Combination therapy with carboplatin and paclitaxel for small cell lung cancer

Background

Although small cell lung cancer (SCLC) is an aggressive cancer, few useful treatment options exist after relapse. Information concerning the efficacy and safety of carboplatin plus paclitaxel in patients with SCLC is limited.

Immune checkpoint inhibitor-related interstitial lung disease in patients with advanced non-small cell lung cancer: systematic review of characteristics,incidence, risk factors,and management

BackgroundImmune checkpoint inhibitors (ICIs) are widely used in cancers with or without other treatments. Immune-related adverse events (irAEs) have been reported as side effects of ICIs and involve various organs. Pneumonitis, which is also called ICI-related interstitial lung disease (ILD), is one of the life-threatening adverse events. In this report, we reviewed the safety of ICIs and risk factors for ICI-related ILD in non-small cell lung cancer (NSCLC) patients.MethodsDatabases (The National Center for Biotechnology Information, PubMed, Cochrane Library, Google Scholar, and Embase) were searched for the literature on pulmonary adverse events and immunotherapy following PRISMA guidelines. All studies published in English between January 2016 and June 2021 were included.ResultsOne-hundred twenty-five articles were included at final. Pre-existing ILD as well as asthma and chronic obstructive lung disease (COPD) were associated with high risk for the development of ICI-related ILD, however, it did not affect the prognosis. The treatment of ICI-related ILD is different according to the severity grades, which includes discontinuation of ICI, corticosteroids, and for steroid-refractory ILD, other immunosuppressants. Rechallenging of ICI should be carefully considered in selected patients.DiscussionPatients with pre-existing lung disease and poor lung function need more attention for the development of ICI-related ILD. It is necessary to be aware of clinical manifestation of ICI-related ILD with prompt management.     

Treatment outcome of patients with unresectable stage III non-small cell lung cancer and interstitial pneumonia

BackgroundThe standard treatment for unresectable stage III non-small cell lung cancer (LC) is chemoradiation therapy (CRT); however, the optimal treatment for LC in patients with interstitial pneumonia (IP) (LC-IP) has not been determined. This study compared the clinical course of LC-IP patients to that of patients without IP (LC without IP) and determined the key factors of survival.MethodsWe retrieved the records of 52 consecutive LC patients treated at our institution between January 2011 and September 2016. The characteristics and outcomes of LC patients with and without IP were compared. Survival was analyzed using the Kaplan-Meier method and univariate and multivariate analyses of two-year survival were also conducted.ResultsForty-two men and 10 women were evaluated. Eleven patients (21%) had IP as their underlying disease. Except for age, the backgrounds of LC patients with and without IP were almost identical. Among LC-IP patients, the median predicted forced vital capacity was 86% and the Gender-Age-Physiology (GAP) index was 3. None of the LC-IP patients received CRT but 32 (78%) of the LC without IP patients underwent CRT. Chemotherapy alone was the main treatment for LC-IP. The median survival times were 485 and 1271 days in LC patients with and without IP, respectively (p=0.419). Multivariate analysis of survival longer than two years revealed CRT as the only predictive factor.ConclusionsCRT was the only predictive factor for longer survival in LC patients; however, no LC-IP patients received CRT, possibly because of the underlying IP.     

Association of specific metastatic organs with the prognosis and chemotherapeutic response in patients with advanced lung cancer

BackgroundThis study was performed to investigate the influence of specific metastatic organs on the prognosis and therapeutic effect in patients with advanced lung cancer.MethodsWe retrospectively analyzed 400 patients with pathologically diagnosed advanced lung cancer to determine the association of the patients’ metastatic status with their prognoses and responses to first-line therapy. Metastases within the chest cavity (pulmonary metastasis, pleural effusion, and pericardial effusion) were counted as one organ.ResultsThe numbers of metastatic organs in the patients were as follows: one (n=199 patients), two (n=99), three (n=61), and four or more (n=41). A multivariate analysis showed that liver and muscle metastases were independently associated with shorter overall survival (median of 207 and 120 days, respectively) and shorter progression-free survival (median of 125 and 53 days, respectively). Chest cavity, bone, brain, and lymph node metastases were not associated with survival. The presence of either muscle or skin metastasis was associated with a lower response rate to first-line therapy than was the absence of each metastasis (14.3% vs. 49.4% and 11.1% vs. 48.9% in patients with vs. without muscle or skin metastasis, respectively).ConclusionsMuscle and liver metastases were associated with poor outcomes. Muscle and skin metastases were associated with a lower response rate to treatment. For patients with advanced lung cancer, oncologists should select treatment strategies considering the patients’ metastatic statuses as well as other clinical characteristics.     

Outcomes of patients with interstitial lung disease referred for lung transplant assessment

Background: Patients with interstitial lung disease (ILD) very frequently die before the opportunity to receive lung transplantation (LTx). This retrospective study describes the clinical course of 86 patients with ILD referred for LTx assessment between January 1999 and December 2002. Aims: (i) To describe the outcomes, (ii) to identify reasons of delay to transplantation, (iii) to describe the causes of death/complications and (iv) to assess the pathological diagnosis and concordance with explanted lung pathology. Methods: Data were collected from the case notes of all patients with ILD referred to the Alfred Hospital over a 4‐year period. Results: Twenty women and 66 men, mean age of 55 ± 8 years, were referred for LTx assessment. Forty‐five patients were deemed not suitable for LTx and 41 were listed. Twenty‐two patients underwent transplantation, 16 died on the waiting list and 7 are still on the waiting list. Complications were frequent (e.g. pulmonary embolism, malignancy and infection) and carried high mortality. Patients dying on the waiting list appeared generally to be in accelerated decline, dying shortly after listing, with no evidence in their lung function test assessment predicting them as a poor prognosis group. Conclusions: Serious complications and death on the waiting list of patients with idiopathic pulmonary fibrosis are high, not apparently because of delayed referral but usually in patients undergoing very rapid decline.     

间质性肺病合并肺癌研究进展

间质性肺病和肺癌是呼吸内科常见疾病.近年来2种疾病的发病率都有明显升高的趋势,而且预后不良,特别是间质性肺病合并肺癌的出现,在其诊断和治疗方面都存在一定的难度和挑战.一方面,2种疾病的发病机制在一定程度上有共同之处;另一方面,肺癌的治疗会诱发间质性肺病的发生和急性加重.本文通过搜集近年来有关间质性肺病合并肺癌的流行病学、发病机制、临床特征、治疗和预后等相关问题的研究进展,并进行总结,以提高临床医师对间质性肺病合并肺癌的诊治水平.     

Fatal interstitial lung disease associated with icotinib

The most serious, and maybe fatal, yet rare, adverse reaction of gefitinib and erlotinib is drug-associated interstitial lung disease (ILD), which has been often described. However, it has been less well described for icotinib, a similar orally small-molecule tyrosine kinase inhibitor (TKI). The case of a 25-year-old female patient with stage IV lung adenocarcinoma who developed fatal ILD is reported here. She denied chemotherapy, and received palliative treatment with icotinib (125 mg po, three times daily) on March 1, 2013. One month after treatment initiation, the patient complained of continuous dry cough and rapid progressive dyspnea. Forty one days after icotinib treatment, icotinib associated ILD was suspected when the patient became increasingly dyspnoeic despite of treatment of pericardial effusion, left pleural effusion and lower respiratory tract infection, and X-ray computed tomography (CT) of chest revealed multiple effusion shadows and ground-glass opacities in bilateral lungs. Then, icotinib was discontinued and intravenous corticosteroid was started (methylprednisolone 40 mg once daily, about 1 mg per kilogram) respectively. Forty three days after icotinib treatment, the patient died of hypoxic respiratory failure. ILD should be considered as a rare, but often fatal side effect associated with icotinib treatment.     

21例间质性肺疾病合并肺癌临床分析

目的探讨间质性肺疾病合并肺癌的临床特点和治疗方法,提高对疾病的诊治水平。方法回顾性分析21例间质性肺病合并肺癌患者的一般资料、临床表现、实验室和特殊检查以及治疗方法。结果21例患者中男性17例,女性4例,年龄51~88岁,中位年龄65岁,15例有吸烟史。临床表现主要为咳嗽、咳痰、活动后气急。胸部CT主要表现为两肺纤维条索及网格影、蜂窝肺样改变合并结节、团块影。病理类型为腺癌47.6%,鳞癌23.8%,小细胞癌28.6%。3例以ILD起病的患者在发现肺癌前,100%NSE升高,66.7%CYFRA21-1升高,33.3%CEA升高。在同时发现ILD和肺癌的18例患者中,50%NSE升高,55.6%CYFRA21-1升高,66.1%CEA升高,16.7%SCC升高。15例接受含铂双药联合化疗,3例接受手术治疗,3例接受最佳支持治疗。5例在治疗过程中出现肺部感染。结论间质性肺疾病合并肺癌临床处置困难,对于以ILD起病的患者,在随访过程中应密切随访血清肿瘤标记物及胸部CT,使ILD-LC得以早期诊断和治疗。治疗过程中易并发肺部感染及间质性肺疾病急性加重。治疗时应对治疗的风险和获益进行充分的评估,并且给予严密的监测。     

Chronic obstructive pulmonary disease and interstitial lung disease in patients with lung cancer

Background and objective:   Although lung cancer is frequently accompanied by COPD and interstitial lung disease (ILD), the precise coincidence of these diseases with lung cancer is not well understood. The objectives of this study were to determine the prevalence of abnormal CT and spirometric findings suggestive of COPD or ILD in a population of patients with untreated lung cancer, and to estimate the lung cancer risk in this population.
Methods:   The study population consisted of 256 patients with untreated lung cancer and 947 subjects participating in a CT screening programme for lung cancer. Semi-quantitative analysis of low attenuation area (LAA), fibrosis and ground glass attenuation (GGA) on CT was performed by scoring. Gender- and age-matched subpopulations, with stratification by smoking status, were compared using the Mantel–Haenszel projection method.
Results:   Inter-observer consistency was excellent for LAA, but not as good for fibrosis or GGA scores. Pooled odds ratios for lung cancer risk using LAA, fibrosis, GGA scores and reduced FEV₁/FVC and %VC were 3.63, 5.10, 2.71, 7.17 and 4.73, respectively ( P  < 0.0001 for all parameters). Multivariate regression analyses confirmed these results.
Conclusion:   Abnormal CT and spirometric parameters suggestive of COPD and ILD were strong risk factors for lung cancer, even after adjusting for gender, age and smoking status.     

Efficacy and safety of pemetrexed maintenance chemotherapy for advanced non-small cell lung cancer in a real-world setting

BackgroundPemetrexed maintenance therapy offers a survival benefit in patients with nonprogressive advanced nonsquamous non-small cell lung cancer (NSCLC) with good tolerability. This study was designed to analyze the efficacy and safety of pemetrexed maintenance chemotherapy in advanced nonsquamous NSCLC patients in a real-world setting.MethodsThe response rate (RR) and adverse events in 71 nonsquamous NSCLC patients treated with pemetrexed-based chemotherapy were observed until disease progression or unacceptable toxicities. Measures of survival were analyzed during follow-up.ResultsOf 69 efficacy-evaluable patients, the objective response rate (ORR) was 46.4% and the disease control rate (DCR) was 98.6%. ORR showed no significant difference between patients who received pemetrexed as first-line therapy and those who received pemetrexed as second-line or higher treatment. The median treatment cycle for all patients was 8. The median progression-free survival (PFS) was 9.5 months (m) and median overall survival (OS) was 30.5 m. The univariate and multivariate analyses showed that the number of chemotherapy cycles was an independent factor for PFS. The most common adverse reactions were grade 1 to 2 hematologic toxicities, gastrointestinal reactions, and liver enzyme abnormalities. Only 1 patient experienced a grade 3 gastrointestinal event.ConclusionsPemetrexed maintenance chemotherapy can improve PFS in patients with advanced nonsquamous NSCLC with good tolerability.     

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

Introduction: Although gefitinib used for the treatment of non‐small‐cell lung cancer is a well‐known cause of interstitial lung disease (ILD), few case reports on erlotinib‐induced ILD have been issued. The common risk factor of both of these two drug‐induced ILDs is idiopathic interstitial pneumonia, but ILD in a patient with radiation fibrosis has not been previously reported. Methods: Report of a case. Results: We recently experienced a case of fatal erlotinib‐induced ILD, diagnosed based on clinical and radiologic findings, which occurred in a patient with radiation fibrosis. A 50‐year‐old male patient was started on erlotinib as a third‐line chemotherapy. Six days after taking erlotinib, a chest radiograph showed rapid progression of reticular infiltration in both lung fields. High‐resolution computed tomography scan findings were consistent with ILD, which was sufficient to diagnose as erlotinib‐induced ILD. The patient died of respiratory failure after 8 days of steroid infusion and erlotinib discontinuation. Conclusion: Our case shows a fatal side effect of erlotinib. This case had radiation fibrosis, so we suggest that radiation fibrosis may be another contributor of the occurrence of ILD in patients taking erlotinib. Please cite this paper as: Um S‐J, Lee S‐K, Yang DK, Son C, Roh MS, Kim KN, Lee K‐N and Choi PJ. Fatal interstitial lung disease after erlotinib administration in a patient with radiation fibrosis. The Clinical Respiratory Journal 2009; 3: 181–184.     

血清CEA和CA125水平对间质性肺病癌变的早期诊断学研究

目的比较ILD患者和ILD合并肺癌患者血清CEA和CA125的水平,探讨其在ILD合并肺癌早期诊断中的临床应用价值。方法设置ILD合并肺癌组(n=42)、ILD组(n=70)和对照组(n=60),测定并比较两组患者血清CEA和CA125的水平,通过受试者工作曲线评价CEA和CA125对ILD合并肺癌的诊断价值。结果 ILD合并肺癌组血清CEA、CA125水平均高于ILD组和对照组(P0.05);ILD组血清CEA、CA125水平均高于对照组(P0.05);血清CEA和CA125在诊断ILD合并肺癌的曲线下面积(area under curve,AUC)分别为0.722(95%CI:0.633~0.769,P0.05),0.751(95%CI:0.658~0.791,P0.05)。当血清CEA为6.2 ng/m L时,其诊断的敏感度为72.3%,特异度为69.2%;当血清CA125为60.4U/m L时,其诊断的敏感度为75.3%,特异度为79.7%。结论 ILD合并肺癌患者血清CEA和CA125较ILD患者要高,血清CEA和CA125对ILD合并肺癌的早期诊断具有参考价值。     

洛铂联合足叶乙甙治疗晚期小细胞肺癌的临床研究

目的观察评价新一代铂类抗癌药物洛铂（LBP）联合足叶乙甙（VP-16）组成的LE方案治疗晚期小细胞肺癌（SCLC）的有效性和安全性。方法26例经病理组织学和／或细胞学检查确诊SCLC,均为初治患者,其中男性22例,女性4例;年龄42～74岁,中位年龄61岁,TNM分期：ⅢA11例,ⅢB6例,Ⅳ期9例。应用LE方案,即LBP30mg／m^2静滴d1;VP-16100mg静滴d1～5;21～28d为一周期,至少接受2个周期化疗。按照WHO标准评价客观疗效和毒性。结果26例患者中,可评价疗效的患者有25例。其中CR3／25,PR20／25,NC2／25,有效率（RR）92．0％。主要毒性反应为可逆性的骨髓抑制和胃肠道反应。结论LBP联合VP-16组成LE方案治疗SCLC疗效好,毒性反应可以耐受,值得进一步研究观察。     

Pemetrexed and carboplatin combination therapy followed by pemetrexed maintenance in Japanese patients with non-squamous non-small cell lung cancer: A subgroup analysis of elderly patients

Background

The combination of pemetrexed and carboplatin is commonly used for the treatment of advanced non-squamous non-small cell lung cancer (NSCLC), mainly because it is comparatively effective and less toxic than other platinum-doublet therapies. Using the JMII (JACAL) study, we report the efficacy and safety of this treatment followed by pemetrexed maintenance in the elderly population (≥70 years of age).

Treatment of secondary pneumothorax with interstitial lung disease: the surgical indications at the start of treatment is important

BackgroundSecondary pneumothorax with interstitial lung disease (ILD) is often difficult to treat in comparison to primary pneumothorax. The purpose of this study was to analyze the actual management and outcome, and to find the most effective treatment.MethodsAmong 180 patients with pneumothorax caused by ILD, who were managed between January 2000 and April 2021, 129 patients were included. Fifty-one patients with observation only were excluded. In the present study, a patient was considered to be cured if their chest tube could be removed.ResultsThe managements included chest tube drainage alone (n=41), pleurodesis (n=67), bronchoscopic treatment (n=14), and surgery (include overlapping cases) (n=25). The mean number of pleurodesis treatments was 2.4 (range, 1–9), and the most frequently used agent was blood-patch. All patients who received bronchoscopic treatment underwent bronchial occlusion with silicon spigots. The surgical procedures included bullectomy (n=20), lung cyst ligation (n=3), pleural covering with oxidized cellulose sheet (n=1), and spraying of fibrin glue alone (n=1). One hundred patients (77.5%) were curatively treated, 27 patients (20.9%) died, and 2 patients were transferred without chest tube removal. Among 25 patients who received surgery [including 6 patients with performance status (PS) ≥2], 24 patients (96.0%) were cured, and 1 patient died due to an acute exacerbation of ILD after surgery. The univariate analysis revealed that PS ≥2 and >3 pleurodesis treatments were significant non-curative factors, while steroid treatment before the development of pneumothorax was not.ConclusionsThe outcomes of surgery for pneumothorax in patients with ILD were good, and it is desirable to consider the surgical indications.     

Pre-existing interstitial lung abnormalities are risk factors for immune checkpoint inhibitor-induced interstitial lung disease in non-small cell lung cancer

BackgroundApproximately 5% of non-small cell lung cancer (NSCLC) patients develop immune checkpoint inhibitor (ICI)-induced interstitial lung disease (ICI-ILD), 10% of whom die. However, there are no established risk factors for its occurrence. Interstitial lung abnormalities (ILA) are areas of increased lung density on lung computed tomography (CT) in individuals with no known ILD. This study retrospectively investigated whether any patient characteristics, including ILA, were risk factors for ICI-ILD in patients with NSCLC.MethodsNSCLC patients who received anti-programmed death (PD)-1 antibody treatment at our hospital between September 2015 and December 2017 were enrolled. Information on patient characteristics before anti-PD-1 antibody administration, including chest CT findings and laboratory data, were obtained.ResultsAmong 83 enrolled patients, the incidence of ICI-ILD was 16.9% (14/83). All ICI-ILD cases developed by the third line of treatment. The incidence of ICI-ILD was significantly higher in patients with pre-existing ILA than that in those without (p = 0.007). Furthermore, patients with ground glass attenuation (GGA) in ILA had a higher incidence of ICI-ILD than that in those without (p < 0.001). In univariate logistic analysis, ILA were significant risk factors for ICI-ILD (p = 0.005). Multivariate logistic analysis revealed that only GGA in ILA was a significant risk factor for ICI-ILD (p < 0.001).ConclusionsPre-existing ILA are risk factors for ICI-ILD and GGA in ILA is an independent risk factor for ICI-ILD. Therefore, we should be more aware of the development of ICI-ILD in patients with ILA, especially those with GGA.     

Diagnostic value and safety of endobronchial ultrasonography with a guide sheath transbronchial biopsy for diagnosing peripheral pulmonary lesions in patients with interstitial lung disease

BackgroundRadial endobronchial ultrasonography transbronchial biopsy with and without a guide sheath is a useful method for diagnosing peripheral pulmonary lesions (PPLs). However, the diagnostic yield and complications of radial endobronchial ultrasonography transbronchial biopsy for PPLs remains elusive in patients with interstitial lung disease (ILD).MethodsWe retrospectively analysed 431 patients (69 with and 362 without ILD) who underwent radial endobronchial ultrasonography with a guide sheath transbronchial biopsy (EBUS-GS TBB) for PPLs from April 1, 2011, to March 31, 2020. We investigated the diagnostic yield and complications of the procedure for PPLs and compared them between patients with and without ILD. We also evaluated the factors contributing to successful diagnosis.ResultsThe diagnostic yield of radial endobronchial ultrasonography in patients with ILD was significantly lower than in those without ILD (62.3% vs. 75.4%, P=0.024). Multivariate analysis showed that the presence of ILD as background lung [odds ratio (OR) =0.517], probe position within the lesion (OR =4.654), and the presence of solid lesion (OR =1.946) significantly affected the diagnostic yield of PPLs. There was a significant difference in the rate of pneumothorax between the patients with ILD and those without ILD (4.3% vs. 0.6%, P=0.031).ConclusionsThe presence of ILD as the background lung significantly affected the diagnostic yield of PPLs with radial EBUS-GS TBB. Regarding the complications, pneumothorax occurred more frequently in patients with ILD than in those without ILD.     

Proton beam radiotherapy for patients with early-stage and advanced lung cancer: a narrative review with contemporary clinical recommendations

Although lung cancer rates are decreasing nationally, lung cancer remains the leading cause of cancer related death. Despite advancements in treatment and technology, overall survival (OS) for lung cancer remains poor. Proton beam therapy (PBT) is an advanced radiation therapy (RT) modality for treatment of lung cancer with the potential to achieve dose escalation to tumor while sparing critical structures due to higher target conformality. In early and late-stage non-small cell lung cancer (NSCLC), dosimetric studies demonstrated reduced doses to organs at risk (OARs) such as the lung, spinal cord, and heart, and clinical studies report limited toxicities with PBT, including hypofractionated regimens. In limited-stage SCLC, studies showed that regimens chemo RT including PBT were well tolerated, which may help optimize clinical outcomes. Improved toxicity profiles may be beneficial in post-operative radiotherapy, for which initial dosimetric and clinical data are encouraging. Sparing of OARs may also increase the proportion of patients able to complete reirradiation for recurrent disease. However, there are various challenges of using PBT including a higher financial burden on healthcare and limited data supporting its cost-effectiveness. Further studies are needed to identify subgroups that benefit from PBT based on prognostic factors, and to evaluate PBT combined with immunotherapy, in order to elucidate the benefit that PBT may offer future lung cancer patients.     

Association of the RAGE/RAGE-ligand axis with interstitial lung disease and its acute exacerbation

The receptor for advanced glycation end product (RAGE) is a transmembrane receptor highly expressed in type 1 pneumocytes of healthy lungs. RAGE is considered to play a homeostatic role in the lung, as RAGE knockout mice develop lung fibrosis as they age. In contrast, RAGE can bind numerous ligands, including high-mobility group box 1 (HMGB1). These interactions initiate pro-inflammatory signaling associated with the pathogenesis of lung injury and interstitial lung disease (ILD), including idiopathic pulmonary fibrosis (IPF).ILD is a broad category of diffuse parenchymal lung disease characterized by various extents of lung fibrosis and inflammation, and IPF is a common and progressive ILD of unknown cause. The prognosis of patients with IPF is poor, and acute exacerbation of IPF (AE-IPF) is one of the main causes of death. Recent reports indicate that acute exacerbations can occur in other ILDs (AE-ILD). Notably, ILD is frequently observed in patients with lung cancer, and AE-ILD after surgical procedures or the initiation of chemotherapy for concomitant lung cancer are clinically important due to their association with increased mortality.In this review, we summarize the associations of RAGE/soluble RAGE (sRAGE)/RAGE ligands with the pathogenesis and clinical course of ILD, including IPF and AE-IPF. Additionally, the potential use of sRAGE and RAGE ligands as predictive markers of AE-IPF and cancer treatment-triggered AE-ILD is also discussed.