Jinekolojik kanserlerde sitoredüktif cerrahi sonrası hipertermik intraperitoneal kemoterapi uygulaması: Teknik detay ve kısa dönem sonuçları

Yıl 2018, Cilt: 21 Sayı: 2, 1 - 7, 15.03.2020

Yagmur Minareci , Hamdullah Sözen , Özgür Aydın Tosun Engin Çelik , Harika Yumru Çeliksoy Merve Baktıroğlu Samet Topuz , Mehmet Yavuz Salihoğlu

Öz

Özet:

Giriş: Sitoredüktif cerrahi (SRC) ve sonrasında uygulanan hipertermik intraperitoneal kemoterapi (HİPEK) ikilisinin amacı, tüm makroskopik hastalıkların eksize edilmesi ve peritoneal boşluğa direkt verilen sıcak (>40 °C) kemoterapötik ajan tedavileri ile hastaların yaşam süresinin uzatılmasıdır. Çalışmamızın birincil hedefi, jinekolojik kanserli hastaların klinik özelliklerini, cerrahi işlemi ve komplikasyonlarını tanımlamak olup; ikincil hedefi ise, kısa dönem genel ve hastalıksız sağkalım sürelerini ortaya koymak olarak belirlenmiştir.

 

Materyal Metod: İ.Ü. İstanbul Tıp Fakültesi Jinekoloji Onkoloji Kliniğinde mayıs 2015 – ekim 2018 tarihleri arasında jinekolojik kanser nedeniyle SRC’yi takiben HİPEK yapılan yirmi beş hasta retrospektif olarak değerlendirilmiştir. Cerrahi komplikasyonlar Clavien - Dindo kriterleri ile sınıflandırılmıştır.

 

Bulgular: Toplam yirmi beş hastanın yirmi üçü nüksü takiben SRC + HİPEK grubunda iken, ikisi neoadjuvan kemoterapi sonrasında interval debulking cerrahisi + HİPEK grubunda idi. Hastaların yirmi üçü over kanseri, ikisi seröz endometrium kanseri idi ve over kanseri olan gruptaki hastaların çoğunluğu platin dirençli hastalardan oluşmakta idi. Ortalama hasta yaşı elli yedi (otuz üç - yetmiş dört) ve ortalama SRC süresi 192 (90 - 420) dakika idi.  Ortalama on iki (bir – otuz beş) aylık izlem süresinde; SRC + HİPEK yapılan hastalarda bir yıllık toplam sağkalım % 72, üç yıllık sağkalım % 8 olarak kaydedilmiştir. On dört hastadan oluşan platin dirençli nüks EOK’li hasta grubu kendi içinde değerlendirmeye alındığında; ortalama sağkalım 12.2 ay ve hastalıksız sağkalım 4.4 ay olarak saptanmıştır.  Peri-operatif ciddi morbidite üç hastada (bir hastada bağırsak rezeksiyonu sonrası anastamoz kaçağı ve iki hastada pelvik abse/hematom) izlenmiş olup, bir hastada ise anastamoz kaçağı sonrası sepsis’e bağlı mortalite gerçekleşmiştir. Bununla birlikte, bir ve ikinci derece komplikasyonlar HİPEK’e bağlı en sık rastlanan morbidite sebepleri olarak saptanmıştır.

 

Sonuç: SRC ve HİPEK, ileri evre over ve endometrium kanserli hastaların tedavisinde deneysel olarak uygulanmakta olup, en iyi sonuçlar geride gözle görülür tümör kalmadığı taktirde alınmaktadır. Özellikle platin dirençli hasta grubu değerlendirildiğinde ve bu hasta grubuna yönelik eldeki tedavi seçeneklerin yetersizliği göz önüne alındığında, kısa dönemli sonuçlarımız umut vericidir. Ayrıca, çalışmamızda raporladığımız yan etki sıklığı, literatür ile benzerdir. Kabul edilebilir yan etki verileri ve makul sağkalım sonuçları olan deneyimlerimiz ülkemizde giderek yaygınlaşan bu tedavi için cesaret verici görünmektedir.

Anahtar Kelimeler

Hipek, hipertermik intraperitoneal kemoterapi, Jinekolojik kanserler, Sitoredüktif cerrahi.

Practice of hyperthermic intraperitoneal chemotherapy after cytoreductive surgery in gynecological cancers: technical detail and short-term results

Öz

 Abstract: 

Introductıon: Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) aim to excise all macroscopic diseases and to extend the survival period of patients with heated (>40 °C) chemotherapeutic agent treatments administered directly to the peritoneal cavity. The primary objective of our study was to describe the clinical features, surgical procedures, and complications of gynecologic cancer patients; its secondary objective was to determine the short term general and disease-free lifespan of the patients.

 

Material and method: Twenty-five patients who underwent HIPEC following CRS due to gynecologic cancer between May 2015 and October 2018 at the Gynecology Oncology Clinic of IU Istanbul Faculty of Medicine were evaluated retrospectively. Surgical complications were classified by Clavien - Dindo criteria.

 

Results: Out of the 25 patients, 23 were in the SRC + HIPEC group following recurrence while two were in the interval debulking surgery + HIPEK group following neoadjuvant chemotherapy. Of the patients, 23 had ovarian cancer while two had serous endometrial cancer, and the majority of the patients with ovarian cancer were platinum-resistant. The mean age of the patients was 57 (33-74) and the mean duration of SRC was 192 (90- 420) minutes.  During the mean follow-up of twelve (one- thirty-five) months, one-year overall survival was 72% and three-year survival was 8% in the patients who underwent SRC + HIPEC. Evaluation of 14 patients with platinum-resistant recurrent EOC revealed mean survival as 12.2 months and disease-free survival as 4.4 months.  Three patients had peri-operative severe morbidity (one patient had anastomosis leakage after bowel resection, and two patients had pelvic abscess/hematoma) while in one patient, sepsis-related mortality occurred after anastomotic leakage. Besides, first and second-degree complications were found to be the most common causes of morbidity due to HIPEC.

 

Conclusıon: SRC and HIPEC are applied experimentally in patients with advanced stage ovarian and endometrial cancer, and the best results are obtained if there are no visible tumors. Considering the platinum-resistant patient group and the inadequacy of the available treatment options for this patient group, our short-term results are promising. Furthermore, the frequency of the side effects reported in our study was similar to the that of in previous studies. Our research, which has acceptable side-effect data and reasonable survival outcomes, seems to be encouraging for this treatment that is increasingly becoming widespread in our country.

Anahtar Kelimeler

Hipec, gynecologic cancers, Cytoreductive surgery, hyperthermic intraperitoneal chemotherapy

Kaynakça

• Mao-Chih Hsieh, Chang-Yun Lu, Wei-Wen Chang, Szu-Yuan Wu, MPH, Ping-Kun Hsiao, Tse-Jia Liu.Experiences with cytoreduction surgery plus hyperthermic intraperitoneal chemotherapy in Taiwan. Medicine (2017) 96:26.
• Díaz-Montes TP, Bristow RE. Secondary cytoreduction for patients with recurrent ovarian cancer. Curr Oncol Rep 2005; 7:451–458.
• Zang RY, Li ZT, Zhang ZY, Cai SM. Surgery and salvage chemotherapy for Chinese women with recurrent advanced epithelial ovarian carcinoma: a retrospective case-control study. Int J Gynecol Cancer 2003; 13: 419–427.
• Daniela Matei, Sharad Ghamande, Lynda Roman, Angeles AlvarezSecord, John Nemunaiti,Merry Jennifer Markham, et al. A Phase I Clinical Trial of Guadecitabine and Carboplatin in Platinum-Resistant, Recurrent Ovarian Cancer: Clinical, Pharmacokinetic, and Pharmacodynamic Analyses. Clin. Cancer res. May 2018.
• Pujade-Lauraine E, Hilpert F, Weber B, Reuss A, Poveda A, Kristensen G, Et al. Bevacizumab combined with chemotherapy for platinum-resistant recurrent ovarian cancer: The AURELIA open-label randomized phase III trial. J Clin Oncol. 2014 May 1;32(13):1302-8.
• Stockler MR, Hilpert F, Friedlander M, King MT, Wenzel L, Lee CK, et al. Patientreported outcome results from the open- label phase III AURELIA trial evaluating bevacizumab-containing therapy for platinum-resistant ovarian cancer. J Clin Oncol. 2014 May 1;32(13):1309-16.
• ES. Han, Monk BJ. Bevacizumab in the treatment of ovarian cancer. Expert Review of Anticancer Therapy 2007 Oct;7(10):1339-45.
• Kobayashi K, Fujimoto S, Takahashi M, Mutou T, Toyosawa T, Ohtsuka Y, et al. [A patient with stage IIIc ovarian cancer with massive ascites who was chemotherapy resistantshowed complete response with intraperitoneal hyperthermic chemoperfusion]. Gan To Kagaku Ryoho. 2003 Oct;30(11):1726-8.
• C.H. Cho, Wust P, Hildebrandt B, Issels RD, Sehouli J, Kerner T, et al. Regional hyperthermia of the abdomen in conjunction with chemotherapy for peritoneal carcinomatosis: Evaluation of two annular-phased-array applicators. International Journal of Hyperthermia 2008. Aug;24(5):399-408.
• Atmaca A. Whole-body hyperthermia (WBH) in combination with carboplatin in patients with recurrent ovarian cancer — A phase II study. Gyn Oncol 2009
• Sugarbaker PH. Peritonectomy procedures. Ann Surg 1995;221:29–42.
• Dindo D, Demartines N, Clavien PA. Classification of surgical complications:a new proposal with evaluation in a cohort of 6336 patients and results of a survey. Ann Surg 2004; 240: 205-213.
• Lampe B, Kroll N, Piso P, Forner DM, Mallmann P. Prognostic significance of Sugarbaker's peritoneal cancer index for the operability of ovarian carcinoma. Int J Gynecol Cancer. 2015 Jan;25(1):135-44.
• Zivanovic O, Chi DS, Filippova O, Randall LM, Bristow RE, O'Cearbhaill RE. It's time to warm up to hyperthermic intraperitoneal chemotherapy for patients with ovarian cancer. Gynecol Oncol. 2018 Sep 22.
• Ceresoli M, Verrengia A, Montori G, Busci L, Coccolini F, Ansaloni L, et al. Effect of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy on relapse pattern in primary epithelial ovarian cancer: a propensity score based case-control study. J Gynecol Oncol. 2018 May;29(3)
• Koray Topgul, Mehmet Bilge Cetinkaya, N. Ciğdem Arslan, Mustafa Kemal Gul, Murat Can, Mahmut Fikret Gursel, et al.Cytoreductive surgery (SRC) and hyperthermic intraperitoneal chemotherapy (HIPEC) for treatment of peritoneal carcinomatosis: Our initial experience and technical details. Ulus Cerrahi Derg 2015; 31: 138-147
• Di Giorgio A, De Iaco P, De Simone M, Garofalo A, Scambia G, Pinna AD, et al Cytoreduction (Peritonectomy Procedures) Combined with Hyperthermic Intraperitoneal Chemotherapy (HIPEC) in Advanced Ovarian Cancer: Retrospective Italian Multicenter Observational Study of 511 Cases. Ann Surg Oncol. 2017 Apr;24(4):914-922.
• Coccolini F, Campanati L, Catena F, Ceni V, Ceresoli M, Jimenez Cruz J, et al. Hyperthermic intraperitoneal chemotherapy with cisplatin and paclitaxel in advanced ovarian cancer: a multicenter prospective observational study. J Gynecol Oncol. 2015 Jan;26(1):54-61.
• Huo YR, Richards A, Liauw W, Morris DL. Hyperthermic intraperitoneal chemotherapy (HIPEC) and cytoreductive surgery (CRS) in ovarian cancer: A systematic review and meta-analysis. Eur J Surg Oncol. 2015 Dec;41(12):1578-89.
• Spiliotis J1, Halkia E, Lianos E, Kalantzi N, Grivas A, Efstathiou E, Giassas S.Cytoreductive surgery and HIPEC in recurrent epithelial ovarian cancer: a prospective randomized phase III study. Ann Surg Oncol. 2015 May;22(5):1570-5.
• Harter P, Reuss A, Sehouli J, Chiva L, du Bois A. Brief Report About the Role of Hyperthermic Intraperitoneal Chemotherapy in a ProspectiveRandomized Phase 3 Study in Recurrent Ovarian Cancer From Spiliotis et al. Int J Gynecol Cancer. 2017 Feb;27(2):246-247.
• van Driel WJ, Koole SN, Sikorska K, Schagen van Leeuwen JH, Schreuder HWR, Hermans RHM, et al. Hyperthermic Intraperitoneal Chemotherapy in Ovarian Cancer. N Engl J Med. 2018 Jan 18;378(3):230-240.
• Harter P, du Bois A, Sehouli J, Mahner S, Vergote I, Chiva L, et al. Is there a role for HIPEC in ovarian cancer? Archives of Gynecology and Obstetrics (2018) 298:859–860.
• Vergote I, Chiva L, du Bois A. Hyperthermic Intraperitoneal Chemotherapy in Ovarian Cancer. N Engl J Med. 2018 Apr 5;378(14):1362-3.
• Fotopoulou C, Sehouli J, Mahner S, Harter P, Van Nieuwenhuysen E, Gonzalez-Martin A, et al. HIPEC: HOPE or HYPE in the fight against advanced ovarian cancer? Ann Oncol. 2018 Aug 1;29(8):1610-1613.
• Sorio R, Roemer-Becuwe C, Hilpert F, Gibbs E, García Y, Kaern J et al. Safety and efficacy of single-agent bevacizumab-containing therapy in elderly patients with platinum-resistant recurrent ovarian cancer: Subgroup analysis of the randomised phase III AURELIA trial. Gynecol Oncol. 2017 Jan;144(1):65-71.