Two-Stage Cytoreductive Surgery and Intraperitoneal Chemotherapy for Diffuse Malignant Peritoneal Mesothelioma: Predictors of Overall Survival in an Intention-to-Treat Series

Our plain-English summary of Two-Stage Cytoreductive Surgery and Intraperitoneal Chemotherapy for Diffuse Malignant Peritoneal Mesothelioma: Predictors of Overall Survival in an Intention-to-Treat Series, by J.C. Leinwand, R.N. Taub, J.A. Chabot, et al (Annals of Surgical Oncology, 2020).

The study

• Authors: J.C. Leinwand, R.N. Taub, J.A. Chabot, M.D. Kluger
• Journal: Annals of Surgical Oncology
• Published: 2020;27(7):2539-2547
• Cited by: 12 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Purpose: Cytoreductive surgery with intraoperative hyperthermic intraperitoneal chemotherapy is standard of care for diffuse malignant peritoneal mesothelioma (DMPM), but there is variability among institutions in the administration of adjuvant chemotherapy. Characterization of the largest series of DMPM patients treated at a single institution and identification of the demographic, disease, and treatment factors associated with overall survival were sought.

Patients And Methods: All DMPM patients who underwent initial cytoreductive surgery with the intention to undergo intraperitoneal chemotherapy and a second-look operation from 1995 to 2016 at our institution were retrospectively reviewed. The primary endpoint was overall survival.

Results: A total of 204 DMPM patients underwent initial cytoreduction. Median overall survival was 32 months from initial cytoreduction. Independent baseline prognostic factors of improved overall survival were female sex, age < 60 years, and epithelioid histology. Independent treatment factors associated with improved overall survival were attempted resection at initial operation, residual disease < 0.5 cm at the end of the initial operation, and dwell intraperitoneal chemotherapy.

Conclusions: Cytoreductive surgery with intraoperative and dwell intraperitoneal chemotherapy is a feasible approach for DMPM. Expanded access to these therapies may offer benefit to a larger population of patients. Demographic and operative parameters associated with overall survival in this large cohort are consistent with previous reports. In the context of this treatment protocol, dwell intraperitoneal chemotherapy is associated with longer overall survival.

In plain English

This study looked back at 204 patients with diffuse malignant peritoneal mesothelioma (cancer of the abdominal lining) treated at Columbia University, New York, between 1995 and 2016. All had a first operation intended to remove tumor, though in 18 the disease proved unresectable. Outpatient "dwell" chemotherapy through abdominal ports and a second-look operation were planned; 128 patients (63%) had the second operation. Median overall survival from the first operation was 32 months (95% CI 22.4–44.9). Survival was 69%, 48% and 36% at one, three and five years. Female sex, age under 60, epithelioid tumor type, attempted tumor removal at the first operation, residual disease under 0.5 cm and receiving dwell chemotherapy were each independently associated with longer survival. Asbestos exposure was yes for 95 patients, no for 81, unknown for 28. Unadjusted median survival was 22.4 months (95% CI 15.4–35.5) for exposed patients and 47.7 months (95% CI 23.1–76.6) for unexposed patients, a difference not statistically significant (p = 0.075). The authors concluded the approach is feasible and dwell chemotherapy was associated with longer survival; they noted it was retrospective.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Retrospective review of a single-institution intention-to-treat series of patients treated with cytoreductive surgery and intraperitoneal chemotherapy
• Who was studied: 204 patients with histologically confirmed diffuse malignant peritoneal mesothelioma who had initial cytoreductive surgery at Columbia University, New York, from May 1995 to December 2016. Median age at diagnosis was 56.4 years; 117 were male and 87 female.
• Exposure: The study examined a treatment, not an exposure. Patients had initial cytoreductive surgery with intraperitoneal catheter placement, then outpatient dwell intraperitoneal chemotherapy (cisplatin, or cisplatin plus gemcitabine, alternating with doxorubicin), then a planned second-look operation with HIPEC. From March 2005, HIPEC was also given at initial surgery. Asbestos exposure history was recorded as a baseline characteristic; no fiber types were reported.
• Main results:
  • All 204 patients: median overall survival from initial surgery was 32 months (95% CI 22.4–44.9 months). One-, three- and five-year overall survival rates were 69%, 48% and 36%.
  • Resectability at the first operation: 18 patients (8.8%) had unresectable disease, with median overall survival of 1.8 months. The 186 patients with resectable disease had median overall survival of 39.4 months. Multivariate hazard ratio 2.20 (95% CI 1.04–4.63).
  • 128 patients (63%) underwent second-look operations
  • Residual disease after the first operation: median overall survival was 54.9 months (95% CI 39.4–68.9) for the 128 patients with residual disease under 0.5 cm. It was 11.6 months for the 76 patients with residual disease over 0.5 cm.
  • Asbestos exposure: 95 patients (46.6%) were exposed, with median overall survival of 22.4 months (95% CI 15.4–35.5). 81 (39.7%) were not exposed, with 47.7 months (95% CI 23.1–76.6). Exposure was unknown for 28 (13.7%). In the univariate comparison p = 0.075, which is not statistically significant at the 0.05 level. Asbestos exposure was not among the independent predictors in the multivariate analysis.
  • Sex: median overall survival was 54.4 months for 87 women and 21.5 months for 117 men. Male sex had a multivariate hazard ratio of 1.82 (95% CI 1.31–2.54).
  • Age: median overall survival was 44.9 months for 122 patients under 60 and 18.1 months for 82 patients aged 60 or older. Multivariate hazard ratio 1.56 (95% CI 1.12–2.17).
  • Histology: median overall survival was 44.9 months for 166 patients with epithelioid disease and 6.4 months for 38 with sarcomatoid or biphasic disease. Sarcomatoid or biphasic histology had a multivariate hazard ratio of 2.27 (95% CI 1.52–3.38).
  • Dwell intraperitoneal chemotherapy: median overall survival was 54.3 months for the 148 patients who received it and 4.3 months for the 56 who did not. It was an independent factor in the multivariate analysis.
  • HIPEC at initial cytoreduction was not a predictor of overall survival on univariate analysis
  • Grade 3 or higher complications occurred in 27 of 204 patients (13.2%) after initial cytoreduction and in 13 of 128 (10.2%) after second-look operation. There were 4 deaths (2.0%) after initial cytoreduction and 1 (0.8%) after second-look operation.
• The authors' conclusion: The authors concluded that cytoreductive surgery with intraoperative and dwell intraperitoneal chemotherapy is a feasible approach for diffuse malignant peritoneal mesothelioma. They also concluded that, within this protocol, dwell intraperitoneal chemotherapy is associated with longer overall survival.
• Limitations the authors state:
  • The study was retrospective and relied on historical controls and comparison with other series, so patient selection may have contributed to differences in outcomes
  • Outcomes of this two-stage protocol cannot be directly compared with other treatment protocols
  • Adding HIPEC at initial cytoreduction and expanding patient inclusion after 2005 may have added variability within the cohort
  • Patients who did not receive dwell chemotherapy likely had complications that prevented it. The authors state that its prognostic value was nonetheless independent of other first-operation parameters.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Mesothelioma, Peritoneal mesothelioma.

Medical terms in this study, explained in our Lexicon: Cytoreductive Surgery, Chemotherapy, Peritoneal Mesothelioma, Overall Survival, HIPEC, Median Overall Survival, Epithelioid, Histology.

Related studies

• Iterative cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for recurrent or progressive diffuse malignant peritoneal mesothelioma: clinicopathologic characteristics and survival outcome — C. Ihemelandu, L. Bijelic, et al. (2015)
• Overall survival of pseudomyxoma peritonei and peritoneal mesothelioma patients after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy can be predicted by computed tomography quantified sarcopenia — A. Galan, P. Rousset, et al. (2018)
• Unresectable peritoneal metastasis treated by pressurized intraperitoneal aerosol chemotherapy (PIPAC) leading to cytoreductive surgery and hyperthermic intraperitoneal chemotherapy — M. Alyami, F. Mercier, et al. (2021)
• Laparoscopic cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for limited peritoneal metastasis. The PSOGI international collaborative registry — A. Arjona-Sanchez, O. Aziz, et al. (2021)
• The role of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in the treatment of peritoneal carcinomatosis: a systematic review including evidence from Japan — T. Kitai (2021)
• Outcomes of cytoreductive surgery with hyperthermic intraperitoneal chemotherapy for peritoneal mesothelioma and predictors of survival — S.N.S. Gilani, A. Mehta, et al. (2018)

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