Nobuhiro Asai

Relapsed small cell lung cancer: treatment options and latest developments

According to recent analyses, there was a modest yet significant improvement in median survival time and 5-year survival rate of limited stage small cell lung cancer (SCLC) in North America, Europe, Japan and other countries over the last 30 years. The median survival time of limited stage SCLC is 15–20 months and 5-year survival rate is 15% or less. In terms of extensive stage SCLC, a median survival time of 9.4–12.8 months and 2-year survival of 5.2–19.5% are still disappointing. Despite being highly sensitive to first-line chemotherapy and radiotherapy treatments, most patients with SCLC experience relapse within 2 years and die from systemic metastasis. While several clinical trials of cytotoxic chemotherapies and molecular targeting agents have been investigated in the treatment of relapsed SCLC, none showed a significant clinical activity to be able to exceed topotecan as second-line chemotherapy. There are problematic issues to address for relapsed SCLC, such as standardizing the treatment for third-line chemotherapy. Topotecan alone was the first approved therapy for second-line treatment for relapsed SCLC. Amrubicin is a promising drug and a variety of trials evaluating its efficacy have been carried out. Amrubicin has shown superiority to topotecan in a Japanese population, but was not superior in a study of western patients. There are some controversial issues for relapsed SCLC, such as treatment for older patients, third-line chemotherapy and efficacy of molecular targeting therapy. This article reviews current standard treatment, recent clinical trials and other topics on relapsed SCLC.

Successful crizotinib rechallenge after crizotinib-induced interstitial lung disease in patients with advanced non-small-cell lung cancer.

� Comparing the 2 successfully treated cases, including ours, with the fatal case previously reported, we found some common characteristics in the successful case and our case, among which was the fact that our patient had no risk of EGFR TKIeinduced ILD. The risk factors for EGFR TKIeinduced ILD may be related to crizotinib-induced ILD. � Although crizotinib-induced ILD may be fatal, some patients might benefit from rechallenge of the drug. It is important to elucidate the clinicopathologic characteristics of ALK TKIeinduced ILD and to determine its risk factors.

Is emphysema a risk factor for pneumothorax in CT-guided lung biopsy?

IntroductionComputed tomography (CT)-guided lung biopsy is commonly used to make a histological diagnosis for pulmonary lesions. Its most common complication is pneumothorax. While it is thought that CT-guided lung biopsy should be avoided in patients with emphysema, however, there is no scientific report documenting the relationship the occurrence of pneumothorax and the severity of emphysema.Purpose and methodsTo investigate the relationship between the severity of emphysema and the frequency of pneumothorax, we retrospectively reviewed all the patients who received CT-guided lung biopsy. Severity of emphysema is evaluated by Goddard classification, a visual scale by which areas of vascular disruption and low attenuation value were scored for each lung field of high resolution CT.Patients’ characteristics, prognostic accuracy of this method, size and location of the lesion, length of intrapulmonary biopsy paths, and frequency of complications such as pneumothorax or intrapulmonary hemorrhage were evaluated.ResultsOne hundred-two patients (69 males and 33 females) received 102 procedures. Diagnostic accuracy was 90.2%. Pneumothorax occurred in 41 of 102 biopsies (40.2%). Chest tube placement was required in 3 out of the 41 cases (7.3%) complicated by pneumothorax (2.9% of all the biopsies). The longer lesion depths from pleura were, the more frequently pneumothorax occurred (6.67 vs 3.66 mm, p=0.019). No correlation was found between location of lesions and frequency of pneumothorax. No significant differences of COPD staging or LAA score were seen between the patients with and without pneumothorax (5.73 vs 4.32 points, p=0.339).ConclusionWe suggest that severity of emphysema such as stage I or II COPD may not be related to the frequency of pneumothorax.

Efficacy and safety of amurubicin for the elderly patients with refractory relapsed small cell lung cancer as third-line chemotherapy

BACKGROUND While more elderly patients are being diagnosed with lung cancer every year, no anti-lung cancer therapy designed specifically for the elderly has been established yet. This is the first retrospective study to examine the efficacy and safety of amurubicin (AMR) for elderly patients with refractory relapsed small cell lung cancer (SCLC) as second or third-line chemotherapy. MATERIALS AND METHODS Thirty-six patients were eligible for analyzing the frequency of hematologic and non-hematologic toxicities and effectiveness of AMR for refractory relapsed SCLC in both elderly (≥ 70 years) and non-elderly (<70 years) groups. RESULTS Among these patients as third-line chemotherapy, the response rate and the disease control rate of refractory relapsed cases were 44.4 and 55.6%, respectively. The median of progression-free survival time was 3.0 months and the median of overall survival time was 5.1 months. There were no significant differences in the frequency of the grade 3-5 hematologic or non-hematologic toxicity between the elderly (≥ 70 years) and non-elderly (<70 years) patients or second and third-line chemotherapies. CONCLUSIONS AMR could be one of the effective tools in the treatment of elderly patients with refractory relapsed SCLC as third-line chemotherapy, and the recommended dose is 30 mg/m 2 for three consecutive days.

Um caso de pneumonia por vírus parainfluenza 3 simulando pneumonia por influenza tratada com sucesso

Portanto, a terapia anti-influenza deve ser iniciada empiricamente caso haja suspeita de pneumonia por influenza.Sabe-se que o virus da parainfluenza (VPI) causou doenca semelhante a gripe durante as pandemias de influenza suina.(2) Relatou-se que o VPI 3 (VPI3) pode causar pneumonia em pacientes imunossuprimidos, tais como adultos que receberam transplantes.(3)Relatamos um caso, tratado com sucesso, de pneumonia por VPI3 simulando pneumonia por influenza em uma paciente asmatica de 31 anos de idade. A paciente apresentou febre alta (39.5°C), fadiga geral, dor articular sistemica e anorexia durante dois dias antes de ser encaminhada a nosso centro medico. Era fumante e apresentava historia de tabagismo (20 anos-maco) e de asma bronquica (sem uso atual de medicacao). A paciente tambem apresentava diabetes mellitus mal controlada e indice de massa corporal de 30 kg/m2. A radiografia de torax revelou opacidades em vidro fosco difusas em ambos os pulmoes (Figura 1). Exames laboratoriais revelaram reacao inflamatoria grave (proteina C reativa = 19,2 mg/dL e VHS = 83 mm/h). A paciente apresentou insuficiencia respiratoria grave e SpO2 de 80% em ar ambiente na primeira visita e passou a receber oxigenoterapia com ventilacao nao invasiva com pressao positiva. Devido a insuficiencia respiratoria grave, nao foi realizada lavagem broncoalveolar. Embora o resultado de um teste rapido para deteccao de antigeno de influenza tenha sido negativo, a paciente recebeu diagnostico de pneumonia por influenza com base em sintomas semelhantes aos da gripe e em achados radiologicos, tais como opacidades difusas em vidro fosco (Figura 2).A paciente passou a receber tratamento empirico com peramivir (600 mg/dia) durante 5 dias (para a infeccao por influenza) associado a pulso de esteroide e eritromicina i.v. (1.000 mg/dia) durante 5 dias (para a insuficiencia respiratoria aguda). Sua funcao respiratoria melhorou gradualmente, e a ventilacao nao invasiva com pressao positiva foi interrompida no 5o dia. A paciente passou entao a receber prednisolona oral (80 mg/dia), e a dose foi sendo gradativamente reduzida uma vez a cada tres dias, da seguinte maneira: para 40 mg/dia no 6o dia; para 30 mg/dia no 9o dia; para 15 mg/dia no 12o dia e suspensa

The ATS/ERS/JRS/ALAT statement “IPF by HRCT” could predict acute exacerbation of interstitial lung disease in non-small cell lung cancer

Introduction Patients with non-small cell lung cancer (NSCLC) and interstitial lung disease (ILD) are at high risk of acute exacerbation of ILD (AE-ILD) when treated with systemic chemotherapy. Standard treatment for NSCLC complicated by ILD has not been established. Purpose and methods To examine whether the type of ILD categorized by the official ATS/ERS/JRS/ALAT statement as “idiopathic pulmonary fibrosis (IPF) by high-resolution computed tomography (HRCT)” could predict chemotherapy-induced AE-ILD in NSCLC patients with ILD, we retrospectively reviewed all patients with NSCLC complicated by ILD who had received chemotherapy at our institute from January 2007 until December 2013. Patients’ characteristics, pathology and clinical staging of lung cancer, chemotherapy, type of ILD and AE-ILD during chemotherapy were evaluated. ILD was classified according to the statement as follows: usual interstitial pneumonia (UIP), possible UIP, and inconsistent with a UIP pattern. Results A total of 46 patients had pre-existing ILD and received chemotherapy. The mean age was 73 years (range 46-83 years). Fifteen (32.6%) of 46 patients with ILD developed chemotherapy-induced AE-ILD, which was seen more frequently in patients with ILD with a UIP pattern or possible UIP pattern than in patients with a pattern inconsistent with UIP (80% versus 9.7%, p<0.001). Multivariate analyses including age, sex, performance status and radiographic patterns of ILD showed that the presence of a UIP or possible UIP pattern was an independent risk factor for chemotherapy-induced AE-ILD. Conclusions ILD with a UIP pattern or possible UIP pattern by the classification could be a risk factor for AE-ILD in NSCLC patients with ILD.

Non-HIV Pneumocystis pneumonia: do conventional community-acquired pneumonia guidelines under estimate its severity?

BackgroundNon-HIV Pneumocystis pneumonia (PCP) can occur in immunosuppressed patients having malignancy or on immunosuppressive agents. To classify severity, the A-DROP scale proposed by the Japanese Respiratory Society (JRS), the CURB-65 score of the British Respiratory Society (BTS) and the Pneumonia Severity Index (PSI) of the Infectious Diseases Society of America (IDSA) are widely used in patients with community-acquired pneumonia (CAP) in Japan. To evaluate how correctly these conventional prognostic guidelines for CAP reflect the severity of non-HIV PCP, we retrospectively analyzed 21 patients with non-HIV PCP.MethodsA total of 21 patients were diagnosed by conventional staining and polymerase chain reaction (PCR) for respiratory samples with chest x-ray and computed tomography (CT) findings. We compared the severity of 21 patients with PCP classified by A-DROP, CURB-65, and PSI. Also, patients’ characteristics, clinical pictures, laboratory results at first visit or admission and intervals from diagnosis to start of specific-PCP therapy were evaluated in both survivor and non-survivor groups.ResultsBased on A-DROP, 18 patients were classified as mild or moderate; respiratory failure developed in 15 of these 18 (83.3%), and 7/15 (46.7%) died. Based on CURB-65, 19 patients were classified as mild or moderate; respiratory failure developed in 16/19 (84.2%), and 8 of the 16 (50%) died. In contrast, PSI classified 14 as severe or extremely severe; all of the 14 (100%) developed respiratory failure and 8/14 (57.1%) died. There were no significant differences in laboratory results in these groups. The time between the initial visit and diagnosis, and the time between the initial visit and starting of specific-PCP therapy were statistically shorter in the survivor group than in the non-survivor group.ConclusionsConventional prognostic guidelines for CAP could underestimate the severity of non-HIV PCP, resulting in a therapeutic delay resulting in high mortality. The most important factor to improve the mortality of non-HIV PCP is early diagnosis and starting of specific-PCP therapy as soon as possible.

Successful Crizotinib Rechallenge after Crizotinib-Induced Organizing Pneumonia in Anaplastic Lymphoma Kinase-Rearranged Non-Small Cell Lung Cancer

Crizotinib, a first-line anaplastic lymphoma kinase (ALK)-tyrosine kinase inhibitor, has shown promising results for the treatment of locally advanced and metastatic lung cancer presenting the ALK rearrangement. On the other hand, secondary organizing pneumonia (OP) caused by anti-cancer drugs has been reported. While it is sometimes needed to rechallenge the suspected drug, the standard therapeutic strategy for secondary OP has not yet been established. We report a 60-year-old male with ALK-rearranged non-small cell lung cancer who developed crizotinib-induced OP and was successfully rechallenged with crizotinib. Six months after the rechallenge, the patient has achieved a partial response. To our knowledge, this is the first case in which crizotinib-induced OP has been successfully treated.

Efficacy of 18F-fluorodeoxyglucose positron emission tomography/computed tomography in evaluating lung cancer recurrence

For patients with non-small cell lung cancer (NSCLC) classified as stage I using the tumor-node-metastasis (TNM) staging system (T1N0M0 or T2N0M0), the standard treatment is complete resection of the affected lobes and associated lymph nodes. However, lung cancer is usually inoperable in elderly patients, mostly because of their poor performance status. In general, resection of these early-stage tumors, typically by lobectomy, has been associated with three-year and five-year survival rates ranging from 60% to 80%. (1,2) Unfortunately, significant complications have been associated with lobectomy in elderly patients or in those with medical comorbidities, such as limited pulmonary reserve and cardiovascular disease. (3-6) With the popularization of CT screening, lung cancers have been increasingly detected at an early stage.

A successful diagnostic case of Pneumocystis pneumonia by the loop-mediated isothermal amplification method in a patient with dermatomyositis

Pneumocystis pneumonia (PCP) can occur in patients with many causes of the immunocompromised state other than human immunodeficiency virus (HIV). It is quite difficult to diagnose PCP without HIV because there is no method for detecting Pneumocystis jirovecii. Thus, non-HIV PCP continues to have high mortality. Recently, loop-mediated isothermal amplification (LAMP) is becoming an established nucleic acid amplification method offering rapid, accurate, and cost-effective diagnosis of infectious diseases. We report a non-HIV PCP case successfully diagnosed by the LAMP method. It was previously reported that PCR in BALF specimens had been the most sensitive method in the diagnosis of PCP without HIV. The LAMP method would be more sensitive than conventional PCR and an effective tool in the early diagnosis of PCP.