The Delphi and GRADE methodology used in the PSOGI 2018 consensus statement on Pseudomyxoma Peritonei and Peritoneal Mesothelioma

Pseudomyxoma Peritonei (PMP) and Peritoneal Mesothelioma (PM) are both rare peritoneal malignancies. Currently, affected patients may be treated with Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy offering long-term survival or even cure in selected patients. However, many issues regarding the optimal treatment strategy are currently under debate. To aid physicians involved in the treatment of these patients in clinical decision making, the PSOGI executive committee proposed to create a consensus statement on PMP and PM. This manuscript describes the methodology of the consensus process. The Delphi technique is a reliable method for attaining consensus on a topic that lacks scientific evidence through multiple voting rounds which feeds back responses to the participants in between rounds. The GRADE system provides a structured framework for presenting and grading the available evidence. Separate questionnaires were created for PMP and PM and sent during two voting rounds to 80 and 38 experts, respectively. A consensus threshold of 51.0% was chosen. After the second round, consensus was reached on 92.9%–100.0% of the questions. The results were presented and discussed in the plenary session at the PSOGI 2018 international meeting in Paris. A third round for the remaining issues is currently in progress. In conclusion, using the Delphi technique and GRADE methodology, consensus was reached in many issues regarding the treatment of PM and PMP amongst an international panel of experts. The main results will be published in the near future

The Delphi and GRADE methodology used in the PSOGI 2018 consensus statement on Pseudomyxoma Peritonei and Peritoneal Mesothelioma.

Pseudomyxoma Peritonei (PMP) and Peritoneal Mesothelioma (PM) are both rare peritoneal malignancies. Currently, affected patients may be treated with Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy offering long-term survival or even cure in selected patients. However, many issues regarding the optimal treatment strategy are currently under debate. To aid physicians involved in the treatment of these patients in clinical decision making, the PSOGI executive committee proposed to create a consensus statement on PMP and PM. This manuscript describes the methodology of the consensus process. The Delphi technique is a reliable method for attaining consensus on a topic that lacks scientific evidence through multiple voting rounds which feeds back responses to the participants in between rounds. The GRADE system provides a structured framework for presenting and grading the available evidence. Separate questionnaires were created for PMP and PM and sent during two voting rounds to 80 and 38 experts, respectively. A consensus threshold of 51.0% was chosen. After the second round, consensus was reached on 92.9%-100.0% of the questions. The results were presented and discussed in the plenary session at the PSOGI 2018 international meeting in Paris. A third round for the remaining issues is currently in progress. In conclusion, using the Delphi technique and GRADE methodology, consensus was reached in many issues regarding the treatment of PM and PMP amongst an international panel of experts. The main results will be published in the near future

An international registry of peritoneal carcinomatosis from appendiceal goblet cell carcinoma treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy

Purpose Peritoneal carcinomatosis from appendiceal goblet cell carcinoma (A-GCC) is a rare and aggressive form of appendiceal tumor. Cytoreductive surgery (CRS) and hyperthermic intra peritoneal chemotherapy (HIPEC) was reported as an interesting alternative regarding survival compared to surgery without HIPEC and/or systemic chemotherapy. Our aim was to evaluate the impact of CRS and HIPEC for patients presenting A-GCC through an international registry. Methods A prospective multicenter international database was retrospectively searched to identify all patients with A-GCC tumor and peritoneal metastases who underwent CRS and HIPEC through the Peritoneal Surface Oncology Group International (PSOGI). The post-operative complications, long-term results, and principal prognostic factors were analyzed. Results The analysis included 83 patients. After a median follow-up of 47 months, the median overall survival (OS) was 34.6 months. The 3- and 5-year OS was 48.5% and 35.7%, respectively. Patients who underwent complete macroscopic CRS had a significantly better survival than those treated with incomplete CRS. The 5-year OS was 44% and 0% for patients who underwent complete, and incomplete CRS, respectively (HR 9.65, p < 0.001). Lymph node involvement and preoperative chemotherapy were also predictive of a worse prognosis. There were 3 postoperative deaths, and 30% of the patients had major complications. Conclusion CRS and HIPEC may increase long-term survival in selected patients with peritoneal metastases of A-GCC origin, especially when complete CRS is achieved. Ideally, randomized control trials or more retrospective data are needed to confirm CRS and HIPEC as the gold standard in this pathology

Peritoneal Carcinomatosis of Rare Ovarian Origin Treated by Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy: A Multi-Institutional Cohort from PSOGI and BIG-RENAPE

International audiencePURPOSE:Ovarian cancer is the most common deadly cancer of gynecologic origin. Patients often are diagnosed at advanced stage with peritoneal metastasis. There are many rare histologies of ovarian cancer; some have outcomes worse than serous ovarian cancer. Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) can be considered for patients with recurrence. This study was designed to assess the impact of CRS and HIPEC on survival of patient with peritoneal metastasis from rare ovarian malignancy.METHODS:A prospective, multicentric, international database was retrospectively searched to identify all patients with rare ovarian tumor (mucinous, clear cells, endometrioid, small cell hypercalcemic, and other) and peritoneal metastasis who underwent CRS and HIPEC through the Peritoneal Surface Oncology Group International (PSOGI) and BIG-RENAPE working group. The postoperative complications, long-term results, and principal prognostic factors were analyzed.RESULTS:The analysis included 210 patients with a median follow-up of 43.5 months. Median overall survival (OS) was 69.3 months, and the 5-year OS was 57.7%. For mucinous tumors, median OS and DFS were not reached at 5 years. For granulosa tumors, median overall survival was not reached at 5 years, and median DFS was 34.6 months. Teratoma or germinal tumor showed median overall survival and DFS that were not reached at 5 years. Differences in OS were not statistically significant between histologies (p = 0.383), whereas differences in DFS were (p < 0.001).CONCLUSIONS:CRS and HIPEC may increases long-term survival in selected patients with peritoneal metastasis from rare ovarian tumors especially in mucinous, granulosa, or teratoma histological subtypes

Is there an oncological interest in the combination of CRS/HIPEC for peritoneal carcinomatosis of HCC? Results of a multicenter international study

International audienceINTRODUCTION:Peritoneal metastasis (PM) of hepatocellular carcinoma (HCC) without distant spread are rare. The related prognosis is poor without standard treatment available. The role of cytoreduction surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) is poorly documented.METHODS:An international multicentric cohort was constituted by retrospective analysis of 21 patients undergoing CRS/HIPEC for PM of HCC between 1992 and 2016 from 10 reference centers of PSOGI. Data on clinical features, treatment strategies, and survival outcomes were analyzed.RESULTS:The median time interval from the diagnosis of PM to the procedure was 4.5 months. The median peritoneal cancer index was 14. Sixteen patients had complete cytoreduction (CCR0-1). Ten patients had grades 3 to 4 complications. The median duration of follow-up was 52.2 months. The median OS was 46.7 months. The projected 3y-OS and 5y-OS were 88.9 and 49.4% respectively. The median OS for patients with CCR0-1 resection was not reached whereas it was 5.9 months for those with CCR2-3 resection after CRS (p = 0.0005). The median RFS was 26.3 months and projected RFS at 3 years of 36.5 months Three prognostic factors were associated with improved RFS in the univariate analysis: preoperative chemotherapy (p = 0.0156), PCI >15 (p = 0.009), Number of chemotherapy agents used for HIPEC (p = 0.005).CONCLUSION:CRS/HIPEC is a safe and effective approach in selected patients with PM of HCC. CRS/HIPEC gives the patient a chance for a good relapse free and overall survival and should be considered as an option

Combined liver resection and cytoreductive surgery with HIPEC for metastatic colorectal cancer: Results of a worldwide analysis of 565 patients from the Peritoneal Surface Oncology Group International (PSOGI).

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Cytoreductive surgery and HIPEC improve survival compared to palliative chemotherapy for biliary carcinoma with peritoneal metastasis: A multi-institutional cohort from PSOGI and BIG RENAPE groups

International audienceBACKGROUND:Peritoneal metastasis from biliary carcinoma (PMC) is associated with poor prognosis when treated with chemotherapy.OBJECTIVE:To evaluate the impact on survival of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC), and compare with conventional palliative chemotherapy for patients with PMC.MATERIAL AND METHODS:A prospective multicenter international database was retrospectively searched to identify all patients with PMC treated with a potentially curative CRS/HIPEC (CRS/HIPEC group). The overall survival (OS) was compared to patients with PMC treated with palliative chemotherapy (systemic chemotherapy group). Survival was analyzed using Kaplan-Meier method and compared with Log-Rank test.RESULTS:Between 1995 and 2015, 34 patients were included in the surgical group, and compared to 21 in the systemic chemotherapy group. In the surgical group, median peritoneal cancer index was 9 (range 3-26), macroscopically complete resection was obtained for 25 patients (73%). There was more gallbladder localization in the surgical group compared to the chemotherapy group (35% vs. 18%, p = 0.001). Median OS was 21.4 and 9.3 months for surgical and chemotherapy group, respectively (p=0.007). Three-year overall survival was 30% and 10% for surgical and chemotherapy group, respectively.CONCLUSION:Treatment with CRS and HIPEC for biliary carcinoma with peritoneal metastasis is feasible and may provide survival benefit when compared to palliative chemotherapy

The role of hyperthermic intraperitoneal chemotherapy in pseudomyxoma peritonei after cytoreductive surgery

This cohort study compares the outcomes of patients with pseudomyxoma peritonei who undergo hyperthermic intraperitoneal chemotherapy with cytoreductive surgery vs cytoreductive surgery alone. 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. Question What is the association of hyperthermic intraperitoneal chemotherapy (HIPEC) with prognosis and surgical outcomes of patients who undergo cytoreductive surgery for pseudomyxoma peritonei (PMP)? Findings In this propensity score-matched cohort study that included 1924 patients with PMP, HIPEC was associated with a better overall survival, generally without worsening the postoperative outcomes in terms of 30- and 90-day mortality, severe morbidity, and return to operating room. Meaning HIPEC should be considered in conjunction with cytoreductive surgery in patients with PMP