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Background
Fibrosing interstitial lung diseases (ILDs) are associated with poor survival and an increased risk of developing lung cancer (LC). Patient and LC characteristics, therapeutic possibilities and survival in this rare patient population are not well established.
Methods
Fibrosing ILD patients treated at the Department of Pulmonology Semme...
Contexts in source publication
Context 1
... verified adenocarcinoma in 13 patients (56%) being the most LC type in this cohort, while six patients (26%) had squamous cell lung cancer. Small cell lung cancer (SCLC) was found only in two patients and in two cases only non-small cell lung cancer (NSCLC) diagnosis could be established (Table 3). Cause of death in the majority of patients was progression of lung cancer (86%), while advanced lung fibrosis was the cause in 14% of cases. ...Similar publications
Background:
Idiopathic pulmonary fibrosis (IPF) is a progressive fibrosing interstitial lung disease characterised by decline in lung function. We evaluated trajectories of forced vital capacity (FVC) and diffusing capacity (DLco) in a cohort of patients with IPF.
Methods:
Patients with IPF that was diagnosed or confirmed at the enrolling centre...
Citations
... The incidence of lung cancer in IPF cases is considerably higher compared to the general population, with reported rates ranging from 3.34 to nearly 5 [62,63]. In a study of NSCLC in patients with ILD, lung cancer was manifested approximately 2.4 years following ILD diagnosis [64]. ...
Simple Summary
Lung cancer is one of the leading causes of cancer-related mortality worldwide. There is proof that interstitial lung disease and lung cancer interact and influence patient outcomes, treatment approaches, and the course of the disease. Common risk factors for both illnesses include smoking, exposure to the environment, and genetic predispositions. When interstitial lung disease is present, lung cancer management is complicated both diagnostically and therapeutically. These challenges include trouble interpreting radiological results and a higher risk of treatment-related toxicities, such as acute exacerbation following surgery and pneumonitis following radiation therapy and immunotherapy. Furthermore, the evidence-based treatment choices for patients with ILDs and lung cancer are still restricted.
Abstract
Lung cancer continues to be one of the leading causes of cancer-related death worldwide. There is evidence of a complex interplay between lung cancer and interstitial lung disease (ILD), affecting disease progression, management strategies, and patient outcomes. Both conditions develop as the result of common risk factors such as smoking, environmental exposures, and genetic predispositions. The presence of ILD poses diagnostic and therapeutic challenges in lung cancer management, including difficulties in interpreting radiological findings and increased susceptibility to treatment-related toxicities, such as acute exacerbation of ILD after surgery and pneumonitis after radiation therapy and immunotherapy. Moreover, due to the lack of large, phase III randomized controlled trials, the evidence-based therapeutic options for patients with ILDs and lung cancer remain limited. Antifibrotic treatment may help prevent pulmonary toxicity due to lung cancer treatment, but its effect is still unclear. Emerging diagnostic modalities and biomarkers and optimizing personalized treatment strategies are essential to improve outcomes in this patient population.
... ILD has been shown to share similar risk factors and pathophysiological mechanisms with lung cancer [1,2]. Notably, ILD is frequently observed in patients with lung cancer, and it is important to develop strategies for the treatment of ILD [3,4]. ...
Background
Acute exacerbation (AE) of interstitial lung disease (ILD) is one of the most serious complications during perioperative period of lung cancer resection. This study aimed to investigate the correlation between preoperative 2- deoxy-2-[18F]fluoro-D-glucose (¹⁸F-FDG) PET/CT findings and AE in lung cancer patients with ILD.
Methods
We retrospectively reviewed the data of 210 patients who underwent lung resection for non-small cell lung cancer. Relationships between clinical data and PET images and AE were evaluated. The patients were divided into an AE(+) and an AE(-) group for multivariate logistic regression analysis. Receiver operating characteristic (ROC) curve analysis was conducted and the area under curve (AUC) was used to assess the predictive values.
Results
Among 210 patients, 48 (22.8%) were diagnosed with ILD based on chest CT. Among them, 9 patients (18.75%) developed AE after lung resection and were defined as AE(+) group. The course of ILD was longer in AE(+) group compared to AE(-) group. More patients in AE(+) group had a history of AE and chronic obstructive pulmonary disease (COPD) than in AE(-) group. The maximum standardized uptake value (SUVmax) of the noncancerous interstitial pneumonia (IP) area and cancers in AE(+) group was significantly higher compared to AE(-) group. Univariate logistic regression analysis showed that AE, COPD, SUVmax of the noncancerous IP area, SUVmax of cancer, surgical method were significantly correlated with AE. The course of ILD[OR(95%CI) 2.919; P = 0.032], SUVmax of the noncancerous IP area[OR(95%CI) 7.630;P = 0.012] and D-Dimer level[OR(95%CI) 38.39;P = 0.041] were identified as independent predictors for AE in patients with ILD after lung cancer surgery. When the three indicators were combined, we found significantly better predictive performance for postoperative AE than that of SUVmax of the noncancerous IP area alone [0.963 (95% CI 0.914-1.00); sensitivity, 100%, specificity 87.2%, P < 0.001 vs. 0.875 (95% CI 0.789 ~ 0.960); sensitivity, 88.9%, specificity, 76.9%, P = 0.001; difference in AUC = 0.088, Z = 1.987, P = 0.04].
Conclusion
The combination of the course of ILD, SUVmax of the noncancerous IP area and D-Dimer levels has high predictive value for the occurrence of AE in patients with concomitant interstitial lesions.
... The incidence of lung cancer in IPF cases is considerably higher compared to the general population, with reported rates ranging from 3.34 to nearly 5 [44,55]. In a study of NSCLC in patients with ILD, lung cancer was manifested approximately 2.4 years following ILD diagnosis [56]. ...
Lung cancer remains one of the leading causes of cancer-related mortality worldwide. There is evidence of a complex interplay between lung cancer and interstitial lung disease (ILD), affecting disease progression, management strategies, and patient outcomes. Both conditions develop as the result of common risk factors such as smoking, environmental exposures, and genetic predispositions. The presence of ILD poses diagnostic and therapeutic challenges in lung cancer management, including difficulties in interpreting radiological findings, increased susceptibility to treatment-related toxicities, such as acute exacerbation of ILD after surgery and pneumonitis after radiation therapy and immunotherapy. Moreover, due to the lack of large, phase III randomized controlled trials in patients with lung cancer and ILDs, the evidence-based therapeutic options remain limited. The role of antifibrotic treatment in the prevention of lung-cancer-related treatment toxicities remains to be elucidated. Emerging diagnostic modalities and biomarkers, and optimizing personalized treatment strategies are essential to improve outcomes in this patient population.
... Although IPF is the most common type of ILD, it only accounts for 17-37% of all ILD diagnoses [10]. Recently, LC has been reported to be an important comorbidity in patients with ILD other than IPF [11,12]. Furthermore, several previous studies have reported that the prevalence of LC is higher in non-IPF ILD patients than in the general population [13,14]. ...
Background
Lung cancer (LC) is an important comorbidity of interstitial lung disease (ILD) and has a poor prognosis. The clinical characteristics and outcome of each ILD subtype in LC patients have not been sufficiently investigated. Therefore, this study aimed to evaluate the difference between idiopathic pulmonary fibrosis (IPF) and non-IPF ILD as well as prognostic factors in patients with ILD-LC.
Methods
The medical records of 163 patients diagnosed with ILD-LC at Asan Medical Center from January 2018 to May 2023 were retrospectively reviewed. Baseline characteristics and clinical outcomes were compared between the IPF-LC and non-IPF ILD-LC groups, and prognostic factors were analyzed using the Cox proportional-hazard model.
Results
The median follow-up period was 11 months after the cancer diagnosis. No statistically significant differences were observed in clinical characteristics and mortality rates (median survival: 26 vs. 20 months, p = 0.530) between the groups. The independent prognostic factors in patients with ILD-LC were higher level of Krebs von den Lungen-6 (≥ 1000 U/mL, hazard ratio [HR] 1.970, 95% confidence interval [CI] 1.026-3.783, p = 0.025) and advanced clinical stage of LC (compared with stage I, HR 3.876 for stage II, p = 0.025, HR 5.092 for stage III, p = 0.002, and HR 5.626 for stage IV, p = 0.002). In terms of treatment, surgery was the significant factor for survival (HR 0.235; 95% CI 0.106-0.520; p < 0.001).
Conclusions
No survival difference was observed between IPF-LC and non-IPF ILD-LC patients. A higher level of Krebs von den Lungen-6 may act as a prognostic marker in ILD-LC patients.
... With the application of new medications, including targeted therapy, immune therapy, and antifibrotic drugs, the prognoses of lung cancer (LC) and interstitial lung diseases (ILDs) have been greatly improved [1][2][3][4][5][6]. However, most patients suffering from lung cancer with concomitant interstitial lung disease (LC-ILD) cannot benefit from these novel treatments because of their complicated condition. ...
This study aimed to explore the general characteristics and spectrum of hospitalized Chinese patients suffering from lung cancer with concomitant interstitial lung disease (LC-ILD). Furthermore, we compared their features before and after the period of immunotherapy for lung cancer. A retrospective analysis of the clinical characteristics of hospitalized LC patients with definite pathological diagnoses was performed from 2014 to 2021. ILD was defined after the review of chest CT imaging. There were 13,085 hospitalized LC patients. Among them, 509 patients (3.89%) had 551 cases of ILD. There were variable underlying causes of ILD, including idiopathic interstitial pneumonia (360 patients), LC treatment-associated ILD (134 cases), and connective tissue disease-associated ILD (55 patients). Although most LC-ILD patients were suffering from adenocarcinoma (204/40.1%), SCLC patients were prone to concomitant ILD (10.8% of all SCLC cases), followed by SCC (9.6% of all SCC cases). All but 10 LC-ILD patients received anti-LC treatment; however, only 39 (10.8%) LC-IIP patients received anti-ILD treatment. There were more LC-ILD patients in the 2018–2021 group than in the 2014–2017 group (5.16% vs. 2.03%, p < 0.001). The underlying causes of ILD were significantly different between the 2018–2021 group and the 2014–2017 group ( p < 0.001). After adjusting for the number of hospitalized patients having the same LC pathological pattern, SCLC was determined to be the most likely to be concomitant with ILD, followed by SCC. Most LC-ILD patients were scheduled for anti-LC therapy; however, treatments for concomitant IIP were usually ignored. LC treatment-associated ILD should receive more attention than before.
... Profbrotic markers (alpha-smooth muscle actin, fbrillar collagens, SMAD3) expressed in histological samples of patients with lung cancer, are correlated to low survival [51]. Other important observations derived from pulmonary idiopathic fbrosis cases and interstitial fbrosis, are considered an independent risk variable for lung adenocarcinoma [52][53][54]. Lung fbrosis also positively correlates with a glycolytic metabolism of the tumor in subjects with IIIA NSCLC [55]. Notably, we have provided a frst biological indication of the possibility to "educate" the benign AMSC toward a malignant-like behavior. ...
Cancer alters both local and distant tissue by influencing the microenvironment. In this regard, the interplay with the stromal fraction is considered critical as this latter can either foster or hamper the progression of the disease. Accordingly, the modality by which tumors may alter distant niches of stromal cells is still unclear, especially at early stages. In this short report, we attempt to better understand the biology of this cross-talk. In our “autologous stromal experimental setting,” we found that remote adipose tissue-derived mesenchymal stem cells (mediastinal AMSC) obtained from patients with lung adenocarcinoma sustain proliferation and clonogenic ability of A549 and human primary lung adenocarcinoma cells similarly to the autologous stromal lung counterpart (LMSC). This effect is not observed in lung benign diseases such as the hamartochondroma. This finding was validated by conditioning benign AMSC with supernatants from LAC for up to 21 days. The new reconditioned media of the stromal fraction so obtained, was able to increase cell proliferation of A549 cells at 14 and 21 days similar to that derived from AMSC of patients with lung adenocarcinoma. The secretome generated by remote AMSC revealed overlapping to the corresponding malignant microenvironment of the autologous local LMSC. Among the plethora of 80 soluble factors analyzed by arrays, a small pool of 5 upregulated molecules including IL1-β, IL-3, MCP-1, TNF-α, and EGF, was commonly shared by both malignant-like autologous A- and L-MSC derived microenvironments vs those benign. The bioinformatics analysis revealed that these proteins were strictly and functionally interconnected to lung fibrosis and proinflammation and that miR-126, 101, 486, and let-7-g were their main targets. Accordingly, we found that in lung cancer tissues and blood samples from the same set of patients here employed, miR-126 and miR-486 displayed the highest expression levels in tissue and blood, respectively. When the miR-126-3p was silenced in A549 treated with AMSC-derived conditioned media from patients with lung adenocarcinoma, cell proliferation decreased compared to control media.
... patients with ILD developed lung cancer. Moreover, a higher incidence (14%) was detected in the study of Barczi and colleagues [10,13,14,16]. ...
Background
The concepts in lung fibrosis and increased lung cancer risk have arisen from clinical observations of the concurrent findings during the autopsy of lung cancer and pulmonary fibrosis. Scar carcinoma attributes the origin of carcinomas to abutting areas of scarring. The association between fibrosis and lung cancer risk immediately raises a query: whether lung fibrosis induces lung cancer?
Aim
The study was done to elucidate the incidence, risk factors, and clinical characteristics of lung cancer in diffuse lung fibrosis.
Patients and methods
A cohort study was done based on a prospective group of 50 patients with diffuse lung fibrosis to evaluate the incidence of lung cancer, as well as a retrospective group of 50 patients with lung cancer to search for background of pulmonary fibrosis between 2019 and 2020. Demographic, radiographic, and histologic characteristics were reviewed for both groups.
Results
Among 50 patients with interstitial lung disease, lung cancer developed in 2/50 (4%) during the follow-up, whereas in the retrospective group, 8/50 (16%) were diagnosed as having lung cancer with diffused lung fibrosis between 2019 and 2020. Lung cancer risk factors were male sex, smoking, and occupational dust exposure. Squamous carcinoma followed by adenocarcinoma was the commonest histologic form.
Conclusion
Evidence shows an association between interstitial lung diseases and lung cancer emergence. Epidemiological evidence differs owing to the various study designs and populations.
... Indeed, clinical cases have shown that tumor patients complicated with different degrees of interstitial lung disease (ILD; such as chronic obstructive pulmonary diseases, idiopathic pulmonary fibrosis [IPF], ICI therapy-related ILD and radiation-induced lung fibrosis, etc.) are often associated with poor outcomes [23]. However, both ICI and anti-angiogenesis therapy may induce the occurrence or aggravation of a series of ILD [24,25]. ...
... On the other hand, one of major difficulties in tumor immunotherapy is complications in other organs [67]. Among these, ILD limited ICI application and severely reduced the prognosis and survival of cancer patients [23,24]. Nintedanib, one of the most effective treatments for ILD, may be a valuable strategy for tumor patients complicated with ILD. ...
Background: Immune checkpoint inhibitors (ICIs), such as programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1), have been widely applied in clinical and scientific research. Despite their effective antitumor effects in clinical tumor therapy, most tumors are still resistant to ICIs and long-term benefits are lacking. In addition, tumor patients complicated with interstitial lung disease limit the application of ICI therapy. Therefore, for these cases, there is an urgent need to develop new methods to relieve lung complications and enhance the efficacy of ICI therapy. Nintedanib, a potent triple angiokinase inhibitor approved for the treatment of progressive fibrotic interstitial lung disease. However, its immunotherapy synergy properties and mechanism are still pending further exploration.
Methods: To explore the therapeutic potential of nintedanib and αPD-L1 combination therapy, MC38, LLC, and 4T1 tumor models were used to investigate antitumor and antimetastatic activities in vivo. An idiopathic pulmonary fibrosis-tumor bearing model was used to evaluate the effect of the synergy therapy on tumor model complicated with lung disease. Moreover, RNA-seq, immunohistochemistry, and flow cytometry were utilized to analyze the effect of combination treatment on the tumor microenvironment. The bioactivity following different treatments was determined by western blotting, CCK-8, and flow cytometry.
Results: In this study, nintedanib and αPD-L1 synergy therapy exhibited significant antitumor, antimetastatic and anti-pulmonary fibrosis effects. Both in vitro and in vivo experiments revealed that these effects included promoting vessel normalization, increasing infiltration and activation of immune cells in tumors, enhancing the response of interferon-gamma, and activating the MHC class I-mediated antigen presentation process. Moreover, our results showed an increased expression of PD-L1 and promoted phosphorylation of STAT3 after nintedanib (1 µM) treatment.
Conclusion: The combination of nintedanib and αPD-L1 increased ICI therapy responses, relieved lung complications and further activated the tumor immune microenvironment; thus, exhibiting a notable antitumor effect. Accordingly, the nintedanib synergy strategy is expected to be a promising candidate therapy for tumor patients complicated with interstitial lung disease in clinical practice.
... 2,7,8 Therefore, patients with lung cancer and ILD often do not receive chemotherapy. 42,43 On the other hand, given evidence suggesting that chemotherapy may prolong survival, uniformly excluding these populations from chemotherapy may not be appropriate. 5,6 The present study showed that patients without sarcopenia were less prone to ILD exacerbation and could hence receive aggressive chemotherapy, which may contribute to a better prognosis. ...
... First, this was a single-center retrospective study with a relatively small sample size, which may have introduced bias. However, lung cancer with ILD is a rare disease with a limited number of patients 3,4,9,10,[12][13][14]42,45 The number of patients included herein does not considerably differ from those included in other studies. Moreover, given the absence of large-scale phase III trials in patients with ILDcomplicated lung cancer to date, evidence has largely been obtained from retrospective studies. ...
Background
While recent evidence has suggested that sarcopenia could predict chemotoxicity, its association with chemotherapy-triggered interstitial lung disease (ILD) exacerbations has yet to be investigated. Thus, the present study sought to determine whether sarcopenia could predict ILD exacerbations and overall survival (OS) in patients with ILD-complicated non-small cell lung cancer (NSCLC).
Methods
From January 2010 to July 2020, 74 patients with ILD-complicated NSCLC who received chemotherapy were retrospectively investigated. After categorizing patients according to the presence or absence of sarcopenia based on the psoas muscle index, ILD exacerbation rates and OS were evaluated.
Results
Among the patients in the study, 39 were included in the sarcopenia group. Moreover, 17 (22.9%) patients developed ILD exacerbations, with the sarcopenia and nonsarcopenia groups having an exacerbation rate of 33.3% and 11.4%, respectively (p = 0.025). Multivariate analysis identified sarcopenia as an independent predictor of ILD exacerbations (p = 0.039). Furthermore, patients with sarcopenia demonstrated a significantly shorter median OS compared to those without the same (9.2 vs. 13.3 months; p = 0.029).
Conclusions
Sarcopenia predicted chemotherapy-triggered ILD exacerbation and OS in patients with ILD-complicated NSCLC, suggesting its utility in determining treatment approaches.
... At baseline and every follow-up, physical examination was performed, and a detailed medical history was taken with special emphasis on symptoms (dry/productive cough, sputum, and chest pain), respiratory infections, and comorbidities (Barczi et al., 2020). In our clinical routine, studied autoantibodies were anti-nuclear antibodies (ANA), rheumatoid factor (RF), anti-cyclic citrullinated peptide antibodies (ACPA), anti-RNA polymerase, anti-centromere, anti-proliferating cell nuclear antigen (APCNA), anti-Ku, anti-P-ribosomal, anticytoplasmatic, anti-cytoskeleton, anti-chromatin, anti-Smith, anti-myeloperoxidase, anti-proteinase-3, anti-Jo-1, anti-SS-A, anti-SS-B, anti-SCL-70, anti-ribonucleoprotein (RNP), and anti-neutrophil cytoplasmic antibodies (ANCA). ...
... The third variable for confirmed faster progression of PF-ILD in our patients was malignancy. Malignancy as a comorbidity is a serious complication associated with ILDs, especially in those showing progression as published previously in our previous study (Barczi et al., 2020). ...
A subset of interstitial lung diseases (ILDs) with autoimmune traits—including connective tissue disease-associated ILD (CTD-ILD) and interstitial pneumonia with autoimmune features (IPAF)—develops progressive fibrosing (PF)-ILD. The aim of our study was to evaluate the clinical characteristics and predictors of longitudinal lung function (LF) changes in autoimmune PF-ILD patients in a real-world setting. All ILD cases with confirmed or suspected autoimmunity discussed by a multidisciplinary team (MDT) between January 2017 and June 2019 (n = 511) were reviewed, including 63 CTD-ILD and 44 IPAF patients. Detailed medical history, LF test, diffusing capacity of the lung for carbon monoxide (DLCO), 6-min walk test (6MWT), blood gas analysis (BGA), and high-resolution computer tomography (HRCT) were performed. Longitudinal follow-up for functional parameters was at least 2 years. Women were overrepresented (70.1%), and the age of the IPAF group was significantly higher as compared to the CTD-ILD group (p < 0.001). Dyspnea, crackles, and weight loss were significantly more common in the IPAF group as compared to the CTD-ILD group (84.1% vs. 58.7%, p = 0.006; 72.7% vs. 49.2%, p = 0.017; 29.6% vs. 4.8%, p = 0.001). Forced vital capacity (FVC) yearly decline was more pronounced in IPAF (53.1 ± 0.3 vs. 16.7 ± 0.2 ml; p = 0.294), while the majority of patients (IPAF: 68% and CTD-ILD 82%) did not deteriorate. Factors influencing progression included malignancy as a comorbidity, anti-SS-A antibodies, and post-exercise pulse increase at 6MWT. Antifibrotic therapy was administered significantly more often in IPAF as compared to CTD-ILD patients (n = 13, 29.5% vs. n = 5, 7.9%; p = 0.007), and importantly, this treatment reduced lung function decline when compared to non-treated patients. Majority of patients improved or were stable regarding lung function, and autoimmune-associated PF-ILD was more common in patients having IPAF. Functional decline predictors were anti-SS-A antibodies and marked post-exercise pulse increase at 6MWT. Antifibrotic treatments reduced progression in progressive fibrosing CTD-ILD and IPAF, emphasizing the need for guidelines including optimal treatment start and combination therapies in this special patient group.
