培美曲塞治疗老年中晚期非小细胞肺癌的临床效果

目的：观察培美曲赛单药治疗老年中晚期非小细胞肺癌的疗效和不良反应。方法：总结分析于本院诊治2008—2009年26例老年（70～81岁）ⅢA-Ⅳ期非小细胞肺癌患者接受培美曲赛单药化疗2周期后行临床疗效和不良反应。结果：完全缓解（CR）0例，部分缓解（PR）6例，总有效率为23．08％，疾病稳定（SD）11例，疾病进展（PD）9例。全组毒性不良反应较轻，主要为骨髓抑制，可耐受。结论：培关曲赛治疗老年非小细胞肺癌疗效较好，不良反应轻，可明显改善老年患者生存质量。     

Feasibility study of metabolically supported chemotherapy with weekly carboplatin/paclitaxel combined with ketogenic diet,hyperthermia and hyperbaric oxygen therapy in metastatic non-small cell lung cancer

Background: Previous evidence suggests that metabolically supported chemotherapy (MSCT), ketogenic diet, hyperthermia and hyperbaric oxygen therapy (HBOT) could all target vulnerabilities of cancer cells. This study aimed to evaluate the efficacy and the tolerability of this combination therapy in the treatment of stage IV non-small cell lung cancer (NSCLC).

Methods: Forty-four NSCLC patients with distant metastasis that received MSCT (administration of chemotherapy regimen following induced hypoglycemia) plus ketogenic diet, hyperthermia and HBOT combination were included in this retrospective study. Survival and treatment response rates as well as toxicities were evaluated.

Results: Overall response rate (ORR, complete response plus partial response) was 61.4%; whereas, 15.9% and 22.7% of patients had stable disease (SD) and progressive disease (PD), respectively. Mean overall survival (OS) and progression-free survival (PFS) was 42.9?months (95% CI: 34.0–51.8) and 41.0?months (95% CI: 31.1–50.9), respectively. A higher Eastern Cooperative Oncology Group (ECOG) performance status (ECOG ≥2) was associated with worse OS and PFS. Patients received chemotherapy cycles with acceptable toxicity and adverse events. No problems were encountered due to fasting, hypoglycemia, ketogenic diet, hyperthermia or hyperbaric oxygen therapy.

Conclusions: Findings of this study suggest that MSCT combined with other modalities targeting multiple pathways and cellular vulnerabilities may bring about remarkable improvements in survival outcomes and treatment response rates in metastatic NSCLC, without additional safety concerns. Large comparative studies are warranted to draw robust conclusions.     

Assessment of Immune-Related Interstitial Lung Disease in Patients With NSCLC Treated with Immune Checkpoint Inhibitors: A Multicenter Prospective Study

IntroductionProgrammed cell death protein 1 immune checkpoint inhibitors (ICIs) have been reported to improve the survival of patients with NSCLC. On the expansion of clinical administration for a variety of cancers, immune-related adverse events have been typically recognized to be associated with ICIs, therefore, necessitating the monitoring and management of these patients. Among immune-related adverse events, immune-related interstitial lung disease (ir-ILD) is a serious complication that interrupts treatment and can occasionally be fatal. However, no prospective studies have investigated the incidence of ir-ILD and associated risk factors for its development in the clinical setting.MethodsThis is a prospective cohort study consisting of patients with NSCLC treated with ICIs. Baseline characteristics, including laboratory data, pulmonary function tests, daily symptoms of dyspnea defined by the modified Medical Research Council, and antitumor response were assessed.ResultsAmong the 138 patients with NSCLC who received anti–programmed cell death protein 1 monotherapy, 20 patients (14.5%) had ir-ILD within median 51.5 days (interquartile range: 29–147). This was approximately three times higher than those in clinical trials. A total of 11 patients (55.0%), including all eight patients with high-grade ir-ILD (≥grade 3), developed ir-ILD within 60 days. Impaired spirometry, decreased forced vital capacity and forced expiratory volume in 1 second, and daily symptoms of dyspnea measured using the modified Medical Research Council scale were identified as risk factors for ir-ILD development. In addition, combination assessment of forced vital capacity and forced expiratory volume in 1 second successfully classified patients at risk for ir-ILD development.ConclusionsThe incidence of ir-ILD was substantially higher in the clinical setting. Assessment of spirometry and daily dyspneic symptoms before ICI treatment may be useful in monitoring and managing patients with NSCLC.     

Stereotactic Ablative Radiotherapy as an Alternative to Lobectomy in Patients With Medically Operable Stage I NSCLC: A Retrospective,Multicenter Analysis

Background

Stereotactic ablative body radiation therapy (SBRT) has evolved as the standard treatment for patients with inoperable stage I non–small-cell lung cancer (NSCLC). We report the results of a retrospective analysis conducted on a large, well-controlled cohort of patients with stage I to II NSCLC who underwent lobectomy (LOB) or SBRT.

Spatial distribution of immune checkpoint proteins in histological subtypes of lung adenocarcinoma

The most prevalent histological type of non-small cell lung cancer (NSCLC) is adenocarcinoma. The WHO classifies this tumor into subtypes according to the predominant growth pattern such as lepidic, acinar, papillary, solid or micropapillary, each harboring specific molecular features. NSCLC adenocarcinoma heterogeneity is discussed to be a reason for therapy failure using targeted therapy or immune checkpoint inhibitors. For successful therapy of immune checkpoint inhibitors the expression and distribution of the involved immune checkpoint proteins is essential. Therefore, we aimed to investigate the distribution of five prominent immune checkpoint proteins in regard of the histological growth patterns of lung adenocarcinoma. We performed immunohistochemical staining of 84 tumor segments from 22 resected tumor samples to evaluate the expression of PD-L1, PD-1, Nectin-2, PVR, and TIGIT in distinct growth patterns of lung adenocarcinoma. We determined a distinct heterogeneity between and within different tumor segments regarding morphological growth patterns. Furthermore, expression of immune checkpoint proteins varied between different growth pattern areas as well as within one distinct growth pattern. Expression of PVR was significantly higher in solid compared to acinar growth pattern (p= 0.00736). Of note, we detected TIGIT not only on tumor infiltrating lymphocytes but also on tumor cells, whereas non-neoplastic lung tissue was consistently TIGIT-negative. The immune checkpoint protein distribution in histologic subtypes of pulmonary adenocarcinoma displays an considerable intra- and intertumoral heterogeneity implying the requirement of either a multiregion or an adjusted analysis when determining the expression status of PD-1:PD-L1 and the TIGIT:PVR/Nectin-2 checkpoint proteins as predictive markers.     

甲孕酮联合长春瑞滨顺铂治疗晚期非小细胞肺癌临床观察

目的：观察甲孕酮合并NP方案（长春瑞滨＋顺铂）化疗及单用NP方案化疗治疗晚期非小细胞肺癌患者的疗效及不良反应。方法：75例接受化疗的晚期非小细胞肺癌患者随机分为单用化疗组（对照组）36例及化疗并用甲孕酮组（治疗组）39例,治疗周期均为21天,2个周期后评价疗效。结果：治疗组、对照组有效率（CR＋PR）分别为43.59%（17/39例）,41.67%（15/36例）,中位疾病进展期分别为4.0、3.6个月,中位生存期分别为9.1、8.9个月;1年生存率分别为38.5%、38.9%;差异无统计学意义（P〉0.05）;主要不良反应是Ⅲ～Ⅳ度骨髓抑制、恶心呕吐。治疗组的白细胞减少（7.69%）、血红蛋白下降（0）、血小板减少（7.69%）发生率与对照组（25.00%、19.44%、13.89%）比较差异有统计学意义（P〈0.05）;治疗组的恶心呕吐发生率为0,显著低于对照组（13.89%）。化疗后治疗组生活质量改善明显并优于对照组,差异具有统计学意义（P〈0.05）。结论：甲孕酮合用长春瑞滨联合顺铂治疗晚期NSCLC疗效较高,毒副反应轻,患者耐受良好。     

Immunohistochemistry-detected microscopic tumor spread affects outcome in en-bloc resection for T3-chest wall lung cancer

Objective: This study is aimed at analyzing the effect of immunohistochemistry-detected microscopic tumor spread on long-term survival after en-bloc lung and chest wall resection for T3-chest wall non-small cell lung cancer (NSCLC). Methods: We retrospectively reviewed 47 patients (mean age 64.4 ± 7.1 years, range 48–77) who underwent radical en-bloc lung and chest wall resection for NSCLC between 1987 and 2000. Resection margins, invasion depth, and lymph nodes were re-assessed by immunohistochemistry with AE1/AE3 anti-cytokeratin and anti-CEA monoclonal antibodies. Results: Operative mortality and morbidity were 2.1% and 34%, respectively. At immunohistochemistry analysis, five patients (10.6%) revealed microinfiltration of the resection margins that was significantly correlated with the development of local recurrence (p < 0.005). Nodal micrometastases were found in 4 out of 33 N0 patients (12.1%), and correlated with distant relapse (p < 0.001). Overall and disease-free survivals were significantly influenced by N-status (p < 0.001), especially after re-evaluation of micrometastases (p < 0.0001), and resection margins microinfiltration (p < 0.0001) being these last two the only significant prognostic factors at Cox regression analysis. Five-year overall survival in radically resected patients was 73%. Conclusions: In this study immunohistochemical analysis allowed to identify patients at higher risk of recurrence following en-bloc resection for T3-chest wall NSCLC.