Abstract Purpose Hyperthermic intraperitoneal chemotherapy (HIPEC) may improve the outcome of patients with initially unresectable ovarian cancer who are eligible for complete cytoreductive surgery ...(CCRS) after neoadjuvant chemotherapy. The main objective of this multicenter phase-I study was to identify the recommended dose of cisplatin for HIPEC at CCRS after neoadjuvant carboplatin and paclitaxel (CP). Methods Patients were treated with 6 cycles of CP followed by CCRS and HIPEC using cisplatin heated for one hour at 42 °C +/− 1 °C. Four cisplatin dose-levels were evaluated: 50, 60, 70, 80 mg/m2 . Dose-limiting toxicities (DLTs) were defined as a grade ≥ IIIb adverse event (Dindo classification). The Continual Reassessment Method was used for this dose-finding study, with a target percentage of DLT set at 20%. Twenty-two cycles (15 mg/kg/cycle) of maintenance bevacizumab therapy were planned after surgery. Results Between June-2011 and September-2012, 30 patients were recruited. No DLT occurred at the first three dose-levels (4, 4 and 5 patients at 50, 60 and 70 mg/m2 respectively). At dose-level 4 (80 mg/m2 , 17 patients), four DLTs occurred: renal failure ( n = 2), peritonitis ( n = 1) and hemorrhage ( n = 1). Eight weeks after surgery, creatinine clearance was reduced to < 30 mL/min in 3 patients, all treated at 80 mg/m2 , and between 30 and 60 mL/min in 6 patients (2, 1, 1 and 2 at the four dose-levels respectively). Twenty patients started maintenance bevacizumab, and 7 received the 22 courses initially planned. Conclusions Based on the observed DLTs and prolonged impairment of renal function, we recommend a dose of 70 mg/m2 of cisplatin for HIPEC.
Abstract Background Despite 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. Patients and methods A retrospective cohort multicentric study from French centres was performed. All consecutive patients with advanced and recurrent EOC treated with CRS and HIPEC were included. Results The 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. Conclusion For 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 patient's selection.
Obesity is a public health concern with an increasing occurrence worldwide. Literature regarding impact of obesity on results after management of peritoneal carcinomatosis is poor. Our aim was to ...compare postoperative and oncological outcomes after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for rare peritoneal malignancies according to the body mass index.
All the patients managed by cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for rare peritoneal malignancies (including mainly pseudomyxoma peritonei and peritoneal mesothelioma), between 1995 and 2020, were retrospectively included from the French national registry of rare peritoneal tumors.
1450 patients were retrospectively included (63.5 % female, mean age 54 ± 13 years). Patients were divided into two groups according to their body mass index: non-obese (n = 1248, 86 %) and obese (n = 202, 14 %). Overall morbidity was significantly lower in non-obese patients in comparison with obese patients (n = 532/1248, 43 % vs n = 106/202, 53 %, p = 0.009). Medical and surgical morbidities were significantly lower in non-obese patients in comparison with obese patients (423/1258, 34 % vs n = 86/202, 43 %, p = 0.02 and n = 321/1248, 26 % vs n = 67/202, 33 %, p = 0.003, respectively). One-, 5- and 10-year overall survivals were similar between non-obese and obese patients (95 %, 82 % and 70 % vs 94 %, 76 % and 63 %; p = 0.1). One-, 5- and 10-year disease free survivals were similar between non-obese and obese patients (84 %, 67 % and 61 % vs 79 %, 62 % and 56 %, p = 0.1).
Obese patients have to be carefully managed after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for rare peritoneal malignancies. Some perioperative prophylactic treatments could be specifically implemented to reduce thromboembolic events, metabolic and wound complications.
•Obesity is a public health concern with an increasing occurrence worldwide.•Postoperative morbidity is increased in obese patients.•Obese patients have more frequently metabolic complications and thromboembolic events.•Oncological prognosis is similar between obese and non-obese patients.
The three principal studies dedicated to the natural history of peritoneal carcinomatosis (PC) from colorectal cancer consistently showed median survival ranging between 6 and 8 months. New ...approaches combining cytoreductive surgery and perioperative intraperitoneal chemotherapy suggest improved survival.
A retrospective multicenter study was performed to evaluate the international experience with this combined treatment and to identify the principal prognostic indicators. All patients had cytoreductive surgery and perioperative intraperitoneal chemotherapy (intraperitoneal chemohyperthermia and/or immediate postoperative intraperitoneal chemotherapy). PC from appendiceal origin was excluded.
The study included 506 patients from 28 institutions operated between May 1987 and December 2002. Their median age was 51 years. The median follow-up was 53 months. The morbidity and mortality rates were 22.9% and 4%, respectively. The overall median survival was 19.2 months. Patients in whom cytoreductive surgery was complete had a median survival of 32.4 months, compared with 8.4 months for patients in whom complete cytoreductive surgery was not possible (P <.001). Positive independent prognostic indicators by multivariate analysis were complete cytoreduction, treatment by a second procedure, limited extent of PC, age less than 65 years, and use of adjuvant chemotherapy. The use of neoadjuvant chemotherapy, lymph node involvement, presence of liver metastasis, and poor histologic differentiation were negative independent prognostic indicators.
The therapeutic approach combining cytoreductive surgery with perioperative intraperitoneal chemotherapy achieved long-term survival in a selected group of patients with PC from colorectal origin with acceptable morbidity and mortality. The complete cytoreductive surgery was the most important prognostic indicator.
The incidence of gastric poorly cohesive carcinoma (PCC) is increasing. The prognosis for patients with peritoneal metastases remains poor and the role of cytoreductive surgery (CRS) and hyperthermic ...intraperitoneal chemotherapy (HIPEC) is controversial. The aim was to clarify the impact of gastric PCC with peritoneal metastases treated by CRS with or without HIPEC.
All patients with peritoneal metastases from gastric cancer treated with CRS with or without HIPEC, in 19 French centres, between 1989 and 2014, were identified from institutional databases. Clinicopathological characteristics and outcomes were compared between PCC and non-PCC subtypes, and the possible benefit of HIPEC was assessed.
In total, 277 patients were included (188 PCC, 89 non-PCC). HIPEC was performed in 180 of 277 patients (65 per cent), including 124 of 188 with PCC (66 per cent). Median overall survival (OS) was 14.7 (95 per cent c.i. 12.7 to 17.3) months in the PCC group versus 21.2 (14.7 to 36.4) months in the non-PCC group (P < 0.001). In multivariable analyses, PCC (hazard ratio (HR) 1.51, 95 per cent c.i. 1.01 to 2.25; P = 0.044) was associated with poorer OS, as were pN3, Peritoneal Cancer Index (PCI), and resection with a completeness of cytoreduction score of 1, whereas HIPEC was associated with improved OS (HR 0.52; P < 0.001). The benefit of CRS-HIPEC over CRS alone was consistent, irrespective of histology, with a median OS of 16.7 versus 11.3 months (HR 0.60, 0.39 to 0.92; P = 0.018) in the PCC group, and 34.5 versus 14.3 months (HR 0.43, 0.25 to 0.75; P = 0.003) in the non-PCC group. Non-PCC and HIPEC were independently associated with improved recurrence-free survival and fewer peritoneal recurrences. In patients who underwent HIPEC, PCI values of below 7 and less than 13 were predictive of OS in PCC and non-PCC populations respectively.
In selected patients, CRS-HIPEC offers acceptable outcomes among those with gastric PCC and long survival for patients without PCC.
Diffuse malignant peritoneal mesothelioma (DMPM) is a severe disease with mainly locoregional evolution. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) is the ...reported treatment with the longest survival. The aim of this study was to evaluate the impact of perioperative systemic chemotherapy strategies on survival and postoperative outcomes in patients with DMPM treated with curative intent with CRS-HIPEC, using a multi-institutional database: the French RENAPE network.
From 1991 to 2014, 126 DMPM patients underwent CRS-HIPEC at 20 tertiary centres. The population was divided into four groups according to perioperative treatment: only neoadjuvant chemotherapy (NA), only adjuvant chemotherapy (ADJ), perioperative chemotherapy (PO) and no chemotherapy before or after CRS-HIPEC (NoC).
All groups (NA: n = 42; ADJ: n = 16; PO: n = 16; NoC: n = 48) were comparable regarding clinicopathological data and main DMPM prognostic factors. After a median follow-up of 61 months, the 5-year overall survival (OS) was 40%, 67%, 62% and 56% in NA, ADJ, PO and NoC groups, respectively (P = 0.049). Major complications occurred for 41%, 45%, 35% and 41% of patients from NA, ADJ, PO and NoC groups, respectively (P = 0.299). In multivariate analysis, NA was independently associated with worse OS (hazard ratio, 2.30; 95% confidence interval, 1.07-4.94; P = 0.033).
This retrospective study suggests that adjuvant chemotherapy may delay recurrence and improve survival and that NA may impact negatively the survival for patients with DMPM who underwent CRS-HIPEC with curative intent. Upfront CRS and HIPEC should be considered when achievable, waiting for stronger level of scientific evidence.
Abstract Objective To analyze a large series of patients with pseudomyxoma peritonei (PMP) treated with cytoreductive surgery associated with perioperative intraperitoneal chemotherapy (PIC) in 18 ...French-speaking centers. Patients and methods From March 1993 to December 2007, 301 patients with diffuse PMP were treated by cytoreductive surgery with PIC. Complete cytoreductive surgery was achieved in 219 patients (73%), and hyperthermic intraperitoneal chemotherapy (HIPEC) was performed in 255 (85%), mainly during the latter period of the study. Results Postoperative mortality and morbidity were 4.4% and 40%, respectively. The mean follow-up was 88 months. The 5-year overall and disease-free survival rates were 73% and 56%, respectively. The multivariate analysis identified 5 prognostic factors: the extent of peritoneal seeding ( p = 0.004), the center ( p = 0.0004), the pathologic grade ( p = 0.03), gender ( p = 0.02), and the use of HIPEC ( p = 0.04). When only the 206 patients with complete cytoreductive surgery were considered, the extent of peritoneal seeding was the only significant prognostic factor ( p = 0.004). Conclusion This large multicentric retrospective study confirms that cytoreductive surgery combined with PIC (with the use of hyperthermia) should be considered as the gold standard treatment of PMP and should be performed in specialized centers. It underlines the prognostic impact of the extent of peritoneal seeding, especially in patients treated by complete cytoreductive surgery. This prognostic impact appears to be greater than that of the pathologic grade.
Abstract Objectives Complete surgery with no macroscopic residual disease (RD) at primary (PDS) or interval debulking surgery (IDS) is the main objective of surgery in advanced epithelial ovarian ...cancer (EOC). The aim of this work was to evaluate the impact on survival of the number of neoadjuvant chemotherapy (NAC) cycles before IDS in EOC patients. Methods Data from EOC patients (stages IIIC–IV), operated on between 1995 and 2010 were consecutively recorded. NAC/IDS patients were analyzed according to the number of preoperative cycles (< 4 = group B1; > 4 = group B2) and compared with patients receiving PDS (group A). Patients with complete resection were specifically analyzed. Results 367 patients were analyzed, 220 received PDS and 147 had IDS/NAC. In group B, 37 patients received more than 4 NAC cycles (group B2). Group B2 patients presented more frequently stage IV disease at diagnosis (p < 0.01) compared to groups A and B1. The rate of complete cytoreduction was higher in group B (p < 0.001). Patients with no RD after IDS and who had received more than 4 NAC cycles had poor survival (p < 0.001) despite complete removal of their tumor (relative risk of death after multivariate analysis of 3 (p < 0.001)) with an independent impact from disease stage and WHO performance status. Conclusions Patients with advanced EOC receiving complete IDS after more than 4 cycles of NAC have poor prognosis. Despite worse prognostic factors observed in this group of patients, our study reinforces the concept of early and complete removal of all macroscopic tumors in the therapeutic sequence of EOC.
Despite being associated with a very poor prognosis, long-term survivors across all series of Desmoplastic Small Round Cell Tumor (DSRCT) have been reported.
To analyze patients ‘characteristics ...associated with a prolonged survival after DSRCT diagnosis.
All consecutive patients treated for DSRCT in nine French expert centers between 1991 and 2018 were retrospectively analyzed. Patients with a follow-up of less than 2 years were excluded and cure defined as being disease-free at least 5 years.
100 pts were identified (median age 25 years, 89% male). 27 had distant metastases at diagnosis and 80 pts underwent upfront chemotherapy (CT). 71 pts were operated, 20 pts without prior CT). Surgery was macroscopically complete (CC0/1) in 50 pts. Hyperthermic intraperitoneal Chemotherapy (HIPEC) was administered during surgery in 15 pts 54 pts had postoperative CT and 26 pts had postoperative whole abdomino-pelvic RT (WAP-RT). After a median follow-up of 103 months (range 23–311), the median overall survival (OS) was 25 months. The 1- year, 3-year and 5-year OS rates were 90%, 35% and 4% respectively. 5 patients were considered cured after a median disease-free interval of 100 months (range 22–139). Predictive factors of cure were female sex (HR = 0.49, p = 0.014), median PCI<12 (HR = 0.32, p = 0.0004), MD Anderson stage I (HR = 0.25, p < 0.0001), CC0/1 (HR = 0.34, p < 0.0001), and WAP-RT (HR = 0.36, p = 0.00013). HIPEC did not statistically improve survival.
Cure in DSRCT is possible in 5% of patients and is best achieved combining systemic chemotherapy, complete cytoreductive surgery and WAP-RT. Despite aggressive treatment, recurrence is common and targeted therapies are urgently needed.
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