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Clinical Relevance of Our Multimodality Prognostic Score
LETTERS TO THE EDITOR
How Can We Use the Multimodality Prognostic Score? To the Editor: We read the article recently published in the Journal of Thoracic Oncology by Opitz et al.1 with great interest, and we appreciate the authors’ efforts to develop a high discriminative prognostic score including external validation. However, we think that two methodological concerns should be emphasized. First, if they want to use this prognostic score for the “inclusion of a patient into multimodality treatment,” why did they use response to chemotherapy, which is not available at application of the first cycle of chemotherapy, as a predictive factor? We think that whether to perform surgery is more important because the extrapleural pneumonectomy is an invasive and sometimes lethal procedure.2 How about developing a score harboring the predictive factors and overall survival defined at the time of extrapleural pneumonectomy? Second, missing values sometimes cause bias.3 So for transparent reporting, missing values should be described Disclosure: The authors declare no conflict of interest. Address for correspondence: Yuki Kataoka, MD, MPH, Higashi-NaniwaCho 2-17-77, Amagasaki, Hyogo 660-8550, Japan. E-mail: youkiti@ gmail.com ª 2015 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved. ISSN: 1556-0864 http://dx.doi.org/10.1016/j.jtho.2015.10.026
Clinical Relevance of Our Multimodality Prognostic Score In Response: We thank Yuki Kataoka et al. for their comments on our Multimodality Prognostic Score and the opportunity to discuss our article more in detail. Disclosure: The authors declare no conflict of interest. Address for correspondence: Walter Weder, MD, Division of Thoracic, Surgery, University Hospital Zurich, Raemistrasse 100, 8091 Zurich, Switzerland. E-mail: [email protected] ª 2016 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved. ISSN: 1556-0864 http://dx.doi.org/10.1016/j.jtho.2015.12.094
with an explanation of how they were handled and details of any imputation method.3 Opitz et al.’s score contains tumor volume before chemotherapy, which was not available for all patients. How did they handle the missing value? Yuki Kataoka, MD, MPH Hospital Care Research Unit Department of Respiratory Medicine Hyogo Prefectural Amagasaki General Medical Center Amagasaki, Hyogo, Japan Hiraku Tsujimoto, MD Hospital Care Research Unit Department of Nephrology Hyogo Prefectural Amagasaki General Medical Center Amagasaki, Hyogo, Japan Yasushi Tsujimoto, MD Department of Healthcare Epidemiology Graduate School of Medicine and Public Health Kyoto University Kyoto, Japan
References 1. Opitz I, Friess M, Kestenholz P, et al. A new prognostic score supporting treatment allocation for multimodality therapy for malignant pleural mesothelioma: a review of 12 years’ experience. J Thorac Oncol. 2015;10:1634–1641. 2. Cao C, Tian D, Manganas C, Matthews P, Yan TD. Systematic review of trimodality therapy for patients with malignant pleural mesothelioma. Ann Cardiothorac Surg. 2012;1:428–437. 3. Moons KGM, Altman DG, Reitsma JB, et al. Transparent reporting of a multivariable prediction model for individual prognosis or diagnosis (TRIPOD): explanation and elaboration. Ann Intern Med. 2015;162:W1–W73.
The first comment is indeed an important question because clinical factors, which are available initially, are needed for decision making before the patient is selected for multimodality treatment. Yuki Kataoka et al. state correctly that response to chemotherapy is available only after induction chemotherapy. We had already validated our Multimodality Prognostic Score before this comment by excluding response to chemotherapy and using only three variables. The results were comparable to those with four variables and showed that patients with a score of 3 had a significantly shorter survival than did patients with a lower score (Fig. 1, Table 1). Their second comment on the problem of missing data is indeed a problem and may be the origin of bias in studies. The missing data for the radiological
Journal of Thoracic Oncology
Vol. 11 No. 3: e39-e44
e40 Letters to the Editor
Journal of Thoracic Oncology
Vol. 11 No. 3
Figure 1. Kaplan-Meier curve of overall survival (OS) in months of the Multimodality Prognostic Score (including 3 variables: tumor volume pre chemotherapy [CTX] > 500ml, CRP pre CTX > 30 mg/l, non-epithelioid histology in pre CTX biopsy). Cum, cumulative survival.
Table 1. MMPS Score and Overall Survival Score
Median OS, mo
95% CI
0 1 2 3
26 13 14 4
15–37 10–16 0–31 3–5
OS, overall survival; CI, confidence interval.
assessment of chemotherapy response by the Response Evaluation Criteria in Solid Tumors and the measurement of tumor volumetry were the main missing items for our score. This is due to the fact that pretreatment computed tomography (CT) scans were often performed at institutions outside our hospital. Although we contacted all referring institutions, including their radiological departments, to
request the CT scans, the quality of the films sent to us—especially that of those obtained in the earlier days—was poor; therefore, measurement of volumetry was not possible. Furthermore, tumor volume could be assessed only in cases in which the CT or positron emission tomography–CT scans were digitally available and the quality of the picture was adequate for the measurement using specialized software. In our current project, we are prospectively evaluating our score for further validation. Isabelle Opitz, MD Walter Weder, MD Division of Thoracic Surgery University Hospital Zurich Zurich, Switzerland
How Can We Use the Multimodality Prognostic Score? To the Editor: We read the article recently published in the Journal of Thoracic Oncology by Opitz et al.1 with great interest, and we appreciate the authors’ efforts to develop a high discriminative prognostic score including external validation. However, we think that two methodological concerns should be emphasized. First, if they want to use this prognostic score for the “inclusion of a patient into multimodality treatment,” why did they use response to chemotherapy, which is not available at application of the first cycle of chemotherapy, as a predictive factor? We think that whether to perform surgery is more important because the extrapleural pneumonectomy is an invasive and sometimes lethal procedure.2 How about developing a score harboring the predictive factors and overall survival defined at the time of extrapleural pneumonectomy? Second, missing values sometimes cause bias.3 So for transparent reporting, missing values should be described Disclosure: The authors declare no conflict of interest. Address for correspondence: Yuki Kataoka, MD, MPH, Higashi-NaniwaCho 2-17-77, Amagasaki, Hyogo 660-8550, Japan. E-mail: youkiti@ gmail.com ª 2015 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved. ISSN: 1556-0864 http://dx.doi.org/10.1016/j.jtho.2015.10.026
Clinical Relevance of Our Multimodality Prognostic Score In Response: We thank Yuki Kataoka et al. for their comments on our Multimodality Prognostic Score and the opportunity to discuss our article more in detail. Disclosure: The authors declare no conflict of interest. Address for correspondence: Walter Weder, MD, Division of Thoracic, Surgery, University Hospital Zurich, Raemistrasse 100, 8091 Zurich, Switzerland. E-mail: [email protected] ª 2016 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved. ISSN: 1556-0864 http://dx.doi.org/10.1016/j.jtho.2015.12.094
with an explanation of how they were handled and details of any imputation method.3 Opitz et al.’s score contains tumor volume before chemotherapy, which was not available for all patients. How did they handle the missing value? Yuki Kataoka, MD, MPH Hospital Care Research Unit Department of Respiratory Medicine Hyogo Prefectural Amagasaki General Medical Center Amagasaki, Hyogo, Japan Hiraku Tsujimoto, MD Hospital Care Research Unit Department of Nephrology Hyogo Prefectural Amagasaki General Medical Center Amagasaki, Hyogo, Japan Yasushi Tsujimoto, MD Department of Healthcare Epidemiology Graduate School of Medicine and Public Health Kyoto University Kyoto, Japan
References 1. Opitz I, Friess M, Kestenholz P, et al. A new prognostic score supporting treatment allocation for multimodality therapy for malignant pleural mesothelioma: a review of 12 years’ experience. J Thorac Oncol. 2015;10:1634–1641. 2. Cao C, Tian D, Manganas C, Matthews P, Yan TD. Systematic review of trimodality therapy for patients with malignant pleural mesothelioma. Ann Cardiothorac Surg. 2012;1:428–437. 3. Moons KGM, Altman DG, Reitsma JB, et al. Transparent reporting of a multivariable prediction model for individual prognosis or diagnosis (TRIPOD): explanation and elaboration. Ann Intern Med. 2015;162:W1–W73.
The first comment is indeed an important question because clinical factors, which are available initially, are needed for decision making before the patient is selected for multimodality treatment. Yuki Kataoka et al. state correctly that response to chemotherapy is available only after induction chemotherapy. We had already validated our Multimodality Prognostic Score before this comment by excluding response to chemotherapy and using only three variables. The results were comparable to those with four variables and showed that patients with a score of 3 had a significantly shorter survival than did patients with a lower score (Fig. 1, Table 1). Their second comment on the problem of missing data is indeed a problem and may be the origin of bias in studies. The missing data for the radiological
Journal of Thoracic Oncology
Vol. 11 No. 3: e39-e44
e40 Letters to the Editor
Journal of Thoracic Oncology
Vol. 11 No. 3
Figure 1. Kaplan-Meier curve of overall survival (OS) in months of the Multimodality Prognostic Score (including 3 variables: tumor volume pre chemotherapy [CTX] > 500ml, CRP pre CTX > 30 mg/l, non-epithelioid histology in pre CTX biopsy). Cum, cumulative survival.
Table 1. MMPS Score and Overall Survival Score
Median OS, mo
95% CI
0 1 2 3
26 13 14 4
15–37 10–16 0–31 3–5
OS, overall survival; CI, confidence interval.
assessment of chemotherapy response by the Response Evaluation Criteria in Solid Tumors and the measurement of tumor volumetry were the main missing items for our score. This is due to the fact that pretreatment computed tomography (CT) scans were often performed at institutions outside our hospital. Although we contacted all referring institutions, including their radiological departments, to
request the CT scans, the quality of the films sent to us—especially that of those obtained in the earlier days—was poor; therefore, measurement of volumetry was not possible. Furthermore, tumor volume could be assessed only in cases in which the CT or positron emission tomography–CT scans were digitally available and the quality of the picture was adequate for the measurement using specialized software. In our current project, we are prospectively evaluating our score for further validation. Isabelle Opitz, MD Walter Weder, MD Division of Thoracic Surgery University Hospital Zurich Zurich, Switzerland