N. Bakrin

Peritoneal carcinomatosis treated with cytoreductive surgery and Hyperthermic Intraperitoneal Chemotherapy (HIPEC) for advanced ovarian carcinoma: a French multicentre retrospective cohort study of 566 patients.

BACKGROUNDnDespite a high response rate to front-line therapy, prognosis of epithelial ovarian carcinoma (EOC) remains poor. Approaches that combine Cytoreductive Surgery (CRS) and Hyperthermic Intraperitoneal Chemotherapy (HIPEC) have been developed recently. The purpose of this study was to assess early and long-term survival in patients treated with this strategy.nnnPATIENTS AND METHODSnA retrospective cohort multicentric study from French centres was performed. All consecutive patients with advanced and recurrent EOC treated with CRS and HIPEC were included.nnnRESULTSnThe study included 566 patients from 13 centres who underwent 607 procedures between 1991 and 2010. There were 92 patients with advanced EOC (first-line treatment), and 474 patients with recurrent EOC. A complete cytoreductive surgery was performed in 74.9% of patients. Mortality and grades 3 to 4 morbidity rates were 0.8% and 31.3%, respectively. The median overall survivals were 35.4 months and 45.7 months for advanced and recurrent EOC, respectively. There was no significant difference in overall survival between patients with chemosensitive and with chemoresistant recurrence. Peritoneal Cancer Index (PCI) that evaluated disease extent was the strongest independent prognostic factor for overall and disease-free survival in all groups.nnnCONCLUSIONnFor advanced and recurrent EOC, curative therapeutic approach combining optimal CRS and HIPEC should be considered as it may achieve long-term survival in patients with a severe prognosis disease, even in patients with chemoresistant disease. PCI should be used for patients selection.

Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy (HIPEC) for Persistent and Recurrent Advanced Ovarian Carcinoma: A Multicenter, Prospective Study of 246 Patients

BackgroundEpithelial ovarian carcinoma is the main cause of death from gynaecological cancers in the western world. The initial response rate to the frontline therapy is high. However, the prognosis of persistent and recurrent disease remains poor. During the two past decades, a new therapeutic approach to peritoneal carcinomatosis has been developed, combining maximal cytoreductive effort with hyperthermic intraperitoneal chemotherapy (HIPEC).MethodsA retrospective, multicentric study of 246 patients with recurrent or persistent ovarian cancer, treated by cytoreductive surgery and HIPEC in two French centers between 1991 and 2008, was performed.ResultsAn optimal cytoreductive surgery was possible in 92.2xa0% of patients. Mortality and morbidity rates were 0.37xa0% and 11.6xa0%, respectively. The overall median survival was 48.9xa0months. There was no significant difference in overall survival in patients with persistent or recurrent disease. In multivariate analysis, performance status was a significant prognostic factor in patients with extensive peritoneal carcinomatosis (peritoneal cancer index >10).ConclusionsSalvage therapy combining optimal cytoreductive surgery and HIPEC is feasible and may achieve long-term survival in highly selected patients with recurrent ovarian carcinoma, including those with platinum resistant disease, with acceptable morbidity.

What made hyperthermic intraperitoneal chemotherapy an effective curative treatment for peritoneal surface malignancy: A 25‐year experience with 1,125 procedures

To review our 25‐year experience with hyperthermic intra‐peritoneal chemotherapy (HIPEC).

Quality of life after cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy: A prospective study of 216 patients

INTRODUCTIONnCytoreductive Surgery (CRS) and Hyperthermic Intraperitoneal Chemotherapy (HIPEC) have demonstrated promising results in the treatment of peritoneal carcinomatosis (PC). The purpose of this study was to assess the impact of this combined procedure on quality of life (QoL).nnnMATERIALS AND METHODSnA prospective single centre study of 216 consecutive patients treated with CRS and HIPEC was conducted using the Gastro-Intestinal Quality of Life Index questionnaire (GIQLI), completed preoperatively and at 1, 3, 6 and 12 months.nnnRESULTSnQuestionnaire compliance was 81%, 90%, 89%, 89% and 74% at baseline, 1, 3, 6 and 12 months respectively. QoL was significantly decreased up to 6 months and returned to baseline at 12 months. In multivariate analysis, factors decreasing QoL were origin of PC at 3 months, presence of stoma at 6 months and length of surgery over 270 min and disease recurrence at 12 months.nnnCONCLUSIONSnDespite morbidity associated with CRS and HIPEC, QoL returned to baseline at one year after surgery. This treatment strategy should be considered for the treatment of peritoneal carcinomatosis.

Hyperthermic intraperitoneal chemotherapy (HIPEC) in ovarian cancer

Ovarian cancer remains the fourth leading cause of cancer death in women in France. It is all too often diagnosed at an advanced stage with peritoneal carcinomatosis (PC), but remains confined to the peritoneal cavity throughout much of its natural history. Because of cellular selection pressure over time, most tumor recurrences eventually develop resistance to systemic platinum. Options for salvage therapy include alternative systemic chemotherapies and further cytoreductive surgery (CRS), but the prognosis remains poor. Over the past two decades, a new therapeutic approach to PC has been developed that combines CRS with hyperthermic intraperitoneal chemotherapy (HIPEC). This treatment strategy has already been shown to be effective in non-gynecologic carcinomatosis in numerous reports. There is a strong rationale for the use of HIPEC for PC of ovarian origin. On the one hand, three prospective randomized trials have demonstrated the superiority of intraperitoneal chemotherapy (without hyperthermia) in selected patients compared to systemic chemotherapy. Moreover, retrospective studies and case-control studies of HIPEC have reported encouraging survival data, especially when used to treat chemoresistant recurrence. However, HIPEC has specific morbidity and mortality; this calls for very careful selection of eligible patients by a multidisciplinary team in specialized centers. HIPEC needs to be evaluated by means of randomized trials for ovarian cancer at different developmental stages: as first line therapy, as consolidation, and for chemoresistant recurrence. Several European phasexa0III studies are currently ongoing.

Postoperative outcomes of laparoscopic vs open cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy for treatment of peritoneal surface malignancies

BACKGROUNDnCytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) are considered the only curative treatment for many peritoneal surface malignancies. The purpose of this study was to evaluate feasibility and safety of CRS combined with HIPEC by laparoscopy for patients with limited peritoneal disease and to compare postoperative outcomes with those for an open procedure.nnnMETHODSnBetween January 2011 and November 2012, all patients with low-grade pseudomyxoma peritonei (PMP) or multicystic mesothelioma (MM) and limited peritoneal disease (Peritoneal Cancer Index [PCI] less than 10) underwent CRS and HIPEC by a laparoscopic approach. The study cohort was matched with a historical cohort of patients with the same characteristics (completeness of cytoreduction, HIPEC agent, PCIxa0±xa011 and agexa0±xa020 years) treated with CRS and HIPEC by laparotomy.nnnRESULTSnEight patients (five low-grade PMP and three MM) treated by a laparoscopic approach were compared to eight patients treated by laparotomy. All patients underwent complete cytoreductive surgery with HIPEC, and no conversion to laparotomy was needed. The median surgical length was 210xa0min (150-300) vs 240 (210-360), with a median hospital stay of 12 days (9-18) vs 19 (13-33). One patient had a postoperative complication (intraperitoneal haematoma treated by radiological drainage) vs four in the laparotomy group.nnnCONCLUSIONnLaparoscopic CRS combined with HIPEC is feasible and safe for curative treatment of strictly selected patients with peritoneal surface malignancy and might reduce postoperative complications and length of hospital stay.

Intraperitoneal Cytokine Level in Patients with Peritoneal Surface Malignancies. A Study of the RENAPE (French Network for Rare Peritoneal Malignancies)

BackgroundPrognosis of peritoneal surface malignancies is influenced by the adequacy of surgical and chemotherapeutic treatment and by tumor spread at the time of diagnosis. By promoting morphological changes in the mesothelium, inflammatory cytokines reflect tumor biology and could be evaluated as biomarkers. Our objective was to evaluate intraperitoneal levels of IL-6, IL-8, IL-10, TNF-alpha, and sICAM in patients with pseudomyxoma peritonei and peritoneal mesothelioma.MethodsSerum and peritoneal fluid samples were prospectively collected in patients managed for peritoneal surface malignancies including pseudomyxoma peritonei (PMP), mesotheliomas, and other rare primitive peritoneal cancers (cancer group) and patients who underwent intraperitoneal laparoscopic surgical procedures for benign diseases (noncancer group). Samples were analyzed for IL-6, IL-8, IL-10, TNF-alpha, and sICAM concentrations. Correlations were assessed with tumor spread related clinical scores.ResultsIn both patient groups, intraperitoneal cytokine levels were higher than serum levels. Cancer patients had significantly higher intraperitoneal cytokine levels than noncancer patients. Peritoneal levels tended to increase in cancer patients with free tumor cells in peritoneal fluid. They were significantly higher in patients with tumor implants ≥2xa0cm and/or patients with peritoneal carcinomatosis index (PCI) >19. Furthermore, patients with malignant pseudomyxoma peritonei (grades II and III) had higher levels than patients with nonmalignant disease (grade I).ConclusionsAssessment of intraperitoneal IL-6, IL-8, IL-10, TNF-alpha, and sICAM levels can be performed in patients with peritoneal surface malignancies. They can be considered as both diagnostic and prognostic biomarkers that could be used as useful adjuncts for therapeutic decision making.

Intraperitoneal vascular endothelial growth factor burden in peritoneal surface malignancies treated with curative intent: The first step before intraperitoneal anti-vascular endothelial growth factor treatment?

INTRODUCTIONnVascular endothelial growth factor (VEGF) is one of the most important angiogenic factors in solid tumours and plays an important role in ascites development in peritoneal surface malignancies (PSM). The main goal of this study was to determine the evolution and factors influencing intraperitoneal (IP) VEGF burden during cytoreductive surgery (CRS) with curative intent.nnnPATIENTS AND METHODSnNinety-seven consecutive patients with PSM were treated with CRS at a single centre with curative intent. Patient data were collected prospectively between February 2012 and October 2012. An enzyme-linked immunosorbent assay technique was used to assess VEGF levels in intravenous (IV) systemic blood samples before incision and after abdominal closure, and in IP samples during abdominal cavity exploration, after completion of CRS, after hyperthermic IP chemotherapy, and at 1 and 24h after abdominal closure.nnnRESULTSnThe IP VEGF burden increased significantly after CRS, and then decreased progressively (p<0.005). In multivariate analysis, neoadjuvant IV bevacizumab significantly decreased the preoperative IP VEGF burden, tumour load according to Peritoneal Cancer Index value increased significantly the preoperative IP VEGF burden and a low preoperative IP VEGF burden was associated with significantly increased postoperative complications. Neoadjuvant IV bevacizumab is the only factor that influences the preoperative IV VEGF concentration.nnnCONCLUSIONnFor patients with PSM who were treated with curative intent, the IP VEGF burden increased after CRS, and was reduced prior to surgery by the administration of neoadjuvant IV bevacizumab.

Ninety-day post-operative morbidity and mortality using the National Cancer Institute’s common terminology criteria for adverse events better describe post-operative outcome after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy

Abstract Background: The post-operative morbidity and mortality after CRS-HIPEC has been widely evaluated. However, there is a major discrepancy between rates reported due to different metrics and time of analysis used. Objective: To evaluate the legitimacy of 90-day morbidity and mortality based on the National Cancer Institute’s Common Terminology Criteria for Adverse Events (NCI-CTCAE) v4.0 classification as criteria of quality for cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC). Methods: A prospective database of all patients undergoing CRS-HIPEC for peritoneal carcinomatosis between 2004 and 2015 was queried for 90-day morbidity and mortality and survival. Results: Among 881 patients, the 90-day major complication rate based on NCI-CTCAE classification and Clavien-Dindo’s classification were 51% (nu2009=u2009447 patients) and 25% (nu2009=u2009222 patients), respectively. Among patients who presented with a 90-day complication based on the NCI-CTCAE classification, 50% (nu2009=u2009225 patients) presented a medical complication not reported by Clavien-Dindo’s classification. After surgery, 24 patients (2.7%) died of post-operative complications, for only 10 (42%) of them the death occurred within 30-day after surgery. Occurrence of major complication based on either NCI-CTCAE classification, Clavien-Dindo’s classification or the medical complication not reported by Clavien-Dindo’s classification all negatively impacts the overall survival. Conclusion: Among commonly reported morbidity’s classification, 90-day morbidity based on NCI-CTCAE classification represents a legitimate metric of CRS-HIPEC quality. Post-operative morbidity after CRS-HIPEC should be reported using 90-day NCI-CTCAE classification.

Intraperitoneal Vascular Endothelial Growth Factor: A Prognostic Factor and the Potential for Intraperitoneal Bevacizumab Use in Peritoneal Surface Malignancies

AbstractIntroductionIntraperitoneal (IP) vascular endothelial growth factor (VEGF) levels have been shown to vary in the peritoneal cavity of patients with peritoneal surface malignancies. nOur purpose was to correlate levels of IP VEGF with overall and disease-free survival to identify whether IP VEGF can be used to prognosticate patients and the possible role of IP bevacizumab.MethodsFrom February to October 2012, 97 consecutive patients with peritoneal carcinomatosis were treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. Intravenous (IV) VEGF levels were taken before surgery, whereas IP VEGF levels were taken at various time points during and after surgery.ResultsMedian follow-up was 19.48xa0months. On univariate analysis, a lower IP VEGF taken just after incision (T1) was associated with improved overall (Pxa0=xa00.0004) and disease-free survival (Pxa0=xa00.0006) at 2xa0years. A lower T1/IV VEGF ratio also was associated with improved overall (Pxa0=xa00.004) and disease-free survival (Pxa0=xa00.0051). On multivariate analysis, a lower T1 was associated with improved overall survival, whereas a lower T1/IV VEGF was associated with improved disease-free survival. On subset analysis, these two variables were associated with improved survival in colorectal cancers.ConclusionsA lower IP VEGF level prior to surgery is associated with improved survival. The use of preoperative intraperitoneal bevacizumab for patients with a heavy disease load should be considered, especially in colorectal cancers.