An association between connective tissue disease (CTD) and lung cancer has been claimed in accumulating studies. However, the management of lung cancer with CTD is challenging because the pre-existing CTDs have proved to be significant risk factors for treatment-related toxicity, resulting in poor survival. In this review, we summarize the available information related to the treatment for lung cancer with CTD, discuss risk factors for treatment-related toxicities and management recommendations, which attempts to approach lung cancer with comorbid CTD systematically. Preliminary data show that: i) limited studies have focused on the effect of traditional therapeutic modalities, such as surgical treatment and chemotherapy; ii) with the development of the modern radiation techniques, radiotherapy would be well tolerated in this challenging clinical situation, but a cautious decision should be made for patients with CTD associated interstitial lung disease (ILD); iii) for patients with inactive CTD, immunotherapy was shown to have excellent local control with acceptable toxicity; iv) little information is available on the effects of tyrosine kinase inhibitors because of acute exacerbation (AE) of ILD risks; v) antiangiogenic therapy might be useful in preventing the progression in both lung cancer and CTD without increasing the AE-ILD risk; vi) Nintedanib would be a potentially promising novel therapy since it has recently been developed with promising results for both lung cancer and CTD-ILD. Further large-scale, randomized, controlled studies are still required to develop better therapeutic management for patients with lung cancer and pre-existing CTD.
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