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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.

Background People with allergic rhinitis often have laryngeal symptoms (LSs) in addition to nasal symptoms during the pollen-scattering season. Objective To clarify the characteristics of the LSs induced by pollen exposure using an environmental challenge chamber. Methods Cypress pollen exposure using an environmental challenge chamber for 25 participants with cypress pollen–induced allergic rhinitis was performed for 3 hours for 2 consecutive days in 3 study courses: namely, pollen exposure under normal nasal breathing and pollen or sham pollen exposure with nasal blockage, which eliminated any allergic reactions in the nasal mucosa. The nasal and LSs scores and the levels of serum inflammatory mediators, including eosinophil cationic protein (ECP), were monitored. Laryngeal examinations and physiologic lung tests were also conducted. Results Various LSs were reported, and these LSs were significantly elevated during pollen exposure and even under sham exposure with artificial nasal blockage. The pollen exposure with artificial nasal blockage exaggerated the LSs in 32% of the participants and also increased the serum ECP levels. The serum ECP levels did not change after sham exposure. The findings of both laryngeal examinations and lung tests failed to reveal any significant changes. Conclusion Nasal obstruction could induce significant LSs even without pollen exposure. LSs were enhanced by pollen exposure and allergic reactions in the larynx could thus be involved in this enhancement. Trial Registration clinicaltrials.gov Identifier: UMIN000015667.

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.

Background Biomarkers for predicting the effect of anti–programmed cell death 1 (PD-1) monoclonal antibody against non–small-cell lung cancer (NSCLC) are urgently required. Although it is known that the blood levels of soluble programmed cell death ligand 1 (sPD-L1) are elevated in various malignancies, the nature of sPD-L1 has not been thoroughly elucidated. We investigated the significance of plasma sPD-L1 levels as a biomarker for anti–PD-1 monoclonal antibody, nivolumab therapy. Patients and Methods The present prospective study included 39 NSCLC patients. The patients were treated with nivolumab at the dose of 3 mg/kg every 2 weeks, and the effects of nivolumab on NSCLC were assessed according to the change in tumor size, time to treatment failure (TTF), and overall survival (OS). The baseline plasma sPD-L1 concentration was determined using an enzyme-linked immunosorbent assay. Results The area under the curve of the receiver operating characteristic curve was 0.761. The calculated optimal cutoff point for sPD-L1 in the plasma samples was 3.357 ng/mL. Of the 39 patients, 59% with low plasma sPD-L1 levels achieved a complete response or partial response and 25% of those with high plasma sPD-L1 levels did so. In addition, 22% of the patients with low plasma sPD-L1 levels developed progressive disease compared with 75% of those with high plasma sPD-L1 levels. The TTF and OS were significantly longer for those patients with low plasma sPD-L1 levels compared with the TTF and OS for those with high plasma sPD-L1 levels. Conclusion The clinical benefit from nivolumab therapy was significantly associated with the baseline plasma sPD-L1 levels. Plasma sPD-L1 levels might represent a novel biomarker for the prediction of the efficacy of nivolumab therapy against NSCLC.

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.

Hepatitis C virus (HCV) infection may result in progression to chronic hepatitis, cirrhosis and hepatocellular carcinoma. Interferon-based treatment in patients with chronic hepatitis C may achieve viral clearance, and as a consequence improve liver histology and prevent progression to hepatocellular carcinoma. At present, the recommended therapy for chronic hepatitis C is peg-interferon-alpha (PEG-IFN-α) in conjunction with the oral nucleoside analog ribavirin. In the current study, we report a case of polymyositis associated with chronic hepatitis C following PEG-IFN-α and ribavirin therapy. The patient, a 64-year-old female who was treated with combination therapy, demonstrated elevated serum CPK, AST, ALT and LDH levels at 28 weeks after treatment onset. As there was an elevation of the serum HCV-RNA levels, combination treatment was ceased at 24 weeks. The patient had received IFN therapy twice previously (IFN-α 2a and IFN-α 2b with ribavirin therapy); however, no adverse side effects were observed. Further laboratory examination, muscle biopsy and imaging data suggested polymyositis, possibly triggered by the PEG-IFN-α treatment. The patient was subsequently administered prednisolone and the dose tapered over 7 months. As a result the polymyositis has remained in remission. Although many autoimmune diseases have been associated with IFN therapy, the development of polymyositis is extremely rare.

Docetaxel monotherapy is one of the standard treatments for non-small-cell lung cancer in elderly patients. The addition of bevacizumab to docetaxel seems promising; however, the feasibility of this combination has not been investigated in such patients. Patients with advanced non-squamous non-small-cell lung cancer aged 70 years or older who had not previously received cytotoxic chemotherapy were enrolled. Patients in the Level 0 cohort received docetaxel 60 mg/m2 and bevacizumab 15 mg/kg, whereas those in the Level-1 cohort received docetaxel 50 mg/m2 and bevacizumab 15 mg/kg. Chemotherapy was repeated 3 weekly for six cycles. The primary endpoint was toxicity and the secondary endpoints were response rate, progression-free survival, overall survival, and proportion of patients who underwent three or more cycles of chemotherapy. Twenty-one patients were enrolled from December 2010 to September 2012 at six institutes. Of the nine patients enrolled in Level 0, two experienced dose-limiting toxicity (febrile neutropenia and prolonged Grade 4 neutropenia in one patient, and Grade 3 infection in another patient) during the first cycle. Enrollment to the Level 0 cohort was terminated because two patients developed Grade 4 sepsis during later cycles. The remaining 12 patients were enrolled in the Level-1 cohort, in which two dose-limiting toxicities (prolonged Grade 4 neutropenia and Grade 3 increased aminotransferase level) were observed. No patient in the Level-1 cohort experienced Grade 4 nonhematologic toxicity. Grade 4 neutropenia occurred in 89 % of Level 0 patients and 50 % of Level-1 patients. The proportion of patients who experienced Grade 3/4 infection, febrile neutropenia or sepsis was 44 % in the Level 0 cohort, and 8 % in the Level-1 cohort. The overall response rate to chemotherapy and progression-free survival were 29 % (95 % CI, 11–52 %) and 5.9 months (95 % CI, 3.6–9.1 months), respectively. Efficacy outcomes did not differ significantly between the cohorts. Toxicities were tolerable in level-1 cohort. The recommended dose of combination chemotherapy with docetaxel and bevacizumab for elderly patients was determined as 50 mg/m2 of docetaxel and 15 mg/kg of bevacizumab and toxicities were tolerable. Further studies are warranted. UMIN Clinical Trial Registry; UMIN000004240 .

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 Low-dose erlotinib may be as effective as gefitinib or erlotinib at full dose in non-small cell lung cancer (NSCLC) patients with activating mutations of the epidermal growth factor receptor ( EGFR ) gene. Methods Patients with chemotherapy pretreated NSCLC harbouring EGFR mutations received erlotinib at 50mg/d until disease progression or unacceptable toxicities. The dose was escalated to 150mg/d in patients showing no response (i.e. without major tumour shrinkage according to Response Evaluation Criteria in Solid Tumours (RECIST)) to the initial dose during the first 4weeks. The primary end-point was the objective response rate at the dose of 50mg/d. Results Thirty-four patients from seven institutes were enrolled. The study was closed early when no response was confirmed in 15 patients, excluding the possibility that the primary end-point would be met. The objective response and disease control rates at the dose of 50mg/d as determined by an independent review committee were 54.5% and 84.8%, respectively. Four additional patients achieved partial response with increased 150mg/d dose. Progression-free survival and median survival times during the entire period of the study were 9.5 and 28.5months, respectively. Treatment-related toxicities were generally mild, the most common being skin disorders and diarrhoea. Only one case experienced grade 3 toxicity, which was transient increase of hepatic enzymes. Conclusion The primary end-point was not met; low-dose erlotinib is not recommended for fit patients with NSCLC harbouring EGFR mutations. However, it may merit further evaluation for elderly or frail 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.

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.

8567Background: Prognostic factors and efficacy of chemotherapy remain unclear in patients with advanced thymic carcinoma. Methods: We performed a multi-institutional, retrospective study named NEJ...

Thymic epithelial neoplasm is a quite rare malignancy arising from the thymic epithelium, and comprises thymoma, thymic carcinoma, and thymic neuroendocrine carcinoma. The incidence of thymic carcinoma and neuroendocrine carcinoma is much less than thymoma, accounting for 1-4%of anterior mediastinal tumors. These rare tumors are called"orphan tumors,"and standards of clinical management(including chemotherapeutic regimens)have not yet been determined for them yet because of their rarity. In the advanced setting, palliative-intent chemotherapy has been applied using cisplatin-based triplet or quartet chemotherapy with second-generation antitumor drugs, with reference to chemotherapeutic regimens for invasive thymoma such as ADOC, CAP, and VIP chemotherapy. However, biological plausibility is lacking for this approach, given that these tumors differ from thymoma in their expression of cellular surface proteins such as c-Kit and epidermal growth factor receptors. While limited to thymic carcinoma, platinum doublet chemotherapy with a third-generation antitumor drug as first-line chemotherapy is anticipated to offer the same clinical efficacy as multiple-agent combination chemotherapy, but with less toxicities. In second-line or later-lines of chemotherapy, single-agent chemotherapy may be optimal. Molecular biological approaches have been under investigation, but molecular targeted agents remain unavailable.

The optimal chemotherapy for thymic carcinoma has yet to be determined based on clinical evidence because of the rarity of this pathological entity. We report the case of a patient with locally advanced thymic carcinoma in whom radical excision was achieved with intensive preoperative chemotherapy followed by curative-intent surgery. A 59-year-old woman was diagnosed with Masaoka-Koga stage III thymic cancer showing squamous cell carcinoma histology. Invasion to the ascending aorta and left brachiocephalic vein was suspected from imaging, so preoperative chemotherapy with three cycles of cisplatin and irinotecan was administered. Partial response to chemotherapy was achieved and the residual tumor was completely resected with subsequent surgery. Histopathological examination of the resected specimen demonstrated stage II thymic carcinoma. The patient has shown no evidence of recurrence or surgical complications as of 46 months after completing preoperative chemotherapy.

Lung cancer patients with HIV infection are expected to become an emerging issue with respect to morbidity and mortality, as the number of such patients is rapidly increasing. However, few reports or textbooks dealing with this issue have documented the details of these cases. Thus, in clinical settings, infectious disease physicians or medical oncologists occasionally hesitate to treat HIV-infected patients with lung cancer. Since 1996, the outcome of HIV-infected patients has improved, because CD4 cell counts and viral load are generally well controlled with the advent of highly active antiretroviral therapy (HAART), which strongly inhibits HIV viral proliferation and restores the patient’s immunological status. Furthermore, the prognosis in the HIV population has improved significantly due to the prevention and treatment of opportunistic infections (OIs). As a result, HIV infection is chronically manageable. In the preHAART era, the median survival time in the HIV population was 10 years, while, at present, 85% of patients survive more than 10 years.(Sepkowitz, 2001) In the pre-HAART era, most HIV-infected patients died of acquired immunodeficiency syndrome (AIDS). Recently, however, one-third of all such patients die of malignant tumor,(Bonnet et al., 2009) and deaths due to AIDS-defining cancers (ADCs), such as Kaposi’s sarcoma (KS), primary central nervous system lymphoma (PCNSL) and non-Hodgkin’s lymphoma (NHL), and invasive cervical carcinoma, which were defined by the Centers for Disease Control and Prevention (CDC), are decreasing. On the other hand, the number of deaths due to non-AIDS-defining cancers (NADCs) is increasing.(Engels et al., 2008, Silverberg et al., 2009) At present, in the population with HIV infection, lung cancer accounts for 5% of all deaths and 15% of all deaths by malignant tumors.(Bonnet et al., 2009) Of all of the NADCs, lung cancer is the most common,(Engels et al., 2006, Lavole et al., 2006, Patel et al., 2008) followed by breast cancer, soft tissue sarcoma, Hodgkin’s lymphoma (HL), penile cancer, lip cancer, and testicular seminoma.(Frisch et al., 2001) In 1984, Irwin et al. reported the first case with simultaneous HIV infection and lung cancer,(Irwin et al., 1984) and several dozen patients have since been reported in the United States and Europe. (Table. 1) The clinical demographics of lung cancer with HIV infection differ slightly from the general population and are characterized by younger age, advanced stage at diagnosis, and aggressive tumor extension. Thus, the prognosis of lung cancer in the HIV population is poorer than that of lung cancer in the general population.(Lavole et al., 2006) Moreover, patient fragility to treatment needs to be considered. In the general population, lung cancer is the most common cause of cancer death worldwide. Furthermore, in the last decade, there has been progress in lung cancer

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.

Recently, the number of human immunodeficiency virus (HIV) -positive patients has increased in Japan. HIV-positive patients are at a higher risk of cancer than the general population. This paper retrospectively reports the acute adverse effects of radiation therapy on HIV-positive patients who were treated at Tokyo Metropolitan Cancer and Infectious diseases Center Komagome Hospital (TMCICK). Thirty-one cases involving 24 HIV-positive cancer patients who were treated at TMCICK from January 1997 to March 2009 were included in this study. All acute adverse effects of radiation therapy were examined during, and one month after, the last radiation therapy session. Acute adverse effects were classified according to the site of radiation therapy treatment and analyzed using the Common Terminology Criteria for Adverse Events (CTCAE) version 3.0. Grade 3 acute adverse effects were seen in 17% of cases, and Grade 2 toxicities were found in 23% of patients. Damage to the skin and mucosa, including stomatitis or diarrhea, tended to occur after low-dose radiation therapy; however, no severe acute adverse effects were seen in other organs, such as the brain, lung, and bone. Acute adverse effects tended to occur earlier in HIV-positive patients and became severe more frequently than in the general population. In particular, disorders of the mucosa, such as those of the oral cavity, pharynx, and intestine, tended to occur rapidly. It was shown that radiation therapy is safe when treatment is performed carefully and that it is a very useful treatment for cancer in HIV-positive patients.

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.

Aim: Thymic carcinomas are considered to be more aggressive than thymomas and carry a worse prognosis. Although a multimodality treatment is made in many cases as for thymic carcinomas, optimal therapeutic strategy still remains controversial. In the present study, we attempted to clarify the prognostic factors based on the survival to establish suitable treatment strategy. Methods: We performed a single-institution retrospective cohort study. Between June 1987 and October 2012, 70 patients were eventually given a diagnosis of thymic carcinoma. Data included patient demographics, stage, first treatment (e.g. chemotherapy (CT), chemoradiotherapy (CRT), and surgery (S)), pathologic findings, and outcomes. Results: The overall 2- and 5-year survival rate was 61.9% and 36.4%, respectively; mean and median observation time was 30M and 24M, respectively. Two-year survival rates in patients treated with CT, CRT, and S group were 38.7, 52.4, and 80.5%, and 5-year survival rates in patients treated with CT, CRT, and S group were 17.4, 21.0, and 55% for all patients. S group showed significantly better prognosis than the others in overall stage (p=0.0006). Patients undergoing S, however, had similar survival compared with undergoing CT or CRT alone in stage IV a,b subset; CT vs. CRT (p=0.6598), CT vs. S (p=0.1159), CRTvs.S (p=0.3030). Univariate analysis among all patients revealed two significant prognostic factors (P Conclusions: Our analyses indicated that stage by the Masaoka system and type of first treatment would have the prognostic impact. If complete excision is possible at earlier than Masaoka stage III, it may be cured completely. The role of debulking surgery at stage IV a,b was negative. Patient selection, accurate staging, and choice of anticancer drug with a high response rate may be critical to optimizing outcomes. Disclosure: All authors have declared no conflicts of interest.

Aim: Repetitive genotyping is useful to assess the genetic evolution of NSCLC during the treatment course, but the need for a biopsy is a major barrier. Digital PCR is a promising procedure for the detection of mutant alleles in the plasma of cancer patients. Methods: This prospective study enrolled patients with NSCLC harboring known EGFR mutations and who had experienced disease progression during ongoing EGFR-TKI therapy. Eligible patients received daily gefitinib (250 mg) and either PEM (500 mg/m2) or S-1 (80 mg/m2, day 1-14). The treatment was repeated every 3 weeks until disease progression or unacceptable toxicity. Plasma was collected before and after the combination therapy, and digital PCR was performed to assess EGFR L858R, exon 19 deletions and T790M. Serum hepatocyte growth factor (HGF) was measured along with tumor evaluation. Results: From May 2012 to January 2014, nine patients were enrolled. Median age was 67 (range, 52-80) years, and seven patients were female. EGFR mutations at the time of disease diagnosis included L858R in six patients and exon 19 deletions in three patients. Patterns of disease progression during adjacent EGFR-TKI therapy were acquired resistance in seven patients, and primary resistance in two patients. Known EGFR mutations were detected in plasma samples from six (67%) patients at study enrollment. Of these, T790M was concurrently detected in three (50%) patients. HGF level was elevated in one patient with T790M mutation. Four patients underwent gefitinib plus PEM therapy, and five patients received treatment with gefitinib and S-1. The median number of cycles delivered was five, and the median progression-free survival was 5.8 months. Efficacy outcomes did not differ between the two treatment regimens. After the combination therapy, plasma T790M status changed to positive in two patients. HGF did not increase in any patient. Conclusions: Data from noninvasive genetic profiling suggest that the retention of the T790M-positive cell population contributed to the better outcomes in response to combination therapy with EGFR-TKI and cytotoxic agents. Disclosure: A. Kagei: The author is an employee of GeneticLab Co., Ltd. (Sapporo, Japan); T. Yamamoto: The author is an employee of GeneticLab Co., Ltd. (Sapporo, Japan). All other authors have declared no conflicts of interest.

Aim: Lung cancer has become a crucial problem among patients living with human immunodeficiency virus (HIV), causing high mortality in Western countries. Japan has an increasing number of newly infected HIV patients. However, the clinical entities in the East-Asian population are unclear given the identification of ethnic differences in lung cancer in the general population. Methods: Nationwide, retrospective surveillance of patients living with HIV diagnosed with lung cancer from 1986 to 2013 in Japan was performed. This study was supported by a Health and Labour Sciences Research Grant from the Ministry of Health, Labour, and Welfare of Japan (Grant number: H25-AIDS-I-002). Results: 43 lung cancer patients living with HIV were diagnosed (median age, 60.0 years; males, 97.7%; 37.2% early stage, 34.9% advanced stage), 41 of whom were in the antiretroviral therapy era. The median CD4-positive T-cell count was 326 cells/µL. Adenocarcinoma was the most frequent histology (55.8%), followed by squamous cell carcinoma (27.9%). Of the 14 patients in whom epidermal growth factor receptor (EGFR) status was examined, 5 (35.7%) had EGFR mutations. Median overall survival was 25.1 months for all stages and 7.9 months for the advanced stage. On univariate and multivariate analyses, the only prognostic factor for overall survival was stage (p=0.02). Conclusions: There appear to be ethnic differences in the prevalence of EGFR mutations even in the population living with HIV and the clinical characteristics or outcome may be provided in the regional differences. Disclosure: All authors have declared no conflicts of interest.

e18556 Background: Thymic epithelial tumor, comprising of thymoma and thymic carcinoma, is a rare cancer, therefore, optimal chemotherapy for advanced thymic epithelial tumor is still controversial...