Does hyperthermic intraoperative chemotherapy lead to improved outcomes in patients with ovarian cancer? A single center cohort study in 111 consecutive patients

Patient Safety in Surgery

Thomas Steffen²  Michael Zünd³  Bruno M Schmied²  Sascha A Müller²  Jochen Lange²  Ignazio Tarantino²  Rene Warschkow¹ 

[1] Institute of Medical Biometry and Informatics, University of Heidelberg, Heidelberg, D- 69120, Germany;Department of Surgery, Kantonsspital St. Gallen (KSSG), St. Gallen, CH-9007, Switzerland;Department of Surgery, Zuger Kantonsspital, Baar, CH-6340, Switzerland

关键词: Peritoneal carcinomatosis;    Epithelial ovarian cancer;    Hyperthermic intraperitoneal chemotherapy;    Peritonectomy;    Cytoreductive surgery;   

Others  :  790350
DOI  :  10.1186/1754-9493-6-12

 received in 2012-04-22, accepted in 2012-06-15,  发布年份 2012

【 摘 要 】

Background

For recurrent disease or primary therapy of advanced ovarian cancer, cytoreductive surgery (CRS) followed by adjuvant chemotherapy is a therapeutic option. The aim of this study was to evaluate the outcome for patients with epithelial ovarian cancer treated with hyperthermic intraoperative chemotherapy (HIPEC) and completeness of cytoreduction (CC).

Methods

Data were retrospectively collected from 111 patients with recurrent or primary ovarian cancer operated with the contribution of visceral surgical oncologists between 1991 and 2006 in a tertiary referral hospital.

Results

Ninety patients received CRS and 21 patients CRS plus HIPEC with cisplatin. Patients with complete cytoreduction (CC0) were more likely to receive HIPEC. Overall, 19 of 21 patients (90.5 %) with HIPEC and 33 of 90 patients (36.7 %) with CRS had a complete cytoreduction (P < 0.001). Incomplete cytoreduction was associated with worse survival rates with a hazard ratio (HR) of 4.4 (95%CI: 2.3-8.4) for CC1/2 and 6.0 (95%CI: 2.9-12.3) for CC3 (P < 0.001). In a Cox-regression limited to 52 patients with CC0 a systemic concomitant chemotherapy (HR 0.3, 95%CI: 0.1-0.96, P = 0.046) but not HIPEC (HR 0.98 with 95 % CI 0.32 to 2.97, P = 0.967) improved survival. Two patients (9.5 %) developed severe renal failure after HIPEC with absolute cisplatin dosages of 90 and 95 mg.

Conclusions

Completeness of cytoreduction was proved to be crucial for long-term outcome. HIPEC procedures in ovarian cancer should be performed in clinical trials to compare CRS, HIPEC and systemic chemotherapy against CRS with systemic chemotherapy. Concerning the safety of HIPEC with cisplatin, the risk of persistent renal failure must be considered when dosage is based on body surface.

【 授权许可】

   
2012 Warschkow et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

【 参考文献 】

• [1]Di Giorgio A, Naticchioni E, Biacchi D, Sibio S, Accarpio F, Rocco M, Tarquini S, Di Seri M, Ciardi A, Montruccoli D, Sammartino P: Cytoreductive surgery (peritonectomy procedures) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) in the treatment of diffuse peritoneal carcinomatosis from ovarian cancer. Cancer 2008, 113:315-325.
• [2]Chan JK, Urban R, Cheung MK, Osann K, Shin JY, Husain A, Teng NN, Kapp DS, Berek JS, Leiserowitz GS: Ovarian cancer in younger vs older women: a population-based analysis. Br J Cancer 2006, 95:1314-1320.
• [3]Jemal A, Siegel R, Ward E, Hao Y, Xu J, Thun MJ: Cancer statistics, 2009. CA Cancer J Clin 2009, 59:225-249.
• [4]Diaz-Montes TP, Bristow RE: Secondary cytoreduction for patients with recurrent ovarian cancer. Curr Oncol Rep 2005, 7:451-458.
• [5]Piccart MJ, Floquet A, Scarfone G, Willemse PH, Emerich J, Vergote I, Giurgea L, Coens C, Awada A, Vermorken JB: Intraperitoneal cisplatin versus no further treatment: 8-year results of EORTC 55875, a randomized phase III study in ovarian cancer patients with a pathologically complete remission after platinum-based intravenous chemotherapy. Int J Gynecol Cancer 2003, 13(Suppl 2):196-203.
• [6]Santillan A, Karam AK, Li AJ, Giuntoli R, Gardner GJ, Cass I, Karlan BY, Bristow RE: Secondary cytoreductive surgery for isolated nodal recurrence in patients with epithelial ovarian cancer. Gynecol Oncol 2007, 104:686-690.
• [7]Vasey PA, Jayson GC, Gordon A, Gabra H, Coleman R, Atkinson R, Parkin D, Paul J, Hay A, Kaye SB: Phase III randomized trial of docetaxel-carboplatin versus paclitaxel-carboplatin as first-line chemotherapy for ovarian carcinoma. J Natl Cancer Inst 2004, 96:1682-1691.
• [8]Chua TC, Robertson G, Liauw W, Farrell R, Yan TD, Morris DL: Intraoperative hyperthermic intraperitoneal chemotherapy after cytoreductive surgery in ovarian cancer peritoneal carcinomatosis: systematic review of current results. J Cancer Res Clin Oncol 2009, 135:1637-1645.
• [9]Ibeanu OA, Bristow RE: Predicting the outcome of cytoreductive surgery for advanced ovarian cancer: a review. Int J Gynecol Cancer 2010, 20(Suppl 1):S1-S11.
• [10]Piso P, Dahlke MH, Loss M, Schlitt HJ: Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in peritoneal carcinomatosis from ovarian cancer. World J Surg Oncol 2004, 2:21. BioMed Central Full Text
• [11]Sugarbaker PH: Peritonectomy procedures. Cancer Treat Res 2007, 134:247-264.
• [12]Markman M: Hyperthermic intraperitoneal chemotherapy in the management of ovarian cancer: A critical need for an evidence-based evaluation. Gynecol Oncol 2009, 113:4-5.
• [13]Bristow RE, Tomacruz RS, Armstrong DK, Trimble EL, Montz FJ: Survival effect of maximal cytoreductive surgery for advanced ovarian carcinoma during the platinum era: A meta-analysis. J Clin Oncol 2002, 20:1248-1259.
• [14]Bristow RE, Puri I, Chi DS: Cytoreductive surgery for recurrent ovarian cancer: a meta-analysis. Gynecol Oncol 2009, 112:265-274.
• [15]Yan TD, Black D, Savady R, Sugarbaker PH: Systematic review on the efficacy of cytoreductive surgery combined with perioperative intraperitoneal chemotherapy for peritoneal carcinomatosis from colorectal carcinoma. J Clin Oncol 2006, 24:4011-4019.
• [16]Yan TD, Black D, Savady R, Sugarbaker PH: A systematic review on the efficacy of cytoreductive surgery and perioperative intraperitoneal chemotherapy for pseudomyxoma peritonei. Ann Surg Oncol 2007, 14:484-492.
• [17]Yan TD, Welch L, Black D, Sugarbaker PH: A systematic review on the efficacy of cytoreductive surgery combined with perioperative intraperitoneal chemotherapy for diffuse malignancy peritoneal mesothelioma. Ann Oncol 2007, 18:827-834.
• [18]Mosteller RD: Simplified calculation of body-surface area. N Engl J Med 1987, 317:1098.
• [19]Witkamp AJ, de Bree E, Van Goethem R, Zoetmulder FA: Rationale and techniques of intra-operative hyperthermic intraperitoneal chemotherapy. Cancer Treat Rev 2001, 27:365-374.
• [20]Agresti A, Coull BA: Approximate is better than "exact" for interval estimation of binomial proportions. Am Stat 1998, 52:119-126.
• [21]Austin P, Tu J: Bootstrap methods for developing predictive models 58, 131–137. Am Stat 2004, 58:131-137.
• [22]Chi DS, Eisenhauer EL, Lang J, Huh J, Haddad L, Abu-Rustum NR, Sonoda Y, Levine DA, Hensley M, Barakat RR: What is the optimal goal of primary cytoreductive surgery for bulky stage IIIC epithelial ovarian carcinoma (EOC)? Gynecol Oncol 2006, 103:559-564.
• [23]Helm CW, Richard SD, Pan J, Bartlett D, Goodman MD, Hoefer R, Lentz SS, Levine EA, Loggie BW, Metzinger DS, Miller B, Parker L, Spellman JE, Sugarbaker PH, Edwards RP, Rai SN: Hyperthermic intraperitoneal chemotherapy in ovarian cancer: first report of the HYPER-O registry. Int J Gynecol Cancer 2010, 20:61-69.
• [24]Benson K, Hartz AJ: A comparison of observational studies and randomized, controlled trials. N Engl J Med 2000, 342:1878-1886.
• [25]Kianmanesh R, Scaringi S, Sabate JM, Castel B, Pons-Kerjean N, Coffin B, Hay JM, Flamant Y, Msika S: Iterative cytoreductive surgery associated with hyperthermic intraperitoneal chemotherapy for treatment of peritoneal carcinomatosis of colorectal origin with or without liver metastases. Ann Surg 2007, 245:597-603.
• [26]Miller AA: Body surface area in dosing anticancer agents: scratch the surface! J Natl Cancer Inst 2002, 94:1822-1823.
• [27]Cho HK, Lush RM, Bartlett DL, Alexander HR, Wu PC, Libutti SK, Lee KB, Venzon DJ, Bauer KS, Reed E, Figg WD: Pharmacokinetics of cisplatin administered by continuous hyperthermic peritoneal perfusion (CHPP) to patients with peritoneal carcinomatosis. J Clin Pharmacol 1999, 39:394-401.
• [28]de Jongh FE, Verweij J, Loos WJ, de Wit R, de Jonge MJ, Planting AS, Nooter K, Stoter G, Sparreboom A: Body-surface area-based dosing does not increase accuracy of predicting cisplatin exposure. J Clin Oncol 2001, 19:3733-3739.
• [29]Dedrick RL, Flessner MF: Pharmacokinetic problems in peritoneal drug administration: tissue penetration and surface exposure. J Natl Cancer Inst 1997, 89:480-487.
• [30]Kaestner SA, Sewell GJ: Chemotherapy dosing part I: scientific basis for current practice and use of body surface area. Clin Oncol (R Coll Radiol) 2007, 19:23-37.