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Hyperthermic intraperitoneal chemotherapy for the treatment of ovarian cancer: A brief overview of recent results
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Critical Reviews in Oncology/Hematology xxx (2015) xxx–xxx
Hyperthermic intraperitoneal chemotherapy for the treatment of ovarian cancer: A brief overview of recent results Franco Roviello a , Giandomenico Roviello b,∗ , Roberto Petrioli b , Daniele Marrelli c a
Department of Medicine, Surgery and Neurosciences, Unit of General and Mini-Invasive Surgery, University of Siena, Policlinico “Le Scotte”, Viale Bracci, 53100 Siena, Italy b Medical Oncology Unit, University of Siena, Viale Bracci 11, 53100 Siena, Italy c Department of Medicine, Surgery and Neurosciences, Unit of General Surgery and Surgical Oncology, University of Siena, Policlinico “Le Scotte”, Viale Bracci, 53100 Siena, Italy Accepted 31 March 2015
Contents 1. 2. 3. 4.
Introduction. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Results of HIPEC for OC: a brief overview . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Morbidity and mortality of HIPEC . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Future prospects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Conflict of interest . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Reviewers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Biographies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
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Abstract Ovarian cancer (OC) is the sixth most common neoplasm in women. Hyperthermic intraperitoneal chemotherapy (HIPEC), a strategy combining maximal cytoreductive surgery with maximal regional chemotherapy, has been proposed to treat OC. At present, less randomized trials has determined HIPEC real impact on patients with OC. In this brief report, we reported results of selected studies of treatment with HIPEC for patients with OC. Future prospects are conclusively discussed. © 2015 Elsevier Ireland Ltd. All rights reserved.
Keywords: Ovarian cancer; HIPEC
1. Introduction Hyperthermic intraperitoneal chemotherapy (HIPEC) is a locoregional treatment that involves the washing of the peritoneal cavity with a heated solution and high drug concentrations [1,2]. The rationale of HIPEC is based on the direct cytotoxicity of hyperthermia for malignant cells, ∗ Corresponding author at: Medical Oncology, University of Siena, Policlinico Le Scotte, Viale Bracci 11, 53100 Siena, Italy. Tel.: +39 0577585418; fax: +39 0577586101. E-mail address: [email protected] (G. Roviello).
the enhancement of this cytotoxicity by anticancer drugs, and the pharmacokinetic advantages of the intraperitoneal route for chemotherapy [3,4]. HIPEC must be linked with complete surgical removal of peritoneal carcinomatosis (PC) because HIPEC does not work in cases of residual tumor; indeed, intraperitoneal chemotherapy, even with hyperthermia, does not reach more than 5 mm deep into the tissue. Therefore, the results of HIPEC treatment seem promising for PC [2] when peritonectomy, as described by Sugarbaker [5], is combined with cytoreductive surgery (CRS). The positive effects of peritonectomy on survival and HIPEC in advanced OC are being reported with increasing frequency [6].
http://dx.doi.org/10.1016/j.critrevonc.2015.03.007 1040-8428/© 2015 Elsevier Ireland Ltd. All rights reserved.
Please cite this article in press as: Roviello F, et al. Hyperthermic intraperitoneal chemotherapy for the treatment of ovarian cancer: A brief overview of recent results. Crit Rev Oncol/Hematol (2015), http://dx.doi.org/10.1016/j.critrevonc.2015.03.007
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The first report of the use of HIPEC for OC was in 1994 [7]. Since that time, there has been a large volume of published research evaluating this modality in conjunction with CRS. Two systematic reviews [1,6] that analyzed nearly almost all of the available international literature (14 and 19 studies) concluded that HIPEC is a viable option for the management of patients with advanced stage III–IV disease that has potential benefits that are comparable with those of the current standard of care (i.e., conventional secondary cytoreduction or systemic chemotherapy). The median overall survivals for primary and recurrent disease based on extrapolation from the reviewed studies ranged from 22 to 64 months with median disease-free survivals that ranged from 10 to 87 months [1,6]. Nevertheless, little is known at present about the real longterm prognostic effects of this treatment modality. Indeed, none of the currently published studies are randomized trials. The levels of evidence of the published studies are primarily class II or class III (i.e., non-randomized comparative studies and observational studies). Additionally, the patient cohort that has been treated is heterogeneous group that includes cases with either advanced or recurrent OC who have undergone previous surgery and chemotherapy. A significant proportion of the patients within these studies also had documented chemoresistance and had undergone multiple treatments [1,6]. Furthermore, the operative procedures, CRS and the HIPEC systems are expensive and complex in design and application in terms of the particular aggressive treatment modality needed for carcinomatosis. These treatments not only require highly specialized human resources but also require complex technological facilities, and a learning curve also exists. Therefore, the HIPEC procedure has not yet been standardized. In this report, we present the results of HIPEC for patients with OC. Future prospects are conclusively discussed.
2. Results of HIPEC for OC: a brief overview The natural history of OC includes several time points at which HIPEC can be performed; the first is primary OC (firstline treatment), the second is as a consolidation treatment, and the third is for persistent, progressive and recurrent disease (second-line treatment) [8]. The selection criteria were as follows: studies that involved adult patients older than 18 years who were diagnosed with OC and treated with HIPEC, studies that enrolled more than 15 patients and studies conducted between the years 2005 and 2014 that reported data about efficacy. The search was limited to articles published in the English language and confined to studies that were conducted on human subjects. The exclusion criteria included patients below the age of 18 years, data presented as abstracts and unpublished reports. The data from several of the selected studies are been summarized in Table 1 . The HIPEC studies concerning primary OC were less in number and size than those involving recurrent disease. In
this regard, a recent retrospective cohort multicentric study from French centers reported 92 patients with advanced OC who received first-line treatment [10]. For these patients, the median overall survival was 35.4 months. The survival rates at 1, 3 and 5 years were 83%, 47% and 17%, respectively. The median recurrence-free survival was 11.8 months. The recurrence-free survival rates at 1, 3, and 5 year were 52%, 18%, and 12%, respectively. The best outcomes were observed after complete CRS because the patients treated with CC-0 CRS exhibited a median survival of 41.5 months. A Korean study (NCT01091636) [36] evaluated the toxicities of and treatment responses to intraoperative HIPEC in patients with advanced epithelial OC. No deaths or grade IV morbidities were observed. Therefore, the authors concluded that HIPEC after extensive cytoreductive surgery for OC is a procedure with an acceptable morbidity that patients can tolerate. Deraco and co-workers [12] achieved complete CRS in 58% of the patients and achieved survival data better than that of a well-experienced center in which the maximal surgical efforts to achieve complete CRS were followed by systemic chemotherapy only (5-years OS: 51 vs. 47%) [1,6]. Similar results were demonstrated by Rufian et al. [16]. These authors reported a median overall survival of 66 months in a small number of patients (19) after complete cytoreduction. Other studies are presented in Table 1. However, considering the weaknesses of the published studies, which were primarily retrospective, it is not possible today to conclude whether the use of HIPEC a frontline treatment and the delayed of first-line chemotherapy influences the overall survival of patients. Conversely, HIPEC has been primarily investigated in the setting of persistent or recurrent disease. The addition of HIPEC is an interesting and promising treatment for recurrent OC when it is combined with complete cytoreduction. Although, a significant number of investigated patients generally presented with early recurrent disease or heavily pre-treated (re-)recurrent disease with diffuse PC, and these patients’ characteristics can be suggestive of poor outcomes, in the majority of the series, the median OS was longer than that reported for secondary CRS only [37]. However, the majority of the studies were heterogeneous and retrospective; therefore, they share some obvious and inevitable limitations with all retrospective analyses. In a recent retrospective study [10] by Bakrin et al., the results from 474 patients with recurrent OC (either chemoresistant or chemosensitive) were reported. For these patients, the median overall survival was 45.7 months. The overall survival rates at 1, 3 and 5 years were 89%, 59% and 37%, respectively. Interestingly, there was no significant difference in overall survival between the patients with chemosensitive and chemoresistant recurrence. Indeed, the patients with chemoresistant and chemosensitive recurrences who were treated with CC-0 CRS exhibited median survivals of 51.6 months and 47.2 months, respectively (P = 0.799). Spiliotis et al. [32] evaluated the role of CRS and HIPEC plus systemic chemotherapy versus CRS plus systemic
Please cite this article in press as: Roviello F, et al. Hyperthermic intraperitoneal chemotherapy for the treatment of ovarian cancer: A brief overview of recent results. Crit Rev Oncol/Hematol (2015), http://dx.doi.org/10.1016/j.critrevonc.2015.03.007
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Table 1 Survival rates and surgical variables of CRS plus HIPEC in patients with OC. Study
Disease status
Ansaloni et al. (2012) Bakrin et al. (2013) Cascales Campos et al. (2014) Deraco et al. (2011) Di Giorgio et al. (2008) Helm et al. (2010) (HYPER-O) Pavlov et al. (2009) Rufian et al. (2006) Frenel et al. (2011) Gori et al. (2005) Kim et al. (2010) Pomel et al. (2010) Helm et al. (2010) (HYPER-O) Roviello et al. (2010) Bakrin et al. (2013) Cascales Campos et al. (2014) Ceelen et al. (2009) Cotte et al. (2007) Deraco et al. (2012) Di Giorgio et al. (2008) Fagotti et al. (2011) Fagotti et al. (2012) Frenel et al. (2011) Helm et al. (2010) (HYPER-O) Koningsrainer et al. (2011) Le Brun et al. (2014) Pavlov et al. (2009) Raspagliesi et al. (2006) Robella et al. (2014) Spiliotis et al. (2011) Zanon et al. (2004) Bae et al. (2007) Ryu et al. (2004)
30 HIPEC in Recurrent OC/9 first line treatment during primary CRS First line treatment during primary CRS First line treatment during primary CRS First line treatment during primary CRS First line treatment during primary CRS First line treatment during primary CRS First line treatment during primary CRS First line treatment during primary CRS HIPEC as Consolidation Treatment HIPEC as Consolidation Treatment HIPEC as Consolidation Treatment HIPEC as Consolidation Treatment HIPEC during interval CRS HIPEC during interval CRS HIPEC in recurrent OC HIPEC in recurrent OC HIPEC in recurrent OC HIPEC in recurrent OC HIPEC in recurrent OC HIPEC in recurrent OC HIPEC in recurrent OC HIPEC in recurrent OC HIPEC in recurrent OC HIPEC in recurrent OC HIPEC in recurrent OC HIPEC in recurrent OC HIPEC in recurrent OC HIPEC in recurrent OC HIPEC in recurrent OC HIPEC in recurrent OC HIPEC in recurrent OC HIPEC during ‘secondary surgery’ HIPEC during ‘secondary surgery’
Drug
No. of patients
Cisplatin + paclitaxel (11)/cisplatin + doxorubicin (26)/paclitaxel + doxorubicin (1)/doxorubicin (1) Cisplatin/doxorubicin/oxaliplatin/mitomycin/cisplatin + mitomycin/cisplatin + doxorubicin Paclitaxel Cisplatin + doxorubicin Cisplatin Cisplatin/carboplatin/mitomycin combination Doxorubicin + cisplatin Paclitaxel Oxaliplatin Cisplatin Paclitaxel Oxaliplatin Cisplatin/carboplatin/mitomycin combination Cisplatin + mitomycin Cisplatin/doxorubicin/oxaliplatin/mitomycin/cisplatin + mitomycin/cisplatin + doxorubicin Paclitaxel Cisplatin/oxaliplatin Cisplatin Cisplatin + doxorubicin/cisplatin + mitomycin-C. Cisplatin Oxaliplatin Oxaliplatin Oxaliplatin Cisplatin/carboplatin/mitomycin combination Cisplatin (25)/oxaliplatin (17) Cisplatin (16), oxaliplatin (6), mitomycin (1)
39 92 52 26 22 26 31 19 19 29 19 31 19 31 474 32 42 81 57 25 41 30 12 83 42 23
Median Follow-up (months) 40 25 18 60 14 64 80 18 27 40 18 21 47 23 38 46 14 18 26 24
Please cite this article in press as: Roviello F, et al. Hyperthermic intraperitoneal chemotherapy for the treatment of ovarian cancer: A brief overview of recent results. Crit Rev Oncol/Hematol (2015), http://dx.doi.org/10.1016/j.critrevonc.2015.03.007
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Table 1 (Continued ) Drug
No. of patients
Doxorubicin + cisplatin Cisplatin + mitomycin/doxorubicin
Cisplatin Carboplatin/paclitaxel Carboplatin Peritoneal carcinomatosis index
CC-0 (%)
11+
90 74
10* 9* 15* 15+
58 68 58
13+ 52 3*
8* 8* 4* 11.5+ 15* 15+ 6*
58 70 75 50 55.5 82 60 95 97
3* 58 65 100 13+ 82.5 77 Median PFS (months) 14 12 63% at 3-years 30 20
25 13 57
19
Duration of procedure (minutes) 90* (HIPEC only) 361* 620* 528 mean 450* 279* 300* 352* 210* 450* 420* 90* (HIPEC only) 300* 498* 258+ (excluding HIPEC) 563* 528* 300* 352* 450* 593*
17
24 42 34 38
61 17 33 55 37
64 84 67 (2-years) 50 58 37 41 23 17 68 24
24+ 16* 21* 22+ 10* 14+ 11* 11* 18* 10* 10* 16* 16* 17+ 28* 10*
17+ 14+ 21+ 12*
279* 410+ 410+
35
37 28 26 24 38
Hospitalization (days)
11* 10*
5-year OS (%)
46
13
60 26
Median OS (months)
69
45% at 3-years 13 19 11 20 24 26 14
Median Follow-up (months)
25 40 70 24 30 44 57
18
Ref. [9] [10] [11] [12] [13] [14] [15] [16] [17] [18] [19] [20] [14] [21] [10] [22] [23] [24] [25] [13] [26] [27] [17] [14] [28]
Please cite this article in press as: Roviello F, et al. Hyperthermic intraperitoneal chemotherapy for the treatment of ovarian cancer: A brief overview of recent results. Crit Rev Oncol/Hematol (2015), http://dx.doi.org/10.1016/j.critrevonc.2015.03.007
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Table 1 (Continued ). Median PFS (months)
Median OS (months)
24 40 41 28 19 28
24
17 56 49 * +
76
5-year OS (%)
Ref.
76 (4-years) 72 15
[29] [15] [30] [31] [32] [33] [34] [35]
50 (3-years) 66 63
Median value. Mean value.
chemotherapy in women with recurrent OC after initial debulking surgery and in a systemic chemotherapy group. The median survival rates were 19.5 months and 11.2 months (P < 0.05), respectively, and the three-year survivals were 50% and 18% in favor of the HIPEC group [32]. However, this study was a compilation of the results of a clinical series of 24 patients compared with a control group without randomization. Fagotti et al. [27] conducted a case–control study in which 30 cases were matched with 37 controls and compared the survival data from platinum-sensitive recurrent OC patients who were submitted to secondary CRS plus HIPEC (cases) and a similar group of women who did not experience HIPEC (controls) with at least 24 months of follow-up. The median follow-up times were 46 months for the cases and 36 months for the controls. Twenty patients (66.6%) among the cases experienced secondary recurrence, and 37 control women (100%) experienced secondary recurrence (P = 0.001). Moreover, 7 (23.3%) and 23 (62.2%) patients died due to disease among the cases and controls, respectively (P = 0.003). The durations of the secondary responses were 26 months in the cases and 15 months in the controls (P = 0.004). Additionally, an Italian study [25] conducted using information extracted from a multi-institutional prospective database on peritoneal surface malignancies (PSMs) revealed that HIPEC benefited wider subsets of patients than the conventional secondary debulking surgery without HIPEC. The 5-year OS and PFS were 23% and 7%, respectively. All of these studies indicate that, in the ‘platinum-sensitive setting’, HIPEC elicited significant improvements in PFS and OS. However, although Bakrin et al. [10] reported no significant difference in overall survival between patients with chemosensitive and chemoresistant recurrence, the exact role of HIPEC in the latter is unclear, and further studies are warranted. Other studies of HIPEC in recurrent OC are summarized in Table 1. HIPEC has been investigated as a consolidation treatment and during interval CRS (Table 1). However, in these setting also, the reported data are only from small retrospective analyses. In a South Korean study, patients with initial stage III OC who were treated with HIPEC at the second laparotomy were compared with patients who exhibited complete responses but did not receive HIPEC [34]. The 5-year survival rates were 66.1% with HIPEC and 31.3% in the
control group. Another study examined 51 patients with OC who underwent frontline surgery with CRS and systemic chemotherapy. Thirty-two patients underwent second-look laparotomy with HIPEC, and the other 19 who refused second-look were used as a control group. The median survivals were 64.4 months in the HIPEC arm and 46.4 months in the control group [18]. Other studies are presented in Table 1. Finally, Fagotti et al. [38] described the first experience of minimally invasive CRS plus HIPEC in OC. These authors retrospectively evaluated a consecutive series of OC patients with isolated platinum-sensitive relapse. Ten cases were treated with laparoscopic/robotic secondary CRS + HIPEC. In all cases, complete debulking was achieved. In all patients, the post-operative FDG-PET/CT scans were negative, and after a median time of 10 months (6–37) from the secondary CRS + HIPEC, no secondary recurrence was observed. Although the small numbers of patients and the retrospective data do not allow the drawing of definitive conclusions, minimally invasive CRS + HIPEC might be a safe option for selected OC patients, and further studies are required.
3. Morbidity and mortality of HIPEC The available data from larger reviewed HIPEC series indicate severe surgical morbidity (the rate approaches 25–35%) and mortality. Data from two systematic reviews [1,6] suggest that the morbidity and mortality rates (0–40% and 0–10%, respectively) can be reduced by accurate patient selection. Surgical complications were frequently encountered and were related to extensive surgery. Unfortunately, many authors have published their experiences using different criteria for defining post-operative morbidity and mortality. Although the locoregional administration of chemoperfusate should reduce the risk of systemic effects of chemotherapy agents, complications that are primarily related to the HIPEC procedure include hematological toxic effects (0–31%) due to transitory bone marrow suppression and renal insufficiency (0–7%), primarily in cisplatin-delivered HIPEC [6]. More recently, a retrospective Italian multicentric study [39] showed that older age, ovarian tumor origin, the presence
Please cite this article in press as: Roviello F, et al. Hyperthermic intraperitoneal chemotherapy for the treatment of ovarian cancer: A brief overview of recent results. Crit Rev Oncol/Hematol (2015), http://dx.doi.org/10.1016/j.critrevonc.2015.03.007
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of ascites, the closed technique and longer operative time were predictors of higher morbidity, while older age and greater PCI values were correlated with increased mortality. Additionally, a recent systematic review demonstrated that, in tertiary high-volume centers, the mortality and morbidity rates might decrease to the ranges of 0.9–5.8% and 12–52%, respectively [40].
4. Future prospects Over the last several years, numerous groups of surgeons have become involved in the use of HIPEC for PC from OC; however, at present, only few centers have experiences that exceed 100 cases, and the HIPEC procedure has not yet been standardized. Some authors have reported that the performance of at least 130 procedures is necessary to consider the physician an expert in cytoreduction using the Sugarbaker technique [41]. Generally, HIPEC seems welltolerated and associated with acceptable morbidity when patient selection is appropriate and adequate experience is gained in a referral center. However, the most essential question is whether this technique provides a survival advantage [24]. All of the mentioned studies were primarily based on small, retrospective, non-consecutive cohorts of patients with heterogeneous management without randomization. This heterogeneity precludes definitive conclusion about the survival results. In the future, large randomized trials are warranted to determine the role of HIPEC in OC treatment. Only recently, the first randomized study evaluating the role of HIPEC in recurrent OC showed that HIPEC significantly prolonged OS (26.7 vs. 13.4 months in the non-HIPEC group, P = 0.006) [42]. Nevertheless, in this regarding, some studies are currently recruiting participants in different stage of disease. The first is a study from the Netherlands (NCT00426257) [43]. This study evaluates the efficacy and safety of the addition of HIPEC to secondary debulking surgery in stage III ovarian cancer. A multicentric phase III trial from France, i.e., the CHIPOR study (NCT01376752) [44], which will compare second-line systemic chemotherapy followed by maximal CRS with or without HIPEC in 444 relapsed OC patients, has begun the recruitment of participants. Additionally, an Italian multicentric phase III trial, i.e., the HORSE study (NCT01539785) [45], will randomize 158 women with platinum-sensitive first relapse to surgery or surgery and HIPEC. The latest published protocol evaluating HIPEC in primary advanced OC (NCT01628380) [46] is the CHORINE study. This is an Italian multicentric trial regarding the role of HIPEC after chemotherapy in patients who have responded to the treatment. Another randomized study of HIPEC conducted by the Italian Society of Integrated Locoregional Therapy (STILO) regarding the role of HIPEC in persistent OC had to be closed prematurely nearly a decade ago due to poor patient accrual [47].
Currently, it is very difficult to evaluate the real influence of HIPEC in terms of overall survival and disease-free survival. There is too much bias that might interfere with the final results. Thus, no standardized HIPEC criteria have yet been adopted. Each protocol applies different methods, e.g., different drug doses, different perfusion times at different temperatures, different criteria for evaluating the completeness of cytoreduction and different classifications of complications. Moreover, the randomizations have been planned at different time points. Many centers treat a small number of patients each year and thus lack the necessary surgical expertise in the treatment of advanced and peritoneally spread cancer. However, the current evidence suggests that optimal CRS and HIPEC might be feasible treatment option with potential benefits. In conclusion, based on the published evidence, HIPEC must be included in clinical research and not in routine treatment. Indeed, it is clear that CRS plus HIPEC is not indicated for all patients with OC but has an established role in select patients. In highly specialized treatment centers, the mortality and morbidity rates are low; therefore, criticism of the feasibility of this procedure is no longer acceptable. Combined treatment with CRS and HIPEC is, at present, suggested by the international consensus group as the treatment that is most likely to favorably affect survival in stage III OC. Patients need to be centralized to the more experienced centers to allow them to participate in the ongoing trials. Centralization might also provide the patients the possibility of undergoing real, complete cytoreduction without the risk of residual disease, which should have a positive influence on survival rates. Additionally, new criteria are needed and should include a uniform method of staging peritoneal disease, the optimal degree of the extension of the surgical resection that should be associated with HIPEC, the best method for performing intraperitoneal chemohyperthermia, and the type and dose of anticancer drug. Conflict of interest The authors have no potential conflicts of interest to declare. Reviewers Cristiana Sessa, L’Istituto Oncologico Della Svizzera Italiana (ISOI), Istituto Oncologico della Svizzera Italiana (IOSI), Ospedale Regionale Bellinzona e Valli, CH-6500 Bellinzona, Switzerland. Luca Bocciolone, European Institute of Oncology, Gynecology, Via Ripamonti 435, Milan, Italy. References [1] Chua TC, Robertson G, Liauw W, et al. Intraoperative hyperthermic intraperitoneal chemotherapy after cytoreductive surgery in ovarian
Please cite this article in press as: Roviello F, et al. Hyperthermic intraperitoneal chemotherapy for the treatment of ovarian cancer: A brief overview of recent results. Crit Rev Oncol/Hematol (2015), http://dx.doi.org/10.1016/j.critrevonc.2015.03.007
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[2]
[3]
[4]
[5] [6]
[7]
[8] [9]
[10]
[11]
[12]
[13]
[14]
[15]
[16]
[17]
[18]
[19]
cancer peritoneal carcinomatosis: systematic review of current results. J Cancer Res Clin Oncol 2009;135:1637–45. Glehen O, Mohamed F, Gilly FN. Peritoneal carcinomatosis from digestive tract cancer: new management by cytoreductive surgery and intraperitoneal chemohyperthermia. Lancet Oncol 2004;5:219–28. Sugarbaker PH. Intraperitoneal chemotherapy and cytoreductive surgery for the prevention and treatment of peritoneal carcinomatosis and sarcomatosis. Semin Surg Oncol 1998;14:254–61. Van der Speeten K, Stuart OA, Sugarbaker PH. Pharmacokinetics and pharmacodynamics of perioperative cancer chemotherapy in peritoneal surface malignancy. Cancer J 2009;15:216–24. Sugarbaker PH. Peritonectomy procedures. Ann Surg 1995;221: 29–42. Bijelic L, Jonson A, Sugarbaker PH. Systematic review of cytoreductive surgery and heated intraoperative intraperitoneal chemotherapy for treatment of peritoneal carcinomatosis in primary and recurrent ovarian cancer. Ann Oncol 2007;18:1943–50. Loggie BW, Sterchi JM, Rogers AT, et al. Intraperitoneal hyperthermic chemotherapy for advanced gastrointestinal and ovarian cancers. Reg Cancer Treat 1995;7(2):78–81. Helm CW. The role of hyperthermic intraperitoneal chemotherapy (HIPEC) in ovarian cancer. Oncologist 2009;14(7):683–94. Ansaloni L, Agnoletti V, Amadori A, Catena F, Cavaliere D, Coccolini F, et al. Evaluation of extensive cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) in patients with advanced epithelial ovarian cancer. Int J Gynecol Cancer 2012;22(June (5)):778–85. 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. Cascales-Campos PA, Gil J, Gil E, Feliciangeli E, González-Gil A, Parrilla JJ, et al. Treatment of microscopic disease with hyperthermic intraoperative intraperitoneal chemotherapy after complete cytoreduction improves disease-free survival in patients with stage IIIC/IV ovarian cancer. Ann Surg Oncol 2014;21(July (7)):2383–9. Deraco M, Kusomura S, Virzi S, et al. Cytoreductive surgery and hyperthermic intra-peritoneal chemotherapy as up front therapy for advanced, EOC: multi-institutional phase II study. Gynecol Oncol 2011;122(2):215–20. Di Giorgio A, Naticchioni E, Biacchi D, Sibio S, Accarpio F, Rocco M, et al. Cytoreductive surgery (peritonectomy procedures) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) in the treatment of diffuse peritoneal carcinomatosis from ovarian cancer. Cancer 2008;113:315–25. Helm CW, Richard SD, Pan J, et al. HIPEC in ovarian cancer: first report of HYPER-O registry. Int J Gynecol Cancer 2010;20(1): 61–9. Pavlov MJ, Kovacevic PA, Ceranic MS, Stamenkovic AB, Ivanovic AM, Kecmanovic DM. Cytoreductive surgery and modified heated intraoperative intraperitoneal chemotherapy (HIPEC) for advanced and recurrent ovarian cancer – 12-year single center experience. Eur J Surg Oncol 2009;35(November (11)):1186–91. Rufian S, Munoz-Casares FC, Briceno J, et al. Radical surgery— peritonectomy and intra-operative intraperitoneal chemotherapy for the treatment of peritoneal carcinomatosis in recurrent or primary ovarian cancer. J Surg Oncol 2006;94(4):316–24. Frenel JS, Leux C, Pouplin L, Ferron G, Berton Rigaud D, Bourbouloux E, et al. Oxaliplatin-based hyperthermic intraperitoneal chemotherapy in primary or recurrent epithelial ovarian cancer: a pilot study of 31 patients. J Surg Oncol 2011;103(January (1)):10–6. Gori J, Casta˜no R, Toziano M, Häbich D, Staringer J, De Quirós DG, et al. Intraperitoneal hyperthermic chemotherapy in ovarian cancer. Gynecol Cancer 2005;15(March–April (2)):233–9. Kim JH, Lee JM, Ryu KS, Lee YS, Park YG, Hur SY, et al. Consolidation hyperthermic intraperitoneal chemotherapy using paclitaxel in
[20]
[21]
[22]
[23]
[24]
[25]
[26]
[27]
[28]
[29]
[30]
[31]
[32]
[33]
[34]
[35]
7
patients with epithelial ovarian cancer. J Surg Oncol 2010;101(February (2)):149–55. Pomel C, Ferron G, Lorimier G, Rey A, Lhomme C, Classe JM, et al. Hyperthermic intra-peritoneal chemotherapy using oxaliplatin as consolidation therapy for advanced epithelial ovarian carcinoma: results of a phase II prospective multicentre trial. CHIPOVAC study. Eur J Surg Oncol 2010;36(June (6)):589–93. Roviello F, Pinto E, Corso G, Pedrazzani C, Caruso S, et al. Safety and potential benefit of hyperthermic intraperitoneal chemotherapy (HIPEC) in peritoneal carcinomatosis from primary or recurrent ovarian cancer. J Surg Oncol 2010;102(November (6)):663–70. Cascales-Campos PA, Gil J, Feliciangeli E, Gil E, González-Gil A, López V, et al. The role of hyperthermic intraperitoneal chemotherapy using paclitaxel in platinum-sensitive recurrent epithelial ovarian cancer patients with microscopic residual disease after cytoreduction. Ann Surg Oncol 2014;(September). Ceelen WP, Van Nieuwenhove Y, Van Belle S, Denys H, Pattyn P. Cytoreduction and hyperthermic intraperitoneal chemoperfusion in women with heavily pretreated recurrent ovarian cancer. Ann Surg Oncol 2012;19(July (7)):2352–9. Cotte E, Glehen O, Mohamed F, Lamy F, Falandry C, Golfier F, et al. Cytoreductive surgery and intraperitoneal chemo-hyperthermia for chemoresistant and recurrent advanced epithelial ovarian cancer: prospective study of 81 patients. World J Surg 2007;31: 1813–20. Deraco M, Virzì S, Iusco DR, et al. Secondary cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for recurrent epithelial ovarian cancer: a multi-institutional study. BJOG 2012;119(June (7)):800–9. Fagotti A, Costantini B, Vizzielli G, et al. HIPEC in recurrent ovarian cancer patients: morbidity-related treatment and long-term analysis of clinical outcome. Gynecol Oncol 2011;122(2):221–5. 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(December (3)):502–5. Königsrainer I, Beckert S, Becker S, Zieker D, Fehm T, Grischke EM, et al. Cytoreductive surgery and HIPEC in peritoneal recurrent ovarian cancer: experience and lessons learned. Langenbecks Arch Surg 2011;396(October (7)):1077–81. Le Brun JF, Campion L, Berton-Rigaud D, Lorimier G, Marchal F, Ferron G, et al. Survival benefit of hyperthermic intraperitoneal chemotherapy for recurrent ovarian cancer: a multi-institutional case control study. Ann Surg Oncol 2014;21(October (11)):3621–7. Raspagliesi F, Kusamura S, Campos Torres JC, de Souza GA, Ditto A, Zanaboni F, et al. Cytoreduction combined with intraperitoneal hyperthermic perfusion chemotherapy in advanced/recurrent ovarian cancer patients: the experience of National Cancer Institute of Milan. Eur J Surg Oncol 2006;32:671–5. Robella M, Vaira M, Marsanic P, Mellano A, Borsano A, Cinquegrana A, et al. Treatment of peritoneal carcinomatosis from ovarian cancer by surgical cytoreduction and hyperthermic intraperitoneal chemotherapy (HIPEC). Minerva Chir 2014;69(February (1)):27–35. Spiliotis J, Vaxevanidou A, Sergouniotis F, Lambropoulou E, Datsis A, Christopoulou A. The role of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in the management of recurrent advanced ovarian cancer: a prospective study. J BUON 2011;16(1):74–9. Zanon C, Clara R, Chiappino I, Bortolini M, Cornaglia S, Simone P, et al. Cytoreductive surgery and intraperitoneal chemohyperthermia for recurrent peritoneal carcinomatosis from ovarian cancer. World J Surg 2004;28(October (10)):1040–5. Bae JH, Lee JM, Ryu KS, et al. Treatment of ovarian cancer with paclitaxel- or carboplatin-based intraperitoneal hyperthermic chemotherapy during secondary surgery. Gynecol Oncol 2007;106(1):193–200. Ryu KS, Kim JH, Ko HS, et al. Effects of intraperitoneal hyperthermic chemotherapy in ovarian cancer. Gynecol Oncol 2004;94:325–32.
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[36] Lim MC, Kang S, Choi J, Song YJ, Park S, Seo SS, et al. Hyperthermic intraperitoneal chemotherapy after extensive cytoreductive surgery in patients with primary advanced epithelial ovarian cancer: interim analysis of a phase II study. Ann Surg Oncol 2009;16(April (4)):993–1000. [37] Bristow RE, Puri I, Chi DS. Cytoreductive surgery for recurrent ovarian cancer: a meta-analysis. Gynecol Oncol 2009;112(January (1)):265–74. [38] Fagotti A, Petrillo M, Costantini B, Fanfani F, Gallotta V, Chiantera V, et al. Minimally invasive secondary cytoreduction plus HIPEC for recurrent ovarian cancer: a case series. Gynecol Oncol 2014;132(February (2)):303–6. [39] Macrì A, Arcoraci V, Belgrano V, Caldana M, Cioppa T, Costantini B, et al. Short-term outcome of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy: preliminary analysis of a multicentre study. Anticancer Res 2014;34(October (10)):5689–93. [40] Chua TC, Yan TD, Saxena A, Morris DL. Should the treatment of peritoneal carcinomatosis by cytoreductive surgery and hyperthermic intraperitoneal chemotherapy still be regarded as a highly morbid procedure?: a systematic review of morbidity and mortality. Ann Surg 2009;249:900–7. [41] Spiliotis JD, Rogdakis A, Vaxevanidou A, Datsis A, Zacharis G, Christopoulou A. Morbidity and mortality of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in the management of peritoneal carcinomatosis. J BUON 2009;14(2):259–64. [42] 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 2014;(November). [43] www.clinicaltrials.gov/ct2/show/record/NCT00426257 [44] www.clinicaltrials.gov/ct2/show/record/NCT01376752 [45] www.clinicaltrials.gov/ct2/show/record/NCT01539785 [46] www.clinicaltrials.gov/ct2/show/record/NCT01628380 [47] Deraco M, Raspagliesi F, Kusamura S. Management of peritoneal surface component of ovarian cancer. Surg Oncol Clin N Am 2003;12(July (3)):561–83 [review].
Biographies Franco Roviello is an Associate Professor of Surgery at the Department of Medicine, Surgery and Neurosciences, Unit of General and Minimally Invasive Surgery, University of Siena, Italy. He is teacher at several Degree Courses (Medicine, Nursing) and Specialization Schools. In 2013 has obtained the National Scientific Ability to Full Professor of Surgery From 2006 to date: President of the Italian Research Group for Gastric Cancer (GIRCG), a multicenter multidisciplinary research group. Coordinator of several GIRCG research protocols, published on important Journals of Surgery and Surgical Oncology; during the coordination of the Scientific Secretary, GIRCG scientific production and international relevance grown considerably. Intense Scientific production, member of the Editorial Board of four European Journal of Surgical Oncology, and invited Reviewer of International Journals. Clinical and surgical activity has been particularly dedicated to Surgical Oncology, including treatment of esophageal, gastric and colorectal cancer, liver and pancreatic cancer, peritoneal carcinomatosis, with the application of modern multimodal therapeutic protocols, as neoadjuvant therapy, locoregional treatments, peritonectomy and intraperitoneal chemohyperthermia (HIPEC) and minivasive surgery.
Giandomenico Roviello is currently a resident Physician in Medical Oncology Residency Program, Università degli Studi di Siena, Oncology Unit, Department of Oncology, Istituto Toscano Tumori (ITT), Azienda USL7, Ospedale Santa Maria delle Scotte, Siena. Dr. Roviello graduated from the School of Medicine, Second University of Naples in 2008, with the thesis about the use of Bortezomib in patients with Multiple Myeloma. His current research interests are genitourinary oncology, and particularly prostate cancer and renal cell carcinoma, gastric cancers and targeted anticancer therapies. Dr. Roviello has published 15 articles in peer-reviewed journals, more than 30 abstracts. He sits on the editorial board and is a reviewer for several oncological journals. Dr. Roviello’s society memberships include: the European Societies for Medical Oncology, the Italian Association of Urological Oncology and the Italian Association for gastric research (GIRCG). Roberto Petrioli MD, is a medical oncologist at Medical Oncology Unit, University of Siena, Italy. He was born in Siena, november 20, 1960. He received a Medical Degree from Siena University, where he also trained in Internal Medicine and Oncology. In 1992 Postgraduate School in Oncology at Pavia University, Italy. He is actually professor at Oncology Postgraduate School at Siena University. Dr. Petrioli is skilled in the management of solid tumors, with particular interest in cases of genitourinary and gastrointestinal tract. He is married and has a son. Daniele Marrelli is an Associate Professor of Surgery at the Department of Medicine, Surgery and Neurosciences, Unit of Surgical Oncology, University of Siena, Italy. He is teacher at several Degree Courses (Medicine, Nursing) and Specialization Schools. In 2013 has obtained the National Scientific Ability to Full Professor of Surgery From 2006 to date: Scientific Secretary of the Italian Research Group for Gastric Cancer (GIRCG), a multicenter multidisciplinary research group. Coordinator of several GIRCG research protocols, published on important Journals of Surgery and Surgical Oncology; during the coordination of the Scientific Secretary, GIRCG scientific production and international relevance grown considerably. Research activity has been conducted in collaboration with other international research groups: IPATIMUP (Porto), University of Munich, University of Seoul, University of San Paolo. Invited Speaker, Chairman or Member of the Scientific Committee to several National and International Congresses. Responsible of the Scientific Committee of the 10th International Gastric Cancer Congress, organized by the International Gastric Cancer Association (IGCA); Verona, June 2013. Member, in representation of European Countries, of the Committee for IGCA Staging Project for the new TNM; San Francisco, January 2014. Intense Scientific production, consisting of 303 publications (151 on international Journals, 20 on Congress Proceedings, 120 Meeting Abstracts, 12 Book chapters) Impact points: 425 (full papers) Citations: 2370 (ISI WEB of Knowledge) h-index: 26 (ISI WEB). Great
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knowledge of statistical programs, such as Statistical Program for Social Science (SPSS), STATA, BMDP, and attendance to several specific statistical courses. Member of the Editorial Board of four International Journals, and invited Reviewer of 25 International Journals. Clinical and surgical activity has been particularly dedicated to Surgical Oncology,
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including treatment of esophageal, gastric and colorectal cancer, liver and pancreatic cancer, peritoneal carcinomatosis, with the application of modern multimodal therapeutic protocols, as neoadjuvant therapy, locoregional treatments, peritonectomy and intraperitoneal chemohyperthermia (HIPEC).
Please cite this article in press as: Roviello F, et al. Hyperthermic intraperitoneal chemotherapy for the treatment of ovarian cancer: A brief overview of recent results. Crit Rev Oncol/Hematol (2015), http://dx.doi.org/10.1016/j.critrevonc.2015.03.007
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Hyperthermic intraperitoneal chemotherapy for the treatment of ovarian cancer: A brief overview of recent results Franco Roviello a , Giandomenico Roviello b,∗ , Roberto Petrioli b , Daniele Marrelli c a
Department of Medicine, Surgery and Neurosciences, Unit of General and Mini-Invasive Surgery, University of Siena, Policlinico “Le Scotte”, Viale Bracci, 53100 Siena, Italy b Medical Oncology Unit, University of Siena, Viale Bracci 11, 53100 Siena, Italy c Department of Medicine, Surgery and Neurosciences, Unit of General Surgery and Surgical Oncology, University of Siena, Policlinico “Le Scotte”, Viale Bracci, 53100 Siena, Italy Accepted 31 March 2015
Contents 1. 2. 3. 4.
Introduction. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Results of HIPEC for OC: a brief overview . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Morbidity and mortality of HIPEC . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Future prospects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Conflict of interest . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Reviewers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Biographies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
00 00 00 00 00 00 00 00
Abstract Ovarian cancer (OC) is the sixth most common neoplasm in women. Hyperthermic intraperitoneal chemotherapy (HIPEC), a strategy combining maximal cytoreductive surgery with maximal regional chemotherapy, has been proposed to treat OC. At present, less randomized trials has determined HIPEC real impact on patients with OC. In this brief report, we reported results of selected studies of treatment with HIPEC for patients with OC. Future prospects are conclusively discussed. © 2015 Elsevier Ireland Ltd. All rights reserved.
Keywords: Ovarian cancer; HIPEC
1. Introduction Hyperthermic intraperitoneal chemotherapy (HIPEC) is a locoregional treatment that involves the washing of the peritoneal cavity with a heated solution and high drug concentrations [1,2]. The rationale of HIPEC is based on the direct cytotoxicity of hyperthermia for malignant cells, ∗ Corresponding author at: Medical Oncology, University of Siena, Policlinico Le Scotte, Viale Bracci 11, 53100 Siena, Italy. Tel.: +39 0577585418; fax: +39 0577586101. E-mail address: [email protected] (G. Roviello).
the enhancement of this cytotoxicity by anticancer drugs, and the pharmacokinetic advantages of the intraperitoneal route for chemotherapy [3,4]. HIPEC must be linked with complete surgical removal of peritoneal carcinomatosis (PC) because HIPEC does not work in cases of residual tumor; indeed, intraperitoneal chemotherapy, even with hyperthermia, does not reach more than 5 mm deep into the tissue. Therefore, the results of HIPEC treatment seem promising for PC [2] when peritonectomy, as described by Sugarbaker [5], is combined with cytoreductive surgery (CRS). The positive effects of peritonectomy on survival and HIPEC in advanced OC are being reported with increasing frequency [6].
http://dx.doi.org/10.1016/j.critrevonc.2015.03.007 1040-8428/© 2015 Elsevier Ireland Ltd. All rights reserved.
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The first report of the use of HIPEC for OC was in 1994 [7]. Since that time, there has been a large volume of published research evaluating this modality in conjunction with CRS. Two systematic reviews [1,6] that analyzed nearly almost all of the available international literature (14 and 19 studies) concluded that HIPEC is a viable option for the management of patients with advanced stage III–IV disease that has potential benefits that are comparable with those of the current standard of care (i.e., conventional secondary cytoreduction or systemic chemotherapy). The median overall survivals for primary and recurrent disease based on extrapolation from the reviewed studies ranged from 22 to 64 months with median disease-free survivals that ranged from 10 to 87 months [1,6]. Nevertheless, little is known at present about the real longterm prognostic effects of this treatment modality. Indeed, none of the currently published studies are randomized trials. The levels of evidence of the published studies are primarily class II or class III (i.e., non-randomized comparative studies and observational studies). Additionally, the patient cohort that has been treated is heterogeneous group that includes cases with either advanced or recurrent OC who have undergone previous surgery and chemotherapy. A significant proportion of the patients within these studies also had documented chemoresistance and had undergone multiple treatments [1,6]. Furthermore, the operative procedures, CRS and the HIPEC systems are expensive and complex in design and application in terms of the particular aggressive treatment modality needed for carcinomatosis. These treatments not only require highly specialized human resources but also require complex technological facilities, and a learning curve also exists. Therefore, the HIPEC procedure has not yet been standardized. In this report, we present the results of HIPEC for patients with OC. Future prospects are conclusively discussed.
2. Results of HIPEC for OC: a brief overview The natural history of OC includes several time points at which HIPEC can be performed; the first is primary OC (firstline treatment), the second is as a consolidation treatment, and the third is for persistent, progressive and recurrent disease (second-line treatment) [8]. The selection criteria were as follows: studies that involved adult patients older than 18 years who were diagnosed with OC and treated with HIPEC, studies that enrolled more than 15 patients and studies conducted between the years 2005 and 2014 that reported data about efficacy. The search was limited to articles published in the English language and confined to studies that were conducted on human subjects. The exclusion criteria included patients below the age of 18 years, data presented as abstracts and unpublished reports. The data from several of the selected studies are been summarized in Table 1 . The HIPEC studies concerning primary OC were less in number and size than those involving recurrent disease. In
this regard, a recent retrospective cohort multicentric study from French centers reported 92 patients with advanced OC who received first-line treatment [10]. For these patients, the median overall survival was 35.4 months. The survival rates at 1, 3 and 5 years were 83%, 47% and 17%, respectively. The median recurrence-free survival was 11.8 months. The recurrence-free survival rates at 1, 3, and 5 year were 52%, 18%, and 12%, respectively. The best outcomes were observed after complete CRS because the patients treated with CC-0 CRS exhibited a median survival of 41.5 months. A Korean study (NCT01091636) [36] evaluated the toxicities of and treatment responses to intraoperative HIPEC in patients with advanced epithelial OC. No deaths or grade IV morbidities were observed. Therefore, the authors concluded that HIPEC after extensive cytoreductive surgery for OC is a procedure with an acceptable morbidity that patients can tolerate. Deraco and co-workers [12] achieved complete CRS in 58% of the patients and achieved survival data better than that of a well-experienced center in which the maximal surgical efforts to achieve complete CRS were followed by systemic chemotherapy only (5-years OS: 51 vs. 47%) [1,6]. Similar results were demonstrated by Rufian et al. [16]. These authors reported a median overall survival of 66 months in a small number of patients (19) after complete cytoreduction. Other studies are presented in Table 1. However, considering the weaknesses of the published studies, which were primarily retrospective, it is not possible today to conclude whether the use of HIPEC a frontline treatment and the delayed of first-line chemotherapy influences the overall survival of patients. Conversely, HIPEC has been primarily investigated in the setting of persistent or recurrent disease. The addition of HIPEC is an interesting and promising treatment for recurrent OC when it is combined with complete cytoreduction. Although, a significant number of investigated patients generally presented with early recurrent disease or heavily pre-treated (re-)recurrent disease with diffuse PC, and these patients’ characteristics can be suggestive of poor outcomes, in the majority of the series, the median OS was longer than that reported for secondary CRS only [37]. However, the majority of the studies were heterogeneous and retrospective; therefore, they share some obvious and inevitable limitations with all retrospective analyses. In a recent retrospective study [10] by Bakrin et al., the results from 474 patients with recurrent OC (either chemoresistant or chemosensitive) were reported. For these patients, the median overall survival was 45.7 months. The overall survival rates at 1, 3 and 5 years were 89%, 59% and 37%, respectively. Interestingly, there was no significant difference in overall survival between the patients with chemosensitive and chemoresistant recurrence. Indeed, the patients with chemoresistant and chemosensitive recurrences who were treated with CC-0 CRS exhibited median survivals of 51.6 months and 47.2 months, respectively (P = 0.799). Spiliotis et al. [32] evaluated the role of CRS and HIPEC plus systemic chemotherapy versus CRS plus systemic
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Table 1 Survival rates and surgical variables of CRS plus HIPEC in patients with OC. Study
Disease status
Ansaloni et al. (2012) Bakrin et al. (2013) Cascales Campos et al. (2014) Deraco et al. (2011) Di Giorgio et al. (2008) Helm et al. (2010) (HYPER-O) Pavlov et al. (2009) Rufian et al. (2006) Frenel et al. (2011) Gori et al. (2005) Kim et al. (2010) Pomel et al. (2010) Helm et al. (2010) (HYPER-O) Roviello et al. (2010) Bakrin et al. (2013) Cascales Campos et al. (2014) Ceelen et al. (2009) Cotte et al. (2007) Deraco et al. (2012) Di Giorgio et al. (2008) Fagotti et al. (2011) Fagotti et al. (2012) Frenel et al. (2011) Helm et al. (2010) (HYPER-O) Koningsrainer et al. (2011) Le Brun et al. (2014) Pavlov et al. (2009) Raspagliesi et al. (2006) Robella et al. (2014) Spiliotis et al. (2011) Zanon et al. (2004) Bae et al. (2007) Ryu et al. (2004)
30 HIPEC in Recurrent OC/9 first line treatment during primary CRS First line treatment during primary CRS First line treatment during primary CRS First line treatment during primary CRS First line treatment during primary CRS First line treatment during primary CRS First line treatment during primary CRS First line treatment during primary CRS HIPEC as Consolidation Treatment HIPEC as Consolidation Treatment HIPEC as Consolidation Treatment HIPEC as Consolidation Treatment HIPEC during interval CRS HIPEC during interval CRS HIPEC in recurrent OC HIPEC in recurrent OC HIPEC in recurrent OC HIPEC in recurrent OC HIPEC in recurrent OC HIPEC in recurrent OC HIPEC in recurrent OC HIPEC in recurrent OC HIPEC in recurrent OC HIPEC in recurrent OC HIPEC in recurrent OC HIPEC in recurrent OC HIPEC in recurrent OC HIPEC in recurrent OC HIPEC in recurrent OC HIPEC in recurrent OC HIPEC in recurrent OC HIPEC during ‘secondary surgery’ HIPEC during ‘secondary surgery’
Drug
No. of patients
Cisplatin + paclitaxel (11)/cisplatin + doxorubicin (26)/paclitaxel + doxorubicin (1)/doxorubicin (1) Cisplatin/doxorubicin/oxaliplatin/mitomycin/cisplatin + mitomycin/cisplatin + doxorubicin Paclitaxel Cisplatin + doxorubicin Cisplatin Cisplatin/carboplatin/mitomycin combination Doxorubicin + cisplatin Paclitaxel Oxaliplatin Cisplatin Paclitaxel Oxaliplatin Cisplatin/carboplatin/mitomycin combination Cisplatin + mitomycin Cisplatin/doxorubicin/oxaliplatin/mitomycin/cisplatin + mitomycin/cisplatin + doxorubicin Paclitaxel Cisplatin/oxaliplatin Cisplatin Cisplatin + doxorubicin/cisplatin + mitomycin-C. Cisplatin Oxaliplatin Oxaliplatin Oxaliplatin Cisplatin/carboplatin/mitomycin combination Cisplatin (25)/oxaliplatin (17) Cisplatin (16), oxaliplatin (6), mitomycin (1)
39 92 52 26 22 26 31 19 19 29 19 31 19 31 474 32 42 81 57 25 41 30 12 83 42 23
Median Follow-up (months) 40 25 18 60 14 64 80 18 27 40 18 21 47 23 38 46 14 18 26 24
Please cite this article in press as: Roviello F, et al. Hyperthermic intraperitoneal chemotherapy for the treatment of ovarian cancer: A brief overview of recent results. Crit Rev Oncol/Hematol (2015), http://dx.doi.org/10.1016/j.critrevonc.2015.03.007
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Table 1 (Continued ) Drug
No. of patients
Doxorubicin + cisplatin Cisplatin + mitomycin/doxorubicin
Cisplatin Carboplatin/paclitaxel Carboplatin Peritoneal carcinomatosis index
CC-0 (%)
11+
90 74
10* 9* 15* 15+
58 68 58
13+ 52 3*
8* 8* 4* 11.5+ 15* 15+ 6*
58 70 75 50 55.5 82 60 95 97
3* 58 65 100 13+ 82.5 77 Median PFS (months) 14 12 63% at 3-years 30 20
25 13 57
19
Duration of procedure (minutes) 90* (HIPEC only) 361* 620* 528 mean 450* 279* 300* 352* 210* 450* 420* 90* (HIPEC only) 300* 498* 258+ (excluding HIPEC) 563* 528* 300* 352* 450* 593*
17
24 42 34 38
61 17 33 55 37
64 84 67 (2-years) 50 58 37 41 23 17 68 24
24+ 16* 21* 22+ 10* 14+ 11* 11* 18* 10* 10* 16* 16* 17+ 28* 10*
17+ 14+ 21+ 12*
279* 410+ 410+
35
37 28 26 24 38
Hospitalization (days)
11* 10*
5-year OS (%)
46
13
60 26
Median OS (months)
69
45% at 3-years 13 19 11 20 24 26 14
Median Follow-up (months)
25 40 70 24 30 44 57
18
Ref. [9] [10] [11] [12] [13] [14] [15] [16] [17] [18] [19] [20] [14] [21] [10] [22] [23] [24] [25] [13] [26] [27] [17] [14] [28]
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Table 1 (Continued ). Median PFS (months)
Median OS (months)
24 40 41 28 19 28
24
17 56 49 * +
76
5-year OS (%)
Ref.
76 (4-years) 72 15
[29] [15] [30] [31] [32] [33] [34] [35]
50 (3-years) 66 63
Median value. Mean value.
chemotherapy in women with recurrent OC after initial debulking surgery and in a systemic chemotherapy group. The median survival rates were 19.5 months and 11.2 months (P < 0.05), respectively, and the three-year survivals were 50% and 18% in favor of the HIPEC group [32]. However, this study was a compilation of the results of a clinical series of 24 patients compared with a control group without randomization. Fagotti et al. [27] conducted a case–control study in which 30 cases were matched with 37 controls and compared the survival data from platinum-sensitive recurrent OC patients who were submitted to secondary CRS plus HIPEC (cases) and a similar group of women who did not experience HIPEC (controls) with at least 24 months of follow-up. The median follow-up times were 46 months for the cases and 36 months for the controls. Twenty patients (66.6%) among the cases experienced secondary recurrence, and 37 control women (100%) experienced secondary recurrence (P = 0.001). Moreover, 7 (23.3%) and 23 (62.2%) patients died due to disease among the cases and controls, respectively (P = 0.003). The durations of the secondary responses were 26 months in the cases and 15 months in the controls (P = 0.004). Additionally, an Italian study [25] conducted using information extracted from a multi-institutional prospective database on peritoneal surface malignancies (PSMs) revealed that HIPEC benefited wider subsets of patients than the conventional secondary debulking surgery without HIPEC. The 5-year OS and PFS were 23% and 7%, respectively. All of these studies indicate that, in the ‘platinum-sensitive setting’, HIPEC elicited significant improvements in PFS and OS. However, although Bakrin et al. [10] reported no significant difference in overall survival between patients with chemosensitive and chemoresistant recurrence, the exact role of HIPEC in the latter is unclear, and further studies are warranted. Other studies of HIPEC in recurrent OC are summarized in Table 1. HIPEC has been investigated as a consolidation treatment and during interval CRS (Table 1). However, in these setting also, the reported data are only from small retrospective analyses. In a South Korean study, patients with initial stage III OC who were treated with HIPEC at the second laparotomy were compared with patients who exhibited complete responses but did not receive HIPEC [34]. The 5-year survival rates were 66.1% with HIPEC and 31.3% in the
control group. Another study examined 51 patients with OC who underwent frontline surgery with CRS and systemic chemotherapy. Thirty-two patients underwent second-look laparotomy with HIPEC, and the other 19 who refused second-look were used as a control group. The median survivals were 64.4 months in the HIPEC arm and 46.4 months in the control group [18]. Other studies are presented in Table 1. Finally, Fagotti et al. [38] described the first experience of minimally invasive CRS plus HIPEC in OC. These authors retrospectively evaluated a consecutive series of OC patients with isolated platinum-sensitive relapse. Ten cases were treated with laparoscopic/robotic secondary CRS + HIPEC. In all cases, complete debulking was achieved. In all patients, the post-operative FDG-PET/CT scans were negative, and after a median time of 10 months (6–37) from the secondary CRS + HIPEC, no secondary recurrence was observed. Although the small numbers of patients and the retrospective data do not allow the drawing of definitive conclusions, minimally invasive CRS + HIPEC might be a safe option for selected OC patients, and further studies are required.
3. Morbidity and mortality of HIPEC The available data from larger reviewed HIPEC series indicate severe surgical morbidity (the rate approaches 25–35%) and mortality. Data from two systematic reviews [1,6] suggest that the morbidity and mortality rates (0–40% and 0–10%, respectively) can be reduced by accurate patient selection. Surgical complications were frequently encountered and were related to extensive surgery. Unfortunately, many authors have published their experiences using different criteria for defining post-operative morbidity and mortality. Although the locoregional administration of chemoperfusate should reduce the risk of systemic effects of chemotherapy agents, complications that are primarily related to the HIPEC procedure include hematological toxic effects (0–31%) due to transitory bone marrow suppression and renal insufficiency (0–7%), primarily in cisplatin-delivered HIPEC [6]. More recently, a retrospective Italian multicentric study [39] showed that older age, ovarian tumor origin, the presence
Please cite this article in press as: Roviello F, et al. Hyperthermic intraperitoneal chemotherapy for the treatment of ovarian cancer: A brief overview of recent results. Crit Rev Oncol/Hematol (2015), http://dx.doi.org/10.1016/j.critrevonc.2015.03.007
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of ascites, the closed technique and longer operative time were predictors of higher morbidity, while older age and greater PCI values were correlated with increased mortality. Additionally, a recent systematic review demonstrated that, in tertiary high-volume centers, the mortality and morbidity rates might decrease to the ranges of 0.9–5.8% and 12–52%, respectively [40].
4. Future prospects Over the last several years, numerous groups of surgeons have become involved in the use of HIPEC for PC from OC; however, at present, only few centers have experiences that exceed 100 cases, and the HIPEC procedure has not yet been standardized. Some authors have reported that the performance of at least 130 procedures is necessary to consider the physician an expert in cytoreduction using the Sugarbaker technique [41]. Generally, HIPEC seems welltolerated and associated with acceptable morbidity when patient selection is appropriate and adequate experience is gained in a referral center. However, the most essential question is whether this technique provides a survival advantage [24]. All of the mentioned studies were primarily based on small, retrospective, non-consecutive cohorts of patients with heterogeneous management without randomization. This heterogeneity precludes definitive conclusion about the survival results. In the future, large randomized trials are warranted to determine the role of HIPEC in OC treatment. Only recently, the first randomized study evaluating the role of HIPEC in recurrent OC showed that HIPEC significantly prolonged OS (26.7 vs. 13.4 months in the non-HIPEC group, P = 0.006) [42]. Nevertheless, in this regarding, some studies are currently recruiting participants in different stage of disease. The first is a study from the Netherlands (NCT00426257) [43]. This study evaluates the efficacy and safety of the addition of HIPEC to secondary debulking surgery in stage III ovarian cancer. A multicentric phase III trial from France, i.e., the CHIPOR study (NCT01376752) [44], which will compare second-line systemic chemotherapy followed by maximal CRS with or without HIPEC in 444 relapsed OC patients, has begun the recruitment of participants. Additionally, an Italian multicentric phase III trial, i.e., the HORSE study (NCT01539785) [45], will randomize 158 women with platinum-sensitive first relapse to surgery or surgery and HIPEC. The latest published protocol evaluating HIPEC in primary advanced OC (NCT01628380) [46] is the CHORINE study. This is an Italian multicentric trial regarding the role of HIPEC after chemotherapy in patients who have responded to the treatment. Another randomized study of HIPEC conducted by the Italian Society of Integrated Locoregional Therapy (STILO) regarding the role of HIPEC in persistent OC had to be closed prematurely nearly a decade ago due to poor patient accrual [47].
Currently, it is very difficult to evaluate the real influence of HIPEC in terms of overall survival and disease-free survival. There is too much bias that might interfere with the final results. Thus, no standardized HIPEC criteria have yet been adopted. Each protocol applies different methods, e.g., different drug doses, different perfusion times at different temperatures, different criteria for evaluating the completeness of cytoreduction and different classifications of complications. Moreover, the randomizations have been planned at different time points. Many centers treat a small number of patients each year and thus lack the necessary surgical expertise in the treatment of advanced and peritoneally spread cancer. However, the current evidence suggests that optimal CRS and HIPEC might be feasible treatment option with potential benefits. In conclusion, based on the published evidence, HIPEC must be included in clinical research and not in routine treatment. Indeed, it is clear that CRS plus HIPEC is not indicated for all patients with OC but has an established role in select patients. In highly specialized treatment centers, the mortality and morbidity rates are low; therefore, criticism of the feasibility of this procedure is no longer acceptable. Combined treatment with CRS and HIPEC is, at present, suggested by the international consensus group as the treatment that is most likely to favorably affect survival in stage III OC. Patients need to be centralized to the more experienced centers to allow them to participate in the ongoing trials. Centralization might also provide the patients the possibility of undergoing real, complete cytoreduction without the risk of residual disease, which should have a positive influence on survival rates. Additionally, new criteria are needed and should include a uniform method of staging peritoneal disease, the optimal degree of the extension of the surgical resection that should be associated with HIPEC, the best method for performing intraperitoneal chemohyperthermia, and the type and dose of anticancer drug. Conflict of interest The authors have no potential conflicts of interest to declare. Reviewers Cristiana Sessa, L’Istituto Oncologico Della Svizzera Italiana (ISOI), Istituto Oncologico della Svizzera Italiana (IOSI), Ospedale Regionale Bellinzona e Valli, CH-6500 Bellinzona, Switzerland. Luca Bocciolone, European Institute of Oncology, Gynecology, Via Ripamonti 435, Milan, Italy. References [1] Chua TC, Robertson G, Liauw W, et al. Intraoperative hyperthermic intraperitoneal chemotherapy after cytoreductive surgery in ovarian
Please cite this article in press as: Roviello F, et al. Hyperthermic intraperitoneal chemotherapy for the treatment of ovarian cancer: A brief overview of recent results. Crit Rev Oncol/Hematol (2015), http://dx.doi.org/10.1016/j.critrevonc.2015.03.007
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[2]
[3]
[4]
[5] [6]
[7]
[8] [9]
[10]
[11]
[12]
[13]
[14]
[15]
[16]
[17]
[18]
[19]
cancer peritoneal carcinomatosis: systematic review of current results. J Cancer Res Clin Oncol 2009;135:1637–45. Glehen O, Mohamed F, Gilly FN. Peritoneal carcinomatosis from digestive tract cancer: new management by cytoreductive surgery and intraperitoneal chemohyperthermia. Lancet Oncol 2004;5:219–28. Sugarbaker PH. Intraperitoneal chemotherapy and cytoreductive surgery for the prevention and treatment of peritoneal carcinomatosis and sarcomatosis. Semin Surg Oncol 1998;14:254–61. Van der Speeten K, Stuart OA, Sugarbaker PH. Pharmacokinetics and pharmacodynamics of perioperative cancer chemotherapy in peritoneal surface malignancy. Cancer J 2009;15:216–24. Sugarbaker PH. Peritonectomy procedures. Ann Surg 1995;221: 29–42. Bijelic L, Jonson A, Sugarbaker PH. Systematic review of cytoreductive surgery and heated intraoperative intraperitoneal chemotherapy for treatment of peritoneal carcinomatosis in primary and recurrent ovarian cancer. Ann Oncol 2007;18:1943–50. Loggie BW, Sterchi JM, Rogers AT, et al. Intraperitoneal hyperthermic chemotherapy for advanced gastrointestinal and ovarian cancers. Reg Cancer Treat 1995;7(2):78–81. Helm CW. The role of hyperthermic intraperitoneal chemotherapy (HIPEC) in ovarian cancer. Oncologist 2009;14(7):683–94. Ansaloni L, Agnoletti V, Amadori A, Catena F, Cavaliere D, Coccolini F, et al. Evaluation of extensive cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) in patients with advanced epithelial ovarian cancer. Int J Gynecol Cancer 2012;22(June (5)):778–85. 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. Cascales-Campos PA, Gil J, Gil E, Feliciangeli E, González-Gil A, Parrilla JJ, et al. Treatment of microscopic disease with hyperthermic intraoperative intraperitoneal chemotherapy after complete cytoreduction improves disease-free survival in patients with stage IIIC/IV ovarian cancer. Ann Surg Oncol 2014;21(July (7)):2383–9. Deraco M, Kusomura S, Virzi S, et al. Cytoreductive surgery and hyperthermic intra-peritoneal chemotherapy as up front therapy for advanced, EOC: multi-institutional phase II study. Gynecol Oncol 2011;122(2):215–20. Di Giorgio A, Naticchioni E, Biacchi D, Sibio S, Accarpio F, Rocco M, et al. Cytoreductive surgery (peritonectomy procedures) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) in the treatment of diffuse peritoneal carcinomatosis from ovarian cancer. Cancer 2008;113:315–25. Helm CW, Richard SD, Pan J, et al. HIPEC in ovarian cancer: first report of HYPER-O registry. Int J Gynecol Cancer 2010;20(1): 61–9. Pavlov MJ, Kovacevic PA, Ceranic MS, Stamenkovic AB, Ivanovic AM, Kecmanovic DM. Cytoreductive surgery and modified heated intraoperative intraperitoneal chemotherapy (HIPEC) for advanced and recurrent ovarian cancer – 12-year single center experience. Eur J Surg Oncol 2009;35(November (11)):1186–91. Rufian S, Munoz-Casares FC, Briceno J, et al. Radical surgery— peritonectomy and intra-operative intraperitoneal chemotherapy for the treatment of peritoneal carcinomatosis in recurrent or primary ovarian cancer. J Surg Oncol 2006;94(4):316–24. Frenel JS, Leux C, Pouplin L, Ferron G, Berton Rigaud D, Bourbouloux E, et al. Oxaliplatin-based hyperthermic intraperitoneal chemotherapy in primary or recurrent epithelial ovarian cancer: a pilot study of 31 patients. J Surg Oncol 2011;103(January (1)):10–6. Gori J, Casta˜no R, Toziano M, Häbich D, Staringer J, De Quirós DG, et al. Intraperitoneal hyperthermic chemotherapy in ovarian cancer. Gynecol Cancer 2005;15(March–April (2)):233–9. Kim JH, Lee JM, Ryu KS, Lee YS, Park YG, Hur SY, et al. Consolidation hyperthermic intraperitoneal chemotherapy using paclitaxel in
[20]
[21]
[22]
[23]
[24]
[25]
[26]
[27]
[28]
[29]
[30]
[31]
[32]
[33]
[34]
[35]
7
patients with epithelial ovarian cancer. J Surg Oncol 2010;101(February (2)):149–55. Pomel C, Ferron G, Lorimier G, Rey A, Lhomme C, Classe JM, et al. Hyperthermic intra-peritoneal chemotherapy using oxaliplatin as consolidation therapy for advanced epithelial ovarian carcinoma: results of a phase II prospective multicentre trial. CHIPOVAC study. Eur J Surg Oncol 2010;36(June (6)):589–93. Roviello F, Pinto E, Corso G, Pedrazzani C, Caruso S, et al. Safety and potential benefit of hyperthermic intraperitoneal chemotherapy (HIPEC) in peritoneal carcinomatosis from primary or recurrent ovarian cancer. J Surg Oncol 2010;102(November (6)):663–70. Cascales-Campos PA, Gil J, Feliciangeli E, Gil E, González-Gil A, López V, et al. The role of hyperthermic intraperitoneal chemotherapy using paclitaxel in platinum-sensitive recurrent epithelial ovarian cancer patients with microscopic residual disease after cytoreduction. Ann Surg Oncol 2014;(September). Ceelen WP, Van Nieuwenhove Y, Van Belle S, Denys H, Pattyn P. Cytoreduction and hyperthermic intraperitoneal chemoperfusion in women with heavily pretreated recurrent ovarian cancer. Ann Surg Oncol 2012;19(July (7)):2352–9. Cotte E, Glehen O, Mohamed F, Lamy F, Falandry C, Golfier F, et al. Cytoreductive surgery and intraperitoneal chemo-hyperthermia for chemoresistant and recurrent advanced epithelial ovarian cancer: prospective study of 81 patients. World J Surg 2007;31: 1813–20. Deraco M, Virzì S, Iusco DR, et al. Secondary cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for recurrent epithelial ovarian cancer: a multi-institutional study. BJOG 2012;119(June (7)):800–9. Fagotti A, Costantini B, Vizzielli G, et al. HIPEC in recurrent ovarian cancer patients: morbidity-related treatment and long-term analysis of clinical outcome. Gynecol Oncol 2011;122(2):221–5. 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(December (3)):502–5. Königsrainer I, Beckert S, Becker S, Zieker D, Fehm T, Grischke EM, et al. Cytoreductive surgery and HIPEC in peritoneal recurrent ovarian cancer: experience and lessons learned. Langenbecks Arch Surg 2011;396(October (7)):1077–81. Le Brun JF, Campion L, Berton-Rigaud D, Lorimier G, Marchal F, Ferron G, et al. Survival benefit of hyperthermic intraperitoneal chemotherapy for recurrent ovarian cancer: a multi-institutional case control study. Ann Surg Oncol 2014;21(October (11)):3621–7. Raspagliesi F, Kusamura S, Campos Torres JC, de Souza GA, Ditto A, Zanaboni F, et al. Cytoreduction combined with intraperitoneal hyperthermic perfusion chemotherapy in advanced/recurrent ovarian cancer patients: the experience of National Cancer Institute of Milan. Eur J Surg Oncol 2006;32:671–5. Robella M, Vaira M, Marsanic P, Mellano A, Borsano A, Cinquegrana A, et al. Treatment of peritoneal carcinomatosis from ovarian cancer by surgical cytoreduction and hyperthermic intraperitoneal chemotherapy (HIPEC). Minerva Chir 2014;69(February (1)):27–35. Spiliotis J, Vaxevanidou A, Sergouniotis F, Lambropoulou E, Datsis A, Christopoulou A. The role of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in the management of recurrent advanced ovarian cancer: a prospective study. J BUON 2011;16(1):74–9. Zanon C, Clara R, Chiappino I, Bortolini M, Cornaglia S, Simone P, et al. Cytoreductive surgery and intraperitoneal chemohyperthermia for recurrent peritoneal carcinomatosis from ovarian cancer. World J Surg 2004;28(October (10)):1040–5. Bae JH, Lee JM, Ryu KS, et al. Treatment of ovarian cancer with paclitaxel- or carboplatin-based intraperitoneal hyperthermic chemotherapy during secondary surgery. Gynecol Oncol 2007;106(1):193–200. Ryu KS, Kim JH, Ko HS, et al. Effects of intraperitoneal hyperthermic chemotherapy in ovarian cancer. Gynecol Oncol 2004;94:325–32.
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[36] Lim MC, Kang S, Choi J, Song YJ, Park S, Seo SS, et al. Hyperthermic intraperitoneal chemotherapy after extensive cytoreductive surgery in patients with primary advanced epithelial ovarian cancer: interim analysis of a phase II study. Ann Surg Oncol 2009;16(April (4)):993–1000. [37] Bristow RE, Puri I, Chi DS. Cytoreductive surgery for recurrent ovarian cancer: a meta-analysis. Gynecol Oncol 2009;112(January (1)):265–74. [38] Fagotti A, Petrillo M, Costantini B, Fanfani F, Gallotta V, Chiantera V, et al. Minimally invasive secondary cytoreduction plus HIPEC for recurrent ovarian cancer: a case series. Gynecol Oncol 2014;132(February (2)):303–6. [39] Macrì A, Arcoraci V, Belgrano V, Caldana M, Cioppa T, Costantini B, et al. Short-term outcome of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy: preliminary analysis of a multicentre study. Anticancer Res 2014;34(October (10)):5689–93. [40] Chua TC, Yan TD, Saxena A, Morris DL. Should the treatment of peritoneal carcinomatosis by cytoreductive surgery and hyperthermic intraperitoneal chemotherapy still be regarded as a highly morbid procedure?: a systematic review of morbidity and mortality. Ann Surg 2009;249:900–7. [41] Spiliotis JD, Rogdakis A, Vaxevanidou A, Datsis A, Zacharis G, Christopoulou A. Morbidity and mortality of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in the management of peritoneal carcinomatosis. J BUON 2009;14(2):259–64. [42] 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 2014;(November). [43] www.clinicaltrials.gov/ct2/show/record/NCT00426257 [44] www.clinicaltrials.gov/ct2/show/record/NCT01376752 [45] www.clinicaltrials.gov/ct2/show/record/NCT01539785 [46] www.clinicaltrials.gov/ct2/show/record/NCT01628380 [47] Deraco M, Raspagliesi F, Kusamura S. Management of peritoneal surface component of ovarian cancer. Surg Oncol Clin N Am 2003;12(July (3)):561–83 [review].
Biographies Franco Roviello is an Associate Professor of Surgery at the Department of Medicine, Surgery and Neurosciences, Unit of General and Minimally Invasive Surgery, University of Siena, Italy. He is teacher at several Degree Courses (Medicine, Nursing) and Specialization Schools. In 2013 has obtained the National Scientific Ability to Full Professor of Surgery From 2006 to date: President of the Italian Research Group for Gastric Cancer (GIRCG), a multicenter multidisciplinary research group. Coordinator of several GIRCG research protocols, published on important Journals of Surgery and Surgical Oncology; during the coordination of the Scientific Secretary, GIRCG scientific production and international relevance grown considerably. Intense Scientific production, member of the Editorial Board of four European Journal of Surgical Oncology, and invited Reviewer of International Journals. Clinical and surgical activity has been particularly dedicated to Surgical Oncology, including treatment of esophageal, gastric and colorectal cancer, liver and pancreatic cancer, peritoneal carcinomatosis, with the application of modern multimodal therapeutic protocols, as neoadjuvant therapy, locoregional treatments, peritonectomy and intraperitoneal chemohyperthermia (HIPEC) and minivasive surgery.
Giandomenico Roviello is currently a resident Physician in Medical Oncology Residency Program, Università degli Studi di Siena, Oncology Unit, Department of Oncology, Istituto Toscano Tumori (ITT), Azienda USL7, Ospedale Santa Maria delle Scotte, Siena. Dr. Roviello graduated from the School of Medicine, Second University of Naples in 2008, with the thesis about the use of Bortezomib in patients with Multiple Myeloma. His current research interests are genitourinary oncology, and particularly prostate cancer and renal cell carcinoma, gastric cancers and targeted anticancer therapies. Dr. Roviello has published 15 articles in peer-reviewed journals, more than 30 abstracts. He sits on the editorial board and is a reviewer for several oncological journals. Dr. Roviello’s society memberships include: the European Societies for Medical Oncology, the Italian Association of Urological Oncology and the Italian Association for gastric research (GIRCG). Roberto Petrioli MD, is a medical oncologist at Medical Oncology Unit, University of Siena, Italy. He was born in Siena, november 20, 1960. He received a Medical Degree from Siena University, where he also trained in Internal Medicine and Oncology. In 1992 Postgraduate School in Oncology at Pavia University, Italy. He is actually professor at Oncology Postgraduate School at Siena University. Dr. Petrioli is skilled in the management of solid tumors, with particular interest in cases of genitourinary and gastrointestinal tract. He is married and has a son. Daniele Marrelli is an Associate Professor of Surgery at the Department of Medicine, Surgery and Neurosciences, Unit of Surgical Oncology, University of Siena, Italy. He is teacher at several Degree Courses (Medicine, Nursing) and Specialization Schools. In 2013 has obtained the National Scientific Ability to Full Professor of Surgery From 2006 to date: Scientific Secretary of the Italian Research Group for Gastric Cancer (GIRCG), a multicenter multidisciplinary research group. Coordinator of several GIRCG research protocols, published on important Journals of Surgery and Surgical Oncology; during the coordination of the Scientific Secretary, GIRCG scientific production and international relevance grown considerably. Research activity has been conducted in collaboration with other international research groups: IPATIMUP (Porto), University of Munich, University of Seoul, University of San Paolo. Invited Speaker, Chairman or Member of the Scientific Committee to several National and International Congresses. Responsible of the Scientific Committee of the 10th International Gastric Cancer Congress, organized by the International Gastric Cancer Association (IGCA); Verona, June 2013. Member, in representation of European Countries, of the Committee for IGCA Staging Project for the new TNM; San Francisco, January 2014. Intense Scientific production, consisting of 303 publications (151 on international Journals, 20 on Congress Proceedings, 120 Meeting Abstracts, 12 Book chapters) Impact points: 425 (full papers) Citations: 2370 (ISI WEB of Knowledge) h-index: 26 (ISI WEB). Great
Please cite this article in press as: Roviello F, et al. Hyperthermic intraperitoneal chemotherapy for the treatment of ovarian cancer: A brief overview of recent results. Crit Rev Oncol/Hematol (2015), http://dx.doi.org/10.1016/j.critrevonc.2015.03.007
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knowledge of statistical programs, such as Statistical Program for Social Science (SPSS), STATA, BMDP, and attendance to several specific statistical courses. Member of the Editorial Board of four International Journals, and invited Reviewer of 25 International Journals. Clinical and surgical activity has been particularly dedicated to Surgical Oncology,
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including treatment of esophageal, gastric and colorectal cancer, liver and pancreatic cancer, peritoneal carcinomatosis, with the application of modern multimodal therapeutic protocols, as neoadjuvant therapy, locoregional treatments, peritonectomy and intraperitoneal chemohyperthermia (HIPEC).
Please cite this article in press as: Roviello F, et al. Hyperthermic intraperitoneal chemotherapy for the treatment of ovarian cancer: A brief overview of recent results. Crit Rev Oncol/Hematol (2015), http://dx.doi.org/10.1016/j.critrevonc.2015.03.007