The current practice of cytoreductive surgery and HIPEC for colorectal peritoneal metastases: Results of a worldwide web-based survey of the Peritoneal Surface Oncology Group International (PSOGI)

Bushati, Matilda; Rovers, Koen P.; Sommariva, Antonio; Sugarbaker, Paul H.; Morris, David L.; Yonemura, Yutaka; Quadros, Claudio Almeida; Somashekhar, S. P.; Ceelen, Wim; Dubé, Pierre; Li, Y.; Verwaal, Victor J.; Gléhen, Olivier; Piso, Pompiliu; Spiliotis, John; Teo, Melissa Ching Ching; González-Moreno, Santiago; Cashin, Peter; Lehmann, Kuno; Deraco, Marcello; Moran, B.; Hingh, Ignace H. J. T. de

doi:10.1016/j.ejso.2018.07.003

Cited by 117 publications

(91 citation statements)

References 24 publications

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“…Retrospective comparisons between oxaliplatin and mitomycin C (MMC), the two drugs most commonly used in HIPEC for PMs from colorectal cancer, generated contradictory results. As a consequence, there is currently no consensus on the choice of chemotherapy, the dose administered or the duration of perfusion. Regardless of the chemotherapy drug used in HIPEC, recurrence rates after CRS–HIPEC are high and more than half of patients experience disease recurrence within 2 years.…”

Section: Introductionmentioning

confidence: 99%

Organoids from colorectal peritoneal metastases as a platform for improving hyperthermic intraperitoneal chemotherapy

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Bolhaqueiro

Elias

et al. 2019

British Journal of Surgery

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Background Patients with peritoneal metastases from colorectal cancer have a poor prognosis. If the intraperitoneal tumour load is limited, patients may be eligible for cytoreductive surgery followed by hyperthermic intraperitoneal chemotherapy (HIPEC). This treatment has improved overall survival, but recurrence rates are high. The aim of this study was to create a preclinical platform for the development of more effective intraperitoneal chemotherapy strategies. Methods Using organoid technology, five tumour cultures were generated from malignant ascites and resected peritoneal metastases. These were used in an in vitro HIPEC model to assess sensitivity to mitomycin C (MMC) and oxaliplatin, the drugs used most commonly in HIPEC. The model was also used to test a rational combination treatment involving MMC and inhibitors of the checkpoint kinase ATR. Results MMC was more effective in eliminating peritoneal metastasis‐derived organoids than oxaliplatin at clinically relevant concentrations. However, the drug concentrations required to eliminate 50 per cent of the tumour cells (IC50) were higher than the median clinical dose in two of five organoid lines for MMC, and all five lines for oxaliplatin, indicating a general resistance to monotherapy. ATR inhibition increased the sensitivity of all peritoneal metastasis‐derived organoids to MMC, as the IC50 decreased 2·6–12·4‐fold to well below concentrations commonly attained in clinical practice. Live‐cell imaging and flow cytometric analysis showed that ATR inhibition did not release cells from MMC‐induced cell cycle arrest, but caused increased replication stress and accelerated cell death. Conclusion Peritoneal metastasis‐derived organoids can be used to evaluate existing HIPEC regimens on an individual‐patient level and for development of more effective treatment strategies. Cytoreductive surgery followed by hyperthermic intraperitoneal chemotherapy (HIPEC) has improved prognosis of patients with peritoneal metastases from colorectal cancer, but disease recurrence is common. More effective and personalized HIPEC is urgently needed. Organoid technology is frequently used for drug screens, as patient‐derived organoids can accurately predict clinical therapeutic response in vitro.A panel of organoids was established from peritoneal metastases from colorectal cancer and used to develop a model for testing HIPEC regimens in vitro. Patient‐derived organoids differed in sensitivity to commonly used chemotherapeutics, in line with variable clinical outcomes following cytoreductive surgery–HIPEC. Combining MMC with an ATR inhibitor improved the efficacy of MMC.Peritoneal metastasis‐derived organoids can be used as a platform to test novel (combination) strategies that increase HIPEC efficacy. In the future, organoids could be used to select patent‐tailored HIPEC regimens.

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Section: Introductionmentioning

confidence: 99%

Organoids from colorectal peritoneal metastases as a platform for improving hyperthermic intraperitoneal chemotherapy

Ubink

Bolhaqueiro

Elias

et al. 2019

British Journal of Surgery

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“…In the last decades, the therapeutic strategy for colorectal peritoneal surface malignancy (PSM) has changed considerably from a palliative approach to an approach with curative intent by the introduction of cytoreductive surgery (CRS) followed by hyperthermic intraperitoneal perioperative chemotherapy (HIPEC) . This combined treatment modality has resulted in significant survival improvements with a median overall survival of 41.7 months and should now be considered standard of care for colorectal PSM (results presented at the American Society of Clinical Oncology [ASCO] annual meeting in Chicago) .…”

Section: Introductionmentioning

confidence: 99%

“…Although, there is now a clearly defined standardization of CRS procedures, based on the work of Sugarbaker et al, there is still a large variety in HIPEC treatment modalities used in current clinical practice. Methodological variations to be considered are: technique (open vs closed), normothermic vs hyperthermic chemotherapy, drug selection, drug dose, exposure time, and dosing regimen …”

Section: Introductionmentioning

confidence: 99%

“…Methodological variations to be considered are: technique (open vs closed), normothermic vs hyperthermic chemotherapy, drug selection, drug dose, exposure time, and dosing regimen. 1,6 The current intraperitoneal (IP) chemotherapy dosing regimens can be divided into body surface area (BSA)-based and concentration-based protocols. BSA-based protocols calculate drug dose based on calculated BSA (mg/m 2 ) and consider the BSA as a measure for the effective peritoneal contact area, the peritoneal surface area in the Dedrick formula.…”

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confidence: 99%

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Body surface area‐based vs concentration‐based perioperative intraperitoneal chemotherapy after optimal cytoreductive surgery in colorectal peritoneal surface malignancy treatment: COBOX trial

Lemoine

Thijssen

Carleer

et al. 2019

Journal of Surgical Oncology

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Background and Objectives Cytoreductive surgery (CRS) and hyperthermic intraperitoneal perioperative chemotherapy (HIPEC) are the standard of care for patients diagnosed with colorectal peritoneal surface malignancy (PSM). Despite a clearly defined standardization of CRS, a large variety of HIPEC modalities are still used in clinical practice. Methods Body surface area (BSA)‐ and concentration‐based HIPEC protocols were clinically and pharmacologically evaluated in a randomized phase III clinical pilot trial. Oxaliplatin dose was 460 mg/m 2 (BSA‐based) in 2 L/m 2 carrier solution (concentration‐based). Platinum quantification was performed using a validated inductively coupled plasma mass spectrometry method. Three‐month morbidity, mortality, and health‐related quality of life (HRQOL) were assessed. Results Thirty‐one patients were randomized to either BSA‐ or concentration‐based HIPEC. Toxicity and efficacy were higher (P < 0.001) in patients receiving concentration‐based HIPEC. There was no difference in pharmacologic advantage between the two groups. A higher drug concentration in the tumor nodule at the end of HIPEC was found in the HIPEC‐concentration group. There was no difference in major morbidity and mortality between the treatment groups. HRQOL was decreased 3 months postoperatively in the HIPEC‐concentration group. Conclusion Concentration‐based chemotherapy delivers the drug in the most standardized way to the tumor nodule, resulting in increasing drug concentrations in the tumor nodule without increasing major morbidity.

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“…They are often chemo-resistant, associated with other peritoneal metastases, and confer a worse prognosis [35,36]. Ovarian metastases from CRC are peritoneal disease and therefore should be treated with CRS and HIPEC [37,38]. A laparoscopy may be performed to evaluate PCI as other peritoneal deposits may be present.…”

Section: Discussionmentioning

confidence: 99%

Perceptions in the management of colorectal peritoneal metastases: A bi-national survey of colorectal surgeons

Narasimhan

Warrier

Michael

et al. 2019

Pleura and Peritoneum

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BackgroundThere is great variability in the uptake of cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) in the management of colorectal peritoneal metastases (CRPM) in Australia and New Zealand. This study aims to provide a snapshot of perceptions among colorectal surgeons in the management of CRPM.MethodsA structured ten-question online survey was sent to all colorectal surgeons, with three questions on clinical experience and demographics, one on health economics and six on hypothetical clinical scenarios. Scores were collated and reported based on Likert scales.ResultsEighty-one respondents (36.2%) completed the survey. Most surgeons (66.7%) strongly disagreed with offering CRS and HIPEC at all hospitals. The majority (87.7%) agreed that CRS and HIPEC offered a higher survival benefit than systemic chemotherapy in pseudomyxoma peritonei (PMP), and 69.1% in CRPM (comparators: 60.5% ovarian cancer, 14.8% gastric cancer). There were mixed strategies in managing low-volume, isolated peritoneal recurrences. The majority did not recommend second-look laparoscopy, but favoured operative management of Krukenberg tumours. In the presence of incidental peritoneal metastases, only 29.6% favoured biopsy only and referring the patient to a peritoneal disease centre.ConclusionsResponse rate was relatively low. In Australia and New Zealand, colorectal surgeons see a strong role for CRS and HIPEC in the management of PMP and CRPM. The role of “second look” surgery in high-risk cases is controversial and not supported. Krukenberg tumours are viewed as surgical disease. Regular updates and collaboration with peritoneal centres may help surgeons stay abreast with latest evidence in the field.

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The current practice of cytoreductive surgery and HIPEC for colorectal peritoneal metastases: Results of a worldwide web-based survey of the Peritoneal Surface Oncology Group International (PSOGI)

Cited by 117 publications

References 24 publications

Organoids from colorectal peritoneal metastases as a platform for improving hyperthermic intraperitoneal chemotherapy

Organoids from colorectal peritoneal metastases as a platform for improving hyperthermic intraperitoneal chemotherapy

Body surface area‐based vs concentration‐based perioperative intraperitoneal chemotherapy after optimal cytoreductive surgery in colorectal peritoneal surface malignancy treatment: COBOX trial

Perceptions in the management of colorectal peritoneal metastases: A bi-national survey of colorectal surgeons

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