Elsevier

Respiratory Investigation

Volume 57, Issue 6, November 2019, Pages 512-533
Respiratory Investigation

Statement
Summary of the Japanese Respiratory Society statement for the treatment of lung cancer with comorbid interstitial pneumonia

https://doi.org/10.1016/j.resinv.2019.06.001Get rights and content

Abstract

Dramatic progress in targeted therapy and immunotherapy has been changing clinical practices in lung cancer. With the accumulation of clinical practice, it has become clear that pre-existing interstitial pneumonia (IP) could be a risk factor for drug-induced lung injury, which has enhanced awareness regarding the difficulty in treating lung cancer with comorbid IP. Unfortunately, there is only low-grade evidence in the field of lung cancer with comorbid IP, because almost all clinical trials exclude such patients. There have been very few specialized clinical trials for patients with lung cancer and underlying IPs thus far. Therefore, it is necessary to treat such cases empirically or to give up on the treatment itself. Considering these circumstances, establishing how to treat lung cancer with comorbid IP is an urgent issue. This paper is a summary of the official statement reported by the Diffuse Lung Disease/Thoracic Oncology Assembly and the Japanese Respiratory Society (JRS) in 2017, which attempts to approach lung cancer with comorbid IP systematically.

Introduction

Recently, there have been remarkable advances in lung cancer treatment, especially drug therapy, including molecular target treatment and immunotherapy. Evaluations in clinical trials are indispensable for new therapeutic development. However, almost all lung cancer clinical trials exclude patients with comorbid interstitial pneumonia (IP) from their registration. For this reason, lung cancer with comorbid IP has been completely left behind, and there is little evidence for its therapy. With little evidence available for assessment, patients with lung cancer and comorbid IP must make the ultimate choice to treat or not to treat the disease.

This paper is a summary of the official statement reported by the Diffuse Lung Disease/Thoracic Oncology Assembly and the JRS in 2017. The statement was made by expert board members, listed as the authors of this paper, and went through the peer-review process by 18 reviewers, with one or two reviewers reviewing per section. The board members always included “interstitial pneumonia,” “pulmonary fibrosis,” and “interstitial lung disease (ILD)” as search words when they searched for related articles. The purpose of the statement is to shed light on any missing pieces of evidence for lung cancer, and to understand how to treat this disease with comorbid IP. Given that most clinical trials exclude not only idiopathic pulmonary fibrosis (IPF), but also other interstitial lung diseases, we defined “IP” in this paper as interstitial lung disease including, idiopathic IPs (IIPs) and secondary IPs, such as drug-induced IP, radiation pneumonitis, and pneumoconiosis.

By carrying out this work, we hope to lead the creation of treatment guidelines for lung cancer with comorbid IP in the future. This paper includes newly published information [1].

Section snippets

Clinical, pathological, and imaging-based classification of IP

  • The classification of IP has been primarily based on pathological diagnosis. In 2002, an international multidisciplinary classification of IIPs was issued by the American Thoracic Society/European Respiratory Society (ATS/ERS). In 2013, a revision of the multidisciplinary classification was published, and has become the current international classification [1]. The JRS adopts this classification [2].

  • IIPs are classified into the following types: IPF, idiopathic non-specific interstitial

Molecular biology of IP and lung cancer

  • Risk factors common to both IP and lung cancer include smoking, environmental or occupational exposure to harmful substances, bacterial or viral infection, and chronic tissue damage [1], [2].

  • Molecular mechanisms common to the development of both IP and lung cancer include genetic and epigenetic mutations, micro-RNA expression abnormalities, inhibition of apoptosis associated with the activation of intracellular signal transduction, and the weakening of cellular interaction [1], [2], [3], [4],

Epidemiology

  • There have only been a few reports on the frequency of lung cancer with comorbid IIPs, other than IPF.

  • The frequency varies between reports, but lung cancer has a high rate of IPF comorbidity, reaching between 2.0–16.7% at the time of IPF diagnosis [1], [2], [3], [4], [5], [6], [7], and a cumulative rate of 2.7–31.3% [1], [2], [3], [4], [5], [6], [7], [8], [9], [10], [11], [12], [13], [14], [15], [16]. Although the rates from some autopsy reports are 17.0–48.2% [17], [18], [19], [20], [21], the

Biomarkers

  • As the molecular profiles of lung cancer and IP have many similarities, it seems possible that there are common factors in their onset [1], [2], [3], [4].

  • The molecular profile of lung cancer with comorbid IP has not been sufficiently elucidated, but as research progresses, biomarkers may be discovered that can be used for early diagnosis of lung cancer with comorbid IP.

  • In lung cancer comorbid with IP, if changes in cell-free DNA and microRNA in the blood were to be identified, they could act as

Treatment for lung cancer with comorbid IP

It is unclear whether chemotherapy prolongs the survival of advanced lung cancer patients with comorbid IP, compared to the best supportive care. In the treatment of lung cancer with comorbid IP, the risk of fatal AE must be considered. Use of anti-cancer agents must take into account the risk versus the benefit. Therefore, it is necessary to carefully assess both lung cancer and IP. It is also necessary to respect the patient’s wishes in the treatment selection.

The Japanese Guideline for the

Combined pulmonary fibrosis and emphysema (CPFE) and lung cancer

  • CPFE is a clinical syndrome characterized by CT findings of emphysema in the upper lung field and of fibrosis in the lower lung field [1], [2], [3], [4], [5], [6].

  • CPFE has a high rate of lung cancer comorbidity, with squamous cell cancer being the most-frequent histological type [7], [8], [9].

  • There are very few reports on the treatment of lung cancer with comorbid CPFE.

  • The incidence of AE of comorbid CPFE after surgery is reported to be 2.0–7.4% [7], [10], thus no higher than in lung cancer

Conflict of interest

JRS statement for the treatment of lung cancer with comorbid interstitial pneumonia

This form is blank, since this statement has been approved by the Board of Directors of the JRS and submitted by the Editorial Office on behalf of the corresponding author.

References (2)

  • S. Homma et al.

    Japanese guidlene for the treatment of idiopathic pulmonary fibrosis

    Respiratory Investigation

    (2018)
There are more references available in the full text version of this article.

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