ACADEMIC AND RESEARCH PEER-REVIEWED MEDICAL JOURNALISSN 1727-2378 (Print)         ISSN 2713-2994 (Online)
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Radical Hysterectomy following Chemotherapy in Patients with Stage IIB Cervical Cancer

For citation: Ovodenko D. L., Khabas G. N., Makarova A. S., Babaeva N. A., Aleshikova O. I., Ashrafyan L. A. Radical Hysterectomy following Chemotherapy in Patients with Stage IIB Cervical Cancer. Doctor.Ru. 2018; 2(146): 46–51.
20 February 11:50

Study Objective: To analyze the results of intravenous and intra-arterial chemotherapy and subsequent radical surgery in patients with stage IIB cervical cancer.

Study Design: This was a pilot study.

Materials and Methods: Fifty-five patients with stage IIB cervical cancer (mean age 38.6 ± 7.5) were included in the study.

The first step in the combined-modality therapy was neoadjuvant chemotherapy, which was given to all the patients. The patients were divided into two groups by mode of administration of the cytostatic agents. The main group was made up of 15 women who received the chemotherapeutic agents via intra-arterial infusion and underwent embolization of the uterine arteries. The control group consisted of 40 patients who received the chemotherapeutic agents via intravenous infusion.

The efficacy of the neoadjuvant chemotherapy was assessed two weeks after administration of the antineoplastic agents. This was done by clinical methods (visual and bimanual examination), magnetic resonance imaging, and ultrasound examination. Cervical cancer response to the cytostatic agents was evaluated by change in tumor volume, measured by all the visualization methods used in the study. Other assessments included toxic reactions and treatment-emergent complications.

Patients with sufficient reduction in tumor volume and parametrial infiltration underwent laparoscopic radical hysterectomy (Piver class III, Querleu-Morrow class C2). Patients whose parametrial infiltration and large cervical tumors remained did not undergo surgery, but received radical chemoradiotherapy.

Study Results: Average tumor size reduction after neoadjuvant chemotherapy was almost 50% in patients in both groups. Complete response was reported in four (7.3%) patients, partial response was seen in 46 (83.6%) patients, and stable disease in five (9.1%) patients. No cases were reported of disease progression during neoadjuvant chemotherapy. There were no statistically significant differences in the efficacy of the neoadjuvant chemotherapy between the groups of patients who received cytostatic agents via different routes.

Treatment was well tolerated in both groups, as assessed by observation of gastrointestinal and hematologic toxic effects during the neoadjuvant chemotherapy. The antineoplastic agents were administered to all the patients up to individually tailored maximum doses. Slightly fewer gastrointestinal and hematologic toxic effects were reported when the chemotherapeutic agents were administered intra-arterially, but this difference was not statistically significant.

Radical surgery was possible in 51 (92.7%) patients: 38 (95.0%) in the control group and 13 (86.7%) in the main group. In 13.3% of the patients in the main group and 5.0% of the patients in the control group, reduction in cervical cancer volume and infiltration was insufficient, and radical surgery was not performed. These patients received chemoradiotherapy.

Adjuvant radiotherapy/chemoradiotherapy was administered after surgery to patients at moderate and high risk for disease progression. The percentage of patients who required adjuvant treatment was 57.5% in the group of women who had received cytostatic agents (neoadjuvant chemotherapy) via intravenous infusion and 60.0% among those to whom these agents had been given intra-arterially. A total of 37.3% of the stage IIB cervical cancer patients who had received neoadjuvant chemotherapy followed by radical surgery did not require adjuvant radiotherapy/chemoradiotherapy.

The mean follow-up period was 29.7 months. Among the women who had been given cytostatic agents intra-arterially, tumor recurrence was seen in one patient (6.7%). In the group of patients who had received neoadjuvant chemotherapy via intravenous infusion, tumor recurrence was reported in three (7.5%) of the women. Three-year disease-free survival was about 87% in both groups.

Conclusion: Neoadjuvant chemotherapy followed by radical surgery in patients with stage IIB cervical cancer is a promising research field in gynecological oncology. Preliminary results of this research show this treatment approach significantly increases both disease-free survival and—by omitting adjuvant radiation therapy in some cases—patients’ quality of life.

D. L. Ovodenko — Academician V. I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Moscow. E-mail: d_ovodenko@oparina4.ru

G. N. Khabas — Academician V. I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Moscow. E-mail: d_chabas@oparina4.ru

A. S. Makarova — Academician V. I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Moscow. E-mail: a_makarova@oparina4.ru

N. A. Babaeva — Russian Scientific Center for Radiology, Moscow. E-mail: natbabaeva@yandex.ru

O. I. Aleshikova — Russian Scientific Center for Radiology, Moscow. E-mail: ol-ga.aleshikova@gmail.com

L. A. Ashrafyan — Academician V. I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Moscow. E-mail: l_ashrafyan@oparina4.ru

Доктор.ру
20 February 11:50
LITERATURE
  1. Каприн А. Д., Старинский В. В., Петрова Г. В., ред. Злокачественные новообразования в россии в 2015 году (заболеваемость и смертность). М.: ФГУ «МНИОИ им. П. А. Герцена»; 2017. 250 с. [Kaprin A. D., Starinskii V. V., Petrova G. V., red. Zlokachestvennye novoobrazovaniya v rossii v 2015 godu (zabolevaemost' i smertnost'). M.: FGU “MNIOI im. P. A. Gertsena”; 2017. 250 s. (in Russian)]
  2. Wu S. G., Zhang W. W., Sun J. Y., Li F. Y., He Z. Y., Zhou J. Multimodal treatment including hysterectomy improves survival in patients with locally advanced cervical cancer: a population­based, propensity score­matched analysis. Int. J. Surg. 2017; 48: 122–7.
  3. Hellman K., Hellström A. C., Pettersson B. F. Uterine cervix cancer treatment at Radiumhemmet: 90 years' experience. Time trends of age, stage, and histopathology distribution. Cancer Med. 2014; 3(2): 284–92.
  4. Бохман Я. В. Руководство по онкогинекологии. СПб.; 2002. 351 с. [Bokhman Ya. V. Rukovodstvo po onkoginekologii. SPb.; 2002. 351 s. (in Russian)]
  5. Lora D., Gómez de la Cámara A., Fernández S. P., Enríquez de Salamanca R., Gómez J. F. P. R. Prognostic models for locally advanced cervical cancer: external validation of the published models. J. Gynecol. Oncol. 2017; 28(5): e58.
  6. Козаченко В. П., ред. Клиническая онкогинекология. Руководство для врачей. М.: Медицина; 2005. 376 с. [Kozachenko V. P., red. Klinicheskaya onkoginekologiya. Rukovodstvo dlya vrachei. M.: Meditsina; 2005. 376 s. (in Russian)]
  7. Lan M. L., Yu X., Xiao H., Zhou P., Hu N., Liu Y. et al. Comparison of chemoradiotherapy with and without brachytherapy as adjuvant therapy after radical surgery in early­stage cervical cancer with poor prognostic factors: an observational study. Medicine (Baltimore). 2017; 96(46): e8384.
  8. Кравец О. А., Марьина Л. А., Чехонадский В. Н., Русанов А. О. Лучевая терапия местнораспространенного рака шейки матки. Роль лучевой терапии в гинекологической онкологии. В кн.: Материалы научно­практической конференции «Роль лучевой терапии в гинекологической онкологии». Обнинск; 2002: 112–14. [Kravets O. A., Mar'ina L. A., Chekhonadskii V. N., Rusanov A. O. Luchevaya terapiya mestnorasprostranennogo raka sheiki matki. Rol' luchevoi terapii v ginekologicheskoi onkologii. V kn.: Materialy nauchno­prakticheskoi konferentsii "Rol' luchevoi terapii v ginekologicheskoi onkologii". Obninsk; 2002: 112–14. (in Russian)]
  9. Tanioka M., Yamaguchi S., Shimada M., Nagao S., Takehara K., Nishimura M. et al. Cisplatin with dose­dense paclitaxel before and after radical hysterectomy for locally advanced cervical cancer: a prospective multicenter phase II trial with a dose­finding study. Med. Oncol. 2017; 34(8): 134.
  10. Limbergen V. Научно обоснованные рекомендации по проведению лучевой терапии при раке шейки матки. В кн.: Мат­лы Европейской школы онкологии Семинар на Красной площади «Современные аспекты онкогинекологии». М.; 2009: 11–27. [Limbergen V. Nauchno obosnovannye rekomendatsii po provedeniyu luchevoi terapii pri rake sheiki matki. Vkn: Mat­ly Evropeiskoi shkoly onkologii Seminar na Krasnoi ploshchadi «Sovremennye aspekty onkoginekologii». M.; 2009: 11–27. (in Russian)]
  11. Moreno­Acosta P., Vallard A., Carrillo S., Gamboa O., Romero­Rojas A., Molano M. et al. Biomarkers of resistance to radiation therapy: a prospective study in cervical carcinoma. Radiat. Oncol. 2017; 12(1): 120.
  12. Ramlov A., Pedersen E. M., Røhl L., Worm E., Fokdal L., Lindegaard J. C. et al. Risk factors for pelvic insufficiency fractures in locally advanced cervical cancer following intensity modulated radiation therapy. Int. J. Radiat. Oncol. Biol. Phys. 2017; 97(5): 1032–9.
  13. Ашрафян Л. А., Антонова И. Б., Алешикова О. И., Добровольская Н. Ю., Чазова Н. Л. Диагностические критерии и факторы прогноза эффективности неоадъюванной химиотерапии местнораспространенного рака шейки матки (IIb–IIIb стадии). Опухоли женской репродуктивной системы. 2007; 4: 63–71. [Ashrafyan L. A., Antonova I. B., Aleshikova O. I., Dobrovol'skaya N. Yu., Chazova N. L. Diagnosticheskie kriterii i faktory prognoza effektivnosti neoad"yuvannoi khimioterapii mestnorasprostranennogo raka sheiki matki (IIb–IIIb stadii). Opukholi zhenskoi reproduktivnoi sistemy. 2007; 4: 63–71. (in Russian)]
  14. Ашрафян Л. А., Антонова И. Б., Алешикова О. И., Добровольская Н. Ю. Хирургический этап как один из основных компонентов в лечении рака шейки матки IIb–IIIb стадий. Рос. онкол. журн. 2007; 3: 21–5. [Ashrafyan L. A., Antonova I. B., Aleshikova O. I., Dobrovol'skaya N. Yu. Khirurgicheskii etap kak odin iz osnovnykh komponentov v lechenii raka sheiki matki IIb–IIIb stadii. Ros. onkol. zhurn. 2007; 3: 21–5. (in Russian)]
  15. Benedetti Panici P., Palaia I., Marchetti C., Ruscito I., Fischetti M., Musella A. et al. Dose­dense neoadjuvant chemotherapy plus radical surgery in locally advanced cervical cancer: a phase II study. Oncology. 2015; 89(2): 103–10.
  16. Raspagliesi F., Bogani G., Spinillo A., Ditto A., Bogliolo S., Casarin J. et al. Introducing nerve­sparing approach during minimally invasive radical hysterectomy for locally­advanced cervical cancer: a multi­institutional experience. Eur. J. Surg. Oncol. 2017; 43(11): 2150–6.
  17. Liu A., Xu W., Xu H., Wang Y., Gu Y. M. [Therapeutic effect of transcatheter arterial chemoembolization combined with ultrasound­guided microwave ablation for treatment of liver cancer in special sites]. Zhonghua Gan Zang Bing Za Zhi. 2017; 25(12): 914–19.
  18. Ma J., Gimenez J. M., Sandow T., Devun D., Kirsch D., Gulotta P. et al. Intraarterial liver­directed therapies: the role of interventional oncology. Ochsner J. 2017; 17(4): 412–6.
  19. Eisenhauer E. A., Therasse P., Bogaerts J., Schwartz L. H., Sargent D., Ford R. et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur. J. Cancer. 2009; 45(2): 228–47.
  20. Piver M. S., Rutledge F., Smith J. P. Five classes of extended hysterectomy for women with cervical cancer. Obstet. Gynecol. 1974; 44(2): 265–72.
  21. Querleu D., Morrow C. P. Classification of radical hysterectomy. Gynecol. Oncol. 2009; 115(2): 314–5; author reply 315–6.
  22. Кравец О. А., Кузнецов В. В., Морхов К. Ю., Нечушкина В. М., Хохлова С. В. Клинические рекомендации по диагностике и лечению рака шейки матки. М.; 2014. 17 с. [Kravets O. A., Kuznetsov V. V., Morkhov K. Yu., Nechushkina V. M., Khokhlova S. V. Klinicheskie rekomendatsii po diagnostike i lecheniyu raka sheiki matki. M.; 2014. 17 s. (in Russian)]
  23. Arbuck S. G., Ivy P., Setser A., Eisenhauer E. A., Wanders J. Common Toxicity Criteria (CTC) version 2.0: highlights and tools. National Cancer Institute of Canada (NCIC). 1999. https://ctep.cancer.gov/protocoldevelopment/electronic_applications/docs/ctcv20_4­30­992.pdf (дата обращения — 15.01.2018).

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