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van den Heuvel TBM, Lurvink RJ, Rovers KPB, van Hellemond IEG, de Hingh IHJT. Systemic chemotherapy in addition to CRS-HIPEC for colorectal peritoneal metastases: A critical systematic review on the impact on overall survival. J Surg Oncol 2024; 130:1378-1389. [PMID: 39257287 PMCID: PMC11825997 DOI: 10.1002/jso.27849] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2024] [Revised: 07/27/2024] [Accepted: 08/14/2024] [Indexed: 09/12/2024]
Abstract
In patients with resectable colorectal peritoneal metastases, it is unclear whether systemic chemotherapy, in addition to cytoreductive surgery-hyperthermic intraperitoneal chemotherapy (CRS-HIPEC), improves overall survival (OS). This systematic review of 12 retrospective studies involving 3721 patients aimed to summarize the available evidence. Contradictory results were found regarding the effectiveness of neoadjuvant, adjuvant, and perioperative systemic therapies on OS, with a high risk of bias. Available evidence remains inconclusive, stressing the need for prospective, randomized trials, like the ongoing Dutch CAIRO6-trial.
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Affiliation(s)
- Teun B. M. van den Heuvel
- Department of SurgeryCatharina Hospital EindhovenEindhovenThe Netherlands
- Department of Oncology and Developmental Biology (GROW), Faculty of Health, Medicine and Life SciencesMaastricht UniversityMaastrichtThe Netherlands
| | - Robin J. Lurvink
- Department of SurgeryCatharina Hospital EindhovenEindhovenThe Netherlands
| | - Koen P. B. Rovers
- Department of SurgeryCatharina Hospital EindhovenEindhovenThe Netherlands
| | | | - Ignace H. J. T. de Hingh
- Department of SurgeryCatharina Hospital EindhovenEindhovenThe Netherlands
- Department of Oncology and Developmental Biology (GROW), Faculty of Health, Medicine and Life SciencesMaastricht UniversityMaastrichtThe Netherlands
- Department of Research & DevelopmentNetherlands Comprehensive Cancer Organisation (IKNL)UtrechtThe Netherlands
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Winicki NM, Greer JB. Is Hyperthermic Intraperitoneal Chemotherapy Appropriate for Colon Cancer? Adv Surg 2024; 58:49-64. [PMID: 39089786 DOI: 10.1016/j.yasu.2024.04.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/04/2024]
Abstract
Colorectal cancer (CRC) with peritoneal metastases is a complex disease and its management presents significant clinical challenges. In well-selected patients at experienced centers, CRS/hyperthermic intraperitoneal chemotherapy (HIPEC) can be performed with acceptable morbidity and is associated with prolonged survival. Based on the results of recent randomized controlled trials, HIPEC using oxaliplatin after CRS with shortened perfusion periods (30 minutes) is no longer recommended. There is a movement toward utilizing mitomycin C as a first-line intraperitoneal agent with extended perfusion times (90-120 minutes); however, there is currently little prospective evidence to support its widespread use.
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Affiliation(s)
- Nolan M Winicki
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
| | - Jonathan B Greer
- Division of Gastrointestinal Surgical Oncology, Peritoneal Surface Malignancy Program, Johns Hopkins University School of Medicine, 600 North Wolfe Street, Halsted 614, Baltimore, MD 21287, USA.
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Xia W, Geng Y, Hu W. Peritoneal Metastasis: A Dilemma and Challenge in the Treatment of Metastatic Colorectal Cancer. Cancers (Basel) 2023; 15:5641. [PMID: 38067347 PMCID: PMC10705712 DOI: 10.3390/cancers15235641] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2023] [Revised: 11/07/2023] [Accepted: 11/13/2023] [Indexed: 10/25/2024] Open
Abstract
Peritoneal metastasis (PM) is a common mode of distant metastasis in colorectal cancer (CRC) and has a poorer prognosis compared to other metastatic sites. The formation of PM foci depends on the synergistic effect of multiple molecules and the modulation of various components of the tumor microenvironment. The current treatment of CRC-PM is based on systemic chemotherapy. However, recent developments in local therapeutic modalities, such as cytoreductive surgery (CRS) and intraperitoneal chemotherapy (IPC), have improved the survival of these patients. This article reviews the research progress on the mechanism, characteristics, diagnosis, and treatment strategies of CRC-PM, and discusses the current challenges, so as to deepen the understanding of CRC-PM among clinicians.
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Affiliation(s)
- Wei Xia
- Department of Oncology, The Third Affiliated Hospital of Soochow University, 185 Juqian Street, Changzhou 213003, China;
| | - Yiting Geng
- Department of Oncology, The Third Affiliated Hospital of Soochow University, 185 Juqian Street, Changzhou 213003, China;
| | - Wenwei Hu
- Department of Oncology, The Third Affiliated Hospital of Soochow University, 185 Juqian Street, Changzhou 213003, China;
- Jiangsu Engineering Research Center for Tumor Immunotherapy, The Third Affiliated Hospital of Soochow University, Changzhou 213003, China
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Wu Z, Qin X, Zhang Y, Luo J, Luo R, Cai Z, Wang H. Effect of BRAF mutation on the prognosis for patients with colorectal cancer undergoing cytoreductive surgery for synchronous peritoneal metastasis. Gastroenterol Rep (Oxf) 2023; 11:goad061. [PMID: 37886242 PMCID: PMC10598839 DOI: 10.1093/gastro/goad061] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/05/2023] [Revised: 08/02/2023] [Accepted: 09/18/2023] [Indexed: 10/28/2023] Open
Abstract
Background KRAS/BRAF mutations (mutKRAS/mutBRAF) are unfavorable prognostic factors for colorectal cancer (CRC) metastases to the liver and lungs. However, their effects on the prognosis for patients with synchronous peritoneal metastasis (S-PM) of CRC after cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) are controversial. In the study, we aimed to determine the effects of mutKRAS/mutBRAF on the prognosis for patients with S-PM who received CRS. Methods A total of 142 patients diagnosed with S-PM between July 2007 and July 2019 were included in this study. The demographics, mutKRAS/mutBRAF status, overall survival (OS), and progression-free survival (PFS) of the patients were evaluated. The Kaplan-Meier method and log-rank test were used to estimate the difference in survival between groups. Results Among 142 patients, 68 (47.9%) showed mutKRAS and 42 (29.5%) showed mutBRAF. The median OS values were 8.4 and 34.3 months for patients with mutBRAF and BRAF wild-type, respectively (P < 0.01). However, KRAS status was not significantly associated with median OS (P = 0.76). Multivariate analysis revealed carcinoembryonic antigen, CRS, HIPEC, and mutBRAF as independent predictors for OS. Based on these findings, a nomogram was constructed. The C-index was 0.789 (95% confidence interval, 0.742-0.836), indicating good predictive ability of the model. Furthermore, the 1- and 2-year survival calibration plots showed good agreement between the predicted and actual OS rates. The area under curves of the 1- and 2-year survival predictions based on the nomogram were 0.807 and 0.682, respectively. Additionally, mutBRAF was significantly associated with lower PFS (P < 0.001). Conclusions mutBRAF is an independent prognostic risk factor for S-PM. The established nomogram predicted the OS of patients with CRC having S-PM with high accuracy, indicating its usefulness as a valuable prognostic tool for the designated patient cohort.
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Affiliation(s)
- Zhijie Wu
- Department of General Surgery (Colorectal Surgery), The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, P. R. China
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, P. R. China
- Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, P. R. China
| | - Xiusen Qin
- Department of General Surgery (Colorectal Surgery), The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, P. R. China
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, P. R. China
- Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, P. R. China
| | - Yuanxin Zhang
- Department of General Surgery (Colorectal Surgery), The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, P. R. China
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, P. R. China
- Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, P. R. China
| | - Jian Luo
- Department of General Surgery (Colorectal Surgery), The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, P. R. China
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, P. R. China
- Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, P. R. China
| | - Rui Luo
- Department of General Surgery (Colorectal Surgery), The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, P. R. China
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, P. R. China
- Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, P. R. China
| | - Zonglu Cai
- Department of General Surgery (Colorectal Surgery), The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, P. R. China
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, P. R. China
- Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, P. R. China
| | - Hui Wang
- Department of General Surgery (Colorectal Surgery), The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, P. R. China
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, P. R. China
- Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, P. R. China
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Park SY, Park JS, Kim HJ, Kim JG, Kang BW, Baek JH, Kim HR, Kim CH, Kim YJ, Choi GS. Oncological impact of intraperitoneal chemotherapy after cytoreductive surgery for patients with colorectal peritoneal metastasis: A bi-institutional retrospective analysis. J Surg Oncol 2023; 127:668-677. [PMID: 36515216 DOI: 10.1002/jso.27171] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2022] [Revised: 10/28/2022] [Accepted: 11/27/2022] [Indexed: 12/15/2022]
Abstract
BACKGROUND AND OBJECTIVES There is a paucity of evidence on the value of intraperitoneal chemotherapy (IPC) following cytoreductive surgery (CRS) for colorectal peritoneal metastasis. This study aimed to evaluate the association between mitomycin C-IPC and survival outcomes following CRS. METHODS The institutional databases of two tertiary hospitals were reviewed to identify patients who underwent CRS for colorectal peritoneal metastasis. The outcomes of patients who underwent CRS without IPC were compared with those of patients who underwent CRS plus early postoperative intraperitoneal chemotherapy (EPIC) or CRS plus hyperthermic intraperitoneal chemotherapy (HIPEC). The primary endpoints were cancer-specific survival (CSS), progression-free survival (PFS), and peritoneal PFS (P-PFS). RESULTS In 149 patients with peritoneal metastasis alone, EPIC and HIPEC use was significantly associated with better CSS, PFS, and P-PFS in the multivariate analysis. CSS was also significantly associated with perioperative systemic chemotherapy. Among 42 patients with both peritoneal and extraperitoneal metastases, CSS was independently related to the completeness of cytoreduction score, location of extraperitoneal metastasis, and grade 3-4 complications. CONCLUSIONS Mitomycin C-IPC after CRS was associated with better survival outcomes than CRS alone in patients with resectable peritoneal metastasis of colorectal cancer. This study found that IPC had beneficial effects regarding P-PFS in patients with both peritoneal and extraperitoneal metastases.
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Affiliation(s)
- Soo Yeun Park
- Colorectal Cancer Center, Kyungpook National University Chilgok Hospital, School of Medicine, Kyungpook National University, Daegu, Republic of Korea
| | - Jun Seok Park
- Colorectal Cancer Center, Kyungpook National University Chilgok Hospital, School of Medicine, Kyungpook National University, Daegu, Republic of Korea
| | - Hye Jin Kim
- Colorectal Cancer Center, Kyungpook National University Chilgok Hospital, School of Medicine, Kyungpook National University, Daegu, Republic of Korea
| | - Jong Gwang Kim
- Department of Oncology/Hematology, Kyungpook National University Chilgok Hospital, School of Medicine, Kyungpook National University, Daegu, Republic of Korea
| | - Byung Woog Kang
- Department of Oncology/Hematology, Kyungpook National University Chilgok Hospital, School of Medicine, Kyungpook National University, Daegu, Republic of Korea
| | - Jin Ho Baek
- Department of Oncology/Hematology, Kyungpook National University Chilgok Hospital, School of Medicine, Kyungpook National University, Daegu, Republic of Korea
| | - Hyeong Rok Kim
- Department of Surgery, Chonnam National University Hwasun Hospital and Medical School, Hwasun, Republic of Korea
| | - Chang Hyun Kim
- Department of Surgery, Chonnam National University Hwasun Hospital and Medical School, Hwasun, Republic of Korea
| | - Young Jin Kim
- Department of Surgery, St. Carollo General Hospital, Suncheon-si, Republic of Korea
| | - Gyu-Seog Choi
- Colorectal Cancer Center, Kyungpook National University Chilgok Hospital, School of Medicine, Kyungpook National University, Daegu, Republic of Korea
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Cashin PH, Esquivel J, Larsen SG, Liauw W, Alzahrani NA, Morris DL, Kepenekian V, Sourrouille I, Dumont F, Tuech JJ, Ceribelli C, Doussot B, Sgarbura O, Quenet F, Glehen O, Fisher OM. Perioperative chemotherapy in colorectal cancer with peritoneal metastases: A global propensity score matched study. EClinicalMedicine 2023; 55:101746. [PMID: 36457647 PMCID: PMC9706515 DOI: 10.1016/j.eclinm.2022.101746] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/12/2022] [Revised: 10/28/2022] [Accepted: 10/28/2022] [Indexed: 11/27/2022] Open
Abstract
BACKGROUND There is a paucity of studies evaluating perioperative systemic chemotherapy in conjunction with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) in patients with colorectal cancer peritoneal metastases (CRCPM). The aim was to evaluate neoadjuvant and/or adjuvant systemic therapy in CRCPM. METHODS Patients with CRCPM from 39 treatment centres globally from January 1, 1991, to December 31, 2018, who underwent CRS+HIPEC were identified and stratified according to neoadjuvant/adjuvant use. Crude data analysis, propensity score matching (PSM) and Cox-proportional hazard modelling was performed. FINDINGS Of 2093 patients, 1613 were included in neoadjuvant crude evaluation with 708 in the PSM cohort (354 patients/arm). In the adjuvant evaluation, 1176 patients were included in the crude cohort with 778 in the PSM cohort (389 patients/arm). The median overall survival (OS) in the PSM cohort receiving no neoadjuvant vs neoadjuvant therapy was 37.0 months (95% CI: 32.6-42.7) vs 34.7 months (95% CI: 31.2-38.8, HR 1.08 95% CI: 0.88-1.32, p = 0.46). The median OS in the PSM cohort receiving no adjuvant therapy vs adjuvant therapy was 37.0 months (95% CI: 32.9-41.8) vs 45.7 months (95% CI: 38.8-56.2, HR 0.79 95% CI: 0.64-0.97, p = 0.022). Recurrence-free survival did not differ in the neoadjuvant evaluation but differed in the adjuvant evaluation - HR 1.04 (95% CI: 0.87-1.25, p = 0.66) and 0.83 (95% CI: 0.70-0.98, p = 0.03), respectively. Multivariable Cox-proportional hazard modelling in the crude cohorts showed hazard ratio 1.08 (95% CI: 0.92-1.26, p = 0.37) for administering neoadjuvant therapy and 0.86 (95% CI: 0.72-1.03, p = 0.095) for administering adjuvant therapy. INTERPRETATION Neoadjuvant therapy did not confer a benefit to patients undergoing CRS+HIPEC for CRCPM, whereas adjuvant therapy was associated with a benefit in this retrospective setting. FUNDING None.
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Affiliation(s)
- Peter H. Cashin
- Department of Surgical Sciences, Section of Surgery, Uppsala University, Akademiska Sjukhuset, Uppsala 75185, Sweden
- Corresponding author. Associate Professor of Surgery, Residency Director of Surgery, Department of Surgery, HIPEC Team, Section of Colorectal Surgery, Uppsala University Hospital, Akademiska Sjukhuset, Uppsala, Sweden.
| | - Jesus Esquivel
- Division of Surgical Oncology, Beebe Healthcare, Lewes, DE, United States of America
| | - Stein G. Larsen
- Section of Surgical Oncology, Department of Gastroenterological Surgery, Oslo University Hospital, Sognsvannsveien 20, Oslo 0372, Norway
| | - Winston Liauw
- St George & Sutherland Clinical School, UNSW Australia, Sydney, Australia
- Department of Medical Oncology, St George Hospital, Sydney, Australia
| | | | - David L. Morris
- Department of Surgery, St George Hospital, Sydney, Australia
| | - Vahan Kepenekian
- Hôspital Lyon Sud, Hospices Civils de Lyon, Lyon, France
- CICLY, Université Lyon 1, Lyon, France
| | | | - Frédéric Dumont
- Department of Oncological Surgery, Institut de Cancérologie de l’Ouest, St Herblain, France
| | - Jean-Jacques Tuech
- Department of Digestive Surgery, Centre Hospitalo-Universitaire de Rouen, Rouen, France
| | - Cécilia Ceribelli
- Department of Surgery, Centre Hospitalo-Universitaire de l’Archet II, Nice, France
| | - Beranger Doussot
- Department of Digestive Surgery, Centre Hospitalo Universitaire Dijon Bourgogne, Dijon, France
| | - Olivia Sgarbura
- Department of Surgical Oncology, Cancer Institute of Montpellier, University of Montpellier, Montpellier, France
| | - Francois Quenet
- Department of Surgical Oncology, Cancer Institute of Montpellier, University of Montpellier, Montpellier, France
| | - Olivier Glehen
- Hôspital Lyon Sud, Hospices Civils de Lyon, Lyon, France
- CICLY, Université Lyon 1, Lyon, France
| | - Oliver M. Fisher
- Department of Medical Oncology, St George Hospital, Sydney, Australia
- Department of Surgery, St George Hospital, Sydney, Australia
- Notre Dame University School of Medicine, Sydney, Australia
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Baron E, Sardi A, King MC, Nikiforchin A, Lopez-Ramirez F, Nieroda C, Gushchin V, Ledakis P. Adjuvant chemotherapy for high-grade appendiceal cancer after cytoreductive surgery with hyperthermic intraperitoneal chemotherapy. EUROPEAN JOURNAL OF SURGICAL ONCOLOGY 2023; 49:179-187. [PMID: 36253240 DOI: 10.1016/j.ejso.2022.08.022] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2022] [Revised: 07/29/2022] [Accepted: 08/21/2022] [Indexed: 01/24/2023]
Abstract
INTRODUCTION There are no available data on the efficacy of adjuvant chemotherapy (ACT) in stage IVA/B high-grade mucinous appendiceal cancer treated with CRS/HIPEC. We evaluated the association between ACT and survival in this cohort. MATERIALS AND METHODS A single-institution retrospective cohort study using a prospective database was conducted. Stage IVA/B high-grade mucinous appendiceal cancer patients who underwent CRS/HIPEC with CC-0/1 were included. Survival was compared between ACT and no chemotherapy (NoCT) patients. Subgroup analysis was performed with adjustment for confounding variables. RESULTS We identified 180 patients: 77 ACT and 103 NoCT. ACT regimens included 5-FU/capecitabine (13%), oxaliplatin-based (63%), and irinotecan-based (21%), combined with bevacizumab in 27% of cases. Median number of cycles was 9 (IQR: 6-12). Median overall survival (OS) did not significantly differ between ACT and NoCT (53 vs 75 months, p = 0.566). Multivariable Cox regression showed no OS benefit for ACT vs NoCT in patients with neoadjuvant chemotherapy (HR 1.14; 95%CI: 0.38-3.39) or without it (HR 1.33; 95%CI: 0.69-2.57), with signet ring cell (HR 0.89; 95%CI: 0.38-2.06) or other histologies (HR 1.11; 95%CI: 0.50-2.46), positive lymph nodes (HR 1.60; 95%CI: 0.74-3.49), or peritoneal cancer index ≥20 (HR 1.08; 95%CI: 0.55-2.11) after adjusting for other factors. CONCLUSIONS In our cohort, colon-type ACT was not associated with better OS in stage IVA/B mucinous appendiceal cancer after CRS/HIPEC, even after adjusting for confounders. This may be due to different tumor biology than colon cancer or small sample size. Prospective collaborative studies are needed.
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Affiliation(s)
- Ekaterina Baron
- Surgical Oncology Department, The Institute for Cancer Care, Mercy Medical Center, Baltimore, MD, 21202, USA
| | - Armando Sardi
- Surgical Oncology Department, The Institute for Cancer Care, Mercy Medical Center, Baltimore, MD, 21202, USA.
| | - Mary Caitlin King
- Surgical Oncology Department, The Institute for Cancer Care, Mercy Medical Center, Baltimore, MD, 21202, USA
| | - Andrei Nikiforchin
- Surgical Oncology Department, The Institute for Cancer Care, Mercy Medical Center, Baltimore, MD, 21202, USA
| | - Felipe Lopez-Ramirez
- Surgical Oncology Department, The Institute for Cancer Care, Mercy Medical Center, Baltimore, MD, 21202, USA
| | - Carol Nieroda
- Surgical Oncology Department, The Institute for Cancer Care, Mercy Medical Center, Baltimore, MD, 21202, USA
| | - Vadim Gushchin
- Surgical Oncology Department, The Institute for Cancer Care, Mercy Medical Center, Baltimore, MD, 21202, USA
| | - Panayotis Ledakis
- Medical Oncology & Hematology Department, The Institute for Cancer Care, Mercy Medical Center, Baltimore, MD, 21202, USA
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Flood MP, Kong JCH, Wilson K, Mohan H, Waters PS, McCormick JJ, Warrier SK, Tie J, Ramsay R, Michael M, Heriot AG. The Impact of Neoadjuvant Chemotherapy on the Surgical Management of Colorectal Peritoneal Metastases: A Systematic Review and Meta-Analysis. Ann Surg Oncol 2022; 29:6619-6631. [PMID: 35397737 PMCID: PMC9492604 DOI: 10.1245/s10434-022-11699-7] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2021] [Accepted: 03/17/2022] [Indexed: 12/14/2022]
Abstract
Abstract
Background
Cytoreductive surgery (CRS) with or without hyperthermic intraperitoneal chemotherapy (HIPEC) is a well-recognised treatment option for the management of colorectal peritoneal metastases (CRPM). However, incorporating the routine use of neoadjuvant chemotherapy (NAC) into this management plan is controversial.
Methods
A systematic review and meta-analysis were conducted to evaluate the impact of neoadjuvant chemotherapy on perioperative morbidity and mortality, and long-term survival of patients with CRPM undergoing CRS and HIPEC.
Results
Twelve studies met the inclusion criteria (n = 2,463 patients). Ten were retrospective cohort, one was prospective cohort, and one was a prospective randomised by design. Patients who received NAC followed by CRS and HIPEC experienced no difference in major perioperative morbidity and mortality compared with patients who underwent surgery first (SF). There was no difference in overall survival at 3 years, but at 5 years NAC patients had superior survival (relative risk [RR] 1.31; 95% confidence interval [CI] 1.11–1.54, P < 0.001). There were no differences in 1- and 3-year, disease-free survival (DFS) between groups. Study heterogeneity was generally high across all outcome measures.
Conclusions
Patients who received neoadjuvant chemotherapy did not experience any increase in perioperative morbidity or mortality. The potential improvement in 5-year overall survival in patients receiving NAC is based on limited confidence due to several limitations in the data, but not sufficiently enough to curtail its use. The practice of NAC in this setting will remain heterogeneous and guided by retrospective evidence until prospective, randomised data are reported.
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García-Fadrique A, Estevan Estevan R, Sabater Ortí L. Quality Standards for Surgery of Colorectal Peritoneal Metastasis After Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy. Ann Surg Oncol 2021; 29:188-202. [PMID: 34435297 DOI: 10.1245/s10434-021-10642-6] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2021] [Accepted: 07/27/2021] [Indexed: 12/23/2022]
Abstract
BACKGROUND The standardization of surgical outcomes throughout surgical procedures is mandatory. Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS + HIPEC) should provide proficient oncological and surgical outcomes. STUDY DESIGN The aim of this study was to identify clinically relevant quality indicators and their quality standard, and to determine their acceptable quality limit. A systematic review on cytoreductive results from 2000 to 2018 was performed focusing on clinical guidelines, consensus conferences, and publications. After the selection of quality indicators, a systematic review of indexed references was performed in order to calculate the quality standard for each indicator. STUDY SELECTION Unicentric/multicentric series, comparative studies, and clinical trials. Studies were to include outcomes after cytoreduction of colorectal origin and series with more than 50 patients. Quality indicators with at least 10 series were mandatory and objective measurements were also mandatory for inclusion. MAIN OUTCOME MEASUREMENTS Quality indicators selected were 1- to 5-year survival, overall disease-free survival, 1- to 5-year disease-free survival, complete surgical resection, duration of surgery, length of stay, overall morbimortality, major morbidity, re-intervention, postoperative hemorrhage, intestinal fistula, anastomotic leakage, wound infection, postoperative medical complications, overall recurrence, and failure to rescue. RESULTS The most relevant quality indicators and critical quality limits were overall disease-free survival and 5-year overall disease-free survival (14 months and <10 months, and 14% and <4%, respectively), completeness of surgical resection (89% and <80%, respectively), overall mortality (3% and >8%, respectively), overall morbidity (47% and >63%, respectively), failure to rescue (12% and <30%, respectively), reintervention (13 and <22%, respectively), anastomotic leakage (6% and <13%, respectively), and overall recurrence (60% and <74%, respectively). CONCLUSION This is the first study to assess quality standards in CRS + HIPEC for colorectal peritoneal metastases. The current data are of particular relevance for future studies to control the variability of this surgery.
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Affiliation(s)
| | | | - Luis Sabater Ortí
- Hospital Clínico Universitario, Department of Surgery, Biomedical Research Institute INCLIVA, University of Valencia, Valencia, Spain
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Synchronous Liver Resection, Cytoreductive Surgery, and Hyperthermic Intraperitoneal Chemotherapy for Colorectal Liver and Peritoneal Metastases: A Systematic Review and Meta-analysis. Dis Colon Rectum 2021; 64:754-764. [PMID: 33742615 DOI: 10.1097/dcr.0000000000002027] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
BACKGROUND Synchronous liver resection, cytoreductive surgery, and hyperthermic intraperitoneal chemotherapy for colorectal liver and peritoneal metastases have traditionally been contraindicated. More recent clinical practice has begun to promote this aggressive treatment in select patients. OBJECTIVE This study aimed to investigate the perioperative and oncological outcomes of patients undergoing cytoreductive surgery and hyperthermic intraperitoneal chemotherapy, with and without liver resection, in the management of metastatic colorectal cancer. DATA SOURCES Medline, Embase, and Cochrane Library databases were searched up to July 2020. STUDY SELECTION Cohort studies comparing outcomes following cytoreductive surgery and hyperthermic intraperitoneal chemotherapy with and without liver resection for metastatic colorectal cancer were reviewed. No randomized controlled trials were available. INTERVENTION Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy with or without synchronous liver resection were compared. MAIN OUTCOME MEASURES The primary outcome measures were perioperative mortality and major morbidity. Secondary outcomes included 3- and 5-year overall survival and 1- and 3-year disease-free survival. RESULTS Fourteen studies fitted the inclusion criteria, with 8 studies included in the meta-analysis. On pooled analysis, there was no significant difference in perioperative morbidity and mortality between the two groups. Patients that underwent concomitant liver resection had worse 1- and 3-year disease-free survival and 3- and 5-year overall survival. LIMITATIONS Only a limited number of studies were available, with a moderate degree of heterogeneity. CONCLUSIONS The addition of synchronous liver resection to cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for the treatment of resectable metastatic colorectal cancer was not associated with increased perioperative major morbidity and mortality in comparison with cytoreduction and hyperthermic intraperitoneal chemotherapy alone. However, the presence of liver metastases was associated with inferior disease-free and overall survival. These data support the continued practice of liver resection, cytoreductive surgery, and hyperthermic intraperitoneal chemotherapy in the management of select patients with such stage IV disease.
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Outcomes following synchronous liver resection, cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for colorectal liver and peritoneal metastases: A bi-institutional study. Surg Oncol 2021; 37:101553. [PMID: 33839444 DOI: 10.1016/j.suronc.2021.101553] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2021] [Revised: 03/04/2021] [Accepted: 03/26/2021] [Indexed: 01/11/2023]
Abstract
PURPOSE Synchronous liver resection, cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) for colorectal liver (CRLM) and peritoneal metastases (CRPM) has traditionally been contraindicated. However, latest practice promotes specialist, multidisciplinary-led consideration for select patients. This study aimed to evaluate the perioperative and oncological outcomes of synchronous resection in the management of CRLM and CRPM from two tertiary referral centres. METHOD This bi-institutional, retrospective, cohort study included patients undergoing simultaneous liver resection, CRS and HIPEC for metastatic colorectal cancer from 2013 to 2020. Patients treated with ablative liver techniques, staged operative approaches and extra abdominal disease were excluded. Overall survival (OS) and disease-free survival (DFS) rates were assessed. Univariate and multivariate analyses identified variables associated with survival and major morbidity (Clavien-Dindo grade III/IV). RESULTS Twenty-three patients were included. The median peritoneal carcinomatosis index (PCI) was 9 (range 0-22). There were two major liver resections and 21 minor resections. CC-0 resections were achieved in all patients. Major morbidity occurred in 7 patients. There were no deaths at 90 days. PCI was independently associated with morbidity (p = 0.04). PCI >10 (p = 0.069), major morbidity (p = 0.083) and presence of KRAS mutation (p = 0.052) approached significance for poor OS. Median follow up was 21 months (4-54 months). Median OS was 37 months, 3-year survival 54%, and median DFS 18 months. CONCLUSION Synchronous liver resection, cytoreductive surgery and HIPEC is feasible in selected patients with low-volume CRPM and CRLM. Increasing PCI is associated with postoperative major morbidity, and should be considered during operative planning.
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Ezzedine W, Mege D, Aubert M, Duclos J, Le Huu Nho R, Sielezneff I, Pirro N. Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy for resectable peritoneal metastases is feasible in elderly patients. Updates Surg 2021; 73:719-730. [PMID: 33548026 DOI: 10.1007/s13304-020-00966-5] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2020] [Accepted: 12/27/2020] [Indexed: 12/22/2022]
Abstract
The aim is to evaluate the feasibility and the prognosis of cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) for resectable peritoneal metastases (RPM) in elderly patients. Patients who underwent CRS with HIPEC for RPM between 2012 and 2018 in one tertiary reference center were retrospectively included and divided according to the age: Group A (< 65 years) and Group B (≥ 65 years). Postoperative outcomes and survivals were compared. Ninety-five patients were included in Groups A (n = 65) and B (n = 30). The incidence of comorbidities was significantly higher in elderly patients (65 vs 90%, p = 0.01), but RPM characteristics were similar between groups. There was no difference between groups in terms of postoperative results: 30-day major morbidity (33 vs 23%, p = 0.4), 30-day mortality (0 vs 3%, p = 0.3), mean length of stay (26.7 ± 19.4 vs 22.4 ± 10.3 days, p = 0.3) and readmission's rate (15 vs 33%, p = 0.06). The only one significant difference was the 90-day mortality which never occurred before 65 years but in 10% of elderly patients (p = 0.03). There was no difference regarding recurrence's rate (56 vs 37%, p = 0.1), neither 1-, 3- and 5-year overall survival rates (86, 64 and 52% vs 85, 74% and not reached, p = 0.8) and disease-free survival rates (61, 28 and 28% vs 56, 45% and not reached, p = 0.6). CRS with HIPEC is feasible in elderly patients. Since the 90-day mortality appeared to be higher in elderly patients, additional criteria are necessary to improve the selection of elderly patients for this major surgery.
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Affiliation(s)
- Walid Ezzedine
- Department of General and Digestive Surgery, Timone University Hospital, Aix Marseille Univ, APHM, 264 Rue Saint-Pierre, 13005, Marseille, France
| | - Diane Mege
- Department of General and Digestive Surgery, Timone University Hospital, Aix Marseille Univ, APHM, 264 Rue Saint-Pierre, 13005, Marseille, France.
| | - Mathilde Aubert
- Department of General and Digestive Surgery, Timone University Hospital, Aix Marseille Univ, APHM, 264 Rue Saint-Pierre, 13005, Marseille, France
| | - Julie Duclos
- Department of General and Digestive Surgery, Timone University Hospital, Aix Marseille Univ, APHM, 264 Rue Saint-Pierre, 13005, Marseille, France
| | - Rémy Le Huu Nho
- Department of General and Digestive Surgery, Timone University Hospital, Aix Marseille Univ, APHM, 264 Rue Saint-Pierre, 13005, Marseille, France
| | - Igor Sielezneff
- Department of General and Digestive Surgery, Timone University Hospital, Aix Marseille Univ, APHM, 264 Rue Saint-Pierre, 13005, Marseille, France
| | - Nicolas Pirro
- Department of General and Digestive Surgery, Timone University Hospital, Aix Marseille Univ, APHM, 264 Rue Saint-Pierre, 13005, Marseille, France
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Repullo DJ, Barbois S, Leonard D, Bohlok A, Van den Audenaeren ET, Hendlisz A, Van den Eynde M, Donckier V, Kartheuser A, Liberale G. The absence of benefit of perioperative chemotherapy in initially resectable peritoneal metastases of colorectal cancer origin treated with complete cytoreductive surgery and hyperthermic intraperitoneal chemotherapy: A retrospective analysis. Eur J Surg Oncol 2021; 47:1661-1667. [PMID: 33602530 DOI: 10.1016/j.ejso.2021.01.018] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2021] [Revised: 01/21/2021] [Accepted: 01/25/2021] [Indexed: 01/28/2023] Open
Abstract
INTRODUCTION The aim of this study was to compare the outcome of patients with peritoneal metastasis (PM) of colorectal origin treated with complete cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) with or without perioperative systemic chemotherapy (PCT+/PCT-). PATIENTS AND METHODS Retrospective analysis of 125 patients treated with complete CRS (R0/R1) and HIPEC for PM from colorectal origin in two Belgian academic centers between 2008 and 2017. Disease-free survival (DFS) and overall survival (OS) were assessed with regard to PCT. Statistical analyses were adjusted for non-balanced survival risk factors. RESULTS The PCT+ group (n = 67) received at least 5 cycles of PCT and the PCT-group (n = 56) did not receive PCT. The groups were well balanced for all prognostic factors except presentation of synchronous disease (more in PCT+). Survival analysis was adjusted to peritoneal cancer index and presentation of synchronous disease. After a median follow-up of 54±5-months, the 1, 3, 5-years OS in the PCT+ group were 98%, 59% and 35% compared to 97%, 77% and 56% in the PCT-group (HR = 1.46; 95% CI:0.87-2.47; p = 0.155). The 1,3 and 5 years DFS in the PCT+ group were 47%, 13% and 6% compared to 58%, 29% and 26% respectively in the PCT- (HR = 1.22; 95% CI:0.78-1.92; p = 0.376). CONCLUSION This study does not show any clear benefit of PCT in carefully selected patients undergoing R0/R1 CRS and HIPEC for colorectal PM. The ongoing CAIRO6 trial randomizing CRS/HIPEC versus CRS/HIPEC and PCT will probably clarify the role of PCT in patients with resectable PM.
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Affiliation(s)
- Deborah J Repullo
- Department of Surgical Oncology, Institut J. Bordet, Université Libre de Bruxelles, Brussels, Belgium
| | - Sandrine Barbois
- Colorectal Surgery Unit, Department of Abdominal Surgery and Transplantation, Cliniques universitaires Saint Luc, Université Catholique de Louvain, Belgium
| | - Daniel Leonard
- Colorectal Surgery Unit, Department of Abdominal Surgery and Transplantation, Cliniques universitaires Saint Luc, Université Catholique de Louvain, Belgium
| | - Ali Bohlok
- Department of Surgical Oncology, Institut J. Bordet, Université Libre de Bruxelles, Brussels, Belgium
| | - Estelle T Van den Audenaeren
- Colorectal Surgery Unit, Department of Abdominal Surgery and Transplantation, Cliniques universitaires Saint Luc, Université Catholique de Louvain, Belgium
| | - Alain Hendlisz
- Department of Medical Oncology, Institut J. Bordet, Université Libre de Bruxelles, Brussels, Belgium
| | - Marc Van den Eynde
- Department of Medical Oncology, Cliniques universitaires Saint Luc, Université Catholique de Louvain, Belgium
| | - Vincent Donckier
- Department of Surgical Oncology, Institut J. Bordet, Université Libre de Bruxelles, Brussels, Belgium
| | - Alex Kartheuser
- Colorectal Surgery Unit, Department of Abdominal Surgery and Transplantation, Cliniques universitaires Saint Luc, Université Catholique de Louvain, Belgium
| | - Gabriel Liberale
- Department of Surgical Oncology, Institut J. Bordet, Université Libre de Bruxelles, Brussels, Belgium.
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Zhou S, Feng Q, Zhang J, Zhou H, Jiang Z, Liu Z, Zheng Z, Chen H, Wang Z, Liang J, Pei W, Liu Q, Zhou Z, Wang X. High-grade postoperative complications affect survival outcomes of patients with colorectal Cancer peritoneal metastases treated with Cytoreductive surgery and Hyperthermic Intraperitoneal chemotherapy. BMC Cancer 2021; 21:41. [PMID: 33413223 PMCID: PMC7791857 DOI: 10.1186/s12885-020-07756-7] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2020] [Accepted: 12/21/2020] [Indexed: 02/06/2023] Open
Abstract
Background This study aimed to evaluate the impact of postoperative complications on long-term survival in patients with peritoneal metastasis (PM) arising from colorectal cancer (CRC) treated with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). Methods Patients with PM arising from CRC treated with CRS and HIPEC were systematically reviewed at the China National Cancer Center and Huanxing Cancer Hospital from June 2017 to June 2019. High-grade complications that occurred within 30 days were defined as grade 3 to 4 events according to the Common Terminology Criteria for Adverse Events (CTCAE) classification. Univariate and multivariable Cox regression models for overall survival were created. Predictors of high-grade postoperative complications were evaluated with univariate and multivariate logistic regression analyses. Results In all, 86 consecutive cases were included in this study. Forty-one patients (47.7%) developed postoperative complications, while 22 patients (25.6%) experienced high-grade complications. No mortality occurred during the postoperative period. The median survival of all patients was 25 months, and the estimated 3-year overall survival (OS) rate was 35.0%. In the multivariable Cox regression analysis, a high peritoneal carcinomatosis index (PCI) score (HR, 1.07, 95% CI, 1.01–1.14; P=0.015) and grade 3–4 postoperative complications (HR, 1.86, 95% CI, 1.22–3.51; P=0.044) correlated with worse overall survival. High estimated blood loss (OR, 1.01, 95% CI, 1.01–1.02; P< 0.001) was identified as an independent risk factor for developing high-grade complications. Conclusion Careful patient selection, high levels of technical skill and improved perioperative management are crucial to ensure patient survival benefits after CRS+HIPEC.
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Affiliation(s)
- Sicheng Zhou
- Department of Colorectal Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China
| | - Qiang Feng
- Department of Colorectal Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China
| | - Jing Zhang
- Department of Abdominal Surgery, Huanxing Cancer Hospital, Beijing, 100122, China
| | - Haitao Zhou
- Department of Colorectal Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China
| | - Zheng Jiang
- Department of Colorectal Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China
| | - Zheng Liu
- Department of Colorectal Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China
| | - Zhaoxu Zheng
- Department of Colorectal Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China
| | - Haipeng Chen
- Department of Colorectal Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China
| | - Zheng Wang
- Department of Colorectal Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China
| | - Jianwei Liang
- Department of Colorectal Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China.
| | - Wei Pei
- Department of Colorectal Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China.
| | - Qian Liu
- Department of Colorectal Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China
| | - Zhixiang Zhou
- Department of Colorectal Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China
| | - Xishan Wang
- Department of Colorectal Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China
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15
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Brind'Amour A, Dubé P, Tremblay JF, Soucisse ML, Mack L, Bouchard-Fortier A, McCart JA, Govindarajan A, Bischof D, Haase E, Giacomantonio C, Hebbard P, Younan R, MacNeill A, Boulanger-Gobeil C, Sidéris L. Canadian guidelines on the management of colorectal peritoneal metastases. Curr Oncol 2020; 27:e621-e631. [PMID: 33380878 PMCID: PMC7755452 DOI: 10.3747/co.27.6919] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
Modern management of colorectal cancer (crc) with peritoneal metastasis (pm) is based on a combination of cytoreductive surgery (crs), systemic chemotherapy, and hyperthermic intraperitoneal chemotherapy (hipec). Although the role of hipec has recently been questioned with respect to results from the prodige 7 trial, the role and benefit of a complete crs were confirmed, as observed with a 41-month gain in median survival in that study, and 15% of patients remaining disease-free at 5 years. Still, crc with pm is associated with a poor prognosis, and good patient selection is essential. Many questions about the optimal management approach for such patients remain, but all patients with pm from crc should be referred to, or discussed with, a pm surgical oncologist, because cure is possible. The objective of the present guideline is to offer a practical approach to the management of pm from crc and to reflect on the new practice standards set by recent publications on the topic.
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Affiliation(s)
- A Brind'Amour
- Department of Surgery, Hôpital Maisonneuve-Rosemont, Montreal
- Department of Surgery, chu de Québec-Université Laval, Quebec City
| | - P Dubé
- Department of Surgery, Hôpital Maisonneuve-Rosemont, Montreal
- Department of Surgery, University of Montreal, Montreal, QC
| | - J F Tremblay
- Department of Surgery, Hôpital Maisonneuve-Rosemont, Montreal
- Department of Surgery, University of Montreal, Montreal, QC
| | - M L Soucisse
- Department of Surgery, Hôpital Maisonneuve-Rosemont, Montreal
- Department of Surgery, University of Montreal, Montreal, QC
| | - L Mack
- Department of Surgery, University of Calgary, Calgary, AB
| | | | - J A McCart
- Department of Surgery, Mount Sinai Hospital, University of Toronto, Toronto, ON
- Department of Surgery, University of Toronto, Toronto, ON
| | - A Govindarajan
- Department of Surgery, Mount Sinai Hospital, University of Toronto, Toronto, ON
- Department of Surgery, University of Toronto, Toronto, ON
| | - D Bischof
- Department of Surgery, Mount Sinai Hospital, University of Toronto, Toronto, ON
- Department of Surgery, University of Toronto, Toronto, ON
| | - E Haase
- Department of Surgery, University of Alberta, Edmonton, AB
| | | | - P Hebbard
- Department of Surgery, University of Manitoba, Winnipeg, MB
| | - R Younan
- Department of Surgery, University of Montreal, Montreal, QC
- Department of Surgery, Centre Hospitalier de l'Université de Montréal, Montreal, QC
| | - A MacNeill
- Department of Surgery, University of British Columbia, Vancouver, BC
| | | | - L Sidéris
- Department of Surgery, Hôpital Maisonneuve-Rosemont, Montreal
- Department of Surgery, University of Montreal, Montreal, QC
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16
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Narasimhan V, Tan S, Kong J, Pham T, Michael M, Ramsay R, Warrier S, Heriot A. Prognostic factors influencing survival in patients undergoing cytoreductive surgery with hyperthermic intraperitoneal chemotherapy for isolated colorectal peritoneal metastases: a systematic review and meta-analysis. Colorectal Dis 2020; 22:1482-1495. [PMID: 32027455 DOI: 10.1111/codi.15003] [Citation(s) in RCA: 33] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/28/2019] [Accepted: 12/15/2019] [Indexed: 12/13/2022]
Abstract
AIM Peritoneal metastases from colorectal cancer confer the worst survival among all metastatic sites. The adoption of cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) can offer selected patients with isolated colorectal peritoneal metastases (CRPM) a favourable long-term survival. There are numerous factors postulated to influence survival in patients undergoing CRS and HIPEC. The aim of this study was to identify the key perioperative prognostic factors that influence survival in patients undergoing CRS and HIPEC for isolated CRPM. METHOD A systematic review and meta-analysis were conducted to evaluate prognostic factors influencing survival in patients undergoing CRS and HIPEC for isolated CRPM. RESULTS Thirty-three studies fitted the inclusion criteria for the systematic review, with 25 studies included in the meta-analysis. On pooled analysis, incomplete cytoreduction, increasing peritoneal carcinoma index (PCI) and lymph node involvement were significantly associated with a worse survival. Additionally, a rectal primary [hazard ratio (HR) 1.93, 95% CI 1.10-3.37], adjuvant chemotherapy (HR 0.71, 95% CI 0.54-0.93) and perioperative grade III/IV morbidity (HR 1.59, 95% CI 1.17-2.16) were also found to significantly influence survival. Notably, tumour differentiation and signet ring cell histology did not influence survival on pooled analysis. CONCLUSION This meta-analysis confirms that in patients undergoing CRS and HIPEC for isolated CRPM, incomplete cytoreduction, high PCI and lymph node involvement have a negative influence on survival. In addition, a rectal primary, adjuvant chemotherapy use and grade III/IV morbidity are important factors that also significantly influence survival.
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Affiliation(s)
- V Narasimhan
- Department of Surgical Oncology, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia
- Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, Victoria, Australia
| | - S Tan
- Department of Surgical Oncology, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia
| | - J Kong
- Department of Surgical Oncology, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia
- Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, Victoria, Australia
| | - T Pham
- Department of Surgical Oncology, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia
| | - M Michael
- Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia
| | - R Ramsay
- Department of Surgical Oncology, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia
- Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, Victoria, Australia
| | - S Warrier
- Department of Surgical Oncology, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia
| | - A Heriot
- Department of Surgical Oncology, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia
- Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, Victoria, Australia
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17
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Survival after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for colorectal peritoneal metastases: A systematic review and discussion of latest controversies. Surgeon 2020; 19:310-320. [PMID: 33023847 DOI: 10.1016/j.surge.2020.08.016] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2020] [Revised: 08/14/2020] [Accepted: 08/31/2020] [Indexed: 12/24/2022]
Abstract
INTRODUCTION Peritoneal metastases confer the worst survival amongst all sites of metastatic colorectal cancer. The adoption of cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) has become an option for patients with isolated colorectal peritoneal metastases (CRPM). The aim of this study was to evaluate the outcomes following CRS and HIPEC for CRPM from published high volume cohort studies and to highlight the latest controversies and future directions of CRPM treatment. MATERIALS AND METHODS A systematic review was performed on published studies on the treatment outcomes of CRS and HIPEC for colorectal peritoneal metastases. RESULTS Twenty studies met the inclusion criteria for the systematic review. The median survival for all patients ranged from 14.6 to 60.1 months. The 5-year overall survival ranged from 23.4% to 52%. For patients with complete cytoreduction, the median survival was 25 to 49 months. Major morbidity and mortality ranged from 15.1% to 47.2% and 0% to 4.5%, respectively. CONCLUSION CRS and HIPEC for the treatment of CRPM is safe and current evidence suggests it improves both median and disease-free survival. However, the efficacy of intraperitoneal chemotherapy, in particular oxaliplatin, has recently come under scrutiny. Accordingly, higher quality evidence is urgently required to contribute to multidisciplinary and international consensus on CRPM treatment strategies.
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Rovers KP, Bakkers C, van Erning FN, Burger JWA, Nienhuijs SW, Simkens GAAM, Creemers GJM, Hemmer PHJ, Punt CJA, Lemmens VEPP, Tanis PJ, de Hingh IHJT. Adjuvant Systemic Chemotherapy vs Active Surveillance Following Up-front Resection of Isolated Synchronous Colorectal Peritoneal Metastases. JAMA Oncol 2020; 6:e202701. [PMID: 32672798 DOI: 10.1001/jamaoncol.2020.2701] [Citation(s) in RCA: 27] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
Importance To date, there are no data on the value of adjuvant systemic chemotherapy following up-front resection of isolated synchronous colorectal peritoneal metastases. Objective To assess the association between adjuvant systemic chemotherapy and overall survival following up-front resection of isolated synchronous colorectal peritoneal metastases. Design, Setting, and Participants In this population-based, observational cohort study using nationwide data from the Netherlands Cancer Registry (diagnoses between January 1, 2005, and December 31, 2017; follow-up until January 31, 2019), 393 patients with isolated synchronous colorectal peritoneal metastases who were alive 3 months after up-front complete cytoreductive surgery with hyperthermic intraperitoneal chemotherapy were included. Patients allocated to the adjuvant systemic chemotherapy group were matched (1:1) with those allocated to the active surveillance group by propensity scores based on patient-, tumor-, and treatment-level covariates. Exposures Adjuvant systemic chemotherapy, defined as systemic chemotherapy without targeted therapy, starting within 3 months postoperatively. Main Outcomes and Measures Overall survival was compared between matched groups using Cox proportional hazards regression analysis adjusted for residual imbalance. A landmark analysis was performed by excluding patients who died within 6 months postoperatively. A sensitivity analysis was performed to adjust for unmeasured confounding by major postoperative morbidity. Results Of 393 patients (mean [SD] age, 61 [10] years; 181 [46%] men), 172 patients (44%) were allocated to the adjuvant systemic chemotherapy group. After propensity score matching of 142 patients in the adjuvant systemic chemotherapy group with 142 patients in the active surveillance group, adjuvant systemic chemotherapy was associated with improved overall survival compared with active surveillance (median, 39.2 [interquartile range, 21.1-111.1] months vs 24.8 [interquartile range, 15.0-58.4] months; adjusted hazard ratio [aHR], 0.66; 95% CI, 0.49-0.88; P = .006), which remained consistent after excluding patients who died within 6 months postoperatively (aHR, 0.68; 95% CI, 0.50-0.93; P = .02) and after adjustment for major postoperative morbidity (aHR, 0.71; 95% CI, 0.53-0.95). Conclusions and Relevance Findings of this study suggest that in patients undergoing up-front resection of isolated synchronous colorectal peritoneal metastases, adjuvant systemic chemotherapy appeared to be associated with improved overall survival. Although randomized trials are needed to address the influence of potential residual confounding and allocation bias on this association, results of this study may be used for clinical decision-making in this patient group for whom no data are available.
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Affiliation(s)
- Koen P Rovers
- Department of Surgery, Catharina Cancer Institute, Eindhoven, the Netherlands
| | - Checca Bakkers
- Department of Surgery, Catharina Cancer Institute, Eindhoven, the Netherlands
| | - Felice N van Erning
- Department of Research, Netherlands Comprehensive Cancer Organization, Utrecht, the Netherlands
| | - Jacobus W A Burger
- Department of Surgery, Catharina Cancer Institute, Eindhoven, the Netherlands
| | - Simon W Nienhuijs
- Department of Surgery, Catharina Cancer Institute, Eindhoven, the Netherlands
| | - Geert A A M Simkens
- Department of Surgery, Catharina Cancer Institute, Eindhoven, the Netherlands
| | - Geert-Jan M Creemers
- Department of Medical Oncology, Catharina Cancer Institute, Eindhoven, the Netherlands
| | - Patrick H J Hemmer
- Department of Surgery, University Medical Centre Groningen, Groningen, the Netherlands
| | - Cornelis J A Punt
- Department of Medical Oncology, Amsterdam University Medical Centers, University of Amsterdam, Cancer Center Amsterdam, Amsterdam, the Netherlands
| | - Valery E P P Lemmens
- Department of Research, Netherlands Comprehensive Cancer Organization, Utrecht, the Netherlands.,Department of Public Health, Erasmus University Medical Centre, Rotterdam, the Netherlands
| | - Pieter J Tanis
- Department of Surgery, Amsterdam University Medical Centers, University of Amsterdam, Cancer Center Amsterdam, Amsterdam, the Netherlands
| | - Ignace H J T de Hingh
- Department of Surgery, Catharina Cancer Institute, Eindhoven, the Netherlands.,Department of Research, Netherlands Comprehensive Cancer Organization, Utrecht, the Netherlands.,GROW-School for Oncology and Development Biology, Maastricht University, Maastricht, the Netherlands
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Verheij FS, Bakkers C, van Eden WJ, Aalbers AGJ, Nienhuijs SW, Jóźwiak K, de Hingh IHJT, Kok NFM. Comparison of the Peritoneal Cancer Index and Dutch region count as tools to stage patients with peritoneal metastases of colorectal cancer. BJS Open 2020; 4:1153-1161. [PMID: 32573969 PMCID: PMC7709381 DOI: 10.1002/bjs5.50313] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2020] [Accepted: 05/19/2020] [Indexed: 01/06/2023] Open
Abstract
BACKGROUND Extent of peritoneal metastases (PM) is among the most powerful prognostic factors for survival after cytoreductive surgery (CRS). This study aimed to compare the Peritoneal Cancer Index (PCI) and the Dutch region count as tools for staging PM of colorectal cancer. The Dutch region count is a simpler classification that distinguishes seven rather than 13 abdominal regions. Presence or absence of PM is recorded. METHODS This was a retrospective cohort study in two tertiary referral centres in the Netherlands. Consecutive patients with colorectal PM who were intentionally treated with CRS and subsequent hyperthermic intraperitoneal chemotherapy in 2016 and 2017 were included. The PCI and Dutch region count were both recorded during laparotomy. Correlation between scoring tools was calculated using Spearman's rank correlation coefficient. Diagnostic values were calculated for different cut-off values of the PCI, alongside the Dutch region count. The correlation of both scores was determined for the exploration and validation cohorts separately. RESULTS In the exploration and validation cohorts, 73 and 85 patients respectively were included. Spearman's correlation coefficients of 0·897 and 0·961 were observed for continuous scores of the Dutch region count and PCI in the exploration and validation group respectively. A cut-off value of 20 for the PCI score and 5 for the Dutch region count showed 91·9 and 94·5 per cent sensitivity, and 81·8 and 91·7 per cent specificity, respectively. CONCLUSION The Dutch region count correlated well with the PCI score, and may help to simplify reporting of the extent of peritoneal disease.
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Affiliation(s)
- F. S. Verheij
- Departments of Surgical OncologyAmsterdamthe Netherlands
| | - C. Bakkers
- Department of Surgical OncologyCatharina HospitalEindhoventhe Netherlands
| | - W. J. van Eden
- Departments of Surgical OncologyAmsterdamthe Netherlands
| | | | - S. W. Nienhuijs
- Department of Surgical OncologyCatharina HospitalEindhoventhe Netherlands
| | - K. Jóźwiak
- Epidemiology and BiostatisticsNetherlands Cancer InstituteAmsterdamthe Netherlands
| | - I. H. J. T. de Hingh
- Department of Surgical OncologyCatharina HospitalEindhoventhe Netherlands
- GROW, School for Oncology and Development BiologyMaastricht UniversityMaastrichtthe Netherlands
| | - N. F. M. Kok
- Departments of Surgical OncologyAmsterdamthe Netherlands
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Baaten ICPA, West NP, Quyn AJ, Seymour MT, Seligmann JF. Colorectal cancer peritoneal metastases: Biology, treatment and next steps. EUROPEAN JOURNAL OF SURGICAL ONCOLOGY 2020; 46:675-683. [PMID: 31806517 DOI: 10.1016/j.ejso.2019.10.035] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2019] [Revised: 10/18/2019] [Accepted: 10/28/2019] [Indexed: 01/22/2023]
Abstract
The presence of peritoneal metastases in patients with advanced colorectal cancer is associated with poor prognosis but the mechanisms for this are unclear. This review summarises the current knowledge of the pathophysiology, clinical features, prevalence, prognosis, and molecular biology of peritoneal metastases and the risk factors for the development of peritoneal metastases following resection of a primary colorectal tumour. Furthermore, the evidence for treatment strategies are described including cytoreductive surgery, hyperthermic intraperitoneal chemotherapy, early post-operative intraperitoneal chemotherapy, sequential post-operative intraperitoneal chemotherapy and emerging novel strategies. Active areas of research should include the identification of individuals at high risk of peritoneal metastases after curative resection of primary tumour, development of a surveillance program for high-risk patients, optimisation of systematic therapies and further investigation of the use of intraperitoneal chemotherapy.
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Affiliation(s)
- Ilona C P A Baaten
- Leeds Institute of Clinical Trial Research, University of Leeds, Leeds, United Kingdom.
| | - Nicholas P West
- Leeds Institute of Medical Research at St. James's, University of Leeds, St James's University Hospital, Beckett Street, Leeds, United Kingdom.
| | - Aaron J Quyn
- Leeds Institute of Medical Research at St. James's, University of Leeds, St James's University Hospital, Beckett Street, Leeds, United Kingdom.
| | - Matthew T Seymour
- Leeds Institute of Medical Research at St. James's, University of Leeds, St James's University Hospital, Beckett Street, Leeds, United Kingdom.
| | - Jenny F Seligmann
- Leeds Institute of Medical Research at St. James's, University of Leeds, St James's University Hospital, Beckett Street, Leeds, United Kingdom.
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Narasimhan V, Warrier S, Michael M, McCormick J, Ramsay R, Lynch C, Heriot A. Perceptions in the management of colorectal peritoneal metastases: A bi-national survey of colorectal surgeons. Pleura Peritoneum 2019; 4:20190022. [PMID: 31799373 PMCID: PMC6881667 DOI: 10.1515/pp-2019-0022] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2019] [Accepted: 10/03/2019] [Indexed: 12/16/2022] Open
Abstract
BACKGROUND There is great variability in the uptake of cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) in the management of colorectal peritoneal metastases (CRPM) in Australia and New Zealand. This study aims to provide a snapshot of perceptions among colorectal surgeons in the management of CRPM. METHODS A structured ten-question online survey was sent to all colorectal surgeons, with three questions on clinical experience and demographics, one on health economics and six on hypothetical clinical scenarios. Scores were collated and reported based on Likert scales. RESULTS Eighty-one respondents (36.2%) completed the survey. Most surgeons (66.7%) strongly disagreed with offering CRS and HIPEC at all hospitals. The majority (87.7%) agreed that CRS and HIPEC offered a higher survival benefit than systemic chemotherapy in pseudomyxoma peritonei (PMP), and 69.1% in CRPM (comparators: 60.5% ovarian cancer, 14.8% gastric cancer). There were mixed strategies in managing low-volume, isolated peritoneal recurrences. The majority did not recommend second-look laparoscopy, but favoured operative management of Krukenberg tumours. In the presence of incidental peritoneal metastases, only 29.6% favoured biopsy only and referring the patient to a peritoneal disease centre. CONCLUSIONS Response rate was relatively low. In Australia and New Zealand, colorectal surgeons see a strong role for CRS and HIPEC in the management of PMP and CRPM. The role of "second look" surgery in high-risk cases is controversial and not supported. Krukenberg tumours are viewed as surgical disease. Regular updates and collaboration with peritoneal centres may help surgeons stay abreast with latest evidence in the field.
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Affiliation(s)
- Vignesh Narasimhan
- Department of Surgery, Peter MacCallum Cancer Centre, Melbourne, Australia
| | - Satish Warrier
- Department of Surgery, Peter MacCallum Cancer Centre, Melbourne, Australia
| | - Michael Michael
- Department of Surgery, Peter MacCallum Cancer Centre, Melbourne, Australia
| | - Jacob McCormick
- Department of Surgery, Peter MacCallum Cancer Centre, Melbourne, Australia
| | - Robert Ramsay
- Department of Surgery, Peter MacCallum Cancer Centre, Melbourne, Australia
| | - Craig Lynch
- Department of Surgery, Peter MacCallum Cancer Centre, Melbourne, Australia
| | - Alexander Heriot
- Department of Surgery, Peter MacCallum Cancer Centre, Melbourne, Australia
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Rovers KP, Bakkers C, Simkens GAAM, Burger JWA, Nienhuijs SW, Creemers GJM, Thijs AMJ, Brandt-Kerkhof ARM, Madsen EVE, Ayez N, de Boer NL, van Meerten E, Tuynman JB, Kusters M, Sluiter NR, Verheul HMW, van der Vliet HJ, Wiezer MJ, Boerma D, Wassenaar ECE, Los M, Hunting CB, Aalbers AGJ, Kok NFM, Kuhlmann KFD, Boot H, Chalabi M, Kruijff S, Been LB, van Ginkel RJ, de Groot DJA, Fehrmann RSN, de Wilt JHW, Bremers AJA, de Reuver PR, Radema SA, Herbschleb KH, van Grevenstein WMU, Witkamp AJ, Koopman M, Haj Mohammad N, van Duyn EB, Mastboom WJB, Mekenkamp LJM, Nederend J, Lahaye MJ, Snaebjornsson P, Verhoef C, van Laarhoven HWM, Zwinderman AH, Bouma JM, Kranenburg O, van 't Erve I, Fijneman RJA, Dijkgraaf MGW, Hemmer PHJ, Punt CJA, Tanis PJ, de Hingh IHJT. Perioperative systemic therapy and cytoreductive surgery with HIPEC versus upfront cytoreductive surgery with HIPEC alone for isolated resectable colorectal peritoneal metastases: protocol of a multicentre, open-label, parallel-group, phase II-III, randomised, superiority study (CAIRO6). BMC Cancer 2019; 19:390. [PMID: 31023318 PMCID: PMC6485075 DOI: 10.1186/s12885-019-5545-0] [Citation(s) in RCA: 90] [Impact Index Per Article: 15.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2019] [Accepted: 03/28/2019] [Indexed: 02/08/2023] Open
Abstract
Background Upfront cytoreductive surgery with HIPEC (CRS-HIPEC) is the standard treatment for isolated resectable colorectal peritoneal metastases (PM) in the Netherlands. This study investigates whether addition of perioperative systemic therapy to CRS-HIPEC improves oncological outcomes. Methods This open-label, parallel-group, phase II-III, randomised, superiority study is performed in nine Dutch tertiary referral centres. Eligible patients are adults who have a good performance status, histologically or cytologically proven resectable PM of a colorectal adenocarcinoma, no systemic colorectal metastases, no systemic therapy for colorectal cancer within six months prior to enrolment, and no previous CRS-HIPEC. Eligible patients are randomised (1:1) to perioperative systemic therapy and CRS-HIPEC (experimental arm) or upfront CRS-HIPEC alone (control arm) by using central randomisation software with minimisation stratified by a peritoneal cancer index of 0–10 or 11–20, metachronous or synchronous PM, previous systemic therapy for colorectal cancer, and HIPEC with oxaliplatin or mitomycin C. At the treating physician’s discretion, perioperative systemic therapy consists of either four 3-weekly neoadjuvant and adjuvant cycles of capecitabine with oxaliplatin (CAPOX), six 2-weekly neoadjuvant and adjuvant cycles of 5-fluorouracil/leucovorin with oxaliplatin (FOLFOX), or six 2-weekly neoadjuvant cycles of 5-fluorouracil/leucovorin with irinotecan (FOLFIRI) followed by four 3-weekly (capecitabine) or six 2-weekly (5-fluorouracil/leucovorin) adjuvant cycles of fluoropyrimidine monotherapy. Bevacizumab is added to the first three (CAPOX) or four (FOLFOX/FOLFIRI) neoadjuvant cycles. The first 80 patients are enrolled in a phase II study to explore the feasibility of accrual and the feasibility, safety, and tolerance of perioperative systemic therapy. If predefined criteria of feasibility and safety are met, the study continues as a phase III study with 3-year overall survival as primary endpoint. A total of 358 patients is needed to detect the hypothesised 15% increase in 3-year overall survival (control arm 50%; experimental arm 65%). Secondary endpoints are surgical characteristics, major postoperative morbidity, progression-free survival, disease-free survival, health-related quality of life, costs, major systemic therapy related toxicity, and objective radiological and histopathological response rates. Discussion This is the first randomised study that prospectively compares oncological outcomes of perioperative systemic therapy and CRS-HIPEC with upfront CRS-HIPEC alone for isolated resectable colorectal PM. Trial registration Clinicaltrials.gov/NCT02758951, NTR/NTR6301, ISRCTN/ISRCTN15977568, EudraCT/2016–001865-99.
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Affiliation(s)
- Koen P Rovers
- Department of Surgery, Catharina Hospital, PO Box 1350, 5602 ZA, Eindhoven, Netherlands
| | - Checca Bakkers
- Department of Surgery, Catharina Hospital, PO Box 1350, 5602 ZA, Eindhoven, Netherlands
| | - Geert A A M Simkens
- Department of Surgery, Catharina Hospital, PO Box 1350, 5602 ZA, Eindhoven, Netherlands
| | - Jacobus W A Burger
- Department of Surgery, Catharina Hospital, PO Box 1350, 5602 ZA, Eindhoven, Netherlands
| | - Simon W Nienhuijs
- Department of Surgery, Catharina Hospital, PO Box 1350, 5602 ZA, Eindhoven, Netherlands
| | - Geert-Jan M Creemers
- Department of Medical Oncology, Catharina Hospital, PO Box 1350, 5602, Eindhoven, ZA, Netherlands
| | - Anna M J Thijs
- Department of Medical Oncology, Catharina Hospital, PO Box 1350, 5602, Eindhoven, ZA, Netherlands
| | | | - Eva V E Madsen
- Department of Surgical Oncology, Erasmus Medical Centre, PO Box 2040, 3000, Rotterdam, CA, Netherlands
| | - Ninos Ayez
- Department of Surgical Oncology, Erasmus Medical Centre, PO Box 2040, 3000, Rotterdam, CA, Netherlands
| | - Nadine L de Boer
- Department of Surgical Oncology, Erasmus Medical Centre, PO Box 2040, 3000, Rotterdam, CA, Netherlands
| | - Esther van Meerten
- Department of Medical Oncology, Erasmus MC Cancer Institute, PO Box 2040, 3000, Rotterdam, CA, Netherlands
| | - Jurriaan B Tuynman
- Department of Surgery, Amsterdam University Medical Centres, Location VUMC, PO Box 7057, 1007, Amsterdam, MB, Netherlands
| | - Miranda Kusters
- Department of Surgery, Amsterdam University Medical Centres, Location VUMC, PO Box 7057, 1007, Amsterdam, MB, Netherlands
| | - Nina R Sluiter
- Department of Surgery, Amsterdam University Medical Centres, Location VUMC, PO Box 7057, 1007, Amsterdam, MB, Netherlands
| | - Henk M W Verheul
- Department of Medical Oncology, Amsterdam University Medical Centres, Location VUMC, PO Box 7057, 1007, Amsterdam, MB, Netherlands
| | - Hans J van der Vliet
- Department of Medical Oncology, Amsterdam University Medical Centres, Location VUMC, PO Box 7057, 1007, Amsterdam, MB, Netherlands
| | - Marinus J Wiezer
- Department of Surgery, St. Antonius Hospital, PO Box 2500, 3430, Nieuwegein, EM, Netherlands
| | - Djamila Boerma
- Department of Surgery, St. Antonius Hospital, PO Box 2500, 3430, Nieuwegein, EM, Netherlands
| | - Emma C E Wassenaar
- Department of Surgery, St. Antonius Hospital, PO Box 2500, 3430, Nieuwegein, EM, Netherlands
| | - Maartje Los
- Department of Medical Oncology, St. Antonius Hospital, PO Box 2500, 3430, Nieuwegein, EM, Netherlands
| | - Cornelis B Hunting
- Department of Medical Oncology, St. Antonius Hospital, PO Box 2500, 3430, Nieuwegein, EM, Netherlands
| | - Arend G J Aalbers
- Department of Surgical Oncology, Netherlands Cancer Institute, PO Box 90203, 1006, Amsterdam, BE, Netherlands
| | - Niels F M Kok
- Department of Surgical Oncology, Netherlands Cancer Institute, PO Box 90203, 1006, Amsterdam, BE, Netherlands
| | - Koert F D Kuhlmann
- Department of Surgical Oncology, Netherlands Cancer Institute, PO Box 90203, 1006, Amsterdam, BE, Netherlands
| | - Henk Boot
- Department of Gastrointestinal Oncology, Netherlands Cancer Institute, PO Box 90203, 1006, Amsterdam, BE, Netherlands
| | - Myriam Chalabi
- Department of Gastrointestinal Oncology, Netherlands Cancer Institute, PO Box 90203, 1006, Amsterdam, BE, Netherlands
| | - Schelto Kruijff
- Department of Surgery, University Medical Centre Groningen, PO Box 30001, 9700 RB, Groningen, RB, Netherlands
| | - Lukas B Been
- Department of Surgery, University Medical Centre Groningen, PO Box 30001, 9700 RB, Groningen, RB, Netherlands
| | - Robert J van Ginkel
- Department of Surgery, University Medical Centre Groningen, PO Box 30001, 9700 RB, Groningen, RB, Netherlands
| | - Derk Jan A de Groot
- Department of Medical Oncology, University Medical Centre Groningen, PO Box 30001, 9700, Groningen, RB, Netherlands
| | - Rudolf S N Fehrmann
- Department of Medical Oncology, University Medical Centre Groningen, PO Box 30001, 9700, Groningen, RB, Netherlands
| | - Johannes H W de Wilt
- Department of Surgery, Radboud University Medical Centre, PO Box 9101, 6500, Nijmegen, HB, Netherlands
| | - Andreas J A Bremers
- Department of Surgery, Radboud University Medical Centre, PO Box 9101, 6500, Nijmegen, HB, Netherlands
| | - Philip R de Reuver
- Department of Surgery, Radboud University Medical Centre, PO Box 9101, 6500, Nijmegen, HB, Netherlands
| | - Sandra A Radema
- Department of Medical Oncology, Radboud University Medical Centre, PO Box 9101, 6500, Nijmegen, HB, Netherlands
| | - Karin H Herbschleb
- Department of Medical Oncology, Radboud University Medical Centre, PO Box 9101, 6500, Nijmegen, HB, Netherlands
| | | | - Arjen J Witkamp
- Department of Surgery, University Medical Centre Utrecht, PO Box 85500, 3508, Utrecht, GA, Netherlands
| | - Miriam Koopman
- Department of Medical Oncology, University Medical Centre Utrecht, PO Box 85500, 3508, Utrecht, GA, Netherlands
| | - Nadia Haj Mohammad
- Department of Medical Oncology, University Medical Centre Utrecht, PO Box 85500, 3508, Utrecht, GA, Netherlands
| | - Eino B van Duyn
- Department of Surgery, Medisch Spectrum Twente, PO Box 50000, 7500, Enschede, KA, Netherlands
| | - Walter J B Mastboom
- Department of Surgery, Medisch Spectrum Twente, PO Box 50000, 7500, Enschede, KA, Netherlands
| | - Leonie J M Mekenkamp
- Department of Medical Oncology, Medisch Spectrum Twente, PO Box 50000, 7500, Enschede, KA, Netherlands
| | - Joost Nederend
- Department of Radiology, Catharina Hospital, PO Box 1350, 5602, Eindhoven, ZA, Netherlands
| | - Max J Lahaye
- Department of Radiology, Netherlands Cancer Institute, PO Box 90203, 1006, Amsterdam, BE, Netherlands
| | - Petur Snaebjornsson
- Department of Pathology, Netherlands Cancer Institute, PO Box 90203, 1006, Amsterdam, BE, Netherlands
| | - Cornelis Verhoef
- Department of Surgical Oncology, Erasmus Medical Centre, PO Box 2040, 3000, Rotterdam, CA, Netherlands
| | - Hanneke W M van Laarhoven
- Department of Medical Oncology, Amsterdam University Medical Centres, Location AMC, PO Box 22660, 1100, Amsterdam, DD, Netherlands
| | - Aeilko H Zwinderman
- Department of Clinical Epidemiology, Biostatistics & Bioinformatics, Amsterdam University Medical Centres, Location AMC, PO Box 22660, 1100, Amsterdam, DD, Netherlands
| | - Jeanette M Bouma
- Clinical Trial Department, Netherlands Comprehensive Cancer Organisation (IKNL), PO Box 19079, 3501, Utrecht, DB, Netherlands
| | - Onno Kranenburg
- UMC Utrecht Cancer Centre, University Medical Centre Utrecht, PO Box 85500, 3508, Utrecht, GA, Netherlands
| | - Iris van 't Erve
- Department of Pathology, Netherlands Cancer Institute, PO Box 90203, 1006, Amsterdam, BE, Netherlands
| | - Remond J A Fijneman
- Department of Pathology, Netherlands Cancer Institute, PO Box 90203, 1006, Amsterdam, BE, Netherlands
| | - Marcel G W Dijkgraaf
- Department of Clinical Epidemiology, Biostatistics & Bioinformatics, Amsterdam University Medical Centres, Location AMC, PO Box 22660, 1100, Amsterdam, DD, Netherlands
| | - Patrick H J Hemmer
- Department of Surgery, University Medical Centre Groningen, PO Box 30001, 9700 RB, Groningen, RB, Netherlands
| | - Cornelis J A Punt
- Department of Medical Oncology, Amsterdam University Medical Centres, Location AMC, PO Box 22660, 1100, Amsterdam, DD, Netherlands
| | - Pieter J Tanis
- Department of Surgery, Amsterdam University Medical Centres, Location AMC, PO Box 22660, 1100, Amsterdam, DD, Netherlands
| | - Ignace H J T de Hingh
- Department of Surgery, Catharina Hospital, PO Box 1350, 5602 ZA, Eindhoven, Netherlands.
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Intraoperative macroscopic tumour consistency is associated with overall survival after cytoreductive surgery and intraperitoneal chemotherapy for appendiceal adenocarcinoma with peritoneal metastases: A retrospective observational study. Am J Surg 2019; 217:704-712. [DOI: 10.1016/j.amjsurg.2018.12.037] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2018] [Revised: 12/17/2018] [Accepted: 12/18/2018] [Indexed: 12/14/2022]
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Bhatt A, Mehta SS, Zaveri S, Rajan F, Ray M, Sethna K, Katdare N, Patel MD, Kammar P, Prabhu R, Sinukumar S, Mishra S, Rangarajan B, Rangole A, Damodaran D, Penumadu P, Ganesh M, Peedicayil A, Raj H, Seshadri R. Treading the beaten path with old and new obstacles: a report from the Indian HIPEC registry. Int J Hyperthermia 2018; 35:361-369. [PMID: 30300029 DOI: 10.1080/02656736.2018.1503345] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022] Open
Abstract
BACKGROUND The Indian HIPEC registry is a self-funded registry instituted by a group of Indian surgeons for patients with peritoneal metastases (PM) undergoing surgical treatment. This work was performed to • Evaluate outcomes of cytoreductive surgery ± HIPEC in patients enrolled in the registry. • Identify operational problems. METHODS A retrospective analysis of patients enrolled in the registry from March 2016 to September 2017 was performed. An online survey was performed to study the surgeons' attitudes and existing practices pertaining to the registry and identify operational problems. RESULTS During the study period, 332 patients were enrolled in 8 participating centres. The common indication was ovarian cancer for three centres and pseudomyxoma peritonei for three others. The median PCI ranged from 3 to 23. A CC-0/1 resection was obtained in 94.7%. There was no significant difference in the morbidity (p = .25) and mortality (p = .19) rates between different centres. There was a high rate of failure-to-rescue (19.3%) patients with complications and the survival in patients with colorectal PM was inferior. A lack of dedicated personnel for data collection and entry was the main reason for only 10/43 surgeons contributing data. The other problem was the lack of complete electronic medical record systems at all centres. CONCLUSIONS These results validate existing practices and identify country-specific problems that need to be addressed. Despite operational problems, the registry is an invaluable tool for audit and research. It shows the feasibility of fruitful collaboration between surgeons in the absence of any regulatory body or funding for the project.
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Affiliation(s)
- Aditi Bhatt
- a Department of Surgical Oncology , Fortis Hospital , Bangalore , India
| | - Sanket S Mehta
- b Department of Peritoneal surface oncology , Saifee Hospital , Mumbai , India
| | - Shabber Zaveri
- c Department of Surgical Oncology , Manipal Hospital , Bangalore , India
| | - Firoz Rajan
- d Department of Surgical Oncology , Kovai Medical Center , Coimbatore , India
| | - Mukurdipi Ray
- e Department of Surgical Oncology , All India Institute of Medical Sciences , New Delhi , India
| | - Kayomarz Sethna
- f Department of Surgery , Lokmanya Tilak Municipal medical college and general hospital , Mumbai , India
| | - Ninad Katdare
- g Department of Surgical Oncology , SL Raheja hospital , Mumbai , India
| | - Mahesh D Patel
- h Department of Surgical Oncology , Zydus Hospital , Ahmedabad , India
| | - Praveen Kammar
- i Department of Surgical Oncology , Global hospitals , Hyderabad , India
| | - Robin Prabhu
- a Department of Surgical Oncology , Fortis Hospital , Bangalore , India
| | - Snita Sinukumar
- j Department of Surgical oncology , Jehangir Hospital , Pune , India
| | - Suniti Mishra
- k Department of Pathology , Fortis Hospital , Bangalore , India
| | - Bharath Rangarajan
- l Department of Medical oncology , Kovai Medical center , Coimbatore , India
| | - Ashvin Rangole
- m Department of Surgical oncology , CHL, CBCC cancer center , Indore , India
| | - Dileep Damodaran
- n Department of Surgical oncology , MVR cancer center and research Institute , Calicut , India
| | - Prasanth Penumadu
- o Department of Surgical oncology , Jawarharlal Institute of Postgraduate Medical Education and Research (JIPMER) , Puducherry , India
| | - Mandakulutur Ganesh
- p Department of Surgical Oncology , Vaidehi Institute of Medical sciences , Bangalore , India
| | - Abraham Peedicayil
- q Department of Gynecologic Oncology , Christian Medical College , Vellore , India
| | - Hemant Raj
- r Department of Surgical Oncology , Cancer Institute (WIA) , Chennai , India
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Glockzin G, Zeman F, Croner RS, Königsrainer A, Pelz J, Ströhlein MA, Rau B, Arnold D, Koller M, Schlitt HJ, Piso P. Perioperative Systemic Chemotherapy, Cytoreductive Surgery, and Hyperthermic Intraperitoneal Chemotherapy in Patients With Colorectal Peritoneal Metastasis: Results of the Prospective Multicenter Phase 2 COMBATAC Trial. Clin Colorectal Cancer 2018; 17:285-296. [PMID: 30131226 DOI: 10.1016/j.clcc.2018.07.011] [Citation(s) in RCA: 30] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2018] [Revised: 07/21/2018] [Accepted: 07/24/2018] [Indexed: 01/29/2023]
Abstract
BACKGROUND Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) as parts of an interdisciplinary treatment concept including systemic chemotherapy can improve survival of selected patients with peritoneal metastatic colorectal cancer (pmCRC). Nevertheless, the sequence of the therapeutic options is still a matter of debate. Thus, the COMBATAC (COMBined Anticancer Treatment of Advanced Colorectal cancer) trial was conducted to evaluate a combined treatment regimen consisting of preoperative systemic polychemotherapy + cetuximab followed by CRS + HIPEC and postoperative systemic polychemotherapy + cetuximab. PATIENTS AND METHODS The COMBATAC trial is a prospective, multicenter, open-label, single-arm, single-stage phase 2 trial. Twenty-six patients with synchronous or metachronous colorectal or appendiceal peritoneal carcinomatosis were included. Enrollment was terminated prematurely by the sponsor because of slow recruitment. Progression-free survival as primary end point and overall survival were estimated by the Kaplan-Meier method. Also evaluated were morbidity according to Common Terminology Criteria for Adverse Events v4.0 and feasibility of the combined treatment concept. RESULTS Median progression-free survival for the intention-to-treat population (n = 25) was 14.9 months. Median overall survival was not reached during the study duration. Ninety-two adverse events were documented in 16 patients, including 14 serious adverse events in 9 patients. The overall morbidity rate was 64%, and the grade 3/4 morbidity rate was 44%. Of all grade 3/4 morbidity events, 36.4% were related to systemic chemotherapy and 22.7% to surgery, whereas 40.9% were not directly related. There was no treatment-related mortality. CONCLUSION The results of the COMBATAC trial show that the multimodal treatment concept consisting of perioperative systemic chemotherapy and CRS + HIPEC is safe and feasible. Progression-free survival in selected patients with colorectal or appendiceal peritoneal metastasis might be improved.
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Affiliation(s)
- Gabriel Glockzin
- Department of Surgery, University Medical Center Regensburg, Regensburg, Germany; Department of Surgery, Klinikum Bogenhausen, Munich, Germany.
| | - Florian Zeman
- Center for Clinical Studies, University Medical Center Regensburg, Regensburg, Germany
| | - Roland S Croner
- Department of Surgery, University of Erlangen-Nuremberg, Erlangen, Germany; Department of Surgery, University Hospital Magdeburg, Magdeburg, Germany
| | - Alfred Königsrainer
- Department of Surgery, University of Tübingen, Comprehensive Cancer Center, Tübingen, Germany
| | - Jörg Pelz
- Department of Surgery, University Hospital Würzburg, Würzburg, Germany; Department of Surgery, St Bernward Hospital, Hildesheim, Germany
| | - Michael A Ströhlein
- Department of Abdominal, Vascular and Transplant Surgery, Cologne-Merheim Medical Center, Witten/Herdecke University, Cologne, Germany
| | - Beate Rau
- Department of Surgery, Campus Virchow and Mitte, Charité, Universitätsmedizin Berlin, Berlin, Germany
| | - Dirk Arnold
- Asklepios Tumor Center Hamburg, AK Altona, Department of Oncology, Hamburg, Germany
| | - Michael Koller
- Center for Clinical Studies, University Medical Center Regensburg, Regensburg, Germany
| | - Hans J Schlitt
- Department of Surgery, University Medical Center Regensburg, Regensburg, Germany
| | - Pompiliu Piso
- Department of Surgery, University Medical Center Regensburg, Regensburg, Germany; Department of Surgery, Krankenhaus Barmherzige Brüder Regensburg, Regensburg, Germany
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Goéré D, Sourrouille I, Gelli M, Benhaim L, Faron M, Honoré C. Peritoneal Metastases from Colorectal Cancer. Surg Oncol Clin N Am 2018; 27:563-583. [DOI: 10.1016/j.soc.2018.02.011] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
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Hammoudi N, Eveno C, Lambert J, Maillet M, Glehen O, Goere D, Lourenco N, Allez M, Aparicio T, Pocard M, Gornet JM. Inflammatory bowel disease drastically affects the prognosis of patients treated for peritoneal metastases with combined cytoreductive surgery and hyperthermic intraperitoneal chemotherapy: A multicenter study. Eur J Surg Oncol 2018; 44:799-804. [PMID: 29650418 DOI: 10.1016/j.ejso.2018.03.006] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2017] [Revised: 03/02/2018] [Accepted: 03/07/2018] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND Complete cytoreductive surgery (CCRS) followed by hyperthermic intraperitoneal chemotherapy (HIPEC) is a validated treatment in selected patients with peritoneal metastases (PM) of intestinal origin. There is an increased risk of Colorectal Cancer (CRC) and Small Bowel Adenocarcinoma (SBA) in Inflammatory Bowel Disease (IBD). The feasibility and benefit of that surgical approach in IBD patients is unknown. METHODS IBD patients with operated PM complicating CRC or SBA were extracted from a French national multicenter prospective database of patients who underwent surgery for PM in HIPEC expert centers from 1995 to 2016. IBD patients who underwent CCRS plus HIPEC were compared with a cohort of 234 patients who had the same surgery for sporadic colon cancer. RESULTS 14 patients (male 57%, median age 40 years, 12 Crohn's disease) with CRC (n = 7) and SBA (n = 7) were included. CCRS followed by HIPEC (oxaliplatin 72.7%) was performed in 11 cases (median peritoneal cancer index 7; range 1-30). The control group had the same characteristics except an older age at HIPEC (56.52 vs 45.74; p = 0.003). Overall survival (HR = 4.47; 90% CI, 1.91 to 10.49), Relapse Free Survival (HR = 2.31; 90% CI, 1.17 to 4.56) and Peritoneal Recurrence Free Survival (HR = 3.30; 90% CI, 1.59 to 6.85) were significantly lower in IBD patients. Six of the 11 patients presented major surgical morbidity with no impact on post-operative treatment. CONCLUSION CCRS followed by HIPEC is less effective in IBD patients with resectable PM complicating CRC or SBA. More careful selection of those patients is needed.
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Affiliation(s)
- Nassim Hammoudi
- Department of Gastroenterology, AP-HP Hôpital Saint Louis, Paris, France
| | - Clarisse Eveno
- Surgical Oncologic and Digestive Unit, Hôpital Lariboisière, Paris, France; Université Paris - Denis Diderot, Paris, France
| | - Jérôme Lambert
- Université Paris - Denis Diderot, Paris, France; Service de Biostatistiques, Hôpital Saint-Louis, Paris, France
| | - Marianne Maillet
- Department of Gastroenterology, AP-HP Hôpital Saint Louis, Paris, France; Department of Digestive Surgery, Centre Hospitalier Lyon-Sud, Lyon, France
| | - Olivier Glehen
- Department of Digestive Surgery, Centre Hospitalier Lyon-Sud, Lyon, France
| | - Diane Goere
- Department of Surgical Oncology, Institut Gustave Roussy, Villejuif, France
| | - Nelson Lourenco
- Department of Gastroenterology, AP-HP Hôpital Saint Louis, Paris, France
| | - Matthieu Allez
- Department of Gastroenterology, AP-HP Hôpital Saint Louis, Paris, France; Université Paris - Denis Diderot, Paris, France
| | - Thomas Aparicio
- Department of Gastroenterology, AP-HP Hôpital Saint Louis, Paris, France; Université Paris - Denis Diderot, Paris, France
| | - Marc Pocard
- Surgical Oncologic and Digestive Unit, Hôpital Lariboisière, Paris, France; Université Paris - Denis Diderot, Paris, France
| | - Jean-Marc Gornet
- Department of Gastroenterology, AP-HP Hôpital Saint Louis, Paris, France.
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Rovers KP, de Bree E, Yonemura Y, de Hingh IH. Treatment of peritoneal metastases from small bowel adenocarcinoma. Int J Hyperthermia 2017; 33:571-578. [DOI: 10.1080/02656736.2016.1266700] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Affiliation(s)
- Koen P. Rovers
- Department of Surgical Oncology, Catharina Hospital, Eindhoven, the Netherlands
| | - Eelco de Bree
- Department of Surgical Oncology, Medical School of Crete University Hospital, Heraklion, Greece
| | - Yutaka Yonemura
- Asian and Japanese School of Peritoneal Surface Oncology, Kyoto, Japan
| | - Ignace H. de Hingh
- Department of Surgical Oncology, Catharina Hospital, Eindhoven, the Netherlands
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Huang CQ, Min Y, Wang SY, Yang XJ, Liu Y, Xiong B, Yonemura Y, Li Y. Cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy improves survival for peritoneal carcinomatosis from colorectal cancer: a systematic review and meta-analysis of current evidence. Oncotarget 2017; 8:55657-55683. [PMID: 28903452 PMCID: PMC5589691 DOI: 10.18632/oncotarget.17497] [Citation(s) in RCA: 86] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2016] [Accepted: 01/24/2017] [Indexed: 12/14/2022] Open
Abstract
Objectives The therapeutic efficacy of cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) for patients with peritoneal carcinomatosis (PC) from colorectal cancer (CRC) is still under debate. This meta-analysis and systematic review of published literature on this comprehensive strategy aims to evaluate its efficacy on CRC patients with PC. Methods A systemic review with meta-analysis of published literatures on treatment of CRS plus HIPEC for patients with PC from CRC was performed. In addition, a summary of study results of published literatures concerning CRS plus HIPEC treating patients with PC from CRC was also conducted. Results A total of 76 studies were selected, including 1 randomized controlled trial, 14 non-randomized controlled studies, and 61 non-controlled studies. The pooled hazard ratios (HRs) for overall survival (OS) in the 15 researches for meta-analysis was 2.67 (95% CI, 2.21-3.23, I2= 0%, P < 0.00001), and no significant evidence of publication bias was found. The difference of chemotherapy regimens of HIPEC was not associated with OS and DFS (disease-free survival) after CRS and HIPEC, with no significant difference of heterogeneity (P = 0.27, I2 = 24.1%). In both groups of mitomycin C based HIPEC group and oxaliplatin group, patients received HIPEC had significant better survival (P < 0.00001). The mean mortality and morbidity for HIPEC program were 2.8% and 33.0%, respectively. Conclusions This meta-analysis revealed that comprehensive therapeutic strategy of CRS plus HIPEC could bring survival benefit for selected patients with PC from CRC with acceptable safety.
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Affiliation(s)
- Chao-Qun Huang
- Department of Gastrointestinal Surgery, Zhongnan Hospital of Wuhan University, Hubei Cancer Clinical Study Center & Hubei Key Laboratory of Tumor Biological Behaviors, Wuhan Clinical Research Center for Peritoneal Carcinomatosis, Wuhan, P.R. China
| | - Yao Min
- Department of Ophthalmology, Central Hospital of Wuhan Affiliated to Tongji Medical College of Huazhong University of Science and Technology, Wuhan, P.R. China
| | - Shu-Yi Wang
- Department of Gastrointestinal Surgery, Zhongnan Hospital of Wuhan University, Hubei Cancer Clinical Study Center & Hubei Key Laboratory of Tumor Biological Behaviors, Wuhan Clinical Research Center for Peritoneal Carcinomatosis, Wuhan, P.R. China
| | - Xiao-Jun Yang
- Department of Gastrointestinal Surgery, Zhongnan Hospital of Wuhan University, Hubei Cancer Clinical Study Center & Hubei Key Laboratory of Tumor Biological Behaviors, Wuhan Clinical Research Center for Peritoneal Carcinomatosis, Wuhan, P.R. China
| | - Yang Liu
- NPO to Support Peritoneal Surface Malignancy Treatment, Osaka, Japan
| | - Bin Xiong
- Department of Gastrointestinal Surgery, Zhongnan Hospital of Wuhan University, Hubei Cancer Clinical Study Center & Hubei Key Laboratory of Tumor Biological Behaviors, Wuhan Clinical Research Center for Peritoneal Carcinomatosis, Wuhan, P.R. China
| | - Yutaka Yonemura
- NPO to Support Peritoneal Surface Malignancy Treatment, Osaka, Japan
| | - Yan Li
- Department of Gastrointestinal Surgery, Zhongnan Hospital of Wuhan University, Hubei Cancer Clinical Study Center & Hubei Key Laboratory of Tumor Biological Behaviors, Wuhan Clinical Research Center for Peritoneal Carcinomatosis, Wuhan, P.R. China.,Department of Peritoneal Cancer Surgery, Beijing Shijitan Hospital of the Capital Medical University, Beijing, P.R. China
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Klaver CEL, Stam R, Sloothaak DAM, Crezee J, Bemelman WA, Punt CJA, Tanis PJ. Colorectal cancer at high risk of peritoneal metastases: long term outcomes of a pilot study on adjuvant laparoscopic HIPEC and future perspectives. Oncotarget 2017; 8:51200-51209. [PMID: 28881641 PMCID: PMC5584242 DOI: 10.18632/oncotarget.17158] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2016] [Accepted: 03/10/2017] [Indexed: 12/12/2022] Open
Abstract
Objective Early detection of peritoneal metastases (PM) of colorectal cancer (CRC) is difficult and treatment options at a clinically overt stage are limited. Potentially, adjuvant laparoscopic hyperthermic intraperitoneal chemotherapy (HIPEC) is of value. The aim of this study was to present long term oncological outcomes of a pilot study on adjuvant HIPEC to reduce development of PMCRC, with systematic review of literature. Methods Long term oncological outcomes of ten patients who underwent laparoscopic HIPEC within eight weeks after resection of primary CRC in the pilot study were retrospectively collected. A systematic search of literature was performed on studies describing the use of HIPEC in patients with CRC at high risk of developing PM. Results The median follow-up was 54 months (range 49-63). All patients were alive at the last follow-up moment and none of them had developed PM. Two patients had developed pulmonary metastases. Systematic review revealed five small cohort studies, including two matched comparisons. Peritoneal recurrences were found in 0% to 9% after adjuvant HIPEC, which was 28% and 43% in the two control groups, respectively. Disease free and overall survival were significantly higher in favour of HIPEC. Conclusion Long term follow-up of ten patients included in a pilot study on adjuvant HIPEC revealed no peritoneal recurrences. This result is in line with other published pilot studies, a promising observation. However, the outcomes of the Dutch randomized COLOPEC trial and similar trials worldwide should be awaited for definitive conclusions on the effectiveness of adjuvant HIPEC.
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Affiliation(s)
- Charlotte E L Klaver
- Department of Surgery, Academic Medical Center, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands
| | - Roos Stam
- Department of Surgery, Academic Medical Center, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands
| | - Didi A M Sloothaak
- Department of Surgery, Academic Medical Center, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands
| | - Johannes Crezee
- Department of Radiation Oncology, Academic Medical Center, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands
| | - Willem A Bemelman
- Department of Surgery, Academic Medical Center, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands
| | - Cornelis J A Punt
- Department of Medical Oncology, Academic Medical Center, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands
| | - Pieter J Tanis
- Department of Surgery, Academic Medical Center, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands
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Rovers KP, Simkens GA, Punt CJ, van Dieren S, Tanis PJ, de Hingh IH. Perioperative systemic therapy for resectable colorectal peritoneal metastases: Sufficient evidence for its widespread use? A critical systematic review. Crit Rev Oncol Hematol 2017; 114:53-62. [PMID: 28477747 DOI: 10.1016/j.critrevonc.2017.03.028] [Citation(s) in RCA: 44] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2016] [Revised: 01/17/2017] [Accepted: 03/22/2017] [Indexed: 12/16/2022] Open
Abstract
BACKGROUND/PURPOSE Despite its widespread use, no randomised studies have investigated the value of perioperative systemic therapy as adjunct to cytoreduction and HIPEC for colorectal peritoneal metastases. This systematic review evaluated the available evidence, which consists of non-randomised studies only. METHODS A systematic search identified studies that investigated the influence of neoadjuvant, adjuvant, or perioperative systemic therapy on overall survival (OS). RESULTS The 11 included studies (n=1708) were clinically heterogeneous and subject to selection bias. Studies on neoadjuvant systemic therapy revealed OS benefit (n=3), no OS benefit (n=1), and superiority of chemotherapy with bevacizumab vs. chemotherapy (n=2). Studies on adjuvant systemic therapy showed no OS benefit (n=3). Studies on perioperative systemic therapy demonstrated OS benefit (n=1), and superiority of modern vs. conventional systemic therapy(n=1). CONCLUSION Significant limitations of available evidence question the widespread use of perioperative systemic therapy in this setting, stress the need for randomised studies, and impede conclusions regarding optimal timing and regimens. Included studies may suggest a survival benefit of neoadjuvant systemic therapy.
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Affiliation(s)
- Koen P Rovers
- Department of Surgical Oncology, Catharina Hospital, Eindhoven, The Netherlands
| | - Geert A Simkens
- Department of Surgical Oncology, Catharina Hospital, Eindhoven, The Netherlands
| | - Cornelis J Punt
- Department of Medical Oncology, Academic Medical Centre, Amsterdam, The Netherlands
| | - Susan van Dieren
- Department of Surgical Oncology, Academic Medical Centre, Amsterdam, The Netherlands
| | - Pieter J Tanis
- Department of Surgical Oncology, Academic Medical Centre, Amsterdam, The Netherlands
| | - Ignace H de Hingh
- Department of Surgical Oncology, Catharina Hospital, Eindhoven, The Netherlands.
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Kok NFM, de Hingh IHJT. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for peritoneal metastases of colorectal origin. Br J Surg 2017; 104:313-315. [PMID: 28112791 DOI: 10.1002/bjs.10422] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2016] [Accepted: 10/05/2016] [Indexed: 11/12/2022]
Abstract
Weak evidence base for clinical trials
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Affiliation(s)
- N F M Kok
- Department of Surgical Oncology, Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands
| | - I H J T de Hingh
- Department of Surgery, Catharina Hospital, Michelangelolaan 2, 5623 EJ, Eindhoven, The Netherlands
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McAuliffe JC, Nash GM. “Adjuvant” Hyperthermic Intraperitoneal Chemotherapy: A Call to Action. Ann Surg Oncol 2016; 24:11-12. [DOI: 10.1245/s10434-016-5496-5] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2016] [Indexed: 11/18/2022]
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Glockzin G, Schlitt HJ, Piso P. Therapeutic options for peritoneal metastasis arising from colorectal cancer. World J Gastrointest Pharmacol Ther 2016; 7:343-352. [PMID: 27602235 PMCID: PMC4986391 DOI: 10.4292/wjgpt.v7.i3.343] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/29/2016] [Revised: 06/22/2016] [Accepted: 07/13/2016] [Indexed: 02/06/2023] Open
Abstract
Peritoneal metastasis is a common sign of advanced tumor stage, tumor progression or tumor recurrence in patients with colorectal cancer. Due to the improvement of systemic chemotherapy, the development of targeted therapy and the introduction of additive treatment options such as cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC), the therapeutic approach to peritoneal metastatic colorectal cancer (pmCRC) has changed over recent decades, and patient survival has improved. Moreover, in contrast to palliative systemic chemotherapy or best supportive care, the inclusion of CRS and HIPEC as inherent components of a multidisciplinary treatment regimen provides a therapeutic approach with curative intent. Although CRS and HIPEC are increasingly accepted as the standard of care for selected patients and have become part of numerous national and international guidelines, the individual role, optimal timing and ideal sequence of the different systemic, local and surgical treatment options remains a matter of debate. Ongoing and future randomized controlled clinical trials may help clarify the impact of the different components, allow for further improvement of patient selection and support the standardization of oncologic treatment regimens for pmCRC. The addition of further therapeutic options such as neoadjuvant intraperitoneal chemotherapy or pressurized intraperitoneal aerosol chemotherapy, should be investigated to optimize therapeutic regimens and further improve the oncological outcome.
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Devilee RA, Simkens GA, van Oudheusden TR, Rutten HJ, Creemers GJ, Ten Tije AJ, de Hingh IH. Increased Survival of Patients with Synchronous Colorectal Peritoneal Metastases Receiving Preoperative Chemotherapy Before Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy. Ann Surg Oncol 2016; 23:2841-8. [PMID: 27044447 DOI: 10.1245/s10434-016-5214-3] [Citation(s) in RCA: 36] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2015] [Indexed: 12/29/2022]
Abstract
BACKGROUND Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS + HIPEC) can result in long-term survival for selected patients with colorectal peritoneal metastases (PM). Most patients are additionally treated with systemic chemotherapy, but timing (adjuvant vs. preoperative) varies between treatment centers. This study aimed to compare short- and long-term outcomes for patients with synchronous colorectal PM undergoing CRS + HIPEC who received preoperative or adjuvant chemotherapy. METHODS This study enrolled patients with synchronous colorectal PM who underwent macroscopically complete or near complete CRS + HIPEC. Data were collected from a prospective database containing all patients between 2007 and 2014. Perioperative outcome and survival were compared between patients who underwent adjuvant chemotherapy (adjuvant strategy [AS]) and those who had preoperative chemotherapy followed by adjuvant systemic chemotherapy if possible (preoperative strategy [PS]). RESULTS The study enrolled 91 patients, 25 (28 %) of whom received preoperative chemotherapy. The peritoneal cancer index (PCI) score was lower and the operation length shorter for the patients receiving preoperative chemotherapy (both p = 0.02). The complication rates were comparable between the two groups. The median survival after diagnosis was 38.6 months in the AS group, whereas median survival was not reached in the PS group (p < 0.01). The 3-year overall survival rates were 50 and 89 %, respectively. After correction for other significant prognostic factors, preoperative chemotherapy was independently associated with improved survival (HR 0.23; 95 % confidence interval, 0.07-0.75; p = 0.01). CONCLUSION Treatment with preoperative chemotherapy was associated with improved long-term survival after CRS + HIPEC compared with adjuvant chemotherapy. Ideally, a randomized controlled trial should be performed to investigate the optimal timing of systemic chemotherapy for colorectal PM patients.
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Affiliation(s)
- R A Devilee
- Department of Surgical Oncology, Catharina Hospital, Eindhoven, The Netherlands.
| | - G A Simkens
- Department of Surgical Oncology, Catharina Hospital, Eindhoven, The Netherlands
| | - T R van Oudheusden
- Department of Surgical Oncology, Catharina Hospital, Eindhoven, The Netherlands
| | - H J Rutten
- Department of Surgical Oncology, Catharina Hospital, Eindhoven, The Netherlands
| | - G J Creemers
- Department of Medical Oncology, Catharina Hospital, Eindhoven, The Netherlands
| | - A J Ten Tije
- Department of Medical Oncology, Amphia Hospital, Breda, The Netherlands
| | - I H de Hingh
- Department of Surgical Oncology, Catharina Hospital, Eindhoven, The Netherlands
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