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BACKGROUND: Osimertinib exhibits good efficacy in patients with T790M-positive non-small cell lung cancer (NSCLC) and acquired resistance to epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs). Compared with the clinical trials, in real-world clinical practice, osimertinib must be administered to older patients and those with poor Eastern Cooperative Oncology Group performance status (ECOG-PS). Therefore, we investigated the association between osimertinib efficacy/safety and PS score, age, and other clinical features in patients with T790M-positive NSCLC. METHODS: We reviewed all patients with T790M-positive NSCLC and acquired resistance to initial EGFR-TKIs who were administered osimertinib between March 2016 and January 2018 at the Tokyo Metropolitan Cancer and Infectious Diseases Center in Komagome Hospital, Japan. RESULTS: In total, 31 patients, including 8 young (

Background Few studies have investigated the clinical efficacy of third- and later-line of chemotherapy after standard chemotherapy for previously treated advanced non-small cell lung cancer (NSCLC). We prospectively evaluated the efficacy and safety of nanoparticle albumin-bound paclitaxel (nab-paclitaxel) following standard chemotherapies for previously treated advanced NSCLC. Methods The eligible patients having adequate organ functions with performance status 0–2 were enrolled after completing standard chemotherapy. They received weekly nab-paclitaxel 100 mg/m2 intravenously on days 1, 8, and 15 every 3 weeks. The primary end point was objective response rate (ORR). Median progression-free survival (PFS), overall survival (OS), and adverse events (AEs) were evaluated as secondary end points. Results This trial was discontinued because of late accrual. Twenty two patients were enrolled from April 2013 and February 2019. The total ORR was 22.7% [95% CI 7.8–45.4] and disease control rate (DCR) was 81.8% [95% CI 59.7–94.8]. Median PFS was 3.4 months [95% CI 2.3–4.1] and median OS was 7.4 months [95% CI 4.2–10.7]. Median follow-up interval was 6.7 months hematological AEs of Grade 3/4 included anemia (18%), leukopenia (18%), and neutropenia (32%), while the most frequent nonhematological AEs were fatigue (50%) and peripheral neuropathy (36.4%). Severe AEs related to treatment were observed in only one patient. Conclusion Nab-paclitaxel may be a safe and effective later-line chemotherapeutic option for previously treated advanced NSCLC after standard of chemotherapies based on other trials.

Immuno-checkpoint inhibitor response and immune-related adverse events remain controversial issues. Managing pericardial effusion during programmed cell death 1 inhibitor treatment is challenging. Here, we report a case of successfully managed cardiac tamponade caused by nivolumab-induced pseudoprogression. A 62-year-old male diagnosed with advanced lung adenocarcinoma started on nivolumab. Seven days later, he experienced cardiac tamponade and required pericardiocentesis, and other lesions were larger on computed tomography. The patient’s condition stabilized after pericardiocentesis. However, although the lesions other than pericardial effusion were reduced on chest CT, cardiac tamponade recurred after 6 weeks. We considered that the case involved cardiac tamponade induced by pseudoprogression and administered intrapericardial bleomycin after pericardiocentesis. Thereafter, the patient was administered nivolumab for 7 months until disease progression.

The advent of antiretroviral therapy has changed the disease spectrum constitution among patients living with human immunodeficiency virus (HIV), while the incidence of death due to non-AIDS-defining cancers, particularly lung cancer, continues to increase in the USA and Europe. However, the availability of detailed reports of the clinical characteristics of lung cancer among Asian populations is limited. The present study retrospectively analyzed the clinical characteristics, treatment regimens and outcomes of lung cancer patients with HIV who were treated in a single institution between 1988 and 2013. Of the 20 lung cancer patients living with HIV included in this study, 90% were diagnosed since 1996 in the post-antiretroviral era. The median CD4+ cell count was 373.5/µl, whereas 65% of the patients were diagnosed with adenocarcinoma and 30% with squamous cell carcinoma. Epidermal growth factor receptor mutations were detected in 3 (27%) of the 11 specimens for which data were available, of which 65% had advanced-stage disease. Of the 20 patients, 9 underwent surgery, 6 received radiotherapy and 5 received chemotherapy as a first-line treatment. Treatment was generally well-tolerated. The median survival period was 35.8 months for all stages and 14.0 months for advanced stages. The treatment outcomes in our institution were favorable in comparison with previous studies from the USA and Europe, although these findings may be due to ethnic differences or the efficacy of treatment for HIV and lung cancer.

Little is known on the efficacy of erlotinib treatment in patients expressing wild-type epidermal growth factor receptor (EGFR). This study is a retrospective review of patients with non-squamous, non-small-cell lung cancer (NS-NSCLC) and wild-type EGFR who were treated with erlotinib alone as second- or later-line chemotherapy at the Tokyo Metropolitan Cancer and Infectious Diseases Center of Komagome Hospital (Tokyo, Japan) between December, 2008 and December, 2013. Thyroid transcription factor-1 (TTF-1) was immunohistochemically analyzed in 26 of 53 patients, among whom 20 (77%) and 6 (23%) were considered as TTF-1-positive and -negative, respectively. The median follow-up of these 26 patients was 133 days (range, 26–873 days). The time-to-treatment failure was significantly longer in TTF-1-positive compared with that in TTF-1-negative patients [49.5 vs. 20.0 days; 95% confidence interval (CI): 28–90 vs. 14–74 days, respectively; P=0.01]. The overall survival was significantly better for TTF-1-positive (227 days; 95% CI: 110–366 days) compared with TTF-1-negative patients (P=0.0002). Therefore, the expression of TTF-1 may serve as a useful tool for predicting the efficacy of erlotinib in patients with NS-NSCLC expressing wild-type EGFR.

A vitamin B12 supplement is required in pemetrexed single agent therapy. Intramuscular administration is the method of choice; however, oral administration is simpler and easier and may be sufficiently effective. We conducted a Phase II study to evaluate the safety of oral administration of vitamin B12 in patients with advanced non-small cell lung cancer who received pemetrexed single agent therapy. Folic acid and vitamin B12 were given orally for ˃1 week before pemetrexed administration. The primary end-point was onset of a grade ≥3 neutropenia ratio (50 % of threshold expression ratios; an expectation expression ratio of 21 %; α, 0.05; β, 0.1). Blood concentration of folic acid and homocysteine which are markers of vitamin B12 deficiency were also examined (UMIN000003180). A total of 25 cases were registered from February 2010 to July 2014. The ratio of grade ≥3 neutropenia was 36 % (95 % CI 22–52 %). Grade ≥3 non-hematologic toxicity and hematologic toxicity were seen in 20 % (5 cases) and 44 % (11 cases) of patients, respectively. In addition, the homocysteine blood concentration just before the first cycle dosage of pemetrexed was significantly elevated relative to the 2–3 cycle. This study failed to meet its primary endpoint. We could not demonstrate the safety and efficacy of the 1-week vitamin B12 oral administration protocol as compared with intramuscular administration.

Choroidal metastasis is rare in cancer patients. Small molecules of molecular targeted agents for lung cancer with actionable mutations were reported to be palliated for symptoms caused by choroidal metastasis. Visual disturbance by choroidal metastasis significantly decreases quality of life during the patient's remaining lifespan; therefore, radiotherapy or laser photocoagulation is proposed with consensus. However, improvement in survival with matched molecular targeted agents for oncogenic driver mutations reminds us to also be concerned with late treatment toxicities. A 30-year-old female patient previously treated with crizotinib harboring ALK rearranged non-small cell lung cancer complained of visual disturbance, fever, and bone pains undergoing anti-PD-1 antibody treatment. A decreased proportion of ALK fusion was demonstrated by fluorescence in situ hybridization in liver metastasis compared to the primary site in a chemo-naive state. She was diagnosed with low vision, choroidal metastasis and retinal detachment. Therefore, she started alectinib treatment and both her ocular and systemic symptoms were palliated in a week. Later, she temporarily discontinued alectinib because of skin rash although the choroidal metastasis and retinal detachment resolved and she regained low vision completely at 2 weeks. She obtained partial response with alectinib for more than 5 months after recovering from skin rash.

Background Clinical efficacy of second- and later-line chemotherapy for patients with thymic carcinoma previously treated with chemotherapy remains uncertain; limited data are available about this carcinoma because of its rarity. The aim of this study was to investigate effective chemotherapy for patients with thymic carcinoma previously treated with chemotherapy using a retrospective analysis of responses and times to event. Patients and Methods We conducted a retrospective review of the medical records of 23 advanced thymic carcinoma patients previously treated with palliative-intent chemotherapy between 1980 and 2014 in our institution. Clinical demographic characteristics, agents, response, and time to treatment failure for each treatment line and overall survival were reviewed. Factors expected to be associated with survival rates were analyzed. Differences in survival were assessed using Kaplan–Meier analysis and univariate and multivariate Cox proportional hazards regression analyses. Results The study included 13 men (56.5%) and 10 women (43.5%). The median age at diagnosis was 58.5 years. The most common histological subtypes were squamous cell carcinoma (16 patients [69.6%]), followed by neuroendocrine carcinoma (4 patients [17.4%]). The objective response rates of first-, second-, third-, and fourth-line chemotherapy were 60.9%, 39.1%, 23.1%, and 25.0%, respectively. The median survival time was 18.8 months (95% confidence interval, 7.5-40.9 months). Uni- and multivariate analyses of all assessed variables failed to identify any statistically significant indicators of overall survival. Conclusion Patients with thymic carcinoma previously treated with palliative-intent chemotherapy might respond to second- or later-lines of cytotoxic chemotherapy.

BACKGROUND/AIM Programmed cell death ligand 1 (PD-L1) expression is a predictive marker for immunotherapy effects in advanced non-small cell lung cancer (NSCLC), but its association with patient characteristics or specimens is controversial. We aimed to retrospectively analyze the association of PD-L1 expression with clinicopathological features of NSCLC patients. MATERIALS AND METHODS The PD-L1 expression and clinicopathological features of NSCLC patients were assessed from January 2017 to June 2017 in the Tokyo Metropolitan Cancer and Infectious Diseases Centre, Komagome Hospital were reviewed (n=108). RESULTS For PD-L1 expressions of 0% and >1%, multivariate analysis showed that lymph node sample results were associated with positive PD-L1 expression. Archival samples and high serum carcinoembryonic antigen (CEA) levels were associated with negative PD-L1 expression. Sample preservation time and CEA levels correlated with PD-L1 expression. CONCLUSION Nodal metastasis, sample preservation time and CEA levels were associated with PD-L1 expression in NSCLC.

Background. Prior supplementation with folic acid and vitamin B12 is required to reduce pemetrexed therapy toxicity; the recommended lead-in time is at least 7 days. On the basis of previous pharmacokinetic and clinical studies, we hypothesized that the lead-in time could be shortened to 24 hours, enabling earlier commencement of standard chemotherapy; thus, we planned the first prospective trial of this regimen. Methods. Patients with advanced nonsquamous non-small cell lung cancer who had not previously received cytotoxic chemotherapy were enrolled. After measurement of homocysteine concentrations, the patients received 1,000 μg of vitamin B12 by intramuscular injection and began taking 350–500 μg of oral folic acid daily. Starting 24–48 hours after the vitamin B12 injection, the patients received intravenous 500 mg/m2 pemetrexed and 75 mg/m2 cisplatin for 4 cycles at 3 weekly intervals. The primary endpoint was the proportion of patients who developed neutropenia grade ≥3. Results. Thirty patients received chemotherapy starting within 48 hours of the vitamin B12 injection. No treatment-related deaths or grade 4 toxicity occurred. Neutropenia grade ≥3, other laboratory toxicities grade ≥3, and nonlaboratory toxicities grade ≥3 occurred in 6.7%, 13%, and 13% of patients, respectively. The baseline homocysteine concentrations were not higher in patients with grade ≥3 toxicities than in the remainder of the cohort (mean values, 8.6 and 10.7 μmol/L, respectively). The response rate to chemotherapy was 43%. Conclusion. The shortened vitamin supplementation was well tolerated and retained antitumor efficacy. Analysis of baseline homocysteine concentrations confirmed the efficacy of short-term vitamin supplementation.

Purpose Thymic malignancies, comprising thymoma and thymic carcinoma, are rare. Consequently, optimal chemotherapy for advanced thymic malignancies remains controversial. Platinum-based chemotherapy is currently the consensus treatment based on the results of single-arm phase II trials and retrospective investigations. However, comparison of cisplatin-based and carboplatin-based chemotherapy has yet to be undertaken; the effectiveness of the addition of anthracycline also remains uncertain. Methods In the present study, clinical trials and retrospective data regarding platinum-based chemotherapy were analyzed. The endpoint was the response rate to each chemotherapy. For advanced thymoma, we compared platinum with anthracycline-based chemotherapy and platinum with non-anthracycline-based chemotherapy. For advanced thymic carcinoma, anthracycline-based versus non-anthracycline-based chemotherapy and carboplatin-based versus cisplatin-based chemotherapy were compared. This analysis included a retrospective study of response of advanced thymic carcinoma to irinotecan and cisplatin in our institution. Results The response rate for the 314 patients from 15 studies with advanced thymoma, including both prospective and retrospective data, was 69.4 % [95 % confidence interval (CI) 63.1–75.0 %] for platinum with anthracycline-based chemotherapy and 37.8 % (95 % CI 28.1–48.6 %; p

Background Heterogenous clinical or biological features are characteristic of thymic carcinoma. Well-defined clinical entities remain unclear because of rarity. The aim of this study was to clarify disease profiles, outcomes, and prognostic factors for survival among patients diagnosed with thymic carcinoma. Patients and methods A retrospective review was conducted of the medical records of 68 thymic carcinoma patients among 187 patients diagnosed with thymic epithelial tumors between 1980 and 2013 in our institution. Clinical demographics, histology, overall survival, and factors expected to predict survival were analyzed. Differences in survival were assessed using Kaplan–Meier analysis and uni- and multivariate Cox proportional hazards regression analyses. Results The study included 38 males (55.9%) and 30 females (44.1%). The median age at diagnosis was 63.5 years. The most common subtypes of thymic carcinoma were squamous cell carcinoma (69.1%), neuroendocrine carcinoma (16.2%), and mucoepidermoid carcinoma (5.9%). Masaoka-Koga staging of the 68 patients demonstrated no patients (0%) in Stage I, 3 (4.3%) in Stage II, 14 (20.6%) in Stage III, 12 (17.6%) in Stage IVa, and 39 (57.4%) in Stage IVb. The median survival time for all stages was 36.4 months (95% confidence interval 23.7–56.4); those for stages II, III, IVa, and IVb were: not reached, 65.8, 24.6, and 27.3 months, respectively. The difference by Masaoka-Koga staging was significant ( p =0.04). Overall survival rates at 1-, 5-, and 10-year were 76.3%, 36.0%, and 6.2%, respectively. By univariate analyses, the only favorable prognostic factor for overall survival was surgical intervention ( p =0.03), and, for Stage IVb, lymphatic metastasis without distant metastasis. However, clinically interesting variants did not differ significantly for predicting survival. Conclusion Surgical intervention results in better survival of thymic carcinoma, even in Stage IVb. The survival value of administration of curative-intent radiotherapy, or of identification of "resectability" in Stage IVb patients must continue to be discussed.

Bronchiolitis obliterans syndrome (BOS) is a rare pulmonary complication of hematopoietic stem cell transplantation (HSCT) with high mortality. Chronic bacterial airway infection (CAI) causes exacerbation and progression of several airway diseases, and bacterial airway colonization was shown to be associated with BOS after lung transplantation. We assessed the association between CAI and clinical course in patients with BOS after HSCT. This retrospective study included 910 patients undergoing allogeneic HSCT between 2005 and 2013 at our institution. BOS diagnosis was reevaluated according to the 2014 US National Institutes of Health criteria. Sputum and bronchial lavage culture results, pulmonary function, and survival were compared between patients with and without CAI. Median follow-up was 974.5 (261.5–2748.5) days. BOS was diagnosed in 27 (3.0%) patients, including 18 males. Median age at BOS diagnosis was 45 (40.5–58) years. Nine patients had ≥2 positive sputum cultures for bacteria or one positive bronchial lavage culture for nontuberculous mycobacteria (CAI+), whereas 9 patients had negative sputum/bronchial lavage culture or only one positive sputum culture (CAI−). Median change in forced expiratory volume in 1 s within 6 months after BOS diagnosis and overall survival were significantly worse in CAI+ patients than in CAI− patients (−250 vs +260 mL, P = .002, and 1340 days vs not reached, P = .04, respectively). No other factors including patient demographics or transplant protocol affected prognosis. There were no differences in clinical characteristics of patients with and without CAI, except for the time from transplantation to BOS diagnosis (214 vs 768 days for CAI+ and CAI−, respectively; P = .02). CAI was associated with worse outcomes in patients with BOS after HSCT. Further prospective studies should assess the association between the airway microbiome and changes in pulmonary function after HSCT to improve prognosis.

Background: Human immunodeficiency virus (HIV)-infected patients are surviving longer since the advent of antiretroviral therapy. Therefore, more patients are developing non-AIDS-defining cancers which increasingly determine mortality. Case Reports: Here we present 2 cases of locally advanced non-small cell lung cancer treated initially with concomitant chemoradiotherapy and antiretroviral therapy. Both patients were male, ages 69 and 66, with known HIV infection and immunologically stable on antiretroviral therapy. Presenting symptoms included superior sulcus tumor with left arm immobility and sensory disturbance in case 1 and right lower bronchus constriction in case 2. Symptoms were controlled by chemoradiotherapy. Conclusion: These cases illustrate that intensive anticancer therapy administered to the HIV-infected population can be tolerated even though these patients seem to be too fragile for both chemotherapy and radiotherapy, especially since the potential benefit remains uncertain. Recent improvements in chemoradiotherapy and supportive care have enhanced tolerance for such therapy.

Yoshiro Nakahara,1,2 Yusuke Takagi,1,3 Yukio Hosomi,1 Akiko Kagei,4 Tomohiro Yamamoto,4 Takeshi Sawada,5 Makiko Yomota,1 Yusuke Okuma,1 Shinichiro Mikura,1,6 Tatsuru Okamura1 1Department of Thoracic Oncology and Respiratory Medicine, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital, Tokyo, 2Department of Respiratory Medicine, Kitasato University School of Medicine, Sagamihara, 3Oncology Scientific Affairs, Merck Sharp & Dohme Corp, 4GeneticLab Co., Ltd., Sapporo, 5Department of Medical Oncology, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital, Tokyo, 6Department of Respiratory Medicine, Fujieda Municipal General Hospital, Fujieda, Japan Background: Repetitive genotyping is useful to assess the genetic evolution of non-small-cell lung cancer (NSCLC) during treatment, but the need for sampling by biopsy is a major obstacle. Digital polymerase chain reaction (PCR) is a promising procedure for the detection of mutant alleles in plasma of cancer patients.Methods: This prospective study enrolled patients with NSCLC and known epidermal growth factor receptor (EGFR) mutations and who had experienced disease progression during ongoing EGFR-tyrosine kinase inhibitor (TKI) therapy. Eligible patients received daily gefitinib and either pemetrexed or S-1 every 3 weeks until disease progression or the development of unacceptable toxicity. Peripheral blood was collected before and after the combination therapy for digital PCR and hepatocyte growth factor measurement.Results: From May 2012 to January 2014, nine patients with a median age of 67 (range 52–80) years were enrolled. Patterns of disease progression during adjacent EGFR-TKI therapy were acquired resistance, observed in seven patients, and primary resistance, observed in two patients. Known EGFR mutations were detected in plasma samples of six (67%) patients at study enrollment. Of these, T790M mutation was concurrently detected in three (50%) patients. Four patients underwent gefitinib plus pemetrexed therapy, and five patients underwent gefitinib and S-1 therapy. The median number of cycles delivered was five, and the median progression-free survival was 5.7 months. Efficacy outcomes did not differ between treatments. After the combination therapy, plasma T790M status changed to positive in two patients. Hepatocyte growth factor level did not significantly change through the combination therapy.Conclusion: The usefulness of monitoring the genetic evolution of EGFR-driven tumors using noninvasive procedures was demonstrated. Since continuation of EGFR-TKI therapy with cytotoxic agents has an acceptable tolerability and a possibility of inducing T790M mutation, the combination therapy may be useful for EGFR-mutant NSCLC resistant to EGFR-TKI therapy without T790M mutation. Keywords: circulating tumor DNA, epidermal growth factor receptor, gefitinib, S-1, pemetrexed

Background Thymic carcinoma is a rare cancer with minimal evidence of a survival benefit following chemotherapy. An oral fluoropyrimidine of S-1, however, is the recommended active cytotoxic chemotherapy agent for refractory thymic carcinoma based on a case series, whereas sunitinib or everolimus are recommended as molecular-targeted agents based on Phase II trials. We retrospectively investigated the efficacy of S-1 for refractory thymic carcinoma and performed a biomarker analysis. Methods We assessed the clinicopathological variables of 14 consecutive patients who underwent S-1 for refractory thymic carcinoma and correlated the clinical outcomes with potential biomarkers using paraffin-embedded cancer tissues of eight patients in the cohort. Results A total of 178 thymic malignancies were identified, of whom 14 patients included 12 cases of squamous cell carcinoma, one lymphoepithelioma-like carcinoma, and one undifferentiated carcinoma. Six patients exhibited a partial response (42.9 %: 95 % confidence interval [CI], 21.4–67.4) and the disease control rate was 85.7 % (60.0–96.0 %). After a median follow-up of 24.2 months, the median progression-free survival was 8.1 months (range, 2.6–12.2 months), and median overall survival was 30.0 months (range, 6.2–41.9 months). No significant correlation between biomarker expression and response was noted. However, thymidine synthase (TS)/dihydropyrimidine dehydrogenase and TS/orotate phosphoribosyltransferase were observed. Conclusions S-1 for refractory thymic carcinoma offered clinical activity and achieved an 85 % disease control rate. Although the biomarkers did not correlate with clinical outcome, the study results showed efficacy of S-1 as a cytotoxic chemotherapy for refractory thymic carcinoma, which warrants future investigation. Electronic supplementary material The online version of this article (doi:10.1186/s12885-016-2159-7) contains supplementary material, which is available to authorized users.

A 70-year-old man was diagnosed with small- cell lung cancer (SCLC) of the left upper lobe, with a TNM classification of cT4N3M1b (PUL, OSS, BRA, HEP). A single asymptomatic brain metastasis 1 cm in diameter was also identified. The patient underwent four cycles of cis- platin plus irinotecan therapy, with a total effect of partial response. Complete remission of the brain metastasis was also achieved, and whole-brain radiation therapy (WBRT) was postponed at the request of the patient. Six months after diagnosis, he was admitted to our hospital with a major complaint of dizziness. Computed tomography showed enlargement of the primary lesion and multiple brain metastases. WBRT was started, but performance status did not improve. While undergoing WBRT, the patient complained of blurred vision. The ophthalmologist found a metastasis on the right iris by chance, although blurred vision was caused by detachment of the left retina. Two months later, the patient died of respiratory failure. Autopsy histologically confirmed the iris metastasis of SCLC. Cases of iris metastasis diagnosed before death are rarely reported. Iris metastases are estimated to account for 9 % of uveal metastases. This may suggest that many iris metastases have few clinical signs and are difficult to diagnose. Asymptomatic iris metastases, particularly among patients with SCLC, are thus likely to be underdi- agnosed. Ocular metastasis should be considered when a cancer patient complains of visual disturbance.

Lung cancer has emerged as a crucial problem among human immunodeficiency virus (HIV)-infected patients, contributing to significant mortality in Western countries. Japan has an increasing number of newly infected HIV patients, but clinical characteristics of lung cancer have not been well investigated in Asian populations with HIV. We retrospectively analyzed patients diagnosed with HIV and lung cancer simultaneously in our institution between 1985 and 2010. Data regarding HIV status, characteristics, treatment, and prognosis of lung cancer were evaluated. We identified 13 consecutive patients (all men; mean age, 59.0 ± 10.2 years) since 1985, 7 of whom had been diagnosed since 2008. Mean CD4 cell count was 332 ± 159 cells/μL, and HIV viral loads were undetectable in 8 patients (61.5%) at the time of lung cancer diagnosis. The mean latency from HIV diagnosis to detection of lung cancer was 4.0 years. Histological examination demonstrated adenocarcinoma in 9 patients (69.2%), followed by squamous cell carcinoma (23.1%), and small cell carcinoma (7.7%). Among the 7 patients available for examination, 2 patients (28.6%) harbored EGFR mutation. Six patients had stage IA–IIIA, and 7 patients had stage IIIB/IV. Among 6 patients treated with chemotherapy for unresectable stages, 5 (83.3%) achieved a partial response. Median overall survival was 17 months for all stages and 14 months for advanced stages. Toxicities for treatment modalities were largely acceptable. Clinical characteristics of Japanese HIV-infected patients with lung cancer resemble those of Western populations. The prognosis for patients in the metastatic stage was better than previously reported.

Background Thymic carcinoma is a rare intrathoracic malignant tumor, and the prognosis for patients with advanced stage of the disease is poor. However, no definitive chemotherapeutic regimen has been established for advanced thymic carcinoma in front-line settings. The efficacy and benefit of second-line or salvage chemotherapy are also unknown, as few cases or case series have been reported. Patients and methods We evaluated the efficacy and toxicity of S-1 monotherapy with S-1, a novel oral fluoropyrimidine agent, as salvage therapy in four consecutive patients with previously treated advanced thymic carcinoma from January, 2008 to May, 2010. Results Two patients achieved stable disease, and two achieved partial response. Median progression-free survival was 8.1 months. Hematological toxicity was mild, but gastrointestinal toxicity led to discontinuation in two of four patients. Conclusions We concluded that oral S-1 monotherapy is useful as second-line or later chemotherapy in previously treated patients with advanced thymic carcinoma and is a potential alternative choice for patients who cannot tolerate platinum-containing treatments.

Human immunodeficiency virus (HIV)-infected patients are likely to develop intracranial events. Due to the spread of highly active antiretroviral therapy (HAART), HIV-infected patients now survive longer, and metastatic non-AIDS-defining carcinoma is increasing. A 49-year-old man with HIV infection undergoing treatment with HAART developed an intratumoral hemorrhage in the right frontal lobe. He was diagnosed as having lung adenocarcinoma and was found to have a brain metastasis with bleeding. After treatment for intratumoral bleeding, a contralateral frontal lobe hemorrhage occurred within a month. The patient underwent a second craniotomy and removal of hematoma, followed by whole-brain radiotherapy. He was then treated with four cycles of cisplatin and gemcitabine combination chemotherapy while receiving HAART. A partial response was achieved, though he developed severe hematological toxicities for which the doses of chemotherapy needed to be decreased. However, as a result of treatment, his activities of daily life recovered gradually. This lung cancer patient had been alive for 17 months despite the coexistence of two disorders with a poor prognosis, HIV infection and bleeding brain metastases from lung cancer. This case revealed that physicians must include non-AIDS-defining cancer metastasis to the brain in the differential diagnosis of HIV-infected patients when they show stroke-like symptoms, and such patients may respond to treatment as well as non-HIV-infected patients with advanced lung cancer.

A 56-year-old male patient complaining of productive cough, hoarseness, and fatigue was found to have extensive disease of small cell lung cancer (ED-SCLC), with staging of cT4N3M1(PUL). He was treated with chemotherapy. While undergoing treatment with chemotherapy, he complained of a right visual disturbance, and choroidal metastasis was diagnosed. Because the primary site responded well to chemotherapy alone and the visual disturbance did not worsen, the patient refused radiotherapy to the choroidal metastasis. Two months after the first diagnosis of the choroidal metastasis, while he was receiving the first treatment regimen for SCLC, the visual disturbance suddenly worsened; emergent radiotherapy was started, with a total dose of 40 Gy, given as 2.0 Gy/fraction per day. The visual disturbance never improved, and the patient lost 80% of his right visual field. Within 6 months of diagnosis, the patient became blind in his right eye. The patient died of septic shock related to treatment received during his third chemotherapy regimen. Choroidal metastasis is very rare with extraocular malignant tumors, though it is common with intraocular malignant tumors. Choroidal metastasis secondary to SCLC has a poor prognosis, but in order to maintain quality of life during the patients' remaining lifespan, aggressive treatment would appear appropriate for these patients, because SCLC is a chemo-sensitive cancer.

Pulmonary veno-occlusive disease (PVOD) is a rare form of pulmonary hypertension with poor prognosis. PVOD may be idiopathic or associated with chronic diseases, but there are only 12 reported cases of PVOD following hematopoietic stem cell transplantation (HSCT). Two cases presenting in our hospital were pathologically diagnosed as PVOD following HSCT. Both cases presented with dyspnea on exertion and low SpO2. X-ray showed bilateral pleural effusion. On transthoracic echocardiography, ejection fraction was normal and there were no indications of pulmonary hypertension (PH) in either patient. Pulmonary function test revealed decreased diffusing capacity of the lung, and perfusion lung scintigraphy showed subsegmental defect. Surgical lung biopsy was performed, and fibrosis remodeling of the intima and occlusion of the lumen were observed, which are suggestive of a definitive PVOD diagnosis. Each case was treated with corticosteroid and their symptoms, SpO2, and pulmonary function improved. One patient died 281 days after diagnosis by bacterial pneumonia, and the other has been alive for 28 months and remains stable. PVOD prognosis is extremely poor, with most reported patients dying within 2 years of diagnosis. In previous reports of PVOD following HSCT, no patient has survived for more than 1 year, and all cases had PH. Four cases underwent surgical biopsy, while the others were diagnosed clinically or at autopsy. Nine patients were given corticosteroids as treatment, and four of these nine patients responded to the treatment. PVOD is rare, but early detection of this disease before the development of severe PH and early treatment or listing for lung transplantation may improve prognosis.

The key drugs for chemotherapy of thymic carcinoma are gradually being revealed in phase II and conventional retrospective studies. Gemcitabine is regarded as one of these key drugs according to the findings of clinical trials in which it was combined with capecitabine. However, the activity of single-agent gemcitabine concerning refractory thymic carcinoma remains unclear. We conducted a retrospective review of the medical records of refractory thymic carcinoma patients previously treated with platinum-containing chemotherapy between 1980 and 2014. Of all 11 patients in this study, the objective response rate regarding gemcitabine was 36.4 % [95 % confidence interval (CI) 15.2–64.6] using the RECIST criteria and the response criteria proposed by the ITMIG. The median progression-free survival time was 4.3 months (95 % CI 0.7–11.0). The survival time from the start of gemcitabine treatment was 28.5 months (95 % CI 5.5–47.8), and from the start of first-line chemotherapy was 46.5 months (95 % CI 7.3–47.8). Gemcitabine achieved a moderate response and has the potential to be used as a key drug for thymic carcinoma. Some patients treated with gemcitabine demonstrated prolonged cancer control even in later lines of chemotherapy.

Prophylactic cranial irradiation (PCI) is an established part of standard therapy for small-cell lung cancer (SCLC). However, the concerns regarding severe late neurotoxicity following PCI have not yet been systematically investigated. Therefore, the aim of this study was to investigate the neurocognitive functioning of SCLC patients treated with PCI. Limited-disease SCLC (LD-SCLC) patients (n=40) treated at Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital (Tokyo, Japan) between January, 2004 and December, 2011 were retrospectively reviewed. A total of 18 LD-SCLC patients were treated with PCI (median age, 65.5 years; range, 52–75 years), whereas 22 LD-SCLC patients did not receive PCI (median age, 65.5 years; range, 57–84 years). The median follow-up for PCI and non-PCI patients was 22 months (range, 4–85 months) and 14.5 months (range, 2–49 months), respectively. Brain metastases occurred in 6 (33%) PCI patients and 11 (50%) non-PCI patients. In the PCI group, dementia occurred in 5 of the 12 PCI patients without brain metastases (42%, 3–40 months after PCI) and in 1 of the 11 non-PCI patients without brain metastases (9%, 4 months after initial treatment). The frequency of dementia in the PCI group was significantly higher compared with that in the non-PCI group (P=0.0357). In the PCI group, all the patients who developed dementia were aged >65 years (range, 66–75 years). Gait disturbance appeared in 25% of the PCI patients without brain metastases (9–27 months after PCI); these patients were also aged >65 years. Patients aged >65 years were significantly more likely to develop dementia (P=0.0028) and gait disturbance (P=0.0291). Therefore, neurotoxicity due to PCI tends to appear more frequently in older patients.

Background Malignant pleural effusion (MPE) can occur during the progression of various cancers. However, factors, such as the incidence of MPE associated with different types of cancers and its potential for diagnosing previously undetected cancers, are unknown. Moreover, MPE may accompany potentially curable cancers or those with a favorable survival prognosis with adequate treatment. The present study determined the types of cancers accompanied by MPE at initial diagnosis and investigated appropriate related methods for diagnosing previously unknown cancers. Methods We retrospectively reviewed the medical records of 35 patients with MPE at initial cancer diagnosis between 2004 and 2012. We evaluated the patient characteristics, final diagnosis, and diagnostic processes. Results Of the 35 patients, 10 had lung cancer, seven ovarian or peritoneal cancer, four malignant pleural mesothelioma, one breast cancer, one lymphoma, one pancreatic cancer, and 11 had cancers of unknown origin. Diagnoses of the primary lesions were confirmed using the MPE cellblock method for seven of 11 patients (63.6%), by excisional biopsy or aspiration from other sites in four of nine patients, by exploratory laparotomy in two of three patients, and by peritoneal washing cytology in five patients. Conclusion Lung cancer and cancer of unknown origin are major causes of MPE at initial presentation. However, these groups also contain cancers that are curable and those with good long-term prognosis. The MPE cellblock method represents an accurate method for identifying cancer origin.

We report a case of small cell lung cancer in a patient with human immunodeficiency virus (HIV) infection. The patient was a 51-year-old man diagnosed 8 years previously as seropositive for HIV, who was admitted to our hospital for re-evaluation of antiretroviral medications due to multidrug resistance. Chest radiograph revealed an abnormal hilar shadow subsequently confirmed to be small cell lung cancer. He received chemotherapy concurrently with highly active antiretroviral therapy (HAART), and lived for 14 months after the diagnosis. The prognosis of lung cancer in HIV-seropositive patients is very poor, and adverse effects of chemotherapy occur more frequently than in other patients. However, the simultaneous antiretroviral agents and combination chemotherapy was successful. Such treatment may be effective despite an otherwise poor prognosis, including HIV infection.

The utility of 111In-DTPA-IgG imaging for the detection of intrathoracic lesions was evaluated in 10 patients with the suspicion of inflammatory or infectious diseases. They were intravenously administered 40 or 80 MBq of 111In-DTPA-IgG, and scanned after 24 or 48 hours. Of these, 8 cases, consisted of 4 cases with pneumonia and 2 cases with lung abscess and one case of pulmonary tuberculosis and one of a tuberculous pleuritis, showed true positive results. Others were one false negative case of pneumonia and one true negative case of lung cancer. Overall sensitivity and specificity were 88.9% and 100%, respectively. There were no cases which showed side effects or abnormal laboratory findings caused by the radiopharmaceuticals administered. Thus, 111In-DTPA-IgG imaging is a useful tool for the detection of intrathoracic infectious lesions.

The phase II NEJ001 trial suggested that gefitinib was active against advanced non-small cell lung cancer (NSCLC) even in patients with poor performance status (PS). Clinical response among the patients harboring epidermal growth factor receptor (EGFR) mutation with poor PS is fair; however, gefitinib does not have as much continued efficacy as in patients with good PS. This study has retrospectively investigated the clinical outcomes of gefitinib treated patients with advanced NSCLC, EGFR mutations, and poor PS.A total of 208 patients with advanced NSCLC and poor PS treated with gefitinib from 2004 to 2013 were retrospectively evaluated. Outcomes were studied after stratification for gender, smoking status, histological subtype, and EGFR mutation status.Fifty-two patients (25.0%) with advanced NSCLC, EGFR mutation, and poor PS were treated with gefitinib. The overall response rate was 65.4%. The median progression-free survival, median survival time, and one-year survival rate was 6.6 months, 19.6 months, and 62.9%, respectively. Death due to interstitial lung disease occurred in 11.5% of the patient population. In multivariate analysis, a PS of 4 was independently associated with poor outcomes (hazard ratio=10.5; 95% Confidence interval=1.92-50.19; p=0.0091).Patients with advanced NSCLC, EGFR mutation, and poor PS have poor outcomes in response to gefitinib. However, the indication of gefitinib for such patients will not be changed in clinical practice and oncologists should treat these patients with more careful follow-up since for those with poor PS, therapy may be more toxic than for patients with good PS.

A 69-year-old male was admitted to our hospital on Jan. 10, 1995 complaining of bloody sputum, left back pain and fever of 39 degrees C. He had a history of pulmonary tuberculosis 45 years ago. His chest X-ray and CT showed the presence of air-fluid level in the left pleural cavity with thickening and calcification of the pleura. Salmonella Enteritidis was isolated from the sputum, bronchoalveolar lavage fluid and stool. He was diagnosed as suffering from Salmonella-empyema with an internal fistula. Based on the in vitro sensitivity test, sulfamethoxazole/trimethoprim was started. However, the efficacy of the antimicrobia was not sufficient. He then underwent left pleuropneumonectomy. Salmonella was cultured also from the specimen obtained at the operation. His course after operation was uneventful. Thus, although Salmonella Enteritidis is known as a common pathogen of food poisoning, it can cause empyema, especially in a case with an impaired host defence system.

Background Thymic carcinoma is a rare, malignant mediastinal tumor that is definitively distinguished from thymoma by its wide extensiveness and poor prognosis. At present, cisplatin-based triplet or quartet chemotherapy with the second generation antitumor agents, referred to as Einhorn's protocol for germ cell tumors, is used as first-line chemotherapy for advanced thymic carcinoma, though an optimal chemotherapeutic regimen has not yet been established. In this retrospective study, the effectiveness and toxicity of cisplatin and irinotecan combination chemotherapy were evaluated over a nine-year period. Patients and methods Patients with advanced thymic carcinoma who were treated with cisplatin and irinotecan combination chemotherapy between January 1, 2002 and December 31, 2010, were retrospectively identified from our database and medical records. The endpoints in this study were disease control, response rate, progression-free survival (PFS), and overall survival (OS). Significant hematological and non-hematological toxicities were also assessed. Results Among identified nine patients, disease control was achieved in 8 patients (88.9%), and a clinical response was achieved in 5 (55.6%). The median PFS was 7.9 months, and the median OS was 33.8 months. One- and two-year OS were 77.7% and 55.6%, respectively. Grade 3/4 hematological toxicities were observed in 2 patients (22.2%), and Grade 3/4 non-hematological toxicities were seen in 2 patients (22.2%). No febrile neutropenia or toxic death was recorded. Conclusion Cisplatin and irinotecan combination chemotherapy appears to be acceptable for advanced thymic carcinoma as first-line chemotherapy with respect to efficacy, toxicity, and usage in the clinical setting.

EGFR-TKI yields a long survival period in cases of non-small cell lung cancer (NSCLC), especially those with EGFR gene mutations, but the effect is limited. The later treatment strategy is still a large problem. Efficacy by re-treatment with EGFR-TKI is sometimes reported, but its clinical significance is not clear.We reviewed retrospectively 22 cases (gefitinib 11 cases and erlotinib 11 cases) of NSCLC re-treated with EGFR-TKI in our hospital from August 2004 to August 2009.After re-treatment with gefitinib, four cases showed disease control. Efficacy of erlotinib was recognized in the cases in which disease control was obtained by initial treatment with gefitinib. The disease control rate was 36% (4/11) in the gefitinib group and 45% (5/11) in the erlotinib group. Median survival time was 212 days and 292 days from re-treatment with EGFR-TKI, respectively.Re-administration of EGFR-TKI was effective, and therefore is considered one of the treatment options for patients who once respond to gefitinib, until new anti-cancer drugs are available.

過去13年間の肺癌における組織型の比率の変遷について検討を行った. 対象は1976年～1988年の13年間に当院で病理組織学的に診断の確定した肺癌患者, 955名 (男711名, 女224名) で, 腺癌患者が45%, 扁平上皮癌患者が33%であった. 肺癌患者は増加しており, その組織型においては, 扁平上皮癌比率の減少と腺癌比率の増加がみられ, その傾向は特に1981年以降, 扁平上皮癌と腺癌の比率逆転という事態になった. この変遷は, 性別や年齢構成の変化によるものではなかった. 1983年までの日本TNM肺癌委貝会の患者登録からみても全国的に腺癌の比率が増加していることが推察される. 従来, 扁平上皮癌が腺癌より多いと言われていたが, 近年では, 腺癌の方が多くなっている可能性が示唆された.

Since HIV infection and opportunistic infections began to be treated by highly active antiretroviral therapy (HAART), the incidence of cancers, especially lung cancer increased. The clinical course of lung cancer in HIV infected patients is more aggressive, and little is known about its features or management. We retrospectively evaluated 6 cases of lung cancer with HIV infected patients in Tokyo Metropolitan Komagome Hospital. All patients were male and current smokers. Adenocarcinoma, squamous cell carcinoma and small cell carcinoma were observed in 3, 2 and 1, respectively. There were 2 cases each of clinical Stage I, IIIB, and IV were each 2 cases. The range of the CD4 cell count was 52-432/microL. HIV infection was confirmed concurrently with the diagnosis of lung cancer or complications in 5 of 6 patients. Some cases treated for both lung cancer and HIV, had a relatively good clinical course. We suggest that cancer treatment concurrently with HAART may be useful for similar cases. Further experience and study are necessary.

Amrubicin, a totally synthetic 9-aminoanthracycline, was evaluated retrospectively for the treatment of refractory and relapsed small-cell lung cancer (SCLC).Retrospective analysis was performed in 32 patients. Amrubicin was infused over 5 min on days 1-3, with courses repeated at 3- or 4-week intervals. Amrubicin was given at a dose of 45 mg/m(2) per day, 40 mg/m(2) per day, 35 mg/m(2) per day, 30 mg/m(2) per day, or 25 mg/m(2) per day depending on medical conditions (patients' age and performance status [PS]), and the dose was modulated according to myelosuppression.The median number of treatment cycles was 3 (range, 1-6). Seventeen patients (53.1%) had a partial response. Median progression-free survival time for all patients was 96 days, and median survival time was 166 days. Grade 3 or 4 hematologic toxicities comprised neutropenia (78.1%), anemia (65.6%), and thrombocytopenia (50.0%). Febrile neutropenia was observed in 8 patients (25.0%). Nonhematologic toxicities were mild. Treatment-related death was observed in 1 patient.Treatment with amrubicin appeared effective in SCLC patients previously treated with chemotherapy, although it was not necessarily safe, because of myelosuppression. Further research is warranted to investigate amrubicin treatment for patients with SCLC.

The percentage of oxidized coenzyme Q10 in total coenzyme Q10 (%CoQ-10) has been shown to indicate the degree of systemic oxidative stress. Chronic obstructive pulmonary disease (COPD) is regarded as a systemic disease that is linked to oxidative stress in its pathogenesis. In this study, the plasma %CoQ-10 levels in COPD patients were determined and assessed. In addition, the effect of oxygen supplementation on plasma %CoQ-10 was also evaluated.Thirteen COPD patients who had not received oxygen supplementation (COPD-Pt), five COPD patients who had received oxygen supplementation (COPD + O2) and 20 age-matched control subjects (CONTROL) were enrolled. We have also enrolled 83 young healthy non/slight smokers (smoking index20 pack-year) and 24 young healthy smokers (smoking indexor = 20 pack-year) in order to assess the effect of smoking history on %CoQ-10 level. Their plasma was collected and plasma %CoQ-10 levels were determined and compared.The plasma %CoQ-10 of COPD-Pt was 6.3 +/- 2.3, significantly higher than that of CONTROL, 4.7 +/- 1.6 (p0.05), indicating an increased oxidative stress in the patients. In contrast, no significant difference in %CoQ-10 was observed between young healthy non/slight smokers (%CoQ-10 = 3.2 +/- 0.9) and young healthy smokers (%CoQ-10 = 3.7 +/- 1.3). Our observation of five COPD patients who received an oxygen supplementation revealed that their %CoQ-10 values (4.0 +/- 1.5) were significantly lower than those in COPD-Pt subjects (p0.05), suggesting that oxygen supplementation ameliorates the oxidative stress. In contrast, our study showed that no significant difference was observed among the three groups in plasma levels of Vitamin C or E. In conclusion, plasma %CoQ-10 levels are increased in COPD patients and oxygen supplementation attenuates this increasing effect by COPD. This implies that %CoQ-10 might be used practically to assess the COPD patients systemically.

We experienced a case in which severe alveolar hemorrhage occurred in the course of gefitinib therapy. A 56-year-old man with non-small cell lung cancer had been treated with CDDP + CPT-11, CDDP + GEM + VNR, CDDP + TXT. After the chemotherapy with these regimens was found to be ineffective, daily oral gefitinib was started. Four weeks later, the patient complained of cough, bloody sputum and dyspnea. Chest X-ray and CT showed bilateral infiltrations with air bronchogram. Fiberoptic bronchoscopy revealed alveolar hemorrhage with an increase of lymphocytes in the BALF. After the cessation of gefitinib therapy and the administration of steroid, he gradually recovered.

A 59-year-old woman whose first clinical manifestations were polyuria and polydipsia was admitted to our hospital. Brain MRI showed multiple mass lesions and a thickened pituitary stalk. Chest CT showed hilar and mediastinal lymphadenopathy and a small nodule measuring about 1.5 cm in the apex of the right lung. Histopathological examination revealed adenocarcinoma of the lung, and primary lung cancer with diabetes insipidus secondary to pituitary stalk metastasis was diagnosed. She received systemic chemotherapy and whole-brain irradiation concurrent with intranasal desmopressin (DDAVP) treatment. Although the size of the tumor was reduced, her symptoms did not improve and the same dose of hormone replacement therapy was required. We present this rare case and review the twenty cases of metastatic pituitary lesions arising from lung cancer reported in the literature.

Backgrounds Small-cell lung carcinoma is recognized as a malignant tumor with high sensitivity to anticancer drug, and it is recommended strongly to carry out the systemic chemotherapy for patients of small-cell lung cancer with enough general condition. However, there are few evidence of the efficiency and toxicity of the chemotherapy for cases presenting poor PS. Methods We reviewed medical charts of patients of extensive small-cell lung cancer with poor PS (ECOG;3,4) treated by systemic chemotherapy from April 2002 to January 2012 at Metropolitan Komagome Hospital. Result The characteristics of the 16 cases were median age 74.5 years, 12 cases with PS 3, 4 cases with PS 4. All cases carried out at least one cycle of chemotherapy including platinum drug. Results and conclusions Previously, the medium survival time for patients of extensive small-cell lung cancer with only best supportive care is reported to be 1–2 months. Our investigation suggested that systemic chemotherapy contributes to the extension of survival time even among cases with poor PS; therefore, chemotherapy can be considered for patients who wish life prolongation.

Background Cisplatin and docetaxel (DP), cisplatin and vinorelbine (CV), calboplatin and paclitaxel (CbP) are optimal regimens for locally advanced non-small-cell lung cancer (LA-NSCLC). Patients and methods We retrospectively analyzed the effectiveness and safety of DP, CV and CbP with the concurrent thoracic radiotherapy (TRT) in patients with unresectable LA-NSCLC between August 2005 and August 2011. Results We identified 76 patients. DP/CV/CbP were undergone in 25/44/7 patients. The median age was 68 years (37–74); male/female, 57/19; PS 0/1, 46/33; Ad/Sq/NOS, 41/29/14; and clinical stage IIB/IIIA/IIIB, 4/32/40. Dose delivery of chemotherapy was 88/92/80% (DP/CV/CbP) and that of TRT was 93/92/99%. Sixty-three patients responded to the therapy, including five CR (2/3/0), 58 PR (19/33/6). Forty-four patients had recurrence (12/27/5). Among them, 21 patients recurred at a local site (8/10/3) and 23 patients at a distant site (4/17/2). Of this, 45 patients developed grade 3 or greater hematological toxicities (10/33/2). Non-hematological toxicities were grade 3 radiation esophagitis in four patients (2/1/1) and grade 3 radiation pneumonitis in seven patients (2/3/2), respectively. Discussion The efficacy, dose delivery and safety in DP and CV arms were similar to previous trials.

Background: The phase II NEJ001 trial suggested that gefitinib was active against advanced non-small cell lung cancer (NSCLC), even in patients with poor performance status (PS). Because the NEJ001 trial established definitive clinical evidence, and a further phase III trial may not be required, there is little additional information on the clinical outcomes of gefitinib in poor PS patients. Patients and methods: This was a retrospective review of patients with EGFR mutation-positive NSCLC and poor PS (PS ≥2 for patients >75 years or PS 3 or 4 for patients of any age) who were treated with first-line gefitinib between 2004 and 2013 at Tokyo Metropolitan Cancer and Infectious Diseases Center at Komagome Hospital. Results: A total of 52 patients (median age, 75 years; range, 54–87 years) met the inclusion criteria. The overall response rate was 65.4%. The median progression-free survival, median survival time, and one-year survival rate were 6.6 months, 19.6 months, and 62.9%, respectively. Gefitinib was terminated in 17 patients (32.7%) due to toxicity (6 patients due to interstitial lung disease, 3 patients due to inability to continue oral intake, and 3 patients due to elevated transaminase levels). Conclusions: Gefitinib is effective in patients with poor PS, even in the clinical setting. The overall response rate, progression-free survival, and median survival time were similar to those in NEJ001. As in NEJ001, progression-free survival was shorter than reported in clinical trials for patients with EGFR mutation and good PS.