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Singh N, Xia W, Need E, McManus K, Huang J, Shi S, Goel S. Tumor agnostic ultrasmall nanoprobes for fluorescence-guided surgical resection in peritoneal metastasis. Eur J Nucl Med Mol Imaging 2025; 52:1149-1165. [PMID: 39446146 DOI: 10.1007/s00259-024-06950-0] [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: 07/19/2024] [Accepted: 10/07/2024] [Indexed: 10/25/2024]
Abstract
PURPOSE Surgical excision of metastases is the only curative treatment strategy in peritoneal carcinomatosis management, and the completeness of tumor resection determines the success of the surgery. Tumor-specific fluorescence-guided probes can improve the outcomes of cytoreductive surgery and thereby prognosis. This study aimed to develop and evaluate the feasibility of fluorescently labeled ultrasmall porous silica nanoparticles (UPSN) for image-guided resection of peritoneally disseminated tumors of different origins. METHODS Ultrasmall fluorescent nanoprobes were synthesized and characterized for their physicochemical properties and stability. Tumor-specific uptake and biodistribution profiles were evaluated in syngeneic CT26 colorectal and KPC-689 pancreatic cancer murine models. The practicability of real-time optical UPSN-guided resection was examined in the CT26 colorectal cancer model using a surgical stereomicroscope. Quantitative measurements of tumor sensitivity and specificity were performed. Histopathological examination validated in vivo findings about tumor-specific accumulation and safety of ultrasmall fluorescent probes. RESULTS As-synthesized UPSNs were successfully surface modified with Cy5 or Cy3 dyes maintaining sub-15 nm size and near neutral charge which is beneficial for optimized in vivo pharmacokinetics. UPSN-Cy5 demonstrated high tumor-specific uptake and favorable biodistribution profiles in peritoneal metastasis models of CT26 and KPC tumors. Dye-conjugated UPSN enabled resection of microscopic lesions and achieved a higher tumor-to-background ratios in comparison to FDA-approved indocyanine green (ICG) dye in both models. Microscopic evaluation showed tumor localization and off-target safety profile of the UPSN-Cy5. CONCLUSION Ultrasmall fluorescent probes were effective in surgical resection of peritoneal metastases with high sensitivity and specificity, thus emerging as promising tumor agnostic agents for image-guided cancer surgery.
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Affiliation(s)
- Neetu Singh
- Department of Molecular Pharmaceutics, University of Utah, Salt Lake City, UT, 84112, USA
| | - Wenxi Xia
- Department of Molecular Pharmaceutics, University of Utah, Salt Lake City, UT, 84112, USA
| | - Esther Need
- Department of Molecular Pharmaceutics, University of Utah, Salt Lake City, UT, 84112, USA
| | - Kylee McManus
- College of Science and Honors College (Biology), University of Utah, Salt Lake City, UT, 84112, USA
| | - Jiemin Huang
- Department of Molecular Pharmaceutics, University of Utah, Salt Lake City, UT, 84112, USA
| | - Sixiang Shi
- Department of Molecular Pharmaceutics, University of Utah, Salt Lake City, UT, 84112, USA.
- Department of Radiology and Imaging Sciences, University of Utah, Salt Lake City, UT, 84112, USA.
| | - Shreya Goel
- Department of Molecular Pharmaceutics, University of Utah, Salt Lake City, UT, 84112, USA.
- Department of Radiology and Imaging Sciences, University of Utah, Salt Lake City, UT, 84112, USA.
- Department of Biomedical Engineering, University of Utah, Salt Lake City, UT, 84112, USA.
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Dumont F, Kepenekian V, Passot C, Ezanno-Manasterski AC, Pocard M, Raoul JL, Lelièvre B, Hiret S, Senellart H, Pein F, Raimbourg J, Campion L, Thibaudeau E, Paul J, Glehen O. PIPAC in patients with peritoneal metastases from gastrointestinal tract (PIPOX01): An open label, non-comparative phase 1/2 dose escalation and expansion trial. EUROPEAN JOURNAL OF SURGICAL ONCOLOGY 2024; 50:108468. [PMID: 38878757 DOI: 10.1016/j.ejso.2024.108468] [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: 04/18/2024] [Revised: 05/20/2024] [Accepted: 06/04/2024] [Indexed: 09/09/2024]
Abstract
BACKGROUND Despite modern systemic chemotherapy, survival remains poor for patients with advanced isolated peritoneal metastases from the gastrointestinal tract. We aimed to assess the safety and efficacy of pressurized intraperitoneal aerosol chemotherapy (PIPAC) with oxaliplatin. PATIENTS AND METHODS We conducted a phase 1/2, open label, non-comparative, dose escalation and expansion trial of PIPAC with oxaliplatin in patients with a peritoneal cancer index (PCI) of more than 5, 13 and 15 for respectively a gastric, small bowel and colorectal primary cancer, and who had received at least three months of systemic chemotherapy. PIPAC cycle lengths were 4-6 weeks with systemic chemotherapy allowed 15 days after each PIPAC. PCI and oxaliplatin tumor concentration were assessed every PIPAC cycle. The main endpoints were tolerability, tumor response, and survival. RESULTS Between 2017 and 2020, 34 patients were enrolled in three centers, in this phase 1/2 study, of whom 25 were evaluable at the recommended dose determined in the phase I trial (90 mg/m2 plus systemic 5-FU). Before inclusion, patients received a median of 2 [1-4] chemotherapy lines and had a median PCI of 22.5 [7-29]. At this dose, the safety profile showed acceptable tolerability. Eight patients (32 %) had grade 3/4 treatment-related adverse events. Minor (grade 1/2) adverse events were mainly abdominal pain (n = 19, 76 %) and nausea (n = 16, 64 %). Median PFS was 6.1 months and median OS was 13 months. CONCLUSION In patients with advanced and refractory peritoneal metastasis, PFS of 6.1 months is encouraging. A prospective randomized phase II study is required.
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Affiliation(s)
- Frédéric Dumont
- Department of Surgical Oncology, Institut de Cancérologie de l'Ouest, Site de Saint Herblain, France.
| | - Vahan Kepenekian
- Department of Surgical Oncology, Centre Hospitalier Lyon Sud, Pierre Bénite, France
| | - Christophe Passot
- Oncopharmacology - Pharmacogenetics, Institut de Cancérologie de l'Ouest, Site d'Angers, France
| | | | - Marc Pocard
- Department of Surgery, Hôpital d'Instruction des armées Begin, Saint-Mande, France
| | - Jean-Luc Raoul
- Department of Medical Oncology, Institut de Cancérologie de l'Ouest, Site de Saint Herblain, France
| | - Bénédicte Lelièvre
- Laboratory of Pharmacology and Toxicology, Centre Hospitalier et Universitaire, Angers, France
| | - Sandrine Hiret
- Department of Medical Oncology, Institut de Cancérologie de l'Ouest, Site de Saint Herblain, France
| | - Hélène Senellart
- Department of Medical Oncology, Institut de Cancérologie de l'Ouest, Site de Saint Herblain, France
| | - Francois Pein
- Department of Clinical Research and Innovation, Institut de Cancérologie de l'Ouest, Site de Saint Herblain, France
| | - Judith Raimbourg
- Department of Medical Oncology, Institut de Cancérologie de l'Ouest, Site de Saint Herblain, France
| | - Loic Campion
- Department of Biostatistics and Methodology, Institut de Cancérologie de l'Ouest, Site de Saint Herblain, France
| | - Emilie Thibaudeau
- Department of Surgical Oncology, Institut de Cancérologie de l'Ouest, Site de Saint Herblain, France
| | - Julie Paul
- Department of Biostatistics and Methodology, Institut de Cancérologie de l'Ouest, Site de Saint Herblain, France
| | - Olivier Glehen
- Department of Surgical Oncology, Centre Hospitalier Lyon Sud, Pierre Bénite, France
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Ota E, Fukunaga Y, Mukai T, Hiyoshi Y, Yamaguchi T, Nagasaki T, Akiyoshi T. Cytoreductive surgery without intra-peritoneal chemotherapy for metachronous colorectal peritoneal metastases. World J Surg Oncol 2024; 22:205. [PMID: 39085860 PMCID: PMC11290162 DOI: 10.1186/s12957-024-03471-w] [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: 01/03/2024] [Accepted: 07/16/2024] [Indexed: 08/02/2024] Open
Abstract
BACKGROUND Cytoreductive surgery and chemotherapy reportedly improve the prognosis of patients with metachronous peritoneal metastases. However, the types of peritoneal metastases indicated for cytoreductive surgery remains unclear. Therefore, we aimed to clarify the category of cases for which cytoreductive surgery would be effective and report the prognosis associated with cytoreductive surgery for metachronous peritoneal metastases. METHODS This study included 52 consecutive patients who underwent cytoreductive surgery for metachronous peritoneal metastases caused by colorectal cancer between January 2005 and December 2018 and fulfilled the selection criteria. The median follow-up period was 54.9 months. Relapse-free survival was calculated as the time from cytoreductive surgery of metachronous peritoneal metastases to recurrence. Overall survival was defined as the time from cytoreductive surgery of metachronous peritoneal metastases to death or the end of the follow-up period. RESULTS The 5-year relapse-free survival rate was 30.0% and the 5-year overall survival rate was 72.3%. None of the patients underwent hyperthermic intraperitoneal chemotherapy. The analysis indicated no potential risk factors for 5-year relapse-free survival. However, for 5-year overall survival, the multivariate analysis revealed that time to diagnosis of metachronous peritoneal metastases of < 2 years after primary surgery (hazard ratio = 4.1, 95% confidence interval = 2.0-8.6, p = 0.0002) and number of metachronous peritoneal metastases ≥ 3 (hazard ratio = 9.8, 95% confidence interval = 2.3-42.3, p = 0.002) as independent factors associated with a poor prognosis. CONCLUSIONS Long intervals of more than 2 years after primary surgery and 2 or less metachronous peritoneal metastases were good selection criteria for cytoreductive surgery for metachronous peritoneal metastases from colorectal cancer.
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Affiliation(s)
- Emi Ota
- Department of Gastroenterological Surgery, Cancer Institute Hospital of the Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Yosuke Fukunaga
- Department of Gastroenterological Surgery, Cancer Institute Hospital of the Japanese Foundation for Cancer Research, Tokyo, Japan.
| | - Toshiki Mukai
- Department of Gastroenterological Surgery, Cancer Institute Hospital of the Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Yukiharu Hiyoshi
- Department of Gastroenterological Surgery, Cancer Institute Hospital of the Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Tomohiro Yamaguchi
- Department of Gastroenterological Surgery, Cancer Institute Hospital of the Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Toshiya Nagasaki
- Department of Gastroenterological Surgery, Cancer Institute Hospital of the Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Takashi Akiyoshi
- Department of Gastroenterological Surgery, Cancer Institute Hospital of the Japanese Foundation for Cancer Research, Tokyo, Japan
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Nguyen QA, Chou WH, Hsieh MC, Chang CM, Luo WT, Tai YT, Chang WC. Genetic alterations in peritoneal metastatic tumors predicted the outcomes for hyperthermic intraperitoneal chemotherapy. Front Oncol 2023; 13:1054406. [PMID: 37182141 PMCID: PMC10170308 DOI: 10.3389/fonc.2023.1054406] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2022] [Accepted: 03/27/2023] [Indexed: 05/16/2023] Open
Abstract
Introduction Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) are considered for patients with peritoneal metastasis (PM). However, patients selection that relies on conventional prognostic factors is not yet optimal. In this study, we performed whole exome sequencing (WES) to establish tumor molecular characteristics and expect to identify prognosis profiles for PM management. Methods In this study, blood and tumor samples were collected from patients with PM before HIPEC. Tumor molecular signatures were determined using WES. Patient cohort was divided into responders and non-responders according to 12-month progression-free survival (PFS). Genomic characteristics between the two cohorts were compared to study potential targets. Results In total, 15 patients with PM were enrolled in this study. Driver genes and enriched pathways were identified from WES results. AGAP5 mutation was found in all responders. This mutation was significantly associated with better OS (p = 0.00652). Conclusions We identified prognostic markers that might be useful to facilitate decision-making before CRS/HIPEC.
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Affiliation(s)
- Quynh-Anh Nguyen
- Department of Clinical Pharmacy, School of Pharmacy, Taipei Medical University, Taipei, Taiwan
| | - Wan-Hsuan Chou
- Department of Clinical Pharmacy, School of Pharmacy, Taipei Medical University, Taipei, Taiwan
| | - Mao-Chih Hsieh
- Department of General Surgery, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan
| | - Che-Mai Chang
- Department of Clinical Pharmacy, School of Pharmacy, Taipei Medical University, Taipei, Taiwan
| | - Wei-Tzu Luo
- Department of Clinical Pharmacy, School of Pharmacy, Taipei Medical University, Taipei, Taiwan
| | - Yu-Ting Tai
- Department of Anesthesiology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
- Department of Anesthesiology, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan
| | - Wei-Chiao Chang
- Department of Clinical Pharmacy, School of Pharmacy, Taipei Medical University, Taipei, Taiwan
- Master Program in Clinical Genomics and Proteomics, School of Pharmacy, Taipei Medical University, Taipei, Taiwan
- Department of Pharmacy, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan
- Integrative Research Center for Critical Care, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan
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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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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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Clinical Factors Affecting Bevacizumab Efficacy With and Without Conventional Chemotherapy in Metastatic Colon Cancer. Am J Ther 2021; 27:e500-e506. [PMID: 32902937 DOI: 10.1097/mjt.0000000000000859] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
PURPOSE Bevacizumab (BZ) combined with first line chemotherapy (CC) has shown good clinical outcomes in metastatic colorectal cancer (mCRC). Overall survival (OS) and/or progression free survival in mCRC patients receiving BZ with or without 5FU-based CC is thought to be affected by clinical and morphological factor(s). PATIENTS AND METHODS We reviewed retrospective medical records of all consecutive mCRC patients treated with BZ with or without CC at tertiary care center between 2003 and 2009 out of which149 patients (m = 77, f = 72) were eligible. RESULTS Our study population had a mean age at diagnosis of 63.5 years (SD = 11) with median follow-up period of 19.4 months. On initial radiological evaluation following BZ therapy, 56 patients (m = 31, f = 25) had complete or partial response categorized as "early responders." Remaining patients (m = 46, f = 47) who were either stable or showed progressive disease were categorized as "non-responders." Fifty percent among early responders and 60% among non-responders [relative risk (RR) 0.67 (95% confidence interval (CI), 0.43-1.06)] demonstrated disease progression on follow up. There was a slightly better OS among early responders compared to non-responders (median 21.5 months days versus 16.8 months, P = 0.07). Cox regression analysis suggested male sex (RR 0.65, 95% CI, 0.43-0.98), hematochezia (RR 0.63, 95% CI, 0.4-0.98), resectable primary tumor (RR 0.42, 95% CI, 0.24-0.72) and resectable metastatic mass (RR 0.32, 95% CI, 0.14-0.74) were found to be associated with longer OS. Abdominal pain (RR 1.76, 95% CI, 1.1-2.8), accompanying diabetes (RR 1.76, 95% CI, 1.09-2.85), and unexplained weight loss (RR 2.73, 95% CI, 1.73-4.29) were associated with poor OS. CONCLUSIONS Better OS among mCRC patients with resectable primary and metastatic tumors was seen. This is the first study to demonstrate slightly better outcome in males and negative influence of diabetes on outcome in mCRC treated with BZ.
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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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van't Erve I, Rovers KP, Constantinides A, Bolhuis K, Wassenaar ECE, Lurvink RJ, Huysentruyt CJ, Snaebjornsson P, Boerma D, van den Broek D, Buffart TE, Lahaye MJ, Aalbers AGJ, Kok NFM, Meijer GA, Punt CJA, Kranenburg O, de Hingh IHJT, Fijneman RJA. Detection of tumor-derived cell-free DNA from colorectal cancer peritoneal metastases in plasma and peritoneal fluid. J Pathol Clin Res 2021; 7:203-208. [PMID: 33635598 PMCID: PMC8073000 DOI: 10.1002/cjp2.207] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2020] [Revised: 01/06/2021] [Accepted: 01/26/2021] [Indexed: 12/13/2022]
Abstract
Tumor-derived cell-free DNA (cfDNA) is an emerging biomarker for guiding the personalized treatment of patients with metastatic colorectal cancer (CRC). While patients with CRC liver metastases (CRC-LM) have relatively high levels of plasma cfDNA, little is known about patients with CRC peritoneal metastases (CRC-PM). This study evaluated the presence of tumor-derived cfDNA in plasma and peritoneal fluid (i.e. ascites or peritoneal washing) in 20 patients with isolated CRC-PM and in the plasma of 100 patients with isolated CRC-LM. Among tumor tissue KRAS/BRAF mutation carriers, tumor-derived cfDNA was detected by droplet digital polymerase chain reaction (ddPCR) in plasma of 93% of CRC-LM and 20% of CRC-PM patients and in peritoneal fluid in all CRC-PM patients. Mutant allele fraction (MAF) and mutant copies per ml (MTc/ml) were lower in CRC-PM plasma than in CRC-LM plasma (median MAF = 0.28 versus 18.9%, p < 0.0001; median MTc/ml = 21 versus 1,758, p < 0.0001). Within patients with CRC-PM, higher cfDNA levels were observed in peritoneal fluid than in plasma (median MAF = 16.4 versus 0.28%, p = 0.0019; median MTc/ml = 305 versus 21, p = 0.0034). These data imply that tumor-derived cfDNA in plasma is a poor biomarker to monitor CRC-PM. Instead, cfDNA detection in peritoneal fluid may offer an alternative to guide CRC-PM treatment decisions.
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Affiliation(s)
- Iris van't Erve
- Department of PathologyThe Netherlands Cancer InstituteAmsterdamThe Netherlands
| | - Koen P Rovers
- Department of SurgeryCatharina Cancer InstituteEindhovenThe Netherlands
| | - Alexander Constantinides
- Department of Surgical Oncology, Division of Imaging and CancerUMC UtrechtUtrechtThe Netherlands
| | - Karen Bolhuis
- Department of Medical OncologyAmsterdam University Medical CentersAmsterdamThe Netherlands
| | | | - Robin J Lurvink
- Department of SurgeryCatharina Cancer InstituteEindhovenThe Netherlands
| | - Clément J Huysentruyt
- Department of PathologyLaboratory for Pathology and Medical Microbiology (PAMM)EindhovenThe Netherlands
| | - Petur Snaebjornsson
- Department of PathologyThe Netherlands Cancer InstituteAmsterdamThe Netherlands
| | - Djamila Boerma
- Department of SurgerySt. Antonius HospitalNieuwegeinThe Netherlands
| | - Daan van den Broek
- Department of Laboratory MedicineThe Netherlands Cancer InstituteAmsterdamThe Netherlands
| | - Tineke E Buffart
- Department of Gastrointestinal OncologyThe Netherlands Cancer InstituteAmsterdamThe Netherlands
| | - Max J Lahaye
- Department of RadiologyThe Netherlands Cancer InstituteAmsterdamThe Netherlands
| | - Arend GJ Aalbers
- Department of SurgeryThe Netherlands Cancer InstituteAmsterdamThe Netherlands
| | - Niels FM Kok
- Department of SurgeryThe Netherlands Cancer InstituteAmsterdamThe Netherlands
| | - Gerrit A Meijer
- Department of PathologyThe Netherlands Cancer InstituteAmsterdamThe Netherlands
| | - Cornelis JA Punt
- Department of Medical OncologyAmsterdam University Medical CentersAmsterdamThe Netherlands
- Julius Center for Health Sciences and Primary CareUniversity Medical Center UtrechtUtrechtThe Netherlands
| | - Onno Kranenburg
- Department of Surgical Oncology, Division of Imaging and CancerUMC UtrechtUtrechtThe Netherlands
- Utrecht Platform for Organoid TechnologyUtrecht UniversityUtrechtThe Netherlands
| | - Ignace HJT de Hingh
- Department of SurgeryCatharina Cancer InstituteEindhovenThe Netherlands
- Department of Epidemiology, GROW‐School for Oncology and Developmental BiologyMaastricht UniversityMaastrichtThe Netherlands
| | - Remond JA Fijneman
- Department of PathologyThe Netherlands Cancer InstituteAmsterdamThe 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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12
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Stewart JH, Blazer DG, Calderon MJG, Carter TM, Eckhoff A, Al Efishat MA, Fernando DG, Foster JM, Hayes-Jordan A, Johnston FM, Lautz TB, Levine EA, Maduekwe UN, Mangieri CW, Moaven O, Mogal H, Shen P, Votanopoulos KI. The Evolving Management of Peritoneal Surface Malignancies. Curr Probl Surg 2020; 58:100860. [PMID: 33832580 DOI: 10.1016/j.cpsurg.2020.100860] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2020] [Accepted: 07/04/2020] [Indexed: 02/07/2023]
Affiliation(s)
| | - Dan G Blazer
- Division of Surgical Oncology, Duke University Medical Center, Durham, NC
| | | | | | | | | | | | - Jason M Foster
- Fred and Pamela Buffet Cancer Center, University of Nebraska, Omaha, NE
| | | | - Fabian M Johnston
- Complex General Surgical Oncology Program, Johns Hopkins University, Baltimore, MD
| | - Timothy B Lautz
- Northwestern University Feinberg School of Medicine, Chicago, IL
| | | | - Ugwuji N Maduekwe
- Division of Surgical Oncology and Endocrine Surgery, University of North Carolina, Chapel Hill, NC
| | | | | | | | - Perry Shen
- Wake Forest University School of Medicine, Winston-Salem, NC
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13
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Miller AM, Lemke-Miltner CD, Blackwell S, Tomanek-Chalkley A, Gibson-Corely KN, Coleman KL, Weiner GJ, Chan CHF. Intraperitoneal CMP-001: A Novel Immunotherapy for Treating Peritoneal Carcinomatosis of Gastrointestinal and Pancreaticobiliary Cancer. Ann Surg Oncol 2020; 28:1187-1197. [PMID: 32409965 DOI: 10.1245/s10434-020-08591-7] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2020] [Indexed: 12/13/2022]
Abstract
BACKGROUND The treatment options for patients with peritoneal carcinomatosis (PC) of gastrointestinal and pancreaticobiliary origins are limited. The virus-like particle, CMP-001, composed of the Qβ bacteriophage capsid protein encapsulating a CpG-A oligodeoxynucleotide, activates plasmacytoid dendritic cells (pDCs) and triggers interferon alpha (IFNα) release, leading to a cascade of anti-tumor immune effects. METHODS To evaluate the ability of CMP-001 to trigger an immune response in patients with PC, peritoneal cells were isolated and stimulated ex vivo with CMP-001. Both IFNα release and percentage of pDC were quantified using enzyme-linked immunosorbent assay (ELISA) and flow cytometry, respectively. To evaluate the anti-tumor response in vivo, murine PC models were generated using mouse cancer cell lines (Panc02 and MC38) in immunocompetent mice treated with intraperitoneal CMP-001 or saline control. Survival was followed, and the immunophenotype of cells in the peritoneal tumor microenvironment was evaluated. RESULTS The pDCs accounted for 1% (range 0.1-3.9%; n = 17) of the isolated peritoneal cells. Ex vivo CMP-001 stimulation of the peritoneal cells released an average of 0.77 ng/ml of IFNα (range, 0-4700 pg/ml; n = 14). The IFNα concentration was proportional to the percentage of pDCs present in the peritoneal cell mixture (r = 0.6; p = 0.037). In murine PC models, intraperitoneal CMP-001 treatment elicited an anti-tumor immune response including an increase in chemokines (RANTES and MIP-1β), pro-inflammatory cytokines (IFNγ, interleukin 6 [IL-6], and IL-12), and peritoneal/tumor immune infiltration (CD4+/CD8+ T and natural killer [NK] cells). The CMP-001 treatment improved survival in both the Panc02 (median, 35 vs 28 days) and the MC38 (median: 57 vs 35 days) PC models (p < 0.05). CONCLUSIONS As a novel immunotherapeutic agent, CMP-001 may be effective for treating patients with PC.
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Affiliation(s)
- Ann M Miller
- Department of Surgery, University of Iowa Hospitals and Clinics, University of Iowa, Iowa City, IA, USA
| | - Caitlin D Lemke-Miltner
- Department of Internal Medicine, University of Iowa Hospitals and Clinics, Iowa City, IA, USA.,Holden Comprehensive Cancer Center, University of Iowa Hospitals and Clinics, Iowa City, IA, USA
| | - Sue Blackwell
- Department of Internal Medicine, University of Iowa Hospitals and Clinics, Iowa City, IA, USA.,Holden Comprehensive Cancer Center, University of Iowa Hospitals and Clinics, Iowa City, IA, USA
| | - Ann Tomanek-Chalkley
- Department of Surgery, University of Iowa Hospitals and Clinics, University of Iowa, Iowa City, IA, USA
| | - Katherine N Gibson-Corely
- Holden Comprehensive Cancer Center, University of Iowa Hospitals and Clinics, Iowa City, IA, USA.,Department of Pathology, University of Iowa Hospitals and Clinics, Iowa City, IA, USA
| | - Kristen L Coleman
- Holden Comprehensive Cancer Center, University of Iowa Hospitals and Clinics, Iowa City, IA, USA
| | - George J Weiner
- Department of Internal Medicine, University of Iowa Hospitals and Clinics, Iowa City, IA, USA.,Holden Comprehensive Cancer Center, University of Iowa Hospitals and Clinics, Iowa City, IA, USA
| | - Carlos H F Chan
- Department of Surgery, University of Iowa Hospitals and Clinics, University of Iowa, Iowa City, IA, USA. .,Holden Comprehensive Cancer Center, University of Iowa Hospitals and Clinics, Iowa City, IA, USA.
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14
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Hallam S, Tyler R, Price M, Beggs A, Youssef H. Meta-analysis of prognostic factors for patients with colorectal peritoneal metastasis undergoing cytoreductive surgery and heated intraperitoneal chemotherapy. BJS Open 2019; 3:585-594. [PMID: 31592510 PMCID: PMC6773657 DOI: 10.1002/bjs5.50179] [Citation(s) in RCA: 60] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2019] [Accepted: 04/03/2019] [Indexed: 12/15/2022] Open
Abstract
Background Up to 15 per cent of colorectal cancers present with peritoneal metastases (CPM). Cytoreductive surgery and heated intraperitoneal chemotherapy (CRS + HIPEC) aims to achieve macroscopic tumour resection combined with HIPEC to destroy microscopic disease. CRS + HIPEC is a major operation with significant morbidity and effects on quality of life (QoL). Improving patient selection is crucial to maximize patient outcomes while minimizing morbidity and mortality. The aim of this study was to identify prognostic factors for patients with CPM undergoing CRS + HIPEC. Methods A systematic search of MEDLINE, Embase and Cochrane Library electronic databases was performed using terms for colorectal cancer, peritoneal metastasis and CRS + HIPEC. Included studies focused on the impact of prognostic factors on overall survival following CRS + HIPEC in patients with CPM. Results Twenty-four studies described 3128 patients. Obstruction or perforation of the primary tumour (hazard ratio (HR) 2·91, 95 per cent c.i. 1·5 to 5·65), extent of peritoneal metastasis as described by the Peritoneal Carcinomatosis Index (PCI) (per increase of 1 PCI point: HR 1·07, 1·02 to 1·12) and the completeness of cytoreduction (CC score above zero: HR 1·75, 1·18 to 2·59) were associated with reduced overall survival after CRS + HIPEC. Conclusion Primary tumour obstruction or perforation, PCI score and CC score are valuable prognostic factors in the selection of patients with CPM for CRS + HIPEC.
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Affiliation(s)
- S Hallam
- Institute of Cancer and Genomic Sciences University of Birmingham Birmingham UK
| | - R Tyler
- Institute of Cancer and Genomic Sciences University of Birmingham Birmingham UK
| | - M Price
- Institute of Applied Health Research University of Birmingham Birmingham UK
| | - A Beggs
- Institute of Cancer and Genomic Sciences University of Birmingham Birmingham UK
| | - H Youssef
- Colorectal Surgery, Good Hope Hospital University Hospitals Birmingham NHS Foundation Trust Birmingham UK
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15
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Peritoneal and extraperitoneal relapse after previous curative treatment of peritoneal metastases from colorectal cancer: What survival can we expect? Eur J Cancer 2018; 100:94-103. [DOI: 10.1016/j.ejca.2018.04.015] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2018] [Revised: 04/09/2018] [Accepted: 04/11/2018] [Indexed: 01/08/2023]
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16
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Glockzin G, Zeman F, Croner RS, Königsrainer A, Pelz J, Ströhlein MA, Rau B, Arnold D, Koller M, Schlitt HJ, Piso P. Perioperative Systemic Chemotherapy, Cytoreductive Surgery, and Hyperthermic Intraperitoneal Chemotherapy in Patients With Colorectal Peritoneal Metastasis: Results of the Prospective Multicenter Phase 2 COMBATAC Trial. Clin Colorectal Cancer 2018; 17:285-296. [PMID: 30131226 DOI: 10.1016/j.clcc.2018.07.011] [Citation(s) in RCA: 30] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2018] [Revised: 07/21/2018] [Accepted: 07/24/2018] [Indexed: 01/29/2023]
Abstract
BACKGROUND Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) as parts of an interdisciplinary treatment concept including systemic chemotherapy can improve survival of selected patients with peritoneal metastatic colorectal cancer (pmCRC). Nevertheless, the sequence of the therapeutic options is still a matter of debate. Thus, the COMBATAC (COMBined Anticancer Treatment of Advanced Colorectal cancer) trial was conducted to evaluate a combined treatment regimen consisting of preoperative systemic polychemotherapy + cetuximab followed by CRS + HIPEC and postoperative systemic polychemotherapy + cetuximab. PATIENTS AND METHODS The COMBATAC trial is a prospective, multicenter, open-label, single-arm, single-stage phase 2 trial. Twenty-six patients with synchronous or metachronous colorectal or appendiceal peritoneal carcinomatosis were included. Enrollment was terminated prematurely by the sponsor because of slow recruitment. Progression-free survival as primary end point and overall survival were estimated by the Kaplan-Meier method. Also evaluated were morbidity according to Common Terminology Criteria for Adverse Events v4.0 and feasibility of the combined treatment concept. RESULTS Median progression-free survival for the intention-to-treat population (n = 25) was 14.9 months. Median overall survival was not reached during the study duration. Ninety-two adverse events were documented in 16 patients, including 14 serious adverse events in 9 patients. The overall morbidity rate was 64%, and the grade 3/4 morbidity rate was 44%. Of all grade 3/4 morbidity events, 36.4% were related to systemic chemotherapy and 22.7% to surgery, whereas 40.9% were not directly related. There was no treatment-related mortality. CONCLUSION The results of the COMBATAC trial show that the multimodal treatment concept consisting of perioperative systemic chemotherapy and CRS + HIPEC is safe and feasible. Progression-free survival in selected patients with colorectal or appendiceal peritoneal metastasis might be improved.
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Affiliation(s)
- Gabriel Glockzin
- Department of Surgery, University Medical Center Regensburg, Regensburg, Germany; Department of Surgery, Klinikum Bogenhausen, Munich, Germany.
| | - Florian Zeman
- Center for Clinical Studies, University Medical Center Regensburg, Regensburg, Germany
| | - Roland S Croner
- Department of Surgery, University of Erlangen-Nuremberg, Erlangen, Germany; Department of Surgery, University Hospital Magdeburg, Magdeburg, Germany
| | - Alfred Königsrainer
- Department of Surgery, University of Tübingen, Comprehensive Cancer Center, Tübingen, Germany
| | - Jörg Pelz
- Department of Surgery, University Hospital Würzburg, Würzburg, Germany; Department of Surgery, St Bernward Hospital, Hildesheim, Germany
| | - Michael A Ströhlein
- Department of Abdominal, Vascular and Transplant Surgery, Cologne-Merheim Medical Center, Witten/Herdecke University, Cologne, Germany
| | - Beate Rau
- Department of Surgery, Campus Virchow and Mitte, Charité, Universitätsmedizin Berlin, Berlin, Germany
| | - Dirk Arnold
- Asklepios Tumor Center Hamburg, AK Altona, Department of Oncology, Hamburg, Germany
| | - Michael Koller
- Center for Clinical Studies, University Medical Center Regensburg, Regensburg, Germany
| | - Hans J Schlitt
- Department of Surgery, University Medical Center Regensburg, Regensburg, Germany
| | - Pompiliu Piso
- Department of Surgery, University Medical Center Regensburg, Regensburg, Germany; Department of Surgery, Krankenhaus Barmherzige Brüder Regensburg, Regensburg, Germany
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17
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Prognostic Impact of Macroscopic Complete Resection and Inflammatory Status for Colorectal Cancer With Peritoneal Dissemination. Int Surg 2018. [DOI: 10.9738/intsurg-d-18-00009.1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
Abstract
Objective:
To clarify the appropriate treatment policy for colorectal cancer with peritoneal metastasis, case series were analyzed retrospectively.
Summary of background data:
The frequency of colorectal cancer and peritoneal dissemination occurring simultaneously is 4% to 7%. The prevention of peritoneal metastasis and the development of a strategy for cure are considered important factors in improving the treatment outcome of colorectal cancer.
Methods:
A total of 60 patients with colorectal cancer with peritoneal dissemination were enrolled in this study. Tumor and host condition characteristics and treatment regimens affecting patient survival were tested by using Kaplan-Meier survival analysis.
Results:
Histologic type, carbohydrate antigen 19-9, macroscopic complete resection, and Glasgow Prognostic Score were found to be independent prognostic factors for overall survival.
Conclusions:
Peritoneal carcinomatosis can result in better patient prognoses in patients with well-differentiated carcinoma, less peritoneal spread, low levels of tumor markers, and a low Glasgow Prognostic Score. In these patients, curative resection of peritoneal metastases followed by intensive chemotherapy might be effective.
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18
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Nagata H, Ishihara S, Hata K, Murono K, Kaneko M, Yasuda K, Otani K, Nishikawa T, Tanaka T, Kiyomatsu T, Kawai K, Nozawa H, Watanabe T. Survival and Prognostic Factors for Metachronous Peritoneal Metastasis in Patients with Colon Cancer. Ann Surg Oncol 2016; 24:1269-1280. [PMID: 27995451 DOI: 10.1245/s10434-016-5732-z] [Citation(s) in RCA: 45] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2016] [Indexed: 12/31/2022]
Abstract
BACKGROUND The clinical course of metachronous peritoneal metastasis of colorectal origin is poorly understood. In this retrospective study, we aimed to elucidate survival and prognostic factors for metachronous peritoneal metastasis. METHODS Patients with metachronous peritoneal metastasis after curative resection for stage I-III colon cancer were retrospectively reviewed, and the incidence and prognosis of metachronous peritoneal metastasis were investigated. Prognostic factors were identified by univariate and multivariate analyses. RESULTS Among 1582 surgically resected stage I-III colon cancer patients, 65 developed metachronous peritoneal metastasis. The 5-year cumulative incidence rate was 4.5%, and the median survival after diagnosis of peritoneal metastasis was 29.6 months. None of the patients underwent peritonectomy or intraperitoneal chemotherapy. Independent prognostic factors included right colon cancer [hazard ratio (HR) 2.69, 95% confidence interval (CI) 1.26-5.64; p = 0.011], time to metachronous peritoneal metastasis of <1 year (HR 2.02, 95% CI 1.04-3.87; p = 0.040), Peritoneal Cancer Index (PCI) >10 (HR 3.68, 95% CI 1.37-8.99; p = 0.012), concurrent metastases (HR 4.09, 95% CI 2.02-8.23; p < 0.001), and peritoneal nodule resection (HR 0.31, 95% CI 0.13-0.65; p = 0.002). CONCLUSIONS A proportion of colon cancer patients with metachronous peritoneal metastasis may benefit from combined peritoneal nodule resection and systemic chemotherapy. Right colon cancer, early peritoneal metastasis, a high PCI, and concurrent metastases negatively affected prognosis in patients with metachronous peritoneal metastasis.
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Affiliation(s)
- Hiroshi Nagata
- Department of Surgical Oncology, The University of Tokyo, Bunkyo, Tokyo, Japan.
| | - Soichiro Ishihara
- Department of Surgical Oncology, The University of Tokyo, Bunkyo, Tokyo, Japan
| | - Keisuke Hata
- Department of Surgical Oncology, The University of Tokyo, Bunkyo, Tokyo, Japan
| | - Koji Murono
- Department of Surgical Oncology, The University of Tokyo, Bunkyo, Tokyo, Japan
| | - Manabu Kaneko
- Department of Surgical Oncology, The University of Tokyo, Bunkyo, Tokyo, Japan
| | - Koji Yasuda
- Department of Surgical Oncology, The University of Tokyo, Bunkyo, Tokyo, Japan
| | - Kensuke Otani
- Department of Surgical Oncology, The University of Tokyo, Bunkyo, Tokyo, Japan
| | - Takeshi Nishikawa
- Department of Surgical Oncology, The University of Tokyo, Bunkyo, Tokyo, Japan
| | - Toshiaki Tanaka
- Department of Surgical Oncology, The University of Tokyo, Bunkyo, Tokyo, Japan
| | - Tomomichi Kiyomatsu
- Department of Surgical Oncology, The University of Tokyo, Bunkyo, Tokyo, Japan
| | - Kazushige Kawai
- Department of Surgical Oncology, The University of Tokyo, Bunkyo, Tokyo, Japan
| | - Hiroaki Nozawa
- Department of Surgical Oncology, The University of Tokyo, Bunkyo, Tokyo, Japan
| | - Toshiaki Watanabe
- Department of Surgical Oncology, The University of Tokyo, Bunkyo, Tokyo, Japan
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19
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Glockzin G, Schlitt HJ, Piso P. Therapeutic options for peritoneal metastasis arising from colorectal cancer. World J Gastrointest Pharmacol Ther 2016; 7:343-352. [PMID: 27602235 PMCID: PMC4986391 DOI: 10.4292/wjgpt.v7.i3.343] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/29/2016] [Revised: 06/22/2016] [Accepted: 07/13/2016] [Indexed: 02/06/2023] Open
Abstract
Peritoneal metastasis is a common sign of advanced tumor stage, tumor progression or tumor recurrence in patients with colorectal cancer. Due to the improvement of systemic chemotherapy, the development of targeted therapy and the introduction of additive treatment options such as cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC), the therapeutic approach to peritoneal metastatic colorectal cancer (pmCRC) has changed over recent decades, and patient survival has improved. Moreover, in contrast to palliative systemic chemotherapy or best supportive care, the inclusion of CRS and HIPEC as inherent components of a multidisciplinary treatment regimen provides a therapeutic approach with curative intent. Although CRS and HIPEC are increasingly accepted as the standard of care for selected patients and have become part of numerous national and international guidelines, the individual role, optimal timing and ideal sequence of the different systemic, local and surgical treatment options remains a matter of debate. Ongoing and future randomized controlled clinical trials may help clarify the impact of the different components, allow for further improvement of patient selection and support the standardization of oncologic treatment regimens for pmCRC. The addition of further therapeutic options such as neoadjuvant intraperitoneal chemotherapy or pressurized intraperitoneal aerosol chemotherapy, should be investigated to optimize therapeutic regimens and further improve the oncological outcome.
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