы лучевая терапии+цисплатин и поэтому может быть рекомендован больным пожилого возраста и пациентам с низким соматическим статусом.Every year, more than 500,000 new cases of head and neck cancer are recorded, but about 40.0 % of patients with this pathology don’t live past one year after the diagnosis. This is primarily due to the fact that in most cases (60.0 %) the disease is already diagnosed in locally advanced stages (III, IVa, IVb) despite the fact that head and neck cancer is dominated by visual forms. At present, the standard of treatment for patients with inoperable locally advanced head and neck cancer is chemoradiotherapy in the classical dose fractionation mode with chemomodification with cisplatin. But this regimen is toxic, therefore, it has significant restrictions on use, such as the age of the patient over 70 years, low somatic status, concomitant heart, kidney and liver disease. That is why an urgent need is present to develop new methods of chemoradiation therapy, which could improve the efficiency of complex treatment and reduce overall toxicity. One of the ways in which this result could be achieved is by using chronomodulated irradiation and chemo-drug administration. The paper presents the results of a study on the efficacy and toxicity of various chemomodification regimens of radiotherapy in patients with squamous cell carcinoma of the head and neck. The study involved 108 patients, who have been divided into 3 groups. In the first group, patients received chronomodulated radiochemotherapy with 5-fluorouracil in the dose hypofractionation mode (n = 39), in the second – radiotherapy in the classical dose fractionation mode with cisplatin (n = 34), in the third – independent radiation therapy (n = 35). All patients received isoeffective total focal dose of 60.0-70.0 Gy. The evaluation of the immediate response to treatment was based on the review and methods of visualization of the tumor cell (CT, MRI) using the criteria of RECIST v.1.1. The obtained data was processed in statistic software STATISTICA v. 12 using nonparametric methods for a small number of elements of the sample population. Also, the overall one-year and two-year survival was studied using the Kaplan-Meier method and life time tables. The obtained results were compared on the basis of the probability criterion of log-rank, p-criterion of significance of statistical differences. In all cases, the difference was considered statistically significant at p < 0.05. The direct results of treatment in radiochemotherapy groups were shown to be equal and amounted to 77.0 % with 5-fluorouracil and 73.5 % with cisplatin (p = 0.35). These rates exceed the results of radiotherapy only treatment – 58.2 % (p < 0.05). Two-year survival rate was higher when using the developed method of chronomodulated radiochemotherapy with 5-fluorouracil in the dose hypofractionation mode than when using radiotherapy alone – (46.2 ± 8.0) versus (25.7 ± 7.4) %, respectively (p = 0.03), whereas, when using radiotherapy with cisplatin, this figure was (38.2 ± 8.3) % (p = 0.13). Median survival when using chronomodulated radiochemotherapy with 5-fluorouracil was (17.5 ± 3.6) months versus (13.2 ± 3.2) in the group using radiochemotherapy with cisplatin (p < 0.0001). The toxicity of therapy is of great importance in the treatment of the patient, because the final result of the process depends on it. Thus, expressed manifestations of unwanted events led to the patient’s refusal from further treatment or to deterioration of their general condition, hematological parameters, appearance of pronounced local reactions, which required the doctor to stop treatment before stabilizing the patient’s condition, and in some cases, their hospitalization. In our study, grade 3-4 radiation mucositis was more commonly observed with cisplatin (47.0 %). With the use of 5-fluorouracil and with only radiotherapy, the development rate of grade 3 radiation mucositis was 35.9 and 25.7 %, respectively (p = 0.17), and no case of grade 4 mucositis was recorded. Dyspeptic events were significantly more frequent in the radiochemotherapy group with cisplatin – 58.8 vs. 5.1 % with chronomodulated administration of 5-fluorouracil (p < 0.0001). This led to a more than 10.0 % decrease in body weight in most patients receiving cisplatin. Concerning hematological toxicity, in the case of cisplatin, grade 2-3 leukopenia was registered in 14.7 % of cases, compared with 5.1 % with the use of chronomodulated administration of 5-fluorouracil. Thus, by analyzing the immediate and long-term results of treatment, there was no significant difference in the indices when using the developed method of chronomodulated radiochemotherapy in comparison with traditional radiochemotherapy with cisplatin. However, high toxicity of radiochemotherapy with cisplatin was noted, in contrast to chronomodulated administration of 5-fluorouracil. That is why it is expedient to use the regimen with 5-fluorouracil in the treatment of patients with reduced somatic status and elderly patients