Recurrence of Optimally Treated Malignant Peritoneal Mesothelioma with Cytoreduction and Heated Intraperitoneal Chemotherapy

Our plain-English summary of Recurrence of Optimally Treated Malignant Peritoneal Mesothelioma with Cytoreduction and Heated Intraperitoneal Chemotherapy, by D.R. Heller, C. Chiuzan, R.N. Taub, et al (Annals of Surgical Oncology, 2017).

The study

• Authors: D.R. Heller, C. Chiuzan, R.N. Taub, J.C. Leinwand, A.M. Greene, G.E. Bates, J.A. Chabot, M.D. Kluger
• Journal: Annals of Surgical Oncology
• Published: 2017;24(13):3818-3824
• Cited by: 9 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Background: The prognosis for patients with diffuse malignant peritoneal mesothelioma has dramatically improved with cytoreductive surgery and intraperitoneal chemotherapy. Little is known about disease recurrence after treatment. We analyzed the time to and predictors of recurrence in a large cohort of optimally treated patients.

Methods: We examined 113 patients completing a two-stage cytoreduction and intraperitoneal chemotherapy protocol. All patients achieved optimal surgical resection with completeness of cytoreduction (CC) score ≤ 1 and were divided into two groups based on absence (Group A) or presence (Group B) of gross disease at the outset of the second operation. Predictors of disease recurrence and recurrence-free survival (RFS) were determined using Cox proportional hazard regression modeling, and estimates were obtained by using the Kaplan-Meier method.

Results: Forty-six percent of patients had no gross evidence of disease at the second operation; the remaining 54% were cytoreduced to CC ≤ 1 (Group B). Forty-two percent of patients developed disease recurrence with a median recurrence-free survival of 38.5 months for the cohort; 79% of these received a form of iterative treatment. There was no statistically significant difference in recurrence-free survival between Group A (median RFS: 44.6 months) and B (median RFS: 35.5 months) (log-rank test, p = 0.06). Additionally, the only variable significantly associated with RFS was male gender (hazard ratio [HR] 1.98, 95% confidence interval [CI] 1.16-3.38).

Conclusions: Absence of gross disease at the second operation was not statistically protective against recurrence compared with presence of quantifiable residual disease (Group B) that was effectively cytoreduced. Long-term disease surveillance is recommended, because recurrence continues years after treatment. Where a question of recurrence arises on surveillance, males may benefit from a higher degree of suspicion.

In plain English

This study followed 113 patients treated for diffuse malignant peritoneal mesothelioma at one institution, 1995 to 2014. Each first had surgery to remove tumor and chemotherapy placed in the abdomen. At a second operation, visible tumor was reduced to deposits under 0.25 cm; 105 patients (93%) received heated chemotherapy. Twelve patients left with more tumor were excluded. Asbestos exposure is not discussed. Forty-seven patients (42%) had recurrence. Median recurrence-free survival (time to recurrence or death) after the second operation was 38.5 months (95% CI 29.5 to 54). It was 44.6 months (95% CI 29 to 136) for patients with no visible tumor at the second operation and 35.5 months (95% CI 23.8 to 48.1) for those with visible tumor that was then reduced, a difference that was not statistically significant. Adjusted for other factors, only male sex was significantly associated with worse recurrence-free survival. Median overall survival from the second operation was 6.65 years (95% CI 5.03 to 14.41). The authors concluded that adequately treated patients need indefinite surveillance imaging, because recurrence occurs years later, and that men may warrant greater suspicion.

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: Cohort study of patients treated under one institution's protocol, analysed with Kaplan-Meier estimates and Cox regression. The authors state that patient data were recorded prospectively in a database.
• Who was studied: 113 patients with diffuse malignant peritoneal mesothelioma treated 1995 to 2014. All completed the two-stage protocol with a completeness of cytoreduction score of 1 or less, which the authors describe as residual disease less than 0.25 cm in diameter. 57 (50%) were male, 94 (83%) were Caucasian, and the median age was 53 (IQR 42 to 62). 104 had epithelioid and 9 had sarcomatoid or biphasic disease, and 24 (21%) had both pleural and peritoneal mesothelioma. Patients were divided into Group A (no gross disease at the second operation, n = 52) and Group B (gross disease at the outset of the second operation, cytoreduced to a completeness score of 1 or less, n = 61). 12 patients with incomplete debulking at the second operation were excluded.
• Exposure: No asbestos exposure is reported. The study examined a treatment. A first operation removed bulky tumor and was followed by repeated intraperitoneal chemotherapy. At a second operation, patients with no residual disease had biopsies and heated intraperitoneal chemotherapy. Patients with tumor present had cytoreduction, aiming to remove all residual tumor, followed by heated chemotherapy. Inclusion required a completeness score of 1 or less at the end of the second operation.
• Main results:
  • At the second operation, 46% of patients had no gross disease (Group A). In the other 54% (Group B), gross disease was cytoreduced to a completeness score of 1 or less. Heated chemotherapy was given to 105 (93%) patients at the second operation.
  • 47 of the 113 patients (42%) had recurrence on routine surveillance imaging.
  • Recurrence-free survival was defined as time from the second operation to first detection of recurrence or death. For the whole cohort, median recurrence-free survival was 38.5 months (95% CI 29.5 to 54).
  • Median recurrence-free survival was 44.6 months (95% CI 29 to 136) for Group A (no gross disease at the second operation). It was 35.5 months (95% CI 23.8 to 48.1) for Group B (gross disease cytoreduced to a completeness score of 1 or less).
  • The difference in recurrence-free survival between Group A and Group B was not statistically significant (log-rank test, p = 0.06).
  • For the entire cohort, recurrence-free survival probabilities were 79% (95% CI 72 to 87) at 1 year, 37% (95% CI 27 to 46) at 5 years, and 29% (95% CI 19 to 39) at 10 years.
  • In the multivariable analysis, male gender was the only variable that remained significantly associated with recurrence-free survival (HR 1.98; 95% CI 1.16 to 3.38), meaning worse recurrence-free survival for men. Table 2 prints this HR as 1.95. In univariable analysis, bulky disease at the first operation was also significant (HR 1.91, 95% CI 1.20 to 3.05).
  • Of the 47 patients who recurred:
• 15 (32%) received both cytoreductive surgery and systemic chemotherapy.
• 14 (30%) received surgery only.
• 8 (17%) received systemic chemotherapy only.
• 10 (21%) received no therapy.
  • Median overall survival for all 113 patients, counted from the second operation, was 6.65 years (95% CI 5.03 to 14.41).
  • Overall survival differed significantly by group. The median was not reached for Group A and was 5.03 years (95% CI 3.82 to 10.1) for Group B.
  • The 12 excluded patients with incomplete cytoreduction at the second operation had a median overall survival of 22.9 months.
• The authors' conclusion: The authors concluded that all adequately treated patients should undergo routine surveillance imaging indefinitely, because recurrence occurs years after complete cytoreduction. They also concluded that males may benefit from a higher degree of suspicion during surveillance.
• Limitations the authors state:
  • Treatment varied between early and later periods. Early on, heated chemotherapy was not given at the first operation, and some patients received gamma interferon and/or abdominal radiation.
  • The findings cannot be generalized to patients whose tumor removal did not reach a completeness score of 1 or less.
  • Too few patients had a documented Peritoneal Cancer Index for its effect on recurrence to be investigated.

Topics

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

Medical terms in this study, explained in our Lexicon: Peritoneal Mesothelioma, Cytoreductive Surgery, Chemotherapy, Prognosis, Surgical Resection, Completeness of Cytoreduction (CC) Score, Recurrence-Free Survival, Hazard Ratio.

Related studies

• Early recurrence after cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) — G.H.C. Tan, C.S. Chia, et al. (2018)
• The Role of Ki-67 and Pre-cytoreduction Parameters in Selecting Diffuse Malignant Peritoneal Mesothelioma (DMPM) Patients for Cytoreductive Surgery (CRS) and Hyperthermic Intraperitoneal Chemotherapy (HIPEC) — S. Kusamura, P.A. Torres Mesa, et al. (2016)
• A Novel Tool for Predicting Major Complications After Cytoreductive Surgery with Hyperthermic Intraperitoneal Chemotherapy — J.M. Baumgartner, T.G. Kwong, et al. (2016)
• Preoperative Thrombocytosis Predicts Shortened Survival in Patients with Malignant Peritoneal Mesothelioma Undergoing Operative Cytoreduction and Hyperthermic Intraperitoneal Chemotherapy — Y.C. Li, T. Khashab, et al. (2017)
• 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)
• Conversion to Complete Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy for Malignant Peritoneal Mesothelioma After Bidirectional Chemotherapy — F. Le Roy, M. Gelli, et al. (2017)

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