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Original Research: Diffuse Lung Disease |

The Impact of Lung Cancer on Survival of Idiopathic Pulmonary FibrosisLung Cancer and Idiopathic Pulmonary Fibrosis FREE TO VIEW

Sara Tomassetti, MD; Christian Gurioli, MD; Jay H. Ryu, MD, FCCP; Paul A. Decker, MS; Claudia Ravaglia, MD; Paola Tantalocco, BME; Matteo Buccioli, BME; Sara Piciucchi, MD; Nicola Sverzellati, MD; Alessandra Dubini, MD; Giampaolo Gavelli, MD; Marco Chilosi, MD; Venerino Poletti, MD, FCCP
Author and Funding Information

From the Department of Diseases of the Thorax (Drs Tomassetti, Gurioli, Ravaglia, Tantalocco, Buccioli, and Poletti), G. B. Morgagni Hospital, Forlì, Italy; Division of Pulmonary and Critical Care Medicine (Dr Ryu) and Biomedical Statistics and Informatics (Mr Decker), Mayo Clinic, Mayo Foundation for Medical Education and Research, Rochester, MN; Department of Radiology (Dr Piciucchi), G. B. Morgagni Hospital, Forlì, Italy; Department of Radiology (Dr Sverzellati), Parma University, Parma, Italy; Department of Pathology (Dr Dubini), G. B. Morgagni Hospital, Forlì, Italy; and Department of Radiology (Dr Gavelli), Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (Istituto di Ricovero e Cura a Carattere Scientifico), Meldola (Forlì), and Department of Pathology (Dr Chilosi), Verona University, Verona, Italy.

CORRESPONDENCE TO: Venerino Poletti, MD, FCCP, U. O. Pneumologia, G. B. Morgagni Hospital, Via C. Forlanini 34, 47100 Forlì (FC), Italy; e-mail: venerino.poletti@gmail.com


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.


Chest. 2015;147(1):157-164. doi:10.1378/chest.14-0359
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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.

Figures in this Article

Idiopathic pulmonary fibrosis (IPF) is a form of chronic progressive interstitial pneumonia with a median survival of 3 to 5 years. The incidence of lung cancer (LC) is markedly increased among patients with IPF ranging from 4.4% to 48%.13 The only retrospective study estimating the cumulative incidence of LC in IPF shows 3.3%, 15.4%, and 54.7% incidences of LC, respectively, after 1, 5, and 10 years of follow-up for IPF.4 A higher incidence of LC has been described in older male smokers and in patients with combined pulmonary fibrosis and emphysema (CPFE),5 in which emphysema shares with IPF and cancer possible pathogenetic links.69 High-resolution CT (HRCT) scan studies have clearly shown that LC arises in the peripheral area of fibrotic lesions and that LC pathology in IPF is peculiar, showing a prevalence of peripheral squamous cell carcinomas or “enteric” adenocarcinoma.1014 Despite large retrospective studies that have compared LC profiles in patients with and without IPF,15,16 the impact of LC on prognosis of patients with IPF is currently unclear; current guidelines discourage LC surveillance in these patients.17 However, there is growing evidence that treating LC in patients with IPF might be indicated, especially at an early stage of LC and in selected patients with an appropriate level of functional impairment.1822 It is still debated whether patients at inoperable stages of LC or postoperative recurrence of cancer could be potential candidates for radiation therapy or chemotherapy. At present, there is neither evidence nor consensus with regard to whether aggressive approaches are appropriate for a noncurative treatment strategy of LC in patients with IPF.2329 It was within this context that we sought to define the outcome for patients with primary pulmonary carcinoma and IPF, and to address whether LC therapy as used in our current clinical practice is associated with any benefit.

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 and pulmonary function tests every 4 months. Among them, five cases were excluded because they were not histologically proven (invasive procedures were not performed due to advanced age and poor general conditions). The remaining 181 cases were categorized in two groups: 23 patients with biopsy-proven LC and IPF (LC-IPF group) and 158 patients with IPF only (IPF group). Sporadic and familial forms of IPF were defined by criteria outlined in current guidelines.17 Acute exacerbation (AE) was defined as acute respiratory worsening for which a cause could not be identified and meeting all criteria for as proposed by Collard et al.30 Survival analyses were performed in all cases from the time of IPF presentation.

LCs were classified according to the World Health Organization classification. Staging of LC has been established by the TNM system current at the time of diagnosis. Side effects of treatments were assessed using the National Cancer Institute Common Toxicities Criteria (NCI-CTC version 3.0). Evaluation of tumor response to chemotherapy was assessed according to the Response Evaluation Criteria in Solid Tumors (RECIST) criteria (version 1.1).31 Operative mortality and mortality related to oncologic treatment were defined as death occurring within 30 days of treatment. Vital status and date of death were verified using phone calls, public records review, Italian death registry review, and review of subsequent patient visits.

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 metastasis of primary lung adenocarcinoma. Cumulative incidence is shown in Figure 1. Clinical and BAL findings in the 181 patients with IPF grouped according to the presence or absence of LC are detailed in Table 1.

Figure Jump LinkFigure 1 –  Cumulative incidence curve of lung cancer in patients with idiopathic pulmonary fibrosis with lung cancer. The cumulative incidence of lung cancer at 1 y and 3 y was 40.9% and 81.8%, respectively, by Kaplan-Meier analysis.Grahic Jump Location
Table Graphic Jump Location
TABLE 1 ]  Baseline Characteristics of the Patients at Time of IPF Diagnosis

Dlco = diffusing capacity of the lung for carbon monoxide; GAP = gender, age, and physiology; HRCT = high-resolution CT; IPF = idiopathic pulmonary fibrosis; LTOT = long-term oxygen treatment; SLB = surgical lung biopsy; UIP = usual interstitial pneumonia.

HRCT Scan Findings

Among the entire cohort of 181 patients with IPF, 94 (52%) showed a “definite UIP” pattern on HRCT scan, with an equal distribution between LC cases and control subjects. The median extent of fibrosis seen on the HRCT scan performed at the time of diagnosis of IPF was 50% (20%-80%) of the total lung parenchyma, with no difference between those with and without LC. CPFE was identified in 12 patients (52%) with primary LC and in 50 patients without LC (32%; P = .052). Median extent of emphysema in the two groups was 35% (range, 10%-50%) and 20% (5%-80%), respectively. HRCT scan characteristics of background parenchyma in which LC arose are reported in Table 2.

Table Graphic Jump Location
TABLE 2 ]  HRCT Scan Characteristics of Lung Carcinomas in Patients With IPF

Radiologists evaluated the background in which lung cancer arose classifying it as follows: fibrotic background (reticular distortion, ground-glass opacity, honeycombing), normal lung, emphysema. See Table 1 legend for expansion of abbreviations.

a 

Tumor was considered central when located in an area 3 cm far from the pleura.

b 

The background was not recorded in one case of squamous cell carcinoma with only bronchial wall involvement.

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 with large-cell LC).

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.

Figure Jump LinkFigure 2 –  LC treatment according to LC stage and idiopathic pulmonary fibrosis severity. GAP = gender, age, and physiology; LC = lung cancer.Grahic Jump Location
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 lobectomies, one patient died 15 days after lobectomy of AE of IPF. Another complication was the late occurrence of persistent pneumothorax in one case of sublobar resection and in one case of radiofrequency ablation; both cases resolved after chest-tube drainage.

Chemotherapy treatment and related complications are reported in Table 3. Among nine patients treated with chemotherapy only, eight patients died with a median survival 8.5 months (range, 4-24 months).

Table Graphic Jump Location
TABLE 3 ]  Chemotherapy Treatment and Related Complications

ADK = adenocarcinoma; AE = acute exacerbation; NSCLC = non-small-cell lung cancer; SCLC = small-cell lung cancer; SQ = squamous. See Table 1 legend for expansion of other abbreviations.

a 

Sex and age.

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 two groups (unadjusted hazard ratio [HR] = 5.0; 95% CI, 2.91-8.57; P < .001) (Fig 3). After adjusting for age, sex, smoking status, % predicted diffusing capacity of the lung for carbon monoxide (Dlco), and % predicted FVC, the HR was 7.0 (95% CI, 3.81-12.90; P < .001). To avoid the bias related to the imbalance of CPFE prevalence in the two groups, we adjusted survival for sex, pack-years, Dlco, and composite physiologic index (CPI) in a separate model. Results did not change with reanalysis (adjusted HR = 6.21; 95% CI, 2.88-13.41; P < .001).

Figure Jump LinkFigure 3 –  Survival curve of patients with IPF with and without LC (time 0 is diagnosis of IPF for both groups). One-y and 3-y survival among the two groups were 78% and 52% in the study group and 92% and 70% in the control group, respectively, by Kaplan-Meier analysis. IPF = idiopathic pulmonary fibrosis. See Figure 2 legend for expansion of other abbreviation.Grahic Jump Location

Comparing survival between the 28 cases of LC (five possible and 23 histologically proven) to the 158 control subjects, the significant difference remained unchanged (unadjusted HR = 5.08; 95% CI, 3.07-8.38; P < .001). Survival analysis adjusted for sex, pack-years, Dlco, FVC HR = 6.35 (95% CI, 3.64-11.05; P < .001); adjusted for sex, pack-years, Dlco, CPI, HR = 5.97 (95% CI, 3.12-11.44; P < .001).

In the LC-IPF group, 10 patients died of respiratory failure related to IPF (43%). Three patients died of LC progression (13%). Four patients (17%) died of lethal complications related to LC diagnosis and treatment (one after bronchoscopy, one after lobectomy, and two after chemotherapy). One patient died of myocardial infarction.

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 (Fig 4) (HR = 1.37; 95% CI, 0.63-2.97; P = .43). After adjusting for age, sex, smoking status, % predicted Dlco, and % predicted FVC, there was no difference (HR = 1.45; 95% CI, 0.66-3.17; P = .36). Moreover, after adjusting progression for sex, pack-years, Dlco, and CPI, results did not change (HR = 1.61; 95% CI, 0.67-3.87; P = .29).

Figure Jump LinkFigure 4 –  IPF rate of disease progression in patients with and without LC (time 0 is diagnosis of IPF for both groups). Median time to disease progression was 20.3 mo in the study group and 21.4 mo in the control group. There was not a significant difference in progression-free survival between the two groups. See Figure 2 and 3 legends for expansion of abbreviation.Grahic Jump Location

Comparing progression-free survival between the 28 cases of LC (five possible and 23 histologically proven) to the 158 control subjects results did not change (unadjusted HR = 1.64 [95% CI, 0.85-3.16; P = .14]; adjusted HR for sex, pack-years, Dlco, FVC = 1.77 [95% CI, 0.91-3.43; P = .091]; adjusted HR for sex, pack-years, Dlco, CPI = 1.93 [95% CI, 0.94-3.97; P = .074]).

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%).

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 several reasons, the age and poor condition of these patients, the risk of invasive diagnosis, and the uncertainty of what benefit we can offer after a biopsy-proven diagnosis of LC in IPF setting. After the study published by Osawa et al,4 this is the second report documenting that cumulative incidence of LC increases remarkably over time after the initial diagnosis of IPF. The cumulative incidence at 1 and 3 years reported in our study is significantly higher compared with what previously reported. Osawa et al compared LC-IPF and IPF-only and showed a median survival of 120 months and 104 months, whereas we observed a median survival of 38.7 months and 63.9 months, respectively, which is consistent with the previously reported survival rate for IPF.17,32

The results of this study confirm previous findings about clinical, radiologic, and pathologic characteristics of LC in IPF. Smoking history is associated with a higher risk of LC, and emphysema combined with pulmonary fibrosis is confirmed to be a specific setting in which the incidence of LC is increased. This study shows that LC in IPF arises in peripheral areas of fibrosis, and the presence of a typical usual interstitial pneumonia-HRCT scan appearance does not influence the risk of developing LC. While acknowledging the limited number cases, we report here for the first time that the prevalence of familial IPF is similar in patients with IPF with and without LC. All these clinical, radiologic, and pathologic findings are in-line with current pathogenetic hypotheses that consider IPF and COPD diseases of premature aging with several links to LC biology.616

It is worth noting that in this study, we clearly show for the first time a statistically significant difference in survival of patients with LC-IPF compared with IPF only, with an adjusted HR of 7 (95% CI, 3.81-12.90; P < .001). We rigorously examined IPF progression according to cancer status. Possible concerns about the small size of the LC cohort are alleviated by the remarkably similar rate of disease progression. Interestingly, our data show for the first time, to our knowledge, that the difference in mortality seen in our study was not due to worsening of pulmonary fibrosis, but mainly to both LC progression and complications of LC treatment. We observed that 80% of AEs in patients with LC were triggered by treatments or diagnostic procedures for LC; this risk makes clinical decisions about LC management in IPF particularly difficult.

Therapeutic decisions were influenced by the severity of IPF and the LC stage. The majority of our patients with stage I LC and mild IPF underwent surgery. Patients with advanced LC were equally treated with chemotherapy or best supportive care only, irrespective of IPF severity. We believe that this heterogeneity in treatment of advanced LC reflects clinicians’ uncertainty in the outcome of this lethal combination of diseases. Thus, when it comes to suggested chemotherapy or radiotherapy for advanced LC the decision seems more arbitrary and probably more influenced by the patient’s point of view.

Many studies tried to explore the impact of surgical resection of LC in patients with IPF. Early postoperative mortality ranges from 0% to 18.2% and postoperative morbidity ranges from 7.1% to 40.7% of patients with IPF.1822 In line with previous findings, our results show unacceptable risk of AE of IPF in patients submitted to lobectomy (25%), whereas sublobar resection seems acceptable (none of our patients submitted to sublobar resection experienced fatal complications). Four of six patients had recurrence of LC during follow-up and the real benefit of surgical resection remains unclear and novel less-invasive treatment of LC, such as thermoablation or cryoablation, should be investigated in future trials.

With the intention to treat LC in patients with IPF in a minimally invasive way, early detection of lung nodules, especially in mild-moderate IPF, might be useful. In our series, all stage I LC were asymptomatic and were detected with annual follow-up HRCT scan. We are tempted to say that follow-up with HRCT scan may be useful for LC screening in these patients, but we acknowledge that before discussing the utility of HRCT scan we have to prove with larger studies that timely treatment of LC is of real benefit in patients with IPF.

Chemotherapy does not seem to be a safe alternative. Six of 12 patients experienced severe complications (41%), and two of 12 were fatal (16%). AE occurred in two patients and was fatal in one. Our data are in-line with previous reports of systemic treatment used in patients with LC and IPF, where the incidence of treatment-related AE ranges between 12.5% and 30% and mortality of treatment-related AE ranges between 9% and 16%.2529 In accordance with previously published studies, our data show a median survival of 8.5 months from diagnosis of LC in patients with stage III/IV treated with chemotherapy. Reported median survival for LC in IPF treated with chemotherapy is 7 to 11 months.2529

We recognize the retrospective, single-center design of this study and the limited number of patients in the study group as important limitations. The optimal management of LC in patients with IPF needs to be addressed in large collaborative prospective multicentric studies.

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.

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 that the results are valid and generalizable to a population similar to that enrolled in this study. S. T., C. G., J. H. R., and P. A. D. contributed to the draft of the submitted article, revised it critically for important content, and made substantial contributions to conception and design, as well as data acquisition, analysis, and interpretation; C. R., P. T., and M. B. contributed to the draft of the submitted article and made substantial contributions to acquisition, analysis, and interpretation of data; S. P., N. S., and G. G. contributed to the draft of the submitted article and made substantial contributions to acquisition, analysis, and interpretation of radiologic data; A. D. and M. C. contributed to the draft of the submitted article and made substantial contributions to acquisition, analysis, and interpretation of pathology data; and V. P. contributed substantially to conception, design, and interpretation of data, and critically revised the submitted article for important content.

Financial/nonfinancial disclosures: The authors have reported to CHEST the following conflicts of interest: Dr Poletti is a member of the advisory committee for InterMune. Drs Tomassetti, Gurioli, Ryu, Ravaglia, Tantalocco, Buccioli, Piciucchi, Sverzellati, Dubini, Gavelli, and Chilosi and Mr Decker have reported that no potential conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article.

Role of sponsors: The sponsor covered publication costs.

AE

acute exacerbation

CPFE

combined pulmonary fibrosis and emphysema

CPI

composite physiologic index

Dlco

diffusing capacity of the lung for carbon monoxide

HR

hazard ratio

HRCT

high-resolution CT

IPF

idiopathic pulmonary fibrosis

LC

lung cancer

UIP

usual interstitial pneumonia

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Watanabe N, Taniguchi H, Kondoh Y, et al. Efficacy of chemotherapy for advanced non-small cell lung cancer with idiopathic pulmonary fibrosis. Respiration. 2013;85(4):326-331. [CrossRef] [PubMed]
 
Kenmotsu H, Naito T, Kimura M, et al. The risk of cytotoxic chemotherapy-related exacerbation of interstitial lung disease with lung cancer. J Thorac Oncol. 2011;6(7):1242-1246. [CrossRef] [PubMed]
 
Collard HR, Moore BB, Flaherty KR, et al; Idiopathic Pulmonary Fibrosis Clinical Research Network Investigators. Acute exacerbations of idiopathic pulmonary fibrosis. Am J Respir Crit Care Med. 2007;176(7):636-643. [CrossRef] [PubMed]
 
Eisenhauer EA, Therasse P, Bogaerts J, et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009;45(2):228-247. [CrossRef] [PubMed]
 
Ley B, Ryerson CJ, Vittinghoff E, et al. A multidimensional index and staging system for idiopathic pulmonary fibrosis. Ann Intern Med. 2012;156(10):684-691. [CrossRef] [PubMed]
 

Figures

Figure Jump LinkFigure 1 –  Cumulative incidence curve of lung cancer in patients with idiopathic pulmonary fibrosis with lung cancer. The cumulative incidence of lung cancer at 1 y and 3 y was 40.9% and 81.8%, respectively, by Kaplan-Meier analysis.Grahic Jump Location
Figure Jump LinkFigure 2 –  LC treatment according to LC stage and idiopathic pulmonary fibrosis severity. GAP = gender, age, and physiology; LC = lung cancer.Grahic Jump Location
Figure Jump LinkFigure 3 –  Survival curve of patients with IPF with and without LC (time 0 is diagnosis of IPF for both groups). One-y and 3-y survival among the two groups were 78% and 52% in the study group and 92% and 70% in the control group, respectively, by Kaplan-Meier analysis. IPF = idiopathic pulmonary fibrosis. See Figure 2 legend for expansion of other abbreviation.Grahic Jump Location
Figure Jump LinkFigure 4 –  IPF rate of disease progression in patients with and without LC (time 0 is diagnosis of IPF for both groups). Median time to disease progression was 20.3 mo in the study group and 21.4 mo in the control group. There was not a significant difference in progression-free survival between the two groups. See Figure 2 and 3 legends for expansion of abbreviation.Grahic Jump Location

Tables

Table Graphic Jump Location
TABLE 1 ]  Baseline Characteristics of the Patients at Time of IPF Diagnosis

Dlco = diffusing capacity of the lung for carbon monoxide; GAP = gender, age, and physiology; HRCT = high-resolution CT; IPF = idiopathic pulmonary fibrosis; LTOT = long-term oxygen treatment; SLB = surgical lung biopsy; UIP = usual interstitial pneumonia.

Table Graphic Jump Location
TABLE 2 ]  HRCT Scan Characteristics of Lung Carcinomas in Patients With IPF

Radiologists evaluated the background in which lung cancer arose classifying it as follows: fibrotic background (reticular distortion, ground-glass opacity, honeycombing), normal lung, emphysema. See Table 1 legend for expansion of abbreviations.

a 

Tumor was considered central when located in an area 3 cm far from the pleura.

b 

The background was not recorded in one case of squamous cell carcinoma with only bronchial wall involvement.

Table Graphic Jump Location
TABLE 3 ]  Chemotherapy Treatment and Related Complications

ADK = adenocarcinoma; AE = acute exacerbation; NSCLC = non-small-cell lung cancer; SCLC = small-cell lung cancer; SQ = squamous. See Table 1 legend for expansion of other abbreviations.

a 

Sex and age.

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Kenmotsu H, Naito T, Kimura M, et al. The risk of cytotoxic chemotherapy-related exacerbation of interstitial lung disease with lung cancer. J Thorac Oncol. 2011;6(7):1242-1246. [CrossRef] [PubMed]
 
Collard HR, Moore BB, Flaherty KR, et al; Idiopathic Pulmonary Fibrosis Clinical Research Network Investigators. Acute exacerbations of idiopathic pulmonary fibrosis. Am J Respir Crit Care Med. 2007;176(7):636-643. [CrossRef] [PubMed]
 
Eisenhauer EA, Therasse P, Bogaerts J, et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009;45(2):228-247. [CrossRef] [PubMed]
 
Ley B, Ryerson CJ, Vittinghoff E, et al. A multidimensional index and staging system for idiopathic pulmonary fibrosis. Ann Intern Med. 2012;156(10):684-691. [CrossRef] [PubMed]
 
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