Lymph node metastases in diffuse malignant peritoneal mesothelioma

Our plain-English summary of Lymph node metastases in diffuse malignant peritoneal mesothelioma, by D. Baratti, S. Kusamura, A.D. Cabras, et al (Annals of Surgical Oncology, 2010).

The study

• Authors: D. Baratti, S. Kusamura, A.D. Cabras, B. Laterza, M.R. Balestra, M. Deraco
• Journal: Annals of Surgical Oncology
• Published: 2010;17(1):45-53
• Cited by: 55 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Background: Improved survival has been reported for diffuse malignant peritoneal mesothelioma (DMPM) treated by surgical cytoreduction and hyperthermic intraperitoneal chemotherapy (HIPEC). The significance of lymph node involvement in this disease is still poorly understood.

Methods: Prospectively collected clinical data on 83 consecutive patients with DMPM undergoing surgical cytoreduction and closed-abdomen HIPEC with cisplatin and doxorubicin were reviewed. Clinically suspicious lymph nodes were submitted to pathological examination. The impact of nodal involvement on survival was assessed by multivariate analysis; 14 clinicopathological control variables were tested.

Results: For the overall series, median follow-up was 52 months (range 1-126 months) and 5-year overall survival (OS) was 49.5%. Lymph nodes were submitted to pathological examination in 38 patients, being positive in 11 and negative in 27. Lymph nodes were not clinically suspicious and not sampled in 45 patients. Iliac (n = 7) and paracolic (n = 2) nodes were the most commonly involved nodes. OS was 18.0% for patients with pathologically positive nodes and 82.5% for those with pathologically negative nodes (P = 0.0024). On multivariate analysis, pathologically negative (versus positive/not assessed) nodes [hazard ratio (HR) = 2.81; 95% confidence interval (CI) = 1.12-7.05; P = 0.027], epithelial subtype (HR = 2.93; CI = 1.24-6.95; P = 0.015), mitotic count <or=5/50 high-power microscopic fields (HPF) (HR = 5.34; CI = 1.96-14.54; P = 0.001), and completeness of cytoreduction (HR = 2.06; CI = 1.19-3.56; P = 0.001) correlated with increased OS. Positive nodes (versus negative/not assessed) did not significantly correlate with survival.

Conclusion: Pathologically negative nodes (as compared with pathological positive and not assessed), along with pathological and biological features, independently correlated with increased survival following comprehensive treatment. This suggests the need for careful node sampling when performing surgical cytoreduction for DMPM patients.

In plain English

This study reviewed prospectively collected data on 83 consecutive patients with diffuse malignant peritoneal mesothelioma. They were treated at the National Cancer Institute in Milan, Italy, between 1996 and 2008 with surgery to remove visible tumor plus heated chemotherapy inside the abdomen (HIPEC). The study asked whether cancer in the lymph nodes affected survival. Asbestos exposure was not studied. Pathologists examined lymph nodes in 38 patients: 11 had cancer in the nodes and 27 did not. The other 45 patients had no nodes sampled. Iliac nodes were the nodes most often involved, in seven patients. Five-year survival was 82.5% for patients with cancer-free nodes, 16.7% for those with positive nodes, and 40.9% for those whose nodes were not examined. In the combined analysis, four things were each linked with longer survival: cancer-free nodes, epithelial tumor type, a low count of dividing cells, and more complete surgery. Positive nodes, compared with all other patients, were not significantly linked with survival. The authors concluded that cancer-free nodes identify patients with a better prognosis and recommended careful node sampling. They said more patients are needed to define reliable prognostic groups.

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: Single-center review of a prospectively collected clinical database (survival analysis of a treated case series)
• Who was studied: 83 consecutive patients with diffuse malignant peritoneal mesothelioma (DMPM) treated with cytoreductive surgery and HIPEC by the same surgical team at the National Cancer Institute, Milan, Italy, from January 1996 to December 2008
• Exposure: Asbestos exposure was not studied. The factor studied was lymph node status (pathologically positive, pathologically negative, or not assessed) in patients treated with surgical cytoreduction and closed-abdomen HIPEC with cisplatin plus doxorubicin. The first ten patients received cisplatin plus mitomycin-C instead.
• Main results:
  • For the overall series of 83 patients, median survival was 44 months, and 5-year and 10-year overall survival were 49.5% and 45.5%.
  • Lymph nodes were pathologically examined in 38 patients (45.8%). Nodes were positive in 11 patients, which was 13.2% of the overall series and 28.9% of those whose nodes were examined. Nodes were negative in 27 patients. No nodes were sampled in 45 patients.
  • Positive nodes were found in 8 of the 20 patients whose nodes were thought suspicious (40%) and in 3 of the 15 patients whose nodes were routinely sampled (20%).
  • Internal, external and common iliac lymph nodes were the most commonly involved nodes, with metastases in seven patients.
  • Five-year overall survival by node group: 82.5% for pathologically negative nodes (median not reached); 16.7% for pathologically positive nodes (median 22 months; P = 0.001 versus negative); 40.9% for nodes not assessed (median 26 months; P = 0.009 versus negative). The difference between positive and not-assessed nodes was not statistically significant (P = 0.331).
  • In the multivariate (Cox) analysis of all 83 patients, pathologically negative nodes (versus positive or not assessed) correlated with increased overall survival: HR 2.81, 95% CI 1.12–7.05, P = 0.027.
  • Other independent factors for increased survival in the multivariate analysis: epithelial subtype (HR 2.93, CI 1.24–6.95, P = 0.015); mitotic count of 5 or fewer per 50 high-power fields (HR 5.34, CI 1.96–14.54, P = 0.001); and completeness of cytoreduction (HR 2.06, CI 1.19–3.56, P = 0.001).
  • Pathologically positive nodes, compared with negative or not-assessed nodes, showed no statistically significant survival difference (univariate P = 0.079).
  • Of the 11 node-positive patients, three were alive with no evidence of disease at the time of analysis. The other eight had disease progression at 2 to 16 months: on the peritoneal surface in seven and in the liver in one. None had recurrence in the nodes.
  • Among patients whose nodes were examined, those with macroscopically complete cytoreduction (CC-0) and negative nodes (n = 13) had a 5-year overall survival of 92.3% (median not reached). Those with CC-0 cytoreduction and positive nodes (n = 6) had a median survival of 26 months (P = 0.002).
• The authors' conclusion: The authors concluded that pathologically negative lymph nodes identify a subset of patients with better prognosis after cytoreduction and HIPEC. They stated that clinical node assessment may be insufficiently accurate and recommended careful sampling of the most commonly involved node sites. They suggested that nodal status could be considered in developing a new staging system for DMPM.
• Limitations the authors state:
  • The authors stated that a larger number of patients would be needed to define reliable prognostic categories.
  • Lymph nodes were not assessed by pathology in a considerable number of patients. The authors suggested that metastatic nodes could have gone undetected in that group.

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: Peritoneal Mesothelioma, Cytoreductive Surgery, HIPEC, Cisplatin, Doxorubicin, Multivariate Analysis, Overall Survival, Hazard Ratio.

Related studies

• 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)
• Impact of Combination Chemotherapy in Peritoneal Mesothelioma Hyperthermic Intraperitoneal Chemotherapy (HIPEC): The RENAPE Study — B. Malgras, E. Gayat, et al. (2018)
• Dose-Dependent Effect of Red Blood Cells Transfusion on Perioperative and Long-Term Outcomes in Peritoneal Surface Malignancies Treated with Cytoreduction and HIPEC — E. Nizri, S. Kusamura, et al. (2018)
• 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)
• Cytoreductive surgery with selective versus complete parietal peritonectomy followed by hyperthermic intraperitoneal chemotherapy in patients with diffuse malignant peritoneal mesothelioma: a controlled study — D. Baratti, S. Kusamura, et al. (2012)
• Iterative cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for recurrent peritoneal metastases — T.C. Chua, L.E. Quinn, et al. (2013)

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