Chronic inflammation in tumor stroma is an independent predictor of prolonged survival in epithelioid malignant pleural mesothelioma patients

Our plain-English summary of Chronic inflammation in tumor stroma is an independent predictor of prolonged survival in epithelioid malignant pleural mesothelioma patients, by K. Suzuki, K. Kadota, C.S. Sima, et al (Cancer Immunology, Immunotherapy, 2011).

The study

• Authors: K. Suzuki, K. Kadota, C.S. Sima, M. Sadelain, V.W. Rusch, W.D. Travis, P.S. Adusumilli
• Journal: Cancer Immunology, Immunotherapy
• Published: 2011;60(12):1721-8
• Cited by: 65 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

This study aims to determine whether a semi-quantitative assessment of inflammatory response in tumor and stroma on routine hematoxylin and eosin-stained (H&E) slides can predict survival in patients with epithelioid malignant pleural mesothelioma (MPM). H&E sections of 175 epithelioid MPM specimens from a single institution (1989-2009) were reviewed. Patients who received neoadjuvant chemotherapy were excluded from analysis. Each tumor was histologically assessed for acute and chronic inflammatory response both within the tumor and the stromal component. Inflammatory response was graded: low (none to mild infiltrate) or high (moderate to severe infiltrate). Log-rank test and Cox proportional hazards regression were used to investigate the association between the degree of inflammation (acute/tumor, acute/stroma, chronic/tumor, and chronic/stroma) and overall survival (OS). Patients with high chronic inflammatory response in stroma (n = 59) had improved survival compared to low (n = 116) (median OS = 19.4 vs. 15.0 months, P = 0.01). This prognostic stratification remained significant in stage III patients (median OS = 16.0 vs. 9.3 months, P = 0.03). In multivariate analysis, chronic inflammation in stroma was an independent predictor of survival (HR = 0.659, 95% CI 0.464-0.937, P = 0.02). While high degree of chronic inflammatory cell infiltration in the stromal component was associated with improved overall survival, degree of other inflammatory responses did not show significant correlation with OS. Our study for the first time investigates inflammatory response in tumor and stroma and not only suggests the prognostic value of inflammatory response in epithelioid MPM but also provides rationale for investigation of immunotherapy to benefit epithelioid MPM patients.

In plain English

This study used tumor slides from 175 patients with epithelioid malignant pleural mesothelioma treated at Memorial Sloan-Kettering Cancer Center in New York between 1989 and 2009. None had received chemotherapy before surgery. Two pathologists graded acute inflammation (neutrophils) and chronic inflammation (lymphocytes and plasma cells), both within the tumor and in the surrounding supporting tissue (stroma). The authors then compared these grades with survival. Patients with high chronic inflammation in the stroma (59 patients) had a median survival of 19.4 months, compared with 15.0 months for the 116 with low levels. The difference was also seen among stage III patients (16.0 versus 9.3 months). It held after accounting for stage, side of the chest and lymphatic and vascular invasion (hazard ratio 0.66, 95% CI 0.46 to 0.94). The other three inflammation measures were not significantly linked with survival. Asbestos exposure, recorded as yes for 77 patients, was not significantly linked with survival, and fiber types were not reported. The authors concluded that high chronic stromal inflammation independently predicted longer survival. They noted that routine slides cannot identify specific immune cell types.

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-institution study of archived tumor slides from a surgical mesothelioma database, with survival analysis (Kaplan-Meier, log-rank test, Cox regression)
• Who was studied: 175 patients with epithelioid malignant pleural mesothelioma diagnosed 1989 to 2009 at Memorial Sloan-Kettering Cancer Center, New York, after excluding 57 who had received neoadjuvant chemotherapy; median age 64, 73% men; 59% stage III
• Exposure: The factor studied was the degree of acute (neutrophil) and chronic (lymphocyte and plasma cell) inflammation in tumor and stroma on routine H&E slides. Asbestos exposure was recorded as yes for 77 (44%), no for 43 (25%) and unknown for 55 (31%); fiber types and doses were not reported.
• Main results:
  • All 175 patients: high chronic inflammation in stroma (n = 59) had median overall survival of 19.4 months versus 15.0 months for low (n = 116), P = 0.01
  • 103 stage III patients: high stromal chronic inflammation (n = 42) had median survival of 16.0 months versus 9.3 months for low (n = 61), P = 0.03
  • Multivariate analysis: chronic stromal inflammation was independently associated with longer survival after controlling for stage, laterality and lymphatic/vascular invasion (HR = 0.66, 95% CI 0.46 to 0.94, P = 0.02; Table 2: 0.659, 0.464 to 0.937)
  • Acute inflammation in tumor, acute inflammation in stroma and chronic inflammation in tumor were not significantly associated with survival
  • Including the 57 neoadjuvant-chemotherapy patients (n = 232), only a trend was seen: median survival of 17.4 months for high stromal chronic inflammation (n = 82) versus 15.0 months for low (n = 150), P = 0.06
  • In patients without neoadjuvant chemotherapy who had blood counts available (76), the high neutrophil-to-lymphocyte ratio group had median survival of 10.2 months (n = 22) versus 18.9 months for low (n = 54), not statistically significant (P = 0.34)
  • Asbestos exposure (yes in 77 patients, 44%) was not significantly associated with overall survival in univariate analysis (P = 0.52). Patients without asbestos exposure tended to have high stromal chronic inflammation more often, but this did not reach significance (P = 0.08).
• The authors' conclusion: The authors concluded that high chronic inflammatory response in the tumor stroma is an independent predictor of longer survival in epithelioid malignant pleural mesothelioma patients. They said it can be assessed on routine slides and gives a rationale for investigating immune-based therapy.
• Limitations the authors state:
  • Assessment on H&E slides does not identify the specific types of immune cells
  • The neutrophil-to-lymphocyte ratio analysis may have lacked significance because few patients had these values; laboratory values were unavailable before 1998

Topics

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

Medical terms in this study, explained in our Lexicon: Chronic Inflammation, Epithelioid, Pleural Mesothelioma, Neoadjuvant Chemotherapy, Inflammation, Overall Survival, Multivariate Analysis, Immunotherapy.

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