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Abstract An 84‐year‐old man with a history of progressive interstitial pneumonia presented to our department with lung cancer (cT2aN0M0‐IB) in right S6. Moreover, computed tomography revealed progressive diffuse pulmonary ossification in the bilateral lower pulmonary lobes. S6 segmentectomy was performed via video‐assisted thoracoscopic surgery. It was difficult to divide the intersegmental plane using a stapler because of severe fibrosis and pulmonary ossification with bone marrow formation. Pulmonary ossification may be an important finding for surgical planning because of severe fibrosis or inflammation associated with severe lung condition. We suggest that the surgical indications and approaches for such cases should be reconsidered because pulmonary ossification can be associated with severe lung conditions.

An 84‐year‐old man with a history of progressive interstitial pneumonia presented to our department with lung cancer (cT2aN0M0‐IB) in right S6. Moreover, computed tomography revealed progressive diffuse pulmonary ossification in the bilateral lower pulmonary lobes. S6 segmentectomy was performed via video‐assisted thoracoscopic surgery. It was difficult to divide the intersegmental plane using a stapler because of severe fibrosis and pulmonary ossification with bone marrow formation. Pulmonary ossification may be an important finding for surgical planning because of severe fibrosis or inflammation associated with severe lung condition. We suggest that the surgical indications and approaches for such cases should be reconsidered because pulmonary ossification can be associated with severe lung conditions. [ABSTRACT FROM AUTHOR]

Abstract Background The S100 calcium‐binding protein A4 (S100A4) and the accumulation of [18F]‐fluoro‐2‐deoxy‐D‐glucose (FDG) in noncancerous interstitial pneumonia (IP) area are predictors of postoperative acute exacerbation (AE) of IP after pulmonary resection for lung cancer with IP. However, the significance of combining these markers for predicting short‐term outcome and long‐term prognosis is not known. Methods Patients diagnosed with IP on preoperative high‐resolution computed tomography and who had undergone pulmonary resection for primary lung cancer between April 2010 and March 2019 at Hiroshima University were included in this study. Predictive factors for the cumulative incidence of death from other than lung cancer (CIDOL) were investigated using the Fine and Gray model. CIDOL, perioperative outcome, and cumulative incidence of all death (CIAD) were retrospectively compared based on serum S100A4 and FDG accumulation. Results A total of 121 patients were included in this study. High S100A4 (hazard ratio [HR], 2.541; p = 0.006) and FDG accumulation (HR, 3.199; p = 0.038) were significant predictors of CIDOL. AE of IP occurred only in patients with high S100A4/FDG (+). CIDOL of patients with high S100A4/FDG (+) was higher than those with high S100A4/FDG (−) or low S100A4/FDG (+) (p

Background: The S100 calcium‐binding protein A4 (S100A4) and the accumulation of [18F]‐fluoro‐2‐deoxy‐D‐glucose (FDG) in noncancerous interstitial pneumonia (IP) area are predictors of postoperative acute exacerbation (AE) of IP after pulmonary resection for lung cancer with IP. However, the significance of combining these markers for predicting short‐term outcome and long‐term prognosis is not known. Methods: Patients diagnosed with IP on preoperative high‐resolution computed tomography and who had undergone pulmonary resection for primary lung cancer between April 2010 and March 2019 at Hiroshima University were included in this study. Predictive factors for the cumulative incidence of death from other than lung cancer (CIDOL) were investigated using the Fine and Gray model. CIDOL, perioperative outcome, and cumulative incidence of all death (CIAD) were retrospectively compared based on serum S100A4 and FDG accumulation. Results: A total of 121 patients were included in this study. High S100A4 (hazard ratio [HR], 2.541; p = 0.006) and FDG accumulation (HR, 3.199; p = 0.038) were significant predictors of CIDOL. AE of IP occurred only in patients with high S100A4/FDG (+). CIDOL of patients with high S100A4/FDG (+) was higher than those with high S100A4/FDG (−) or low S100A4/FDG (+) (p < 0.001), and CIAD of patients with high S100A4/FDG (+) was also higher than those with high S100A4/FDG (−) or low S100A4/FDG (+) patients (p = 0.021). Conclusions: Serum S100A4 and FDG accumulation in the noncancerous IP area were significant predictors of CIDOL after lung resection for lung cancer with IP and may help decide the treatment strategy. [ABSTRACT FROM AUTHOR]

Abstract Background We conducted a phase II study of carboplatin plus nab‐paclitaxel for the treatment of small cell lung cancer (SCLC) after the failure of a prior standard chemotherapy containing platinum, etoposide, irinotecan, and amrubicin if indicated. Patients with interstitial pneumonia complications were included in the study. Methods Patients received 100 mg/m2 of nab‐paclitaxel weekly (on days 1, 8, and 15) and an AUC 5 of carboplatin on day 1. The study treatment was repeated every 3 weeks until disease progression or the appearance of unacceptable toxicities. The primary endpoint was the objective response rate. Results A total of 21 patients were enrolled, all of whom were eligible for inclusion in the analysis. Twelve patients had pre‐existing interstitial pneumonia. The overall response rate was 19.0% (90% confidence interval [CI]: 6.8%–38.4%). The lower limit of the 90% CI for the response rate did not exceed the prespecified threshold value of 10%. Among the 12 patients with pre‐existing interstitial pneumonia, the response rate was 25%. The median progression‐free survival time was 2.5 months (95% CI: 1.5–3.4 months), and the median survival time was 5.1 months (95% CI: 2.1–8.1 months). Two patients developed interstitial lung disease; both of these patients had pre‐existing interstitial pneumonia. One of the patients died from interstitial lung disease. Conclusion Combination chemotherapy with carboplatin plus nab‐paclitaxel for recurrent SCLC had a modest activity, although the primary study endpoint was not met. Further investigation of this regimen for patients with recurrent SCLC and interstitial pneumonia is warranted.

Abstract Background The safety profile of systemic chemotherapy for lung cancer patients with interstitial pneumonia (IP) in clinical practice remains unclear. Using Diagnostic Procedure Combination (DPC) data from the Japanese administrative database, we investigated the mortality of hospitalized lung cancer patients with IP as they underwent a course of systemic chemotherapy nationwide. Methods The DPC data of patients with stage IIIB or IV lung cancer as defined by the Union for International Cancer Control Tumor‐Nodes‐Metastases 6th and 7th editions from April 2014 to March 2016 were obtained. Among those patients, only patients with concomitant IP and receiving systemic chemotherapy without radiotherapy were included. Results Among 1524 included patients, 70 (4.6%) died in the hospital. Multivariate analysis revealed that low activities of daily living (ADL) scores on admission (hazard ratio [HR] 2.26, 95% confidence interval [CI] 1.24–4.12, p = 0.008) and high‐dose corticosteroid therapy following chemotherapy (HR 2.62, 95% CI 1.44–4.77, p = 0.002) were strongly associated with in‐hospital mortality. It was determined that patients possibly received high‐dose corticosteroids for IP exacerbations; these patients had a higher in‐hospital mortality rate of 67.7% (21/31 patients) and a significantly shorter median survival time of 55 days (95% CI 31–69 days, p

Abstract Pulmonary pleomorphic carcinoma is often refractory to chemotherapy and follows an aggressive clinical course. Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of advanced lung cancer, and a few cases with pleomorphic carcinoma have been reported to show tumor shrinkage after therapy with ICIs. When treating patients with ICIs, patient selection is essential, and monitoring and management of immune‐related adverse events, including pneumonitis, are needed. We herein report a case of pulmonary pleomorphic carcinoma with preexisting interstitial pneumonia treated with pembrolizumab, antiprogrammed cell death 1 antibody. Our report highlights important considerations necessary when treating advanced pleomorphic carcinoma patients complicated with interstitial pneumonia. We also review the literature regarding the use of ICIs in such patients.

Background: We conducted a phase II study of carboplatin plus nab‐paclitaxel for the treatment of small cell lung cancer (SCLC) after the failure of a prior standard chemotherapy containing platinum, etoposide, irinotecan, and amrubicin if indicated. Patients with interstitial pneumonia complications were included in the study. Methods: Patients received 100 mg/m2 of nab‐paclitaxel weekly (on days 1, 8, and 15) and an AUC 5 of carboplatin on day 1. The study treatment was repeated every 3 weeks until disease progression or the appearance of unacceptable toxicities. The primary endpoint was the objective response rate. Results: A total of 21 patients were enrolled, all of whom were eligible for inclusion in the analysis. Twelve patients had pre‐existing interstitial pneumonia. The overall response rate was 19.0% (90% confidence interval [CI]: 6.8%–38.4%). The lower limit of the 90% CI for the response rate did not exceed the prespecified threshold value of 10%. Among the 12 patients with pre‐existing interstitial pneumonia, the response rate was 25%. The median progression‐free survival time was 2.5 months (95% CI: 1.5–3.4 months), and the median survival time was 5.1 months (95% CI: 2.1–8.1 months). Two patients developed interstitial lung disease; both of these patients had pre‐existing interstitial pneumonia. One of the patients died from interstitial lung disease. Conclusion: Combination chemotherapy with carboplatin plus nab‐paclitaxel for recurrent SCLC had a modest activity, although the primary study endpoint was not met. Further investigation of this regimen for patients with recurrent SCLC and interstitial pneumonia is warranted. [ABSTRACT FROM AUTHOR]

Background: The safety profile of systemic chemotherapy for lung cancer patients with interstitial pneumonia (IP) in clinical practice remains unclear. Using Diagnostic Procedure Combination (DPC) data from the Japanese administrative database, we investigated the mortality of hospitalized lung cancer patients with IP as they underwent a course of systemic chemotherapy nationwide. Methods: The DPC data of patients with stage IIIB or IV lung cancer as defined by the Union for International Cancer Control Tumor‐Nodes‐Metastases 6th and 7th editions from April 2014 to March 2016 were obtained. Among those patients, only patients with concomitant IP and receiving systemic chemotherapy without radiotherapy were included. Results: Among 1524 included patients, 70 (4.6%) died in the hospital. Multivariate analysis revealed that low activities of daily living (ADL) scores on admission (hazard ratio [HR] 2.26, 95% confidence interval [CI] 1.24–4.12, p = 0.008) and high‐dose corticosteroid therapy following chemotherapy (HR 2.62, 95% CI 1.44–4.77, p = 0.002) were strongly associated with in‐hospital mortality. It was determined that patients possibly received high‐dose corticosteroids for IP exacerbations; these patients had a higher in‐hospital mortality rate of 67.7% (21/31 patients) and a significantly shorter median survival time of 55 days (95% CI 31–69 days, p < 0.001) than those who did not receive high‐dose corticosteroids. Conclusion: Acute exacerbation of IP treated with systemic high‐dose corticosteroids is significantly associated with in‐hospital mortality, and a low ADL score on admission is a risk factor for in‐hospital mortality in lung cancer patients with IP who undergo systemic chemotherapy. [ABSTRACT FROM AUTHOR]

Pulmonary pleomorphic carcinoma is often refractory to chemotherapy and follows an aggressive clinical course. Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of advanced lung cancer, and a few cases with pleomorphic carcinoma have been reported to show tumor shrinkage after therapy with ICIs. When treating patients with ICIs, patient selection is essential, and monitoring and management of immune‐related adverse events, including pneumonitis, are needed. We herein report a case of pulmonary pleomorphic carcinoma with preexisting interstitial pneumonia treated with pembrolizumab, antiprogrammed cell death 1 antibody. Our report highlights important considerations necessary when treating advanced pleomorphic carcinoma patients complicated with interstitial pneumonia. We also review the literature regarding the use of ICIs in such patients. [ABSTRACT FROM AUTHOR]

Background Pirfenidone is an antifibrotic agent that is potentially effective for the treatment of idiopathic pulmonary fibrosis (IPF). However, no study has reported on its prophylactic value against chemotherapy‐associated acute IPF exacerbations when combined with chemotherapy for non‐small cell lung cancer (NSCLC). The present study assessed the safety and effectiveness of pirfenidone combined with carboplatin‐based chemotherapy or immune checkpoint inhibitors (ICIs) in patients with IPF and NSCLC. Methods A total of 14 patients with IPF and NSCLC who received treatment from 2013 to 2019 were included. Patients were treated with pirfenidone combined with carboplatin and nanoparticle albumin‐bound paclitaxel or S‐1 as first‐line chemotherapy. After confirming disease progression, patients received cytotoxic agents or ICIs, including nivolumab and pembrolizumab. Pirfenidone was continued regardless of chemotherapy changes. Overall survival (OS) and progression‐free survival (PFS) for lung cancer and IPF were calculated. Moreover, the cumulative incidence of acute exacerbation of IPF (AE‐IPF) within one year was evaluated. Results Median PFS for lung cancer was 110 days (95% confidence interval [CI]: 57–199 days), while the median OS was 362 days (95% CI: 220–526 days). Moreover, PFS for IPF was 447 days (95% CI: 286–indeterminate days), and the cumulative incidence of AE‐IPF within one year was 18%. Notably, none of the patients developed AE‐IPF associated with first‐line chemotherapy. Among the included patients, four received ICIs, none of whom developed ICI‐associated AE‐IPF. Conclusions The present study found that pirfenidone combined with carboplatin‐based regimens or ICIs might be safe first‐line chemotherapy for patients with IPF and NSCLC. Key points Significant findings of the study No patients with IPF and NSCLC who received pirfenidone in combination with first‐line carboplatin‐based chemotherapy or late‐line ICIs developed acute IPF exacerbations. What this study adds Pirfenidone might have a prophylactic effect against chemotherapy‐associated AE‐IPF.

The association between gut microbiota and the lung immune system has been attracting increasing interest. Here, we report a case of pancreatic cancer in which the dipeptidyl peptidase‐4 inhibitor vildagliptin induced unusual manifestations of interstitial pneumonia, possibly under the influence of Lactobacillus paraplantarum probiotic supplementation. Chest computed tomography and positron emission tomography showed multiple ground‐glass nodules (GGNs) mimicking metastatic lung cancer. Transbronchial biopsy specimens showed mild fibrosis and infiltration of lymphocytes consisting of more CD4+ than CD8+ cells. The CD4+ cells did not include FOXP3+ regulatory T cells. Bronchoalveolar lavage confirmed lymphocytosis with a markedly increased CD4+/CD8+ ratio of 7.4. The nodules disappeared shortly after vildagliptin and probiotics were withheld. If unusual interstitial pneumonia is observed in some cancer patients, physicians should pay careful attention to their medication history, including probiotic supplements.

Here, we report a rare case of thymic carcinoma (TC) associated with dermatomyositis (DM) and interstitial pneumonia (IP) in a 68‐year‐old man. The patient presented with the characteristic features of a skin rash with Gottron's papules and increased serum levels of muscle‐associated enzymes. Computed tomography (CT) showed the presence of an anterior mediastinal soft tissue mass with IP, which was diagnosed as TC by CT‐guided tumor biopsy. The patients DM and IP disappeared completely after radical resection of the tumor. After a 20‐month follow‐up period, the patient was in good clinical condition without disease recidivism.

Background: Pirfenidone is an antifibrotic agent that is potentially effective for the treatment of idiopathic pulmonary fibrosis (IPF). However, no study has reported on its prophylactic value against chemotherapy‐associated acute IPF exacerbations when combined with chemotherapy for non‐small cell lung cancer (NSCLC). The present study assessed the safety and effectiveness of pirfenidone combined with carboplatin‐based chemotherapy or immune checkpoint inhibitors (ICIs) in patients with IPF and NSCLC. Methods: A total of 14 patients with IPF and NSCLC who received treatment from 2013 to 2019 were included. Patients were treated with pirfenidone combined with carboplatin and nanoparticle albumin‐bound paclitaxel or S‐1 as first‐line chemotherapy. After confirming disease progression, patients received cytotoxic agents or ICIs, including nivolumab and pembrolizumab. Pirfenidone was continued regardless of chemotherapy changes. Overall survival (OS) and progression‐free survival (PFS) for lung cancer and IPF were calculated. Moreover, the cumulative incidence of acute exacerbation of IPF (AE‐IPF) within one year was evaluated. Results: Median PFS for lung cancer was 110 days (95% confidence interval [CI]: 57–199 days), while the median OS was 362 days (95% CI: 220–526 days). Moreover, PFS for IPF was 447 days (95% CI: 286–indeterminate days), and the cumulative incidence of AE‐IPF within one year was 18%. Notably, none of the patients developed AE‐IPF associated with first‐line chemotherapy. Among the included patients, four received ICIs, none of whom developed ICI‐associated AE‐IPF. Conclusions: The present study found that pirfenidone combined with carboplatin‐based regimens or ICIs might be safe first‐line chemotherapy for patients with IPF and NSCLC. Key points: Significant findings of the study: No patients with IPF and NSCLC who received pirfenidone in combination with first‐line carboplatin‐based chemotherapy or late‐line ICIs developed acute IPF exacerbations. What this study addsPirfenidone might have a prophylactic effect against chemotherapy‐associated AE‐IPF. [ABSTRACT FROM AUTHOR]

The association between gut microbiota and the lung immune system has been attracting increasing interest. Here, we report a case of pancreatic cancer in which the dipeptidyl peptidase‐4 inhibitor vildagliptin induced unusual manifestations of interstitial pneumonia, possibly under the influence of Lactobacillus paraplantarum probiotic supplementation. Chest computed tomography and positron emission tomography showed multiple ground‐glass nodules (GGNs) mimicking metastatic lung cancer. Transbronchial biopsy specimens showed mild fibrosis and infiltration of lymphocytes consisting of more CD4+ than CD8+ cells. The CD4+ cells did not include FOXP3+ regulatory T cells. Bronchoalveolar lavage confirmed lymphocytosis with a markedly increased CD4+/CD8+ ratio of 7.4. The nodules disappeared shortly after vildagliptin and probiotics were withheld. If unusual interstitial pneumonia is observed in some cancer patients, physicians should pay careful attention to their medication history, including probiotic supplements. [ABSTRACT FROM AUTHOR]

Here, we report a rare case of thymic carcinoma (TC) associated with dermatomyositis (DM) and interstitial pneumonia (IP) in a 68‐year‐old man. The patient presented with the characteristic features of a skin rash with Gottron's papules and increased serum levels of muscle‐associated enzymes. Computed tomography (CT) showed the presence of an anterior mediastinal soft tissue mass with IP, which was diagnosed as TC by CT‐guided tumor biopsy. The patients DM and IP disappeared completely after radical resection of the tumor. After a 20‐month follow‐up period, the patient was in good clinical condition without disease recidivism. [ABSTRACT FROM AUTHOR]