Optimization of response classification criteria for patients with malignant pleural mesothelioma

Our plain-English summary of Optimization of response classification criteria for patients with malignant pleural mesothelioma, by Z.E. Labby, S.G. Armato, H.L. Kindler, et al (Journal of Thoracic Oncology, 2012).

The study

• Authors: Z.E. Labby, S.G. Armato, H.L. Kindler, J.J. Dignam, A. Hasani, A.K. Nowak
• Journal: Journal of Thoracic Oncology
• Published: 2012;7(11):1728-34
• Cited by: 17 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Introduction: Response-assessment metrics play an important role in clinical trials and routine patient management. For patients with malignant pleural mesothelioma (MPM), the standard for response assessment is image-based measurements of tumor thickness made according to the modified RECIST (Response Evaluation Criteria in Solid Tumors) protocol. To classify tumor response, changes in tumor thickness are compared with the standard RECIST -30% and +20% cutoffs for partial response (PR) and progressive disease (PD), respectively, which are not specific to MPM. The purpose of this work is to optimize the correlation between tumor response and patient survival by assessing the validity of existing response criteria in MPM and proposing alternative criteria.

Methods: Computed tomography measurements of tumor thickness were acquired at baseline and throughout treatment for 78 patients undergoing standard-of-care chemotherapy. Overall survival was correlated with best response and first follow-up response using Harrell's C statistic. The response criteria for PD and PR were each varied in 1% increments to obtain optimized classification criteria. The performance was cross-validated using a leave-one-out approach.

Results: Median survival was 14.9 months. The performance of the standard RECIST criteria in correlating response with survival was C=0.778, whereas the optimized performance of C=0.855 was obtained with criteria of -64% for PR and +50% for PD. After cross-validation, this performance was slightly reduced to C=0.829.

Conclusions: Optimized tumor-response classification criteria were obtained for patients with MPM. These criteria improve the correlation between image-based response and patient survival.

In plain English

This study examined how tumor response to chemotherapy is classified in malignant pleural mesothelioma (MPM). The authors used CT scan measurements of tumor thickness, made under the modified RECIST protocol, from 78 patients at Sir Charles Gairdner Hospital in Western Australia, enrolled from late 2003 to 2010. The patients received chemotherapy, first cisplatin and gemcitabine and later cisplatin and pemetrexed. The authors tried every pair of cutoffs for partial response and progressive disease, in 1% steps, to find the pair that best matched survival. They measured that match with a score called Harrell's C. Median survival was 14.9 months. Using each patient's best response, the standard cutoffs (minus 30% and plus 20%) scored 0.778. Optimized cutoffs of minus 64% and plus 50% scored 0.855 (p value 0.039). In a cross-validation check the score was 0.829, higher than the standard but not statistically significantly so (p value 0.121). Under the new cutoffs, no patient had progressive disease as best response. The authors concluded that the new cutoffs improved the link between response and survival. They said the cutoffs must be tested in larger, independent patient 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: Retrospective analysis of imaging and clinical data from an earlier prospective imaging study. CT-based response cutoffs were optimized against overall survival and checked by leave-one-out cross-validation and bootstrap samples.
• Who was studied: 78 patients with malignant pleural mesothelioma (66 men, 12 women) with no prior chemotherapy or radiotherapy, enrolled from late 2003 to 2010 at Sir Charles Gairdner Hospital, Nedlands, Western Australia
• Exposure: Not an asbestos exposure study. Patients received standard-of-care combination chemotherapy (cisplatin and gemcitabine, later cisplatin and pemetrexed), and tumor thickness on CT scans was measured under modified RECIST.
• Main results:
  • Median overall survival from diagnosis for the 78 patients was 14.9 months (range 2.5 to 60 months)
  • With the standard RECIST cutoffs (minus 30% for partial response, plus 20% for progressive disease), the match between best response and survival was C = 0.778
  • The optimized cutoffs derived from the full cohort were minus 64% for partial response and plus 50% for progressive disease
  • Using best response, the optimized cutoffs scored C = 0.855
  • Compared with the standard cutoffs, the full-cohort optimized result had a p value of 0.039. The cross-validated result had a p value of 0.121, higher than the standard but not statistically significantly so.
  • Under the standard cutoffs, median survival by best response was 11.5 months for progressive disease, 11.6 months for stable disease and 23.0 months for partial response
  • Under the optimized cutoffs, median survival by best response was 12.9 months for stable disease and 24.8 months for partial response
  • Under the optimized cutoffs, no patient was classified as having progressive disease as best response
  • For response at the first follow-up scan, the wider cutoffs classified nearly all patients (77 of 78) as stable disease
• The authors' conclusion: The authors concluded that changing the cutoffs to minus 64% and plus 50% improved the correlation between tumor response and overall survival in MPM. They wrote that the new cutoffs seem better suited to mesothelioma's shape and growth pattern.
• Limitations the authors state:
  • The cutoffs came from a moderately sized database and must be tested on larger independent patient cohorts. Cross-validation is not a substitute for that.
  • It is unclear whether the cutoffs would apply to patients receiving targeted therapy rather than cytotoxic chemotherapy
  • Measurements by different observers might have produced different optimized cutoffs
  • Because the original study was not an intervention study, the authors could not determine the cutoffs' effect on starting treatment
  • The absence of any progressive-disease classification under the new cutoffs was a byproduct of this particular patient sample
  • Despite the higher scores for first follow-up response, the authors did not advocate assessing response after only one follow-up scan

Topics

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

Medical terms in this study, explained in our Lexicon: Pleural Mesothelioma, Clinical Trial, Modified RECIST (mRECIST), Chemotherapy, Overall Survival, Median Survival.

Related studies

• Lung volume measurements as a surrogate marker for patient response in malignant pleural mesothelioma — Z.E. Labby, S.G. Armato, et al. (2013)
• A phase II study of intermittent sunitinib malate as second-line therapy in progressive malignant pleural mesothelioma — A.K. Nowak, M.J. Millward, et al. (2012)
• Disease volumes as a marker for patient response in malignant pleural mesothelioma — Z.E. Labby, A.K. Nowak, et al. (2013)
• Revised Modified Response Evaluation Criteria in Solid Tumors for Assessment of Response in Malignant Pleural Mesothelioma (Version 1.1) — S.G. Armato, A.K. Nowak (2018)
• Thymidylate synthase and folyl-polyglutamate synthase are not clinically useful markers of response to pemetrexed in patients with malignant pleural mesothelioma — D.E. Lustgarten, C. Deshpande, et al. (2013)
• Soluble mesothelin, megakaryocyte potentiating factor, and osteopontin as markers of patient response and outcome in mesothelioma — K. Hollevoet, K. Nackaerts, et al. (2011)

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