The role of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in the treatment of ovarian cancer relapse.
Saladino E,Fleres F,Irato S,Famulari C,Macrì A
Updates in surgery
Nowadays the standard clinical management for advanced epithelial ovarian cancer is constituted by primary cytoreductive surgery associated to adjuvant systemic chemotherapy. Even if this first-line chemotherapy shows a high rate of complete responses, the disease recurrences occur especially in stage-III patients. Actually an option for this subset of patients is represented by secondary cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy that represents a promising therapy, having shown positive results in terms of median overall survival, progression free survival and overall survival. However, a much more research is still required especially by prospective randomised trials to improve outcomes in recurrent ovarian cancer.
Failure to rescue following cytoreductive surgery and hyperthermic intraperitoneal chemotherapy.
Li Kevin Y,Mokdad Ali A,Minter Rebecca M,Mansour John C,Choti Michael A,Augustine Mathew M,Polanco Patricio M
The Journal of surgical research
BACKGROUND:Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) can significantly improve the survival in selected patients with peritoneal carcinomatosis. This study aims to identify perioperative patient characteristics predictive of failure to rescue (FTR), mortality following postoperative complications from CRS/HIPEC. METHODS:Patients suffering a complication following CRS/HIPEC between 2005 and 2013 were identified in the American College of Surgeons National Surgical Quality Improvement Program data set. FTR was defined as 30-d mortality in the setting of a complication. Patients who suffered FTR were compared against those who survived a complication (non-FTR). Predictors of FTR were identified using a multivariable logistic regression model. RESULTS:A total of 915 eligible CRS/HIPEC cases were identified. In all, 382 patients (42%) developed ≥1 postoperative complication, and 88 patients (10%) suffered ≥1 major complication. Seventeen patients died following a complication, amounting to an FTR rate of 4%. FTR patients were more likely than non-FTR patients to have dependent functional status (18% versus 2%, P = 0.01), have American Society of Anesthesiologists (ASA) class 4 status (29% versus 8%, P = 0.01), develop ≥3 complications (65% versus 24%, P < 0.01), and suffer a major complication (94% versus 20%, P < 0.01). The following were independently associated with FTR: ASA class 4 (odds ratio [OR]: 13.4, 95% confidence interval [CI], 1.2-146.8) and major complications (OR: 66.0, 95% CI, 8.4-516.6). CONCLUSIONS:ASA class 4, major morbidity, and likely dependent functional status are independent predictors of FTR following CRS/HIPEC to treat peritoneal carcinomatosis. Therefore, ASA class 4 and dependent functional status should be considered as contraindications for CRS/HIPEC and only offered in highly selective cases.
Cytoreductive Surgery Plus Hyperthermic Intraperitoneal Chemotherapy for Patients with Peritoneal Metastases from Endometrial Cancer.
Cornali Tommaso,Sammartino Paolo,Kopanakis Nikolaos,Christopoulou Athina,Framarino Dei Malatesta Marialuisa,Efstathiou Elias,Spagnoli Alessandra,Ciardi Antonio,Biacchi Daniele,Spiliotis John
Annals of surgical oncology
BACKGROUND:More information is needed for selection of patients with peritoneal metastases from endometrial cancer (EC) to undergo cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC). METHODS:This study analyzed clinical, pathologic, and treatment data for patients with peritoneal metastases from EC who underwent CRS plus HIPEC at two tertiary centers. The outcome measures were morbidity, overall survival (OS), and progression-free survival (PFS) during a median 5 year follow-up period. Uni- and multivariate analyses were performed to identify significant factors related to outcome. RESULTS:A total of 33 patients met the inclusion criteria and completed the follow-up period. At laparotomy, the median peritoneal cancer index (PCI) was 15 (range 3-35). The CRS procedure required a mean 8.3 surgical procedures per patient, and for 22 patients (66.6%), a complete cytoreduction was achieved. The mean hospital stay was 18 days, and major morbidity developed in 21% of the patients. The operative mortality was 3%. When surgery ended, HIPEC was administered with cisplatin 75 mg/m for 60 min at 43 °C. During a median follow-up period of 73 months, Kaplan-Meier analysis indicated a 5 year OS of 30% (median 33.1 months) and a PFS of 15.5% (median 18 months). Multivariate analysis identified the completeness of cytoreduction (CC) score as the only significant factor independently influencing OS. Logistic regression for the clinicopathologic variables associated with complete cytoreduction (CC0) for patients with metachronous peritoneal spread from EC who underwent secondary CRS plus HIPEC identified the PCI as the only outcome predictor. CONCLUSIONS:For selected patients with peritoneal metastases from EC, when CRS leaves no residual disease, CRS plus HIPEC achieves outcomes approaching those for other indications such as colon and ovarian carcinoma.
Postoperative complications affect long-term outcomes after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for colorectal peritoneal carcinomatosis.
Lee Lawrence,Alie-Cusson Fanny,Dubé Pierre,Sideris Lucas
Journal of surgical oncology
BACKGROUND AND OBJECTIVES:Morbidity after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS + HIPEC) for colorectal peritoneal carcinomatosis (PC) may negatively affect survival. The objective was to determine the impact of postoperative complications (CX) on survival in patients undergoing CRS + HIPEC for colorectal PC. METHODS:All patients undergoing laparotomy for planned CRS + HIPEC for colorectal PC at a single institution from 1999 to 2014 were included. Patients were divided into three groups: CRS + HIPEC without CX (+HIPEC-CX); CRS + HIPEC with postoperative complication (+HIPEC + CX); and aborted CRS and HIPEC due to unresectable disease (-HIPEC). Postoperative morbidity were defined as Clavien II+ complications. Kaplan-Meier survival analyses and multivariable Cox proportional hazard modeling were used to describe the disease-free (DFS) and overall survival (OS). RESULTS:One hundred and twenty-two patients were included in the analysis (50 +HIPEC - CX, 40 +HIPEC + CX, 32-HIPEC). Overall complication rate was 42%. OS at 1-, 3-, and 5-years in patients undergoing successful CRS + HIPEC were 97%, 67%, and 45%. CX after successful CRS + HIPEC was independently associated with worsened OS (HR1.58, 95%CI, 1.19-1.97) but not DFS (HR1.11, 95%CI, 0.56-2.20). PCI also independently predicted worsened DFS (HR1.12, 95%CI, 1.06-1.18) and OS (HR1.08, 95%CI, 1.04-1.12). Patients with unresectable disease had significantly worse OS (HR6.50, 95%CI, 1.37-7.01). CONCLUSIONS:CX after CRS + HIPEC significantly affect OS. Patient selection and perioperative care are of paramount importance in the management of CRS + HIPEC for colorectal PC.
Hyperthermic intraperitoneal chemotherapy for the treatment of ovarian cancer: A brief overview of recent results.
Roviello Franco,Roviello Giandomenico,Petrioli Roberto,Marrelli Daniele
Critical reviews in oncology/hematology
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.
Early recurrence after cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC).
Tan Grace Hwei Ching,Chia Claramae Shulyn,Tan Sze Huey,Soo Khee Chee,Teo Melissa Ching Ching
International journal of clinical oncology
BACKGROUND:Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) are used in the management of selected peritoneal malignancies. While most patients achieve long-term disease-free survival, there remains a group with early recurrence (ER). We aim to investigate the clinical factors associated with ER. METHODS:A retrospective review of a prospectively maintained database of CRS-HIPEC patients treated between April 2001 and Feb 2016 was performed. ER was defined as recurrence within 12 months of CRS-HIPEC. Patients were stratified according to time to recurrence and only patients with at least 12-month follow-up were included. Perioperative factors were investigated, and subgroup analyses of colorectal, ovarian and appendiceal groups were performed. RESULTS:Of the 144 patients included, 30.6% were colorectal, 36.8% ovarian and primary peritoneal, 24.3% appendiceal, 2.1% mesothelioma and 6.3% were of other origins. Thirty-nine patients (27%) suffered ER. Univariable and multivariable analyses revealed that primary tumour type (p = 0.02) and post-CRS adjuvant treatment (p = 0.04) were associated with ER. Appendiceal patients had a lower odds of ER compared to colorectal patients [OR = 0.15 (0.043-0.502) p < 0.002]. Patients who received post-CRS adjuvant treatment had a lower odds of ER than patients without adjuvant treatment [OR = 0.32; (0.128-0.818) p = 0.02]. CONCLUSION:There remains a 27% risk of ER after CRS-HIPEC. Better patient selection and the administration of adjuvant chemotherapy may help to reduce ER.
Hyperthermic intraperitoneal chemotherapy + early postoperative intraperitoneal chemotherapy versus hyperthermic intraperitoneal chemotherapy alone: assessment of survival outcomes for colorectal and high-grade appendiceal peritoneal carcinomatosis.
Lam Jennifer Y,McConnell Yarrow J,Rivard Justin D,Temple Walley J,Mack Lloyd A
American journal of surgery
BACKGROUND:Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) have improved survival for colorectal and high-grade appendiceal carcinomatosis. We compared the overall and recurrence-free survival (OS and RFS) of patients treated with HIPEC with mitomycin c and early postoperative intraperitoneal chemotherapy (EPIC) with fluorouracil versus HIPEC alone using oxaliplatin and simultaneous IV infusion of fluorouracil. METHODS:Ninety-three patients with colorectal or high-grade appendiceal carcinomatosis were treated with CRS and HIPEC + EPIC or HIPEC alone. OS and RFS were analyzed using Kaplan-Meier curves and log-rank testing. RESULTS:Survival did not differ between HIPEC regimens. The 3-year OS and RFS rates were 50% and 21% for HIPEC + EPIC and 46% and 6% for HIPEC alone (P = .72 and P = .89, respectively). HIPEC + EPIC patients experienced more grade III/IV complications (43.2% vs 19.6%, P = .01). CONCLUSIONS:There was no difference in OS and RFS between colorectal and high-grade appendiceal adenocarcinoma patients treated with CRS and HIPEC + EPIC versus HIPEC alone. However, HIPEC + EPIC patients suffered greater morbidity, making HIPEC alone the preferable regimen.
Both heat and new chemotherapeutic drug dioxadet in hyperthermic intraperitoneal chemoperfusion improved survival in rat ovarian cancer model.
Bespalov Vladimir G,Kireeva Galina S,Belyaeva Olesya A,Kalinin Oleksiy E,Senchik Konstantin Y,Stukov Alexandr N,Gafton Georgy I,Guseynov Konstantin D,Belyaev Alexey M
Journal of surgical oncology
BACKGROUND AND OBJECTIVES:Hyperthermic Intraperitoneal Chemotherapy (HIPEC) at the time of Cytoreductive Surgery (CRS) is an actively researched treatment in patients with advanced ovarian cancer. Relative contribution of heat and chemotherapeutic agents during HIPEC as well as efficacy of a new agent dioxadet for regional chemotherapy in a rat model of ovarian cancer was studied. METHODS:Sixty rats were divided into three groups: no treatment control group (n = 19), hyperthermia without chemotherapy (HIPEP) (n = 14), HIPEC + cisplatin (n = 14), HIPEC + dioxadet (n = 13). The intra-abdominal tumor was not resected. End points were: median survival (primary), cause of death (secondary). RESULTS:The median survival of the animals in the control group, HIPEP group, HIPEC + cisplatin, HIPEC + dioxadet were 9 (CI; 8-23), 22.5 (CI; 12-43), 25.5 (CI; 13-62), 49 (Cl; 28-70) days, respectively. The P-values control versus HIPEP, HIPEC + cisplatin versus HIPEC + dioxadet were 0.006, 0.002, and 0.001, respectively. CONCLUSION:During HIPEC both the heat and the cytotoxic drug had antitumor effects in a rat ovarian cancer model. Dioxadet showed potential as a drug for regional chemotherapy. J. Surg. Oncol. 2016;113:438-442. © 2015 Wiley Periodicals, Inc.
Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) for disseminated intra-abdominal malignancies in children-a single-institution experience.
Zmora Osnat,Hayes-Jordan Andrea,Nissan Aviram,Kventsel Iris,Newmann Yoram,Itskovsky Kira,Ash Shifra,Levy-Mendelovich Sarina,Shinhar Daniel,Ben-Yaakov Almog,Toren Amos,Bilik Ron
Journal of pediatric surgery
PURPOSE:Our purpose was to present our institutional experience with performing complete cytoreduction surgery and heated intraoperative chemotherapy (CRS-HIPEC) for children with disseminated intraabdominal malignancies, guided by a leading international center performing CRS-HIPEC in children. METHODS:Retrospective chart review of all cases of CRS-HIPEC in children in our institution, examining diagnosis, preoperative management, operative management, postoperative treatment, short term outcome including length of stay and complications, and long term outcome including survival and recurrence of disease. RESULTS:9 children underwent CRS-HIPEC over 48months. The mean age of the patients was 8years. Tumors were: rhabdomyosarcoma (RMS), mesothelioma, Sertoli-Leydig, desmoplastic small round cell tumor, colon carcinoma and Wilms' tumor. Most patients received intraperitoneal cisplatin. Short term outcome was very good with median length of hospital stay of 13days and low rate of complications. Seven patients were alive at last follow up. Five patients developed a recurrent disease. Recurrence was intraabdominal in two of these patients. CONCLUSIONS:CRS-HIPEC for children with disseminated intraabdominal malignancies performed in a dedicated institution and with guidance by a leading international center can be performed safely. TYPE OF STUDY:Treatment study. LEVEL OF EVIDENCE:IV.
Life after hyperthermic intraperitoneal chemotherapy; measuring quality of life and performance status after cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy.
Ford Jennifer,Hanna Michael,Boston Anna,Berri Richard
American journal of surgery
BACKGROUND:Patients who undergo cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) can return to an acceptable performance status (PS) and quality of life 3 months postoperative. METHODS:An HIPEC specific questionnaire was developed based on the validated Functional Assessment of Cancer Therapy Questionnaire. Each patient was contacted and questionnaire completed. An averaged score was calculated and stratified to an Eastern Cooperative Oncology Group PS. A retrospective chart review gathered patient characteristics and correlated to the patient's 3 months postoperative PS. RESULTS:Between October 2011 and July 2014, 43 patients underwent complete CRS with HIPEC. The most common indications for surgery were colorectal (35%) and appendiceal malignancy (47%). Average scores were: physical well-being 15.4 of 20, social well-being 17.5 of 20, recovery 15 of 20, mental well-being 13.4 of 20, and functional well-being 18.1 of 24. These correlated to an Eastern Cooperative Oncology Group PS of 1, 0, 1, 1, and 1. Patient's age (P = .235), operative length (P = .181), hospital duration (P = .43), complications or peritoneal carcinomatosis index (P = .815) demonstrated no significance relative to postoperative PS. CONCLUSIONS:Patients can recovery well from CRS with HIPEC. It is possible to return to an acceptable functional status within 3 months postoperative. Age, operative time, length of hospital stay, or peritoneal carcinomatosis index have no prohibitive effects on a long-term recovery.
Indications for cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in elderly patients with peritoneal malignancy.
Kitai Toshiyuki,Yamanaka Kenya,Miyauchi Yuya,Kawashima Masahiro
International journal of clinical oncology
PURPOSE:A combination of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS + HIPEC) is effective for some peritoneal malignancies. However, the indications for elderly patients remain unclear, with substantial postoperative morbidity and mortality being problematic. MATERIALS:Clinical data were analyzed in 42 patients undergoing CRS + HIPEC for peritoneal malignancy. The primary tumor was located in the appendix in 32 cases and elsewhere in 10 cases. Operative results and survival data were compared between patients aged ≥70 and <70 years. RESULTS:Fourteen patients were older than 70 years. Elderly patients had a higher peritoneal cancer index (32.0 vs. 21.5), higher CA19-9 level (189.0 vs. 28.1), and higher frequency of grade 4-5 complications (5/9 vs. 2/26) than the younger patients. Grade 4-5 respiratory failure occurred in three elderly patients. There was a significant difference of postoperative survival between the elderly patients and younger patients, with 5-year survival rates being 41.3 and 74.2%, respectively (p = 0.0166). The poor prognosis of elderly patients was related to the higher frequency of grade 4-5 complications. CONCLUSIONS:Elderly patients were referred for treatment with more advanced disease than younger patients. An age ≥70 years was associated with more frequent grade 4-5 complications and worse survival. Performing CRS + HIPEC in elderly patients should be considered carefully due to the risk of severe complications, especially respiratory failure.
Factors associated with palliative care use in patients undergoing cytoreductive surgery and hyperthermic intraperitoneal chemotherapy.
Morris Rachel S,Gani Faiz,Hammad Abdulrahman Y,Peltier Wendy,Gamblin T Clark,Turaga Kiran K,Johnston Fabian M
The Journal of surgical research
BACKGROUND:Peritoneal carcinomatosis represents widespread metastatic disease throughout the abdomen and/or pelvis. Cytoreductive surgery/hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) improves the overall survival compared to standard therapy alone. The role palliative care (PC) plays however, remains poorly studied among these patients. METHODS:Patients who had previously undergone HIPEC and who underwent an inpatient admission from 7/1/2013 to 6/30/2014 were identified to determine which patients were referred for inpatient or outpatient palliative consultation. Multivariable logistic regression analysis was performed to identify risk factors associated with the use of PC. RESULTS:Of the 60 patients analyzed, 23 (38.3%) had a PC consultation with a median time to PC referral of 310 (IQR: 151-484 days). Patients who were prescribed opioids (no PC referral versus PC referral: 46.0% versus 91.3%, P < 0.001), patients who reported the use of a cancer-related emetic (35.1% versus 87.0%, P < 0.001), patients reporting the use of total parenteral nutrition (16.2% versus 39.1%, P = 0.046), and patients dependent on a gastric tube for nutrition (5.4% versus 43.5%, P < 0.001) were more likely to be referred to a PC consultation. On multivariable analysis, use of opioids, use of a cancer-related antiemetic, and the use of a G-tube were independently associated with a greater odds for being referred to PC (all P < 0.05). CONCLUSIONS:Approximately one-third of patients were referred to PC following cytoreductive surgery/hyperthermic intraperitoneal chemotherapy. Palliative care referrals were most commonly used for patients with chronic symptoms, which are difficult to manage, especially toward the end of life.
[Clinical Evaluation of Hyperthermic Intraperitoneal Chemotherapy(HIPEC)in Colorectal Cancer Patients at High Risk of Peritoneal Recurrence].
Ohta Hiroyuki,Shimizu Tomoharu,Sonoda Hiromichi,Ueki Tomoyuki,Miyake Toru,Mekata Eiji,Endo Yoshihiro,Yamaguchi Tsuyoshi,Kaida Sachiko,Takebayashi Katsushi,Murata Satoshi,Yamamoto Hiroshi,Akabori Hiroya,Naka Shigeyuki,Tani Masaji
Gan to kagaku ryoho. Cancer & chemotherapy
PURPOSE:We herein report the clinical outcomes of hyperthermic intraperitoneal chemotherapy(HIPEC)in patients at high risk of colorectal peritoneal metastasis. PATIENTS AND METHODS:We enrolled 21 patients with advanced colorectal cancer who were received HIPEC between 2009 and 2014. Retrospectively, we evaluated the short-term and long-term outcomes of these cases. RESULTS:We performed HIPEC for 12 patients with primary cancer and 9 with recurrent cancer. Perioperative complications characteristic of HIPEC did not occur. Seventeen patients(81%)had postoperative recurrence, 5 of whom had a peritoneal recurrence, and all of them already had synchronous peritoneal metastasis at the time of HIPEC. Patients with a higher peritoneal cancer index(PCI)had a tendency towards a higher rate of peritoneal recurrence than those with a lower PCI(11[median]vs 4; p=0.08).
[Safety and efficacy of intraperitoneal hyperthermic perfusion chemotherapy following laparoscopic palliative resection for gastric cancer patients with peritoneal metastasis].
Xia Weichao,Hu Yanfeng,Mou Tingyu,Chen Tao,Yu Jiang,Li Guoxin
Zhonghua wei chang wai ke za zhi = Chinese journal of gastrointestinal surgery
OBJECTIVE:To investigate the safety and efficacy of postoperative intraperitoneal hyperthermic perfusion chemotherapy(IHPEC) following laparoscopic palliative resection for advanced gastric cancer patients with peritoneal metastasis. METHODS:Between March 2010 and October 2013, 37 patients with advanced gastric cancer were treated by IHPEC(cisplatin 100 mg, 5-fluorouracil 1000 mg and saline 2000 mL) following laparoscopic palliative resection in our department between March 2010 and October 2013 were analyzed retrospectively. Short-term efficacy and adverse reactions were observed. RESULTS:Complete remission (CR), partial remission (PR), stable disease (SD) and progressive disease (PD) were found in 18, 4, 8 and 7 cases respectively, and the total progression-free rate was 59.5%(22/37). The significant improved, improved, stable and progressive cases of Karnofsky performance status were 6, 13, 10 and 8 respectively, and the rate of improved and stable cases was 78.4% (29/37). Serious adverse reactions (class III ( or IIII) were noted in 3 cases (8.1%), including 2 cases of abdominal pain (class III), 1 case of nausea and vomiting. CONCLUSIONS:The modality of IHPEC adopting cisplatin plus 5-fluorouracil regimen following laparoscopic palliative resection for advanced gastric cancer patients with peritoneal metastasis is technically feasible and safe, which has certain effect on postponing the progression of gastric cancer.
Neoadjuvant chemotherapy followed by cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for colorectal cancer: a feasibility and safety study.
Leimkühler M,Hemmer P H J,Reyners A K L,de Groot D J A,van Ginkel R J,Been L B,de Bock G H,van Leeuwen B L
World journal of surgical oncology
BACKGROUND:Standard treatment for colorectal peritoneal carcinomatosis typically involves cytoreductive surgery, hyperthermic intraperitoneal chemotherapy (HIPEC), and if possible, postoperative adjuvant chemotherapy. However, a substantial percentage of patients never receive adjuvant chemotherapy because of postoperative complications. Neoadjuvant chemotherapy could be beneficial in this setting, so we assessed its feasibility and safety when used before cytoreductive surgery and HIPEC. METHODS:In this non-randomized, single-center, observational feasibility study, patients were scheduled to receive six cycles of capecitabine and oxaliplatin before cytoreductive surgery and HIPEC. Computed tomography was performed after the third and sixth chemotherapy cycles to evaluate tumor response, and patients underwent cytoreductive surgery and HIPEC if there were no pulmonary and/or hepatic metastases. Postoperative complications, graded according to the Clavien-Dindo classification, were compared with those of a historic control group that received postoperative adjuvant chemotherapy. RESULTS:Of the 14 patients included in the study, 4 and 3 had to terminate neoadjuvant chemotherapy early because of toxicity and tumor progression, respectively. Cytoreductive surgery and HIPEC were performed in eight patients, and the timing and severity of complications were comparable to those of patients in the historic control group treated without neoadjuvant chemotherapy. CONCLUSION:Patients with peritoneal metastases due to colorectal carcinoma can be treated safely with neoadjuvant chemotherapy before definitive therapy with cytoreductive surgery and HIPEC. TRIAL REGISTRATION NUMBER:NTR 3905, registered on 20th march, 2013, http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=3905.
Ascites do not affect the rate of complete cytoreductive surgery and prognosis in patients with primary ovarian cancer with ascites treated with hyperthermic intraperitoneal chemotherapy.
Ba Mingchen,Long Hui,Zhang Xiangliang,Yan Zhaofei,Wang Shuai,Wu Yinbing,Gong Yuanfeng,Cui Shuzhong
Cytoreductive surgery (CRS) is the current standard therapy procedure for patients with advanced ovarian cancer (OC), but numerous patients with OC are complicated with ascites. The aim of the present study was to assess whether massive ascites affect the rate of complete CRS and prognosis for patients with primary OC treated with hyperthermic intraperitoneal chemotherapy (HIPEC). Between December 2006 and December 2015, 1,293 patients with primary OC from the Intracelom Hyperthermic Perfusion Therapy Center of the Cancer Hospital of Guangzhou Medical University prospective database were treated with CRS combined with HIPEC. A total of 1,225 patients were without malignant ascites or small amounts of ascites and 68 had massive malignant ascites. The rate of complete CRS, overall survival (OS), disease-free survival (DFS) and resolution of ascites for patients with massive ascites were analyzed between patients without/small ascites, and with massive ascites. Complete CRS was successful in 86.8% (1,063/1,225) of patients without/small ascites, and 85.3% (58/68) of patients with massive ascites. No statistical differences were identified in complete CRS success between patients with ascites and patients without/small ascites (P=0.080). For patients with massive ascites, all symptoms exhibited regression; the total objective remission rate was 100% (68/68), even for patients with incomplete CRS (10/68) (P=0.100). The mean OS was 58 months and the mean DFS was 26 months in patients without/small ascite, vs. 57 months and 28 months in patients with massive ascites. No significant differences were noted in median DFS and median OS between patients with ascites, and patients without/small ascites (All P>0.05). In conclusion, the results of the present study suggest that ascites does not affect the rate of complete CRS and the prognosis of patients with massive ascites following HIPEC. CRS is suitable for the majority of patients with primary OC and massive ascites.
Cost Effectiveness of Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy for Management of Colorectal Peritoneal Carcinomatosis.
Lee Z J,Chia S L,Tan G,Soo K C,Teo C C M
Annals of surgical oncology
BACKGROUND:Peritoneal carcinomatosis from colorectal cancer is a stage 4 disease for which palliative chemotherapy has traditionally been considered the mainstay of treatment. Since the development of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) by Sugarbaker, this combined method treatment has resulted in improved survival outcomes with acceptable morbidity for selected patients with peritoneal carcinomatosis. This study examined the cost effectiveness of CRS and HIPEC compared with palliative chemotherapy for patients with peritoneal carcinomatosis from colorectal cancer within the context of the Singaporean health care system. METHODS:A retrospective review of patients with peritoneal carcinomatosis from histologically proven colorectal cancer treated at the National Cancer Centre Singapore (NCCS) was conducted. RESULTS:The average cost of CRS and HIPEC per patient was S$83,680.26, and the median overall survival period was 47 months. The calculated cost per life year attained for a patient who underwent CRS and HIPEC was S$21,365.19 per life year. In comparison, the average cost of palliative chemotherapy was S$44,478.87, with a median overall survival of 9 months, and the calculated cost per life year attained for a patient in this treatment group was S$59,305.16 per life year. CONCLUSION:The findings show that CRS and HIPEC results in prolonged survival for selected patients with colorectal peritoneal carcinomatosis and a lower cost per life year attained than for the traditionally used palliative chemotherapy. It should logically be the preferred treatment of choice for selected patients with colorectal peritoneal metastasis.
Peritoneal carcinomatosis from unusual cancer origins: Is there a role for hyperthermic intraperitoneal chemotherapy?
Honoré C,Goéré D,Macovei R,Colace L,Benhaim L,Elias D
Journal of visceral surgery
INTRODUCTION:Complete cytoreductive surgery (CCRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) is the gold standard for curative treatment of peritoneal carcinomatosis (PC) arising from colorectal cancer, peritoneal mesothelioma and peritoneal pseudomyxoma peritonei (PMP). The results of HIPEC remain controversial in PC that originates from ovarian cancer, stomach cancer, neuroendocrine tumors, or sarcoma. HIPEC has also been used, although very rarely, for other malignant carcinomatoses. Its use has been exceptional due either to the rarity of the tumor or because such disease is usually widespread and rarely confined to the peritoneum. The aim of this study was to evaluate the results of CCRS plus HIPEC in patients with PC of unusual origin. METHODS:We performed a retrospective analysis of all patients who underwent CCRS plus HIPEC for PC whose origin was neither gastric, ovarian or colorectal carcinoma, nor neuroendocrine tumor, mesothelioma, PMP or sarcoma. RESULTS:Between 1995 and 2013, 31 patients with 15 PC arising from unusual primary tumors underwent CCRS plus HIPEC. After a median follow-up of 90 months, 10 patients were alive and without recurrence. The overall survival rate at 5 years was 33% with a median survival of 37 months. In univariate analysis, factors of poor prognosis and predictors of recurrence were the performance of immediate postoperative intraperitoneal chemotherapy instead of HIPEC and a peritoneal index ≥ 12. No prognostic impact due to tumor origin could be demonstrated. CONCLUSION:The decision to perform CCRS plus HIPEC for PC arising from unusual cancer origins remains difficult. These patients should be prospectively entered into registries of rare tumors that involve the peritoneum in order to better define indications.
Interval between cytoreductions as a marker of tumor biology in selecting patients for repeat cytoreductive surgery with hyperthermic intraperitoneal chemotherapy.
Konstantinidis Ioannis T,Levine Edward A,Chouliaras Konstantinos,Russell Gregory,Shen Perry,Votanopoulos Konstantinos I
Journal of surgical oncology
BACKGROUND AND OBJECTIVES:Repeat cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) for recurrence of peritoneal surface malignancies is safe and effective. Patient selection and factors associated with a favorable outcome are still evolving. METHODS:A prospectively maintained institutional database consisting of 1314 CRS/HIPEC procedures performed between February 1993 and December 2015 was reviewed. Clinicopathologic data from 103 patients and 112 (8.5%) repeat CRS/HIPEC procedures were retrospectively analyzed. RESULTS:Primary tumors were appendiceal for 60 patients (58.3%), mesothelioma for 14 (13.6%), colorectal for 9 (8.7%), ovarian for 8 (7.8%). R0/R1 resection was achieved in 46 (46.5%) patients. The time interval between the initial and the repeat CRS/HIPEC was <1 year for 21 (20.4%), 1-2 years for 40 (38.8%), and >2 years for 42 patients (40.8%). Overall median survival was 4.3 years and correlated with the time interval (1.3 years for <1 years, 3.7 years for 1-2 years, and 7 years for >2 years; P < 0.001). In multivariate analysis, the R status (P = 0.005) and a time interval of more than 2 years (P = 0.0002) were strongly associated with survival with each additional month between the surgeries conferring a 2.6% reduction in the risk of death. CONCLUSIONS:The current series validates time interval between cytoreductions as a major surrogate of tumor biology in selection of patients with recurrent peritoneal surface malignancies for repeat CRS/HIPEC. Complete repeat cytoreduction more than 2 years from the initial surgery is associated with a favorable outcome.
Hyperthermic Intraperitoneal Perfusion Chemotherapy and Cytoreductive Surgery for Controlling Malignant Ascites From Ovarian Cancer.
Ba Mingchen,Long Hui,Zhang Xiangliang,Tang Yunqiang,Wu Yinbing,Wang Shuai,Yan Zhaofei,Zhang Bohuo,Cui Shuzhong
International journal of gynecological cancer : official journal of the International Gynecological Cancer Society
BACKGROUND:Malignant ascites, a complication often seen in patients with ovarian cancer (OC), is difficult to treat, but hyperthermic intraperitoneal chemotherapy (HIPEC) has a good efficacy. OBJECTIVE:The aim of this study was to assess the efficacy of cytoreductive surgery (CRS) combined with HIPEC for controlling malignant ascites from OC. MATERIALS AND METHODS:From December 2009 until December 2014, 53 patients with OC and malignant ascites were treated with CRS and HIPEC. Patients in good health condition were treated with CRS followed by HIPEC (CRS + HIPEC), and patients in poor health condition were treated initially with B-mode ultrasound-guided HIPEC followed by delayed CRS upon improvement of their health condition (HIPEC + delayed CRS). Resolution of ascites, complete CRS, overall survival, and disease-free survival were analyzed. RESULTS:All patients showed ascites regression. The total objective remission rate was 100%, even for patients in the poor condition group before CRS. Complete CRS was successful in 30 (88.23%) of 34 patients in the good condition group, and 17 (89.47%) of 19 patients in the poor condition group (P > 0.05). Median disease-free survival and median overall survival were 21 and 39 months in the good condition group, and 22 and 38 months in the poor condition group, respectively (P > 0.05). CONCLUSIONS:Hyperthermic intraperitoneal chemotherapy is effective at controlling ascites in patients with OC, even for patients in poor condition before CRS, or when complete CRS is not feasible. Furthermore, the regression of ascites appears not to be dependent on complete resection.
Adjuvant Hyperthermic Intraperitoneal Chemotherapy (HIPEC) for patients at High-Risk of Peritoneal Metastases.
Morris Mackenzie C,Dhar Vikrom K,Stevenson Megan A,Winer Leah K,Lee Tiffany C,Wang Jiang,Ahmad Syed A,Patel Sameer H,Sussman Jeffrey J,Abbott Daniel E
BACKGROUND:Selection of patients for hyperthermic intraperitoneal chemotherapy (HIPEC) continues to evolve. We hypothesized that adjuvant HIPEC for patients at high-risk of peritoneal progression is safe and associated with favorable outcomes. METHODS:The institutional database of a high-volume center was queried for patients with high-risk disease undergoing HIPEC with a peritoneal carcinomatosis index (PCI) of 0. High-risk patients were defined as those with ruptured primary tumors or locally advanced (T) disease. RESULTS:37 patients underwent adjuvant HIPEC, with a median follow-up of 5.2 years. 54% had low-grade (LG) tumors while 46% had high-grade (HG) tumors. No patients underwent neoadjuvant chemotherapy, while eleven patients (32.4%) received adjuvant chemotherapy. There were no perioperative mortalities, and the overall complication rate was 43%. For the entire cohort, five year recurrence-free survival (RFS) and overall survival (OS) were 77% and 100%, respectively. Five year RFS and OS were 75% and 100% for LG patients and 81% and 100% for HG patients, respectively. CONCLUSIONS:Adjuvant HIPEC for patients at high-risk of peritoneal progression, with PCI 0, is safe and associated with favorable long-term survival. Additional prospective investigation is needed to identify patient populations who may benefit most from HIPEC.
Survival prognostic factors in patients undergoing cytoreductive surgery and hyperthermic intraperitoneal chemotherapy treatment: analysis from a single oncological center.
Graziosi L,Marino E,De Angelis V,Rebonato A,Donini A
World journal of surgical oncology
BACKGROUND:The aim of our study is to analyze survival, treatment-related morbidity, and safety in our experience of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. METHODS:Sixty-four patients were treated. Survival curves were calculated according to the Kaplan-Meier method. Univariate and multivariate analyses were done, and Cox's proportional hazard model was used to identify significant factors. RESULTS:Global 5-year overall survival was 55%. Overall survival was also evaluated according to neutrophils to lymphocytes ratio and neutrophils to platelets ratio. Overall survival according to pre-operative serum albumin level shows a difference in the two groups (P < 0.05). We observed minor or no adverse events in 53 cases (89.8%), while 3 patients (5.1%) showed a grade III-IV complication and 3 post-operative deaths (5.1%). Post-operative complication also influenced overall survival; patients in whom a minor complication occurred had a 3-year overall survival (OS) of 62% vs. a 3-year OS of 28% in patients who underwent a major complication (P < 0.1). CONCLUSIONS:Hyperthermic intraperitoneal chemotherapy (HIPEC) could be a valid and feasible option for selected patients affected by gastrointestinal malignancies' peritoneal carcinomatosis. Pre-operative parameters could be evaluated to choose patient who could benefit from cytoreductive surgery and hyperthermic intraperitoneal chemotherapy.
Efficacy and safety of ultrasound-guided continuous hyperthermic intraperitoneal perfusion chemotherapy for the treatment of malignant ascites: a midterm study of 36 patients.
Wu Yinbing,Pan Mingxin,Cui Shuzhong,Ba Mingchen,Chen Zulong,Ruan Qiang
OncoTargets and therapy
BACKGROUND:This study aimed to evaluate the efficacy and safety of ultrasound-guided continuous hyperthermic intraperitoneal perfusion chemotherapy (CHIPC) for the treatment of malignant ascites (MA). METHODS:Between July 2011 and June 2013, 36 MA patients were prospectively and consecutively hospitalized for three cycles of elective CHIPC under ultrasound guidance, maintained at a constant flow rate of 400-600 mL/min normal saline containing 5-fluorouracil plus mitomycin or carboplatin and at a constant temperature of 43°C±0.2°C, for 90 minutes. Main outcome measures were ascites resolution, Karnofsky performance status (KPS), and serum tumor biomarkers at 2 weeks after the last cycle of CHIPC. All the patients underwent uneventful CHIPC as scheduled, and vital signs remained stable over CHIPC. RESULTS:At 2 weeks after the last cycle of CHIPC, MA completely and partially resolved in 26 (72.2%) patients and eight (22.2%) patients, respectively; mean KPS score increased from pretreatment 61±9 to posttreatment 76±9 (P<0.001), and serum carcinoembryonic antigen and carbohydrate antigens 12-5 and 19-9 significantly decreased (all P<0.01). CONCLUSION:The current study indicated that ultrasound-guided CHIPC is an effective and safe palliative treatment modality for MA with respect to MA resolution, patient's general well-being, and systemic disease control. The long-term benefit of CHIPC on overall survival remains to be investigated in MA patients.
Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy versus palliative systemic chemotherapy in stomach cancer patients with peritoneal dissemination, the study protocol of a multicentre randomised controlled trial (PERISCOPE II).
Koemans W J,van der Kaaij R T,Boot H,Buffart T,Veenhof A A F A,Hartemink K J,Grootscholten C,Snaebjornsson P,Retel V P,van Tinteren H,Vanhoutvin S,van der Noort V,Houwink A,Hahn C,Huitema A D R,Lahaye M,Los M,van den Barselaar P,Imhof O,Aalbers A,van Dam G M,van Etten B,Wijnhoven B P L,Luyer M D P,Boerma D,van Sandick J W
BACKGROUND:At present, palliative systemic chemotherapy is the standard treatment in the Netherlands for gastric cancer patients with peritoneal dissemination. In contrast to lymphatic and haematogenous dissemination, peritoneal dissemination may be regarded as locoregional spread of disease. Administering cytotoxic drugs directly into the peritoneal cavity has an advantage over systemic chemotherapy since high concentrations can be delivered directly into the peritoneal cavity with limited systemic toxicity. The combination of a radical gastrectomy with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) has shown promising results in patients with gastric cancer in Asia. However, the results obtained in Asian patients cannot be extrapolated to Western patients. The aim of this study is to compare the overall survival between patients with gastric cancer with limited peritoneal dissemination and/or tumour positive peritoneal cytology treated with palliative systemic chemotherapy, and those treated with gastrectomy, CRS and HIPEC after neoadjuvant systemic chemotherapy. METHODS:In this multicentre randomised controlled two-armed phase III trial, 106 patients will be randomised (1:1) between palliative systemic chemotherapy only (standard treatment) and gastrectomy, CRS and HIPEC (experimental treatment) after 3-4 cycles of systemic chemotherapy.Patients with gastric cancer are eligible for inclusion if (1) the primary cT3-cT4 gastric tumour including regional lymph nodes is considered to be resectable, (2) limited peritoneal dissemination (Peritoneal Cancer Index < 7) and/or tumour positive peritoneal cytology are confirmed by laparoscopy or laparotomy, and (3) systemic chemotherapy was given (prior to inclusion) without disease progression. DISCUSSION:The PERISCOPE II study will determine whether gastric cancer patients with limited peritoneal dissemination and/or tumour positive peritoneal cytology treated with systemic chemotherapy, gastrectomy, CRS and HIPEC have a survival benefit over patients treated with palliative systemic chemotherapy only. TRIAL REGISTRATION:clinicaltrials.gov NCT03348150 ; registration date November 2017; first enrolment November 2017; expected end date December 2022; trial status: Ongoing.
Selection of chemotherapy for hyperthermic intraperitoneal use in gastric cancer.
Braam H J,Schellens J H,Boot H,van Sandick J W,Knibbe C A,Boerma D,van Ramshorst B
Critical reviews in oncology/hematology
PURPOSE:Several studies have shown the potential benefit of cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy (HIPEC) in gastric cancer patients. At present the most effective chemotherapeutic regime in HIPEC for gastric cancer is unknown. The aim of this review was to provide a comprehensive overview of chemotherapeutic agents used for HIPEC in gastric cancer. METHODS:A literature search was conducted using the PubMed database to identify studies on chemotherapy used for HIPEC in gastric cancer patients. RESULTS AND CONCLUSION:The chemotherapeutic regime of choice in HIPEC for gastric cancer has yet to be determined. The wide variety in studies and study parameters, such as chemotherapeutic agents, dosage, patient characteristics, temperature of perfusate, duration of perfusion, carrier solutions, intraperitoneal pressure and open or closed perfusion techniques, warrant more experimental and clinical studies to determine the optimal treatment schedule. A combination of drugs probably results in a more effective treatment.
Peritoneal carcinomatosis arising from rectal or colonic adenocarcinoma treated with cytoreductive surgery (CRS) hyperthermic intraperitoneal chemotherapy (HIPEC): two different diseases.
Tonello M,Ortega-Perez G,Alonso-Casado O,Torres-Mesa P,Guiñez G,Gonzalez-Moreno S
Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico
PURPOSE:Peritoneal carcinomatosis (PC) from colorectal cancer (CRC) has poor survival. Multi-modal treatment including systemic chemotherapy, cytoreductive surgery (CRS), and hyperthermic intraperitoneal chemotherapy (HIPEC) can be used in selected patients with curative intent. The majority published works consider PC of CRC origin as a homogenous disease. Aim of this study is to stress the different biological behaviors and survival of PC according to colonic or rectal origin. METHODS:Data of CRS and HIPEC procedures for PC of CRC origin performed at MD Anderson Cancer Center-Madrid (Spain) have been collected, dividing patients into two groups according to colonic or rectal PC. Clinical, operatory, and postoperatory variables of the two groups have been analyzed to compare survival-related rates and PC origin. RESULTS:In the years 2004-2015, 114 procedures of CRS followed by HIPEC for peritoneal metastasis of different origin have been performed; of these, 36 procedures were for colorectal PC (31 patients in colonic and 5 in rectal group). Two groups are homogenous after analysis of clinical, operatory, and follow-up data. Median survival (OS) is significantly higher in colonic compared to rectal group (47.83 vs. 22.0 months, p 0.008). 3- and 5-year survival rate is 74 and 50% in colonic group vs. 20 and 0% in rectal group. CONCLUSION:Rectal origin PC has a more aggressive behavior compared to colonic origin, reflecting in a worst prognosis of patients affected by rectal origin PC. According to our data and literature, indications of multi-modal treatment including CRS and HIPEC should be more restrictive for rectal cancer PC. Authors should differentiate colonic and rectal origin of PC when reporting cases in the literature.
Cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy for the treatment of primary peritoneal serous carcinoma: Results of a Chinese retrospective study.
Sun Jian-Hua,Ji Zhong-He,Peng Kai-Wen,Wu Hai-Tao,Zhang Qian,Yonemura Yukata,Li Yan
International journal of hyperthermia : the official journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group
Purpose Primary peritoneal serous carcinoma (PPSC) is a rare condition with a poor survival rate, even after treatment with debulking surgery followed by systemic chemotherapy. This study evaluated the efficacy and safety of cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) for the treatment of PPSC. Patients and methods This retrospective study included 22 female patients with primary advanced PPSC (group A, n = 12) or recurrent PPSC (group B, n = 10) treated with 25 CRS + HIPEC procedures. The primary end point was overall survival (OS), and the secondary end points were safety profiles. Results A total of 25 CRS + HIPEC procedures were performed in these 22 patients. The median OS was 31.0 months (95% confidence interval (CI) 22.3-39.7), and the 1-, 3-, and 5-year survival rates were 100%, 45.5%, and 27.3%, respectively. Subgroup analyses revealed that the median OS was 31.0 months (95% CI 19.8-42.2) for group A vs. 38.5 months (95% CI 9.6-67.4) for group B (P = 0.832, log rank test); 51.5 months (95% CI 34.9-68.1) for peritoneal cancer index (PCI) ≤ 15 vs. 20.3 months (95% CI 12.6-28.0) for PCI > 15 (P = 0.000, log rank test); and 38.5 months (95% CI 22.5-54.5) for completeness of cytoreduction (CC) of 0-1 vs. 23.5 months (95% CI 15.3-31.7) for CC of 2-3 (P = 0.178, log rank test). There were no perioperative deaths. Serious adverse events (SAEs) occurred in two patients (9.1%). A univariate analysis identified PCI ≤ 15 as the only prognostic predicator (hazard ratio (HR) 13.1, 95% CI 2.7-63.4, P = 0.001). Conclusions CRS + HIPEC could contribute to favourable outcomes for select PPSC patients with acceptable safety profiles.
Implications of Hyperthermic Intraperitoneal Chemotherapy Perfusion-Related Hyperglycemia.
Stewart Camille L,Gleisner Ana,Halpern Alison,Ibrahim-Zada Irada,Luna Rodrigo Asturias,Pearlman Nathan,Gajdos Csaba,Edil Barish,McCarter Martin
Annals of surgical oncology
BACKGROUND:Hyperthermic intraperitoneal chemotherapy (HIPEC) administration can be associated with hyperglycemia during perfusion. Little is known about this effect, and no previous studies have examined patient characteristics associated with perfusion-related hyperglycemia. METHODS:We retrospectively identified consecutive patients at a single institution treated with HIPEC from 8/2003 to 10/2016 who had intraoperative blood glucose measured. Hypertonic 1.5% dextrose-containing peritoneal dialysate was used as carrier solution in all patients. Comparisons were made using parametric [Student's t test, analysis of variance (ANOVA)], and nonparametric tests (χ , Kruskal-Wallis) where appropriate. RESULTS:There were 85 patients identified, with average age of 53 ± 12 years, 69 (81%) with appendiceal or colorectal peritoneal cancer. Most patients were perfused with mitomycin C (69%) or oxaliplatin (24%). Intraoperative hyperglycemia (> 180 mg/dL) affected the majority of patients (86%), with values up to 651 mg/dL. Insulin was required for treatment in 66% of patients. Peak hyperglycemia occurred within an hour of perfusion in 91%, and resolved by postoperative day one in 91% of patients. Glucose > 309 mg/dL (highest quartile) was associated with longer operating time (p = 0.03) and with use of oxaliplatin compared with mitomycin C (p = 0.01). No association was found with other comorbidities, peritoneal carcinomatosis index score, or postoperative outcomes. CONCLUSIONS:Most patients experience hyperglycemia during HIPEC. This is not clearly associated with patient factors, and may be due to use of dextrose-containing carrier solution. Since perioperative hyperglycemia has potential negative impact, use of dextrose-containing carrier solution should be questioned and is worth investigating further.
Early Postoperative Chemotherapy After Complete Cytoreduction and Hyperthermic Intraperitoneal Chemotherapy for Isolated Peritoneal Carcinomatosis of Colon Cancer: A Multicenter Study.
Maillet Marianne,Glehen Olivier,Lambert Jerome,Goere Diane,Pocard Marc,Msika Simon,Passot Guillaume,Elias Dominique,Eveno Clarisse,Sabaté Jean-Marc,Lourenco Nelson,André Thierry,Gornet Jean-Marc,
Annals of surgical oncology
PURPOSE:The prognosis of peritoneal carcinomatosis (PC) from colorectal cancer has been improved with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). However, benefits of postoperative chemotherapy (CT) are unclear. METHODS:This retrospective, multicenter study included 231 patients treated by CRS and HIPEC for isolated PC of colon cancer in four expert's centers. Overall survival (OS), progression-free survival (PFS), and peritoneal recurrence-free survival (PRFS) were compared between patients with adjuvant CT (started within 3 months after surgery) and patients with surveillance only. RESULTS:After exclusion of 10 patients for early postoperative death (4%), 221 patients were included (CT group: n = 151; surveillance group: n = 70). Main postoperative CT regimens (median of 6 cycles) were Folfox (28%), Folfiri bevacizumab (24.5%), Folfiri (16%), and Folfiri cetuximab (12.5%). The median OS after surgery was 43.3 months with no difference between CT and surveillance groups. In multivariate analysis, a low peritoneal cancer index (p < 0.0001) and a long delay between diagnosis of CP and HIPEC (p = 0.001) were associated with increased OS. The median PFS and PRFS were 12.4 and 17 months, respectively. At 1 year, more patients were without progression (p = 0.001) or PC recurrence (0.0004) in the CT group, but with prolonged follow-up this difference was no longer significant. CONCLUSIONS:Early postoperative CT does not improve OS after CRS and HIPEC for colon carcinomatosis. However, a transient effect on PFS and PRFS was observed. A subgroup of patients who may benefit more from CT remain to be defined.
Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for treatment of ovarian cancer.
Polom Karol,Roviello Giandomenico,Generali Daniele,Marano Luigi,Petrioli Roberto,Marsili Stefania,Caputo Edda,Marrelli Daniele,Roviello Franco
International journal of hyperthermia : the official journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group
Hyperthermic intraperitoneal chemotherapy (HIPEC), a strategy combining maximal cytoreductive surgery and maximal regional chemotherapy, has been applied to treat ovarian cancer resulting in long-term survival rates in selected patients. However, the status of HIPEC in ovarian cancer remains an experimental procedure, given the many variables among the data and trials reviewed, to enable us to derive strong conclusions about its role from this overview. In this review we discuss treatment with HIPEC in patients with ovarian cancer and future prospective of its use in clinical setting. HIPEC is an effective tool in the treatment of selected patients with peritoneal carcinomatosis from ovarian cancer. Unfortunately, due to the lack of randomised trials, the evidence of HIPEC is very limited. Future randomised studies are awaited to define the role and clinical impact of HIPEC in ovarian cancer.
Laparoscopic Hyperthermic Intraperitoneal Perfusion Chemotherapy for Patients with Malignant Ascites Secondary to Unresectable Gastric Cancer.
Ba Ming-Chen,Long Hui,Zhang Xiang-Liang,Gong Yuan-Feng,Tang Yun-Qiang,Wu Yin-Bing,Yu Fei-Hong,Cui Shu-Zhong
Journal of laparoendoscopic & advanced surgical techniques. Part A
BACKGROUND:To compare the efficacy of three chemotherapeutic combinations for laparoscopic hyperthermic intraperitoneal perfusion chemotherapy (HIPPC) in the treatment of malignant ascites secondary to unresectable gastric cancer (GC). MATERIALS AND METHODS:From January 2010 to December 2013, 38 GC patients were randomly divided into three groups and treated by laparoscopic HIPPC with one of the three following chemotherapy combinations: raltitrexed (Ra) with oxaliplatin [trans-(±)-diaminocyclohexane oxalatoplatinum (l-OHP)], Ra with cisplatin (DDP), and Ra with mitomycin C (MMC). Perioperative complications, patients' quality of life, and survival were recorded and compared among the three groups. RESULTS:The intraoperative course was successful in all patients, and no perioperative death or complication related to laparoscopic HIPPC was documented. The median follow-up period was 9 months, and the median survival was 7.5 months for all patients. Patients in the Ra/l-OHP group had a median survival of 8.7 months, the Ra/DDP group had a median survival of 5.6 months, and the Ra/MMC group had a median survival of 7.5 months. Patients' median survival in the Ra/l-OHP group and Ra/MMC group was significantly longer than in the Ra/DDP group (P < .05). No significant difference was found in total remission rate of ascites, increase in the Karnofsky Performance Scale, and incidence rate of port-site metastases among the three groups. CONCLUSIONS:Laparoscopy-assisted HIPPC provides modest yet encouraging efficacy for malignant ascites secondary to disseminated GC. Our preliminary data indicate that the chemotherapeutic combination of Ra/l-OHP and Ra/MMC might be more beneficial compared with Ra/DDP in terms of patients' survival.
Impact of Combination Chemotherapy in Peritoneal Mesothelioma Hyperthermic Intraperitoneal Chemotherapy (HIPEC): The RENAPE Study.
Malgras Brice,Gayat Etienne,Aoun Olivier,Lo Dico Réa,Eveno Clarisse,Pautrat Karine,Delhorme Jean-Baptiste,Passot Guillaume,Marchal Frédéric,Sgarbura Olivia,Ferron Gwenael,Goéré Diane,Andre Thierry,Pocard Marc,
Annals of surgical oncology
BACKGROUND:The introduction of cytoreductive surgery (CRS) in combination with hyperthermic intraperitoneal chemotherapy (HIPEC) improved the prognosis of selected patients with peritoneal mesothelioma (PM). OBJECTIVE:The objective of our study was to evaluate whether different HIPEC agents were associated with different outcomes in patients with PM. METHODS:From the RENAPE database, we selected all patients with histology-proven PM who underwent CRS + HIPEC from 1989 to 2014. Inclusion criteria were age ≤ 80 years, performance status ≤ 2, and no extraperitoneal metastases. RESULTS:Overall, 249 patients underwent CRS + HIPEC for PM. The HIPEC regimen included five chemotherapeutic agents (CAs), consisting of cisplatin, doxorubicin, mitomycin-C, oxaliplatin, and irinotecan. When considering all CAs (alone or in combination), there was no significant statistical difference in regard to postoperative overall survival (OS). However, OS was better when using two CAs (group 2 drugs) versus one CA (group 1 drug) (p = 0.03). The different CA regimens were equally distributed between the two groups. This association between OS and HIPEC agent, as well as a trend for better progression-free survival, were both observed in the two-drug group versus the one-drug group (p = 0.009) for patients undergoing complete cytoreductive surgery (CC-0) with an epithelioid subtype. CONCLUSIONS:This large study seems to show improved OS when combined CAs, especially with platinum-based regimens, are used for HIPEC in patients with PM, but needs to be confirmed by a randomized controlled trial.
Cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy with lobaplatin and docetaxel improves survival for patients with peritoneal carcinomatosis from abdominal and pelvic malignancies.
Wu Hai-Tao,Yang Xiao-Jun,Huang Chao-Qun,Sun Jian-Hua,Ji Zhong-He,Peng Kai-Wen,Zhang Qian,Li Yan
World journal of surgical oncology
BACKGROUND:This work was to evaluate the perioperative safety and efficacy of cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) with lobaplatin and docetaxel in patients with peritoneal carcinomatosis (PC) from gastrointestinal and gynecological cancers. METHODS:Patients were treated by CRS + HIPEC with lobaplatin 50 mg/m(2) and docetaxel 60 mg/m(2) in 6000 mL of normal saline at 43 ± 0.5 °C for 60 min. Vital signs were recorded for 6 days after CRS + HIPEC procedures. Perioperative serious adverse events (SAE), hematological, hepatic, renal, and electrolytes parameters, the changes in serum tumor markers (TM) before and after operation, patient recovery, and overall survival (OS) were analyzed. RESULTS:One hundred consecutive PC patients underwent 105 CRS + HIPEC procedures and postoperative chemotherapy. The median CRS + HIPEC duration was 463 (range, 245-820) min, and the highest temperature and heart rate during six postoperative days were 38.6 °C (median 37.5 °C) and 124 bpm (median 100 bpm), respectively. The 30-day perioperative SAE occurred in 16 (15.2 %) and mortality occurred in 2 (1.9 %) patients. Most routine blood laboratory tests at 1 week after surgery turned normal. Among 82 cases with increased preoperative TM CEA, CA125, and CA199, 71 cases had TM levels reduced or turned normal. Median time to nasogastric tube removal was 5 (range, 3-23) days, to liquid food intake 6 (range, 4-24) days, and to abdominal suture removal 15 (range, 10-30) days. At the median follow-up of 19.7 (range, 7.5-89.2) months, the median OS was 24.2 (95 % CI, 15.0-33.4) months, and the 1-, 3-, and 5-year OS rates were 77.5, 32.5, and 19.8 %, respectively. Univariate analysis identified five independent prognostic factors on OS: the origin of PC, peritoneal cancer index, completeness of CRS, cycles of adjuvant chemotherapy, and SAE. CONCLUSIONS:CRS + HIPEC with lobaplatin and docetaxel to treat PC is a feasible procedure with acceptable safety and can prolong the survival in selected patients with PC. TRIAL REGISTRATION:ClinicalTrials.gov, NCT00454519.
Clinical study of cisplatin hyperthermic intraperitoneal perfusion chemotherapy in combination with docetaxel, 5-flourouracil and leucovorin intravenous chemotherapy for the treatment of advanced-stage gastric carcinoma.
Zhibing Wu,Qinghua Deng,Shenglin Ma,Ke Zhang,Kan Wu,Xiadong Li,Pengjun Zhao,Ruzhen Zheng
BACKGROUND/AIMS:The purpose of this study is to observe and compare the preliminary efficacy and side effects of docetaxel, 5-fluorouracil and leucovorin intravenous chemotherapy in combination with cisplatin hyperthermic intraperitoneal perfusion chemotherapy for the treatment of advanced gastric cancer. METHODOLOGY:Retrospectively analyzed 101 patients with advanced gastric cancer receiving docetaxel, 5-fluorouracil, leucovorin and cisplatin intravenous chemotherapy or intravenous administration of docetaxel, 5-fluorouracil and leucovorin combined with cisplatin hyperthermic intraperitoneal perfusion chemotherapy, 49 patients in intravenous chemotherapy (VC) group, 52 patients in hyperthermic intraperitoneal perfusion chemotherapy (HIPEC) group. RESULTS:The response rate was 44.9% (22/49) in VC group and 65.4% (34/52) in HIPEC group, among which there was 1 case of CR, and the difference was statistically significant (p= 0.038). For CBR evaluation, the effective rate was 65.3% (32/49) in VC group and 82.7% (43/52) in HIPEC group, and the difference was statistically significant (p= 0.0458). The median progress free survival time (PFS) was 3.4 months in VC group and 4.6 months in HIPEC group, the difference was statistically significant (p= 0.045). The median overall survival time (OS) was 6.7 months in VC group and 7.5 months in HIPEC group, the difference was not statistically significant (p= 0.201). The main side effects in two groups were well tolerated, and there was no statistically significant difference. CONCLUSIONS:The short-term efficacy and PFS of HIPEC plus intravenous chemotherapy were better than single intravenous chemotherapy, and there was no significant improvement in OS, the side effects were similar in two groups with good tolerability.
Docetaxel combined with intraperitoneal hyperthermic perfusion chemotherapy and hyperthermia in the treatment of advanced ovarian cancer.
Zhang Ting,Pan Qiong,Xiao Songshu,Li Lijie,Xue Min
Ovarian cancer is a clinical type of gynecological malignant tumor with poor prognosis and a high mortality rate. At present, the primary treatment method used is surgery, with chemotherapy as an ajdunctive therapy. Thus, new short-term treatments should be identified. The aim of the present study was to investigate the short-term curative effects and safety of docetaxel combined with intraperitoneal cisplatin chemotherapy and hyperthermia treatment of advanced ovarian cancer. A total of 112 cases of advanced (stage III-IV) ovarian cancer patients confirmed by clinical diagnosis between October 2014 and December 2015 were included in the study. The patients were randomly divided into the study and control groups (n=56 cases). The control group was treated with docetaxel and intraperitoneal cisplatin hyperthermic perfusion chemotherapy, while the study group was treated with docetaxel venous chemotherapy and intraperitoneal cisplatin cyclical hyperthermic perfusion chemotherapy with BR-TRG-1 body cavity hyperthermic perfusion treatment system. Clinical treatment results for short-term curative effects and adverse reactions were compared and analyzed 8 weeks after treatment. The total effective rate of the study and control groups were 87.5 and 62.5%, respectively, and the difference was statistically significant (P<0.05). The controlled rate of ascites, remission rate of tumor and descent rate of CA125 of patients in the study group were better than patients in the control group (P<0.05). The rate of adverse reactions of patients in the study group was 39.3%, and the grade of toxicity was from I to II, while the rate of adverse reactions of patients in the control group was 55.4%, and the grade of toxicity was from II to III. The difference between the two groups was statistically significant (P<0.05). In conclusion, applying the combination of docetaxel, intraperitoneal cisplatin hyperthermic perfusion chemotherapy and hyperthermia to treat advanced ovarian cancer can improve the curative effects with little toxicity; thus, it is worthy of promotion and application.
Surgical outcomes of hyperthermic intraperitoneal chemotherapy: analysis of the american college of surgeons national surgical quality improvement program.
Jafari Mehraneh D,Halabi Wissam J,Stamos Michael J,Nguyen Vinh Q,Carmichael Joseph C,Mills Steven D,Pigazzi Alessio
IMPORTANCE:Hyperthermic intraperitoneal chemotherapy (HIPEC) and cytoreductive surgery have been shown to benefit selected patients with peritoneal carcinomatosis. However, these procedures are associated with high morbidity and mortality. Available data investigating the outcomes of HIPEC are mostly limited to single-center studies. To date, there have been few large-scale studies investigating the postoperative outcomes of HIPEC. OBJECTIVE:To determine the associated 30-day morbidity and mortality of cytoreductive surgery-HIPEC in the treatment of metastatic and primary peritoneal cancer in American College of Surgeons National Surgical Quality Improvement Program centers. DESIGN, SETTING, AND PARTICIPANTS:A retrospective review of HIPEC cases performed for primary and metastatic peritoneal cancer diagnoses was conducted. The cytoreductive surgical procedures were sampled, and disease processes were identified. Patient demographics, intraoperative occurrences, and postoperative complications were reviewed from the American College of Surgeons National Surgical Quality Improvement Program from 2005-2011. MAIN OUTCOMES AND MEASURES:Thirty-day mortality and morbidity. RESULTS:Of the cancers identified among the 694 sampled cases, 14% of patients had appendiceal cancer, 11% had primary peritoneal cancer, and 8% had colorectal cancer. The American Society of Anesthesiologists classification was 3 for 70% of patients. The average operative time was 7.6 hours, with 15% of patients requiring intraoperative transfusions. Postoperative bleeding (17%), septic shock (16%), pulmonary complications (15%), and organ-space infections (9%) were the most prevalent postoperative complications. The average length of stay was 13 days, with a 30-day readmission rate of 11%. The rate of reoperation was 10%, with an overall mortality rate of 2%. CONCLUSIONS AND RELEVANCE:American College of Surgeons National Surgical Quality Improvement Program hospitals performing HIPEC have acceptable rates of morbidity and mortality.
Clinicopathological Parameters in Patient Selection for Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy for Colorectal Cancer Metastases: A Meta-analysis.
Kwakman Riom,Schrama Anne M,van Olmen Josefien P,Otten René H,de Lange-de Klerk Elly S,de Cuba Erienne M,Kazemier Geert,Te Velde Elisabeth A
Annals of surgery
OBJECTIVE:To improve patient selection for cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) by evaluating various preoperatively assessable clinicopathological parameters as markers for survival after CRS and HIPEC. SUMMARY BACKGROUND DATA:Peritoneal metastases (PMs) originating from colorectal cancer are treated with CRS and HIPEC. Despite increasing survival, high morbidity and mortality warrant selection of patients with optimal benefit from this treatment. Many studies report a number of variables to be associated with survival after CRS and HIPEC, but no definitive analysis has been made to validate various markers. METHODS:In concordance with PRISMA guidelines, we performed a literature search encompassing 4110 articles to select 50 articles that reported the influence of 1 or more clinicopathological variables on overall survival after CRS and HIPEC. In absence of RCTs, 25 cohort studies could be used to perform a meta-analysis on 10 prognostic variables. RESULTS:We determined that concurrent liver metastasis, lymph node metastasis, Eastern Cooperative Oncology Group score, tumor differentiation, and signet ring cell histology are all negative prognostic variables on overall survival after CRS and HIPEC. Conversely, sex and location of primary could not be validated as prognostic markers. More research is required to make definitive conclusions about neoadjuvant chemotherapy, onset of PMs, and mucinous histology. CONCLUSIONS:Current clinical practice, which selects patients based on extraperitoneal metastasis, lymph node stage, performance status, and tumor histology, is validated by our pooled analysis. Our data merit further research into neoadjuvant chemotherapy in the setting of CRS and HIPEC for PMs.
Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in the management of gastrointestinal cancers with peritoneal metastases: Progress toward a new standard of care.
Sugarbaker Paul H
Cancer treatment reviews
Peritoneal metastases from gastrointestinal cancer was, in the past, accepted as an inevitable component of the natural history of these diseases. It is a major cause of intestinal obstruction, fistula formation, and bowel perforation as the recurrent malignancy progresses to a terminal condition. Peritoneal metastases may be caused by full thickness penetration of the bowel wall by the primary cancer or by spilled cancer cells released into the peritoneal space by surgical trauma. Two new surgical technologies that have evolved to manage peritoneal metastases are cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). This combined treatment strategy uses peritonectomy procedures and visceral resections to reduce the disease in the abdomen and pelvis to a macroscopic volume. Then, HIPEC is used to preserve the complete cytoreduction by controlling the minimal residual disease. Since the extent of peritoneal metastases, as measured by the peritoneal cancer index (PCI), is crucial to a favorable outcome, prognostic indicators are used to select patients for treatment. The combined treatment may be used to prevent peritoneal metastases in gastrointestinal cancer patients having a resection of the primary malignancy. This is especially important in gastric cancer patients with serosal invasion. The combined treatment may be used synchronously with the primary cancer resection if peritoneal metastases are already apparent. The treatment is most frequently used with metachronous peritoneal metastases diagnosed in follow-up. Cure of peritoneal metastases is an option in selected patients and its knowledgeable use is progressing towards a new standard of care.
Clinical efficacy of type-B ultrasound-guided intraperitoneal hyperthermic chemoperfusion combined with systemic chemotherapy in advanced gastric cancer patients with malignant ascites.
Lu C,Li L,Luo Z,Cui Y,Fu P,Zhou J,Ma N,Zhou Y
OBJECTIVES:To evaluate the clinical efficacy of systemic chemotherapy combined with intraperitoneal hyperthermic perfusion in advanced gastric cancer patients with malignant ascites. PATIENTS AND METHODS:Forty-eight gastric cancer patients with malignant ascites who were admitted to our hospital were selected and randomly divided into the hyperthermic perfusion and control groups. The control group only received systemic chemotherapy, and the hyperthermic perfusion group received systemic chemotherapy combined with intraperitoneal hyperthermic chemoperfusion. The therapeutic efficacy, the survival time and the associated toxicity were determined for the two groups. RESULTS:The efficacy was significantly higher in the hyperthermic perfusion group (85.7%) than in the control group (30.0%) (P 0.05). The median progression-free survival (PFS) was significantly longer in the hyperthermic perfusion group (12 months) compared with the control group (6 months) (P < 0.05). The median overall survival (OS) was significantly longer in the hyperthermic perfusion group (21 months) compared with the control group (9 months) (P < 0.05). There was a significantly higher 1-year survival rate in the hyperthermic perfusion group (89.3%) than in the control group (36.4%) (P < 0.05); however, there was no significant difference in the 3-year survival rate (10.7% vs. 10.0%). The Karnofsky Performance Status (KPS) score in the hyperthermic perfusion group increased significantly from 62.8 ± 1.84 to 74.3 ± 5.0 after hyperthermic chemoperfusion (P < 0.05). CONCLUSION:Systemic chemotherapy combined with intraperitoneal hyperthermic perfusion exhibited significant clinical efficacy in advanced gastric cancer patients with malignant ascites, helped control ascites, improved the quality of life and extended PFS and OS. This treatment regimen is worth promoting.