Publications by authors named "Olivier Glehen"

196 Publications

Patterns of peritoneal dissemination and response to systemic chemotherapy in common and rare peritoneal tumours treated by cytoreductive surgery: study protocol of a prospective, multicentre, observational study.

BMJ Open 2021 07 5;11(7):e046819. Epub 2021 Jul 5.

Radiology, Zydus Hospital, Ahmedabad, India.

Introduction: Despite optimal patient selection and surgical effort, recurrence is seen in over 70% of patients undergoing cytoreductive surgery (CRS) for peritoneal metastases (PM). Apart from the Peritoneal Cancer Index (PCI), completeness of cytoreduction and tumour grade, there are other factors like disease distribution in the peritoneal cavity, pathological response to systemic chemotherapy (SC), lymph node metastases and morphology of PM which may have prognostic value. One reason for the underutilisation of these factors is that they are known only after surgery. Identifying clinical predictors, specifically radiological predictors, could lead to better utilisation of these factors in clinical decision making and the extent of peritoneal resection performed for different tumours. This study aims to study these factors, their impact on survival and identify clinical and radiological predictors.

Methods And Analysis: There is no therapeutic intervention in the study. All patients with biopsy-proven PM from colorectal, appendiceal, gastric and ovarian cancer and peritoneal mesothelioma undergoing CRS will be included. The demographic, clinical, radiological, surgical and pathological details will be collected according to a prespecified format that includes details regarding distribution of disease, morphology of PM, regional node involvement and pathological response to SC. In addition to the absolute value of PCI, the structures bearing the largest tumour nodules and a description of the morphology in each region will be recorded. A correlation between the surgical, radiological and pathological findings will be performed and the impact of these potential prognostic factors on progression-free and overall survival determined. The practices pertaining to radiological and pathological reporting at different centres will be studied.

Ethics And Dissemination: The study protocol has been approved by the Zydus Hospital ethics committee (27 July, 2020) and Lyon-Sud ethics committee (A15-128).

Trial Registration Number: CTRI/2020/09/027709; Pre-results.
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http://dx.doi.org/10.1136/bmjopen-2020-046819DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8258594PMC
July 2021

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 Jun 13;13(12). Epub 2021 Jun 13.

Department of Surgical Oncology, Centre Hospitalier Lyon-Sud, 69310 Lyon, France.

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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http://dx.doi.org/10.3390/cancers13122964DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8231850PMC
June 2021

Combined grade and nuclear grade are prognosis predictors of epithelioid malignant peritoneal mesothelioma: a multi-institutional retrospective study.

Virchows Arch 2021 Jun 24. Epub 2021 Jun 24.

Department of Pathology, Institut de Pathologie Multisite, Groupement Hospitalier Sud, Hospices Civils de Lyon, 165 Chemin du Grand-Revoyet, 69310, Pierre-Bénite, France.

Epithelioid mesothelioma is the most prevalent subtype of diffuse malignant peritoneal mesothelioma. A recently described nuclear-grading system predicted survival in patients with epithelioid malignant pleural mesothelioma. The present study was undertaken to validate this grading system in epithelioid malignant peritoneal mesothelioma (EMPM) and to compare to combined grade, including nuclear atypia, mitotic count, and tumor necrosis. Cases of EMPM, from 1995 to 2018, were analyzed from 7 French institutions from RENAPE network. Solid growth, tumor necrosis, nuclear atypia, and mitotic count were evaluated by at least 3 pathologists from the RENAPATH group. The predictions in terms of OS and PFS of nuclear grade and combined grade were analyzed. Nuclear grade was computed combining nuclear atypia score and mitotic count into a grade of I-III. Another system combining nuclear atypia score, mitotic score, and tumor necrosis was evaluated and defined as a combined grade I-III. A total of 138 cases were identified. The median follow-up was 38.9 months (range: 1.1-196.6). Nuclear and combined grades III were independently associated with a shorter OS (p < 0.05), and a shorter PFS (p < 0.05). Patients with combined grade I tumors had the best overall and progression-free survivals, in comparison to nuclear grade I. In this large multicentric study, combined grade and nuclear grade were the best independent predictors of OS and PFS in EMPM. These systems should be easily described by pathologists involved into the management of malignant peritoneal mesothelioma, because of their potential therapeutic implications.
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http://dx.doi.org/10.1007/s00428-021-03144-zDOI Listing
June 2021

HIPEC Methodology and Regimens: The Need for an Expert Consensus.

Ann Surg Oncol 2021 Jun 17. Epub 2021 Jun 17.

Department of Surgical Oncology, Centre Hospitalier Lyon-sud, Lyon, France.

Background: Hyperthermic intraperitoneal chemotherapy (HIPEC) is performed with a wide variation in methodology, drugs, and other elements vital to the procedure. Adoption of a limited number of regimens could increase the collective experience of peritoneal oncologists, make comparison between studies more meaningful, and lead to a greater acceptance of results from randomized trials. This study aimed to determine the possibility of standardizing HIPEC methodology and regimens and to identify the best method of performing such a standardization.

Methods: A critical review of preclinical and clinical studies evaluating the pharmacokinetic aspects of different HIPEC drugs and drug regimens, the impact of hyperthermia, and the efficacy of various HIPEC regimens as well as studies comparing different regimens was performed.

Results: The preclinical and clinical data were limited, and studies comparing different regimens were scarce. Many of the regimens were neither supported by preclinical rationale or data nor validated by a dose-escalating formal phase 1 trial. All the regimens were based on pharmacokinetic data and did not take chemosensitivity of peritoneal metastases into account. Personalized medicine approaches such as patient-derived tumor organoids could offer a solution to this problem, although clinical validation is likely to be challenging.

Conclusions: Apart from randomized trials, more translational research and phases 1 and 2 studies are needed. While waiting for better preclinical and clinical evidence, the best way to minimize heterogeneity is by an expert consensus that aims to identify and define a limited number of regimens for each indication and primary site. The choice of regimen then can be tailored to the patient profile and its expected toxicity and the methodology according regional factors.
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http://dx.doi.org/10.1245/s10434-021-10193-wDOI Listing
June 2021

Associations between the severity of medical and surgical complications and perception of surgeon empathy in esophageal and gastric cancer patients.

Support Care Cancer 2021 Jun 10. Epub 2021 Jun 10.

SCALab UMR CNRS 9193, University of Lille, Villeneuve D'AscqCedex, Rue du Barreau BP 60149, Lille, France.

Objective: To assess the impact of global physician empathy and its three subdimensions (establishing rapport, emotional and cognitive processes) on the severity of postoperative complications in a sample of cancer patients.

Methods: We retrospectively analyzed data on 256 patients with esogastric cancer from the French national FREGAT database. Empathy and its subdimensions were assessed using the patient-reported CARE scale and the severity of medical and surgical complications was reported with the Clavien-Dindo classification system. The usual covariates were included in multinomial logistic regression analyses.

Results: Physician empathy predicted the odds of reporting major complications. When patients perceived high empathy, they were less likely to report major complications compared to no complications (OR = .95, 95% CI = [.91-.99], p = .029). Among the three dimensions, only "establishing rapport" (OR = .84, 95% CI = [.73-.98], p = .019) and the "emotional process" (OR = .85, 95% CI = [.74-.98], p = .022) predicted major complications.

Conclusions: Physician empathy is essential before surgery. Further research is needed to understand the mechanisms associating empathy with health outcomes in cancer. Physicians should be trained to establish good rapport with patients, especially in the preoperative period.
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http://dx.doi.org/10.1007/s00520-021-06257-yDOI Listing
June 2021

ASO Author Reflections: Standardizing HIPEC Methodology and Regimens: a Prelude to the PSOGI Expert Consensus.

Ann Surg Oncol 2021 Jun 4. Epub 2021 Jun 4.

Department of Surgical Oncology, Centre Hospitalier Lyon-Sud, Hospices Civils de Lyon, Lyon, Pierre Bénite, France.

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http://dx.doi.org/10.1245/s10434-021-10205-9DOI Listing
June 2021

Multicystic peritoneal mesothelioma treated with cytoreductive surgery followed or not by hyperthermic intraperitoneal chemotherapy: results from a large multicentric cohort.

Int J Hyperthermia 2021 ;38(1):805-814

Service de Chirurgie Digestive et Endocrinienne, Centre Hospitalier Lyon Sud, Hospices Civils de Lyon, Lyon, France.

Background: Multicystic peritoneal mesothelioma (MCPM) is a rare, slowly growing, condition prone to recur after surgery. The role of hyperthermic intraperitoneal chemotherapy (HIPEC) added to complete cytoreductive surgery (CRS) remains controversial and difficult to assess. As patients are mostly reproductive age women, surgical approach, and fertility considerations are important aspects of the management. This observational retrospective review aimed to accurate treatment strategy reflections.

Methods: The RENAPE database (French expert centers network) was analyzed over a 1999-2019 period. MCPM patients treated with CRS were included. A special focus on HIPEC, mini-invasive approach, and fertility considerations was performed.

Results: Overall 60 patients (50 women) were included with a median PCI of 10 (4-14) allowing 97% of complete surgery, followed by HIPEC in 82% of patients. A quarter of patients had a laparoscopic approach. Twelve patients (20%) recurred with a 3-year recurrence free survival of 84.2% (95% confidence interval 74.7-95.0). The hazard of recurrence was numerically reduced among patients receiving HIPEC, however, not statistically significant (hazard ratio 0.41, 0.12-1.42,  = 0.200). A severe post-operative adverse event occurred in 22% of patients with five patients submitted to a subsequent reoperation. Among four patients with a childbearing desire, three were successful (two had a laparoscopic-CRS-HIPEC and one a conventional CRS without HIPEC).

Conclusion: MCPM patients treatment should aim at a complete CRS. The intraoperative treatment options as laparoscopic approach, fertility function sparing and HIPEC should be discussed in expert centers to propose the most appropriate strategy.
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http://dx.doi.org/10.1080/02656736.2021.1903585DOI Listing
July 2021

Greater-omentum lesion-score (GOLS) as a predictor of residual disease in different regions of the peritoneal cavity in patients undergoing interval cytoreductive surgery for advanced ovarian cancer and its potential clinical utility.

Eur J Surg Oncol 2021 May 18. Epub 2021 May 18.

Dept. of Surgical Oncology, Centre Hospitalier Lyon-sud, Lyon, France. Electronic address:

Background And Aim: The greater omentum(GO) is a common site of residual disease in patients receiving neoadjuvant chemotherapy for advanced epithelial ovarian cancer. The presence of tumor in the GO could predict presence of disease in other peritoneal regions. The goal of this study was to perform a correlation between the greater-omentum lesion-score(GOLS) and presence of disease in different peritoneal regions and determine its potential utility in guiding interval cytoreductive surgery(CRS).

Methods: This prospective study included 134 patients undergoing interval CRS from July 1, 2018 to June 30, 2020. Each region of Sugarbaker's Peritobneal Cancer Index(PCI) was given a lesion score(LS) from 0 to 3 according to the diameter of the largest tumor in the region. The GOLS was recorded separately from other structures in the region. Correlation between the GOLS and surgical and pathological LS in each region was performed.

Results: As the GOLS increased, the incidence of disease(surgical LS) in other regions of the peritoneal cavity increased. Receiver operating characteristic(ROC) curves showed area under curve more than 80% for regions 1-2 and 7-8 indicating a high probability of disease in these regions in patients with GOLS 1-3. The positive predictive value(PPV) of preoperative imaging for GOLS was 95.7%. No cut-off of the GOLS could predict presence of disease on pathology with more than 70% accuracy.

Conclusions: Presence of disease in the GO warrants performing upper abdominal exploration and/or cytoreduction and interval CRS should be planned accordingly in these patients. Imaging has a high PPV in detecting disease in the GO.
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http://dx.doi.org/10.1016/j.ejso.2021.05.028DOI Listing
May 2021

The impact of PRODIGE 7 on the current worldwide practice of CRS-HIPEC for colorectal peritoneal metastases: A web-based survey and 2021 statement by Peritoneal Surface Oncology Group International (PSOGI).

Eur J Surg Oncol 2021 May 13. Epub 2021 May 13.

Department of Surgery, Catharina Hospital, Eindhoven, the Netherlands; GROW - School for Oncology and Developmental Biology, Maastricht University, Maastricht, Netherlands. Electronic address:

Introduction: The PRODIGE 7-trial investigated the additional value of Hyperthermic Intraperitoneal Chemotherapy (HIPEC) to cytoreductive surgery (CRS) for patients with colorectal peritoneal metastases (CPM). The results of PRODIGE 7 were presented at the 2018 ASCO meeting showing that 30 min oxaliplatin-based HIPEC did not improve overall survival. The current study investigated the impact of PRODIGE 7 on the worldwide practice of CRS and HIPEC.

Materials And Methods: CRS-HIPEC experts from 19 countries were invited through the Peritoneal Surface Oncology Group International (PSOGI) to complete an online survey concerning the current CRS-HIPEC practice in their hospital and country, and were asked to appraise the effect of PRODIGE 7.

Results: The survey was completed by 18/19 experts. Although their personal opinions of CRS-HIPEC were barely influenced by PRODIGE 7, they reported a substantial impact on daily practice. This included a switch towards Mitomycin-C based HIPEC-regimens and prolongation of HIPEC perfusion time, a reduction in the number of referrals from non-HIPEC centers, a reduction in national consensus, the removal of HIPEC from national guidelines, and a reduced reimbursement rate.

Conclusion: The PRODIGE 7 has had a major impact on the practice of CRS-HIPEC for CPM worldwide. HIPEC remains an attractive option with potential for control and eradication of disease and further studies into the optimal HIPEC-regimen are urgently needed. Meanwhile, given the complexity of the treatment of patients with CPM, and the proven benefits of optimal CRS, referral of patients with potentially resectable CPM to expert centers is recommended whilst the precise role of HIPEC is further evaluated.
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http://dx.doi.org/10.1016/j.ejso.2021.05.023DOI Listing
May 2021

Limitations of the PRODIGE 7 trial - Authors' reply.

Lancet Oncol 2021 05;22(5):e179-e180

Department of Digestive Surgery Hôpital Saint Louis, Paris, France.

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http://dx.doi.org/10.1016/S1470-2045(21)00192-3DOI Listing
May 2021

Tertiary lymphoid structures in epithelioid malignant peritoneal mesothelioma are associated with neoadjuvant chemotherapy, but not with prognosis.

Virchows Arch 2021 Apr 14. Epub 2021 Apr 14.

Department of Pathology, Caen University Hospital, University of Caen Normandie, Caen, France.

Epithelioid mesothelioma is the most prevalent subtype of diffuse malignant peritoneal mesothelioma. The relationship between a strong adaptive immune response and a better prognosis in malignant solid tumors is widely known. Due to the low incidence of epithelioid malignant peritoneal mesothelioma (EMPM), very little is known about their immune micro-environment. We encountered several cases of tertiary lymphoid structures in EMPM in a previous study and aimed to investigate in the same series the prevalence, clinicopathological features, and the prognostic impact associated with tertiary lymphoid structures in EMPM (TLS-EMPM). Cases of EMPM, from 1995 to 2018, were retrieved from 7 French institutions from the RENAPE Network. The predictions in terms of overall survival (OS) and progression-free survival (PFS) of TLS-EMPM were analyzed. We report 52 cases of TLS-EMPM among a series of 138 cases of EMPM. TLS-EMPM was significantly associated with neoadjuvant chemotherapy, and was not a prognostic indicator for OS (p = 0.652) and PFS (p = 0.804) in our series. TLS is a component of the host immune response to EMPM significantly associated with neoadjuvant chemotherapy, but was not a predictor of prognosis for overall and progression-free survivals in this series. These findings provide another possible etiology for tertiary lymphoid structures.
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http://dx.doi.org/10.1007/s00428-021-03099-1DOI Listing
April 2021

Adherence to French and ESGO Quality Indicators in Ovarian Cancer Surgery: An Ad-Hoc Analysis from the Prospective Multicentric CURSOC Study.

Cancers (Basel) 2021 Mar 30;13(7). Epub 2021 Mar 30.

Department of Gynecologic Oncology, Agostino Gemelli University Hospital, 00168 Rome, Italy.

Background: Quality Indicators for ovarian cancer (OC) have been developed by the European Society of Gynaecological Oncology (ESGO) and by the French National Cancer Institute (Institut National du Cancer, INCa). The aim of the study was to characterize OC care distribution in France by case-volume and to prospectively evaluate the adherence of high-volume institutions to INCa/ESGO quality indicators.

Methods: The cost-utility of radical surgery in ovarian cancer (CURSOC) trial is a prospective, multicenter, comparative and non-randomized study that includes patients with stage IIIC-IV epithelial OC treated in nine French health care tertiary institutions. Adherence to institutional quality indicators were anonymously assessed by an independent committee. OC care distribution in France were provided by the nationwide database of hospital procedures.

Results: More than half of patients are treated in low-volume institutions. Among the nine high-volume centers participating in the study, four (44.4%) met all institutional INCa/ESGO quality indicators. The other five (55.6%) did not fulfil one of the quality indicator criteria.

Conclusions: Access to high-volume OC providers in France is restricted to a minority of patients, and yet half of the referral institutions included in this study failed to meet all recommended institutional quality indicators. It is mandatory that national authorities work both to improve OC centralization and to incorporate quality assurance programs into certified centers.
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http://dx.doi.org/10.3390/cancers13071593DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8037412PMC
March 2021

Does neoadjuvant FOLFOX chemotherapy improve the prognosis of high-risk Stage II and III colon cancers? Three years' follow-up results of the PRODIGE 22 phase II randomized multicentre trial.

Colorectal Dis 2021 Jun 10;23(6):1357-1369. Epub 2021 Mar 10.

Department of Hepato-gastroenterology and Digestive Oncology, Hôpital Européen Georges Pompidou, AP-HP, Paris University, Paris, France.

Aim: Neoadjuvant chemotherapy has proven valuable in locally advanced resectable colon cancer (CC) but its effect on oncological outcomes is uncertain. The aim of the present paper was to report 3-year oncological outcomes, representing the secondary endpoints of the PRODIGE 22 trial.

Method: PRODIGE 22 was a randomized multicentre phase II trial in high-risk T3, T4 and/or N2 CC patients on CT scan. Patients were randomized between 6 months of adjuvant FOLFOX (upfront surgery) or perioperative FOLFOX (four cycles before surgery and eight cycles after; FOLFOX perioperative). In wild-type RAS patients, a third arm testing perioperative FOLFOX-cetuximab was added. The primary endpoint was the tumour regression grade. Secondary endpoints were 3-year overall survival (OS), disease-free survival (DFS), recurrence-free survival (RFS) and time to recurrence (TTR).

Results: Overall, 120 patients were enrolled. At interim analysis, the FOLFOX-cetuximab arm was stopped for futility. The remaining 104 patients represented our intention-to-treat population. In the perioperative group, 96% received the scheduled four neoadjuvant cycles and all but one had adjuvant FOLFOX for eight cycles. In the control arm, 38 (73%) patients received adjuvant FOLFOX. The median follow-up was 54.3 months. Three-year OS was 90.4% in both arms [hazard ratio (HR) = 0.85], 3-year DFS, RFS and TTR were, respectively, 76.8% and 69.2% (HR=0.94), 73% and 69.2% (HR = 0.86) and 82% and 72% (HR = 0.67) in the perioperative and control arms, respectively. Forest plots did not show any subgroup with significant difference for survival outcomes. No benefit from adding cetuximab was observed.

Conclusion: Perioperative FOLFOX has no detrimental effect on long-term oncological outcomes and may be an option for some patients with locally advanced CC.
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http://dx.doi.org/10.1111/codi.15585DOI Listing
June 2021

The Role of Hyperthermic Intraperitoneal Chemotherapy in Pseudomyxoma Peritonei After Cytoreductive Surgery.

JAMA Surg 2021 Mar 10;156(3):e206363. Epub 2021 Mar 10.

Peritoneal Surface Malignancies Unit, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Istituto Nazionale Tumori dei Tumori di Milano, Milano, Italy.

Importance: Studies on the prognostic role of hyperthermic intraperitoneal chemotherapy (HIPEC) in pseudomyxoma peritonei (PMP) are currently not available.

Objectives: To evaluate outcomes after cytoreductive surgery (CRS) and HIPEC compared with CRS alone in patients with PMP.

Design, Setting, And Participants: This cohort study analyzed data from the Peritoneal Surface Oncology Group International (PSOGI) registry, including 1924 patients with histologically confirmed PMP due to an appendiceal mucinous neoplasm. Eligible patients were treated with CRS with or without HIPEC from February 1, 1993, to December 31, 2017, and had complete information on the main prognostic factors and intraperitoneal treatments. Inverse probability treatment weights based on the propensity score for HIPEC treatment containing the main prognostic factors were applied to all models to balance comparisons between the CRS-HIPEC vs CRS-alone groups in the entire series and in the following subsets: optimal cytoreduction, suboptimal cytoreduction, high- and low-grade histologic findings, and different HIPEC drug regimens. Data were analyzed from March 1 to June 1, 2018.

Interventions: HIPEC including oxaliplatin plus combined fluorouracil-leucovorin, cisplatin plus mitomycin, mitomycin, and other oxaliplatin-based regimens.

Main Outcomes And Measures: Overall survival, severe morbidity (determined using the National Cancer Institute Common Terminology for Adverse Events, version 3.0), return to operating room, and 30- and 90-day mortality. Differences in overall survival were compared using weighted Kaplan-Meier curves, log-rank tests, and Cox proportional hazards multivariable models. A sensitivity analysis was based on the E-value from the results of the main Cox proportional hazards model. Differences in surgical outcomes were compared using weighted multivariable logistic models.

Results: Of the 1924 patients included in the analysis (997 [51.8%] men; median age, 56 [interquartile range extremes (IQRE), 45-65] years), 376 were in the CRS-alone group and 1548 in the CRS-HIPEC group. Patients with CRS alone were older (median age, 60 [IQRE, 48-70] vs 54 [IQRE, 44-63] years), had less lymph node involvement (14 [3.7%] vs 119 [7.7%]), received more preoperative systemic chemotherapy (198 [52.7%] vs 529 [34.2%]), and had higher proportions of high-grade disease (179 [47.6%] vs 492 [31.8%]) and suboptimal cytoreduction residual disease (grade 3, 175 [46.5%] vs 117 [7.6%]). HIPEC was not associated with a higher risk of worse surgical outcomes except with mitomycin, with higher odds of morbidity (1.99; 95% CI, 1.25-3.19; P = .004). HIPEC was associated with a significantly better overall survival in all subsets (adjusted hazard ratios [HRs], 0.60-0.68, with 95% CIs not crossing 1.00). The weighted 5-year overall survival was 57.8% (95% CI, 50.8%-65.7%) vs 46.2% (95% CI, 40.3%-52.8%) for CRS-HIPEC and CRS alone, respectively (weighted HR, 0.65; 95% CI, 0.50-0.83; P < .001; E-value, 2.03). Such prognostic advantage was associated with oxaliplatin plus fluorouracil-leucovorin (HR, 0.42; 95% CI, 0.19-0.93; P = .03) and cisplatin plus mitomycin (HR, 0.57; 95% CI, 0.42-0.78; P = .001) schedules.

Conclusions And Relevance: In this cohort study, HIPEC was associated with better overall survival when performed after CRS in PMP, generally without adverse effects on surgical outcomes.
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http://dx.doi.org/10.1001/jamasurg.2020.6363DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7841579PMC
March 2021

Implications of Pathologic Findings in Cytoreductive Surgery Specimens on Treatment of Colorectal Peritoneal Metastases: Results of a Prospective Multicentric Study.

Dis Colon Rectum 2021 May;64(5):534-544

1 Department of Surgical Oncology, Zydus Hospital, Ahmedabad, India 2 Department of Pathology, Centre Hospitalier Lyon-Sud, Lyon, France 3 Department of Surgical Oncology, Centre Hospitalier Lyon-Sud, Lyon, France 4 Department of Surgical Oncology, Saifee Hospital, Mumbai, India.

Background: A surgical peritoneal cancer index of >20 is often used to exclude patients from cytoreductive surgery for colorectal peritoneal metastases. The pathologic peritoneal cancer index in these patients may be <20.

Objective: The purpose of this study was to compare the pathologic and surgical findings and to look at potential pathologic prognostic factors.

Design: This is a prospective observational study including patients undergoing cytoreductive surgery.

Settings: The study was carried out at 3 peritoneal surface malignancy centers, 1 in France and 2 in India.

Patients: One-hundred patients were included from July 1, 2018, to June 30, 2019.

Main Outcome Measures: The pathologic peritoneal cancer index, peritoneal disease distribution, pathologic response to chemotherapy, factors affecting them and their relation with surgical findings, and potential prognostic value were explored.

Results: Ninety percent had colonic primaries. Fifty-one percent had left-sided tumors. The median surgical peritoneal cancer index was 4 (range, 0-35). Upper regions were involved in 32% and small bowel regions in 26%, and their involvement increased with a higher peritoneal cancer index (p < 0.001). The median pathologic peritoneal cancer index was 2 (range, 0-27) and was less than the surgical peritoneal cancer index in 57%. A pathologic complete response was obtained in 25%. Patients with pathologic complete response received more antiepidermal growth factor receptor therapy (p = 0.008); more leucovorin, 5-fluorouracil, and oxaliplatin; and folinic acid, fluorouracilirin, irinotecan hydrochloride, and oxaliplatin (p < 0.001). In 7 patients with a surgical peritoneal cancer index of >20, pathologic peritoneal cancer index was <20 in 4 patients. Disease in the primary tumor/anastomotic site was found in ≈80%.

Limitations: Survival outcomes are not available.

Conclusions: Surgical peritoneal cancer index of >20 should not be the sole factor to exclude patients from surgery, especially in responders to systemic therapies. The pathologic peritoneal cancer index, pathologic response to systemic chemotherapy, and disease distribution in the peritoneal cavity should be meticulously documented. Correlation with survival will define their future prognostic value. The primary anastomotic site is a common site for peritoneal disease and should be carefully evaluated in all patients. See Video Abstract at http://links.lww.com/DCR/B490. IMPLICACIONES DE LOS HALLAZGOS PATOLÓGICOS EN MUESTRAS DE CIRUGÍA CITORREDUCTORA EN EL TRATAMIENTO DE METÁSTASIS PERITONEALES COLORRECTALES: RESULTADOS DE UN ESTUDIO PROSPECTIVO MULTICÉNTRICO: Una ICP quirúrgica de >20 se utiliza a menudo para excluir a los pacientes de la cirugía citorreductora por metástasis peritoneales colorrectales. La PCI patológica en estos pacientes puede ser <20.Comparar los hallazgos patológicos y quirúrgicos y observar los posibles factores pronósticos patológicos.Se trata de un estudio observacional prospectivo que incluye a pacientes sometidos a cirugía citorreductora.El estudio se llevó a cabo en tres centros de malignidad de la superficie peritoneal, 1 en Francia y 2 en India.Se incluyeron 100 pacientes desde el 1 de julio de 2018 al 30 de junio de 2019.No hubo intervención terapéutica.Se exploró la ICP patológica, la distribución de la enfermedad peritoneal, la respuesta patológica a la quimioterapia, los factores que la afectan y su relación con los hallazgos quirúrgicos y el valor pronóstico potencial.El noventa por ciento tenía lesiones primarias colónicas. El 51% tenía tumores del lado izquierdo. La mediana de la ICP quirúrgica 4 [0-35]. Las regiones superiores estuvieron involucradas en el 32% y las regiones del intestino delgado en un 26% y su participación aumentó con una ICP más alta (p <0,001). La mediana de la ICP patológica fue 2 [0-27] y fue menor que la ICP quirúrgica en el 57%. Se obtuvo respuesta patológica completa en el 25%. Los pacientes con respuesta patológica completa recibieron más terapia anti-EGFR (p = 0,008) y más FOLFOX y FOLFIRINOX (p <0,001). En 7 pacientes con una ICP quirúrgica de> 20, la ICP patológica fue menor de 20 en 4 pacientes. Se encontró enfermedad en el tumor primario/anastomósis en casi el 80%.Los resultados de supervivencia no están disponibles.La ICP quirúrgica de> 20 no debería ser el único factor para excluir a los pacientes de la cirugía, especialmente en los que responden a las terapias sistémicas. La PCI patológica, la respuesta patológica a la quimioterapia sistémica y la distribución de la enfermedad en la cavidad peritoneal deben documentarse meticulosamente. La correlación con la supervivencia definirá su valor pronóstico futuro. El sitio anastomótico primario es un sitio común de enfermedad peritoneal y debe evaluarse cuidadosamente en todos los pacientes. Consulte Video Resumen en http://links.lww.com/DCR/Bxxx. (Traducción-Dr. Gonzalo Hagerman).
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http://dx.doi.org/10.1097/DCR.0000000000001904DOI Listing
May 2021

Site of Recurrence and Survival After Surgery for Colorectal Peritoneal Metastasis.

J Natl Cancer Inst 2021 Aug;113(8):1027-1035

Department of Surgery & Transplantation, Surgical Oncology Research Laboratory, University Hospital of Zurich, Zurich, Switzerland.

Background: Multimodal treatment, including systemic treatment and surgery, improved the prognosis of peritoneal metastasis (PM). Despite all efforts, recurrence rates remain high, and little data are available about clinical behavior or molecular patterns of PM in comparison to hematogenous metastasis. Here, we aimed to analyze recurrence patterns after multimodal treatment for PM from colorectal cancer.

Methods: Patients with colorectal PM undergoing multimodal treatment including systemic chemotherapy and cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) between 2005 and 2017 at 4 centers were analyzed retrospectively.

Results: A total of 505 patients undergoing CRS/HIPEC were analyzed. Of the patients, 82.1% received preoperative chemotherapy. Median peritoneal cancer index was 6 (interquartile range = 3-11). Median disease-free and overall survival was 12 (95% confidence interval [CI] = 11 to 14) months and 51 (95% CI = 43 to 62) months, respectively. Disease recurred in 361 (71.5%) patients, presenting as isolated peritoneal recurrence in 24.6%, isolated hematogenous recurrence in 28.3%, and mixed recurrence in 13.9% of patients. Recurrence to the peritoneum was associated with an impaired time from recurrence to death of 21 (95% CI = 18 to 31) months for isolated peritoneal and 22 (95% CI = 16 to 30) months for mixed recurrence, compared with 43 (95% CI = 31 to >121) months for hematogenous recurrence (hazard ratio [HR] = 1.79, 95% CI = 1.27 to 2.53; P = .001; and HR = 2.44, 95% CI = 1.61 to 3.79; P < .001). On multiple logistic regression analysis, RAS mutational status (odds ratio [OR] = 2.42, 95% CI = 1.11 to 5.47; P = .03) and positive nodal stage of the primary (OR = 3.88, 95% CI = 1.40 to 11.86; P = .01) were identified as predictive factors for peritoneal recurrence.

Conclusions: This study highlights the heterogeneity of peritoneal metastasis in patients with colorectal cancer. Recurrent peritoneal metastasis after radical treatment represents a more aggressive subset of metastatic colorectal cancer.
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http://dx.doi.org/10.1093/jnci/djab001DOI Listing
August 2021

Cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy versus cytoreductive surgery alone for colorectal peritoneal metastases (PRODIGE 7): a multicentre, randomised, open-label, phase 3 trial.

Lancet Oncol 2021 02 18;22(2):256-266. Epub 2021 Jan 18.

Department of Digestive Surgery, Centre Hospitalier Lyon Sud, Pierre Bénite, France.

Background: The addition of hyperthermic intraperitoneal chemotherapy (HIPEC) to cytoreductive surgery has been associated with encouraging survival results in some patients with colorectal peritoneal metastases who were eligible for complete macroscopic resection. We aimed to assess the specific benefit of adding HIPEC to cytoreductive surgery compared with receiving cytoreductive surgery alone.

Methods: We did a randomised, open-label, phase 3 trial at 17 cancer centres in France. Eligible patients were aged 18-70 years and had histologically proven colorectal cancer with peritoneal metastases, WHO performance status of 0 or 1, a Peritoneal Cancer Index of 25 or less, and were eligible to receive systemic chemotherapy for 6 months (ie, they had adequate organ function and life expectancy of at least 12 weeks). Patients in whom complete macroscopic resection or surgical resection with less than 1 mm residual tumour tissue was completed were randomly assigned (1:1) to cytoreductive surgery with or without oxaliplatin-based HIPEC. Randomisation was done centrally using minimisation, and stratified by centre, completeness of cytoreduction, number of previous systemic chemotherapy lines, and timing of protocol-mandated systemic chemotherapy. Oxaliplatin HIPEC was administered by the closed (360 mg/m) or open (460 mg/m) abdomen techniques, and systemic chemotherapy (400 mg/m fluorouracil and 20 mg/m folinic acid) was delivered intravenously 20 min before HIPEC. All individuals received systemic chemotherapy (of investigators' choosing) with or without targeted therapy before or after surgery, or both. The primary endpoint was overall survival, which was analysed in the intention-to-treat population. Safety was assessed in all patients who received surgery. This trial is registed with ClinicalTrials.gov, NCT00769405, and is now completed.

Findings: Between Feb 11, 2008, and Jan 6, 2014, 265 patients were included and randomly assigned, 133 to the cytoreductive surgery plus HIPEC group and 132 to the cytoreductive surgery alone group. After median follow-up of 63·8 months (IQR 53·0-77·1), median overall survival was 41·7 months (95% CI 36·2-53·8) in the cytoreductive surgery plus HIPEC group and 41·2 months (35·1-49·7) in the cytoreductive surgery group (hazard ratio 1·00 [95·37% CI 0·63-1·58]; stratified log-rank p=0·99). At 30 days, two (2%) treatment-related deaths had occurred in each group.. Grade 3 or worse adverse events at 30 days were similar in frequency between groups (56 [42%] of 133 patients in the cytoreductive surgery plus HIPEC group vs 42 [32%] of 132 patients in the cytoreductive surgery group; p=0·083); however, at 60 days, grade 3 or worse adverse events were more common in the cytoreductive surgery plus HIPEC group (34 [26%] of 131 vs 20 [15%] of 130; p=0·035).

Interpretation: Considering the absence of an overall survival benefit after adding HIPEC to cytoreductive surgery and more frequent postoperative late complications with this combination, our data suggest that cytoreductive surgery alone should be the cornerstone of therapeutic strategies with curative intent for colorectal peritoneal metastases.

Funding: Institut National du Cancer, Programme Hospitalier de Recherche Clinique du Cancer, Ligue Contre le Cancer.
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http://dx.doi.org/10.1016/S1470-2045(20)30599-4DOI Listing
February 2021

RAS/TP53 co-Mutation is Associated with Worse Survival after Concurrent Resection of Colorectal Liver Metastases and Extrahepatic Disease.

Ann Surg 2020 Dec 18;Publish Ahead of Print. Epub 2020 Dec 18.

Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA Department of Surgical Oncology, CHU Lyon Sud, Hospices Civils de Lyon, Pierre-Bénite, France EMR 3738, CICLY, Université Claude Bernard Lyon 1, Lyon, France Cancer Research Center of Lyon, Université de Lyon, Université Claude Bernard Lyon 1, Lyon, France / Department of Biochemistry and Molecular Biology, Lyon University Hospital, Hospices Civils de Lyon, Centre Hospitalier Lyon-Sud, Lyon, France.

Objective: To determine if tumor genetics are associated with overall survival (OS) after concurrent resection of colorectal liver metastases (CLM) and extrahepatic disease (EHD).

Summary Background Data: The prognosis for patients who undergo concurrent resection of CLM/EHD is unclear and the impact of somatic mutations has not been reported.

Methods: Patients undergoing concurrent resection of CLM and EHD from 2007-2017 were identified from two academic centers. From 1 center, patients were selected from a pre-existing database of patients undergoing cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (HIPEC). The Kaplan-Meier method was used to construct survival curves, compared using the log-rank test. Multivariable Cox analysis for OS was performed.

Results: One hundred nine patients were included. Most common EHD sites included lung (33 patients), peritoneum (32), and portal lymph nodes (14). TP53 mutation was the most common mutation, identified in 75 patients (69%), and RAS/TP53 co-mutation was identified in 31 patients (28%). The median OS was 49 months (IQR, 24-125), and 3- and 5-year OS rates were 66% and 44%, respectively. Compared to patients without RAS/TP53 co-mutation, patients with RAS/TP53 co-mutation had lower median OS: 39 vs. 51 months (P = .02). On multivariable analysis, lung EHD (hazard ratio [HR], 0.7; 95% CI, 0.3-1.4), peritoneal EHD (HR, 2.2; 95% CI, 1.1-4.2) and RAS/TP53 co-mutation (HR, 2.8; 95% CI, 1.1-7.2) were independently associated with OS.

Conclusions: RAS/TP53 co-mutation is associated with worse OS after concurrent CLM/EHD resection. Mutational status and site of EHD should be included in the evaluation of patients considered for concurrent resection.
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http://dx.doi.org/10.1097/SLA.0000000000004672DOI Listing
December 2020

ASO Author Reflections: Potential Therapeutic Implications and Prediction of Pathological Complete Response to Systemic Chemotherapy in Colorectal Peritoneal Metastases.

Ann Surg Oncol 2021 Jul 19;28(7):3850-3851. Epub 2020 Nov 19.

Department of Surgical Oncology, Centre Hospitalier Lyon-Sud, Hospices Civils de Lyon, Pierre Bénite, Lyon, France.

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http://dx.doi.org/10.1245/s10434-020-09378-6DOI Listing
July 2021

Clinical and Radiologic Predictors of a Pathologic Complete Response to Neoadjuvant Chemotherapy (NACT) in Patients Undergoing Cytoreductive Surgery for Colorectal Peritoneal Metastases: Results of a Prospective Multi-center Study.

Ann Surg Oncol 2021 Jul 18;28(7):3840-3849. Epub 2020 Nov 18.

Department of Surgical Oncology, Centre Hospitalier Lyon-Sud, Lyon, France.

Background: Patients undergoing cytoreductive surgery for colorectal peritoneal metastases who have a pathologic complete response (pCR) to neoadjuvant chemotherapy experience a significantly longer survival than those with residual disease. This response is known only after surgery. This study aimed to examine clinical and radiologic predictors of a pCR.

Methods: From July 2018 to December 2019, the study prospectively enrolled 120 patients. The clinical and radiologic findings were compared between patients with and without a pCR. A protocol for pathologic evaluation was followed.

Results: A pCR was observed in 34 patients (28.3%). Receiver operating characteristic (ROC) curves showed that patients with a surgical Peritoneal Cancer Index (sPCI) of 3 or lower had an 80% probability of experiencing a pCR, and that patients with a radiologic PCI (rPCI) of 2 or lower had a 70% probability of experiencing a pCR. A pCR was correctly predicted for 47% of the patients by imaging and for 44.4% of the patients by surgical evaluation. The site of primary tumor, the timing of peritoneal metastasis (PM), histology, tumor marker positivity, and mutations in known poor prognostic genes (KRAS) did not differ between the patients with and those without pCR. The primary tumor showed residual disease in 23.5% and regional nodes in 26.4% of the patients with pCR.

Conclusions: The rPCI and sPCI concurred with a pCR in less than 50% of the patients. The patients with a lower PCI had greater concordance. An sPCI of 3 or lower was predictive of a pCR in 80% of the patients. The impact of KRAS mutations on pCR should be evaluated in a larger series. The predictors of pCR and response to systemic chemotherapy should be incorporated in prognostic scores used to select patients for surgery.
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http://dx.doi.org/10.1245/s10434-020-09330-8DOI Listing
July 2021

Long term survival in patients with peritoneal metastasised gastric cancer treated with cytoreductive surgery and HIPEC: A multi-institutional cohort from PSOGI.

Eur J Surg Oncol 2021 01 14;47(1):172-180. Epub 2020 Oct 14.

Department of Surgery, Campus Virchow-Klinikum and Charité Campus Mitte, Charité - Universitätsmedizin Berlin, Berlin, Germany. Electronic address:

Background: Peritoneal metastasis (PM) of gastric cancer (GC) is relatively common (17%) and is associated with poor survival. Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) is still controversially discussed, as it has proven an increase in survival in selected patients, but only a small subgroup reached long-term survival. The aim of this study was to collect and analyse a worldwide cohort of patients treated with CRS and HIPEC with long-term survival in order to explore relevant patient characteristics.

Methods: We conducted a questionnaire, which was distributed to all collaborators of the Peritoneal Surface Oncology Group International (PSOGI). Inclusion criteria were: histopathologic proven PM of GC, treated with CRS and HIPEC, and overall survival >5 years. Patient, tumour, and therapeutic details were collected and analysed.

Results: From an analysis of 448 patients treated between 1994 and 2014, a total of 28 patients with a mean age of 53.0 years and mean PCI of 3.3 were included. The overall median survival was 11.0 years (min 5.0; max 27.9). The predictors completeness of cytoreduction (CC-0) and PCI<6 were present in 22/28 patients. 12/28 patients developed at a median of 9.6 years tumour recurrence, and was associated with inferior median overall survival compared to patients without recurrence (8.8 years vs. not reached; p = 0.002).

Conclusions: Long-term survival and even cure are possible in patients with PM of GC treated with CRS and HIPEC. Completeness of cytoreduction and low PCI seemed to be crucial. Further studies are needed in order to improve existing selection criteria.
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http://dx.doi.org/10.1016/j.ejso.2020.10.006DOI Listing
January 2021

Distribution of residual disease in the peritoneum following neoadjuvant chemotherapy in advanced epithelial ovarian cancer and its potential therapeutic implications.

Eur J Surg Oncol 2021 01 14;47(1):181-187. Epub 2020 Oct 14.

Dept. of Surgical Oncology, Centre Hospitalier Lyon-sud, Lyon, France. Electronic address:

Introduction: Residual disease in 'normal appearing' peritoneum is seen in nearly 30% of the patients following neoadjuvant chemotherapy (NACT) for advanced ovarian cancer. The goal was to study the sequence of response in different regions, the commonest sites of occult residual disease, its incidence in different peritoneal regions and the potential therapeutic implications of these.

Methods: This was a prospective multi-centre study (July 2018-June 2019). Pathological evaluation of cytoreductive surgery specimens was performed according to a fixed protocol. Prevalence of residual disease in different regions was used to study patterns of response and distribution of residual disease.

Result: In 85 patients treated between July 2018 to June 2019, microscopic disease in 'normal appearing' peritoneal regions was seen in 22 (25.2%) and in normal peritoneum around tumor nodules in 30 (35.2%) patients. Regions 4 and 8 of Sugarbaker's PCI had the highest incidence of occult disease and regions 9 and 10 the lowest. The response to chemotherapy occurred in a similar manner in over 95%- the least common site of residual disease was the small bowel mesentery, followed by upper regions (regions 1-3), omentum and middle regions (regions 0, 4, 8), lower regions (regions 5-7) and lastly the ovaries.

Conclusions: During interval CRS, based on the disease mapping provided in this manuscript, regions that have a high probability of residual disease should be explored and dissected. Complete resection of involved the peritoneal region can completely address the occult disease. The role of resection of the entire region as well as 'normal appearing' parietal peritoneal regions should be prospectively evaluated.
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http://dx.doi.org/10.1016/j.ejso.2020.10.012DOI Listing
January 2021

A phase I dose-escalation study of oxaliplatin delivered via a laparoscopic approach using pressurised intraperitoneal aerosol chemotherapy for advanced peritoneal metastases of gastrointestinal tract cancers.

Eur J Cancer 2020 11 8;140:37-44. Epub 2020 Oct 8.

Department of Surgical Oncology, Centre Hospitalier Lyon Sud, Pierre Bénite, France.

Objective: The objectives were to define the maximum tolerated dose (MTD), safety profile and pharmacokinetics (PKs) of intraperitoneal oxaliplatin delivered by pressurised intraperitoneal aerosol chemotherapy (PIPAC) in patients with advanced peritoneal carcinomatosis from gastrointestinal tract cancers.

Methods: PIPAC was applied every 4-6 weeks, for 5 cycles, in a phase I dose-escalation study using a 3 + 3 design. The first dose level was 90 mg/m with planned increases of 50 mg/m per level. Platinum concentration was measured in plasma, tissues and intraperitoneal fluid samples. The trial was registered at ClinicalTrials.gov (NCT03294252).

Results: Ten patients with 33 PIPAC sessions were included. No dose limiting toxicity (DLT) occurred at 90 mg/m and two at 140 mg/m. The MTD was therefore set at 90 mg/m. Overall treatment included a median number of three PIPAC sessions (range: 1-5) and secondary complete cytoreductive surgery for two patients. Overall safety showed 67 grade I-II and 11 grade III-IV toxicities, usually haematologic, digestive (nausea/vomiting, abdominal pain), and fatigue. Oxaliplatin concentrations were three- to four-fold higher in tissue in contact with aerosol than in muscle without contact. At 140 mg/m, the plasma oxaliplatin concentration was high with Cmax and area under the curve (AUC) of 1035 μg/l and 9028 μg h/L, respectively.

Conclusions: The MTD of oxaliplatin during PIPAC is 90 mg/m. PK data demonstrate a high tumour concentration and a significant systemic absorption.
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http://dx.doi.org/10.1016/j.ejca.2020.09.010DOI Listing
November 2020

Expanding Uses of HIPEC for Locally Advanced Colorectal Cancer: A European Perspective.

Clin Colon Rectal Surg 2020 Sep 18;33(5):253-257. Epub 2020 Sep 18.

General Surgery Department (Surgical Oncology), Centre Hospitalier Lyon Sud (Hospices Civils de Lyon), Lyon, France.

Locally advanced colorectal cancer is a challenge for surgeons and medical oncologist; 10 to 20% colorectal cancer debut as locally advanced disease, with tumors extending through the colon wall with perforation and/or invasion of adjacent organs or structures. Those locally advanced tumors have a worse prognostic at any stage due not only to systemic dissemination but also in a high percentage of patients, to locoregional recurrence, in fact, peritoneal carcinomatosis of colorectal origin is so predictable that we can assess the risk for each patient according to some histopathological and clinical features: small peritoneal nodules resected in the first surgery (70% probability), ovarian metastases (60%), perforated tumor onset or intraoperative tumor rupture (50%), positive cytology (40%), and pT4/mucinous pT3 up to 40%. Prophylactic or adjuvant hyperthermic intraperitoneal chemotherapy seems to be a promising strategy for patients with advanced colorectal cancer to prevent the development of peritoneal recurrence and improve prognosis of this group of patients.
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http://dx.doi.org/10.1055/s-0040-1713742DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7500959PMC
September 2020

Decision-Making Analysis for Hyperthermic Intraperitoneal Chemotherapy in Ovarian Cancer: A Survey by the Executive Committee of the Peritoneal Surface Oncology Group International (PSOGI).

Oncology 2021 11;99(1):41-48. Epub 2020 Sep 11.

Department of Radiation Oncology, Cantonal Hospital of St. Gallen, St. Gallen, Switzerland.

Objectives: To assess the individual treatment strategies among international experts in peritoneal carcinosis, specifically their decision-making in the process of patient selection for hyperthermic intraperitoneal chemotherapy (HIPEC) in women suffering from ovarian cancer, to identify relevant decision-making criteria, and to quantify the level of consensus for or against HIPEC.

Methods: The members of the executive committee of the Peritoneal Surface Oncology Group International (PSOGI) were asked to describe the clinical conditions under which they would recommend HIPEC in patients with ovarian cancer and to describe any disease or patient characteristics relevant to their decision. All answers were then merged and converted into decision trees. The decision trees were then analyzed by applying the objective consensus methodology.

Results: Nine experts in surgical oncology provided information on their multidisciplinary treatment strategy including HIPEC for patients with advanced ovarian cancer. Three of the total of 12 experts did not perform HIPEC. Five criteria relevant to the decision on whether HIPEC is performed were applied. In patients with resectable disease, a peritoneal cancer index (PCI) <21, and epithelial ovarian cancer without distant metastasis, consent was received by 75% to perform HIPEC for women suffering from recurrent disease. Furthermore, in the primary disease setting, consent was received by 67% to perform HIPEC according to the same criteria.

Discussion And Conclusion: Among surgical oncology experts in peritoneal surface malignancy and HIPEC, HIPEC plays an important role in primary and recurrent ovarian cancer, and the PCI is the most important criterion in this decision.
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http://dx.doi.org/10.1159/000510098DOI Listing
January 2021

Patient Selection for Hyperthermic Intraperitoneal Chemotherapy in Patients With Colorectal Cancer: Consensus on Decision Making Among International Experts.

Clin Colorectal Cancer 2020 12 15;19(4):277-284. Epub 2020 Jul 15.

Department of Radiation Oncology, Hospital of the Canton of St Gallen, St Gallen, Switzerland.

Background: Colorectal cancer (CRC) treatment for patients with peritoneal metastases is complex. The use of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) has continued to be debated. The aim of the present study was to assess the consensus among international experts for decision-making regarding the use of CRS and HIPEC for patients with CRC.

Materials And Methods: Of 15 experts invited, 12 had provided their decision algorithms for CRS and HIPEC for patients with, or at high risk of, peritoneal metastases from CRC. Using the objective consensus method, the results were transformed into decision trees to provide information on the consensus and discordance.

Results: Only 1 scenario was found for which the consensus on performing HIPEC had reached 100%. The scenario was the treatment of young patients with complete cytoreduction and a peritoneal carcinomatosis index (PCI) of < 16 in the presence of certain risk factors. Five major decision criteria were identified: age, PCI, completeness of cytoreduction, extent of extraperitoneal metastases (EoMs), and, in the case of unverified EoMs, additional risk factors. Consensus was found regarding refraining from using HIPEC for older patients with a high PCI. The consensus further increased when addressing incomplete cytoreduction and an extensive extent of EoMs.

Conclusion: A definite consensus concerning the use of HIPEC was only determined for very selected scenarios. These findings can be used for general guidance; however, owing to the heterogeneity of each individual situation, the impracticality of presenting the information through decision trees, and the unclear future of the role of HIPEC in the adjuvant setting, a one-on-one transfer to daily clinical practice could not be achieved.
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http://dx.doi.org/10.1016/j.clcc.2020.06.010DOI Listing
December 2020

Impact of multidisciplinary tumour board in the management of ovarian carcinoma in the first-line setting. Exhaustive analysis from the Rhone-Alpes region.

Eur J Cancer Care (Engl) 2020 Nov 7;29(6):e13313. Epub 2020 Sep 7.

Oncology Department, Leon Berard Cancer Center, Lyon, France.

Objective: Epithelial ovarian cancer (EOC) is a poor prognosis disease partly linked to diagnosis at an advanced stage. The quality of care management is a factor that needs to be explored, more specifically optimal organisation of first-line treatment.

Methods: A retrospective study, dealing with all patients diagnosed within the Rhone-Alpes region with initial diagnosis EOC in 2012, was performed. The aim was to describe the impact of multidisciplinary tumour boards (MTB) in the organisation of care and the consequence on the patient's outcomes.

Results: 271 EOC were analysed. 206 patients had an advanced EOC. Median progression-free survival (PFS) is 17.8 months (CI95%, 14.6-21.2) for AOC. 157 patients (57.9%) had a front-line surgery versus 114 patients (42.1%) interval debulking surgery. PFS for AOC patients with no residual disease is 24.3 months compared with 15.3 months for patients with residual disease (p = .01). No macroscopic residual disease is more frequent in the patients discussed before surgery in MTB compared with patients not submitted before surgery (73% vs. 56.2%, p < .001).

Conclusion: These results highlight the heterogeneity of medical practices in terms of front-line surgery versus interval surgery, in the administration of neoadjuvant chemotherapy and in the setting of MTB discussion.
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http://dx.doi.org/10.1111/ecc.13313DOI Listing
November 2020

Guidelines for Perioperative Care in Cytoreductive Surgery (CRS) with or without hyperthermic IntraPEritoneal chemotherapy (HIPEC): Enhanced recovery after surgery (ERAS®) Society Recommendations - Part I: Preoperative and intraoperative management.

Eur J Surg Oncol 2020 12 25;46(12):2292-2310. Epub 2020 Aug 25.

Division of Gynecologic Oncology, Tom Baker Cancer Centre, University of Calgary, Calgary, Alberta, Canada.

Background: Enhanced recovery after surgery (ERAS) pathways have been shown to considerably reduce complications, length of stay and costs after most of surgical procedures by standardised application of best evidence-based perioperative care. The aim was to elaborate dedicated recommendations for cytoreductive surgery (CRS) ± hyperthermic intraperitoneal chemotherapy (HIPEC) in a two-part series of guidelines based on expert consensus. The present part I of the guidelines highlights preoperative and intraoperative management.

Methods: The core group assembled a multidisciplinary panel of 24 experts involved in peritoneal surface malignancy surgery representing the fields of general surgery (n = 12), gynaecological surgery (n = 6), and anaesthesia (n = 6). Experts systematically reviewed and summarized the available evidence on 72 identified perioperative care items, following the GRADE (grading of recommendations, assessment, development, evaluation) system. Final consensus (defined as ≥50%, or ≥70% of weak/strong recommendations combined) was reached by a standardised 2-round Delphi process, regarding the strength of recommendations.

Results: Response rates were 100% for both Delphi rounds. Quality of evidence was evaluated high, moderate low and very low, for 15 (21%), 26 (36%), 29 (40%) and 2 items, respectively. Consensus was reached for 71/72(98.6%) items. Strong recommendations were defined for 37 items, No consensus could be reached regarding the preemptive use of fresh frozen plasma.

Conclusion: The present ERAS recommendations for CRS±HIPEC are based on a standardised expert consensus process providing clinicians with valuable guidance. There is an urgent need to produce high quality studies for CRS±HIPEC and to prospectively evaluate recommendations in clinical practice.
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http://dx.doi.org/10.1016/j.ejso.2020.07.041DOI Listing
December 2020

Front-Line Maintenance Therapy in Advanced Ovarian Cancer-Current Advances and Perspectives.

Cancers (Basel) 2020 Aug 25;12(9). Epub 2020 Aug 25.

Oncology Department, Hôpital Lyon Sud, Institut de Cancérologie des Hospices Civils de Lyon (IC-HCL) and Université de Lyon, 69310 Lyon, France.

Ovarian tumor is the gynecological cancer associated with the highest mortality. Most diseases are diagnosed at an advanced stage, which impairs the chances of prolonged complete remission. The standard front-line treatment of advanced stages combines surgery in an expert center with platinum-based chemotherapy. Most patients experience a relapse in the years following the initial treatment. During the last decade, anti-angiogenic agents used in the maintenance setting improved progression free survival (PFS) over chemotherapy alone. More recently, PARP inhibitors demonstrated substantial efficacy, mainly in patients with germinal or somatic mutations or other homologous recombination deficiencies (HRD), all involved in double strand DNA Damage Repair (DDR). Other therapeutic paradigms are currently being explored, including combinations of immune-checkpoints inhibitors, chemotherapy, bevacizumab and PARP inhibitors. In addition to these clinical advances, molecular characterization of the tumors and their correlations with drugs efficacy are needed to better understand which patient will benefit the most from the various treatments available to date.
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http://dx.doi.org/10.3390/cancers12092414DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7564452PMC
August 2020

Centralization and Oncologic Training Reduce Postoperative Morbidity and Failure-to-rescue Rates After Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy for Peritoneal Surface Malignancies: Study on a 10-year National French Practice.

Ann Surg 2020 11;272(5):847-854

Department of Digestive and Oncological Surgery, Claude Huriez University Hospital, Lille, France.

Objective: Evaluate at a national level the postoperative mortality (POM), major morbidity (MM) and failure-to-rescue (FTR) after cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) across time and according to hospital-volume.

Background: CRS/HIPEC is an effective therapeutic strategy commonly used to treat peritoneal surface malignancies. However, this aggressive approach has the reputation to be associated with a high POM and MM.

Methods: All patients treated with CRS/HIPEC between 2009 and 2018 in France were identified through a national medical database. Patients and perioperative outcomes were analyzed. A cut-off value of the annual CRS/HIPEC caseload affecting the 90-day POM was calculated using the Chi-squared Automatic Interaction Detector method. A multivariable logistic model was used to identify factors mediating 90-day POM.

Results: A total of 7476 CRS/HIPEC were analyzed. Median age was 59 years with a mean Elixhauser comorbidity index of 3.1, both increasing over time (P < 0.001). Ninety-day POM was 2.6%. MM occurred in 44.2% with a FTR rate of 5.1%. The threshold of CRS/HIPEC number per center per year above which the 90-day POM was significantly reduced was 45 (3.2% vs 1.9%, P = 0.01). High-volume centers had more extended surgery (P < 0.001) with increased MM (55.8% vs 40.4%, P < 0.001) but lower FTR (3.1% vs 6.3%, P = 0.001). After multivariate analysis, independent factors associated with 90-day POM were: age >70 years (P = 0.002), Elixhauser comorbidity index ≥8 (P = 0.006), lower gastro-intestinal origin, (P < 0.010), MM (P < 0.001), and <45 procedures/yr (P = 0.002).

Conclusion: In France, CRS/HIPEC is a safe procedure with an acceptable 90-day POM that could even be improved through centralization in high-volume centers.
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http://dx.doi.org/10.1097/SLA.0000000000004326DOI Listing
November 2020
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