Assessment of therapy responses and prediction of survival in malignant pleural mesothelioma through computer-aided volumetric measurement on computed tomography scans

Our plain-English summary of Assessment of therapy responses and prediction of survival in malignant pleural mesothelioma through computer-aided volumetric measurement on computed tomography scans, by F. Liu, B. Zhao, L.M. Krug, et al (Journal of Thoracic Oncology, 2010).

The study

• Authors: F. Liu, B. Zhao, L.M. Krug, N.M. Ishill, R.C. Lim, P. Guo, M. Gorski, R. Flores, C.S. Moskowitz, V.W. Rusch, L.H. Schwartz
• Journal: Journal of Thoracic Oncology
• Published: 2010;5(6):879-84
• Cited by: 68 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Purpose: The purposes of this study were (1) to calculate the tumor volume in patients with malignant pleural mesothelioma using computed tomography (CT) scan images and a computer-aided measurement technique and (2) to investigate whether the baseline volume, or volume change after chemotherapy, predicts patient survival.

Methods: We compiled the clinical characteristics and outcome from 30 patients enrolled in two clinical trials at our cancer center in which the patients were treated with induction chemotherapy followed by surgery and radiation. CT scans of 30 patients were obtained at baseline and after two cycles of chemotherapy. Tumor volumes were calculated using a semiautomated computer algorithm. Overall survival was measured using a landmark time at 3 months post-treatment start date such that all patients had already received two cycles of chemotherapy and a follow-up scan. Association of volume changes with overall survival were determined by a Cox Proportional Hazards Model or log-rank test. The relationship between both pre and postoperative clinical stage and baseline tumor volume was analyzed using the rank sum test.

Results: The median baseline tumor volume was 473 cm(3) (range, 61 cm(3)-2108 cm(3)). Patients with high preoperative stages (III and IV) had larger baseline tumor volume than those with low preoperative stages (I and II) (p = 0.05). Patients with baseline volumes smaller than 619 cm(3) tended to survive longer than those with baseline volumes larger than or equal to 619 cm(3) (p = 0.07). Percentage change of tumor volume from baseline to first follow-up CT after two cycles of chemotherapy was significantly associated with overall survival (hazard ratio: 1.94 [95% confidence interval, 1.05-3.60], p = 0.04). Whereas the relative change in modified RECIST measurements was not significantly associated with overall survival (hazard ratio: 1.06 [95% confidence interval, 0.96-1.16], p = 0.25). By classifying changes of tumor volumes between two scans into two groups, i.e., "increase" and "decrease," a significant difference in survival was found between those who increased and decreased after two cycles of chemotherapy (p = 0.03).

Conclusions: Changes in tumor volume after two cycles of chemotherapy predicted overall survival in patients with malignant pleural mesothelioma. Tumor volume at baseline was shown to be associated with preoperative clinical stage and survival. Computer-aided volumetric measurements may enable more reliable therapeutic response assessment and could provide additional prognostic information.

In plain English

This study reviewed CT scans and records of 30 patients with malignant pleural mesothelioma from two phase II trials. Patients received induction chemotherapy (gemcitabine/cisplatin or pemetrexed/cisplatin). Those without progression were referred for extrapleural pneumonectomy followed by radiation; 23 of the 30 had surgery. A semiautomatic computer method, reviewed and corrected by a radiologist, measured tumor volume. The median baseline volume was 473 cm3. Higher preoperative stage (III and IV) went with larger baseline volumes (p = 0.05). Patients with baseline volumes below the authors' cut point tended to live longer (median 21.5 versus 10.2 months), but the difference was not statistically significant (p = 0.07). In 27 patients scanned after two chemotherapy cycles, percentage change in tumor volume was associated with survival (hazard ratio 1.94, 95% CI 1.05–3.60). In 25 patients, change in modified RECIST measurement was not statistically significantly associated with survival (hazard ratio 1.06, 95% CI 0.96–1.16). Median survival was 18.1 months when tumors shrank and 11.5 months when they grew. The authors noted a small sample and that other factors, including asbestos exposure, were not considered.

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 patients in two phase II clinical trials, using computer-aided tumor volume measurement on CT scans
• Who was studied: 30 patients with pathologically proven malignant pleural mesothelioma (23 males, 7 females; ages 34 to 76, average 60) from two phase II trials at the authors' referral-based cancer center (author affiliations: Memorial Sloan-Kettering Cancer Center and Columbia University, New York). Dates of the trials are not given in the text.
• Exposure: The study did not examine asbestos exposure. Patients received up to four cycles of induction chemotherapy (gemcitabine/cisplatin or pemetrexed/cisplatin). Patients without disease progression were then referred for extrapleural pneumonectomy followed by postoperative hemithoracic radiation. The factors studied were CT-measured tumor volume at baseline and its change after two chemotherapy cycles.
• Main results:
  • Most patients (23 of the 30) had surgery after chemotherapy.
  • On baseline scans, the median tumor volume among the 30 patients was 473 cm3 (range 61 to 2108 cm3).
  • Using a cut point of 618.49 cm3, the 10 patients with larger baseline volumes had a median survival of 10.2 months, and the 20 patients with smaller volumes had a median survival of 21.5 months. The authors described this as a slight tendency for the smaller-volume group to survive longer (p = 0.07). Splitting patients at the median volume showed no significant survival difference.
  • Baseline volume by preoperative radiologic stage: 13 patients with low stage (I and II) had a median volume of 290 cm3, and 17 patients with high stage (III and IV) had a median volume of 596 cm3. The authors reported the high-stage group's volume as significantly larger (p = 0.05). Among 23 patients with postoperative staging, there was no significant volume difference between low stage (n = 8) and high stage (n = 15).
  • Among 27 patients with a follow-up CT after two chemotherapy cycles, change in tumor volume was significantly associated with overall survival (hazard ratio 1.94, 95% confidence interval 1.05 to 3.60, p = 0.04).
  • Among 25 patients with modified RECIST measurements, relative change from baseline to follow-up was not significantly associated with overall survival (hazard ratio 1.06, 95% confidence interval 0.96 to 1.16, p = 0.25).
  • The predictive ability (C-index) of the volume measurement was 0.74, compared with 0.5 for the modified RECIST measurement. The authors reported the volume measurement's C-index as significantly higher.
  • Patients whose tumor volume increased after chemotherapy (n = 10) had a median survival of 11.5 months. Those whose volume decreased (n = 17) had a median survival of 18.1 months. The difference was significant (p = 0.03).
  • Agreement between the two radiologists was good for baseline volume (concordance correlation coefficient 0.993) and follow-up volume (0.991). It was slightly lower for the percent change from baseline to follow-up (0.872).
  • Median overall survival for all 30 patients was 16 months. There were 26 deaths.
• The authors' conclusion: The authors concluded that changes in tumor volume after two cycles of chemotherapy predicted overall survival in malignant pleural mesothelioma, and that baseline volume was associated with preoperative clinical stage and survival. They also concluded that computer-aided volume measurements may allow more reliable response assessment and could provide additional prognostic information.
• Limitations the authors state:
  • Only tumor volume and volume change were considered. Other factors that can affect survival, such as histology, pathologic stage, gender, asbestos exposure, smoking, symptoms and laterality, were not.
  • About half the patients had talc pleurodesis, and its effect on the results is difficult to determine.
  • Results may have been affected by observer bias and by varying, thick CT slice thicknesses.
  • The study population was small, which made statistical significance hard to reach for several results. The findings need validation in larger trials.

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, Chemotherapy, Clinical Trial, CT Scan, Overall Survival, Hazard Ratio, confidence interval, Modified RECIST (mRECIST).

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