ASO Visual Abstract: Non-resectable Malignant Peritoneal Mesothelioma Treated with Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC) Plus Systemic Chemotherapy Could Lead to Secondary Complete Cytoreductive Surgery: A Cohort Study

2021 ◽  
Author(s):  
Vahan Kepenekian ◽  
Julien Péron ◽  
Benoit You ◽  
Isabelle Bonnefoy ◽  
Laurent Villeneuve ◽  
...  
Keyword(s):  
Cohort Study ◽  
Cytoreductive Surgery ◽  
Systemic Chemotherapy ◽  
Peritoneal Mesothelioma ◽  
Malignant Peritoneal Mesothelioma

scholarly journals Adjuvant dendritic cell based immunotherapy (DCBI) after cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) for peritoneal mesothelioma, a phase II single centre open-label clinical trial: rationale and design of the MESOPEC trial

BMJ Open ◽  
2019 ◽  
Vol 9 (5) ◽  
pp. e026779 ◽  
Author(s):  
Nadine L de Boer ◽  
Job P van Kooten ◽  
Jacobus W A Burger ◽  
Cornelis Verhoef ◽  
Joachim G J V Aerts ◽  
...  
Keyword(s):  
Dendritic Cell ◽  
Phase Ii ◽  
Intraperitoneal Chemotherapy ◽  
Cytoreductive Surgery ◽  
Hyperthermic Intraperitoneal Chemotherapy ◽  
Systemic Chemotherapy ◽  
Peritoneal Mesothelioma ◽  
Malignant Peritoneal Mesothelioma ◽  
Single Centre ◽  
Open Label

IntroductionMalignant peritoneal mesothelioma (MPM) is an uncommon but aggressive neoplasm and has a strong association with asbestos exposure. MPM has low survival rates of approximately 1 year even after (palliative) surgery and/or systemic chemotherapy. Recent advances in treatment strategies focusing on cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) have resulted in improved median survival of 53 months and a 5 year survival of 47%. However, recurrence rates are high. Current systemic chemotherapy in the adjuvant setting is of limited efficacy, while immunotherapy with dendritic cell based immunotherapy (DCBI) has yielded promising results in murine models with peritoneal mesothelioma and in patients with pleural mesothelioma.Methods and analysisThe MESOPEC trial is an open-label single centre phase II study. The study population are adult patients with histological/cytological confirmed diagnosis of epithelioid malignant peritoneal mesothelioma. Intervention: 4 to 6 weeks before CRS-HIPEC a leukapheresis is performed of which the monocytes are used for differentiation to dendritic cells (DCs). Autologous DCs pulsed with allogeneic tumour associated antigens (MesoPher) are re-injected 8 to 10 weeks after surgery, three times biweekly. Additional booster vaccinations are given at 3 and 6 months.Primary objective is to determine the feasibility of administering DCBI after CRS-HIPEC in patients with malignant peritoneal mesothelioma. Secondary objectives are to assess safety of DCBI in patients with peritoneal mesothelioma and determine whether a specific immunological response against the tumour occurs as a result of this adjuvant immunotherapy.Ethics and disseminationPermission to carry out this study protocol has been granted by the Central Committee on Research Involving Human Subjects (CCMO in Dutch) and the Research Ethics Committee (METC in Dutch). The results of this trial will be submitted for publication in a peer-reviewed journal.Trial registration numberNTR7060. EudraCT: 2017-000897-12; Pre-Results.

Two Decades of Progress in the Management of a Rare Disease—Peritoneal Mesothelioma

2015 ◽  
Vol 11 (01) ◽  
pp. 67
Author(s):  
Paul H ugarbaker ◽  
Keyword(s):  
Cytoreductive Surgery ◽  
Systemic Chemotherapy ◽  
Treatment Options ◽  
Management Plan ◽  
Regional Chemotherapy ◽  
Peritoneal Mesothelioma ◽  
Perioperative Chemotherapy ◽  
Term Survival ◽  
Peritoneal Space

Diffuse malignant peritoneal mesothelioma (DMPM) is a rare but aggressive disease with a poor sustained response to systemic chemotherapy. Historically, the median survival has been less than 1 year. The disease rarely disseminates outside of the peritoneal space suggesting that local-regional treatment options may be effective in the long-term control of this malignancy. Establishment of a referral center to concentrate experience with the management of this disease has contributed greatly to progress in its management.Materials and methods:Through a series of Institutional Review Board-approved protocols, a long-standing morbidity/mortality assessment, numerous manuscripts published in the peer-reviewed literature, and participation in numerous national and international workshops, a new standard of care with expectations of long-term survival in a majority of patients has evolved.Results:The surgery for this disease has evolved through a sequence of peritonectomy procedures and visceral resections whose goal is to remove all visible evidence of disease. The first step in successful treatment is a complete cytoreduction. After the cancer resection in the operating room, hyperthermic perioperative chemotherapy (HIPEC) is used. A three-drug protocol combines heat-augmented chemotherapy within the peritoneal space and systemic chemotherapy that is heat-augmented as a continuous infusion intravenously. Catheters are placed for early postoperative intraperitoneal chemotherapy using paclitaxel for 5 days. Also placed at the time of the cytoreductive surgery is an intraperitoneal port for long-term combined intraperitoneal and systemic chemotherapy using cisplatin and pemetrexed for 6 months. Patients having the long-term bidirectional chemotherapy have shown statistically significant improved survival compared with those patients who had surgery alone plus the perioperative chemotherapy. There have been no mortality and the grade 4 adverse events have been prospectively accumulated as 12 %.Conclusions:With continued effort, the surgery and long-term regional chemotherapy for DMPM has continued to improve over 20 years. Currently, a management plan that involves cytoreductive surgery, perioperative chemotherapy, and long-term bidirectional chemotherapy has changed the natural history of this disease. A global registry has been initiated to confirm the benefits of these extended treatments.

A proposed staging system for diffuse malignant peritoneal mesothelioma patients undergoing cytoreductive surgery and perioperative intraperitoneal chemotherapy

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 4150-4150
Author(s):  
P. H. Sugarbaker ◽  
T. Yan ◽  
D. Yoo ◽  
E. Brun ◽  
C. Cerruto ◽  
...  
Keyword(s):  
Overall Survival ◽  
Intraperitoneal Chemotherapy ◽  
Cytoreductive Surgery ◽  
Staging System ◽  
Peritoneal Mesothelioma ◽  
Nuclear Size ◽  
Prognostic Parameters ◽  
Malignant Peritoneal Mesothelioma ◽  
Diffuse Malignant Peritoneal Mesothelioma ◽  
The Mean

4150 Background: There is no staging system available for diffuse malignant peritoneal mesothelioma (DMPM). This study evaluated seven clinical, seven radiological and twelve histopathologic prognostic parameters for survival of patients with DMPM. Methods: Between September 1989 and September 2005, sixty-two DMPM patients who were treated in a uniform fashion utilizing cytoreductive surgery combined with heated intraoperative intraperitoneal chemotherapy, with cisplatin and doxorubicin, followed by early postoperative intraperitoneal paclitaxel from postoperative day 1 to day 5 were included in this study. All prognostic parameters were analyzed in univariate and multivariate analyses using overall survival as the endpoint. The clinical and radiological data were obtained prospectively. A review of the histopathological features of DMPM was performed by two experienced pathologists, who individually evaluated each case. The mean number of specimens taken from separate anatomic sites was 11 ± 4 per patient. The mean number of slides studied was 20 ± 8 per patient. Results: The median follow-up was 37 months (range 8 to 143 months). The overall survival was 79 months (range 1 to 143 months) and 5-year survival was 50%. The following 14 prognostic variables were significant for survival in the univariate analysis: gender (p = 0.045), peritoneal cancer index (p = 0.038), completeness of cytoreduction score (p = 0.010), interpretive CT findings of the small bowel (p = 0.001), histologic type (p < 0.001), nuclear size (p < 0.001), nuclear/cytoplasmic ratio (p < 0.001), mitotic count (p < 0.001), atypical mitosis (p < 0.001), chromatin pattern (p < 0.001), cellular necrosis (p < 0.001), perineural invasion (p = 0.037), stroma pattern (p < 0.001) and depth of invasion (p = 0.014). In the multivariate analysis, the only factor that was independently associated with an improved survival was nuclear size. The 3-year survival rates with nuclear size of 10–20 μm, 21–30 μm, 31–40 μm and > 40 μm were 100%, 87%, 27% and 0%, respectively. Conclusions: Nuclear size was the dominant factor determining overall survival in patients with DMPM. A histopathological staging system based on measurement of the nuclear size was proposed. No significant financial relationships to disclose.

Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy for Malignant Peritoneal Mesothelioma: Multi-Institutional Experience

2009 ◽  
Vol 27 (36) ◽  
pp. 6237-6242 ◽  
Author(s):  
Tristan D. Yan ◽  
Marcello Deraco ◽  
Dario Baratti ◽  
Shigeki Kusamura ◽  
Dominique Elias ◽  
...  
Keyword(s):  
Overall Survival ◽  
Intraperitoneal Chemotherapy ◽  
Cytoreductive Surgery ◽  
Hyperthermic Intraperitoneal Chemotherapy ◽  
Peritoneal Cancer Index ◽  
Peritoneal Mesothelioma ◽  
Malignant Peritoneal Mesothelioma ◽  
End Point ◽  
The Mean

Purpose This multi-institutional registry study evaluated cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) for diffuse malignant peritoneal mesothelioma (DMPM). Patients and Methods A multi-institutional data registry that included 405 patients with DMPM treated by a uniform approach that used CRS and HIPEC was established. The primary end point was overall survival. The secondary end point was evaluation of prognostic variables for overall survival. Results Follow-up was complete in 401 patients (99%). The median follow-up period for the patients who were alive was 33 months (range, 1 to 235 months). The mean age was 50 years (standard deviation [SD], 14 years). Three hundred eighteen patients (79%) had epithelial tumors. Twenty-five patients (6%) had positive lymph nodes. The mean peritoneal cancer index was 20. One hundred eighty-seven patients (46%) had complete or near-complete cytoreduction. Three hundred seventy-two patients (92%) received HIPEC. One hundred twenty-seven patients (31%) had grades 3 to 4 complications. Nine patients (2%) died perioperatively. The mean length of hospital stay was 22 days (SD, 15 days). The overall median survival was 53 months (1 to 235 months), and 3- and 5-year survival rates were 60% and 47%, respectively. Four prognostic factors were independently associated with improved survival in the multivariate analysis: epithelial subtype (P < .001), absence of lymph node metastasis (P < .001), completeness of cytoreduction scores of CC-0 or CC-1 (P < .001), and HIPEC (P = .002). Conclusion The data suggest that CRS combined with HIPEC achieved prolonged survival in selected patients with DMPM.

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