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Ray MD, Kapoor R, Bn N. Multimodal management of peritoneal sarcomatosis in uterine sarcoma: Long term outcomes from a single institute in India. Eur J Obstet Gynecol Reprod Biol 2025; 311:114042. [PMID: 40359870 DOI: 10.1016/j.ejogrb.2025.114042] [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: 03/21/2025] [Revised: 05/06/2025] [Accepted: 05/09/2025] [Indexed: 05/15/2025]
Abstract
OBJECTIVE To assess the outcomes of cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) in peritoneal sarcomatosis (PS) from uterine sarcoma at a tertiary oncology center in India. METHODS A retrospective analysis of uterine sarcoma patients with PS who underwent CRS + HIPEC. Key outcomes included survival, completeness of cytoreduction (CC score), and postoperative morbidity. RESULTS Median patient age was 53 years, with uterine leiomyosarcoma and endometrial stromal sarcoma as the predominant histology. All patients received preoperative chemotherapy, mainly gemcitabine/docetaxel or ifosfamide. The median Peritoneal Carcinomatosis Index (PCI) was 12, with 85 % of patients having PCI < 15. Complete cytoreduction (CC-0) was achieved in 94 %. Median overall survival (OS) was 34 months, with 1-year, 3-year, and 5-year OS rates of 78 %, 53 %, and 35 %. Disease recurrence remained high (67 %), with a median progression-free survival (PFS) of 14 months. CONCLUSION CRS + HIPEC is a promising therapeutic approach for select uterine sarcoma patients with PS, offering high cytoreduction rates and extended survival. Further studies are needed to optimize patient selection and refine treatment protocols.
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Affiliation(s)
- M D Ray
- Department of Surgical Oncology, All India Institute of Medical Sciences, New Delhi, India.
| | - Rohan Kapoor
- Department of Surgical Oncology, All India Institute of Medical Sciences, New Delhi, India
| | - Nikhil Bn
- Department of Surgical Oncology, All India Institute of Medical Sciences, New Delhi, India
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Sigler GI, Murtha J, Varley PR. Diagnostic Advances and Novel Therapeutics in Peritoneal Metastasis. Surg Oncol Clin N Am 2025; 34:173-194. [PMID: 40015798 DOI: 10.1016/j.soc.2024.12.005] [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: 03/01/2025]
Abstract
Appropriate assessment of disease burden in patients with peritoneal surface malignancy (PSM) is critical for treatment decision-making, and conventional cross-sectional imaging (computed tomography and/or MRI) often underestimates burden of disease. Advances in imaging for PSM include novel functional imaging modalities that target cells unique to the tumor microenvironment. Novel alternative methods of diagnosis and disease monitoring are also potentially applicable to management of PSM. These include forms of "liquid biopsy" targeting circulating tumor DNA. Novel regional therapies include both new therapeutic agents (immune-based and nanoparticle-based), as well as new methods of delivery such as pressurized intraperitoneal aerosolized chemotherapy.
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Affiliation(s)
- Gregory I Sigler
- Division of Surgical Oncology, Department of General Surgery, Complex General Surgical Oncology, University of Wisconsin School of Medicine and Public Health, 600 Highland Avenue, Mail Code 7375, Madison, WI 53792, USA
| | - Jacqueline Murtha
- Department of General Surgery, General Surgery, University of Wisconsin School of Medicine and Public Health, 600 Highland Avenue, Mail Code 7375, Madison, WI 53792, USA
| | - Patrick R Varley
- Division of Surgical Oncology, Department of General Surgery, University of Wisconsin School of Medicine and Public Health, 600 Highland Avenue, Mail Code 7375, Madison, WI 53792, USA; William S. Middleton Memorial Veterans Affairs Hospital, Madison, WI, USA.
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Hamm JJM, van den Berg R, Andrinopoulou ER, Zwanenburg ES, Musters GD, Tanis PJ, Arjona-Sanchez A. Adjuvant hyperthermic intraperitoneal chemotherapy in patients with colon cancer at high risk of peritoneal metastases: individual patient data meta-analysis. Br J Surg 2025; 112:znaf076. [PMID: 40296220 PMCID: PMC12037274 DOI: 10.1093/bjs/znaf076] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/24/2024] [Revised: 02/28/2025] [Accepted: 03/14/2025] [Indexed: 04/30/2025]
Abstract
BACKGROUND About a quarter of patients with locally advanced colon cancer (pT4) develop locoregional recurrence, including peritoneal metastases. The aim of this individual patient data meta-analysis (IPDMA) was to evaluate the efficacy of adjuvant hyperthermic intraperitoneal chemotherapy (HIPEC) with regard to reducing the locoregional recurrence rate in the overall population and high-risk subgroups of patients with locally advanced colon cancer. METHODS A systematic literature search was conducted in July 2024 to identify RCTs on adjuvant HIPEC in addition to routine adjuvant systemic chemotherapy in locally advanced colon carcinoma. An IPDMA was performed, with the locoregional recurrence rate as the primary endpoint and disease-free survival (DFS) and overall survival (OS) as secondary endpoints. RESULTS The search identified two trials (COLOPEC and HIPECT4). Individual patient data were pooled for 386 patients, of whom 189 patients received adjuvant HIPEC and 197 patients constituted the control group. The median follow-up was 36 (interquartile range 32-60) months. A modified intention-to-treat analysis showed a 36-month locoregional recurrence rate of 16.0% for HIPEC patients and 21.2% for control patients (P = 0.295). Predefined subgroup analyses revealed a significant reduction in locoregional recurrence after HIPEC in patients with right-sided tumours (HR 0.56 (95% c.i. 0.48 to 0.67)) (P < 0.001). No significant differences in survival were found for the overall study population; low event rates in subgroups did not allow for survival analyses. CONCLUSION Adjuvant HIPEC significantly reduced the locoregional recurrence rate in right-sided locally advanced colon cancer, but not in the overall study population. Definitive conclusions on DFS and OS require longer follow-up.
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Affiliation(s)
- Julie J M Hamm
- Department of Surgical Oncology and Gastrointestinal Surgery, Erasmus University Medical Centre, Rotterdam, The Netherlands
| | - Rudolf van den Berg
- Department of Surgery, Erasmus University Medical Centre, Rotterdam, The Netherlands
| | | | - E Sophie Zwanenburg
- Department of Surgery, Amsterdam University Medical Centre, University of Amsterdam, Amsterdam, The Netherlands
| | | | - Pieter J Tanis
- Department of Surgical Oncology and Gastrointestinal Surgery, Erasmus University Medical Centre, Rotterdam, The Netherlands
- Department of Surgery, Amsterdam University Medical Centre, University of Amsterdam, Amsterdam, The Netherlands
| | - Alvaro Arjona-Sanchez
- Unit of Oncological and Pancreatic Surgery, Reina Sofía University Hospital, Córdoba, Spain
- Maimónides Biomedical Research Institute of Córdoba (IMIBIC), Reina Sofia University Hospital, University of Córdoba, Córdoba, Spain
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Zhang Y, Jin Z, Wang Z, Yan L, Liu A, Li F, Li Y, Zhang Y. Trends in Colorectal Cancer Peritoneal Metastases Research: A Comprehensive Bibliometric Analysis. J Gastrointest Cancer 2025; 56:51. [PMID: 39847239 DOI: 10.1007/s12029-025-01176-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/11/2025] [Indexed: 01/24/2025]
Abstract
BACKGROUND Colorectal cancer (CRC) stands as the third most prevalent malignancy globally and is recognized as the second leading cause of cancer-related mortality. Notably, nearly 50% of individuals diagnosed with CRC ultimately develop metastatic disease, with the peritoneum emerging as the second most frequent site for metastatic spread. Recent advancements in therapeutic frameworks have enhanced both survival rates and quality of life metrics for patients afflicted with colorectal cancer peritoneal metastases (CRCPM). OBJECTIVE This study endeavors to facilitate an in-depth review of the current scientific landscape surrounding CRCPM, ultimately aiming to delineate future avenues for investigative research in this realm. METHODS Employing R software through the Bibliometrix package, alongside analytical tools such as CiteSpace and VOSviewer, we performed a comprehensive bibliometric analysis. This enabled us to assess pivotal keywords, prominent authors, influential countries, notable institutions, relevant literature, and key journals pertinent to the field of CRCPM research. RESULTS Our findings illustrate a significant uptick in the volume of publications addressing CRCPM, with the USA leading in overall contribution, complemented by substantial input from distinguished scholars in the Netherlands and France. The author Ignace H. J. T. de Hingh emerged as the most prolific contributor. Current research endeavors have predominantly focused on the characterization of primary malignancies with peritoneal metastases, therapeutic interventions for CRCPM, and the orchestration of clinical trials. CONCLUSION This analysis culminates in a systematic encapsulation of the prevailing research findings concerning CRCPM, underscoring current hotspots and predicting future trends within the global research spectrum. The exploration of treatment modalities for CRCPM remains vibrant, and ongoing multicenter clinical trials are anticipated to further enrich our understanding and management of this challenging clinical issue.
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Affiliation(s)
- Yuzhe Zhang
- The First Laboratory of Cancer Institute, The First Hospital of China Medical University, Shenyang, 110001, China
| | - Zi Jin
- Nuclear Medicine Department, Shenyang Fifth People's Hospital, Shenyang, 110001, China
| | - Zhongqing Wang
- Department of Information Center, The First Hospital of China Medical University, Shenyang, 110001, China
| | - Lirong Yan
- The First Laboratory of Cancer Institute, The First Hospital of China Medical University, Shenyang, 110001, China
| | - Aoran Liu
- The First Laboratory of Cancer Institute, The First Hospital of China Medical University, Shenyang, 110001, China
| | - Fang Li
- The First Laboratory of Cancer Institute, The First Hospital of China Medical University, Shenyang, 110001, China
| | - Yanke Li
- Department of Anorectal Surgery, The First Hospital of China Medical University, Shenyang, 110001, China.
| | - Ye Zhang
- The First Laboratory of Cancer Institute, The First Hospital of China Medical University, Shenyang, 110001, China.
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Sourrouille I, Pastier C, Gelli M, Benhaïm L, Cattan P, Ducreux M, Aparicio T, Goéré D. Results of complete cytoreductive strategy in patients with peritoneal metastases of colorectal origin with or without extraperitoneal metastases: A bicentric analysis. EUROPEAN JOURNAL OF SURGICAL ONCOLOGY 2025; 51:108788. [PMID: 39531916 DOI: 10.1016/j.ejso.2024.108788] [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: 08/01/2024] [Revised: 10/03/2024] [Accepted: 10/24/2024] [Indexed: 11/16/2024]
Abstract
BACKGROUND Increased survival can be achieved in patients with colorectal cancer peritoneal metastases (CRPM) treated with cytoreductive surgery. The benefit of this strategy remains uncertain when CRPM are associated with extraperitoneal metastases (EPM). The aim of this study was to compare short- and long-term outcomes of patients treated with CRS for CRPM, with or without EPM. METHODS This study included 413 consecutive patients who underwent CRS for CRPM: 120 with EPM (EPM+) and 293 without (EPM-). Patients with isolated ovarian metastases were included in EPM-group (n = 83). RESULTS EPM were mainly located to the liver (66 %,n = 79), retroperitoneal lymph nodes (33 %,n = 40); less frequently to the spleen (9 %,n = 12), lung (9 %,n = 10) or pleura (1 %,n = 1). Ovarian metastases were present in 126 patients (83 in EMP-, 43 in EPM+). Peritoneal carcinomatosis index (PCI) was similar in EPM- (8 [4-14]) and EPM+ (8 [3-13],p = 0.335) groups, as postoperative mortality (3 % vs 3 %,p = 1) and major morbidity rates (28 % vs 35 %,p = 0.223). Median overall survival (mOS) and disease-free survival were significantly higher in the EPM-group (58m vs 39m, and 16m vs 10m,p = 0.003). We highlighted 3 prognostic groups 1) EPM-with PCI<10 (mOS 93m), 2) EPM+ with PCI<10 (mOS 57m), 3) EPM-with 10 15 regardless EPM (mOS 26m, p < 0.001). CONCLUSION Complete cytoreductive surgery seems to be feasible in patients with EPM, without increase in postoperative morbidity and mortality compared to patients without EPM. This strategy provides prolonged survival in selected patients with limited peritoneal metastases from colorectal cancer.
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Affiliation(s)
| | - Clément Pastier
- Department of Surgical Oncology, Hopital Saint Louis, Paris, France
| | | | - Léonor Benhaïm
- Department of Surgical Oncology, Gustave Roussy, Villejuif, France
| | - Pierre Cattan
- Department of Surgical Oncology, Hopital Saint Louis, Paris, France
| | - Michel Ducreux
- Department of Medical Oncology, Gustave Roussy, Villejuif, France
| | - Thomas Aparicio
- Department of Medical Oncology, Hopital Saint Louis, Paris, France
| | - Diane Goéré
- Department of Surgical Oncology, Hopital Saint Louis, Paris, France.
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Furukawa S, Hiraki M, Kimura N, Okuyama K, Kohya N, Sakai M, Kawaguchi A, Ikubo A, Samejima R. The clinical impact of intraoperative bleeding on peritoneal recurrence after surgery for stage II to III colorectal cancer. Asian J Surg 2024:S1015-9584(24)02314-5. [PMID: 39505635 DOI: 10.1016/j.asjsur.2024.10.005] [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: 02/21/2024] [Revised: 07/17/2024] [Accepted: 10/04/2024] [Indexed: 11/08/2024] Open
Abstract
BACKGROUND This study aimed to investigate the risk factors for peritoneal recurrence (PR) in patients with stage II to III colorectal cancer who underwent colorectal surgery. METHODS A retrospective study was conducted on 232 patients who underwent colorectal surgery for stage II to III colorectal cancer. Univariate and multivariate analyses were performed to determine risk factors for PR. RESULTS The overall incidence of PR was 8.2 % (19/232). A univariate Cox regression analysis showed that a higher level of carcinoembryonic antigen (CEA) (P = 0.039), higher levels of carbohydrate antigen 19-9 (CA19-9) (P < 0.001), preoperative bowel obstruction (P = 0.011), tumor invasion of T4 category (P = 0.019), lymph node metastasis (P = 0.016), poorly differentiated, mucinous or signet-ring histological type (P = 0.010), larger amount of intraoperative bleeding (P = 0.002), R1 resection (P = 0.003), anastomotic leakage Clavien-Dindo classification (CD) ≥2 (P = 0.018), longer postoperative stay (P = 0.002), and recurrence of other organs preceding disseminated recurrence (P = 0.004) were observed significantly more frequently in patients with PR than in patients without PR. A multivariate Cox regression analysis revealed that poorly differentiated, mucinous, or signet-ring histological type (HR: 5.067, 95 % CI: 1.192-21.534, P = 0.028) and intraoperative bleeding (HR: 1.003, 95 % CI: 1.000-1.005, P = 0.017) were independent risk factors for PR. Peritoneal recurrence-free survival curves generated using the Kaplan-Meier method gradually worsened with increasing intraoperative bleeding (P < 0.001). In addition, the sub-analyses between stage II and stage III and between ≤ cT3 and cT4 also demonstrated that peritoneal recurrence-free survival worsened with increasing intraoperative bleeding. CONCLUSIONS Our findings suggest that histological type, and intraoperative bleeding are risk factors for PR in patients who undergo colorectal surgery for stage II to III colorectal cancer. In particular, peritoneal recurrence is associated with increased intraoperative bleeding.
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Affiliation(s)
- Shunsuke Furukawa
- Department of Surgery, Japanese Red Cross Society Karatsu Red Cross Hospital, 2430 Watada, Karatsu, Saga, 847-8588, Japan
| | - Masatsugu Hiraki
- Department of Surgery, Japanese Red Cross Society Karatsu Red Cross Hospital, 2430 Watada, Karatsu, Saga, 847-8588, Japan.
| | - Naoya Kimura
- Department of Surgery, Japanese Red Cross Society Karatsu Red Cross Hospital, 2430 Watada, Karatsu, Saga, 847-8588, Japan
| | - Keiichiro Okuyama
- Department of Surgery, Japanese Red Cross Society Karatsu Red Cross Hospital, 2430 Watada, Karatsu, Saga, 847-8588, Japan
| | - Naohiko Kohya
- Department of Surgery, Japanese Red Cross Society Karatsu Red Cross Hospital, 2430 Watada, Karatsu, Saga, 847-8588, Japan
| | - Masashi Sakai
- Department of Surgery, Japanese Red Cross Society Karatsu Red Cross Hospital, 2430 Watada, Karatsu, Saga, 847-8588, Japan
| | - Atsushi Kawaguchi
- Education and Research Center for Community Medicine, Saga University Faculty of Medicine, 5-1-1 Nabeshima, Saga, 849-8501, Japan
| | - Akashi Ikubo
- Department of Surgery, Japanese Red Cross Society Karatsu Red Cross Hospital, 2430 Watada, Karatsu, Saga, 847-8588, Japan
| | - Ryuichiro Samejima
- Department of Surgery, Japanese Red Cross Society Karatsu Red Cross Hospital, 2430 Watada, Karatsu, Saga, 847-8588, Japan
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Sleiman MJ, Jelip A, Buchs N, Toso C, Liot E, Koessler T, Meyer J, Meurette G, Ris F. Pressurized Intraperitoneal Aerosol Chemotherapy for Peritoneal Carcinomatosis in Colorectal Cancer Patients: A Systematic Review of the Evidence. Cancers (Basel) 2024; 16:3661. [PMID: 39518099 PMCID: PMC11544814 DOI: 10.3390/cancers16213661] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2024] [Revised: 10/21/2024] [Accepted: 10/28/2024] [Indexed: 11/16/2024] Open
Abstract
INTRODUCTION Pressurized intraperitoneal aerosol chemotherapy (PIPAC) consists of the administration of aerosolized chemotherapy into the abdominal cavity of patients suffering from peritoneal carcinomatosis. Our aim was to review the evidence supporting PIPAC in patients with peritoneal carcinomatosis from colorectal cancer. METHODS A systematic review was performed in accordance with the 2020 PRISMA guideline. MEDLINE and CENTRAL were searched using combinations of terms including "Peritoneal carcinomatosis", "Peritoneal metastasis", "PIPAC", "Pressurized intraperitoneal aerosol chemotherapy" and "Colorectal cancer". Original studies, in English, including patients treated with PIPAC for colorectal peritoneal carcinomatosis, were considered eligible. Case reports, non-English or French language articles and secondary analyses were excluded. RESULTS A total of 385 articles were screened and 374 articles were excluded, leaving 11 publications for inclusion in the qualitative analysis. The included studies totalized 949 patients who received PIPAC for peritoneal carcinomatosis due to colorectal cancer. The median peritoneal carcinomatosis index (PCI) ranged from 10 to 31. In all studies, the complete PIPAC protocol was achieved with an average of two to three 3 PIPAC sessions per patient. Oxaliplatin (OX) was used as a chemotherapeutic agent in all studies and could be associated with intravenous 5-FU and leucovorin. Most post-operative adverse events were recorded as mild to moderate with no intraoperative complications. Only four studies reported a decrease in the average PCI score for 50% of the patients. Median overall survival ranged from 8 to 37.8 months. Quality of life indicators were stable between PIPAC-OX cycles with a small but not statistically significant trend of improvement of most functional scales. CONCLUSIONS PIPAC for peritoneal carcinomatosis from colorectal origin is feasible, safe and tolerable. Its impact on survival outcomes or quality of life remains to be demonstrated by randomized trials.
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Affiliation(s)
- Marwan-Julien Sleiman
- Division of Digestive Surgery, University Hospitals of Geneva, 1205 Geneva, Switzerland; (A.J.); (C.T.); (E.L.); (J.M.); (G.M.); (F.R.)
| | - Annamaria Jelip
- Division of Digestive Surgery, University Hospitals of Geneva, 1205 Geneva, Switzerland; (A.J.); (C.T.); (E.L.); (J.M.); (G.M.); (F.R.)
| | - Nicolas Buchs
- Division of Digestive Surgery, Hôpital La Tour, 1217 Meyrin, Switzerland;
| | - Christian Toso
- Division of Digestive Surgery, University Hospitals of Geneva, 1205 Geneva, Switzerland; (A.J.); (C.T.); (E.L.); (J.M.); (G.M.); (F.R.)
| | - Emilie Liot
- Division of Digestive Surgery, University Hospitals of Geneva, 1205 Geneva, Switzerland; (A.J.); (C.T.); (E.L.); (J.M.); (G.M.); (F.R.)
| | - Thibaud Koessler
- Division of Oncology, University Hospitals of Geneva, 1205 Geneva, Switzerland;
| | - Jeremy Meyer
- Division of Digestive Surgery, University Hospitals of Geneva, 1205 Geneva, Switzerland; (A.J.); (C.T.); (E.L.); (J.M.); (G.M.); (F.R.)
| | - Guillaume Meurette
- Division of Digestive Surgery, University Hospitals of Geneva, 1205 Geneva, Switzerland; (A.J.); (C.T.); (E.L.); (J.M.); (G.M.); (F.R.)
| | - Frederic Ris
- Division of Digestive Surgery, University Hospitals of Geneva, 1205 Geneva, Switzerland; (A.J.); (C.T.); (E.L.); (J.M.); (G.M.); (F.R.)
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Ha YJ, Park SH, Tak KH, Lee JL, Kim CW, Kim JH, Kim SY, Kim SK, Yoon YS. CILP2 is a potential biomarker for the prediction and therapeutic target of peritoneal metastases in colorectal cancer. Sci Rep 2024; 14:12487. [PMID: 38816545 PMCID: PMC11139887 DOI: 10.1038/s41598-024-63366-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2024] [Accepted: 05/28/2024] [Indexed: 06/01/2024] Open
Abstract
Peritoneal metastases (PM) in colorectal cancer (CRC) is associated with a dismal prognosis. Identifying and exploiting new biomarkers, signatures, and molecular targets for personalised interventions in the treatment of PM in CRC is imperative. We conducted transcriptomic profiling using RNA-seq data generated from the primary tissues of 19 CRC patients with PM. Using our dataset established in a previous study, we identified 1422 differentially expressed genes compared to non-metastatic CRC. The profiling demonstrated no differential expression in liver and lung metastatic CRC. We selected 12 genes based on stringent criteria and evaluated their expression patterns in a validation cohort of 32 PM patients and 84 without PM using real-time reverse transcription-polymerase chain reaction. We selected cartilage intermediate layer protein 2 (CILP2) because of high mRNA expression in PM patients in our validation cohort and its association with a poor prognosis in The Cancer Genome Atlas. Kaplan-Meier survival analysis in our validation cohort demonstrated that CRC patients with high CILP2 expression had significantly poor survival outcomes. Knockdown of CILP2 significantly reduced the proliferation, colony-forming ability, invasiveness, and migratory capacity and downregulated the expression of molecules related to epithelial-mesenchymal transition in HCT116 cells. In an in vivo peritoneal dissemination mouse knockdown of CILP2 also inhibited CRC growth. Therefore, CILP2 is a promising biomarker for the prediction and treatment of PM in CRC.
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Affiliation(s)
- Ye Jin Ha
- Asan Institute for Life Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul, 05505, Korea
| | - Seong-Hwan Park
- Aging Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon, 34141, Korea
- Department of Bioscience, University of Science and Technology, Daejeon, 34113, Korea
| | - Ka Hee Tak
- Asan Institute for Life Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul, 05505, Korea
| | - Jong Lyul Lee
- Asan Institute for Life Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul, 05505, Korea
- Division of Colon and Rectal Surgery, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, 05505, Korea
| | - Chan Wook Kim
- Asan Institute for Life Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul, 05505, Korea
- Division of Colon and Rectal Surgery, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, 05505, Korea
| | - Jeong-Hwan Kim
- Aging Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon, 34141, Korea
- Personalized Genomic Medicine Research Center, KRIBB, Daejeon, 34141, Korea
| | - Seon-Young Kim
- Department of Bioscience, University of Science and Technology, Daejeon, 34113, Korea
- Korea Bioinformation Center, KRIBB, Daejeon, 34141, Korea
| | - Seon-Kyu Kim
- Aging Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon, 34141, Korea.
- Department of Bioscience, University of Science and Technology, Daejeon, 34113, Korea.
- Personalized Genomic Medicine Research Center, KRIBB, Daejeon, 34141, Korea.
| | - Yong Sik Yoon
- Asan Institute for Life Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul, 05505, Korea.
- Division of Colon and Rectal Surgery, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, 05505, Korea.
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Sikora A, Sullivan KM, Dineen S, Raoof M, Karolak A. Emerging therapeutic approaches for peritoneal metastases from gastrointestinal cancers. MOLECULAR THERAPY. ONCOLOGY 2024; 32:200767. [PMID: 38596287 PMCID: PMC10873742 DOI: 10.1016/j.omton.2024.200767] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Indexed: 04/11/2024]
Abstract
Peritoneal metastases from gastrointestinal malignancies present difficult management decisions, with options consisting primarily of systemic chemotherapy or major surgery with or without hyperthermic intraperitoneal chemotherapy. Current research is investigating expanding therapeutic modalities, and the aim of this review is to provide an overview of the existing and emerging therapies for the peritoneal metastases from gastrointestinal cancers, primarily through the recent literature (2015 and newer). These include the current data with systemic therapy and cytoreduction with hyperthermic intraperitoneal or pressurized intraperitoneal aerosol chemotherapy, as well as novel promising modalities under investigation, including dominating oncolytic viral therapy and adoptive cellular, biologic, and bacteria therapy, or nanotechnology. The novel diverse strategies, although preliminary and preclinical in murine models, individually and collectively contribute to the treatment of peritoneal metastases, offering hope for improved outcomes and quality of life. We foresee that these evolving treatment approaches will facilitate the transfer of knowledge and data among studies and advance discovery of new drugs and optimized treatments for patients with peritoneal metastases.
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Affiliation(s)
- Aleksandra Sikora
- Department of Medicine, Medical University of Warsaw, 02-091 Warsaw, Poland
| | - Kevin M. Sullivan
- Division of Surgical Oncology, Department of Surgery, City of Hope National Medical Center, Duarte, CA 91010, USA
| | - Sean Dineen
- Department of Gastrointestinal Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA
| | - Mustafa Raoof
- Division of Surgical Oncology, Department of Surgery, City of Hope National Medical Center, Duarte, CA 91010, USA
- Department of Cancer Genetics and Epigenetics, City of Hope National Medical Center, Duarte, CA 91010, USA
| | - Aleksandra Karolak
- Department of Gastrointestinal Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA
- Department of Machine Learning, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA
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10
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Mirza MB, Smith PM, Wang Y, Naveed A, Washington MK, Xu Y, Idrees K. Intra-Patient Heterogeneity in Micro-satellite-stable Colorectal Metastases: Does Immunotherapy Have a Role in Colorectal Peritoneal Metastases? Ann Surg Oncol 2024; 31:1440-1443. [PMID: 38110752 DOI: 10.1245/s10434-023-14694-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2023] [Accepted: 11/16/2023] [Indexed: 12/20/2023]
Affiliation(s)
- M B Mirza
- Division of Surgical Oncology and Endocrine Surgery, Department of Surgical Sciences, Vanderbilt University Medical Center, Nashville, TN, USA
| | - P Marincola Smith
- Division of Surgical Oncology and Endocrine Surgery, Department of Surgical Sciences, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Y Wang
- Department of Biostatistics, Vanderbilt University Medical Center, Nashville, TN, USA
| | - A Naveed
- Division of Otolaryngology, Head and Neck Surgery, Department of Surgical Sciences, Vanderbilt University Medical Center, Nashville, TN, USA
| | - M K Washington
- Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Y Xu
- Department of Biostatistics, Vanderbilt University Medical Center, Nashville, TN, USA
| | - K Idrees
- Division of Surgical Oncology and Endocrine Surgery, Department of Surgical Sciences, Vanderbilt University Medical Center, Nashville, TN, USA.
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11
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Fu C, Zhang B, Guo T, Li J. Imaging Evaluation of Peritoneal Metastasis: Current and Promising Techniques. Korean J Radiol 2024; 25:86-102. [PMID: 38184772 PMCID: PMC10788608 DOI: 10.3348/kjr.2023.0840] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2023] [Revised: 09/28/2023] [Accepted: 10/08/2023] [Indexed: 01/08/2024] Open
Abstract
Early diagnosis, accurate assessment, and localization of peritoneal metastasis (PM) are essential for the selection of appropriate treatments and surgical guidance. However, available imaging modalities (computed tomography [CT], conventional magnetic resonance imaging [MRI], and 18fluorodeoxyglucose positron emission tomography [PET]/CT) have limitations. The advent of new imaging techniques and novel molecular imaging agents have revealed molecular processes in the tumor microenvironment as an application for the early diagnosis and assessment of PM as well as real-time guided surgical resection, which has changed clinical management. In contrast to clinical imaging, which is purely qualitative and subjective for interpreting macroscopic structures, radiomics and artificial intelligence (AI) capitalize on high-dimensional numerical data from images that may reflect tumor pathophysiology. A predictive model can be used to predict the occurrence, recurrence, and prognosis of PM, thereby avoiding unnecessary exploratory surgeries. This review summarizes the role and status of different imaging techniques, especially new imaging strategies such as spectral photon-counting CT, fibroblast activation protein inhibitor (FAPI) PET/CT, near-infrared fluorescence imaging, and PET/MRI, for early diagnosis, assessment of surgical indications, and recurrence monitoring in patients with PM. The clinical applications, limitations, and solutions for fluorescence imaging, radiomics, and AI are also discussed.
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Affiliation(s)
- Chen Fu
- The First School of Clinical Medical, Gansu University of Chinese Medicine, Lanzhou, Gansu, China
| | - Bangxing Zhang
- School of Clinical Medicine, Ningxia Medical University, Yinchuan, Ningxia, China
| | - Tiankang Guo
- Department of General Surgery, Gansu Provincial Hospital, Lanzhou, Gansu, China
- Key Laboratory of Molecular Diagnostics and Precision Medicine for Surgical Oncology in Gansu Province, Gansu Provincial Hospital, Gansu, China
- NHC Key Laboratory of Diagnosis and Therapy of Gastrointestinal Tumor, Gansu Provincial Hospital, Lanzhou, Gansu, China
| | - Junliang Li
- The First School of Clinical Medical, Gansu University of Chinese Medicine, Lanzhou, Gansu, China
- Department of General Surgery, Gansu Provincial Hospital, Lanzhou, Gansu, China
- Key Laboratory of Molecular Diagnostics and Precision Medicine for Surgical Oncology in Gansu Province, Gansu Provincial Hospital, Gansu, China
- NHC Key Laboratory of Diagnosis and Therapy of Gastrointestinal Tumor, Gansu Provincial Hospital, Lanzhou, Gansu, China.
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12
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Wintjens AGWE, Fransen PPKH, Lenaerts K, Liu H, van Almen GC, van Steensel S, Gijbels MJ, de Hingh IHJT, Dankers PYW, Bouvy ND. Development of a Supramolecular Hydrogel for Intraperitoneal Injections. Macromol Biosci 2024; 24:e2300005. [PMID: 36934315 DOI: 10.1002/mabi.202300005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2023] [Revised: 02/22/2023] [Indexed: 03/20/2023]
Abstract
Local intraperitoneal drug administration is considered a challenging drug delivery route. The therapeutic efficiency is low, mainly due to rapid clearance of drugs. To increase the intraperitoneal retention time of specific drugs, a pH-sensitive supramolecular hydrogel that can act as a drug delivery vehicle is developed. To establish the optimal formulation of the hydrogel and to study its feasibility, safety, and tissue compatibility, in vitro, postmortem, and in vivo experiments are performed. In vitro tests reveal that a hydrogelator formulation with pH ≥ 9 results in a constant viscosity of 0.1 Pa·s. After administration postmortem, the hydrogel covers the parietal and visceral peritoneum with a thin, soft layer. In the subsequent in vivo experiments, 14 healthy rats are subjected to intraperitoneal injection with the hydrogel. Fourteen and 28 days after implantation, the animals are euthanized. Intraperitoneal exposure to the hydrogel is not resulted in significant weight loss or discomfort. Moreover, no macroscopic adverse effects or signs of organ damage are detected. In several intra-abdominal tissues, vacuolated macrophages are found indicating a physiological degradation of the synthetic hydrogel. This study demonstrates that the supramolecular hydrogel is safe for intraperitoneal application and that the hydrogel shows good tissue compatibility in rats.
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Affiliation(s)
- Anne G W E Wintjens
- Department of Surgery, Maastricht University Medical Center+, Maastricht, 6202AZ, The Netherlands
- NUTRIM - School of Nutrition and Translational Research in Metabolism, Maastricht University, Maastricht, 6211LK, The Netherlands
| | | | - Kaatje Lenaerts
- Department of Surgery, Maastricht University Medical Center+, Maastricht, 6202AZ, The Netherlands
- NUTRIM - School of Nutrition and Translational Research in Metabolism, Maastricht University, Maastricht, 6211LK, The Netherlands
| | - Hong Liu
- Department of Surgery, Maastricht University Medical Center+, Maastricht, 6202AZ, The Netherlands
- NUTRIM - School of Nutrition and Translational Research in Metabolism, Maastricht University, Maastricht, 6211LK, The Netherlands
| | | | - Sebastiaan van Steensel
- Department of Surgery, Maastricht University Medical Center+, Maastricht, 6202AZ, The Netherlands
| | - Marion J Gijbels
- NUTRIM - School of Nutrition and Translational Research in Metabolism, Maastricht University, Maastricht, 6211LK, The Netherlands
- Department of Pathology, Maastricht University Medical Center+, Maastricht, 6202AZ, The Netherlands
- Department of Medical Biochemistry, Experimental Vascular Biology, Amsterdam Cardiovascular Sciences, Amsterdam Infection and Immunity, Amsterdam University Medical Center, Amsterdam, 1081HV, The Netherlands
| | - Ignace H J T de Hingh
- GROW - School for Oncology and Reproduction, Maastricht University, Maastricht, 6211LK, The Netherlands
- Department of Surgery, Catharina Hospital Eindhoven, Eindhoven, 5623EJ, The Netherlands
| | - Patricia Y W Dankers
- Institute for Complex Molecular Systems, Eindhoven University of Technology, Eindhoven, 5612AE, The Netherlands
- Department of Biomedical Engineering, Laboratory of Chemical Biology, Eindhoven University of Technology, Eindhoven, 5612AE, The Netherlands
| | - Nicole D Bouvy
- Department of Surgery, Maastricht University Medical Center+, Maastricht, 6202AZ, The Netherlands
- Department of Medical Biochemistry, Experimental Vascular Biology, Amsterdam Cardiovascular Sciences, Amsterdam Infection and Immunity, Amsterdam University Medical Center, Amsterdam, 1081HV, The Netherlands
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13
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Li Y, Duan HY, Yang KD, Ye JF. Advancements and challenges in oncolytic virus therapy for gastrointestinal tumors. Biomed Pharmacother 2023; 168:115627. [PMID: 37812894 DOI: 10.1016/j.biopha.2023.115627] [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: 07/25/2023] [Revised: 09/25/2023] [Accepted: 10/03/2023] [Indexed: 10/11/2023] Open
Abstract
BACKGROUND Tumors of the gastrointestinal tract impose a substantial healthcare burden due to their prevalence and challenging prognosis. METHODS We conducted a review of peer-reviewed scientific literature using reputable databases (PubMed, Scopus, Web of Science) with a focus on oncolytic virus therapy within the context of gastrointestinal tumors. Our search covered the period up to the study's completion in June 2023. INCLUSION AND EXCLUSION CRITERIA This study includes articles from peer-reviewed scientific journals, written in English, that specifically address oncolytic virus therapy for gastrointestinal tumors, encompassing genetic engineering advances, combined therapeutic strategies, and safety and efficacy concerns. Excluded are articles not meeting these criteria or focusing on non-primary gastrointestinal metastatic tumors. RESULTS Our review revealed the remarkable specificity of oncolytic viruses in targeting tumor cells and their potential to enhance anti-tumor immune responses. However, challenges related to safety and efficacy persist, underscoring the need for ongoing research and improvement. CONCLUSION This study highlights the promising role of oncolytic virus therapy in enhancing gastrointestinal tumor treatments. Continued investigation and innovative combination therapies hold the key to reducing the burden of these tumors on patients and healthcare systems.
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Affiliation(s)
- Yang Li
- General Surgery Center, First Hospital of Jilin University, Changchun, Jilin, China; School of Nursing, Jilin University, Changchun, China
| | - Hao-Yu Duan
- General Surgery Center, First Hospital of Jilin University, Changchun, Jilin, China
| | - Kai-di Yang
- School of Nursing, Jilin University, Changchun, China
| | - Jun-Feng Ye
- General Surgery Center, First Hospital of Jilin University, Changchun, Jilin, China.
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14
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van Eerden RAG, de Boer NL, van Kooten JP, Bakkers C, Dietz MV, Creemers GJM, Buijs SM, Bax R, de Man FM, Lurvink RJ, Diepeveen M, Brandt-Kerkhof ARM, van Meerten E, Koolen SLW, de Hingh IHJT, Verhoef C, Mathijssen RHJ, Burger JWA. Phase I study of intraperitoneal irinotecan combined with palliative systemic chemotherapy in patients with colorectal peritoneal metastases. Br J Surg 2023; 110:1502-1510. [PMID: 37467389 DOI: 10.1093/bjs/znad228] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2023] [Revised: 06/18/2023] [Accepted: 06/28/2023] [Indexed: 07/21/2023]
Abstract
BACKGROUND Patients with colorectal peritoneal metastases who are not eligible for cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) owing to extensive peritoneal disease have a poor prognosis. It was hypothesized that these patients may benefit from the addition of intraperitoneal irinotecan to standard palliative systemic chemotherapy. METHODS This was a classical 3 + 3 phase I dose-escalation trial in patients with colorectal peritoneal metastases who were not eligible for CRS-HIPEC. Intraperitoneal irinotecan was administered every 2 weeks, concomitantly with systemic FOLFOX (5-fluorouracil, folinic acid, oxaliplatin)-bevacizumab. The primary objective was to determine the maximum tolerated dose and dose-limiting toxicities. Secondary objectives were to elucidate the systemic and intraperitoneal pharmacokinetics, safety profile, and efficacy. RESULTS Eighteen patients were treated. No dose-limiting toxicities were observed with 50 mg (4 patients) and 75 mg (9 patients) intraperitoneal irinotecan. Two dose-limiting toxicities occurred with 100 mg irinotecan among five patients. The maximum tolerated dose of intraperitoneal irinotecan was established to be 75 mg, and it was well tolerated. Intraperitoneal exposure to SN-38 (active metabolite of irinotecan) was high compared with systemic exposure (median intraperitoneal area under the curve (AUC) to systemic AUC ratio 4.6). Thirteen patients had a partial radiological response and five had stable disease. Four patients showed a complete response during post-treatment diagnostic laparoscopy. Five patients underwent salvage resection or CRS-HIPEC. Median overall survival was 23.9 months. CONCLUSION Administration of 75 mg intraperitoneal irinotecan concomitantly with systemic FOLFOX-bevacizumab was safe and well tolerated. Intraperitoneal SN-38 exposure was high and prolonged. As oncological outcomes were promising, intraperitoneal administration of irinotecan may be a good alternative to other, more invasive and costly treatment options. A phase II study is currently accruing.
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Affiliation(s)
- Ruben A G van Eerden
- Department of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, the Netherlands
| | - Nadine L de Boer
- Department of Surgical Oncology, Erasmus MC Cancer Institute, Rotterdam, the Netherlands
| | - Job P van Kooten
- Department of Surgical Oncology, Erasmus MC Cancer Institute, Rotterdam, the Netherlands
| | - Checca Bakkers
- Department of Surgery, Catharina Cancer Institute, Eindhoven, the Netherlands
| | - Michelle V Dietz
- Department of Surgical Oncology, Erasmus MC Cancer Institute, Rotterdam, the Netherlands
| | - Geert-Jan M Creemers
- Department of Medical Oncology, Catharina Cancer Institute, Eindhoven, the Netherlands
| | - Sanne M Buijs
- Department of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, the Netherlands
| | - Ramon Bax
- Department of Medical Oncology, Catharina Cancer Institute, Eindhoven, the Netherlands
| | - Femke M de Man
- Department of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, the Netherlands
| | - Robin J Lurvink
- Department of Surgery, Catharina Cancer Institute, Eindhoven, the Netherlands
| | - Marjolein Diepeveen
- Department of Surgical Oncology, Erasmus MC Cancer Institute, Rotterdam, the Netherlands
| | | | - Esther van Meerten
- Department of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, the Netherlands
| | - Stijn L W Koolen
- Department of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, the Netherlands
- Department of Hospital Pharmacy, Erasmus MC, Rotterdam, the Netherlands
| | | | - Cornelis Verhoef
- Department of Surgical Oncology, Erasmus MC Cancer Institute, Rotterdam, the Netherlands
| | - Ron H J Mathijssen
- Department of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, the Netherlands
| | - Jacobus W A Burger
- Department of Surgery, Catharina Cancer Institute, Eindhoven, the Netherlands
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15
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Kano Y, Suenaga M, Uetake H. Strategic Insight into the Combination Therapies for Metastatic Colorectal Cancer. Curr Oncol 2023; 30:6546-6558. [PMID: 37504340 PMCID: PMC10378516 DOI: 10.3390/curroncol30070480] [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: 06/07/2023] [Revised: 07/05/2023] [Accepted: 07/06/2023] [Indexed: 07/29/2023] Open
Abstract
Colorectal cancer (CRC) is the second most common cause of cancer-related deaths worldwide. The 5-year survival rate after curative resection is almost 80%, however, it is still less than satisfactory for metastatic CRC (mCRC). The combination approach including surgery, chemotherapy, molecular targeted therapy, and immunotherapy is a promising strategy due to its synergistic anticancer effect. Moreover, circulating tumor DNA (ctDNA) analysis has been reported to stratify the post-operative risk of recurrence, thus providing clinically valuable information for deciding to conduct adjuvant chemotherapy. Furthermore, multiple new drugs that potentially target undruggable genes, including KRAS, have been developed. In this review, we discuss the current management of patients with mCRC and future perspectives in the light of a combination therapeutic strategy.
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Affiliation(s)
- Yoshihito Kano
- Department of Clinical Oncology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (TMDU), Tokyo 113-8510, Japan
| | - Mitsukuni Suenaga
- Department of Clinical Oncology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (TMDU), Tokyo 113-8510, Japan
| | - Hiroyuki Uetake
- Department of Clinical Research, National Hospital Organization Disaster Medical Center, Tokyo 190-0014, Japan
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Rijken A, van de Vlasakker VCJ, Simkens GA, Rovers KP, van Erning FN, Koopman M, Verhoef C, de Wilt JHW, de Hingh IHJT. Primary tumor resection or systemic treatment as palliative treatment for patients with isolated synchronous colorectal cancer peritoneal metastases in a nationwide cohort study. Clin Exp Metastasis 2023:10.1007/s10585-023-10212-y. [PMID: 37209222 DOI: 10.1007/s10585-023-10212-y] [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: 12/29/2022] [Accepted: 05/15/2023] [Indexed: 05/22/2023]
Abstract
Limited data are available to guide the decision-making process for clinicians and their patients regarding palliative treatment options for patients with isolated synchronous colorectal cancer peritoneal metastases (CRC-PM). Therefore, the aim of this study is to analyze the outcome of the different palliative treatments for these patients. All patients diagnosed with isolated synchronous CRC-PM between 2009 and 2020 (Netherlands Cancer Registry) who underwent palliative treatment were included. Patients who underwent emergency surgery or curative intent treatment were excluded. Patients were categorized into upfront palliative primary tumor resection (with or without additional systemic treatment) or palliative systemic treatment only. Overall survival (OS) was compared between both groups and multivariable cox regression analysis was performed. Of 1031 included patients, 364 (35%) patients underwent primary tumor resection and 667 (65%) patients received systemic treatment only. Sixty-day mortality was 9% in the primary tumor resection group and 5% in the systemic treatment group (P = 0.007). OS was 13.8 months in the primary tumor resection group and 10.3 months in the systemic treatment group (P < 0.001). Multivariable analysis showed that primary tumor resection was associated with improved OS (HR 0.68; 95%CI 0.57-0.81; P < 0.001). Palliative primary tumor resection appeared to be associated with improved survival compared to palliative systemic treatment alone in patients with isolated synchronous CRC-PM despite a higher 60-day mortality. This finding must be interpreted with care as residual bias probably played a significant role. Nevertheless, this option may be considered in the decision-making process by clinicians and their patients.
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Affiliation(s)
- Anouk Rijken
- Department of Surgery, Catharina Hospital, Eindhoven, the Netherlands
- Department of Research and Development, Netherlands Comprehensive Cancer Organization, Utrecht, the Netherlands
| | | | - Geert A Simkens
- Department of Surgery, Catharina Hospital, Eindhoven, the Netherlands
| | - Koen P Rovers
- Department of Surgery, Catharina Hospital, Eindhoven, the Netherlands
| | - Felice N van Erning
- Department of Surgery, Catharina Hospital, Eindhoven, the Netherlands
- Department of Research and Development, Netherlands Comprehensive Cancer Organization, Utrecht, the Netherlands
| | - Miriam Koopman
- Department of Medical Oncology, University Medical Centre Utrecht, Utrecht University, Utrecht, the Netherlands
| | - Cornelis Verhoef
- Department of Surgery, Erasmus Medical Centre, Rotterdam, the Netherlands
| | - Johannes H W de Wilt
- Department of Surgery, Radboud University Medical Centre, Nijmegen, the Netherlands
| | - Ignace H J T de Hingh
- Department of Surgery, Catharina Hospital, Eindhoven, the Netherlands.
- Department of Research and Development, Netherlands Comprehensive Cancer Organization, Utrecht, the Netherlands.
- GROW- School for Oncology and Development Biology, Maastricht University, Maastricht, the Netherlands.
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17
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Dietz MV, Ziekman MJ, van Kooten JP, Brandt-Kerkhof ARM, van Meerten E, Verhoef C, Madsen EVE. Treatment and Survival Outcomes for Patients with Colorectal Peritoneal Metastases Deemed Ineligible for Cytoreductive Surgery (CRS) with Hyperthermic Intraperitoneal Chemotherapy (HIPEC): Results of a Retrospective Study. Ann Surg Oncol 2023; 30:2048-2056. [PMID: 36566258 DOI: 10.1245/s10434-022-12969-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2022] [Accepted: 12/08/2022] [Indexed: 12/25/2022]
Abstract
BACKGROUND Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) is a treatment option for selected patients with colorectal peritoneal metastases (PM). This report provides an overview of treatment and survival outcomes for patients deemed ineligible for CRS-HIPEC. METHODS Colorectal PM patients referred to a tertiary center from 2014 to 2020 that were ineligible for CRS-HIPEC were included. Patient, tumor, and treatment characteristics were provided. Survival analyses were performed using the Kaplan-Meier method. RESULTS Of 476 patients referred for CRS-HIPEC, 227 (48%) were deemed ineligible. Median follow-up was 15 months [IQR 10-22]. Data on follow-up treatment was available for 198 patients, of which 73% received systemic therapy. These patients had a median overall survival (OS) of 17 months [IQR 9-25]. For patients receiving best supportive care (BSC) median OS was 4 months [IQR 2-9]. The main reason for ineligibility was extensive PM (42%), with a median OS of 11 months [IQR 5-18]. Patients deemed ineligible due to (extensive) liver (9%) or lung metastases (8%) showed longer OS (median 22 months, IQR 8-27, and 24 months, IQR 12-29, respectively) than patients with extensive PM (median 11 months, IQR 5-18) or distant lymph node metastases (median 14 months, IQR 4-25). CONCLUSION The main reason for CRS-HIPEC ineligibility was extensive PM. The majority of patients received systemic therapy. Patients deemed ineligible due to extra-peritoneal metastases had better survival outcomes than patients deemed ineligible due to extensive PM.
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Affiliation(s)
- Michelle V Dietz
- Department of Surgical Oncology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands.
| | - Merijn J Ziekman
- Department of Surgical Oncology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands
| | - Job P van Kooten
- Department of Surgical Oncology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands
| | | | - Esther van Meerten
- Department of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands
| | - Cornelis Verhoef
- Department of Surgical Oncology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands
| | - Eva V E Madsen
- Department of Surgical Oncology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands
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Mishra N, Kumar M, Singh S, Rani K. Re-do cytoreductive surgery with hyperthermic intra-peritoneal chemotherapy (HIPEC): Risk factors and complications. J Cancer Res Ther 2023; 19:S921-S924. [PMID: 38384080 DOI: 10.4103/jcrt.jcrt_354_22] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/12/2022] [Accepted: 06/20/2022] [Indexed: 02/23/2024]
Abstract
ABSTRACT An effective multi-modal treatment option for patients with peritoneal surface metastatic malignancies has progressed and developed over the decades as cytoreductive surgery (CRS), and hyperthermic intra-peritoneal chemotherapy (HIPEC) delivers highly concentrated, heated chemotherapy drugs directly to the abdomen during surgery. Peritoneal metastasis and high staging abdominal malignancies were considered incurable and end up with the palliation only; the CRS+HIPEC combination approach increases the median survival rate and gives a better quality of life to these patients. It is a complicated surgery which poses a high rate of complications and challenges which are difficult to manage and requires a multi-disciplinary approach. The aim of this study is to elaborate the perioperative possible physiological changes, risk factors, and related complications after re-do HIPEC.
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Affiliation(s)
- Namita Mishra
- Department of Anesthesiology, All India Institute of Medical Sciences, Patna, Bihar, India
| | - Madhav Kumar
- Department of Cardiothoracic Surgery, All India Institute of Medical Sciences, Patna, Bihar, India
| | - Soumya Singh
- Department of Anesthesiology, All India Institute of Medical Sciences, Patna, Bihar, India
| | - Khushbu Rani
- Department of Anesthesiology, All India Institute of Medical Sciences, Patna, Bihar, India
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Foster JM, Zhang C, Rehman S, Sharma P, Alexander HR. The contemporary management of peritoneal metastasis: A journey from the cold past of treatment futility to a warm present and a bright future. CA Cancer J Clin 2023; 73:49-71. [PMID: 35969103 DOI: 10.3322/caac.21749] [Citation(s) in RCA: 43] [Impact Index Per Article: 21.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/23/2022] [Revised: 05/12/2022] [Accepted: 06/15/2022] [Indexed: 01/17/2023] Open
Abstract
Peritoneal metastasis (PM) is often regarded as a less frequent pattern of spread; however, collectively across all spectra of primary tumors, the consequences of PM impact a large population of patients annually. Unlike other modes of metastasis, symptoms at presentation or during the treatment course are common, representing an additional challenge in the management of PM. Early efforts with chemotherapy and incomplete surgical interventions transiently improved symptoms, but durable symptom control and survival extension were rare, which established a perspective of treatment futility for PM through most of the 20th century. Notably, the continued development of better systemic therapy combinations, optimization of cytoreductive surgery (CRS), and rigorous investigation of combining regional therapy-specifically hyperthermic intraperitoneal chemotherapy-with CRS, have resulted in more effective multimodal treatment options for patients with PM. In this article, the authors provide a comprehensive review of the data establishing the contemporary approach for tumors with a high frequency of PM, including appendix, colorectal, mesothelioma, and gastric cancers. The authors also explore the emerging role of adding hyperthermic intraperitoneal chemotherapy to the well established paradigm of CRS and systemic therapy for advanced ovarian cancer, as well as the recent clinical trials identifying the efficacy of poly(adenosine diphosphate ribose) polymerase maintenance therapy. Finally, recent data are included that explore the role of precision medicine technology in PM management that, in the future, may help further improve patient selection, identify the best systemic therapy regimens, detect actionable mutations, and identify new targets for drug development.
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Affiliation(s)
- Jason M Foster
- Division of Surgical Oncology, Department of Surgery, University of Nebraska Medical Center, Omaha, Nebraska, USA
| | - Chunmeng Zhang
- Division of Surgical Oncology, Department of Surgery, University of Nebraska Medical Center, Omaha, Nebraska, USA
| | - Shahyan Rehman
- Division of Surgical Oncology, Rutgers Cancer Institute of New Jersey
| | - Prateek Sharma
- Division of Surgical Oncology, Department of Surgery, University of Nebraska Medical Center, Omaha, Nebraska, USA
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20
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Račkauskas R, Baušys A, Jurgaitis J, Paškonis M, Strupas K. Initial Experience of Cytoreductive Surgery (CRS) and Hyperthermic Intraperitoneal Chemotherapy (HIPEC) in Baltic Country Center. J Clin Med 2022; 11:jcm11195554. [PMID: 36233421 PMCID: PMC9572244 DOI: 10.3390/jcm11195554] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2022] [Revised: 09/13/2022] [Accepted: 09/21/2022] [Indexed: 11/16/2022] Open
Abstract
Background: Peritoneal surface malignancies (PSMs) are a heterogenous group of primary and metastatic cancers affecting the peritoneum. They are associated with poor long-term outcomes. Many centers around the world adopt cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) in routine clinical practice for these otherwise condemned patients despite a lack of high-level evidence from randomized control trials. This study aimed to investigate and present our 10-year experience with this controversial method, CRS and HIPEC, for PSM in a single tertiary center in a Baltic country. Methods: Patients who underwent CRS and HIPEC at Vilnius University Hospital Santaros Klinikos between 2011 and 2021 were included in this retrospective study. Overall survival was the primary study outcome. Secondary outcomes included postoperative morbidity and mortality, and local or systemic recurrence rates. Results: Sixty-nine patients who underwent CRS and HIPEC were included in the study. Most patients underwent treatment for peritoneal metastases from colorectal, ovarian, and appendiceal cancers. Six (8.7%) patients received CRS and HIPEC for primary peritoneal neoplasm—pseudomyxoma peritonei. The mean peritoneal carcinomatosis index score was 12 ± 7. Complete cytoreduction was achieved in 62 (89.9%) patients. The mean OS was 39 ± 29 months. The mean survival of patients with PSMs of different origin was as follows: 39 ± 25 (95% CI: 28–50) months for colorectal cancer, 44 ± 31 (95% CI: 30–58) months for ovarian cancer, 32 ± 21 (95% CI: 21–43) months for appendiceal cancer, 422 ± 1 (95% CI: 12–97) months for pseudomyxoma peritonei, and 7 months for gastric cancer. Conclusions: The current study demonstrated the results of the CRS and HIPEC program in a single Baltic country tertiary center. Patients who underwent CRS and HIPEC for PSMs achieved moderate survival rates with acceptable postoperative morbidity and mortality risk.
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21
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Zhang Y, Qin X, Li Y, Zhang X, Luo R, Wu Z, Li V, Han S, Wang H, Wang H. A Prediction Model Intended for Exploratory Laparoscopy Risk Stratification in Colorectal Cancer Patients With Potential Occult Peritoneal Metastasis. Front Oncol 2022; 12:943951. [PMID: 35912189 PMCID: PMC9326510 DOI: 10.3389/fonc.2022.943951] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2022] [Accepted: 06/22/2022] [Indexed: 11/20/2022] Open
Abstract
BACKGROUND The early diagnosis of occult peritoneal metastasis (PM) remains a challenge due to the low sensitivity on computed tomography (CT) images. Exploratory laparoscopy is the gold standard to confirm PM but should only be proposed in selected patients due to its invasiveness, high cost, and port-site metastasis risk. In this study, we aimed to develop an individualized prediction model to identify occult PM status and determine optimal candidates for exploratory laparoscopy. METHOD A total of 622 colorectal cancer (CRC) patients from 2 centers were divided into training and external validation cohorts. All patients' PM status was first detected as negative on CT imaging but later confirmed by exploratory laparoscopy. Multivariate analysis was used to identify independent predictors, which were used to build a prediction model for identifying occult PM in CRC. The concordance index (C-index), calibration plot and decision curve analysis were used to evaluate its predictive accuracy and clinical utility. RESULTS The C-indices of the model in the development and validation groups were 0.850 (95% CI 0.815-0.885) and 0.794 (95% CI, 0.690-0.899), respectively. The calibration curve showed consistency between the observed and predicted probabilities. The decision curve analysis indicated that the prediction model has a great clinical value between thresholds of 0.10 and 0.72. At a risk threshold of 30%, a total of 40% of exploratory laparoscopies could have been prevented, while still identifying 76.7% of clinically occult PM cases. A dynamic online platform was also developed to facilitate the usage of the proposed model. CONCLUSIONS Our individualized risk model could reduce the number of unnecessary exploratory laparoscopies while maintaining a high rate of diagnosis of clinically occult PM. These results warrant further validation in prospective studies. CLINICAL TRIAL REGISTRATION https://www.isrctn.com, identifier ISRCTN76852032.
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Affiliation(s)
- Yuanxin Zhang
- Department of Colorectal Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Xiusen Qin
- Department of Colorectal Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Disease, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Yang Li
- Department of Colorectal Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Xi Zhang
- General Surgery Center, Department of Gastrointestinal Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou, China
| | - Rui Luo
- Department of Colorectal Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Zhijie Wu
- Department of Colorectal Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Victoria Li
- Department of Secondary Education, Yew Chung International School, Kowloon Tong, Hong Kong, China
| | - Shuai Han
- General Surgery Center, Department of Gastrointestinal Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou, China
| | - Hui Wang
- Department of Colorectal Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Disease, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Huaiming Wang
- Department of Colorectal Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Disease, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
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22
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Huang B, Rouvelas I, Nilsson M. Gastric and gastroesophageal junction cancer: Risk factors and prophylactic treatments for prevention of peritoneal recurrence after curative intent surgery. Ann Gastroenterol Surg 2022; 6:474-485. [PMID: 35847435 PMCID: PMC9271029 DOI: 10.1002/ags3.12565] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/23/2021] [Revised: 02/13/2022] [Accepted: 03/01/2022] [Indexed: 11/08/2022] Open
Abstract
Aim Relapse after curative treatment for advanced gastric cancer, and especially peritoneal recurrence, is very common and has a dismal prognosis. The aim of this review is to summarize existing evidence regarding risk factors and prophylactic treatments intending to prevent peritoneal recurrence. Methods A structured search of relevant studies was conducted in MEDLINE, Embase, and the Cochrane Library. Results The main risk factors identified are advanced pathological T-stage (pT ≥ 3), regional lymph node involvement, diffuse/poorly cohesive type tumor, poorly differentiated cancer, and positive peritoneal wash cytology. Systemic chemotherapy in the perioperative or adjuvant setting improves survival for the patients but despite this peritoneal recurrence remains a common and yet an unsolved clinical problem. Different approaches of intraperitoneal chemotherapy such as hyperthermic intraperitoneal chemotherapy and early postoperative intraperitoneal chemotherapy have shown promising results as prophylactic treatments aiming to prevent peritoneal recurrence. Conclusion Future studies are warranted to find safe and effective treatments to prevent peritoneal recurrence.
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Affiliation(s)
- Biying Huang
- Department of Upper Abdominal DiseasesKarolinska University HospitalStockholmSweden
| | - Ioannis Rouvelas
- Department of Upper Abdominal DiseasesKarolinska University HospitalStockholmSweden
- Division of SurgeryDepartment of Clinical Science, Intervention and Technology (CLINTEC)Karolinska InstitutetStockholmSweden
| | - Magnus Nilsson
- Department of Upper Abdominal DiseasesKarolinska University HospitalStockholmSweden
- Division of SurgeryDepartment of Clinical Science, Intervention and Technology (CLINTEC)Karolinska InstitutetStockholmSweden
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23
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Zhang Y, Qin X, Luo R, Wang H, Wang H, Luo H. Risk Factors for Synchronous Peritoneal Metastases in Colorectal Cancer: A Systematic Review and Meta-Analysis. Front Oncol 2022; 12:885504. [PMID: 35795042 PMCID: PMC9251319 DOI: 10.3389/fonc.2022.885504] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2022] [Accepted: 05/23/2022] [Indexed: 11/13/2022] Open
Abstract
Background Early detection of synchronous colorectal peritoneal metastases (CPMs) is difficult due to the absence of typical symptoms and the low accuracy of imaging examinations. Increasing the knowledge of the risk factors for synchronous CPM may be essential for early diagnosis and improving their management. This study aimed to identify the risk factors for synchronous CPM. Method The study was registered at PROSPERO (CRD42020198548). The PubMed, Embase and Cochrane Library databases were searched for studies comparing the clinicopathological and molecular features between patients with or without synchronous CPM. The pooled data were assessed by a random-effects model. Results Twenty-five studies were included. A synchronous CPM was positively associated with female sex (OR 1.299; 1.118 to 1.509; P = 0.001), PROK1/PROKR2-positivity (OR 2.244; 1.031 to 4.884; P = 0.042), right-sided colon cancer (OR 2.468; 2.050 to 2.970; P < 0.001), poorly differentiated grade (OR 2.560; 1.537 to 4.265; P < 0.001), BRAF mutation (OR 2.586; 1.674 to 3.994; P < 0.001), mucinous adenocarcinoma (OR 3.565; 2.095 to 6.064; P < 0.001), signet-ring cell carcinoma (OR 4.480; 1.836 to 10.933; P = 0.001), N1-2 (OR 5.665; 3.628 to 8.848; P < 0.001), T4 (OR 12.331; 7.734 to 19.660; P < 0.001) and elevated serum CA19-9 (OR 12.868; 5.196 to 31.867; P < 0.001). Conclusions These evidence-based risk factors are indicators that could predict the presence of synchronous CPMs and can improve their management. Systematic Review Registration www.crd.york.ac.uk/prospero, identifier: CRD42020198548.
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Affiliation(s)
- Yuanxin Zhang
- Department of Colorectal Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Xiusen Qin
- Department of Colorectal Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Disease, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Rui Luo
- Department of Colorectal Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Hui Wang
- Department of Colorectal Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Disease, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Huaiming Wang
- Department of Colorectal Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Disease, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
- *Correspondence: Huaiming Wang, ; Hongzhi Luo,
| | - Hongzhi Luo
- Department of Tumor Surgery, Zhongshan City People’s Hospital, Zhongshan, China
- *Correspondence: Huaiming Wang, ; Hongzhi Luo,
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24
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Tonello M, Baratti D, Sammartino P, Di Giorgio A, Robella M, Sassaroli C, Framarini M, Valle M, Macrì A, Graziosi L, Coccolini F, Lippolis PV, Gelmini R, Deraco M, Biacchi D, Santullo F, Vaira M, Di Lauro K, D'Acapito F, Carboni F, Giuffrè G, Donini A, Fugazzola P, Faviana P, Sorrentino L, Scapinello A, Del Bianco P, Sommariva A. Microsatellite and RAS/RAF Mutational Status as Prognostic Factors in Colorectal Peritoneal Metastases Treated with Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy (HIPEC). Ann Surg Oncol 2022; 29:3405-3417. [PMID: 34783946 DOI: 10.1245/s10434-021-11045-3] [Citation(s) in RCA: 22] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2021] [Accepted: 10/20/2021] [Indexed: 12/16/2022]
Abstract
BACKGROUND Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) leads to prolonged survival for selected patients with colorectal (CRC) peritoneal metastases (PM). This study aimed to analyze the prognostic role of micro-satellite (MS) status and RAS/RAF mutations for patients treated with CRS. METHODS Data were collected from 13 Italian centers with PM expertise within a collaborative group of the Italian Society of Surgical Oncology. Clinical and pathologic variables and KRAS/NRAS/BRAF mutational and MS status were correlated with overall survival (OS) and disease-free survival (DFS). RESULTS The study enrolled 437 patients treated with CRS-HIPEC. The median OS was 42.3 months [95% confidence interval (CI), 33.4-51.2 months], and the median DFS was 13.6 months (95% CI, 12.3-14.9 months). The local (peritoneal) DFS was 20.5 months (95% CI, 16.4-24.6 months). In addition to the known clinical factors, KRAS mutations (p = 0.005), BRAF mutations (p = 0.01), and MS status (p = 0.04) were related to survival. The KRAS- and BRAF-mutated patients had a shorter survival than the wild-type (WT) patients (5-year OS, 29.4% and 26.8% vs 51.5%, respectively). The patients with micro-satellite instability (MSI) had a longer survival than the patients with micro-satellite stability (MSS) (5-year OS, 58.3% vs 36.7%). The MSI/WT patients had the best prognosis. The MSS/WT and MSI/mutated patients had similar survivals, whereas the MSS/mutated patients showed the worst prognosis (5-year OS, 70.6%, 48.1%, 23.4%; p = 0.0001). In the multivariable analysis, OS was related to the Peritoneal Cancer Index [hazard ratio (HR), 1.05 per point], completeness of cytoreduction (CC) score (HR, 2.8), N status (HR, 1.6), signet-ring (HR, 2.4), MSI/WT (HR, 0.5), and MSS/WT-MSI/mutation (HR, 0.4). Similar results were obtained for DFS. CONCLUSION For patients affected by CRC-PM who are eligible for CRS, clinical and pathologic criteria need to be integrated with molecular features (KRAS/BRAF mutation). Micro-satellite status should be strongly considered because MSI confers a survival advantage over MSS, even for mutated patients.
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Affiliation(s)
- Marco Tonello
- Unit of Surgical Oncology of the Esophagus and Digestive Tract, Surgical Oncology Department, Veneto Institute of Oncology IOV-IRCCS, Padua, Italy
| | - Dario Baratti
- Peritoneal Surface Malignancy Unit, Department of Surgery, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
| | - Paolo Sammartino
- Cytoreductive Surgery and HIPEC Unit, Department of Surgery "Pietro Valdoni", Sapienza University of Rome, Rome, Italy
| | - Andrea Di Giorgio
- Surgical Unit of Peritoneum and Retroperitoneum, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
| | - Manuela Robella
- Candiolo Cancer Institute, FPO-IRCCS, Candiolo, Turin, Italy
| | - Cinzia Sassaroli
- Colorectal Surgical Oncology, Abdominal Oncology Department, Fondazione Giovanni Pascale" IRCCS, Naples, Italy
| | - Massimo Framarini
- General and Oncologic Surgery, Morgagni-Pierantoni Hospital, AUSL Romagna, Forlì, Italy
| | - Mario Valle
- Peritoneal Malignancies Unit, INT "Regina Elena", Rome, Italy
| | - Antonio Macrì
- Peritoneal Surface Malignancy and Soft Tissue Sarcoma Program, University of Messina, Messina, Italy
| | - Luigina Graziosi
- General and Emergency Surgery Department, Santa Maria della Misericordia Hospital, University of Perugia, Perugia, Italy
| | - Federico Coccolini
- General Emergency and Trauma Surgery, Bufalini Hospital, Cesena, Italy
- General Emergency and Trauma Surgery, Pisa University Hospital, Pisa, Italy
| | - Piero Vincenzo Lippolis
- General and Peritoneal Surgery, Department of Surgery, Hospital University Pisa (AOUP), Pisa, Italy
| | - Roberta Gelmini
- General and Oncological Surgery Unit, AOU of Modena University of Modena and Reggio Emilia, Modena, Italy
| | - Marcello Deraco
- Peritoneal Surface Malignancy Unit, Department of Surgery, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
| | - Daniele Biacchi
- Cytoreductive Surgery and HIPEC Unit, Department of Surgery "Pietro Valdoni", Sapienza University of Rome, Rome, Italy
| | - Francesco Santullo
- Surgical Unit of Peritoneum and Retroperitoneum, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
| | - Marco Vaira
- Candiolo Cancer Institute, FPO-IRCCS, Candiolo, Turin, Italy
| | - Katia Di Lauro
- Department of Advanced Biomedical Sciences, "Federico II" University, Naples, Italy
| | - Fabrizio D'Acapito
- General and Oncologic Surgery, Morgagni-Pierantoni Hospital, AUSL Romagna, Forlì, Italy
| | - Fabio Carboni
- Peritoneal Malignancies Unit, INT "Regina Elena", Rome, Italy
| | - Giuseppe Giuffrè
- Department of Human Pathology in Adult and Developmental Age 'Gaetano Barresi', Section of Pathology, University of Messina, Messina, Italy
| | - Annibale Donini
- General and Emergency Surgery Department, Santa Maria della Misericordia Hospital, University of Perugia, Perugia, Italy
| | - Paola Fugazzola
- General Emergency and Trauma Surgery, Bufalini Hospital, Cesena, Italy
| | - Pinuccia Faviana
- Pathological Anatomy III, Laboratory Medicine Department, Hospital University Pisa (AOUP), Pisa, Italy
| | - Lorena Sorrentino
- General and Oncological Surgery Unit, AOU of Modena University of Modena and Reggio Emilia, Modena, Italy
| | | | - Paola Del Bianco
- Clinical Research Unit, Veneto Institute of Oncology IOV-IRCCS, Padua, Italy
| | - Antonio Sommariva
- Unit of Surgical Oncology of the Esophagus and Digestive Tract, Surgical Oncology Department, Veneto Institute of Oncology IOV-IRCCS, Padua, Italy.
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Minami T, Miyake H, Nagai H, Yoshioka Y, Shibata K, Takahashi D, Yuasa N, Fujino M. Long-term survivor who underwent surgical resections of repeated peritoneal oligometastases from colon cancer : a rare case report. THE JOURNAL OF MEDICAL INVESTIGATION 2022; 69:302-307. [DOI: 10.2152/jmi.69.302] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Affiliation(s)
- Takayuki Minami
- Department of Gastrointestinal Surgery, Japanese Red Cross Aichi Medical Center, Nagoya Daiichi Hospital, Nagoya, Japan
| | - Hideo Miyake
- Department of Gastrointestinal Surgery, Japanese Red Cross Aichi Medical Center, Nagoya Daiichi Hospital, Nagoya, Japan
| | - Hidemasa Nagai
- Department of Gastrointestinal Surgery, Japanese Red Cross Aichi Medical Center, Nagoya Daiichi Hospital, Nagoya, Japan
| | - Yuichiro Yoshioka
- Department of Gastrointestinal Surgery, Japanese Red Cross Aichi Medical Center, Nagoya Daiichi Hospital, Nagoya, Japan
| | - Koji Shibata
- Department of Gastrointestinal Surgery, Japanese Red Cross Aichi Medical Center, Nagoya Daiichi Hospital, Nagoya, Japan
| | - Daigoro Takahashi
- Department of Gastrointestinal Surgery, Japanese Red Cross Aichi Medical Center, Nagoya Daiichi Hospital, Nagoya, Japan
| | - Norihiro Yuasa
- Department of Gastrointestinal Surgery, Japanese Red Cross Aichi Medical Center, Nagoya Daiichi Hospital, Nagoya, Japan
| | - Masahiko Fujino
- Department of Cytology and Molecular Pathology, Japanese Red Cross Aichi Medical Center, Nagoya Daiichi Hospital, Nagoya, Japan
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26
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Kim YJ, Kim CH. Treatment for Peritoneal Metastasis of Patients With Colorectal Cancer. Ann Coloproctol 2021; 37:425-433. [PMID: 34961304 PMCID: PMC8717073 DOI: 10.3393/ac.2021.00920.0131] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/25/2021] [Accepted: 11/15/2021] [Indexed: 02/06/2023] Open
Abstract
From the perspective of survival outcomes, the cancer survival of colorectal cancer (CRC) in the whole stage has improved. Peritoneal metastasis (PM) is found in approximately 8% to 15% of patients with CRC, with a poorer prognosis than that associated with other sites of metastases. Randomized controlled trials and up-to-date meta-analyses provide firm evidence that cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) could significantly improve overall survival compared with systemic chemotherapy alone in selected patients with CRC-PM. Practical guidelines recommend that the management of CRC-PM should be led by a multidisciplinary team carried out in experienced centers and consider CRS plus HIPEC for selected patients. In this review, we aim to provide the latest results of land mark studies and an overview of recent insights with regard to the management of CRC-PM.
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Affiliation(s)
- Young Jin Kim
- Department of Surgery, Seokjeong Wellpark Hospital, Gochang, Korea
| | - Chang Hyun Kim
- Division of Colorectal Surgery, Department of Surgery, Chonnam National University Hwasun Hospital, Chonnam National University Medical School, Hwasun, Korea
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27
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Simkens GA, Wintjens AGWE, Rovers KP, Nienhuijs SW, de Hingh IH. Effective Strategies to Predict Survival of Colorectal Peritoneal Metastases Patients Eligible for Cytoreductive Surgery and HIPEC. Cancer Manag Res 2021; 13:5239-5249. [PMID: 34234566 PMCID: PMC8257566 DOI: 10.2147/cmar.s277912] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2021] [Accepted: 06/16/2021] [Indexed: 12/11/2022] Open
Abstract
Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC), often combined with systemic therapy, can be offered to selected colorectal peritoneal metastases (PM) patients. However, clinical heterogeneity and the lack of high-level evidence challenges determination of the correct treatment strategy. This review aims to provide an overview of current strategies to predict survival of colorectal PM patients treated with CRS and HIPEC, guiding clinicians to select a suitable treatment-strategy and to inform patients about their prognosis. First, the prognostic relevance of several clinicopathological prognostic factors, such as extent of PM, location of primary tumor, histology type, and the presence of lymph node or liver metastases will be discussed. Subsequently, special attention will be given to recent developments in several aspects of tumor biology such as RAF/RAS mutations, circulating tumor DNA, immunoprofiling, and consensus molecular subtypes. Finally, currently available prognostic models to predict survival will be evaluated, concluding these models perform moderate to good, but most of them partly rely on intra-operative data. New insights in tumor biology, as well as the reliable assessment of extent of peritoneal disease by diffusion weighted MRI pose promising opportunities to establish an adequate and clinically meaningful preoperative prognostic model in the near future.
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Affiliation(s)
- Geert A Simkens
- Department of Surgery, Catharina Cancer Institute, Eindhoven, The Netherlands.,Department of Surgery, Maastricht University Medical Centre, Maastricht, The Netherlands
| | - Anne G W E Wintjens
- NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University, Maastricht, The Netherlands
| | - Koen P Rovers
- Department of Surgery, Catharina Cancer Institute, Eindhoven, The Netherlands
| | - Simon W Nienhuijs
- Department of Surgery, Catharina Cancer Institute, Eindhoven, The Netherlands
| | - Ignace H de Hingh
- Department of Surgery, Catharina Cancer Institute, Eindhoven, The Netherlands.,GROW - School for Oncology and Development Biology, Maastricht University, Maastricht, The Netherlands
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The Characteristics of 206 Long-Term Survivors with Peritoneal Metastases from Colorectal Cancer Treated with Curative Intent Surgery: A Multi-Center Cohort from PSOGI. Cancers (Basel) 2021; 13:cancers13122964. [PMID: 34199234 PMCID: PMC8231850 DOI: 10.3390/cancers13122964] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2021] [Revised: 06/01/2021] [Accepted: 06/09/2021] [Indexed: 01/04/2023] Open
Abstract
Simple Summary Cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy improves survival in selected patients with peritoneal metastases from colorectal cancer (CRC). However, the characteristics of long-term survivors are not well documented. This study set out to investigate the patient characteristics associated with the long-term survival of peritoneal metastases from CRC. We retrospectively analyzed 206 long-term survivors who underwent CRS for peritoneal metastases from CRC. We found that most long-term survivors showed low peritoneal cancer index (PCI), low PCI of small bowel subsets, and complete cytoreduction (CC-0), while some exhibited characteristics considered associated with poor prognosis. Abstract Background: We conducted this study to review the patient characteristics associated with long-term survival in patients with peritoneal metastases from colorectal cancer who underwent cytoreductive surgery (CRS). Methods: We retrospectively investigated patients with peritoneal metastases from CRC treated with curative intent surgery with or without hyperthermic intraperitoneal chemotherapy at 13 institutions worldwide between January 1985 and April 2015 and survived longer than five years after the first CRS for peritoneal metastases. Clinical and oncological features and therapeutic parameters were described and analyzed. Results: Two hundred six long-term survivors were available for study. The median peritoneal cancer index (PCI) of this cohort was 4 (interquartile range (IQR), 2–7), and the median score of the small bowel regions of the PCI (SB-PCI) was 0 (IQR, 0–2). Complete cytoreduction (CC-0) was achieved in 180 (87.4%) patients. Recurrence was observed in 122 (59.2%) patients at a median of 1.8 (IQR, 1.2–2.6) years. Conclusions: While most long-term survivors showed low PCI/SB-PCI and CCR-0, some had characteristics considered associated with poor prognosis. Curative intent treatments may be considered in well-informed and fit patients showing negative factors affecting survival outcome.
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Sugita Y, Yamashita K, Fujita M, Saito M, Yamada K, Agawa K, Watanabe A, Fukuoka E, Hasegawa H, Kanaji S, Oshikiri T, Matsuda T, Nakamura T, Suzuki S, Kakeji Y. CD244 + polymorphonuclear myeloid‑derived suppressor cells reflect the status of peritoneal dissemination in a colon cancer mouse model. Oncol Rep 2021; 45:106. [PMID: 33907826 PMCID: PMC8072829 DOI: 10.3892/or.2021.8057] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2021] [Accepted: 03/29/2021] [Indexed: 12/24/2022] Open
Abstract
Despite the recent development of chemotherapeutic agents, the prognosis of colorectal cancer (CRC) patients with peritoneal dissemination (PD) remains poor. The tumor immune microenvironment (TIME) has drawn attention as a key contributing factor of tumor progression. Of TIME components, myeloid-derived suppressor cells (MDSCs) are considered to play a responsible role in the immunosuppressive characteristics of the TIME. MDSCs are classified into two major subsets: Monocytic MDSCs (M-MDSCs) and polymorphonuclear MDSCs (PMN-MDSCs). Therefore, we hypothesize that MDSCs would play important roles in the PD-relevant TIME and PD progression. To address this hypothesis, we established PD mouse models. As the PD nodules consisted scarcely of immune cells, we focused on the peritoneal cavity, but not PD nodule, to evaluate the PD-relevant TIME. As a result, intraperitoneal PMN-MDSCs were found to be substantially increased in association with PD progression. Based on these results, we phenotypically and functionally verified the usefulness of CD244 for identifying PMN-MDSCs. In addition, the concentrations of interleukin (IL)-6 and granulocyte-colony stimulating factor (G-CSF) were significantly increased in the peritoneal cavity, both of which were produced by the tumors and thought to contribute to the increases in the PMN-MDSCs. In vivo depletion of the PMN-MDSCs by anti-Ly6G monoclonal antibody (mAb) significantly inhibited the PD progression and reverted CD4+ and CD8+ T cells in the peritoneal cavity and the peripheral blood. Collectively, these results suggest that the targeted therapy for PMN-MDSCs would provide not only new therapeutic value but also a novel strategy to synergize with T-cell-based immunotherapy for CRC-derived PD.
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Affiliation(s)
- Yutaka Sugita
- Division of Gastrointestinal Surgery, Department of Surgery, Kobe University Graduate School of Medicine, Kobe, Hyogo 650‑0017, Japan
| | - Kimihiro Yamashita
- Division of Gastrointestinal Surgery, Department of Surgery, Kobe University Graduate School of Medicine, Kobe, Hyogo 650‑0017, Japan
| | - Mitsugu Fujita
- Division of Gastrointestinal Surgery, Department of Surgery, Kobe University Graduate School of Medicine, Kobe, Hyogo 650‑0017, Japan
| | - Masafumi Saito
- Department of Disaster and Emergency and Critical Care Medicine, Kobe University Graduate School of Medicine, Kobe, Hyogo 650‑0017, Japan
| | - Kota Yamada
- Division of Gastrointestinal Surgery, Department of Surgery, Kobe University Graduate School of Medicine, Kobe, Hyogo 650‑0017, Japan
| | - Kyosuke Agawa
- Division of Gastrointestinal Surgery, Department of Surgery, Kobe University Graduate School of Medicine, Kobe, Hyogo 650‑0017, Japan
| | - Akihiro Watanabe
- Division of Gastrointestinal Surgery, Department of Surgery, Kobe University Graduate School of Medicine, Kobe, Hyogo 650‑0017, Japan
| | - Eiji Fukuoka
- Department of Gastroenterological Surgery, Hyogo Cancer Center, Akashi, Hyogo 673‑8558, Japan
| | - Hiroshi Hasegawa
- Division of Gastrointestinal Surgery, Department of Surgery, Kobe University Graduate School of Medicine, Kobe, Hyogo 650‑0017, Japan
| | - Shingo Kanaji
- Division of Gastrointestinal Surgery, Department of Surgery, Kobe University Graduate School of Medicine, Kobe, Hyogo 650‑0017, Japan
| | - Taro Oshikiri
- Division of Gastrointestinal Surgery, Department of Surgery, Kobe University Graduate School of Medicine, Kobe, Hyogo 650‑0017, Japan
| | - Takeru Matsuda
- Division of Gastrointestinal Surgery, Department of Surgery, Kobe University Graduate School of Medicine, Kobe, Hyogo 650‑0017, Japan
| | - Tetsu Nakamura
- Division of Gastrointestinal Surgery, Department of Surgery, Kobe University Graduate School of Medicine, Kobe, Hyogo 650‑0017, Japan
| | - Satoshi Suzuki
- Division of Community Medicine and Medical Network, Department of Social Community Medicine and Health Science, Kobe University Graduate School of Medicine, Kobe, Hyogo 650‑0017, Japan
| | - Yoshihiro Kakeji
- Division of Gastrointestinal Surgery, Department of Surgery, Kobe University Graduate School of Medicine, Kobe, Hyogo 650‑0017, Japan
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Ray MD, Dhall K. Hyperthermic Intraperitoneal Chemotherapy (HIPEC) in the management of peritoneal surface malignancies - An evidence-based review. Curr Probl Cancer 2021; 45:100737. [PMID: 34116836 DOI: 10.1016/j.currproblcancer.2021.100737] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2020] [Revised: 02/27/2021] [Accepted: 03/15/2021] [Indexed: 12/23/2022]
Abstract
BACKGROUND Traditionally, peritoneal surface malignancies (PSM) were considered terminal diseases because of their advanced nature, therefore, systemic chemotherapy was given with palliative intent only. As a result, very poor survival outcomes were observed. But with the introduction of complete Cytoreductive surgery (CRS) and Hyperthermic intraperitoneal chemotherapy (HIPEC), the scenario has changed dramatically. METHODOLOGY An objective electronic database search was performed in Pubmed, NLM Catalog, Google scholar, Bookshelf, and Pubmed Central published in the time period from 2000 till 2020. All the randomized studies were included. In the absence of randomized studies, both prospective and retrospective studies were included. The outcomes of HIPEC were measured in terms of median survival, disease-free survival, overall survival, complications and drug toxicities. RESULTS CRS and HIPEC are considered the standard of care for PMP and MPM even in the absence of level 1 evidence due to lack of an effective alternative treatment. In colorectal and gastric cancer, several phase-three trials are showing overall survival benefit in selected cases while there is a prophylactic and palliative role of HIPEC in gastric cancer. Three reported phase 3 trials showed positive results in ovarian cancer. In peritoneal sarcomatosis, the role of HIPEC is yet to be proven. CONCLUSION The patient selection is the key to the successful outcomes after HIPEC. HIPEC should be performed by the experienced surgeons in specialized centres with a strong critical care and intensive care support to reduce the morbidity and mortality. Ongoing trials and future directions will prove to be an indispensable arm in the oncological armamentarium.
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Affiliation(s)
- Mukur Dipi Ray
- Department of Surgical Oncology, All India Institute of Medical Sciences, New Delhi, India
| | - Kunal Dhall
- Department of Surgical Oncology, All India Institute of Medical Sciences, New Delhi, India.
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Shuayb M, Mehedi Hasan M, Hoque MR, Mushtaq Hussain Q, Begum R, Reza MS. Survival and prognostic association in stage IV colorectal cancer patients treated with chemotherapy in Bangladesh. Jpn J Clin Oncol 2021; 51:552-559. [PMID: 33341898 DOI: 10.1093/jjco/hyaa228] [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: 08/31/2020] [Accepted: 11/03/2020] [Indexed: 11/13/2022] Open
Abstract
OBJECTIVE Prognostic factors in colorectal cancer have lesser been evaluated in developing countries. This study aims to determine overall survival and prognostic factors for metastatic colorectal cancer patients who were non-operable and received chemotherapy. METHODS The study retrospectively investigated 67 inoperable metastatic colorectal cancer patients at Square Hospital, Bangladesh. The primary endpoint was overall survival, and the secondary endpoints were prognostic association with factors. Survival probabilities were calculated by non-parametric Kaplan-Meier method and compared by log-rank test. Univariate and multivariable Cox proportional hazard models were implemented to assess the prognostic association. RESULTS Median survival of the entire cohort was 14 months (95% confidence interval: 11-25). In multivariable analysis, two prognostic factors were independently associated with survival: Karnofsky performance status and carcinoembryonic antigen. Patients with Karnofsky performance status <70 had significant higher risk of death than those with Karnofsky performance status ≥70 (adjusted hazard ratio 4.25, 95% confidence interval: 2.15-8.39). Higher risk of death was found to be associated with higher carcinoembryonic antigen: adjusted hazard ratio was 1.72 (95% confidence interval: 0.81-3.68) and 2.96 (95% confidence interval: 1.25-7.01) for patients with carcinoembryonic antigen 10-100 and >100 ng/ml, respectively, while comparing with carcinoembryonic antigen <10 ng/ml. The presence of peritoneal metastasis and grade-III tumour significantly worsened the survival in univariate analysis (hazard ratio 2.46, 95% confidence interval: 1.32-4.57 and hazard ratio 1.74, 95% confidence interval: 1.01-3.03, respectively) but not in multivariable analysis (adjusted hazard ratio 1.92, 95% confidence interval: 0.88-4.18 and adjusted hazard ratio 1.25, 95% confidence interval: 0.66-2.36, respectively). CONCLUSION The study reported survival of stage IV colorectal cancer patients undergo chemotherapy and identified that Karnofsky performance status and carcinoembryonic antigen are the poor prognostic factors to this cohort adjusting for other factors.
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Affiliation(s)
- Md Shuayb
- Square Oncology & Radiotherapy Centre, Square Hospitals Ltd, Dhaka, Bangladesh.,Vancouver General Hospital, University of British Columbia, Vancouver, BC, Canada
| | - Md Mehedi Hasan
- Square Oncology & Radiotherapy Centre, Square Hospitals Ltd, Dhaka, Bangladesh
| | - Md Rashedul Hoque
- Faculty of Health Sciences, Simon Fraser University, Burnaby, BC, Canada
| | | | - Rabeya Begum
- Faculty of Health Sciences, Simon Fraser University, Burnaby, BC, Canada
| | - Md Salim Reza
- Square Oncology & Radiotherapy Centre, Square Hospitals Ltd, Dhaka, Bangladesh
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Prabhu A, Brandl A, Wakama S, Sako S, Ishibashi H, Mizumoto A, Takao N, Ichinose M, Motoi S, Liu Y, Yonemura Y. Effect of oxaliplatin-based chemotherapy on chemosensitivity in patients with peritoneal metastasis from colorectal cancer treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy: proof-of-concept study. BJS Open 2021; 5:6220267. [PMID: 33839755 PMCID: PMC8038512 DOI: 10.1093/bjsopen/zraa075] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2020] [Accepted: 08/13/2020] [Indexed: 12/15/2022] Open
Abstract
Background Chemosensitivity testing, including collagen gel droplet‐embedded culture drug sensitivity test, has proven to be a useful tool in therapeutic decision‐making. This retrospective analysis investigated chemosensitivity testing of peritoneal metastases collected during cytoreductive surgery (CRS), and its impact on survival in patients with colorectal cancer. Methods All patients with peritoneal metastasis from colorectal cancer who underwent CRS with or without hyperthermic intraperitoneal chemotherapy (HIPEC) between November 2008 and October 2014 were included. The growth inhibition rate was expressed as the ratio between the image density after treatment (T) and that before treatment (control, C). Tumours with a reduction in T/C ratio of less than 20 per cent were defined as resistant and those with a reduction of 20 per cent or more as sensitive. Groups were compared for overall (OS) and disease‐free (DFS) survival. Results Of 84 eligible patients, 81 received neoadjuvant chemotherapy (NACT), including 56 patients with an oxaliplatin‐based regimen. Mean(s.d.) follow‐up was 23·4(22·9) months. The median overall survival of all patients was 19·0 (i.q.r. 5·7–36·1) months, with a progression‐free survival time of 10·1 (4·5–17·0) months. Patients who received oxaliplatin‐based NACT had significantly altered chemosensitivity to oxaliplatin; only 20 of 51 such patients showed chemosensitivity to oxaliplatin compared with 16 of 24 who did not undergo oxaliplatin‐based NACT (P = 0·046). However, patients who showed chemoresistance to oxaliplatin had similar OS to those with chemosensitivity (18·8 versus 18·1 months; P = 0·835). The choice of HIPEC agents in patients who received oxaliplatin‐based NACT did not significantly influence survival (oxaliplatin versus mitomycin C: median OS 20·6 (10·9–24·8) versus 19·0 (10·5–34·6) months, P = 0·811; DFS 6·6 (2·8–25·7) versus 9·3 (4·1–13·9) months, P = 0·191). Conclusion Patients who had oxaliplatin‐based NACT showed a higher rate of chemoresistance to oxaliplatin at the time of CRS and HIPEC. The impact of chemosensitivity testing on OS remains unclear and needs further investigation.
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Affiliation(s)
- A Prabhu
- Department of Surgical Oncology Thangam Cancer Centre, Namakkal India
| | - A Brandl
- Digestive Unit Champalimaud Foundation, Lisbon, Portugal
| | - S Wakama
- Department of Surgery Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - S Sako
- Non-Profit Organization to Support Peritoneal Surface Malignancy Treatment Japanese/Asian School of Peritoneal Surface Oncology, Kyoto Japan.,Department of Regional Cancer Therapy Peritoneal Surface Malignancy Centre, Kishiwada, Tokushukai Hospital Kishiwada Japan
| | - H Ishibashi
- Department of Regional Cancer Therapy Peritoneal Surface Malignancy Centre, Kishiwada, Tokushukai Hospital Kishiwada Japan
| | - A Mizumoto
- Department of Regional Cancer Therapy Peritoneal Surface Malignancy Centre, Kusatsu General Hospital Shiga Japan
| | - N Takao
- Department of Regional Cancer Therapy Peritoneal Surface Malignancy Centre, Kusatsu General Hospital Shiga Japan
| | - M Ichinose
- Department of Regional Cancer Therapy Peritoneal Surface Malignancy Centre, Kusatsu General Hospital Shiga Japan
| | - S Motoi
- Department of Regional Cancer Therapy Peritoneal Surface Malignancy Centre, Kusatsu General Hospital Shiga Japan
| | - Y Liu
- Non-Profit Organization to Support Peritoneal Surface Malignancy Treatment Japanese/Asian School of Peritoneal Surface Oncology, Kyoto Japan
| | - Y Yonemura
- Non-Profit Organization to Support Peritoneal Surface Malignancy Treatment Japanese/Asian School of Peritoneal Surface Oncology, Kyoto Japan.,Department of Regional Cancer Therapy Peritoneal Surface Malignancy Centre, Kishiwada, Tokushukai Hospital Kishiwada Japan.,Department of Regional Cancer Therapy Peritoneal Surface Malignancy Centre, Kusatsu General Hospital Shiga Japan
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Lurvink RJ, Rovers KP, Nienhuijs SW, Creemers GJ, Burger JWA, de Hingh IHJ. Pressurized intraperitoneal aerosol chemotherapy with oxaliplatin (PIPAC-OX) in patients with colorectal peritoneal metastases-a systematic review. J Gastrointest Oncol 2021; 12:S242-S258. [PMID: 33968441 DOI: 10.21037/jgo-20-257] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
Pressurized intraperitoneal aerosol chemotherapy with oxaliplatin (PIPAC-OX) is increasingly used as a palliative treatment option for patients with colorectal peritoneal metastases (CPM). The present study aimed to systematically review all clinical studies reporting safety and efficacy outcomes of PIPAC-OX in patients with CPM. PubMed, EMBASE, The Cochrane Library, and CINAHL were systematically searched to identify all clinical studies that included at least one patient with CPM treated with PIPAC-OX and reported one of the following outcomes: adverse events, tumor response, quality of life, secondary cytoreductive surgery, progression-free survival, overall survival, and environmental safety of PIPAC-OX. Results were narratively described. Of 28 included studies, only 14 non-comparative studies separately reported at least one outcome of PIPAC-OX for CPM, of which only two studies specifically focused on this group. These 14 studies reported adverse events (5 studies), tumor response (5 studies), secondary cytoreductive surgery (4 studies), progression-free survival (1 study), overall survival (5 studies), and environmental safety (2 studies). Except for 5 studies (describing 26 patients), none of the included studies stratified their results for PIPAC-OX monotherapy and PIPAC-OX with concomitant systemic therapy, and none of the studies reporting survival outcomes stratified results for line of palliative treatment, complicating interpretation. No PIPAC-OX related deaths were reported. No occupational platinum was detected during PIPAC-OX. The available evidence regarding PIPAC-OX for CPM is limited and difficult to interpret. Despite these limitations, PIPAC-OX appears safe in patients with CPM and safe for operating personnel. To increase insight in the role of PIPAC-OX in this setting, investigators of ongoing and future studies are encouraged to report separate outcomes of PIPAC-OX for CPM, to stratify their results for PIPAC-OX monotherapy and PIPAC-OX with concomitant systemic therapy, and to stratify survival results for line of palliative treatment.
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Affiliation(s)
- Robin J Lurvink
- Department of Surgery, Catharina Hospital, Eindhoven, The Netherlands
| | - Koen P Rovers
- Department of Surgery, Catharina Hospital, Eindhoven, The Netherlands
| | - Simon W Nienhuijs
- Department of Surgery, Catharina Hospital, Eindhoven, The Netherlands
| | - Geert-Jan Creemers
- Department of Medical Oncology, Catharina Hospital, Eindhoven, The Netherlands
| | | | - Ignace H J de Hingh
- Department of Surgery, Catharina Hospital, Eindhoven, The Netherlands.,GROW-School for Oncology and Developmental Biology, Maastricht University, Maastricht, The Netherlands
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34
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de Boer NL, Brandt-Kerkhof ARM, Madsen EVE, Doukas M, Verhoef C, Burger JWA. The Accuracy of the Surgical Peritoneal Cancer Index in Patients with Peritoneal Metastases of Colorectal Cancer. Dig Surg 2021; 38:205-211. [PMID: 33657551 DOI: 10.1159/000513353] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/10/2020] [Accepted: 11/15/2020] [Indexed: 12/10/2022]
Abstract
INTRODUCTION The peritoneal cancer index (PCI) is one of the most important prognostic factors in patients with peritoneal metastases from colorectal cancer undergoing cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC). The PCI is determined during laparotomy by 2 experienced surgeons and plays a major role in the decision to proceed with CRS-HIPEC. The primary objective of this study was to determine the accuracy of the surgical PCI (sPCI) by comparing it with the PCI confirmed by the pathologist (pPCI). METHODS All consecutive patients who underwent CRS-HIPEC for colorectal peritoneal metastases between February 2015 and June 2018 were identified. Relevant patient- and tumor-related characteristics were collected. RESULTS In total, 119 patients were included, 60 males (50.4%). The median age was 64 (IQR 55-71). The median sPCI (sPCI = 11, IQR 6-16) was significantly higher than the median pPCI (pPCI = 8, IQR 3-13, p < 0.001). The total pPCI was lower than the total sPCI in 80 patients (67.2%). In 21 patients (17.6%), the sPCI was overestimated with ≥5 points. Small lesions are more likely to be negative. In patients that underwent resection of their primary tumor prior to CRS-HIPEC, the difference between the sPCI and pPCI was significantly larger (p < 0.05). CONCLUSIONS Surgical calculation of the PCI often results in overestimation. Far-reaching consequences are tied to the macroscopic evaluation of the sPCI, but this evaluation seems not very reliable.
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Affiliation(s)
- Nadine L de Boer
- Department of Surgical Oncology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands,
| | | | - Eva V E Madsen
- Department of Surgical Oncology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands
| | - Michael Doukas
- Department of Pathology, Erasmus MC, Rotterdam, The Netherlands
| | - Cornelis Verhoef
- Department of Surgical Oncology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands
| | - Jacobus W A Burger
- Department of Surgical Oncology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands.,Department of Surgery, Catharina Cancer Institute, Eindhoven, The Netherlands
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Nindra U, Shahnam A, Mahon KL. Review of systemic chemotherapy in unresectable colorectal peritoneal carcinomatosis. Asia Pac J Clin Oncol 2021; 18:7-12. [PMID: 33609014 DOI: 10.1111/ajco.13552] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2020] [Accepted: 12/02/2020] [Indexed: 01/02/2023]
Abstract
Colorectal cancer remains the third most common malignancy in Australia with the peritoneum being the second most common metastatic site. Colorectal peritoneal carcinomatosis (CPC) can be treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy but this is only limited to a small subset of patients. Those with inoperable disease have a particularly poor prognosis. While the ideal systemic regimen has not been defined, 5-fluorouracil-based chemotherapy regimens appear to provide overall and progression free survival benefits. The role of targeted agents such as bevacizumab (vascular endothelial growth factor inhibitor) or cetuximab (epidermal growth factor inhibitor) in the setting of CPC is still evolving. Currently, retrospective analyses have shown promising results for the use of bevacizumab in addition to systemic chemotherapy but similar results have not been seen with cetuximab or panitumumab. However, there is significant heterogeneity in the trial data, lack of prospective randomized controlled trials and demonstrated treatment variability based on age and tumour characteristics. This review summarises the current literature in regard to treatment in the unresectable CPC setting as well as discussing issues with the current data and highlighting the need for further trials.
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Affiliation(s)
- Udit Nindra
- Royal Prince Alfred Hospital, Sydney, Australia.,Chris O'Brien Lifehouse, Sydney, Australia
| | - Adel Shahnam
- Royal Prince Alfred Hospital, Sydney, Australia.,Chris O'Brien Lifehouse, Sydney, Australia
| | - Kate L Mahon
- Chris O'Brien Lifehouse, Sydney, Australia.,Garvan Institute of Medical Research, Sydney, Australia.,University of NSW, Sydney, Australia.,University of Sydney, Sydney, Australia
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Kamada Y, Hida K, Ishibashi H, Sako S, Mizumoto A, Ichinose M, Padmanabhan N, Yoshida S, Yonemura Y. Thirty-three long-term survivors after cytoreductive surgery in patients with peritoneal metastases from colorectal cancer: a retrospective descriptive study. World J Surg Oncol 2021; 19:31. [PMID: 33509224 PMCID: PMC7845127 DOI: 10.1186/s12957-021-02145-1] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2020] [Accepted: 01/20/2021] [Indexed: 12/23/2022] Open
Abstract
BACKGROUND Cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) improves survival in selected patients with peritoneal metastasis (PM) from colorectal cancer (CRC). However, little has been reported on characteristics and clinical course of long-term survivors with CRC-PM beyond 5 years. The objective of this study was to identify the clinical and oncological features affecting long-term survival of CRC-PM after comprehensive treatment. METHODS Between January 1990 and April 2015, CRC-PM patients who underwent CRS with or without HIPEC in two Japanese tertiary hospitals were analyzed. Clinicopathological parameters and therapeutic details for long-term survivors (patients surviving ≥ 5 years after CRS) were described and compared with those for non-survivors (patients surviving < 5 years). RESULTS The study identified 236 patients with CRC-PM who underwent CRS, with a median follow-up period of 2.5 years. Thirty-three patients (14.0%) were considered as long-term survivors. Compared with non-survivors, long-term survivors had a lower median peritoneal cancer index (PCI) [4 (1-27) vs 9 (0-39), p < 0.001]. Complete cytoreduction (CCR-0) was achieved in all long-term survivors, with a significantly higher rate [33/33 (100%) vs 141/203 (69.8%), p < 0.001]. Metachronous onsets of PM were more frequently observed in the long-term survivor group [26/33 (78.8%) vs 103/203 (50.3%), p = 0.018]. Regarding histopathology, long-term survivors more frequently had mucinous adenocarcinoma than non-survivors [8/33 (24.2%) vs 27/203 (13.3%)] and less likely exhibited poorly differentiated or signet ring cell carcinoma [2/33 (6.1%) vs 48/203 (23.7%)] (p < 0.001). CONCLUSIONS One in seven patients with CRC-PM achieved the long-term milestone after CRS. A long-term survival was associated with the presence of low PCI, CCR-0, metachronous onset, and mucinous histology.
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Affiliation(s)
- Yasuyuki Kamada
- Department of Surgery, Graduate School of Medicine, Kyoto University, 54, Shogoin-Kawahara-Cho, Sakyo-Ku, Kyoto, Japan. .,NPO to support Peritoneal Surface Malignancy Treatment, Japanese/Asian School of Peritoneal Surface Oncology, Kyoto, Japan. .,Department of Regional Cancer Therapy, Peritoneal Surface Malignancy Center, Kishiwada Tokushukai Hospital, Kishiwada, Japan.
| | - Koya Hida
- Department of Surgery, Graduate School of Medicine, Kyoto University, 54, Shogoin-Kawahara-Cho, Sakyo-Ku, Kyoto, Japan
| | - Haruaki Ishibashi
- NPO to support Peritoneal Surface Malignancy Treatment, Japanese/Asian School of Peritoneal Surface Oncology, Kyoto, Japan.,Department of Regional Cancer Therapy, Peritoneal Surface Malignancy Center, Kishiwada Tokushukai Hospital, Kishiwada, Japan
| | - Shouzou Sako
- NPO to support Peritoneal Surface Malignancy Treatment, Japanese/Asian School of Peritoneal Surface Oncology, Kyoto, Japan.,Department of Regional Cancer Therapy, Peritoneal Surface Malignancy Center, Kishiwada Tokushukai Hospital, Kishiwada, Japan
| | - Akiyoshi Mizumoto
- Department of Regional Cancer Therapy, Peritoneal Surface Malignancy Center, Kusatsu General Hospital, Shiga, Japan
| | - Masumi Ichinose
- Department of Regional Cancer Therapy, Peritoneal Surface Malignancy Center, Kusatsu General Hospital, Shiga, Japan
| | - Naveen Padmanabhan
- Department of Regional Cancer Therapy, Peritoneal Surface Malignancy Center, Kishiwada Tokushukai Hospital, Kishiwada, Japan.,Department of Surgical Oncology, Apollo Cancer Institute, Chennai, India
| | - Shinya Yoshida
- Department of Surgery, Graduate School of Medicine, Kyoto University, 54, Shogoin-Kawahara-Cho, Sakyo-Ku, Kyoto, Japan
| | - Yutaka Yonemura
- NPO to support Peritoneal Surface Malignancy Treatment, Japanese/Asian School of Peritoneal Surface Oncology, Kyoto, Japan.,Department of Regional Cancer Therapy, Peritoneal Surface Malignancy Center, Kishiwada Tokushukai Hospital, Kishiwada, Japan.,Department of Regional Cancer Therapy, Peritoneal Surface Malignancy Center, Kusatsu General Hospital, Shiga, Japan
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Tabchouri N, Buggisch J, Demtröder CR, Thiery J, Rezniczek G, Tempfer CB, Fischer B, Dogan C, Lecomte T, Ouaissi M, Giger-Pabst U. Pressurized Intraperitoneal Aerosol Chemotherapy for Colorectal Peritoneal Metastases. Ann Surg Oncol 2021; 28:5275-5286. [PMID: 33471267 DOI: 10.1245/s10434-020-09508-0] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2020] [Accepted: 12/01/2020] [Indexed: 01/29/2023]
Abstract
BACKGROUND The benefit of repetitive PIPAC specifically in CPM patients has yet to be demonstrated in terms of oncological and functional outcomes. OBJECTIVE The aim of this study was to evaluate the outcome of patients with non-resectable colorectal peritoneal metastases (CPM) treated with pressurized intraperitoneal aerosol chemotherapy (PIPAC). METHODS We conducted an analysis of a prospective single-center database of all CPM patients who underwent PIPAC with oxaliplatin 92 mg/m2 body surface (PIPAC-Ox). The outcome criteria were adverse events (Common Terminology Criteria for Adverse Events version 4.0), Peritoneal Regression Grading Score (PRGS), and survival. RESULTS Overall, 102 patients with a median age of 64 years (33-88) were scheduled for PIPAC-Ox. Access to the abdominal cavity for the first application failed in 22/102 (21.6%) patients. A total of 185 PIPACs were performed, with 26/102 (25.5%), 20/102 (19.6%), 17/102 (16.7%), and 17/102 (16.7%) patients undergoing one, two, three, and four or more PIPACs, respectively. Perioperative overall morbidity/mortality Grade I-V occurred in 14 (7.6%), 29 (15.8%), 6 (3.2%), 1 (0.5%), and 1 (0.5%) patient without significant differences between each cycle. Of 27 patients who underwent three or more PIPACs, 20/102 (19.6%) had major/complete CPM regression (PRGS 1-2). In a multivariate analysis, independent predictive factors for > 12 months' survival following the first PIPAC-Ox administration were three or more PIPACs (odds ratio [OR] 4.5, 95% confidence interval [CI] 1.35-15.2; p = 0.014) and younger patient age (OR 1.058, 95% CI 1.00-1.12; p = 0.039). CONCLUSIONS Repetitive PIPAC-Ox for CPM patients, alone or combined with perioperative systemic chemotherapy, is feasible. Our data suggest that three or more consecutive PIPAC-Ox cycles for advanced CPM can improve survival.
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Affiliation(s)
- Nicolas Tabchouri
- Department of Digestive Oncological, Endocrine, Hepato-Biliary, Pancreatic and Liver Transplant Surgery, Trousseau Hospital, Chambray Les Tours, France
| | - Jonathan Buggisch
- Department of General-, Visceral- and Transplant Surgery, University Hospital of Münster, Münster, Germany
| | - Cédric Rémy Demtröder
- Department of Surgery and Therapy Center for Peritoneal Carcinomatosis, Marien Hospital Herne, Ruhr-Universität Bochum, Herne, Germany.,Department of General and Visceral Surgery, Therapy Center for Metabolic and Bariatric Surgery, St. Martinus Hospital Düsseldorf, Düsseldorf, Germany
| | - Julien Thiery
- Department of Digestive Oncological, Endocrine, Hepato-Biliary, Pancreatic and Liver Transplant Surgery, Trousseau Hospital, Chambray Les Tours, France
| | - Günther Rezniczek
- Department of Obstetrics and Gynecology, and Therapy Center for Peritoneal Carcinomatosis, Marien Hospital Herne, Ruhr-Universität Bochum, Herne, Germany
| | - Clemens B Tempfer
- Department of Obstetrics and Gynecology, and Therapy Center for Peritoneal Carcinomatosis, Marien Hospital Herne, Ruhr-Universität Bochum, Herne, Germany
| | - Britta Fischer
- Department of Surgery and Therapy Center for Peritoneal Carcinomatosis, Marien Hospital Herne, Ruhr-Universität Bochum, Herne, Germany
| | - Can Dogan
- Department of Obstetrics and Gynecology, and Therapy Center for Peritoneal Carcinomatosis, Marien Hospital Herne, Ruhr-Universität Bochum, Herne, Germany
| | - Thierry Lecomte
- Department of Hepatogastroenterology and Digestive Oncology, University Hospital Trousseau, Tours, France
| | - Mehdi Ouaissi
- Department of Digestive Oncological, Endocrine, Hepato-Biliary, Pancreatic and Liver Transplant Surgery, Trousseau Hospital, Chambray Les Tours, France. .,Colorectal Surgery Unit, Trousseau Hospital, Avenue de la République, Chambray Les Tours, France.
| | - Urs Giger-Pabst
- Department of General-, Visceral- and Transplant Surgery, University Hospital of Münster, Münster, Germany.,Department of Surgery and Therapy Center for Peritoneal Carcinomatosis, Marien Hospital Herne, Ruhr-Universität Bochum, Herne, Germany
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Sommariva A, Ansaloni L, Baiocchi GL, Cascinu S, Cirocchi R, Coccolini F, Deraco M, Fiorentini G, Gelmini R, Di Giorgio A, Lippolis PV, Pasqual EM, Sassaroli C, Macrì A, Sammartino P, Scaringi S, Valle M, Vaira M. Diagnostic and therapeutic algorithm for colorectal peritoneal metastases. A consensus of the peritoneal surface malignancies onco-team of the Italian society of surgical oncology. EUROPEAN JOURNAL OF SURGICAL ONCOLOGY 2021; 47:164-171. [PMID: 33028502 DOI: 10.1016/j.ejso.2020.09.035] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2020] [Revised: 09/04/2020] [Accepted: 09/26/2020] [Indexed: 11/30/2022]
Abstract
AIM the surgical workup for colorectal cancer peritoneal metastases (CRCPM) is complex and should be managed in specialized centers. Diagnostic and therapeutic algorithms (DTA) have been proposed to balance optimal patients management and correct use of resources. Aim of this study was to establish a consensus on DTA for CRCPM patients in Italy. METHOD a panel of 18 delegated members of centers afferent to Peritoneal Surface Malignancies Onco-team of the Italian Society of Surgical Oncology was established. A list of statements regarding the DTA of patients with CRCPM was prepared according to different activities and decision-making nodes with a defined entry and exit point. Consensus was obtained through RAND UCLA methodology. RESULTS two different DTA were defined and approved according to the modality of presentation of CRCPM (synchronous and metachronous). A consensus was also obtained on 17 of the 19 statements related to DTA. CONCLUSION a shared model of DTA is now available for healthcare providers to monitor appropriateness in diagnosis and treatment of patients with isolated peritoneal metastases from CRC.
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Affiliation(s)
- Antonio Sommariva
- Unit of Surgical Oncology of the Esophagus and Digestive Tract, Veneto Institute of Oncology IOV-IRCCS, Padua, Italy
| | - Luca Ansaloni
- Unit of General and Emergency Surgery, Bufalini Hospital, Cesena, Italy
| | - Gian Luca Baiocchi
- Department of Clinical and Experimental Sciences, University of Brescia, Italy
| | - Stefano Cascinu
- Department of Medical Oncology Vita-Salute, San Raffaele University IRCCS, Milan, Italy
| | - Roberto Cirocchi
- General Surgery and Clinical Anatomy, University of Perugia, Perugia, Italy
| | | | - Marcello Deraco
- Peritoneal Surface Malignancies Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
| | - Gianmaria Fiorentini
- Department of Onco-Hematology, Azienda Ospedaliera 'Ospedali Riuniti Marche Nord', Pesaro, Italy
| | - Roberta Gelmini
- General and Oncological Surgery Unit, AOU of Modena University of Modena and Reggio Emilia, Italy
| | - Andrea Di Giorgio
- Surgical Unit of Peritoneum and Retroperitoneum, Fondazione Policlinico Universitario A. Gemelli - IRCCS, Rome, Italy
| | | | - Enrico Maria Pasqual
- Advanced Surgical Oncology Unit, Department Area Medica, University of Udine, Italy
| | - Cinzia Sassaroli
- Abdominal Oncology Department, Fondazione Giovanni Pascale, IRCCS, Naples, Italy
| | - Antonio Macrì
- Department of Human Pathology, Peritoneal Surface Malignancy and Soft Tissue Sarcoma Program, University of Messina, Italy
| | - Paolo Sammartino
- Department of Surgery 'P. Valdoni', Sapienza University of Rome, Rome, Italy
| | - Stefano Scaringi
- Digestive Surgery Unit - IBD Unit, Careggi University Hospital, Florence, Italy
| | - Mario Valle
- Surgical Oncology Peritoneum and Abdomen Pathologies, National Cancer Institute "Regina Elena" Rome, Italy
| | - Marco Vaira
- Unit of Surgical Oncology, Candiolo Cancer Institute, Turin, Italy
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Cho WC, Kim M, Park JW, Jeong SY, Ku JL. Exosomal miR-193a and let-7g accelerate cancer progression on primary colorectal cancer and paired peritoneal metastatic cancer. Transl Oncol 2020; 14:101000. [PMID: 33352502 PMCID: PMC7758376 DOI: 10.1016/j.tranon.2020.101000] [Citation(s) in RCA: 25] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2020] [Accepted: 12/11/2020] [Indexed: 02/08/2023] Open
Abstract
A metastasis of colorectal cancer is difficult to diagnose, and has a poor prognosis. Therefore, we tried to elucidate the possibility of a diagnostic and prognostic marker. Exosomal miR-193a and let-7g were sorted by miRNA microarray. The expression of miR-193a in the PTM group was lower than that of the primary CRC group, and the expression of let-7g was higher than that of the primary CRC. MMP16 and CDKN1A expression was confirmed respectively for target genes of two miRNAs. When the mimics of these miRNAs were treated with cell lines, both MMP16 and CDKN1A decreased intracellular expression. Cell invasiveness and proliferation were decreased by miR-193a and increased by let-7g. The differences in expression of exosomal miR-193a and let-7g extracted from the plasma of patients were classified as cancer progression indicators. Furthermore, the survival rate decreased in the group with low miR-193a expression and high let-7g expression. Our study confirmed the possibility of using this as a diagnostic and prognostic marker for colorectal cancer by measuring the expression levels of exosomal miR-193a and let-7g in blood.
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Affiliation(s)
- Woo-Cheol Cho
- Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul 03080, Korea; Laboratory of Cell Biology, Cancer Research Institute, Seoul National University College of Medicine, Seoul 03080, Korea; Cancer Research Institute, Seoul National University, Seoul 03080, Republic of Korea
| | - Minjung Kim
- Cancer Research Institute, Seoul National University, Seoul 03080, Republic of Korea; Department of Surgery, Seoul National University College of Medicine, Seoul 03080, Korea; Division of Colorectal Surgery, Department of Surgery, Seoul National University Hospital, Seoul 03080, Korea
| | - Ji Won Park
- Cancer Research Institute, Seoul National University, Seoul 03080, Republic of Korea; Department of Surgery, Seoul National University College of Medicine, Seoul 03080, Korea; Division of Colorectal Surgery, Department of Surgery, Seoul National University Hospital, Seoul 03080, Korea
| | - Seung-Yong Jeong
- Cancer Research Institute, Seoul National University, Seoul 03080, Republic of Korea; Department of Surgery, Seoul National University College of Medicine, Seoul 03080, Korea; Division of Colorectal Surgery, Department of Surgery, Seoul National University Hospital, Seoul 03080, Korea.
| | - Ja-Lok Ku
- Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul 03080, Korea; Laboratory of Cell Biology, Cancer Research Institute, Seoul National University College of Medicine, Seoul 03080, Korea; Cancer Research Institute, Seoul National University, Seoul 03080, Republic of Korea.
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40
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Gasser E, Kogler P, Lorenz A, Kafka-Ritsch R, Öfner D, Perathoner A. Do we still need CRS and HIPEC in colorectal cancer in times of modern chemotherapy and immunotherapy? MEMO - MAGAZINE OF EUROPEAN MEDICAL ONCOLOGY 2020; 13:430-433. [DOI: 10.1007/s12254-020-00647-4] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/14/2020] [Accepted: 08/18/2020] [Indexed: 08/30/2023]
Abstract
SummaryPeritoneal carcinomatosis from colorectal cancer is associated with a poor prognosis and is usually treated with systemic chemotherapy and immunotherapy alone. In patients with isolated peritoneal carcinomatosis (PC) without nonperitoneal metastases, however, cytoreductive surgery (CRS) has been shown to significantly improve outcome and to achieve even cure in selected patients in combination with systemic therapy. The additional use of a hyperthermic intraperitoneal chemotherapy (HIPEC) is primarily indicated to control microscopical residual tumor tissue in the peritoneal cavity after successful CRS. Another more recent option is the application of an adjuvant HIPEC to prevent peritoneal carcinomatosis in high risk patients with pT4 cancer or perforated cancer at the time of or after primary surgery. The aim of this short review is to highlight the corresponding available literature and assess the role of CRS and HIPEC in the context of modern chemotherapy and immunotherapy.
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41
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Tzivanakis A, Moran BJ. Perforated Colorectal Cancer. Clin Colon Rectal Surg 2020; 33:247-252. [PMID: 32968359 DOI: 10.1055/s-0040-1713741] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/23/2022]
Abstract
The majority of patients with colorectal tumors will present via the elective route. However, one-fifth of patients will present as an emergency. The most common cause of emergency presentation of colorectal cancer is obstruction followed by perforation, and in many cases, patients will present with both. We discuss the management of the patient presenting with a perforated colorectal tumor covering the acute presentation and also how to deal with consequences of a perforated tumor, namely, the management of colorectal peritoneal metastasis (CPM). CPM used to be considered a terminal condition; however, a strategy of early detection of CPM, careful patient selection for cytoreductive surgery and hyperthermic intraperitoneal chemotherapy, leads to much improved outcomes and even cure, in some patient compared with systemic chemotherapy alone.
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Affiliation(s)
| | - Brendan J Moran
- Peritoneal Malignancy Institute, Basingstoke, Hampshire, United Kingdom
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42
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Baratti D, Kusamura S, Niger M, Perrone F, Milione M, Cattaneo L, Guaglio M, Bartolini V, Pietrantonio F, Deraco M. Prognostic Impact of Primary Side and RAS/RAF Mutations in a Surgical Series of Colorectal Cancer with Peritoneal Metastases. Ann Surg Oncol 2020; 28:3332-3342. [PMID: 32974694 DOI: 10.1245/s10434-020-09161-7] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2020] [Accepted: 08/31/2020] [Indexed: 01/06/2023]
Abstract
BACKGROUND Selecting patients with colorectal cancer peritoneal metastases (CRC-PMs) for surgery is still a concern. Biological features have the potential to improve prognostic stratification, but their significance in this clinical setting is still unclear. We assessed the prognostic impact of primary side and KRAS/NRAS/BRAF/PIK3CA mutations in patients treated with either cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) or CRS alone. METHODS We reviewed a prospective database of 152 CRC-PM patients selected to undergo perioperative systemic chemotherapy and CRS with or without HIPEC. Extensive mutational analysis of KRAS, NRAS, BRAF, and PIK3CA was performed by polymerase chain reaction (PCR). In 68 patients, Ion Torrent next-generation sequencing technology was used to characterize the hotspot regions of 50 genes. RESULTS The primary tumor was right-sided in 61 patients (40.1%) and left-sided in 91 patients (59.9%). Right-sided primaries were associated with mutated KRAS (p = 0.01) and normal carcinoembryonic antigen (CEA; p = 0.03). KRAS was mutated in 71/152 patients (46.7%), NRAS in 7/152 patients (4.6%), BRAF in 10/152 patients (6.6%), PIK3CA in 17/78 patients (25.0%), TP53 in 37/68 patients (54.4%), APC in 25/68 patients (36.7%), SMAD4 in 13/68 patients (19.1%), and FBXW7 in 5/68 patients (7.4%). Median follow-up was 54.9 months and median survival from PM diagnosis was 45.1 months. The right-sided primary (hazard ratio [HR] 1.62, 95% confidence interval [CI] 0.43-0.89; p = 0.011), BRAF mutations (HR 2.21, 95% CI 1.05-4.63; p = 0.038), and Peritoneal Cancer Index (HR 1.47, 95% CI 1.03-2.10; p = 0.036) independently correlated with poorer survival, while APC mutations univariately correlated with better survival (p = 0.03). CONCLUSIONS BRAF mutations and right-sided primary are adverse prognostic factors that may be used to optimize therapeutic strategies. APC may be involved in CRC-PM development and progression.
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Affiliation(s)
- Dario Baratti
- Peritoneal Malignancy Program, Department of Surgery, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
| | - Shigeki Kusamura
- Peritoneal Malignancy Program, Department of Surgery, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
| | - Monica Niger
- Department of Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
| | - Federica Perrone
- Laboratory of Molecular Pathology, Department of Pathology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
| | - Massimo Milione
- Department of Pathology and Laboratory Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
| | - Laura Cattaneo
- Department of Pathology and Laboratory Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
| | - Marcello Guaglio
- Peritoneal Malignancy Program, Department of Surgery, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
| | - Valentina Bartolini
- Peritoneal Malignancy Program, Department of Surgery, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
| | - Filippo Pietrantonio
- Department of Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
| | - Marcello Deraco
- Peritoneal Malignancy Program, Department of Surgery, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
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Prabhu A, Brandl A, Wakama S, Sako S, Ishibashi H, Mizumoto A, Takao N, Noguchi K, Motoi S, Ichinose M, Liu Y, Yonemura Y. Retrospective Analysis of Patients with Signet Ring Subtype of Colorectal Cancer with Peritoneal Metastasis Treated with CRS & HIPEC. Cancers (Basel) 2020; 12:E2536. [PMID: 32906609 PMCID: PMC7565458 DOI: 10.3390/cancers12092536] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2020] [Revised: 08/21/2020] [Accepted: 08/26/2020] [Indexed: 02/06/2023] Open
Abstract
Signet ring cell subtype (SRC) of colorectal cancer (CRC) is a rare subtype and occurs in approximately 1% of all patients with CRC. Patients with peritoneal metastasis (PM) of SRC have a poor prognosis, and this subtype is frequently considered as a contra-indication for extensive surgical treatment. This retrospective study from two dedicated peritoneal surface malignancy centers in Japan included all patients treated with CRS ± hyperthermic intraperitoneal chemotherapy (HIPEC) between July 1994 and December 2017 from a prospectively maintained database. Preoperative, operative, and postoperative parameters were recorded, including complication rates and follow-up. Sixty of the 320 patients treated with CRS due to CRC were diagnosed with SRC subtype. The mean age of the patients was 51.4 years, and the mean peritoneal carcinomatosis index (PCI) was 13.1. Complete cytoreduction was achieved in 61.7% of cases. The postoperative morbidity rate was 25% and the mortality rate was 1.7%. The median overall survival (OS) was 14.4 months. Cox regression analysis revealed small bowel PCI > 2 (hazard ratio (HR) 6.5; p = 0.008) as the most important factor for OS. With accurate patient selection (e.g., PCI ≤ 12 or small bowel PCI ≤ 2), even patients with PM of CRC with SRC subtype may benefit from CRS and HIPEC, with median OS from 17.8 to 20.8 months and 5-year OS of 11.6%.
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Affiliation(s)
- Aruna Prabhu
- Department of Surgical Oncology, Thangam Cancer Center, Namakkal 637001, Tamil Nadu, India;
| | - Andreas Brandl
- Digestive Unit, Champalimaud Foundation, 1400-038 Lisbon, Portugal;
| | - Satoshi Wakama
- Department of surgery, Graduate school of medicine, Kyoto University, Kyoto 606-8303, Japan;
| | - Shouzou Sako
- Department of Regional Cancer therapy, Peritoneal Surface Malignancy Center, Kishiwada Tokushukai Hospital, Kishiwada, Osaka 596-0042, Japan; (S.S.); (H.I.); (Y.L.)
- NPO to Support Peritoneal Surface Malignancy Treatment, Japanese/Asian School of Peritoneal Surface Oncology, Kyoto 600-8189, Japan
| | - Haruaki Ishibashi
- Department of Regional Cancer therapy, Peritoneal Surface Malignancy Center, Kishiwada Tokushukai Hospital, Kishiwada, Osaka 596-0042, Japan; (S.S.); (H.I.); (Y.L.)
| | - Akiyoshi Mizumoto
- Department of Regional Cancer Therapy, Peritoneal Surface Malignancy Center, Kusatsu General Hospital, Shiga 525-8585, Japan; (A.M.); (N.T.); (K.N.); (S.M.); (M.I.)
| | - Nobuyuki Takao
- Department of Regional Cancer Therapy, Peritoneal Surface Malignancy Center, Kusatsu General Hospital, Shiga 525-8585, Japan; (A.M.); (N.T.); (K.N.); (S.M.); (M.I.)
| | - Kousuke Noguchi
- Department of Regional Cancer Therapy, Peritoneal Surface Malignancy Center, Kusatsu General Hospital, Shiga 525-8585, Japan; (A.M.); (N.T.); (K.N.); (S.M.); (M.I.)
| | - Shunsuke Motoi
- Department of Regional Cancer Therapy, Peritoneal Surface Malignancy Center, Kusatsu General Hospital, Shiga 525-8585, Japan; (A.M.); (N.T.); (K.N.); (S.M.); (M.I.)
| | - Masumi Ichinose
- Department of Regional Cancer Therapy, Peritoneal Surface Malignancy Center, Kusatsu General Hospital, Shiga 525-8585, Japan; (A.M.); (N.T.); (K.N.); (S.M.); (M.I.)
| | - Yang Liu
- Department of Regional Cancer therapy, Peritoneal Surface Malignancy Center, Kishiwada Tokushukai Hospital, Kishiwada, Osaka 596-0042, Japan; (S.S.); (H.I.); (Y.L.)
| | - Yutaka Yonemura
- Department of Regional Cancer therapy, Peritoneal Surface Malignancy Center, Kishiwada Tokushukai Hospital, Kishiwada, Osaka 596-0042, Japan; (S.S.); (H.I.); (Y.L.)
- NPO to Support Peritoneal Surface Malignancy Treatment, Japanese/Asian School of Peritoneal Surface Oncology, Kyoto 600-8189, Japan
- Department of Regional Cancer Therapy, Peritoneal Surface Malignancy Center, Kusatsu General Hospital, Shiga 525-8585, Japan; (A.M.); (N.T.); (K.N.); (S.M.); (M.I.)
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Kooijman BJL, Hentzen JEKR, van der Hilst CS, Been LB, van Ginkel RJ, Hemmer PHJ, Klaase JM, Kruijff S. Impact of extent of disease on 1-year healthcare costs in patients who undergo cytoreductive surgery with hyperthermic intraperitoneal chemotherapy for colorectal peritoneal metastases: retrospective observational cohort study. BJS Open 2020; 4:954-962. [PMID: 32652904 PMCID: PMC7528507 DOI: 10.1002/bjs5.50320] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2020] [Accepted: 06/01/2020] [Indexed: 11/17/2022] Open
Abstract
Background The goal of this retrospective observational study was to determine the impact of the extent of peritoneal disease on 1‐year healthcare costs in patients with colorectal peritoneal metastases (PM) who undergo cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS + HIPEC). The extent of peritoneal disease, expressed by the Peritoneal Cancer Index (PCI), directly affects the complexity of CRS + HIPEC and ultimately survival outcomes. The impact of the PCI on treatment‐related healthcare costs remains unknown. Methods Data from patients with colorectal PM who underwent CRS + HIPEC between January 2012 and November 2017 were extracted retrospectively from an institutional database. Patients were divided into four subgroups with PCI scores ranging from 0 to 20. Treatment‐related costs up to 1 year after CRS + HIPEC were obtained from the financial department. Differences in costs and survival outcomes were compared using the χ2 test and Kruskal−Wallis H test. Results Seventy‐three patients were included (PCI 0–5, 22 patients; PCI 6–10, 19 patients; PCI 11–15, 17 patients; PCI 16–20, 15 patients). Median (i.q.r.) costs were significantly increased for the PCI 11–15 and PCI 16–20 groups (€51 029 (42 500–58 575) and €46 548 (35 194–60 533) respectively) compared with those for the PCI 0–5 and PCI 6–10 groups (€33 856 (25 293–42 235) and €39 013 (30 519–51 334) respectively) (P = 0·009). Conclusion Treatment‐related healthcare costs are significantly increased among patients with extensive tumour burden (PCI score 10 or above) who undergo CRS + HIPEC for the treatment of colorectal PM.
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Affiliation(s)
- B J L Kooijman
- Departments of Surgery, Division of Surgical Oncology, Groningen, the Netherlands
| | - J E K R Hentzen
- Departments of Surgery, Division of Surgical Oncology, Groningen, the Netherlands
| | - C S van der Hilst
- Division of Hepatopancreatobiliary Surgery and Liver Transplantation, University Medical Centre Groningen, University of Groningen, Groningen, the Netherlands
| | - L B Been
- Departments of Surgery, Division of Surgical Oncology, Groningen, the Netherlands
| | - R J van Ginkel
- Departments of Surgery, Division of Surgical Oncology, Groningen, the Netherlands
| | - P H J Hemmer
- Departments of Surgery, Division of Surgical Oncology, Groningen, the Netherlands
| | - J M Klaase
- Division of Hepatopancreatobiliary Surgery and Liver Transplantation, University Medical Centre Groningen, University of Groningen, Groningen, the Netherlands
| | - S Kruijff
- Departments of Surgery, Division of Surgical Oncology, Groningen, the Netherlands
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45
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de Jong LAW, Elekonawo FMK, Lambert M, de Gooyer JM, Verheul HMW, Burger DM, de Wilt JHW, Chatelut E, Ter Heine R, de Reuver PR, Bremers AJA, van Erp NP. Wide variation in tissue, systemic, and drain fluid exposure after oxaliplatin-based HIPEC: results of the GUTOX study. Cancer Chemother Pharmacol 2020; 86:141-150. [PMID: 32594200 PMCID: PMC7338818 DOI: 10.1007/s00280-020-04107-y] [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: 03/20/2020] [Accepted: 06/24/2020] [Indexed: 01/02/2023]
Abstract
Purpose In this exploratory study, the effect of postprocedural flushing with crystalloids after oxaliplatin-based hyperthermic intraperitoneal chemotherapy (HIPEC) on platinum concentrations in peritoneal tissue, blood, and drain fluid was studied. Interpatient variability in oxaliplatin pharmacokinetics and the relation between platinum concentration in peritoneal fluid and platinum exposure in tissue and blood was explored. Methods Ten patients with peritoneal carcinomatosis of colorectal origin were treated with HIPEC including postprocedural flushing, followed by ten patients without flushing afterwards. Tissue, peritoneal fluid, blood, and drain fluid samples were collected for measurement of total and ultrafiltered platinum concentrations. Results Peritoneal tissue concentration and systemic ultrafiltered platinum exposure showed large inter individual variability, ranging from 65 to 1640 µg/g dry weight and 10.5 to 28.0 µg*h/ml, respectively. No effect of flushing was found on geometric mean platinum concentration in peritoneal tissue (348 vs. 356 µg/g dry weight), blood (14.8 vs. 18.1 µg*h/ml), or drain fluid (day 1: 7.6 vs. 7.7 µg/ml; day 2: 1.7 vs. 1.9 µg/ml). The platinum concentration in peritoneal fluid at the start of HIPEC differed twofold between patients and was positively correlated with systemic exposure (p = .04) and peak plasma concentration (p = .04). Conclusion In this exploratory study, no effect was found for postprocedural flushing on platinum concentrations in peritoneal tissue, blood, or drain fluid. BSA-based HIPEC procedure leads to large interpatient variability in platinum exposure in all compartments. The study was registered at ClinicalTrials.gov on 7 December 2017 under registration number NCT03364907.
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Affiliation(s)
- Loek A W de Jong
- Department of Pharmacy, Radboud Institute for Health Sciences, Radboud University Medical Center (RUMC), P.O. Box 9101, 6500 HB, Nijmegen, The Netherlands.
| | - Fortuné M K Elekonawo
- Department of Radiology and Nuclear Medicine, Radboud Institute for Health Sciences, Radboud University Medical Center (RUMC), P.O. Box 9101, 6500 HB, Nijmegen, The Netherlands.,Department of Surgery, Radboud Institute for Health Sciences, Radboud University Medical Center (RUMC), P.O. Box 9101, 6500 HB, Nijmegen, The Netherlands
| | - Marie Lambert
- Institut Claudius‑Regaud, IUCT‑Oncopole, and CRCT, Université de Toulouse, Inserm, 1, avenue Irène Joliot‑Curie, Toulouse, France
| | - Jan Marie de Gooyer
- Department of Radiology and Nuclear Medicine, Radboud Institute for Health Sciences, Radboud University Medical Center (RUMC), P.O. Box 9101, 6500 HB, Nijmegen, The Netherlands.,Department of Surgery, Radboud Institute for Health Sciences, Radboud University Medical Center (RUMC), P.O. Box 9101, 6500 HB, Nijmegen, The Netherlands
| | - Henk M W Verheul
- Department of Medical Oncology, Radboud Institute for Health Sciences, Radboud University Medical Center (RUMC), P.O. Box 9101, 6500 HB, Nijmegen, The Netherlands
| | - David M Burger
- Department of Pharmacy, Radboud Institute for Health Sciences, Radboud University Medical Center (RUMC), P.O. Box 9101, 6500 HB, Nijmegen, The Netherlands
| | - Johannes H W de Wilt
- Department of Surgery, Radboud Institute for Health Sciences, Radboud University Medical Center (RUMC), P.O. Box 9101, 6500 HB, Nijmegen, The Netherlands
| | - Etienne Chatelut
- Institut Claudius‑Regaud, IUCT‑Oncopole, and CRCT, Université de Toulouse, Inserm, 1, avenue Irène Joliot‑Curie, Toulouse, France
| | - Rob Ter Heine
- Department of Pharmacy, Radboud Institute for Health Sciences, Radboud University Medical Center (RUMC), P.O. Box 9101, 6500 HB, Nijmegen, The Netherlands
| | - Philip R de Reuver
- Department of Surgery, Radboud Institute for Health Sciences, Radboud University Medical Center (RUMC), P.O. Box 9101, 6500 HB, Nijmegen, The Netherlands
| | - Andre J A Bremers
- Department of Surgery, Radboud Institute for Health Sciences, Radboud University Medical Center (RUMC), P.O. Box 9101, 6500 HB, Nijmegen, The Netherlands
| | - Nielka P van Erp
- Department of Pharmacy, Radboud Institute for Health Sciences, Radboud University Medical Center (RUMC), P.O. Box 9101, 6500 HB, Nijmegen, The Netherlands
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Lurvink RJ, Tajzai R, Rovers KP, Wassenaar ECE, Moes DJAR, Pluimakers G, Boerma D, Burger JWA, Nienhuijs SW, de Hingh IHJT, Deenen MJ. Systemic Pharmacokinetics of Oxaliplatin After Intraperitoneal Administration by Electrostatic Pressurized Intraperitoneal Aerosol Chemotherapy (ePIPAC) in Patients with Unresectable Colorectal Peritoneal Metastases in the CRC-PIPAC Trial. Ann Surg Oncol 2020; 28:265-272. [PMID: 32572849 DOI: 10.1245/s10434-020-08743-9] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2020] [Indexed: 12/14/2022]
Abstract
BACKGROUND Electrostatic pressurized intraperitoneal aerosol chemotherapy (ePIPAC) is a palliative treatment for unresectable peritoneal metastases from various primary cancers. However, little is known about the systemic pharmacokinetics of oxaliplatin after ePIPAC. METHODS Twenty patients with unresectable colorectal peritoneal metastases were treated with repetitive ePIPAC monotherapy with oxaliplatin (92 mg/m2) and a simultaneous intravenous bolus of leucovorin (20 mg/m2) and 5-fluorouracil (400 mg/m2). Samples were collected during each ePIPAC: whole blood at t = 0, t = 5, t = 10, t = 20, t = 30, t = 60, t = 120, t = 240, t = 360 and t = 1080 min for plasma and plasma ultrafiltrate concentrations; urine at t = 0, t = 1, t = 3, t = 5 and t = 7 days. Samples were analyzed using atomic absorption spectrometry. Pharmacokinetics were analyzed using nonlinear mixed-effects modeling. RESULTS Four patients received one ePIPAC, three patients received two ePIPAC, and thirteen patients received ≥ 3 ePIPAC. The population pharmacokinetic models adequately described the pharmacokinetics of oxaliplatin after ePIPAC. The plasma ultrafiltrate Cmax of oxaliplatin reached 1.36-1.90 µg/mL after 30 min with an AUC0-24 h of 9.6-11.7 µg/mL * h. The plasma Cmax reached 2.67-3.28 µg/mL after 90 min with an AUC0-24 h of 49.0-59.5 µg/mL * h. The absorption rate constant (Ka) was 1.13/h. Urine concentrations of oxaliplatin rapidly decreased to less than 3.60 µg/mL in 90% of the samples at day 7. DISCUSSION Systemic exposure to oxaliplatin after ePIPAC seemed comparable to that after systemic chemotherapy, as described in other literature. Since this is an indirect comparison, future research should focus on the direct comparison between the systemic exposure to oxaliplatin after ePIPAC and after systemic chemotherapy. TRIAL REGISTRATION NCT03246321, Pre-results; ISRCTN89947480, Pre-results; NTR6603, Pre-results; EudraCT: 2017-000927-29, Pre-results.
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Affiliation(s)
- Robin J Lurvink
- Department of Surgery, Catharina Hospital, Michelangelolaan 2, 5623 EJ, Eindhoven, The Netherlands
| | - Rudaba Tajzai
- Department of Surgery, Catharina Hospital, Michelangelolaan 2, 5623 EJ, Eindhoven, The Netherlands.,Department of Clinical Pharmacy, Catharina Hospital Eindhoven, Michelangelolaan 2, 5623 EJ, Eindhoven, The Netherlands
| | - Koen P Rovers
- Department of Surgery, Catharina Hospital, Michelangelolaan 2, 5623 EJ, Eindhoven, The Netherlands
| | - Emma C E Wassenaar
- Department of Surgery, St. Antonius Hospital, Koekoekslaan 1, 3435 CM, Nieuwegein, The Netherlands
| | - Dirk-Jan A R Moes
- Department of Clinical Pharmacy and Toxicology, Leiden University Medical Center, Leiden, The Netherlands
| | - Giulia Pluimakers
- Department of Clinical Pharmacy, Catharina Hospital Eindhoven, Michelangelolaan 2, 5623 EJ, Eindhoven, The Netherlands
| | - Djamila Boerma
- Department of Surgery, St. Antonius Hospital, Koekoekslaan 1, 3435 CM, Nieuwegein, The Netherlands
| | - Jacobus W A Burger
- Department of Surgery, Catharina Hospital, Michelangelolaan 2, 5623 EJ, Eindhoven, The Netherlands
| | - Simon W Nienhuijs
- Department of Surgery, Catharina Hospital, Michelangelolaan 2, 5623 EJ, Eindhoven, The Netherlands
| | - Ignace H J T de Hingh
- Department of Surgery, Catharina Hospital, Michelangelolaan 2, 5623 EJ, Eindhoven, The Netherlands.,GROW - School for Oncology and Developmental Biology, Maastricht University, Maastricht, The Netherlands
| | - Maarten J Deenen
- Department of Clinical Pharmacy, Catharina Hospital Eindhoven, Michelangelolaan 2, 5623 EJ, Eindhoven, The Netherlands. .,Department of Clinical Pharmacy and Toxicology, Leiden University Medical Center, Leiden, The Netherlands.
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Van de Sande L, Cosyns S, Willaert W, Ceelen W. Albumin-based cancer therapeutics for intraperitoneal drug delivery: a review. Drug Deliv 2020; 27:40-53. [PMID: 31858848 PMCID: PMC6968566 DOI: 10.1080/10717544.2019.1704945] [Citation(s) in RCA: 49] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
Abstract
Albumin is a remarkable carrier protein with multiple cellular receptor and ligand binding sites, which are able to bind and transport numerous endogenous and exogenous compounds. The development of albumin-bound drugs is gaining increased importance in the targeted delivery of cancer therapy. Intraperitoneal (IP) drug delivery represents an attractive strategy for the local treatment of peritoneal metastasis (PM). PM is characterized by the presence of widespread metastatic tumor nodules on the peritoneum, mostly originating from gastro-intestinal or gynaecological cancers. Albumin as a carrier for chemotherapy holds considerable promise for IP delivery in patients with PM. Data from recent (pre)clinical trials suggest that IP albumin-bound chemotherapy may result in superior efficacy in the treatment of PM compared to standard chemotherapy formulations. Here, we review the evidence on albumin-bound chemotherapy with a focus on IP administration and its efficacy in PM.
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Affiliation(s)
- Leen Van de Sande
- Laboratory of Experimental Surgery, Department of Human Structure and Repair, Ghent University, Ghent, Belgium.,Cancer Research Institute Ghent (CRIG), Ghent University, Ghent, Belgium
| | - Sarah Cosyns
- Laboratory of Experimental Surgery, Department of Human Structure and Repair, Ghent University, Ghent, Belgium.,Cancer Research Institute Ghent (CRIG), Ghent University, Ghent, Belgium
| | - Wouter Willaert
- Laboratory of Experimental Surgery, Department of Human Structure and Repair, Ghent University, Ghent, Belgium.,Cancer Research Institute Ghent (CRIG), Ghent University, Ghent, Belgium
| | - Wim Ceelen
- Laboratory of Experimental Surgery, Department of Human Structure and Repair, Ghent University, Ghent, Belgium.,Cancer Research Institute Ghent (CRIG), Ghent University, Ghent, Belgium
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48
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van der Kaaij RT, Wassenaar ECE, Koemans WJ, Sikorska K, Grootscholten C, Los M, Huitema A, Schellens JHM, Veenhof AAFA, Hartemink KJ, Aalbers AGJ, van Ramshorst B, Boerma D, Boot H, van Sandick JW. Treatment of PERItoneal disease in Stomach Cancer with cytOreductive surgery and hyperthermic intraPEritoneal chemotherapy: PERISCOPE I initial results. Br J Surg 2020; 107:1520-1528. [PMID: 32277764 DOI: 10.1002/bjs.11588] [Citation(s) in RCA: 27] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2019] [Revised: 02/04/2020] [Accepted: 02/14/2020] [Indexed: 12/12/2022]
Abstract
BACKGROUND The role of cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy (HIPEC) in gastric cancer is unknown. This non-randomized dose-finding phase I-II study was designed to assess the safety and feasibility of HIPEC, following systemic chemotherapy, in patients with gastric cancer and limited peritoneal dissemination. The maximum tolerated dose of normothermic intraperitoneal docetaxel in combination with a fixed dose of intraperitoneal oxaliplatin was also explored. METHODS Patients with resectable cT3-cT4a gastric adenocarcinoma with limited peritoneal metastases and/or tumour-positive peritoneal cytology were included. An open HIPEC technique was used with 460 mg/m2 hyperthermic oxaliplatin for 30 min followed by normothermic docetaxel for 90 min in escalating doses (0, 50, 75 mg/m2 ). RESULTS Between 2014 and 2017, 37 patients were included. Of 25 patients who completed the full study protocol, four were treated at dose level 1 (0 mg/m2 docetaxel), six at dose level 2 (50 mg/m2 ) and four at dose level 3 (75 mg/m2 ). At dose level 3, two dose-limiting toxicities occurred, both associated with postoperative ileus. Thereafter, another 11 patients were treated at dose level 2, with no more dose-limiting toxicities. Based on this, the maximum tolerated dose was 50 mg/m2 intraperitoneal docetaxel. Serious adverse events were scored in 17 of 25 patients. The reoperation rate was 16 per cent (4 of 25) and the treatment-related mortality rate was 8 per cent (2 patients, both in dose level 3). CONCLUSION Gastrectomy combined with cytoreductive surgery and HIPEC was feasible using 460 mg/m2 oxaliplatin and 50 mg/m2 normothermic docetaxel.
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Affiliation(s)
| | | | - W J Koemans
- Department of Surgical Oncology, Amsterdam, the Netherlands
| | - K Sikorska
- Department of Biometrics, Amsterdam, the Netherlands
| | - C Grootscholten
- Department of Gastrointestinal Oncology, Amsterdam, the Netherlands
| | - M Los
- Department of Medical Oncology, St Antonius Hospital, Nieuwegein, the Netherlands
| | - A Huitema
- Department of Pharmacy, Amsterdam, the Netherlands
| | - J H M Schellens
- >Department of Clinical Pharmacology, Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Amsterdam, the Netherlands
| | | | - K J Hartemink
- Department of Surgical Oncology, Amsterdam, the Netherlands
| | - A G J Aalbers
- Department of Surgical Oncology, Amsterdam, the Netherlands
| | | | - D Boerma
- Department of Surgery, Nieuwegein, the Netherlands
| | - H Boot
- Department of Gastrointestinal Oncology, Amsterdam, the Netherlands
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49
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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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50
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Fields AC, Lu PW, Li GZ, Welten V, Jolissaint JS, Vierra BM, Saadat LV, Larson AC, Atkinson RB, Melnitchouk N. Current practices and future steps for hyperthermic intraperitoneal chemotherapy. Curr Probl Surg 2020; 57:100727. [PMID: 32151327 DOI: 10.1016/j.cpsurg.2019.100727] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2019] [Accepted: 12/23/2019] [Indexed: 11/20/2022]
Affiliation(s)
- Adam C Fields
- Department of Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
| | - Pamela W Lu
- Department of Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA; Center for Surgery and Public Health, Brigham and Women's Hospital, Harvard Medical School, Boston, MA
| | - George Z Li
- Department of Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA
| | - Vanessa Welten
- Department of Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA
| | - Joshua S Jolissaint
- Department of Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA
| | | | - Lily V Saadat
- Department of Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA
| | - Abby C Larson
- Department of Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA
| | - Rachel B Atkinson
- Department of Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA; Center for Surgery and Public Health, Brigham and Women's Hospital, Harvard Medical School, Boston, MA
| | - Nelya Melnitchouk
- Department of Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA; Center for Surgery and Public Health, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
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