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• Author response to Dr. Wada and Dr. Kataoka
  Hyungjin Kim, Chang Min Park
  Published on: 25 June 2018
• Comment on, “Validation of prediction models for risk stratification of incidentally detected pulmonary subsolid nodules: a retrospective cohort study in a Korean tertiary medical center”
  Nobuko Wada, Yuki Kataoka
  Published on: 7 June 2018

• Published on: 25 June 2018

  Author response to Dr. Wada and Dr. Kataoka

  • Hyungjin Kim, Radiologist Seoul National University Hospital
  • Other Contributors:
    • Chang Min Park, Radiologist

  We thank Dr. Wada and Dr. Kataoka for showing interest in our validation study. Dr. Wada and his colleague raised two important questions: 1) how was the pathologic diagnosis established in our study; and 2) the effect of selection bias (e.g. non-surgically diagnosed patients).
  First, in our study, all pathologic diagnoses were determined by the attending pathologists according to the 2011 lung adenocarcinoma classification described by the International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society.1 In our institution, 10% buffered formalin was infused to inflate and fix all surgical specimens containing subsolid nodules (SSNs) via the transpleural and transbronchial approach to precisely measure the invasive adenocarcinoma component.2 Furthermore, pathologic examination was performed independently as a part of routine clinical practice. Thus, pathologic diagnosis was not affected by the predictor variables we collected and vice versa.
  Second, we admit that exclusion of the non-surgically diagnosed patients might have caused selection bias in our study. The current study population comprised solely surgically resected lung nodules. However, this was inevitable given the indolent nature of SSNs and the unique characteristics of SSNs’ definitive diagnosis. SSNs grow slowly and even the SSNs with invasive adenocarcinoma components may remain unchanged over years of CT surveillance. Thus, definitive diagnosis of S...

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  We thank Dr. Wada and Dr. Kataoka for showing interest in our validation study. Dr. Wada and his colleague raised two important questions: 1) how was the pathologic diagnosis established in our study; and 2) the effect of selection bias (e.g. non-surgically diagnosed patients).
  First, in our study, all pathologic diagnoses were determined by the attending pathologists according to the 2011 lung adenocarcinoma classification described by the International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society.1 In our institution, 10% buffered formalin was infused to inflate and fix all surgical specimens containing subsolid nodules (SSNs) via the transpleural and transbronchial approach to precisely measure the invasive adenocarcinoma component.2 Furthermore, pathologic examination was performed independently as a part of routine clinical practice. Thus, pathologic diagnosis was not affected by the predictor variables we collected and vice versa.
  Second, we admit that exclusion of the non-surgically diagnosed patients might have caused selection bias in our study. The current study population comprised solely surgically resected lung nodules. However, this was inevitable given the indolent nature of SSNs and the unique characteristics of SSNs’ definitive diagnosis. SSNs grow slowly and even the SSNs with invasive adenocarcinoma components may remain unchanged over years of CT surveillance. Thus, definitive diagnosis of SSNs could not be determined based on follow-up studies, and meticulous pathologic examination to evaluate the exact extent of invasive adenocarcinoma component should be a requisite for the definitive diagnosis. However, we agree that exclusion of the small SSNs (mostly pure ground-glass nodules), which are usually followed up with CT scan, would be the major limitation in our study. Therefore, our study results may not be directly applicable to the small or indolent SSNs. Further investigation including the small or indolent SSNs is warranted to evaluate the performance of diagnostic models in each clinical setting. As for the SSNs diagnosed by biopsy, either percutaneous needle lung biopsy or bronchoscopic biopsy can underestimate the invasive adenocarcinoma component of SSNs due to sampling error. Actually, the role of biopsy is relatively limited for SSNs.3 4 Accordingly, in our institution, SSNs with solid portions larger than 5 mm have been diagnosed and treated via surgical resection without prior biopsy.5 Therefore, the excluded subset, in which biopsy was indicated but not resected, would be small among SSNs, and might had little impact on the current study results.

  References
  1. Travis WD, Brambilla E, Noguchi M, et al. International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society international multidisciplinary classification of lung adenocarcinoma. J Thorac Oncol 2011;6:244-85.
  2. Lee KH, Goo JM, Park SJ, et al. Correlation between the size of the solid component on thin-section CT and the invasive component on pathology in small lung adenocarcinomas manifesting as ground-glass nodules. J Thorac Oncol 2014;9:74-82.
  3. Jhun BW, Um SW, Suh GY, et al. Preoperative flexible bronchoscopy in patients with persistent ground-glass nodule. PLoS One 2015;10:e0121250.
  4. Kim JI, Park CM, Kim H, et al. Non-specific benign pathological results on transthoracic core-needle biopsy: how to differentiate false-negatives? Eur Radiol 2017;27:3888-95.
  5. Lee SM, Park CM, Song YS, et al. CT assessment-based direct surgical resection of part-solid nodules with solid component larger than 5 mm without preoperative biopsy: experience at a single tertiary hospital. Eur Radiol 2017;27:5119-26.

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  Conflict of Interest:
  None declared.

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• Published on: 7 June 2018

  Comment on, “Validation of prediction models for risk stratification of incidentally detected pulmonary subsolid nodules: a retrospective cohort study in a Korean tertiary medical center”

  • Nobuko Wada, MD Hyogo Prefectural Amagasaki General Medical Center
  • Other Contributors:
    • Yuki Kataoka, MD/MPH

  To the Editor:
  We read the recent articles from Kim et al. with great interest and appreciate the authors’ efforts to evaluate the suitability of the two models regarding the prediction of incidentally-detected pulmonary subsolid nodules (SSNs), as well as their reports that there were substantial differences. However, we would like to highlight two concerns that we have regarding their study.

  First, there is a lack of description regarding whether an adequate pathological diagnosis was performed. We would like to know who performed the diagnosis and how it was made. In predictive model research, it is preferable that outcomes are evaluated with masked predictors, as there might be bias in estimating associations between predictors and outcomes. [1]

  Secondly, there might have been a sampling bias before surgery selection. Among patients with SSNs, surgery might be preferentially performed, especially for patients who show a high possibility of lung cancer. Further, additional upper lobes and peripheral nodules, which were difficult to diagnose by bronchoscopy examination, might be selected and resected. Thus, cases of atypical adenomatous hyperplasia (AAH)/ adenocarcinoma in situ (AIS) might comprise a smaller portion of the study cohort, and minimally invasive adenocarcinoma (MIA)/ invasive pulmonary adenocarcinoma (IPA) might be diagnosed more frequently. Clinically, we often struggle to decide whether the nodule is malignant in a case where surgery c...

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  To the Editor:
  We read the recent articles from Kim et al. with great interest and appreciate the authors’ efforts to evaluate the suitability of the two models regarding the prediction of incidentally-detected pulmonary subsolid nodules (SSNs), as well as their reports that there were substantial differences. However, we would like to highlight two concerns that we have regarding their study.

  First, there is a lack of description regarding whether an adequate pathological diagnosis was performed. We would like to know who performed the diagnosis and how it was made. In predictive model research, it is preferable that outcomes are evaluated with masked predictors, as there might be bias in estimating associations between predictors and outcomes. [1]

  Secondly, there might have been a sampling bias before surgery selection. Among patients with SSNs, surgery might be preferentially performed, especially for patients who show a high possibility of lung cancer. Further, additional upper lobes and peripheral nodules, which were difficult to diagnose by bronchoscopy examination, might be selected and resected. Thus, cases of atypical adenomatous hyperplasia (AAH)/ adenocarcinoma in situ (AIS) might comprise a smaller portion of the study cohort, and minimally invasive adenocarcinoma (MIA)/ invasive pulmonary adenocarcinoma (IPA) might be diagnosed more frequently. Clinically, we often struggle to decide whether the nodule is malignant in a case where surgery cannot be performed because of age, lung capacity, or social background. We urge Kim et al. to reanalyze and include patients who were diagnosed by non-surgical means, such as bronchoscopy.

  Best regards,

  References:

  [1] 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. , p. 162:W1–73., 2015.

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  Conflict of Interest:
  None declared.

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