Factors predictive of survival among 337 patients with mesothelioma treated between 1984 and 1994 by the Cancer and Leukemia Group B

Our plain-English summary of Factors predictive of survival among 337 patients with mesothelioma treated between 1984 and 1994 by the Cancer and Leukemia Group B, by J.E. Herndon, M.R. Green, A.P. Chahinian, et al (Chest, 1998).

The study

• Authors: J.E. Herndon, M.R. Green, A.P. Chahinian, J.M. Corson, Y. Suzuki, N.J. Vogelzang
• Journal: Chest
• Published: 1998;113(3):723-31
• Cited by: 392 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Purpose: To examine the individual and joint effect of various pretreatment clinical characteristics on the survival of patients with mesothelioma treated by the Cancer and Leukemia Group B (CALGB).

Patients And Methods: Between June 1984 and September 1994, 337 patients with malignant mesothelioma and no prior chemotherapy were accrued to seven phase II studies conducted by the CALGB which screened the efficacy of 10 treatment regimens or dose levels. The eligibility criteria for all studies were virtually identical. Patient characteristics include the following: age older than 60 years (63%); male (83%); performance status (PS) of 0 or 1 (81%); chest pain (60%); definite asbestos exposure (62%); >5% weight loss (41%); and pleural involvement (94%). Median survival time (MST) for the 10 treatment regimens ranged from 3.9 to 9.8 months (overall=7.2; 95% confidence interval [CI], 6.5 to 8.3), with 1-year survival between 14% and 50% (overall=27%; 95% CI, 23 to 33%).

Results: Cox survival models and exponential regression trees were used to examine the prognostic importance of pretreatment patient characteristics. Univariate analyses show that patients with poor Eastern Cooperative Oncology Group PS, chest pain, dyspnea, platelet count (PLT) >400,000/microL, weight loss, serum lactate dehydrogenase (LDH) level >500 IU/L, pleural involvement, low hemoglobin (HGB) level, high WBC count, and increasing age over 75 years have a worse prognosis. With decreasing risk ratio, multivariate Cox analyses showed that pleural involvement, LDH >500 IU/L, poor PS, chest pain, PLT >400,000/microL, nonepithelial histology, and increasing age older than 75 years jointly predict poor survival. PS was the most important prognostic split in the regression tree. Terminal nodes were amalgamated to form six distinct prognostic subgroups with MST (2-year survival) of 13.9 (38%) in 36 patients, 9.5 (21%) in 36 patients, 9.2 (10%) in 146 patients, 6.5 (3%) in 33 patients, 4.4 (0%) in 73 patients, and 1.4 (0%) in 13 patients (p<0.0001).

Conclusions: The subgroup with the best survival (MST=13.9 months) included patients with PS=0 and age younger than 49 years, and patients with PS=0, age of 49 years or older, and HGB > or =14.6. The worst survival (MST= 1.4 months) occurred for patients with PS= 1/2 and WBC > or =15.6/microL.

In plain English

This retrospective analysis related pretreatment characteristics to survival in 337 patients with malignant mesothelioma and no prior chemotherapy. They were treated in seven Cancer and Leukemia Group B phase II studies, June 1984 to September 1994. Asbestos exposure was recorded only as yes, no or unknown (62% yes); no fiber types were named. Overall median survival was 7.2 months (95% confidence interval 6.5 to 8.3); one-year survival was 27% (interval 23 to 33%). In the multivariate analysis of 309 patients, those with pleural involvement had 2.64 times the risk of death of those without (interval 1.48 to 4.69). Other predictors of worse survival were LDH above 500 IU/L (a cutoff chosen for convenience), poorer performance status, platelet count above 400,000 per microliter, nonepithelial histology and each year of age beyond 75. Six regression-tree prognostic groups had median survival from 13.9 months (interval 11.1 to 31.4; 36 patients) to 1.4 months (interval 0.5 to 3.6; 13 patients). The authors concluded these factors, with chest pain, independently predict poorer survival. They noted staging was not collected and treatment comparisons had limited power.

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 pooled analysis of prognostic factors using data from seven multi-institutional phase II chemotherapy studies (Cox survival models and exponential regression trees)
• Who was studied: 337 eligible patients with malignant mesothelioma and no prior chemotherapy, treated and followed in seven Cancer and Leukemia Group B (CALGB) phase II studies in the United States, June 1984 to September 1994 (347 registered; 10 excluded). 83% were male and 94% had pleural involvement.
• Exposure: This was not an exposure study. Asbestos exposure was one recorded pretreatment characteristic (no/yes/unknown): yes in 209 (62%), no in 89 (26%), unknown in 39 (12%). No fiber types were specified. Patients received one of 10 chemotherapy regimens or dose levels.
• Main results:
  • All 337 patients: median survival for the 10 regimens ranged from 3.9 to 9.8 months (overall 7.2; 95% CI 6.5 to 8.3). One-year survival ranged from 14% to 50% (overall 27%; 95% CI 23 to 33%).
  • Univariate analysis by ECOG performance status (0 is best): median survival was 3.3, 7.6 and 10.9 months for performance status 2, 1 and 0 respectively (p less than 0.001).
  • Univariate analysis: median survival was 7.1 months with pleural involvement and 12.3 months without (p=0.003). Only 19 of the 337 patients (6%) had no pleural involvement.
  • Univariate analysis: median survival was 6.2 months with a platelet count above 400,000 per microliter and 9.4 months with a lower count (p less than 0.001).
  • Univariate analysis: hemoglobin and white blood cell count each had a statistically significant linear relationship with survival (p less than 0.001).
  • Multivariate model of 309 patients: the risk of death with pleural involvement was 2.64 times the risk without it (95% CI 1.48 to 4.69 in Table 3).
  • Multivariate model of 309 patients: compared with performance status 0, risk was 1.65 times greater for performance status 1 and 2.71 times greater for performance status 2.
  • Multivariate model of 309 patients: compared with patients without these characteristics, the risk of dying early was 1.33 times greater with nonepithelial histology, 1.57 times greater with a platelet count above 400,000 per microliter, and 1.91 times greater with LDH above 500 IU/L.
  • Multivariate model of 309 patients: for patients older than 75, each additional year over 75 increased the hazard by a factor of 1.34.
  • Multivariate model of 195 patients from the five studies that collected all variables: LDH above 500 IU/L, poor performance status, chest pain, a platelet count above 400,000 per microliter and increasing age over 75 predicted a greater risk of dying early.
  • Regression tree, best group (group 1, 36 patients): performance status 0 with age under 49, or performance status 0 with age 49 or older and hemoglobin 14.6 or higher. Median survival was 13.9 months (95% CI 11.1 to 31.4) and 2-year survival was 38% (95% CI 23 to 55%).
  • Regression tree, worst group (group 6, 13 patients): performance status 1 or 2 with a white blood cell count of 15.6 or higher. Median survival was 1.4 months (95% CI 0.5 to 3.6), and no patient lived longer than 9 months.
  • Treatment arm: the 309-patient analysis found no significant difference among the 10 regimens. In the 195-patient analysis, survival on study 9031 (cisplatin plus DHAC) and study 9234 (paclitaxel) was significantly worse than on both arms of studies 9131 and 8933.
• The authors' conclusion: The authors concluded that pleural disease involvement, LDH above 500 IU/L, poor performance status, chest pain, a platelet count above 400,000 per microliter, nonepithelial histology and increasing age over 75 independently predict poorer survival. They suggested the prognostic groups could help interpret phase II trials and serve as a type of historical control for assessing new regimens.
• Limitations the authors state:
  • Staging information was not collected. One author approximated local versus regional/distant disease from site-of-involvement data and radiograph reports.
  • The primary site of the mesothelioma was not available. The pleural variable only indicates whether the pleura was involved.
  • Institutional normal ranges for LDH were not available, so the cutoff of 500 IU/L was chosen for convenience.
  • Some prognostic factors (chest pain, dyspnea, symptom duration, weight loss, smoking) were not collected in studies 8435 and 8638.
  • Comparisons between treatment arms had limited power because of small numbers per regimen, and may be confounded by secular trends.
  • Phase II studies are not designed with enough patients for definitive comparisons within and between studies.

Topics

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

Medical terms in this study, explained in our Lexicon: Mesothelioma, Malignant Mesothelioma, Chemotherapy, Performance Status, Asbestos Exposure, Median Survival, confidence interval, Dyspnea.

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