Tepotinib in patients with non-small cell lung cancer with high-level MET amplification detected by liquid biopsy: VISION Cohort B.

High-level MET amplification (METamp) is a primary driver in ∼1%-2% of non-small cell lung cancers (NSCLCs). Cohort B of the phase 2 VISION trial evaluates tepotinib, an oral MET inhibitor, in patients with advanced NSCLC with high-level METamp who were enrolled by liquid biopsy. While the study was halted before the enrollment of the planned 60 patients, the results of 24 enrolled patients are presented here. The objective response rate (ORR) is 41.7% (95% confidence interval [CI], 22.1-63.4), and the median duration of response is 14.3 months (95% CI, 2.8-not estimable). In exploratory biomarker analyses, focal METamp, RB1 wild-type, MYC diploidy, low circulating tumor DNA (ctDNA) burden at baseline, and early molecular response are associated with better outcomes. Adverse events include edema (composite term; any grade: 58.3%; grade 3: 12.5%) and constipation (any grade: 41.7%; grade 3: 4.2%). Tepotinib provides antitumor activity in high-level METamp NSCLC (ClinicalTrials.gov: NCT02864992).

Clinical outcomes of hyperprogression based on volumetry in non-small cell lung cancer after immune checkpoint inhibitor treatment.

BACKGROUND: Hyperprogressive disease (HPD) is a novel pattern of the treatment course after immune checkpoint inhibitor (ICI) therapy in patients with non-small cell lung cancer (NSCLC). This study aimed to investigate the clinical characteristics, outcomes, and associated factors of HPD using a semiautomatic volume measurement. METHODS: This retrospective study enrolled patients with recurrent and/or metastatic NSCLC treated with ICIs between January 2015 and August 2019 at eight tertiary centers in Korea. HPD was defined according to the tumor growth kinetics and time to treatment failure. Tumor volume was measured using a semiautomatic software. RESULTS: A total of 219 NSCLC patients with 35 HPD by volumetric measurement (HPDv) (15.9%) were enrolled. The median duration of overall survival (OS) and OS after ICI treatment (ICI-OS) were 34.5 and 18.4 months, respectively. HPDv patients had significantly worse progression-free survival (PFS) than progressive disease patients without HPDv (1.16 vs. 1.82 months, p-value <0.001). ICI-OS did not significantly differ between patients with HPDv and those without HPDv (2.66 vs. 5.4 months, p = 0.105). PD-L1 expression lower than 50%, more than three metastatic sites, neutrophil-to-lymphocyte ratio equal to or higher than 3.3, and hemoglobin level lower than 10 were found to be associated with HPDv. CONCLUSIONS: There is no standardized definition of HPD. However, defining HPD in NSCLC patients treated with ICI using a semiautomatic volume measurement software is feasible.

Prognostic Factors of Second-line Immune Checkpoint Inhibitors in Patients With Advanced-stage Non-Small Cell Lung Cancer: A Multicenter, Retrospective Study.

OBJECTIVES: Immune checkpoint inhibitors (ICIs) targeting the programmed cell death receptor-1 and its ligand have achieved impressive success in treating patients with advanced-stage non-small cell lung cancer (NSCLC) after failed first-line cytotoxic chemotherapy. However, knowledge on clinical biomarkers that could help select patients who will respond well to second-line ICI therapy is limited. PATIENTS AND METHODS: Medical records of patients with NSCLC treated with first-line platinum-based chemotherapy and subsequent second-line ICI were collected from 6 medical centers between January 2018 and June 2020. Clinical information, pathologic variables, and radiologic findings of the data collected were reviewed. The patients were followed up until the date of the last visit, the death of any cause, or the end of data recording (December 31, 2020). RESULTS: A total of 181 patients with NSCLC were treated with second-line ICI following first-line platinum-based doublet chemotherapy. The median progression-free survival was 2.0 months (interquartile range, 1.0 to 5.5 mo), and the median overall survival was 12.0 months (interquartile range, 6.0 to 20.0 mo). Low body mass index (BMI) was independently associated with progression-free survival (odds ratio [OR], 0.826; 95% confidence interval [CI], 0.723-0.945; P=0.005). Similarly, a low BMI (OR, 0.839; 95% CI, 0.740-0.952; P=0.005) and a high number of metastatic organs (OR, 1.682; 95% CI, 1.156-2.448; P=0.007) were independently associated with the overall survival after second-line ICI therapy. CONCLUSION: BMI and the number of metastatic sites were significantly associated with second-line ICI therapy outcomes in patients with NSCLC receiving first-line platinum-based chemotherapy.

Veliparib in Combination with Carboplatin and Etoposide in Patients with Treatment-Naïve Extensive-Stage Small Cell Lung Cancer: A Phase 2 Randomized Study.

PURPOSE: This study investigated the efficacy and safety of oral PARP inhibitor veliparib, plus carboplatin and etoposide in patients with treatment-naïve, extensive-stage small cell lung cancer (ED-SCLC). PATIENTS AND METHODS: Patients were randomized 1:1:1 to veliparib [240 mg twice daily (BID) for 14 days] plus chemotherapy followed by veliparib maintenance (400 mg BID; veliparib throughout), veliparib plus chemotherapy followed by placebo (veliparib combination only), or placebo plus chemotherapy followed by placebo (control). Patients received 4-6 cycles of combination therapy, then maintenance until unacceptable toxicity/progression. The primary endpoint was progression-free survival (PFS) with veliparib throughout versus control. RESULTS: Overall (N = 181), PFS was improved with veliparib throughout versus control [hazard ratio (HR), 0.67; 80% confidence interval (CI), 0.50-0.88; P = 0.059]; median PFS was 5.8 and 5.6 months, respectively. There was a trend toward improved PFS with veliparib throughout versus control in SLFN11-positive patients (HR, 0.6; 80% CI, 0.36-0.97). Median overall survival (OS) was 10.1 versus 12.4 months in the veliparib throughout and control arms, respectively (HR, 1.43; 80% CI, 1.09-1.88). Grade 3/4 adverse events were experienced by 82%, 88%, and 68% of patients in the veliparib throughout, veliparib combination-only and control arms, most commonly hematologic. CONCLUSIONS: Veliparib plus platinum chemotherapy followed by veliparib maintenance demonstrated improved PFS as first-line treatment for ED-SCLC with an acceptable safety profile, but there was no corresponding benefit in OS. Further investigation is warranted to define the role of biomarkers in this setting.

Correlation of epidermal growth factor receptor mutation status in plasma and tissue samples of patients with non-small cell lung cancer.

BACKGROUND: Somatic mutations of the gene encoding epidermal growth factor receptor (EGFR) are detected in approximately 30%-50% of patients with non-small cell lung cancers (NSCLC), so detection of EGFR mutation is the pivotal step of treatment in patients with advanced NSCLC. However, difficulty in obtaining sufficient tissue and bias from the heterogeneity of the tumor samples are the major obstacles. Although analyzing EGFR with circulating tumor DNA (ctDNA) in plasma is a breakthrough, accuracy is the problem in variable methods. Peptide nucleic acid (PNA) clamping-assisted fluorescence melting curve analysis (PANAMutyper®) is a novel and highly sensitive method of detecting EGFR mutation in tumor tissues. AIMS AND OBJECTIVES: This study was designed to evaluate PANAMutyper® for detecting EGFR mutation with ctDNA of patients with lung cancer. MATERIALS AND METHODS: EGFR mutation status detected by PNA clamp with tissue samples and by PANAMutyper® with ctDNA was compared. Tissue biopsy was done in 158 patients with lung tumor, in which 23 cases were excluded and 135 cases were enrolled. EGFR mutation rate was 23.0% (31/135) in overall patients. All the plasma samples of the cases with mutant EGFR in tissue samples were verified by an already known highly sensitive method of droplet digital polymerase chain reaction (ddPCR). RESULTS: The concordance rate of tissue and plasma samples was 91.9% (124/135). The sensitivity, specificity, negative predictive value, and positive predictive value were 64.5%, 100%, 90.4%, and 100%, respectively, according to the tissue samples as a standard. PANAMutyper® method was not inferior to ddPCR for the detection of EGFR mutation including T790M with ctDNA. These results suggest that the detection of EGFR mutation status using ctDNA in plasma by PANAMutyper® is a feasible test prior to tissue biopsy.

Is Severe and Long-lasting Linezolid-induced Optic Neuropathy Reversible?

Linezolid is a useful drug for treating drug-resistant tuberculosis. However, the associated toxicities, especially optic neuritis, are a major obstacle for its long-term use. We recently experienced a case of severe optic and peripheral neuropathy during the treatment of multidrug-resistant tuberculosis. The treatment continued for 12 months despite severe optic and peripheral neuropathy. At eight months after the discontinuation of the drug, the optic neuropathy recovered, but the peripheral neuropathy did not. Considering the grave prognosis of drug-resistant tuberculosis, the continuation of linezolid despite neurotoxicity under close observation may be a suitable option.

Phase II trial of epidermal growth factor ointment for patients with Erlotinib-related skin effects.

PURPOSE: The efficacy of erlotinib, the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, has been demonstrated in patients with non-small cell lung cancer (NSCLC) and pancreatic cancer (PC). In the present study, we evaluated the effect of epidermal growth factor (EGF) ointment on erlotinib-related skin effects (ERSEs). METHODS: This was an open-label, non-comparative, multicenter, phase II trial. The patients included those diagnosed with NSCLC or PC who were treated with erlotinib. The effectiveness of the ointment was defined as follows: (1) grade 2, 3, or 4 ERSEs downgraded to ≤ grade 1 or (2) grade 3 or 4 ERSEs downgraded to grade 2 and persisted for at least 2 weeks. RESULTS: Fifty-two patients from seven institutes in Korea were enrolled with informed consent. The final assessment included 46 patients (30 males, 16 females). According to the definition of effectiveness, the EGF ointment was effective in 36 (69.2%) intention to treat patients. There were no statistically significant differences in the effectiveness of the EGF ointment by gender (p = 0.465), age (p = 0.547), tumor type (p = 0.085), erlotinib dosage (p = 0.117), and number of prior chemotherapy sessions (p = 0.547). The grading for the average National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI-CTCAE) rating of rash/acne and itching improved from 2.02 ± 0.83 to 1.13 ± 0.89 and 1.52 ± 0.84 to 0.67 ± 0.90, respectively (p < 0.001). The most common reason for discontinuing the study was progression of cancer (37%). CONCLUSIONS: Based on the results, the EGF ointment is effective for ERSEs, regardless of gender, age, type of tumor, and dosage of erlotinib. The EGF ointment evenly improved all kinds of symptoms of ERSEs. CLINICAL TRIAL REGISTRATION NO: ClinicalTrials.gov identifier: NCT01593995.

Strategic management of transthoracic needle aspirates for histological subtyping and EGFR testing in patients with peripheral lung cancer: An institutional experience.

BACKGROUND: Lung cancer therapy is personalized based on the histological subtype and molecular status. Totally, 70% of lung cancer patients present in advanced stages and are diagnosed on small biopsy or cytology specimens, hence an accurate but tissue-sparing approach is necessary. This study aimed to demonstrate efficient utilization of cell block (CB) on transthoracic needle aspiration (TTNA) for lung cancer subtyping, and to investigate the usefulness of needle washing after TTNA for assessing EGFR molecular status. METHODS: Each TTNA specimen from the 79 peripheral lung masses was divided into three parts; liquid-based cytology (LBC), CB (with or without immunohistochemistry), and needle washing for analysis of EGFR mutation using peptide nucleic acid-mediated real-time PCR clamping. RESULTS: Totally 79 specimens were diagnosed as malignancy, 75 (94.9%), benign, 3 (3.8%), and inadequate specimen, 1 (1.3%). The combination of LBC and CB (92.0%) showed a higher diagnostic yield for definitive subtyping of lung cancer than LBC alone (72.0%). Of the 75 malignant cases, 17 (22.7%) showed an EGFR mutation in needle washing specimens. EGFR mutational status was compared in all paired needle washing and scraped CBs with a 100% concordance. CONCLUSIONS: We hereby proposed a strategy to maximize biological information retrieval from a limited TTNA specimen in patients with peripheral lung cancer. This algorithm indicated CB preparation for accurate histological subtyping and waste needle washing for molecular testing.

Role of the neutrophil-lymphocyte count ratio in the differential diagnosis between pulmonary tuberculosis and bacterial community-acquired pneumonia.

BACKGROUND: Differential diagnosis between pulmonary tuberculosis (TB) and bacterial community-acquired pneumonia (CAP) is often challenging. The neutrophil-lymphocyte count ratio (NLR), a convenient marker of inflammation, has been demonstrated to be a useful biomarker for predicting bacteremia. We investigated the usefulness of the NLR for discriminating pulmonary TB from bacterial CAP in an intermediate TB-burden country. METHODS: We retrospectively analyzed the clinical and laboratory characteristics of 206 patients suspected of having pulmonary TB or bacterial CAP from January 2009 to February 2011. The diagnostic ability of the NLR for differential diagnosis was evaluated and compared with that of C-reactive protein. RESULTS: Serum NLR levels were significantly lower in patients with pulmonary TB than in patients with bacterial CAP (3.67±2.12 vs. 14.64±9.72, P<0.001). A NLR <7 was an optimal cut-off value to discriminate patients with pulmonary TB from patients with bacterial CAP (sensitivity 91.1%, specificity 81.9%, positive predictive value 85.7%, negative predictive value 88.5%). The area under the curve for the NLR (0.95, 95% confidence interval [CI], 0.91-0.98) was significantly greater than that of C-reactive protein (0.83, 95% CI, 0.76-0.88; P=0.0015). CONCLUSIONS: The NLR obtained at the initial diagnostic stage is a useful laboratory marker to discriminate patients with pulmonary TB from patients with bacterial CAP in an intermediate TB-burden country.

Characteristics of additional primary malignancies in Korean patients with non-small cell lung cancer.

BACKGROUND: Long-term cancer survival results in increasing numbers of multiple primary malignancies in one person, which represents growing clinical challenge in patients with lung cancer. This study was intended to assess the incidence rate, temporal relationship, and characteristics of additional primary malignancies (APM) in Korean patients with non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: We reviewed all 632 NSCLCs (313 adenocarcinomas, 276 squamous cell carcinomas, and 43 other NSCLCs) patients who underwent curative resection of NSCLC at the Dong-A University Medical Center from January 1991 to December 2009. We used the hospital information system and medical record to collect data about these patients and their tumors. In the data base, the following parameters were recorded: patient's demographics (age, gender and smoking habit), time interval between the diagnosis of the NSCLC and APM, NSCLC characteristics (date of diagnosis, histology, TNM staging, operative details, and survival) and characteristics of APM (site of tumor, date of diagnosis, histology, TNM staging, operative details, and survival). RESULTS: Eighty-one (12.8%) of the 632 patients with NSCLC had APMs. Thirty-three patients (40.8%) had APM in their history [occurring earlier than six months or more before NSCLC diagnosis; prior (P) group], 18 patients (22.2%) were diagnosed with an APM synchronously [diagnosed within six months before or after NSCLC; synchronous (S) group], and the remaining 30 patients (37.0%) were diagnosed with an APM during the follow-up period [occurring six months or more after NSCLC diagnosis; metachronous (M) group]. The second primary malignancy occurred most often two to five years in both P group (39.4%) and M group (36.7%). The most frequent APM was stomach cancer (25.0%), followed by colorectal cancer (19.0%), and thyroid cancer (10.7%). Interestingly, we found difference in the incidence of APM between different NSCLC histotypes. In the adenocarcinoma group, colorectal cancer was the most frequently discovered [12 of 46 events (26.1%)], followed by thyroid cancer [9 of 46 events (19.6%)]. In the squamous cell carcinoma group, stomach cancer occurred most frequently [12 of 36 events (33.3%)]. CONCLUSIONS: APMs are commonly seen in patients with NSCLC, either preceding or following its occurrence. Therefore, it is important to recognize the characteristic of NSCLC patients with APM in order to detect the second primary malignancy as early as possible and to achieve a possible cure of disease.

Primary Pulmonary Myxoid Liposarcoma with Translocation t(12;16)(q13;p11) in a Young Female Patient: A Brief Case Report.

Primary liposarcoma of the lung is an extremely rare disease. To date, only 14 cases have been reported in the literature. We experienced a case of myxoid liposarcoma of the lung treated by surgery. The tumor was well-defined, solid, lobulated mass measuring 3.5×2 cm, involving the bronchus of the left lower lobe. Microscopically, myxoid liposarcoma was identified. The fluorescence in situ hybridization confirmed the presence of a reciprocal translocation involving DNA damage-inducible transcript 3 (DDIT3) and fused in sarcoma (FUS) genes. The patient is still alive with no recurrence or metastasis at the time of writing this report (on 20 months postoperatively). To our knowledge, this is the first cytogenetic case report of pulmonary myxoid liposarcoma.

Gefitinib in Selected Patients with Pre-Treated Non-Small-Cell Lung Cancer: Results from a Phase IV, Multicenter, Non-Randomized Study (SELINE).

BACKGROUND: This study was designed to analyze the efficacy of gefitinib as a second-line therapy, according to the clinical characteristics in Korean patients with non-small-cell lung cancer (NSCLC). METHODS: In this Phase IV observational study, we recruited patients, previously failed first-line chemotherapy, who had locally advanced or metastatic NSCLC, and who were found to be either epidermal growth factor receptor (EGFR) mutation-positive or satisfied 2 or more of the 3 characteristics: adenocarcinoma, female, and non-smoker. These patients were administered with gefitinib 250 mg/day, orally. The primary endpoints were to evaluate the objective response rate (ORR) and to determine the relationship of ORRs, depending on each patient's characteristics of modified intent-to-treat population. RESULTS: A total of 138 patients participated in this study. One subject achieved complete response, and 42 subjects achieved partial response (ORR, 31.2%). The subgroup analysis demonstrated that the ORR was significantly higher in patients with EGFR mutation-positive, compared to that of EGFR mutation-negative (45.8% vs. 14.0%, p=0.0004). In a secondary efficacy variable, the median progression-free survival (PFS) was 5.7 months (95% confidence interval, 3.9~8.4 months) and the 6-month PFS and overall survival were 49.6% and 87.9%, respectively. The most common reported adverse events were rash (34.4%), diarrhea (26.6%), pruritus (17.5%), and cough (15.6%). CONCLUSION: Gefitinib was observed in anti-tumor activity with favorable tolerability profile as a second-line therapy in these selected patients. When looking at EGFR mutation status, EGFR mutation-positive showed strong association with gefitinib by greater response and prolonged PFS, compared with that of EGFR mutation-negative.

Liver cirrhosis as a delayed complication of Stevens-Johnson syndrome.

A 26-year-old woman was referred to our department due to fever and skin rash after having taken medication for a common cold. Physical examination revealed erythematous skin changes on her body associated with mucosal involvement in her eyes and oral cavity. Peripheral blood examination revealed leukopenia and thrombocytopenia. Liver function test showed hyperbilirubinemia. She was managed with high dose intravenous immunoglobulin (IVIG) at 1.0 gm/kg of body weight infused for 5 consecutive days. Although the patient's skin lesion improved dramatically with IVIG therapy, her hyperbilirubinemia aggravated progressively. Eighteen months after her presentation, liver cirrhosis was diagnosed by ultrasonography, laboratory and liver biopsy findings.

Absence of hyper-responsiveness to methacholine after specific bronchial provocation tests in a worker with hydroxyapatite-induced occupational asthma.

Hydroxyapatite is commonly used as a filler to replace amputated bone or as a coating to promote bone ingrowth into prosthetic implants. Many modern implants, such as hip replacements and dental implants, are coated with hydroxyapatite. We report a patient with occupational asthma due to hydroxyapatite, proven by a specific inhalation challenge, who experienced an early asthmatic reaction after exposure to hydroxyapatite, without increased airway responsiveness to methacholine despite an increased eosinophil count in the peripheral blood. A 38-year-old male dental implant worker visited our allergy department for the evaluation of occupational asthma. He had treated dental implant titanium surfaces with hydroxyapatite for 1.5 years. One year after starting his employment, he noticed symptoms of rhinorrhea, paroxysmal cough, and chest tightness. His symptoms were aggravated during and shortly after work and subsided several hours after work. When he stopped working for 2 months because of his chest symptoms, he became asymptomatic. After restarting his work, his symptoms reappeared and were aggravated. A methacholine bronchial challenge test had a negative response. The following day, a specific bronchial provocation test with wheat powder was negative. On the third day, a specific bronchial provocation test with hydroxyapatite powder produced an early asthmatic response. On the fourth day, a methacholine bronchial challenge test was negative. Further studies are needed to evaluate the exact pathogenetic mechanism of hydroxyapatite-induced occupational asthma.

Phase I study of autologous dendritic cell tumor vaccine in patients with non-small cell lung cancer.

BACKGROUND: A dendritic cell vaccine has been developed as a novel strategy for generating antitumor immunity in the treatment of cancer. The purpose of this study was to assess the maximal tolerated dose, safety, and immunologic response of a new dendritic cell vaccine (DC-Vac) into which tumor lysate was loaded by electroporation and pulse in patients with advanced non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: Fifteen patients with inoperable stage III or IV NSCLC were assigned to cohorts that received 3, 6, or 12 × 10(6) DC-Vac intradermally 3 times at 2 week intervals. We also evaluated immunologic and tumor responses. RESULTS: The maximum dose of DC-Vac (12 × 10(6)) was shown to be safe. In 5 of 9 patients, the vaccine resulted in increased interferon (IFN)-γ production by CD8+ cells after exposure to tumor lysate. Additionally, there were mixed responses which do fulfill progressive disease definition but demonstrate some clinical benefit in two patients. CONCLUSION: The administration of tumor lysate-loaded autologous dendritic cells by electroporation and pulse was non-toxic and induced immunologic responses to tumor antigens. The two mixed tumor responses which were achieved may represent a potential benefit of this new DC-Vac.

Catamenial hemoptysis: a nationwide analysis in Korea.

BACKGROUND: Hemoptysis is a potentially serious clinical problem. However, there is no consensus on the clinical characteristics, treatment and patient outcome of catamenial hemoptysis. OBJECTIVE: Clinical characteristics, treatments and outcome in patients of catamenial hemoptysis were evaluated. METHODS: We conducted a retrospective nationwide observational analysis of Korean patients with catamenial hemoptysis. RESULTS: Nineteen patients with catamenial hemoptysis were evaluated from 13 tertiary-care hospitals in Korea. The median age of the patients was 25 years; 8 (42%) were ever-smokers. Eight patients were pathologically diagnosed; 11 were diagnosed by clinical criteria. Sixteen (84%) patients had a history of obstetric or gynecological procedures before developing hemoptysis. The mean amount of hemoptysis (mean +/- SD) was 58.3 +/- 71.3 for surgery, 46.4 +/- 33.2 for hormonal and 29.1 +/- 26.3 for conservative treatment groups. Hemoptysis did not recur in 8 (89%) of 9 patients after surgery. None of the patients in the hormonal or conservative treatment groups had persistent hemoptysis. There was an excellent outcome (complete remission and partial responses) in all patients with conservative treatment, suggesting that endometrial cells implanted into the lung may have a benign course. CONCLUSION: Patients without massive hemoptysis can be treated conservatively or with hormonal agents.

Four cases of a cerebral air embolism complicating a percutaneous transthoracic needle biopsy.

A percutaneous transthoracic needle biopsy is a common procedure in the practice of pulmonology. An air embolism is a rare but potentially fatal complication of a percutaneous transthoracic needle biopsy. We report four cases of a cerebral air embolism that developed after a percutaneous transthoracic needle biopsy. Early diagnosis and the rapid application of hyperbaric oxygen therapy is the mainstay of therapy for an embolism. Prevention is the best course and it is essential that possible risk factors be avoided.

An aortoesophageal fistula in patient with lung cancer after chemo-irradiation and subsequent esophageal stent implantation.

An aortoesophageal fistula (AEF) is uncommon but is frequently fatal. Most cases are attributable to a thoracic aortic aneurysm. Other common causes include malignant intrathoracic neoplasm, foreign body ingestion, endovascular stent graft repair for thoracic aortic disease, and esophageal surgery. We report a case of an AEF that developed after chemo-irradiation and subsequent esophageal stent implantation in patient with non-small cell lung cancer. The patient underwent self expanding metallic esophageal stent implantation for an esophageal stricture after chemotherapy and radiotherapy. However, 1 month later, he presented with hematemesis. Chest computed tomography and aortography revealed a fistula from the descending thoracic aorta to the stented esophagus. The patient expired 36 hours after initial hematemesis. To our knowledge, this is the first confirmed report of an AEF in patient with a nonesophageal malignancy that had undergone chemo-irradiation and subsequent esophageal stent implantation. We recommend that special caution be exercised when performing esophageal stent implantation in patients who have received prior radiotherapy to the thorax including the esophagus.

Fatal interstitial lung disease after erlotinib administration in a patient with radiation fibrosis.

INTRODUCTION: Although gefitinib used for the treatment of non-small-cell lung cancer is a well-known cause of interstitial lung disease (ILD), few case reports on erlotinib-induced ILD have been issued. The common risk factor of both of these two drug-induced ILDs is idiopathic interstitial pneumonia, but ILD in a patient with radiation fibrosis has not been previously reported. METHODS: Report of a case. RESULTS: We recently experienced a case of fatal erlotinib-induced ILD, diagnosed based on clinical and radiologic findings, which occurred in a patient with radiation fibrosis. A 50-year-old male patient was started on erlotinib as a third-line chemotherapy. Six days after taking erlotinib, a chest radiograph showed rapid progression of reticular infiltration in both lung fields. High-resolution computed tomography scan findings were consistent with ILD, which was sufficient to diagnose as erlotinib-induced ILD. The patient died of respiratory failure after 8 days of steroid infusion and erlotinib discontinuation. CONCLUSION: Our case shows a fatal side effect of erlotinib. This case had radiation fibrosis, so we suggest that radiation fibrosis may be another contributor of the occurrence of ILD in patients taking erlotinib.