A new prognostic index for overall survival in malignant pleural mesothelioma: the rPHS (regimen, PS, histology or stage) index

Our plain-English summary of A new prognostic index for overall survival in malignant pleural mesothelioma: the rPHS (regimen, PS, histology or stage) index, by Y. Kataoka, Y. Yamamoto, T. Otsuki, et al (Japanese Journal of Clinical Oncology, 2015).

The study

• Authors: Y. Kataoka, Y. Yamamoto, T. Otsuki, M. Shinomiya, T. Terada, S. Fukuma, S. Yamazaki, M. Hirabayashi, T. Nakano, S. Fukuhara
• Journal: Japanese Journal of Clinical Oncology
• Published: 2015;45(6):562-8
• Cited by: 14 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Objective: Existing prognostic indices for malignant pleural mesothelioma do not incorporate the recent advances in oncology care. The purpose of this study was to provide a prognostic index for overall survival in malignant pleural mesothelioma patients treated with chemotherapy with pemetrexed or best supportive care in the recent clinical setting.

Methods: A retrospective cohort study was performed in two hospitals in Japan (2007-13). The primary outcome was overall survival. The Cox proportional hazards model was used for multivariable analyses to identify prognostic factors. A final model was chosen based on both clinical and statistical significance.

Results: A total of 283 patients (chemotherapy: n = 228, best supportive care: n = 55) were enrolled in the study. On multivariate analysis, regimen including platinum plus pemetrexed, a performance status >0, non-epithelial histological type and Stage IV disease predicted poor overall survival in chemotherapy patients. As hazard ratios of individual risk factors were approximately similar, a prognostic index for overall survival was constructed by counting the risk factors. Median overall survival in chemotherapy patients decreased by each one-point increase in this count: 1030 days for zero; 658 days for one; 373 days for two; 327 days for three; 125 days for four. Internal validation using the bootstrapping technique showed robustness of the model (c-index, 0.677; 95% confidence interval, 0.624-0.729). Further, the discrimination was consistent in best supportive care patients (c-index, 0.799; 95% confidence interval, 0.725-0.874).

Conclusions: This novel index can provide clinicians and malignant pleural mesothelioma patients with a better framework for discussing prognosis at the time of diagnosis.

© The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: [email protected].

In plain English

This retrospective cohort study from two Japanese hospitals built a tool for estimating survival in malignant pleural mesothelioma. It covered 283 patients diagnosed between April 2007 and March 2013: 228 treated with chemotherapy containing pemetrexed and 55 who received best supportive care. Patients who had surgery were excluded. Asbestos exposure was one of many factors examined. It was linked to shorter survival when factors were tested one at a time, but did not stay in the final model. Four factors did: performance status above 0, non-epithelial histological type, stage IV disease, and chemotherapy regimen; the article is inconsistent about which regimen counts as the risk factor. Among chemotherapy patients, median survival was 1030 days (95% CI 661–1399) for 24 patients with none of the four factors and 125 days (95% CI 16–234) for only 5 patients with all four. The index's c-index, a measure of how well it ranks patients, was 0.677 (95% CI 0.624–0.729), and 0.799 (0.725–0.874) in supportive care patients. The authors concluded it could aid prognosis discussions. They noted missing data and no outside validation.

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 cohort study developing and internally validating a prognostic (survival-prediction) index
• Who was studied: 283 patients with histologically proven malignant pleural mesothelioma at two tertiary hospitals serving the South Hanshin medical region of Japan, 1 April 2007 to 31 March 2013. 228 were treated with chemotherapy with pemetrexed and 55 received best supportive care. Patients with surgery, trimodal therapy, prior chemotherapy or radiotherapy, more than one cancer, autopsy, or chemotherapy without pemetrexed were excluded.
• Exposure: This was not a study of asbestos as a cause. The factors studied were treatment (pemetrexed alone, platinum plus pemetrexed, or best supportive care) and patient and tumor characteristics. Asbestos exposure history (no fiber types named) was one candidate prognostic factor. 197 chemotherapy patients (87.6%) had exposure recorded as yes and 28 (12.4%) as no, with 3 missing.
• Main results:
  • In the chemotherapy group, asbestos exposure was among 15 factors significantly associated with overall survival in one-factor-at-a-time analysis. Median survival was 710 days for those without recorded exposure and 397 days for those with it (P = 0.0480).
  • In the backward multivariable model, asbestos exposure had a hazard ratio of 1.64 (95% CI 0.75–3.58). Only performance status, histology, stage and regimen remained significant.
  • In the final model for chemotherapy patients, the hazard ratios were: performance status 1 or more, 2.06 (1.22–3.44); non-epithelial histology, 2.15 (1.41–3.26); stage IV, 1.82 (1.23–2.69); pemetrexed monotherapy compared with platinum plus pemetrexed, 2.25 (1.16–4.36).
  • Median overall survival among chemotherapy patients by number of risk factors: 0 factors, 1030 days (95% CI 661–1399, n = 24); 1, 658 days (444–872, n = 57); 2, 373 days (223–522, n = 56); 3, 327 days (189–465, n = 22); 4, 125 days (16–234, n = 5). These groups total 164 of the 228 chemotherapy patients. The sensitivity analysis using multiple imputation gave 926, 603, 367, 240 and 48 days.
  • In the chemotherapy group, the index had a c-index of 0.677 (bootstrap 95% CI 0.624–0.729). The EORTC prognostic index scored 0.569 and the EORTC progression-free index 0.552. The differences were 0.108 (95% CI 0.053–0.163) and 0.125 (95% CI 0.082–0.166).
  • In the best supportive care group, the c-index was 0.799 (95% CI 0.725–0.874). Median survival there ranged from 573 days with 1 factor (n = 6) to 26 days with 4 factors (n = 6).
  • During follow-up, 161 chemotherapy patients (70.6%) and 40 best supportive care patients (72.7%) died. Median follow-up was 345.5 days and 250 days respectively.
• The authors' conclusion: The authors concluded that the new index can give clinicians and patients with malignant pleural mesothelioma a better framework for discussing prognosis at the time of diagnosis, and that further prospective studies using it are warranted.
• Limitations the authors state:
  • Retrospective design, with a substantial amount of missing performance status data; the authors addressed this with multiple imputation.
  • The reasons each patient received a given treatment were unknown, because treatment allocation was not protocol based.
  • The sample size did not allow external validation, so validation studies are needed.

Topics

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

Medical terms in this study, explained in our Lexicon: Overall Survival, Pleural Mesothelioma, Histology, Chemotherapy, Pemetrexed (Alimta), Cohort Study, Statistical Significance, Multivariate Analysis.

Related studies

• External validation of prognostic indices for overall survival of malignant pleural mesothelioma — Y. Kataoka, Y. Yamamoto, et al. (2017)
• Second-line gemcitabine-based chemotherapy regimens improve overall 3-year survival rate in patients with malignant pleural mesothelioma: a multicenter retrospective study — H. Mutlu, S. Gündüz, et al. (2014)
• Computed tomography in the evaluation of malignant pleural mesothelioma-Association of tumor size to a sarcomatoid histology, a more advanced TNM stage and poor survival — J. Paajanen, S. Laaksonen, et al. (2018)
• Survival and prognostic factors in malignant pleural mesothelioma: a retrospective study of 314 patients in the west part of Japan — S. Nojiri, K. Gemba, et al. (2011)
• Importance of excision repair cross-complementation group 1 and ribonucleotide reductase M1 as prognostic biomarkers in malignant pleural mesothelioma treated with platinum-based induction chemotherapy followed by surgery — L. Frischknecht, M. Meerang, et al. (2015)
• Prognostic factors for progression-free and overall survival in malignant pleural mesothelioma — J. Guzmán-Casta, S. Carrasco-CaraChards, et al. (2021)

Browse more research in Japanese Journal of Clinical Oncology, or return to medical research.