Chest
Volume 147, Issue 1, January 2015, Pages 157-164
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Original Research: Diffuse Lung Disease
The Impact of Lung Cancer on Survival of Idiopathic Pulmonary Fibrosis

https://doi.org/10.1378/chest.14-0359Get rights and content

BACKGROUND

Lung cancer (LC) is frequently associated with idiopathic pulmonary fibrosis (IPF). Despite this well-known association, the outcome of LC in patients with IPF is unclear. The objective of this study was to evaluate the impact of LC on survival of patients with associated IPF.

METHODS

A total of 260 patients with IPF were reviewed, and 186 IPF cases had complete clinical and follow-up data. Among these, five cases were excluded because LC was radiologically suspected but not histologically proven. The remaining 181 cases were categorized in two groups: 23 patients with biopsy-proven LC and IPF (LC-IPF) and 158 patients with IPF only (IPF). Survival and clinical characteristics of the two groups were compared.

RESULTS

Prevalence of histologically proven LC was 13%, and among those with LC-IPF cumulative incidence at 1 and 3 years was 41% and 82%. Patients with LC were more frequently smokers (91.3% vs 71.6%, P = .001), with combined pulmonary fibrosis and emphysema (52% vs 32%, P = .052). Survival in patients with LC-IPF was significantly worse than in patients with IPF without LC (median survival, 38.7 months vs 63.9 months; hazard ratio = 5.0; 95% CI, 2.91-8.57; P < .001). Causes of death in the study group were respiratory failure in 43% of patients, LC progression in 13%, and LC treatment-related complications in 17%.

CONCLUSIONS

In patients with IPF, LC has a significant adverse impact on survival. Diagnosis and treatment of LC in IPF are burdened by an increased incidence of severe complicating events, apparently as lethal as the cancer itself.

Section snippets

Materials and Methods

This study was approved by the Area Vasta Romagna Review Board, Italy (#2614/2010). Systematic search of the patient database revealed 260 patients who satisfied the current diagnostic criteria for IPF17 seen at Pulmonary Unit, G. B. Morgagni Hospital, Forlì, Italy, during the period of January 1, 2000 to March 31, 2012. We selected 186 patients diagnosed with IPF and then followed at our institution according to a prospective protocol of clinical management that include one annual HRCT scan

Statistical Methods

Patient demographics and characteristics were compared using the two-sample rank-sum test for continuous variables and the χ2 (exact) test for categorical variables. Cumulative time-to-event distributions (survival, progression, AE) were estimated using the Kaplan-Meier method. Time-to-event outcomes were compared between the LC and non-LC groups using time-dependent proportional hazards regression models. In all cases, P values < .05 were considered statistically significant.

Patient Characteristics

Among 181 patients with IPF followed at our institution, we found 23 patients with LC-IPF (13%). Among the 23 patients with LC-IPF, seven (30%) were diagnosed as having primary pulmonary LC at the same time of IPF diagnosis. The other 16 patients (70%) developed LC 18.5 ± 23.8 months (median, 30 months; range, −27.5-84.1 months) after diagnosis of IPF during the observational period. All cases of LC were incidental findings, except for one symptomatic patient with back pain due to a vertebral

Pathology Findings

Eighty-eight patients (48.6%) had histologically proven definite UIP pattern on surgical lung biopsy (n = 84) or lung resection for LC (n = 4). The most frequently encountered histologic types of carcinomas were peripheral squamous cell (n = 9, 39%) and adenocarcinomas (n = 8, 35%). Small-cell LC was encountered for three cases (13%) and in one case was diagnosed a rare lymphoepithelioma-like large-cell LC. The remaining two cases were mixed tumor (small-cell LC with adenocarcinoma and squamous

LC Staging

Case distribution according to LC stage is reported in Figure 2. All early-stage LC (stage I, nine cases, 39%) were incidentally detected with annual HRCT scan follow-up for IPF.

LC Treatment

LC treatment according to LC TNM staging and IPF severity (gender, age, and physiology [GAP] index) is reported in Figure 2. Surgery for early LCs consisted of four lobectomies and three sublobar resections. Five patients (two lobectomies, two sublobar resections, one radiofrequency ablation) experienced a recurrence of LC after a median follow-up of 16 months (range, 13-28 months). Six of seven patients who were operated on died; survival after surgery was 20 months (1-36 months). Among four

Survival

Survival curve of patients with IPF with and without LC is displayed in Figure 3. In the group of patients with LC-IPF, 18 (78.3%) died, median survival was 38.7 months. Among the 158 patients with IPF without LC, 69 (43.7%) died (median survival, 63.9 months), and 14 (8.9%) underwent lung transplantation. One-and 3-year survivals among the two groups were 78% and 52% in the LC-IPF group and 92% and 70% in the IPF group, respectively. There was a significant difference in survival between the

Progression of IPF

Median follow-up duration was 16.2 months (range, 6.5-72.4 months) in the LC-IPF group and 40.2 months (range, 7.0-124.1 months) in the IPF group. During the follow-up period, 13 patients among 23 with LC (56.5%) and 109 among 158 without LC (69%) experienced disease progression, as previously defined. Median time-to-disease progression was 20.3 months in the LC-IPF group and 21.4 months in the IPF group. There was not a significant difference in progression-free survival between the two groups

AE of IPF

Among 61 patients experiencing AE-IPF, five were in the LC-IPF group (21.7%), and 56 were in the IPF group (35.4%). Mortality for AE was 80% (four of five) and 78.6% (44 of 56) in LC-IPF and IPF-only, respectively. In patients with LC-IPF, the AEs were triggered by medical procedure/treatment of LC in four cases (80%): two chemotherapy (of 12 patients treated, 16.7%), one lobectomy (of four lobectomies, 25%), one transbronchial biopsy (of 20, 5%).

Discussion

This study shows that in patients with IPF, LC has a significantly adverse impact on survival. Diagnosis and treatment of LC in IPF are burdened by an increased incidence of severe complicating events, apparently as lethal as the LC itself.

Including only cases with biopsy-proven LC, the prevalence of LC in our cohort of patients is 13%. Even though the suspicion of LC was high, clinicians decided not to biopsy the 3% of cases. The difficult clinical decision of declining the biopsy is driven by

Conclusions

We found a poorer survival of patients with IPF developing LC, mainly due to LC progression, and to complications of treatment. Diagnosis and treatment of LC in IPF are burdened by an increased incidence of severe complicating events, apparently as lethal as the cancer itself. Lobectomy and chemotherapy have a high incidence of lethal complicating events and their indiscriminate use in patients with LC-IPF is questionable.

Acknowledgments

Author contributions: All authors have provided final approval of the version to be published and have agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. V. P. confirms that the study objectives and procedures are honestly disclosed. Moreover, he has reviewed study execution data and confirms that procedures were followed to an extent that convinces all authors

References (32)

  • H Matsushita et al.

    Lung cancer associated with usual interstitial pneumonia

    Pathol Int

    (1995)
  • M Turner-Warwick et al.

    Cryptogenic fibrosing alveolitis and lung cancer

    Thorax

    (1980)
  • Y Ozawa et al.

    Cumulative incidence of and predictive factors for lung cancer in IPF

    Respirology

    (2009)
  • K Usui et al.

    The prevalence of pulmonary fibrosis combined with emphysema in patients with lung cancer

    Respirology

    (2011)
  • M Chilosi et al.

    Epithelial stem cell exhaustion in the pathogenesis of idiopathic pulmonary fibrosis

    Sarcoidosis Vasc Diffuse Lung Dis

    (2010)
  • C Vancheri

    Common pathways in idiopathic pulmonary fibrosis and cancer

    Eur Respir Rev

    (2013)
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    Drs Tomassetti and Gurioli contributed equally.

    Part of this article was presented at the ERS Annual Congress, September 24-28, 2011, Amsterdam, The Netherlands.

    FUNDING/SUPPORT: This study was supported by Associazione Morgagni per le Malattie Polmonari (AMMP).

    Reproduction of this article is prohibited without written permission from the American College of Chest Physicians. See online for more details.

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