- 作者列表："Dess RT","Sun Y","Muenz DG","Paximadis PA","Dominello MM","Grills IS","Kestin LL","Movsas B","Masi KJ","Matuszak MM","Radawski JD","Moran JM","Pierce LJ","Hayman JA","Schipper MJ","Jolly S","Michigan Radiation Oncology Quality Consortium.
PURPOSE:The heart has been identified as a potential significant organ at risk in patients with locally advanced non-small cell lung cancer treated with radiation. Practice patterns and radiation dose delivered to the heart in routine practice in academic and community settings are unknown. METHODS AND MATERIALS:Between 2012 and 2017, 746 patients with stage III non-small cell lung cancer were treated with radiation within the statewide Michigan Radiation Oncology Quality Consortium (MROQC). Cardiac radiation dose was characterized, including mean and those exceeding historical or recently proposed Radiation Therapy Oncology Group and NRG Oncology constraints. Sites were surveyed to determine dose constraints used in practice. Patient-, anatomic-, and treatment-related associations with cardiac dose were analyzed using multivariable regression analysis and inverse probability weighting. RESULTS:Thirty-eight percent of patients had a left-sided primary, and 80% had N2 or N3 disease. Median prescription was 60 Gy (interquartile range, 60-66 Gy). Twenty-two percent of patients were prescribed 60 Gy in 2012, which increased to 62% by 2017 (P < .001). Median mean heart dose was 12 Gy (interquartile range, 5-19 Gy). The volume receiving 30 Gy (V30 Gy) exceeded 50% in 5% of patients, and V40 Gy was >35% in 3% of cases. No heart dose constraint was uniformly applied. Intensity modulated radiation therapy (IMRT) usage increased from 33% in 2012 to 86% in 2017 (P < .001) and was significantly associated with more complex cases (larger planning target volume, higher stage, and preexisting cardiac disease). In multivariable regression analysis, IMRT was associated with a lower percent of the heart receiving V30 Gy (absolute reduction = 3.0%; 95% confidence interval, 0.5%-5.4%) and V50 Gy (absolute reduction = 3.6%; 95% confidence interval, 2.4%-4.8%) but not mean dose. In inverse probability weighting analysis, IMRT was associated with 29% to 48% relative reduction in percent of the heart receiving V40-V60 Gy without increasing lung or esophageal dose or compromising planning target volume coverage. CONCLUSIONS:Within MROQC, historical cardiac constraints were met in most cases, yet 1 in 4 patients received a mean heart dose exceeding 20 Gy. Future work is required to standardize heart dose constraints and to develop treatment approaches that allow for constraints to be met without compromising other planning goals.
目的: 在接受放射治疗的局部晚期非小细胞肺癌患者中，心脏已被确定为潜在的重要危险器官。在学术和社区环境中的常规实践中，向心脏递送的实践模式和辐射剂量是未知的。 方法和材料: 在 2012 至 2017 之间，746 例III期非小细胞肺癌患者在全州密歇根放射肿瘤学质量联盟 (MROQC) 内接受放射治疗。对心脏放射剂量进行了表征，包括平均值和超过历史或最近提出的放射治疗肿瘤学组和NRG肿瘤学约束的那些。调查位点以确定在实践中使用的剂量限制。使用多变量回归分析和逆概率加权分析患者、解剖和治疗与心脏剂量的相关性。 结果: 38% 的患者有左侧原发性，80% 有N2 或N3 疾病。中位处方为 60 Gy (四分位距，60-66 Gy)。2012 年，22% 的患者接受了 60 Gy的处方，到 2017 年，这一比例增加到 62% (P <.001)。平均心脏剂量中位数为 12 Gy (四分位距，5-19 Gy)。50% 的患者接受 30 gy (v30gy) 的体积超过 5%，35% 的患者v40gy> 3%。没有均匀地施加心脏剂量约束。调强放射治疗 (IMRT) 使用率从 2012 年的 33% 增加到 2017 年的 86% (P <.001)，并且与更复杂的病例显著相关 (更大的计划目标量，更高的阶段，和预先存在的心脏疾病)。在多变量回归分析中，IMRT与接受V30 Gy的心脏百分比较低相关 (绝对降低 = 3.0%; 95% 置信区间，0.5%-5.4%) 和v50gy (绝对减少 = 3.6%; 95% 置信区间，2.4%-4.8%)，但不是平均剂量。在逆概率加权分析中，IMRT与接受V40-V60 Gy的心脏百分比相对减少 29% 至 48% 相关，但不增加肺或食管剂量或影响计划目标体积覆盖。 结论: 在MROQC中，大多数病例都符合历史心脏限制，但每 4 例患者中就有 1 例接受了超过 20 gy的平均心脏剂量。未来的工作需要标准化心脏剂量限制，并开发治疗方法，允许在不损害其他规划目标的情况下满足限制。
METHODS::Pulmonary artery sling is a rare congenital anomaly of the origin and course of the left pulmonary artery. Patients with this condition typically present with respiratory failure in young infancy, and asymptomatic cases are uncommon. We describe the case of an adult patient with a lung adenocarcinoma of the right upper lobe, extending into the hilum and superior mediastinum, and with a previously unknown pulmonary artery sling anomaly. The local invasiveness of the tumor and the peculiar vascular anatomy contributed to a unique surgical scenario, wherein multiple reconstructive procedures were required.
METHODS::Patients with idiopathic pulmonary fibrosis (IPF) have higher risk of developing lung cancer, for example, squamous cell carcinoma (SCC), and show poor prognosis, while the molecular basis has not been fully investigated. Here we conducted DNA methylome analysis of lung SCC using 20 SCC samples with/without IPF, and noncancerous lung tissue samples from smokers/nonsmokers, using Infinium HumanMethylation 450K array. SCC was clustered into low- and high-methylation epigenotypes by hierarchical clustering analysis. Genes hypermethylated in SCC significantly included genes targeted by polycomb repressive complex in embryonic stem cells, and genes associated with Gene Ontology terms, for example, "transcription" and "cell adhesion," while genes hypermethylated specifically in high-methylation subgroup significantly included genes associated with "negative regulation of growth." Low-methylation subgroup significantly correlated with IPF (78%, vs. 17% in high-methylation subgroup, p = 0.04), and the correlation was validated by additional Infinium analysis of SCC samples (n = 44 in total), and data from The Cancer Genome Atlas (n = 390). The correlation between low-methylation subgroup and IPF was further validated by quantitative methylation analysis of marker genes commonly hypermethylated in SCC (HOXA2, HOXA9 and PCDHGB6), and markers specifically hypermethylated in high-methylation subgroup (DLEC1, CFTR, MT1M, CRIP3 and ALDH7A1) in 77 SCC cases using pyrosequencing (p = 0.003). Furthermore, low-methylation epigenotype significantly correlated with poorer prognosis among all SCC patients, or among patients without IPF. Multivariate analysis showed that low-methylation epigenotype is an independent predictor of poor prognosis. These may suggest that lung SCC could be stratified into molecular subtypes with distinct prognosis, and low-methylation lung SCC that significantly correlates with IPF shows unfavorable outcome.
METHODS::The role of Fyn-related kinase (FRK) in malignant tumors remains controversial. Our study investigated the function of FRK in lung cancer. Immunohistochemistry staining and generating a knockout of FRK by CRISPR/Cas9 in H1299 (FRK-KO-H1299) cells were strategies used to explore the role of FRK. Immunohistochemistry staining indicated that FRK expression was elevated in 223 lung cancer tissues compared to 26 distant normal lung tissues. FRK contributed to poor survival status in lung cancer patients and acted as a predictor for poor prognosis of lung cancer. Knockout of FRK by CRISPR/Cas9 markedly inhibited proliferation, invasion, colony formation and epithelial-mesenchymal transition (EMT) process in the lung cancer cell line H1299. Further exploration indicated that FRK-KO damaged the stemness phenotype of H1299 by inhibiting CD44 and CD133 expression. Seahorse detection and a U-13 C flux assay revealed that FRK-KO induced metabolism reprogramming by inhibiting the Warburg effect and changing the energy type in H1299 cells. Epidermal growth factor stimulation recovered the expression of FRK and biological functions, metabolic reprogramming and stemness phenotype of H1299 cells. FRK plays an oncogenic role in lung cancer cells via a novel regulation mechanism of enhancing the stemness of H1299 cells by inducing metabolism reprogramming, which finally promotes EMT and metastasis. Our study also indicates that FRK could be used as a potential therapeutic target for drug development.