J Cancer Res Clin Oncol DOI 10.1007/s00432-014-1692-5
Original Article – Cancer Research
Different sequential approaches of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in treating ovarian cancer with malignant ascites Mingchen Ba · Hui Long · Xiangliang Zhang · Yunqiang Tang · Yinbing Wu · Feihong Yu · Shuai Wang · Shuzhong Cui
Received: 22 January 2014 / Accepted: 19 April 2014 © Springer-Verlag Berlin Heidelberg 2014
Abstract Background and objectives Treatment for malignant ascites in advanced ovarian cancer (OC) patients remains controversial. The objective of this study was to investigate the efficacy of combined continuous circulatory hyperthermic intraperitoneal chemotherapy (HIPEC) preceded or followed by cytoreductive surgery (CRS) for malignant ascites in OC patients. Methods Female OC patients (n = 32) with malignant ascites were divided based on stable (n = 17) or unstable (n = 15) vital signs. Stable patients were treated with CRS immediately followed by HIPEC (CRS + HIPEC). Unstable patients were treated using B-mode ultrasound-guided HIPEC followed by delayed CRS upon vital sign stability (HIPEC + dCRS). All patients were followed up until death or until December 2012. Results Median follow-up was 29 months. All patients showed ascite regression [objective remission rates (ORR) = 100 %]. Among stable patients, CRS + HIPEC was successful in 14/17 (83.4 %). Among unstable patients, HIPEC + dCRS was successful in 13/15 (86.7 %). Median survival times were 19 and 17 months in the stable and unstable groups, respectively. No significant differences
Mingchen Ba and Hui Long are co-first authors. M. Ba (*) · X. Zhang · Y. Tang · Y. Wu · F. Yu · S. Wang · S. Cui Intracelom Hyperthermic Perfusion Therapy Center, Cancer Hospital of Guangzhou Medical College, Guangzhou 510095, China e-mail: [email protected] H. Long (*) Department of Pharmacy, Guangzhou Dermatology Institute, Guangzhou 510095, China e-mail: [email protected]
in CRS rates, ascites ORR, Karnofsky performance status scores, or survival rates were observed between groups (P > 0.05). Conclusion Cytoreductive surgery with immediate HIPEC and HIPEC with dCRS, determined by vital sign stability, may lead to similar outcomes in OC patients with malignant ascites. Keywords Hyperthermic intraperitoneal chemotherapy · Ultrasonography · Cytoreductive surgery · Ovarian cancer · Carcinomatosis · Malignant ascites
Introduction Ovarian cancer (OC) is a common malignancy responsible for more deaths worldwide than any other malignancy of the female reproductive system (Woopen and Sehouli 2009). The formation of malignant ascites, an accumulation of abdominal fluid-filled pockets as a direct effect of cancer, is a typical complication during late-stage OC. The formation of malignant ascites occurs in virtually all OC patients upon cancer progression (Becker et al. 2006). As the amount of ascites increases, patients generally report progressive symptoms of abdominal swelling, pain, nausea, and dyspnea (Becker et al. 2006). Indeed, discomforts and decreased quality of life (QOL) associated with symptomatic malignant ascites often exceed that of the cancer itself, resulting in detrimental physiological and psychological states leading to poor prognosis (Becker et al. 2006; Woopen and Sehouli 2009). In clinical settings, treatment of malignant ascites due to OC is controversial. Some clinicians advocate firstline treatments with simple drainage, while others select chemotherapy and debulking to treat the underlying cancer
13
(Woopen and Sehouli 2009; Becker et al. 2006). However, neither type of treatment has been completely successful in reducing ascites and in limiting additional ascites development (Woopen and Sehouli 2009). As a first-line treatment, simple drainage is often accomplished using diuretics, but their efficacy is relatively low and dosage increases are limited (Woopen and Sehouli 2009). Similarly, paracentesis or manual removal of accumulated fluid from the abdominal cavity produces only temporary relief and must be repeated regularly to prevent symptoms recurrence (Woopen and Sehouli 2009). Thus, there is a need for improved treatment options for treating the underlying cancer, thereby preventing symptomatic recurrence. Hyperthermic intraperitoneal chemotherapy (HIPEC) is a relatively new therapeutic approach for treatment of peritoneal carcinomatosis (Al-Shammaa et al. 2008; Benoit et al. 2008; Ceelen et al. 2008; Hagendoorn et al. 2009; Roviello et al. 2006; Shido et al. 2000). Recently, debulking through cytoreductive surgery (CRS) immediately followed by HIPEC has been used to treat peritoneum-disseminated gastric cancer (Fujimoto et al. 1988; Scaringi et al. 2008; Spratt et al. 1980a, b), colorectal cancer (Elias et al. 2009; Huh et al. 2009; Zanon et al. 2006), and pseudomyxoma peritonei (Baratti et al. 2008, 2009b; Deraco et al. 2003; McQuellon et al. 2008). In combined CRS and HIPEC (CRS + HIPEC), CRS removes bulky tumor tissue and HIPEC eradicates residual microscopic tumor lesions or free cancer cells in the peritoneal cavity (Di Giorgio et al. 2008). Ovarian cancer typically metastasizes via peritoneal carcinomatosis and is often limited to the peritoneal cavity (Becker et al. 2006; Woopen and Sehouli 2009). Less frequently, OC metastasizes via the hematogenous or lymphatic routes (Woopen and Sehouli 2009; Becker et al. 2006). CRS + HIPEC has not yet widely been reported as a treatment for OC, but this unique combination of treatments could have the ability to potentially intensify peritoneal therapy and to completely eradicate loco-regional tumors (Ceelen et al. 2012; Helm et al. 2008; Parson et al. 2011; Roviello et al. 2010; Votanopoulos et al. 2012). However, the best timing of CRS and HIPEC, i.e. which one first, is currently unknown. Ovarian cancer patients present highly variable overall health conditions. Many patients are not eligible for surgery due to poor physical condition and unstable vital signs (Ba et al. 2010; Cui et al. 2012; Facchiano et al. 2008; Ferron et al. 2005; Garofalo et al. 2006). Consequently, laparoscopic approaches for HIPEC have recently been proposed for patients who are not eligible to CRS (Ba et al. 2010; Facchiano et al. 2008; Ferron et al. 2005; Garofalo et al. 2006). Based on increasing reports of successful outcomes following laparoscopic-assisted HIPEC techniques (Cui et al. 2012; Baratti et al. 2009a), B-mode ultrasound-guided
13
J Cancer Res Clin Oncol
HIPEC was developed. The use of this technique has been reported to produce satisfactory therapeutic results (Cui et al. 2012). Consequently, different treatment strategies are recommended to improve the prognosis of OC patients with malignant ascites. Therefore, the aim of the present study was to investigate the timing of HIPEC and CRS in OC patients with malignant ascites, based on the stability of their vital signs. This work provides a basis for improving the treatments strategies using HIPEC and CRS in OC patients with malignant ascites.
Materials and methods Study design A prospective interventional clinical trial was conducted in 32 female OC patients with malignant ascites treated between December 2007 and December 2011 at the Cancer Hospital of the Guangzhou Medical University (Guangzhou, China). Patients were divided according to their health condition, resulting in a stable vital signs group and an unstable vital signs group. Stable patients were treated with immediate CRS followed by HIPEC (CRS + HIPEC), while unstable patients were treated with HIPEC followed by delayed CRS once vital signs were stabilized (HIPEC + dCRS). The study was approved by the Medical Ethics Committee of the Cancer Hospital of Guangzhou Medical University (no. GZMCY20080825). Written informed consent was obtained from all patients. Patients and grouping Inclusion criteria were (1) age ≥18 years; (2) confirmed OC by computed tomography (CT), magnetic resonance imaging (MRI), serum OC-associated antigen 125 (CA125), ascite cytology, and/or laparotomy; and (3) malignant ascites confirmed by B-mode ultrasound and/or CT. Exclusion criteria were (1) minimal or no malignant ascites; (2) limited encapsulation of intraperitoneal effusions; (3) extensive abdominal adhesions due to multiple previous operations; or (4) complete intestinal obstruction. Patients were classified as unstable if all three vital sign criteria were fulfilled: (1) heart rate >100 beats/min; (2) respiration rate of >20 breaths/min; and (3) blood oxygen saturation
Original Article – Cancer Research
Different sequential approaches of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in treating ovarian cancer with malignant ascites Mingchen Ba · Hui Long · Xiangliang Zhang · Yunqiang Tang · Yinbing Wu · Feihong Yu · Shuai Wang · Shuzhong Cui
Received: 22 January 2014 / Accepted: 19 April 2014 © Springer-Verlag Berlin Heidelberg 2014
Abstract Background and objectives Treatment for malignant ascites in advanced ovarian cancer (OC) patients remains controversial. The objective of this study was to investigate the efficacy of combined continuous circulatory hyperthermic intraperitoneal chemotherapy (HIPEC) preceded or followed by cytoreductive surgery (CRS) for malignant ascites in OC patients. Methods Female OC patients (n = 32) with malignant ascites were divided based on stable (n = 17) or unstable (n = 15) vital signs. Stable patients were treated with CRS immediately followed by HIPEC (CRS + HIPEC). Unstable patients were treated using B-mode ultrasound-guided HIPEC followed by delayed CRS upon vital sign stability (HIPEC + dCRS). All patients were followed up until death or until December 2012. Results Median follow-up was 29 months. All patients showed ascite regression [objective remission rates (ORR) = 100 %]. Among stable patients, CRS + HIPEC was successful in 14/17 (83.4 %). Among unstable patients, HIPEC + dCRS was successful in 13/15 (86.7 %). Median survival times were 19 and 17 months in the stable and unstable groups, respectively. No significant differences
Mingchen Ba and Hui Long are co-first authors. M. Ba (*) · X. Zhang · Y. Tang · Y. Wu · F. Yu · S. Wang · S. Cui Intracelom Hyperthermic Perfusion Therapy Center, Cancer Hospital of Guangzhou Medical College, Guangzhou 510095, China e-mail: [email protected] H. Long (*) Department of Pharmacy, Guangzhou Dermatology Institute, Guangzhou 510095, China e-mail: [email protected]
in CRS rates, ascites ORR, Karnofsky performance status scores, or survival rates were observed between groups (P > 0.05). Conclusion Cytoreductive surgery with immediate HIPEC and HIPEC with dCRS, determined by vital sign stability, may lead to similar outcomes in OC patients with malignant ascites. Keywords Hyperthermic intraperitoneal chemotherapy · Ultrasonography · Cytoreductive surgery · Ovarian cancer · Carcinomatosis · Malignant ascites
Introduction Ovarian cancer (OC) is a common malignancy responsible for more deaths worldwide than any other malignancy of the female reproductive system (Woopen and Sehouli 2009). The formation of malignant ascites, an accumulation of abdominal fluid-filled pockets as a direct effect of cancer, is a typical complication during late-stage OC. The formation of malignant ascites occurs in virtually all OC patients upon cancer progression (Becker et al. 2006). As the amount of ascites increases, patients generally report progressive symptoms of abdominal swelling, pain, nausea, and dyspnea (Becker et al. 2006). Indeed, discomforts and decreased quality of life (QOL) associated with symptomatic malignant ascites often exceed that of the cancer itself, resulting in detrimental physiological and psychological states leading to poor prognosis (Becker et al. 2006; Woopen and Sehouli 2009). In clinical settings, treatment of malignant ascites due to OC is controversial. Some clinicians advocate firstline treatments with simple drainage, while others select chemotherapy and debulking to treat the underlying cancer
13
(Woopen and Sehouli 2009; Becker et al. 2006). However, neither type of treatment has been completely successful in reducing ascites and in limiting additional ascites development (Woopen and Sehouli 2009). As a first-line treatment, simple drainage is often accomplished using diuretics, but their efficacy is relatively low and dosage increases are limited (Woopen and Sehouli 2009). Similarly, paracentesis or manual removal of accumulated fluid from the abdominal cavity produces only temporary relief and must be repeated regularly to prevent symptoms recurrence (Woopen and Sehouli 2009). Thus, there is a need for improved treatment options for treating the underlying cancer, thereby preventing symptomatic recurrence. Hyperthermic intraperitoneal chemotherapy (HIPEC) is a relatively new therapeutic approach for treatment of peritoneal carcinomatosis (Al-Shammaa et al. 2008; Benoit et al. 2008; Ceelen et al. 2008; Hagendoorn et al. 2009; Roviello et al. 2006; Shido et al. 2000). Recently, debulking through cytoreductive surgery (CRS) immediately followed by HIPEC has been used to treat peritoneum-disseminated gastric cancer (Fujimoto et al. 1988; Scaringi et al. 2008; Spratt et al. 1980a, b), colorectal cancer (Elias et al. 2009; Huh et al. 2009; Zanon et al. 2006), and pseudomyxoma peritonei (Baratti et al. 2008, 2009b; Deraco et al. 2003; McQuellon et al. 2008). In combined CRS and HIPEC (CRS + HIPEC), CRS removes bulky tumor tissue and HIPEC eradicates residual microscopic tumor lesions or free cancer cells in the peritoneal cavity (Di Giorgio et al. 2008). Ovarian cancer typically metastasizes via peritoneal carcinomatosis and is often limited to the peritoneal cavity (Becker et al. 2006; Woopen and Sehouli 2009). Less frequently, OC metastasizes via the hematogenous or lymphatic routes (Woopen and Sehouli 2009; Becker et al. 2006). CRS + HIPEC has not yet widely been reported as a treatment for OC, but this unique combination of treatments could have the ability to potentially intensify peritoneal therapy and to completely eradicate loco-regional tumors (Ceelen et al. 2012; Helm et al. 2008; Parson et al. 2011; Roviello et al. 2010; Votanopoulos et al. 2012). However, the best timing of CRS and HIPEC, i.e. which one first, is currently unknown. Ovarian cancer patients present highly variable overall health conditions. Many patients are not eligible for surgery due to poor physical condition and unstable vital signs (Ba et al. 2010; Cui et al. 2012; Facchiano et al. 2008; Ferron et al. 2005; Garofalo et al. 2006). Consequently, laparoscopic approaches for HIPEC have recently been proposed for patients who are not eligible to CRS (Ba et al. 2010; Facchiano et al. 2008; Ferron et al. 2005; Garofalo et al. 2006). Based on increasing reports of successful outcomes following laparoscopic-assisted HIPEC techniques (Cui et al. 2012; Baratti et al. 2009a), B-mode ultrasound-guided
13
J Cancer Res Clin Oncol
HIPEC was developed. The use of this technique has been reported to produce satisfactory therapeutic results (Cui et al. 2012). Consequently, different treatment strategies are recommended to improve the prognosis of OC patients with malignant ascites. Therefore, the aim of the present study was to investigate the timing of HIPEC and CRS in OC patients with malignant ascites, based on the stability of their vital signs. This work provides a basis for improving the treatments strategies using HIPEC and CRS in OC patients with malignant ascites.
Materials and methods Study design A prospective interventional clinical trial was conducted in 32 female OC patients with malignant ascites treated between December 2007 and December 2011 at the Cancer Hospital of the Guangzhou Medical University (Guangzhou, China). Patients were divided according to their health condition, resulting in a stable vital signs group and an unstable vital signs group. Stable patients were treated with immediate CRS followed by HIPEC (CRS + HIPEC), while unstable patients were treated with HIPEC followed by delayed CRS once vital signs were stabilized (HIPEC + dCRS). The study was approved by the Medical Ethics Committee of the Cancer Hospital of Guangzhou Medical University (no. GZMCY20080825). Written informed consent was obtained from all patients. Patients and grouping Inclusion criteria were (1) age ≥18 years; (2) confirmed OC by computed tomography (CT), magnetic resonance imaging (MRI), serum OC-associated antigen 125 (CA125), ascite cytology, and/or laparotomy; and (3) malignant ascites confirmed by B-mode ultrasound and/or CT. Exclusion criteria were (1) minimal or no malignant ascites; (2) limited encapsulation of intraperitoneal effusions; (3) extensive abdominal adhesions due to multiple previous operations; or (4) complete intestinal obstruction. Patients were classified as unstable if all three vital sign criteria were fulfilled: (1) heart rate >100 beats/min; (2) respiration rate of >20 breaths/min; and (3) blood oxygen saturation
