Effect of Hyperthermic Intraperitoneal Chemotherapy application on survival in platinum-resistant and partially sensitive recurrent epithelial ovarian cancer after maximal cytoreduction

Öz

Aim: Recurrence in ovarian cancers is usually observed with peritoneal metastasis. In this cases, cytoreductive surgery (SRC) and hyperthermic intraperitoneal chemotherapy(HIPEC) have an important role among the treatment options. This treatment modality becomes more important especially in platinum-resistant and partially sensitive recurrent epithelial ovarian cancers. In our study, we analyzed the results of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy treatment applied to this patient group. Materials and Method: We retrospectively analyzed the patients with high-grade serous ovarian carcinoma with platinum-resistant and partially sensitive pathology who were operated for peritoneal recurrence between 2014-2021. We only included the patients who underwent SRC and HIPEC without macroscopic residual tumor in the study. Early and long-term results of the patients, the development of relapse during the follow-up period, disease-free and overall survival times were analyzed. Results: A total of 13 patients were included in the study. The peritoneal carcinomatosis index (PCI) of the patients were between 3-25 and the median age was 54. One of our patient recieved both secondary and tertiary SRS and HIPEC. Median length of hospital stay and follow-up were 14 days and 42 months, respectively. Post operative complications were observed in five patients. The median disease-free survival (DFS) of all patients was 41 months, and the median overall survival (OS) was 49 months. Conclusion: In platinum-resistant and partially sensitive recurrent epithelial ovarian cancers, SRC and HIPEC can be performed with acceptable morbidity rates. Long survival can be achieved with complete cytoreduction. Secondary and tertiary surgeries are beneficial in selected patients.

Anahtar Kelimeler

• cytoreductive surgery
• hyperthermic intraperitoneal chemotherapy
• epithelial ovarian carcinoma
• survival

Maksimal sitoredüksiyon sonrası Hipertermik İntraperitoneal Kemoterapi uygulamasının platin dirençli ve parsiyel duyarlı rekürren epitelyal over kanserinde sağ kalıma etkisi

Öz

Amaç: Over kanserlerinde nüks genellikle peritoneal metastaz ile olmaktadır. Bu durumda tedavi seçenekleri arasında sitoredüktüf cerrahi (SRC) ve hipertermik intraperitoneal kemoterapi (HİPEK) önemli yer tutmaktadır. Özellikle platin dirençli ve parsiyel duyarlı rekürren epitelyal over kanserlerinde bu tedavi daha da önem kazanmaktadır. Çalışmamızda bu hasta grubuna uyguladığımız sitoredüktüf cerrahi ve hipertermik intraperitoneal kemoterapi tedavisin sonuçlarını analiz ettik. Gereç ve Yöntemler: 2014-2021 tarihleri arasında peritoneal nüks nedeni ile opere edilen platin dirençli ve parsiyel duyarlı patolojisi yüksek dereceli seröz over karsinom olan hastalar geriye dönük olarak incelendi. Çalışmaya sadece makroskopik rezidü tümör kalmayacak şekilde SRC ve HİPEK uygulanan hastalar dahil edildi. Hastaların erken ve uzun dönem sonuçları, takip sürecinde nüks gelişimi, hastalıksız ve toplam sağ kalım süreleri analiz edildi. Bulgular: Toplam 13 hasta çalışmaya dahil edildi. Hastaların, peritoneal karsinomatoz indeksi (PKİ), 3-25 arasında ve ortanca yaş 54 (32-77  11,5 SD) olarak saptandı. Bir hastaya hem sekonder hem tersiyer SRC ve HİPEK uygulandı. Ortanca hastane yatış süreleri ve takip süreleri sırası ile 14 gün ve 42 ay olarak bulundu. Beş hastada post operatif komplikasyon gözlendi. Tüm hastaların median hastalıksız sağ kalım (DFS) 41 ay, median sağ kalım (OS) 49 ay olarak bulundu. Sonuç: Platin dirençli ve parsiyel duyarlı rekürren epitelyal over kanserlerinde SRC ve HİPEK, kabul edilebilir morbidite oranları ile yapılabilmektedir. Makroskopik tümör bırakılmadan uygulanan sitoredüksiyon ile uzun sağ kalım sağlanabilmektedir. Sekonder ve tersiyer cerrahiler seçilmiş hastalarda faydalıdır.

Anahtar Kelimeler

• sitoredüksiyon
• Hipertermik İntraperitoneal Kemoterapi
• epitelyal over karsinomu
• sağ kalım

Kaynakça

1. 1. Kurman RJ, Shih Ie M. Molecular pathogenesis and extraovarian origin of epithelial ovarian cancer--shifting the paradigm. Hum Pathol. 2011;42(7):918-31.
2. 2. Siegel R, Naishadham D, Jemal A. Cancer statistics, 2013. CA Cancer J Clin. 2013;63(1):11-30.
3. 3. Vaughan S, Coward JI, Bast RC, Jr., Berchuck A, Berek JS, Brenton JD, et al. Rethinking ovarian cancer: recommendations for improving outcomes. Nat Rev Cancer. 2011;11(10):719-25.
4. 4. van der Burg ME, van Lent M, Buyse M, Kobierska A, Colombo N, Favalli G, et al. The effect of debulking surgery after induction chemotherapy on the prognosis in advanced epithelial ovarian cancer. Gynecological Cancer Cooperative Group of the European Organization for Research and Treatment of Cancer. N Engl J Med. 1995;332(10):629-34.
5. 5. Armstrong DK. Relapsed ovarian cancer: challenges and management strategies for a chronic disease. Oncologist. 2002;7 Suppl 5:20-8.
6. 6. Leitao MM, Jr., Chi DS. Surgical management of recurrent ovarian cancer. Semin Oncol. 2009;36(2):106-11.
7. 7. Sehouli J, Grabowski JP. Surgery in recurrent ovarian cancer. Cancer. 2019;125 Suppl 24:4598-601.
8. 8. Foley OW, Rauh-Hain JA, del Carmen MG. Recurrent epithelial ovarian cancer: an update on treatment. Oncology (Williston Park). 2013;27(4):288-94, 98.

9. 9. Cress RD, Chen YS, Morris CR, Petersen M, Leiserowitz GS. Characteristics of Long-Term Survivors of Epithelial Ovarian Cancer. Obstet Gynecol. 2015;126(3):491-7.
10. 10. Rose PG, Java JJ, Salani R, Geller MA, Secord AA, Tewari KS, et al. Nomogram for Predicting Individual Survival After Recurrence of Advanced-Stage, High-Grade Ovarian Carcinoma. Obstet Gynecol. 2019;133(2):245-54.
11. 11. 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;378(3):230-40.
12. 12. Ohno S, Siddik ZH, Kido Y, Zwelling LA, Bull JM. Thermal enhancement of drug uptake and DNA adducts as a possible mechanism for the effect of sequencing hyperthermia on cisplatin-induced cytotoxicity in L1210 cells. Cancer Chemother Pharmacol. 1994;34(4):302-6.
13. 13. Panteix G, Beaujard A, Garbit F, Chaduiron-Faye C, Guillaumont M, Gilly F, et al. Population pharmacokinetics of cisplatin in patients with advanced ovarian cancer during intraperitoneal hyperthermia chemotherapy. Anticancer Res. 2002;22(2B):1329-36.
14. 14. van de Vaart PJ, van der Vange N, Zoetmulder FA, van Goethem AR, van Tellingen O, ten Bokkel Huinink WW, et al. Intraperitoneal cisplatin with regional hyperthermia in advanced ovarian cancer: pharmacokinetics and cisplatin-DNA adduct formation in patients and ovarian cancer cell lines. Eur J Cancer. 1998;34(1):148-54.
15. 15. Jou J, Zimmer Z, Charo L, Yau C, Saenz C, Eskander R, et al. HIPEC after neoadjuvant chemotherapy and interval debulking is associated with development of platinum-refractory or -resistant disease. Gynecol Oncol. 2021;161(1):25-33.
16. 16. Oken MM, Creech RH, Tormey DC, Horton J, Davis TE, McFadden ET, et al. Toxicity and response criteria of the Eastern Cooperative Oncology Group. Am J Clin Oncol. 1982;5(6):649-55.
17. 17. Warschkow R, Tarantino I, Lange J, Muller SA, Schmied BM, Zund M, et al. Does hyperthermic intraoperative chemotherapy lead to improved outcomes in patients with ovarian cancer? A single center cohort study in 111 consecutive patients. Patient Saf Surg. 2012;6(1):12.
18. 18. Ryu KS, Kim JH, Ko HS, Kim JW, Ahn WS, Park YG, et al. Effects of intraperitoneal hyperthermic chemotherapy in ovarian cancer. Gynecol Oncol. 2004;94(2):325-32.
19. 19. Safra T, Grisaru D, Inbar M, Abu-Abeid S, Dayan D, Matceyevsky D, et al. Cytoreduction surgery with hyperthermic intraperitoneal chemotherapy in recurrent ovarian cancer improves progression-free survival, especially in BRCA-positive patients- a case-control study. J Surg Oncol. 2014;110(6):661-5.
20. 20. Baiocchi G, Ferreira FO, Mantoan H, da Costa AA, Faloppa CC, Kumagai LY, et al. Hyperthermic Intraperitoneal Chemotherapy after Secondary Cytoreduction in Epithelial Ovarian Cancer: A Single-center Comparative Analysis. Ann Surg Oncol. 2016;23(4):1294-301.
21. 21. Mendivil AA, Rettenmaier MA, Abaid LN, Brown JV, 3rd, Mori KM, Lopez KL, et al. Consolidation hyperthermic intraperitoneal chemotherapy for the treatment of advanced stage ovarian carcinoma: a 3 year experience. Cancer Chemother Pharmacol. 2017;80(2):405-10.
22. 22. Zhang G, Zhu Y, Liu C, Chao G, Cui R, Zhang Z. The prognosis impact of hyperthermic intraperitoneal chemotherapy (HIPEC) plus cytoreductive surgery (CRS) in advanced ovarian cancer: the meta-analysis. J Ovarian Res. 2019;12(1):33.
23. 23. Spiliotis J, Halkia E, Lianos E, Kalantzi N, Grivas A, Efstathiou E, et al. Cytoreductive surgery and HIPEC in recurrent epithelial ovarian cancer: a prospective randomized phase III study. Ann Surg Oncol. 2015;22(5):1570-5.
24. 24. Bakrin N, Bereder JM, Decullier E, Classe JM, Msika S, Lorimier G, et al. Peritoneal carcinomatosis treated with cytoreductive surgery and Hyperthermic Intraperitoneal Chemotherapy (HIPEC) for advanced ovarian carcinoma: a French multicentre retrospective cohort study of 566 patients. Eur J Surg Oncol. 2013;39(12):1435-43.
25. 25. Fagotti A, Costantini B, Petrillo M, Vizzielli G, Fanfani F, Margariti PA, et al. Cytoreductive surgery plus HIPEC in platinum-sensitive recurrent ovarian cancer patients: a case-control study on survival in patients with two year follow-up. Gynecol Oncol. 2012;127(3):502-5.
26. 26. Classe JM, Glehen O, Decullier E, Bereder JM, Msika S, Lorimier G, et al. Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy for First Relapse of Ovarian Cancer. Anticancer Res. 2015;35(9):4997-5005.
27. 27. Costales AB, Chambers L, Chichura A, Rose PG, Mahdi H, Michener CM, et al. Effect of platinum sensitivity on the efficacy of hyperthermic intraperitoneal chemotherapy (HIPEC) in recurrent epithelial ovarian cancer. J Gynecol Obstet Hum Reprod. 2021;50(5):101844.
28. 28. Eng KH, Hanlon BM, Bradley WH, Szender JB. Prognostic factors modifying the treatment-free interval in recurrent ovarian cancer. Gynecol Oncol. 2015;139(2):228-35.
29. 29. Musella A, Marchetti C, Palaia I, Perniola G, Giorgini M, Lecce F, et al. Secondary Cytoreduction in Platinum-Resistant Recurrent Ovarian Cancer: A Single-Institution Experience. Ann Surg Oncol. 2015;22(13):4211-6.