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Immune checkpoint inhibitors (ICIs) have caused revolutionary changes in cancer treatment, but low response rates remain a challenge. Semaphorin 4A (Sema4A) modulates the immune system through multiple mechanisms in mice, although the role of human Sema4A in the tumor microenvironment remains unclear. This study demonstrates that histologically Sema4A-positive non–small cell lung cancer (NSCLC) responded significantly better to anti–programmed cell death 1 (PD-1) antibody than Sema4A-negative NSCLC. Intriguingly, SEMA4A expression in human NSCLC was mainly derived from tumor cells and was associated with T cell activation. Sema4A promoted cytotoxicity and proliferation of tumor-specific CD8 + T cells without terminal exhaustion by enhancing mammalian target of rapamycin complex 1 and polyamine synthesis, which led to improved efficacy of PD-1 inhibitors in murine models. Improved T cell activation by recombinant Sema4A was also confirmed using isolated tumor-infiltrating T cells from patients with cancer. Thus, Sema4A might be a promising therapeutic target and biomarker for predicting and promoting ICI efficacy.

Osimertinib is the standard of care in the initial treatment for advanced epidermal growth factor receptor (EGFR) mutation-positive lung cancer. However, clinical data and reliable prognostic biomarkers are insufficient.We performed a retrospective multicentre cohort study for 538 EGFR mutation-positive patients, who received osimertinib as the initial treatment between August 2018 and December 2019. The main outcome was progression-free survival (PFS).The median observation period was 14.7 months (interquartile range 11.4-20.0). The median PFS was 20.5 months (95% confidence interval [CI] 18.6-not reached). Multivariate analysis showed that sex (male) (hazard ratio [HR] 1.99, 95% CI 1.35-2.93, P = 0.001), malignant effusions (HR 1.51, 95% CI 1.11-2.04, P = 0.008), liver metastasis (HR 1.55, 95% CI 1.03-2.33, P = 0.037), advanced unresectable cases (HR 1.71, 95% CI, 1.04-2.82, P = 0.036), mutation type and programmed cell death-ligand 1 (PD-L1) expression were associated with PFS. The L858R (HR 1.55, 95% CI 1.01-2.38, P = 0.043) and uncommon mutations (HR 3.15, 95% CI 1.70-5.83, P 0.001) were associated with PFS. PD-L1 expression of 1-49% (HR 1.66, 95% CI 1.05-2.63, P = 0.029), ≥50% (HR 2.24, 95% CI 1.17-4.30, P = 0.015) and unknown (HR 1.53, 95% CI 1.05-2.22, P = 0.026) was associated with PFS. The main reasons for treatment discontinuation among 219 patients were disease progression (44.3%), pneumonitis (25.5%) and other adverse events (16.0%).During initial treatment with osimertinib, PD-L1 expression is significantly related to PFS. Adverse events are a noteworthy reason for discontinuation.

Pulmonary pleomorphic carcinoma is a rare malignant tumor that grows rapidly and has a poor prognosis. Although no effective treatments have so far been established, immune checkpoint inhibitors (ICIs) have shown clinical improvement in some cases of pleomorphic carcinoma. However, pseudoprogression is a major concern for treatment of this carcinoma using ICIs. Here, we report the case of a 61‐year‐old man who was diagnosed with large cell carcinoma of the lung with brain metastases. Systemic chemotherapy comprising carboplatin and pemetrexed was administered as a first‐line therapy; however, disease progression was observed. A tonsillar lesion grew rapidly after the administration of nivolumab as a second‐line therapy. Tracheostomy was planned to avoid suffocation, but the patient naturally expectorated the tumor. Pathological examination revealed that it was a palatine tonsillar metastasis of pulmonary pleomorphic carcinoma with infiltration of CD8+/CD4‐ lymphocytes and necrosis. The primary lesion expanded after nivolumab administration and shrank with no additional nivolumab administration. We therefore concluded that pseudoprogression caused expectoration of the tonsillar metastasis. Hence, ICIs can cause serious adverse events due to pseudoprogression., We report a case of expectoration of tonsillar metastasis of pulmonary pleomorphic carcinoma after administration of nivolumab. We concluded that pseudoprogression caused expectoration of tonsillar metastasis, since the specimen of biopsy from tonsillar metastasis showed infiltration of CD8+/4‐ cells. This rare condition assists in elucidating the mechanism of pseudoprogression.

Here, we report a rare case involving a 66‐year‐old man with epidermal growth factor receptor (EGFR)‐mutant lung adenocarcinoma and antisynthetase syndrome (ASS) treated with osimertinib. The patient presented with respiratory failure and bilateral pulmonary opacities; he was diagnosed with ASS accompanied by interstitial lung disease (ILD), consistent with paraneoplastic syndrome. After steroid pulse therapy, osimertinib was administered for lung adenocarcinoma without ILD exacerbation. Osimertinib could therefore be a treatment option for EGFR‐mutant lung cancer with paraneoplastic ILD., We report a case involving a patient with epidermal growth factor receptor‐mutant lung adenocarcinoma and antisynthetase syndrome accompanied by interstitial lung disease (ILD), treated with osimertinib. After steroid pulse therapy, osimertinib was administered for the lung adenocarcinoma, without ILD exacerbation. Osimertinib could be a treatment option for EGFR‐mutant lung cancer with paraneoplastic ILD.

Background and objective: Osimertinib as first-line treatment for patients with non-small cell lung cancer (NSCLC) harboring epidermal growth factor (EGFR) mutations remains controversial. Sequential EGFR-tyrosine kinase inhibitor (TKI) might be superior to the first line osimertinib in patients at risk of developing acquired T790M mutations.Methods: We enrolled consecutive patients with EGFR-mutated (deletion 19 or L858R) advanced NSCLC treated with first-line drugs and evaluated predictive markers using classification and regression tree (CART) for the detection of T790M mutations based on patient backgrounds prior to initial treatment.Results: Patients without acquired T790M mutations had worse outcomes than those with T790M mutations (median OS: 798 days vs. not reached; HR: 2.70; P

Obstructive endobronchial tumours often cause decreased quality of life. Bronchial ethanol injection (BEI) therapy is considered an effective modality for airway dilatation or haemoptysis without specialist equipment. Here, we report experiences of two cases in which BEI therapy was effective for obstructive endobronchial tumours. In Case 1 with adenoid cystic carcinoma of the lung, BEI therapy and balloon dilatation were performed as treatment for the left main bronchus restenosis after metallic stent insertion. In Case 2 with squamous cell carcinoma of the lung, BEI therapy was performed after radiation therapy to the lesion that recurred in the entrance of the superior segment of the right lower lobe. Tumour progression was controlled with multiple BEI therapy. We consider BEI therapy useful because this procedure is easy to conduct, has low cost and can be done under particular conditions including post‐tracheobronchial stent placement and post‐radiation., Obstructive endobronchial tumours often cause decreased quality of life. Bronchial ethanol injection (BEI) therapy is considered an effective modality for airway dilatation or haemoptysis without specialist equipment. Here, we report experiences of two cases in which BEI therapy was effective for obstructive endobronchial tumours.

The incidence of real-world pneumonitis and durvalumab rechallenge during chemoradiotherapy and durvalumab consolidation for non-small cell lung cancer is unknown.We retrospectively evaluated the medical records of 302 consecutive patients diagnosed with non-small cell lung cancer who started chemoradiotherapy between May 2018 and May 2019.Median age was 70 (range: 40-87) years. Volume of lung parenchyma that received 20 Gy (V20) exceeded 35% in 2% and mean lung dose exceeded 20 Gy in 1% of patients. Durvalumab consolidation was delivered to 225 patients (75%). Overall, 83% (n = 251), 34% (n = 103), 7% (n = 21), and 1% (n = 4) of the patients developed any grade of pneumonitis, symptomatic pneumonitis, ≥grade 3 pneumonitis, and fatal (grade 5) pneumonitis, respectively. Corticosteroids were administered to 25% of the patients to treat pneumonitis. Multivariate analysis identified the predictive factors for the development of symptomatic pneumonitis: V20 Gy or more ≥ 25% (odds ratio [OR]: 2.37, P = 0.008) and mean lung dose (MLD) ≥ 10 Gy (OR: 1.93, P 0.0047). Of the 52 patients who received corticosteroids for pneumonitis after durvalumab initiation, 21 were rechallenged with durvalumab. Overall, 81% of patients met the PACIFIC study's rechallenge criteria and did not experience a severe pneumonitis relapse.High V20 and MLD were independent risk factors of symptomatic pneumonitis. More than 80% of the patients who were rechallenged with durvalumab after pneumonitis met the PACIFIC study's rechallenge criteria. Consequently, severe relapse did not occur. Cooperation between radiation and medical oncologists is important for safe chemoradiotherapy and the safe completion of durvalumab consolidation therapy.

BACKGROUND Nivolumab is an anti-PD-1 blocking monoclonal antibody approved for the treatment of non-small cell lung cancer (NSCLC). However, some patients on immunotherapy may experience rapid progression and worsening clinical status, known as hyperprogressive disease. We retrospectively reviewed the clinical records of patients with NSCLC administered nivolumab therapy at Toneyama National Hospital, Japan, from January 2016 to January 2018. Of the 87 patients administered nivolumab therapy, five experienced rapid progression during one cycle of nivolumab therapy. Four patients were treated with corticosteroids to overcome their symptomatic events. Nivolumab exhibited efficacy after temporal progression, so-called "pseudoprogression", in three patients, and their symptoms and laboratory results improved. In the other patient, pleural and pericardial effusions increased after nivolumab therapy, and drainage was required, with no subsequent recurrence. The clinical courses of our case series indicate that alternative treatment, namely high-dose corticosteroids, antibiotics, and drainage, effectively treated the symptoms of rapid tumor progression. Of note, corticosteroids suppressed the temporary inflammatory reaction to nivolumab. Although hyperprogressive disease is thought to be associated with poor quality of life and survival, these treatment strategies may be useful in patients with expected responses to immunotherapy.

Background Immune checkpoint inhibitors (ICIs) have emerged as promising therapeutic agents in non-small cell lung cancer (NSCLC). However, the duration for which ICIs should be continued remains a clinical problem. Methods We examined the efficacy of anti-PD-1/PD-L1 inhibitors after the discontinuation of antibodies due to adverse events (AEs) in patients with NSCLC. This was a multicenter retrospective study that analyzed NSCLC patients who were treated with PD-1/PD-L1 inhibitors by August 2016. Results The patients with NSCLC were 18 males and 1 female at a median 67 years of age (range: 49–80 years). Eighteen of 19 patients were treated with nivolumab, one was with atezolizumab. Approximately half of AEs were interstitial pneumonia. Fourteen patients (73.7%) were treated with steroid therapy. The median number of treatment cycles was 7 (range, 1–70), and the median duration of treatment was 2.8 months (range, 1 day-32.9 months). The overall response rate with confirmation during treatment was 21.1%. The median progression-free survival (PFS) was 10.2 months (95% confidence interval [CI] = 3.2–17.1 months) and 5.6 months (95% CI = 0–12.2 months) from the initiation and the discontinuation of PD-1/PD-L1 treatment, respectively. The median PFS after discontinuation according to the confirmed response during administration was not reached for partial response (PR) and 4.9 months (95% CI, 3.7–6.0) for stable disease (SD) patients (P = 0.02). Conclusion The PFS of the PR patients was completely different from that of the SD patients. The cases with PR prior to the onset of AE tended to show a durable response after the discontinuation of PD-1/PD-L1 inhibitors. Electronic supplementary material The online version of this article (10.1186/s12885-018-4819-2) contains supplementary material, which is available to authorized users.

We conducted a phase II trial to evaluate the efficacy and safety of induction chemotherapy of pemetrexed plus split-dose cisplatin followed by pemetrexed maintenance for advanced non-squamous non-small-cell lung cancer (NSCLC). Patients with advanced or recurrent untreated non-squamous NSCLC received split-dose cisplatin (40 mg/m2, days 1 and 8) plus pemetrexed (500 mg/m2, day 1) tri-weekly. After four cycles of induction, patients without disease progression received pemetrexed maintenance until disease progression or unacceptable toxicity. The primary endpoint was the 1-year survival rate. The secondary endpoints were progression-free survival (PFS), overall survival (OS), response in induction phase, and safety. From February 2012 to September 2014, 53 assessable patients were enrolled in this study. Thirty-eight (71.7%) patients completed induction therapy, while 35 (66.0%) received maintenance therapy. The 1-year survival rate was 67.7%. The median PFS and OS were 5.3 and 18.6 months, respectively. The response rate and disease control rate (DCR) during the induction phase were 37.7 and 86.8%, respectively. Eight patients (15.1%) discontinued the therapy due to adverse events (AEs) during the induction phase, but both hematological and non-hematological AEs were infrequent. Treatment with induction chemotherapy of pemetrexed plus split-dose cisplatin showed a promising 1-year survival rate, DCR, and transition rate into maintenance phase. This regimen is feasible and well-tolerated. A phase III study comparing this regimen with conventional tri-weekly regimen is warranted.

A 59-year-old woman suffering from dry cough and dyspnea was admitted to our hospital. She had undergone concurrent chemo-radiotherapy five months earlier. Chest computed tomography revealed bilateral ground-glass opacities extending outside the irradiated lung field. Her eosinophil numbers were increased in both the peripheral blood and the bronchoalveolar lavage fluid; therefore, she was diagnosed with radiation pneumonitis accompanied by eosinophilic alveolitis. Steroid therapy promptly improved the pneumonitis. Radiation pneumonitis accompanied by eosinophilic alveolitis extending outside the irradiated field is rare. Bronchoalveolar lavage is useful for a diagnosis, and steroid therapy is effective for treatment.

Pleomorphic carcinoma (PC) of the lung is a rare type of non-small cell lung cancer, exhibiting aggressive behavior and resistance to chemotherapy and radiotherapy. A previous study reported that PCs expressed high levels of PD-L1, suggesting the potential efficacy of immune checkpoint inhibitors in these tumors. We retrospectively reviewed the clinical records of three patients with PC of the lung treated with nivolumab: a 59-year-old woman (Case 1), a 66-year-old man (Case 2), and an 83-year-old man (Case 3). PD-L1 was highly expressed in their tumor cells. Two cases showed a partial response with long progression-free survival. However, in Case 2, brain and bone metastases progressed during nivolumab treatment in spite of high PD-L1 expression. This case series indicates that nivolumab is effective to some extent for PC of the lung. However, the clinical course of patients treated with nivolumab should be carefully observed, even when PD-L1 is highly expressed.

This multicenter, single-arm, open-label, phase 2 study assessed the efficacy and safety of carboplatin plus weekly nanoparticle albumin-bound paclitaxel in elderly patients with previously untreated advanced squamous non-small-cell lung cancer, selected based on the Mini Nutritional Assessment short-form scores (MNA-SF). Patients received carboplatin (area under the curve: 6) on Day 1, and nanoparticle albumin-bound paclitaxel (100 mg/m2) on Days 1, 8, and 15, every 28 days for ≤4 cycles. Eligibility criteria included an MNA-SF score of ≥8 points. The primary endpoint was the objective response rate. Thirty patients with a median age of 76 (range 70–83) years were enrolled. The objective response rate was 50.0% (95% confidence interval: 31.3–68.7%), which met the primary objective of this study. The disease control rate was 73.3% (95% CI: 54.1–87.7%). At a median follow-up of 15.0 months, the median progression-free and overall survival was 7.1 and 19.1 months, respectively. The most common treatment-related adverse event of Grade ≥3 was neutropenia (66.7%). Non-hematological adverse events of Grade ≥3 were minor. Well-nourished patients, based on the MNA-SF, experienced fewer adverse events of Grade ≥3 compared to patients at risk of malnutrition. All treatment-related adverse events were tolerable and reversible. There were no treatment-related deaths. Carboplatin plus weekly nanoparticle albumin-bound paclitaxel is effective and well tolerated as a first-line treatment for elderly patients with advanced squamous non-small-cell lung cancer. Eligibility based on MNA-SF screening may be useful in determining acceptable toxicity.

Background RET fusions were recently identified in non-small cell lung cancer (NSCLC) and are considered as a potential therapeutic target of NSCLC. Sorafenib, a multi-kinase inhibitor, has potent anti- RET activity. We conducted a study to evaluate the efficacy of sorafenib in a small number of patients with RET fusion-positive NSCLC. Materials and methods Eligible patients had advanced or recurrent NSCLC, were more than 20 years old, had undergone treatment with one or more previous chemotherapy regimens, had an Eastern Cooperative Oncology Group performance status 0–2, had adequate organ function, and provided informed consent. The presence of the RET fusion gene was confirmed by a split FISH assay. The patients were treated twice daily with 400 mg of sorafenib taken orally. The treatment was continued until either disease progression or unacceptable toxicity. Results From March 2012 to April 2013, three patients were enrolled. The responses to sorafenib included one patient with stable disease (SD) and two patients with progressive disease (PD). One patient took sorafenib for twelve months. The most common toxicities were palmar–plantar erythrodysesthesia syndrome, hypertension, and diarrhea. Conclusion Since sorafenib did not show dramatic responses, we suggest testing other RET inhibitors for the treatment of RET fusion-positive NSCLC. This study was registered at UMIN as trial number 000007515.

e21076 Background: PD-L1 inhibitor, durvalumab has been approved since the PACIFIC study showed its efficacy as consolidation therapy after CCRT for locally advanced NSCLC. But predictive factor for the efficacy of CCRT on this post PACIFIC era have not been known. LIPI has been proposed as a new biomarker for the anti-PD-1 therapy of advanced NSCLC. In this study, we investigated the usefulness of LIPI as a predictive marker in multicenter cohort of patients with locally advanced NSCLC who received CCRT as initial treatment. Methods: 219 patients with available baseline LIPI were reviewed. The progression free survival (PFS) was estimated by the Kaplan-Meier method, and LIPI were calculated at baseline. Kaplan-Meier estimates of PFS and recurrence were compared using the log-rank test for trend. Multivariable analysis was conducted using the Cox and logistic regression models, respectively, adjusted for age, sex, ECOG-PS, smoking, histology, TNM stage, chemotherapy regimens, Body mass index (BMI), PD-L1 status, EGFR or ALK mutation, and baseline LIPI. Results: 62.5% (n = 137) of the patients had a good (0 factors) LIPI, while 37.5% (n = 82) had intermediate (1 factor) and poor (2 factors) LIPI respectively. In multivariable analysis, good LIPI (0 factors) were significantly associated with longer PFS (HR = 0.46, 95% CI 0.28-0.75; P < 0.01) as did ECOG-PS0 (P < 0.01), ≤stageIIIA (P < 0.01), being treated with durvalumab after CRT (P = 0.04). There were no difference in the patient characteristics between good LIPI and intermediate/poor LIPI, significantly. Higher LIPI (1 or 2 factors) were strongly prognostic factor for recurrence after CCRT in multivariate analysis (P = 0.04), along with ECOG-PS1≤ (P < 0.01), stage IIIB≤ (P < 0.01). Conclusions: The good LIPI predictive value for PFS and disease control in patients treated with CCRT was confirmed. Although a strong statistical significance, we needs to be confirmed further with longer follow-up and prospective study.

9039 Background: Durvalumab was approved as a consolidation therapy after chemoradiotherapy (CRT) for locally advanced non-small cell lung cancer (NSCLC) and established as the standard of care. However, since the approval of durvalumab, little has been reported on the frequency, severity, or clinical course of pneumonitis/radiation pneumonitis throughout the course of CRT. Methods: We conducted a 17-center, retrospective cohort study of consecutive patients with locally advanced NSCLC who received concurrent chemoradiotherapy (CCRT) with platinum-based chemotherapy between May 2018 and May 2019. Results: A total of 275 patients were included; their median age was 69.9 (range, 40.3-87.5), mean V20 was 19.4% (range, 1.4-37.9), and mean "mean lung dose" was 10.9 Gy (range, 1.5-31.3). Of these, 204 patients received durvalumab consolidation therapy (74.2%). Median follow-up time from the initiation of CCRT was 8.4 months (range, 1.5-15.7). During follow-up, 225 patients (81.8%) developed any-grade pneumonitis/radiation pneumonitis. Of these, more than half (134 of 225) were asymptomatic (grade 1), 18 (6.5%) were ≥grade 3, and 4 patients (1.5%) had fatal pneumonitis/radiation pneumonitis. By the time of initial assessment of response to CCRT, 64 (23.3%) patients had developed radiation pneumonitis. Logistic regression revealed that only V20 ≥25 % was an independent risk factor of symptomatic (≥grade 2) pneumonitis/radiation pneumonitis (OR: 2.74, 95% CI: 1.35-5.53, p = 0.0045). Of the 275 patients, 67 were treated with corticosteroids for pneumonitis/radiation pneumonitis (24.7%), and 14 (5.1%) needed home oxygen therapy after the treatment of pneumonitis/radiation pneumonitis. Among patients treated with corticosteroids, 21 patients received durvalumab rechallenge. Of the 21 patients, 6 (29%) showed pneumonitis/radiation pneumonitis relapse, of which 3 (14%) resulted in suspension of durvalumab rechallenge, but none were fatal. Conclusions: Although over four-fifths of the patients treated with CCRT after the approval of durvalumab developed pneumonitis/radiation pneumonitis, more than half of them were asymptomatic, and ≥grade 3 events accounted for 6.5%. Sometimes patients needed corticosteroid therapy, which was in many occasions effective, and some also underwent durvalumab rechallenge. V20 was an independent risk factor of symptomatic pneumonitis/radiation pneumonitis.

Key Clinical Message The symptoms of infection can be minimal or absent in patients with febrile neutropenia at first. The focal site of infection, which may be the main cause of a fever or be a complication of neutropenia, can develop as neutrophils increase during the clinical course of febrile neutropenia.

Recently, the immune checkpoint inhibitor (ICI) pembrolizumab was demonstrated to be superior to platinum doublet chemotherapy in the first-line setting in patients with tumor programmed death-ligand 1 (PD-L1) expression of at least 50%. However, because patients with epidermal growth factor receptor (EGFR) mutations or anaplastic lymphoma kinase (ALK) rearrangements were not included in that study, the efficacy of pembrolizumab in lung cancers carrying EGFR mutations could not be determined. Here we describe two cases of response to pembrolizumab in EGFR mutated lung adenocarcinoma patients with PD-L1 overexpression. These cases indicate that ICI is an effective treatment for EGFR mutated lung adenocarcinoma patients with PD-L1 overexpression.

Nivolumab, an anti-programmed cell death-1 protein monoclonal antibody, is effective for treating patients with late-stage non-small-cell lung cancer. Immune checkpoint inhibitors such as nivolumab induce various kinds of immune-related adverse events, including vitiligo. Vitiligo has been reported in patients with melanoma but not lung cancer. We describe a 75-year-old man with lung adenocarcinoma, stage 4 with pleural and pericardial effusion, that progressed after first-line chemotherapy. Subsequently, he was treated with nivolumab as second-line therapy. After 6days of administering nivolumab, he developed vitiligo suddenly on the trunk of his body. Except for vitiligo, his physical examination was normal, and treatment with nivolumab was well tolerated. Therefore, this treatment was continued without further development or expansion of vitiligo. A computed tomography scan showed a reduction in the size of the lung nodule and stabilization of the pleural and pericardial effusion. This is the first case of vitiligo associated with the use of nivolumab in a patient with lung adenocarcinoma.

背景．肺癌は高頻度に脳転移をきたすが，他疾患との鑑別は画像で評価せざるを得ない．剖検にて脳膿瘍および細菌性髄膜炎の併発が判明した肺癌・多発脳転移の症例を経験した．症例．57歳男性．胸部異常陰影の精査目的に紹介入院となる．胸部CTと頭部CTより左上葉肺門部肺癌，多発性脳転移と臨床診断した．入院後急速に意識障害が進行し，放射線治療とステロイドの投与を開始したが第4病日に死亡した．剖検では肺扁平上皮癌と多発脳転移を認め，その壊死巣に肺炎球菌の感染による脳膿瘍，細菌性髄膜炎が併発していた．癌の転移巣自体は小さかったため，末期の意識障害は膿瘍拡大による影響と思われた．結論．脳膿瘍の頭部CT所見は転移性脳腫瘍と類似しており，神経症状の進行が速い場合にはまれではあるが留意すべき併発症である．

Objectives The effectiveness of treatment after cessation of nivolumab in patients with advanced non-small cell lung cancer (NSCLC) has not been well investigated. The aim of the present study was to clarify the clinical benefit of post-nivolumab treatment in such patients. Materials and methods A retrospective review was conducted on patients who received treatment after cessation of nivolumab due to disease progression or adverse events at the Toneyama National Hospital between January 2016 and April 2017. Results Among 64 patients treated with nivolumab, 26 patients received treatment after cessation of nivolumab due to disease progression (n = 21) or adverse events (n = 5). The median age of the patients was 68 years and 19 patients were male. Nineteen patients had performance status (PS) 1 or less at initiation of post-nivolumab treatment. Four, 20, and 2 patients were treated with platinum doublets, a single agent, and molecular targeting agents, respectively. Response rate, disease control rate, and median progression-free survival of first-line post-nivolumab treatment were 34.6% (9 patients), 73.1% (19 patients), and 2.8 months (95% confidence interval [CI]: 1.7–5.2), respectively. Adverse events (≥ grade 3) and treatment cessation were observed in 57.7% (15 patients) and 19.2% (5 patients), respectively. There were no statistically significant differences for the majority of patient characteristics between the groups with (n = 26) and without post-nivolumab treatment. However, PS at cessation of nivolumab and post-progression survival (PPS) after cessation of nivolumab (median PPS: 12.6 vs. 1.4 months, 95% CI: 3.8–14.7 vs. 0.4–2.2) were significantly different between the groups. A multivariate Cox regression analysis showed significant correlation of PS at cessation of nivolumab (hazard ratio [HR]: 0.34, 95% CI: 0.13–0.87) and post-nivolumab treatment (HR: 0.19, 95% CI: 0.08–0.43) with prolonged PPS after nivolumab. Conclusion Median post-progression survival in patients with advanced NSCLC who received post-nivolumab treatment was approximately 1 year.

Little evidence exists regarding a relationship between survivin expression and prognosis in small cell lung cancer (SCLC). We investigated the relationship between survivin expression, clinical characteristics and prognosis in SCLC patients.We retrospectively reviewed medical records of study patients and analyzed their tumor sections using nuclear survivin labeling index (LI).A significant correlation between nuclear survivin LI and clinical stage was found (p=0.012). In multivariate analysis, a significant association was found between survival and clinical stage (hazard ratio (HR)=2.09; 95 % confidence interval (CI)=1.08-4.31; p=0.027) but not between survival and nuclear survivin LI (HR=0.96; 95 % CI=0.91-1.02; p=0.2).We did not find any positive relationship between nuclear survivin expression and survival in SCLC patients. Conversely, we found a positive relationship between clinical stage and nuclear survivin LI, which is considered to be useful in deciding treatment strategies.

A 61-year-old man was diagnosed with lung squamous cell carcinoma in the lower lobe of the right lung. He had received first-line chemotherapy consisting of cisplatin and docetaxel (DTX); however, an allergic/hypersensitivity reaction occurred shortly after administration of the second course of DTX. Thirty-nine months later, he received nanoparticle albumin-bound paclitaxel (nab-PTX) as sixth-line chemotherapy, which did not produce a hypersensitivity reaction. Hypersensitivity after DTX administration may have been due to the DTX vehicle. Therefore, nab-PTX administered under close supervision is a valid therapeutic option in similar cases.

A 49-year-old-woman was diagnosed with tuberculosis of the left humerus. She had received treatment, including rifampicin, for tuberculosis 17 years previously. Treatment was begun with isoniazid, rifampicin, ethambutol, and pyrazinamide, but these were discontinued because of mild neutropenia and thrombocytopenia 2 weeks posttreatment. Rifampicin and ethambutol were readministered after a 4-day interruption; however, generalized purpura appeared several hours later. By the next day, her platelet count was reduced from 160 × 10(3) to 3 × 10(3)/μl. The patient improved rapidly after platelet transfusion and steroid treatment. Readministration of drugs other than rifampicin did not induce thrombocytopenia; therefore, thrombocytopenia was likely due to rifampicin.

Manuscript received July 26 , 2012 ; revision accepted September 19, 2012. Affi liations: From the Department of Respiratory Medicine (Drs Uenami, Hayama, Tsuruta, Saito, Niju, and Ikeda), Department of Pathology (Dr Ayata), and Department of Respiratory Surgery (Dr Higaki), Nishinomiya Municipal Central Hospital, Hyogo; and Department of Respiratory Medicine, Allergy and Rheumatic Diseases (Dr Kijima), Graduate School of Medicine/Faculty of Medicine, Osaka University, Osaka, Japan . Drs Uenami and Kijima contributed equally to this article as fi rst authors. Correspondence to: Takeshi Uenami, MD, Department of Respiratory Medicine, Nishinomiya Municipal Central Hospital, 8-24 Hayashida-cho, Nishinomiya, Hyogo 663-8014, Japan; e-mail: med31@nishi-hp.jp © 2013 American College of Chest Physicians. Reproduction of this article is prohibited without written permission from the American College of Chest Physicians. See online for more details. DOI: 10.1378/chest.12-1874 Figure 1. Chest radiograph showing an atelectasis of the right lower lobe. An atelectasis of the right lower lobe of the lung was noted on chest radiograph ( Fig 1 ). Chest CT scan revealed a protruding tumor in the right-side intermedius bronchus with diameters of 18 3 16 mm and a complete atelectasis of the right lower lobe ( Fig 2A ). No findings of invasion, extrabronchial spread, or mediastinal lymphadenopathy were noted. Bronchoscopic examination revealed a soft mass occluding the lumen of the right-side intermedius bronchus, which was immobile and bled easily on contact ( Fig 2B ). The patient underwent middle and lower lobectomy because the possibility of malignancy could not be excluded. On gross examination, the surgically resected specimen consisted of a well-circumscribed mass obstructing the truncus intermedius. The surface of the cross-section was smooth and yellow ( Fig 3A ).

Fluoroquinolones are widely used in the management of infectious diseases, and are generally safe and well tolerated. However, immediate hypersensitivity reactions, including anaphylactic reactions, have been reported. We present here a case of anaphylactic shock in a 26-year-old man following intravenous levofloxacin administration. Skin tests confirmed an immediate hypersensitivity reaction to levofloxacin. Subsequent oral challenge tests for garenoxacin, which showed negative skin test results, confirmed that garenoxacin was well tolerated. This is the first report of tolerance to full-dose garenoxacin in a patient who developed an immediate hypersensitivity reaction to levofloxacin.

Background: The features of pulmonary disease caused by rapidly growing mycobacteria (RGM) have not been sufficiently documented. Objectives: To establish these features, we retrospectively evaluated 44 patients. Methods: We screened respiratory isolates at the National Toneyama Hospital (Osaka, Japan) between 2003 and 2007. Diagnosis was based on the latest guidelines of the American Thoracic Society. The patients were classified into 3 types according to their radiographic findings: fibrocavitary, nodular bronchiectatic and unclassified variant. Results: We obtained 1,348 nontuberculous mycobacteria respiratory isolates from 1,187 patients, including 119 RGM isolates from 100 patients. Forty-four of these 100 patients were definitively diagnosed with respiratory disease due to RGM. The most common pathogen was Mycobacteriumabscessus, which accounted for 65.9% of cases, followed by Mycobacterium fortuitum at 20.5%. There was a statistically significant difference in smoking history between patients infected with these 4 RGM species (excluding those with an unknown smoking history; p = 0.039). The overall evaluation of radiographic findings revealed 18.2% as fibrocavitary, 43.2% as nodular bronchiectatic and 38.6% as unclassified variants in these 44 patients. There was a significant difference in radiographic findings between the 4 RGM species (p = 0.002). There was also a significant difference in radiographic findings between M. abscessus and M. fortuitum infected patients (p = 0.022). Conclusions: Patients with M. abscessus seem to have less of a smoking history and more frequent nodular bronchiectatic radiographic patterns than patients with M. fortuitum. In contrast, fibrocavitary patterns might be more frequent with M. fortuitum infection.

A 63-year-old male smoker with left chest pain was admitted for examination of an abnormal chest shadow. A chest computed tomography (CT) scan revealed a tumor in S6 of the left lung, and left pleural effusion. Histological examination by CT-guided needle biopsy revealed a proliferation of spindle-shaped tumor cells with sarcomatous features. Immunohistochemical staining confirmed the tumor cells to be of epidermal origin, indicating a diagnosis of sarcomatoid carcinoma of the lung. No distant metastases were found, and his disease was judged to be clinical stage IV (T3N2M1a). He received 5 courses of systemic chemotherapy consisting of carboplatin, paclitaxel and bevacizumab, and the tumor shrank. Systemic chemotherapy is generally ineffective for sarcomatoid carcinoma of the lung. However, in the present case this chemotherapy was effective with the addition of bevacizumab.

e19135 Background: The treatment protocol using bevacizumab, pemetrexed (PEM) and cisplatin (CDDP) is considered to one of the strongest regimens for advanced non-squamous (Nsq) non-small cell lung...

e22060 Background: Several targeted agents and gene analysis are important for treatment of non-small cell lung cancer (NSCLC). The single gene examination is not sufficient to make the decision of...