Status of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in patients with peritoneal carcinomatosis from colorectal cancer.
ABSTRACT: Peritoneal carcinomatosis (PC) was previously considered an incurable disease with a poor survival outcome. As our understanding of its biology evolved, the paradigm of the management of PC from colorectal cancer (CRC) has changed, including the combination of macroscopic disease control, cytoreductive surgery (CRS), maximal regional chemotherapy to treat residual microscopic disease, and hyperthermic intraperitoneal chemotherapy (HIPEC). As with many surgical innovations, CRS with HIPEC has evolved faster than data to support it, leaving many skeptics and critics. This review highlights the recent evidence of current practice and outcome of CRS with HIPEC. Furthermore, it also summarizes the ongoing clinical trials and potential future progress of this treatment modality.
Project description:BACKGROUND:This randomized phase III study was to evaluate the efficacy and safety of cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) for the treatment of peritoneal carcinomatosis (PC) from gastric cancer. METHODS:Sixty-eight gastric PC patients were randomized into CRS alone (n = 34) or CRS + HIPEC (n = 34) receiving cisplatin 120 mg and mitomycin C 30 mg each in 6000 ml of normal saline at 43 ± 0.5°C for 60-90 min. The primary end point was overall survival, and the secondary end points were safety profiles. RESULTS:Major clinicopathological characteristics were balanced between the 2 groups. The PC index was 2-36 (median 15) in the CRS + HIPEC and 3-23 (median 15) in the CRS groups (P = 0.489). The completeness of CRS score (CC 0-1) was 58.8% (20 of 34) in the CRS and 58.8% (20 of 34) in the CRS + HIPEC groups (P = 1.000). At a median follow-up of 32 months (7.5-83.5 months), death occurred in 33 of 34 (97.1%) cases in the CRS group and 29 of 34 (85.3%) cases of the CRS + HIPEC group. The median survival was 6.5 months (95% confidence interval 4.8-8.2 months) in CRS and 11.0 months (95% confidence interval 10.0-11.9 months) in the CRS + HIPEC groups (P = 0.046). Four patients (11.7%) in the CRS group and 5 (14.7%) patients in the CRS + HIPEC group developed serious adverse events (P = 0.839). Multivariate analysis found CRS + HIPEC, synchronous PC, CC 0-1, systemic chemotherapy ? 6 cycles, and no serious adverse events were independent predictors for better survival. CONCLUSIONS:For synchronous gastric PC, CRS + HIPEC with mitomycin C 30 mg and cisplatin 120 mg may improve survival with acceptable morbidity.
Project description: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.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.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.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.ClinicalTrials.gov, NCT00454519.
Project description:<h4>Background</h4>Peritoneal carcinomatosis (PC) is a difficult clinical challenge in colorectal cancer (CRC) because conventional treatment modalities could not produce significant survival benefit, which highlights the acute need for new treatment strategies. Our previous case-control study demonstrated the potential survival advantage of cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) over CRS alone. This phase II study was to further investigate the efficacy and adverse events of CRS+HIPEC for Chinese patients with CRC PC.<h4>Methods</h4>A total of 60 consecutive CRC PC patients underwent 63 procedures consisting of CRS+HIPEC and postoperative chemotherapy, all by a designated team focusing on this combined treatment modality. All the clinico-pathological information was systematically integrated into a prospective database. The primary end point was disease-specific overall survival (OS), and the secondary end points were perioperative safety profiles.<h4>Results</h4>By the most recent database update, the median follow-up was 29.9 (range 3.5-108.9) months. The peritoneal cancer index (PCI) ?20 was in 47.0% of patients, complete cytoreductive surgery (CC0-1) was performed in 53.0% of patients. The median OS was 16.0 (95% confidence interval [CI] 12.2-19.8) months, and the 1-, 2-, 3-, and 5-year survival rates were 70.5%, 34.2%, 22.0% and 22.0%, respectively. Mortality and grades 3 to 5 morbidity rates in postoperative 30 days were 0.0% and 30.2%, respectively. Univariate analysis identified 3 parameters with significant effects on OS: PCI ?20, CC0-1 and adjuvant chemotherapy over 6 cycles. On multivariate analysis, however, only CC0-1 and adjuvant chemotherapy ?6 cycles were found to be independent factors for OS benefit.<h4>Discussion</h4>CRS+HIPEC at a specialized treatment center could improve OS for selected CRC PC patients from China, with acceptable perioperative safety.
Project description:Gastric cancer associated peritoneal carcinomatosis (GCPC) has a poor prognosis with a median survival of less than one year. Systemic chemotherapy including targeted agents has not been found to significantly increase the survival in GCPC. Since recurrent gastric cancer remains confined to the abdominal cavity in many patients, regional therapies like aggressive cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) have been investigated for GCPC. HIPEC has been used for three indications in GC- as an adjuvant therapy after a curative surgery, HIPEC has been shown to improve survival and reduce peritoneal recurrences in many randomised trials in Asian countries; as a definitive treatment in established PC, HIPEC along with CRS is the only therapeutic modality that has resulted in long-term survival in select groups of patients; as a palliative treatment in advanced PC with intractable ascites, HIPEC has been shown to control ascites and reduce the need for frequent paracentesis. While the results of randomised trials of adjuvant HIPEC from western centres are awaited, the role of HIPEC in the treatment of GCPC is still evolving and needs larger studies before it is accepted as a standard of care.
Project description:The management of peritoneal metastases from gastric cancer origin has evolved considerably over the last three decades with the establishment of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) as efficacious therapies in carefully selected patients. Other approaches such as the use of prophylactic/adjuvant HIPEC in patients who are considered high-risk and those with positive peritoneal cytology will benefit from additional data before being adopted into routine clinical practice. Lastly, there are new and emerging intraperitoneal chemotherapy techniques such as early post-operative intraperitoneal chemotherapy (EPIC) for residual microscopic disease, and pressurized intraperitoneal aerosolized chemotherapy (PIPAC) for patients with advanced unresectable peritoneal carcinomatosis, which are currently under evaluation in clinical trials. The following review outlines the natural history of gastric cancer, currently available neoadjuvant and adjuvant therapies for resectable disease, and existing evidence supporting various approaches to CRS and intraperitoneal chemotherapy.
Project description:Background:The role of hyperthermic intraperitoneal chemotherapy (HIPEC) for peritoneal carcinomatosis (PC) from colorectal cancer (CRC) is debated. Melphalan as a perfusion agent has also demonstrated survival benefit in other recurrent and chemoresistant malignancies. Thus, we hypothesize that melphalan as a HIPEC agent may improve overall survival (OS) and progression-free survival (PFS) in patients with PC from CRC. Methods:A retrospective review of a prospective database of 48 patients who underwent optimal CRS (CC-0/1) and HIPEC from 2001-2016 was performed. Nineteen had CRS/HIPEC with melphalan (group I) and 29 with mitomycin-C (group II). Survival was estimated using the Kaplan-Meier method. Cox regression was used for multivariate analysis. Perioperative variables were compared. Results:Mean age at CRS/HIPEC was 53±10 years. Median peritoneal cancer index (PCI) was 17 vs 13 in groups I and II, respectively (p=0.86). PCI?20 occurred in 9 (47%) and 13 (45%) patients in groups I and II, respectively. Positive lymph nodes were identified in 8/19 (42%) vs 12/29 (41%) in groups I and II, respectively (p=0.73). Multivariate analysis identified PCI?20 as a predictive factor of survival (HR: 7.5). Median OS in groups I and II was 36 and 28 months, respectively (p=0.54). Median PFS in groups I and II was 10 and 20 months, respectively (p=0.05). Conclusions:CRS/HIPEC with MMC had longer median PFS in PC from CRC. PCI?20 was the only independent predictive factor for survival. Until longer follow-up is available, we recommend using MMC in CRS/HIPEC for PC from CRC. Further prospective randomized studies are necessary.
Project description:The treatment of peritoneal carcinomatosis (PC) of colorectal origin with cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) has a 5-year recurrence-free or cure rate of at least 16%, so it is no longer labeled as a fatal disease, and offers prolonged survival for patients with a low peritoneal carcinomatosis index. Metachronous PC of colorectal origin is so predictable that there is a model which has been used to successfully determine the individual risk of each patient. Patients at risk are clearly identified; those with the highest risk have small peritoneal nodules present in the first surgery (70% probability of developing PC), ovarian metastases (60%), perforated tumor onset or intraoperative tumor rupture (50%). Current clinical, biological and imaging techniques still lack sufficient sensitivity to diagnose PC in its initial stages, when CRS plus HIPEC has a greater impact and a higher cure rate. Second-look surgery with HIPEC or prophylactic HIPEC at the time of the first intervention have been proposed as means of preventing and/or anticipating clinical or radiological relapse in at-risk patients. Both techniques have shown a significant decrease in peritoneal relapses and should be considered essential weapons in the management of colorectal cancer.
Project description:<h4>Background</h4>Gastric perforation after cytoreductive surgery (CRS) is an infrequent complication. There is lack of evidence regarding the risk factors for this postoperative complication. The aim of this study was to assess the prevalence of postoperative gastric perforation in patients undergoing CRS for peritoneal carcinomatosis (PC) and to evaluate risk factors predisposing to this complication.<h4>Methods</h4>We designed a unicentric retrospective study to identify all patients who underwent an open upfront or interval CRS after a primary diagnosis of PC of different origins between March 2007 and December 2018 at a French Comprehensive Cancer Center. The main outcome was the occurrence of postoperative gastric perforation.<h4>Results</h4>Five hundred thirty-three patients underwent a CRS for PC during the study period and 13 (2.4%) presented a postoperative gastric perforation with a mortality rate of 23% (3/13). Neoadjuvant chemotherapy was administered in 283 (53.1%) patients and 99 (18.6%) received hyperthermic intraperitoneal chemotherapy (HIPEC). In the univariate analysis, body mass index (BMI), peritoneal cancer index, splenectomy, distal pancreatectomy, and histology were significantly associated with postoperative gastric perforation. After multivariate analysis, BMI (OR [95%CI] = 1.13 [1.05-1.22], p = 0.002) and splenectomy (OR [95%CI] = 26.65 [1.39-509.67], p = 0.029) remained significantly related to the primary outcome.<h4>Conclusions</h4>Gastric perforation after CRS is a rare event with a high rate of mortality. While splenectomy and increased BMI are risk factors associated with this complication, HIPEC does not seem to be related. Gastric perforation is probably an ischemic complication due to a multifactorial process. Preventive measures such as preservation of the gastroepiploic arcade and prophylactic suture of the greater gastric curvature require further assessment.
Project description:INTRODUCTION:Cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) is a well-established treatment for peritoneal cancer (PC). However, this kind of combination therapy is associated with a high incidence of complications. Moreover, relative studies have indicated that traditional laboratory testing is insufficient to demonstrate the overall haemostatic physiology of CRS/HIPEC. Thromboelastography (TEG), administered by monitoring dynamic changes in haemostasis, has been shown to contribute to reducing transfusion requirements and improving survival. However, there is no evidence to verify whether TEG can be applied to guide transfusion strategies during CRS/HIPEC. Therefore, we aim to investigate whether TEG-guided blood product transfusion (TEG-BT) therapy is superior to traditional blood product transfusion (T-BT) therapy for guiding perioperative blood transfusion treatment and improving the prognosis of patients undergoing CRS/HIPEC. METHODS AND ANALYSIS:The TEG-BT versus T-BT study is a single-centre, randomised, blinded outcome assessment clinical trial of 162 patients with PC, aged 18-64 years and undergoing CRS/HIPEC. Participants will be randomly allocated to receive TEG-BT or T-BT. The primary outcome will be the evaluation of perioperative blood transfusion, which refers to the total amount of blood transfusion given from the time patients enter the operating room up to 72?hours postoperatively. The secondary outcomes will include the transfusion volume during surgery, total amount of intraoperative infusion, amount of blood lost during the operation, total blood transfusion between 0 and 72 hours after surgery, lowest haemoglobin level within 72 hours after surgery, intensive care unit duration, overall length of stay, total cost of hospitalisation and adverse events. Data will be analysed according to the intention-to-treat principle. ETHICS AND DISSEMINATION:The study protocol has been approved by the Scientific Research Ethics Committee of Beijing Shijitan Hospital Affiliated with Capital Medical University (Approval Number: sjtkyll-lx-2020-3). The results will be published in peer-reviewed journals. TRIAL REGISTRATION NUMBER:Chinese Clinical Trial Registry (ChiCTR2000028835).
Project description:Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) has an emerging role in the treatment of peritoneal malignancies. The CRS-HIPEC approach has known treatment-related toxicities. This study sought to determine the predictors of major postoperative complications after CRS-HIPEC in a high-volume center.From a single-institution database, this study investigated complications experienced by patients undergoing CRS-HIPEC. Multiple preoperative and operative factors were analyzed for their ability to predict 60-day Clavien grade 3 and greater (major) complications by logistic regression. A predictive model was created from preoperative factors using multivariate logistic regression. The model was tested by Akaike's information criterion, the Hosmer and Lemeshow Goodness-of-Fit Test, the receiver operating characteristic, and the Youden Index.The study evaluated 247 patients undergoing CRS-HIPEC. The primary tumor site was the appendix in 166 cases (67.2 %), the colorectal area in 51 cases (20.6 %), the peritoneum (mesothelioma) in 22 cases (8.9 %), the ovary in 5 cases (2 %), and the small bowel in 3 cases (1.2 %). The median peritoneal cancer index was 14 (range 0-29), and 235 patients (95.1 %) had a complete (CC-0/1) cytoreduction. Major complications occurred for 41 patients (16.6 %), classified as grade 3 in 33 cases (13.4 %), grade 4 in 5 cases (2 %), and grade 5 (deaths) in 3 cases (1.2 %). The factors predictive of major complications in the multivariate analysis were a Charlson Comorbidity Index (CCI) score higher than 0 [odds ratio (OR), 2.505; p = 0.035], presence of preoperative symptoms (OR 1.951; p = 0.064), and prior resection status [no resection or prior CRS-HIPEC (OR 2.087) vs. prior resection without CRS-HIPEC (OR 3.209); p = 0.046]. These variables were used to create a tool predictive of postoperative complications.Presence of symptoms, CCI, and prior resection status predict major complications and define a low-risk population after CRS-HIPEC.