Radiographic response to neoadjuvant therapy in pleural mesothelioma should serve as a guide for patient selection for cytoreductive operations

Our plain-English summary of Radiographic response to neoadjuvant therapy in pleural mesothelioma should serve as a guide for patient selection for cytoreductive operations, by N. Deboever, N. Zhou, D.J. McGrail, et al (Frontiers in Oncology, 2023).

The study

• Authors: N. Deboever, N. Zhou, D.J. McGrail, K. Tomczak, J.L. Oliva, H.A. Feldman, E. Parra, J. Zhang, P.P. Lee, M.B. Antonoff, W.L. Hofstetter, R.J. Mehran, R. Rajaram, D.C. Rice, J.A. Roth, S.S. Swisher, A.A. Vaporciyan, M. Altan, A. Weissferdt, A.S. Tsao, C.L. Haymaker, B. Sepesi
• Journal: Frontiers in Oncology
• Published: 2023;13:1216999
• Read it: PubMed · Publisher · Free full text

Abstract

Background: Malignant pleural mesothelioma (MPM) is associated with poor prognosis despite advances in multimodal therapeutic strategies. While patients with resectable disease may benefit from added survival with oncologic resection, patient selection for mesothelioma operations often relies on both objective and subjective evaluation metrics. We sought to evaluate factors associated with improved overall survival (OS) in patients with mesothelioma who underwent macroscopic complete resection (MCR).

Methods: Patients with MPM who received neoadjuvant therapy and underwent MCR were identified in a prospectively maintained departmental database. Clinicopathologic, blood-based, and radiographic variables were collected and included in a Cox regression analysis (CRA). Response to neoadjuvant therapy was characterized by a change in tumor thickness from pretherapy to preoperative scans using the modified RECIST criteria.

Results: In this study, 99 patients met the inclusion criteria. The median age of the included patients was 64.7 years, who were predominantly men, had smoking and asbestos exposure, and who received neoadjuvant therapy. The median change in tumor thickness following neoadjuvant therapy was -16.5% (interquartile range of -49.7% to +14.2%). CRA demonstrated reduced OS associated with non-epithelioid histology [hazard ratio (HR): 3.06, 95% confidence interval (CI): 1.62-5.78, p < 0.001] and a response to neoadjuvant therapy inferior to the median (HR: 2.70, CI: 1.55-4.72, p < 0.001). Patients who responded poorly (below median) to neoadjuvant therapy had lower median survival (15.8 months compared to 38.2 months, p < 0.001).

Conclusion: Poor response to neoadjuvant therapy in patients with MPM is associated with poor outcomes even following maximum surgical cytoreduction and should warrant a patient-centered discussion regarding goals of care and may therefore help guide further therapeutic decisions.

Copyright © 2023 Deboever, Zhou, McGrail, Tomczak, Oliva, Feldman, Parra, Zhang, Lee, Antonoff, Hofstetter, Mehran, Rajaram, Rice, Roth, Swisher, Vaporciyan, Altan, Weissferdt, Tsao, Haymaker and Sepesi.

In plain English

This study reviewed records of 99 patients with malignant pleural mesothelioma treated at the University of Texas MD Anderson Cancer Center between April 2005 and September 2019. All received neoadjuvant therapy (treatment before surgery), then an operation removing all visible tumor (macroscopic complete resection). Most patients (74, or 74.7%) had asbestos exposure. Asbestos exposure was not statistically significantly associated with survival in this analysis. The median change in tumor thickness on CT scans, from the start of therapy to surgery, was a 16.5% decrease. In a multivariable analysis, three groups had a higher risk of death: patients whose tumors shrank by 16.5% or less (hazard ratio 2.70, 95% CI 1.55–4.72), patients with non-epithelioid tumors (3.06, 1.62–5.78), and patients with lymph node involvement proven on pathology (1.92, 1.06–3.48). Measured from the start of neoadjuvant therapy, median survival was 15.77 months (CI 11.83–23.78) for poorer responders and 38.17 months (CI 25.59–54.66) for better responders. The authors concluded that surgery should be considered with increased carefulness in patients not responding to neoadjuvant therapy. Follow-up imaging varied between patients, the authors noted.

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 a prospectively maintained single-institution database of patients who had surgery after neoadjuvant therapy between April 2005 and September 2019
• Who was studied: 99 patients with malignant pleural mesothelioma who received neoadjuvant therapy and then macroscopic complete resection at the University of Texas MD Anderson Cancer Center; median age 64.7 years, 74 men (74.7%)
• Exposure: The factor studied was radiographic response to neoadjuvant therapy: the percentage change in tumor thickness on CT scans, measured by modified RECIST criteria, from before therapy to the last scan before surgery. Asbestos exposure was recorded as one of the patient variables. Fiber types and doses were not described.
• Main results:
  • 74 of 99 patients (74.7%) had asbestos exposure.
  • In the whole cohort, asbestos exposure was not statistically significantly associated with survival in univariable analysis (HR 1.19, 95% CI 0.64-2.18, p = 0.584).
  • Median change in tumor thickness from the pre-therapy scan to the last preoperative scan was -16.5% (IQR -49.7 to 14.2). By modified RECIST, 41 patients (41.4%) had partial response, 39 (39.4%) had stable disease and 19 (19.2%) had progressive disease.
  • Whole cohort, multivariable analysis: patients with non-epithelioid mesothelioma had a higher risk of death (HR 3.06, 95% CI 1.62–5.78, p = 0.001).
  • Whole cohort, multivariable analysis: patients with pathologically proven nodal disease had a higher risk of death (HR 1.92, CI 1.06–3.48, p = 0.031).
  • Whole cohort, multivariable analysis: a response worse than the median (tumors that shrank by 16.5% or less) was associated with a greater risk of death (HR 2.70, CI 1.55–4.72, p less than 0.001).
  • Whole cohort, with survival counted from the start of neoadjuvant therapy: median survival was 15.77 months (CI 11.83–23.78) for patients with a response worse than a 16.5% decrease or with progression. It was 38.17 months (CI 25.59–54.66) for those with a better response (p less than 0.001).
  • Epithelioid subgroup, multivariable analysis: smoking status (HR 3.29, CI 1.41–7.66, p = 0.006) and change in tumor thickness (HR 2.88, CI 1.31–6.30, p = 0.008) were associated with mortality.
  • Epithelioid subgroup: median survival was 17.33 months (CI 11.86–29.83) for poor responders and 49.11 months (CI 26.31 to not reached) for good responders (p = 0.001).
• The authors' conclusion: The authors concluded that cytoreductive operations should be considered with increased carefulness in patients who do not respond to neoadjuvant therapy, as defined by radiographic measures. In their view, when response is suboptimal, the patient's wishes and quality of life must be weighed before surgery.
• Limitations the authors state:
  • Surveillance imaging varied between patients in the cohort.
  • Clinical stage was not reliable because many patients were upstaged after surgery, so pathological tumor and nodal status were used instead.
  • Overall survival was counted from the start of neoadjuvant therapy rather than from diagnosis. The authors say this may not reflect true overall survival.
  • A small group of patients first appeared to respond well to therapy but ultimately had progressive disease.

Topics

Medical terms in this study, explained in our Lexicon: Neoadjuvant Therapy, Pleural Mesothelioma, Cytoreductive Surgery, Prognosis, Mesothelioma, Overall Survival, Modified RECIST (mRECIST), Asbestos Exposure.

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