非小细胞肺癌术后三维适形放疗与常规放疗的疗效比较

背景与目的：非小细胞肺癌术后三维适形放疗与常规放疗的疗效比较目前尚缺乏长期随访结果．本研究回顾性分析非小细胞肺癌（NSCLC）术后分别采用三维适形放疗和常规放疗的疗效及放疗反应，比较不同放疗技术对疗效及放疗反应的影响。方法：收集1990年12月-2002年8月美国M．D．安德森癌症研究中心收治的167例Ⅲ．期NSCLC患者的术后放疗资料进行回顾性分析。其中常规放疗组（CV组）90例．三维适形放疗组（CF组）77例。CV组放疗中位剂量为54．3Gy／27次．CF组放疗中位刹龟为53．9Gy／26次．均在5～6周内完成。结果：两组患者病例特征具有可比性。CV组和CF组中位随访时间分别为36个月和24个月，两组无瘤生存率、局部控制率及无远处转移生存率差异无显著性，但两组总生存率差异有显著性（P=0．014）。CF组在肺部纤维化、心脏损伤和血液系统放疔反应发生率显著性上要低于CV组，其余放疗反应差异基本尤最著性。两组死亡原因差异有显著性，CV组有8例患者死于与心脏损伤有关的并发症，而CF组没有。结论：Ⅲ、期NSCLC术后采用改进的三维适形放疗技术不仅可以取得与常规放疗类似的疗效，还可提高总生存率，同时降低了肺部纤维化、心脏损伤和血液系统反应发生率，三维适形放疗的治疗优势值得关注．

Intensity-modulated radiation therapy with concurrent chemotherapy for locally advanced cervical and upper thoracic esophageal cancer

AIM： To evaluate the dosimetry, efficacy and toxicity of intensity-modulated radiation therapy （IMRT） and concurrent chemotherapy for patients with locally advanced cervical and upper thoracic esophageal cancer. METHODS： A retrospective study was performed on 7 patients who were definitively treated with IMRT and concurrent chemotherapy. Patients who did not receive IMRT radiation and concurrent chemotherapy were not included in this analysis. IMRT plans were evaluated to assess the tumor coverage and normal tissue avoidance. Treatment response was evaluated and toxicities were assessed. RESULTS： Five- to nine-beam IMRT were used to deliver a total dose of 59.4-66 Gy （median： 64.8 Gy） to the primary tumor with 6-MV photons. The minimum dose received by the planning tumor volume （PTV） of the gross tumor volume boost was 91.2%-98.2% of the prescription dose （standard deviation [SD]： 3.7%-5.7%）. The minimum dose received by the PTV Of the clinical tumor volume was 93.8%-104.8% （SD： 4.3%-11.1%） of the prescribed dose. With a median follow-up of 15 rno （range： 3-21 too）, all 6 evaluable patients achieved complete response. Of them, 2 developed local recurrences and 2 had distant metastases, 3 survived with no evidence of disease. After treatment, 2 patients developed esophageal stricture requiring frequent dilation and 1 patient developed tracheal-esophageal fistula. CONCLUSION： Concurrent IMRT and chemotherapy resulted in an excellent early response in patients with locally advanced cervical and upper thoracic esophageal cancer. However, local and distant recurrence and toxicity remain to be a problem. Innovative approaches are needed to improve the outcome.

应用最大似然率及随机效应模型探讨非小细胞肺癌放化疗中急性放射性食管炎与照射剂量和疗程的关系

背景与目的：局部晚期非小细胞肺癌的治疗疗效差，增加治疗强度如同期放化疗是提高疗效的方法，但毒性反应较大。本研究探讨非小细胞肺癌同期放化疗的治疗方式中，应用最大似然率及随机效应模型探讨非小细胞肺癌放化疗中急性放射性食管炎的发生率与照射剂量和疗程时间因素的关系。方法：本研究中的39例病例资料来自于1998年3月-2000年11月间在M．D．Anderson癌症治疗中心进入随机临床Ⅲ期的同期放化疗治疗研究不能手术的Ⅱ期和Ⅲ期非小细胞肺癌患者。所有的患者在放疗前均接受顺铂和口服依托泊苷（VP-16）的化疗。放疗方案为每次1．2Gy，bid，前后野对照治疗至肿瘤剂量达40～50Gy后，采用避开脊髓的斜野放疗至总剂量69．6Gy。病例分布为amifostine治疗组，19例；非amifostine治疗组，20例。还原三维治疗计划设计并计算了剂量-体积直方图（DVHs）。治疗开始后每周对急性放射性食管炎程度评估1次，在放疗结束后1个月再随访评估1次。评分的标准是根据美国放射治疗研究组（RTOG）的急性反应的标准。采用了多因素的随机效应模型及最大似然率的分析以研究在这39例病例中急性放射性食管炎的严重程度与照射剂量和疗程时间因素的关系，并考虑了不同病例个体间的敏感性差异。结果：在amifostine治疗组有11％（2／19），非amifostine治疗组有30％（6／20）的患者发生Ⅲ度的急性食管炎。在这两组中，急性食管炎的发生率在开始治疗后第4周（累计剂量为48Gy）达高峰并呈一稳定状态。随治疗后期剂量的进一步增加，急性食管炎发生的危险性并不明显增加。原因可能是食管粘膜上皮组织的修复和在治疗后的上皮细胞加速再增殖。疗程中的周剂量或累计周剂量要比整个疗程的总剂量更好地预测急性食管炎的发生。结论：肿瘤累积剂量和患者的内在敏感性与Ⅲ度急性放射性食管炎的发生率有关。欲将发生急性食管炎的危险性降低至10％以下，需限制第4周的累计剂量在36Gy以下，或9Gy／周。这可能为开展IMRT等新技术的治疗提供有用的参考信息。

Evaluation of conventional radiotherapy vs. conformal radiotherapy in the treatment of non-small-cell lung cancer after surgical resection

Objective： To compare the survival fractions and radiation-induced complications of conventional radiotherapy （CV） vs. conformal radiotherapy （CF） for non-small-cell lung cancer （NSCLC） after surgical resection. Methods： Between 1990 and 2002, 167 patients underwent post-radiotherapy either CV （n = 90） or CF （n = 77） for pathological IliA NSCLC at the University of Texas M.D. Anderson Cancer Center. Patients and tumor charactedstics were balanced in the two treatment groups. Surgical resection mainly consisted of Iobectomy and mediastinal lymph node dissection. In the CV group, postoperative radiotherapy was delivered to 54.3 Gy （range 22-69.6 Gy） in 27 fractions （range 11-58 f） for 5-6 weeks, while the CF group with RT to 53.9 Gy （range 50-63 Gy） in 26 fractions （range 25-33 f） for 5-6 weeks. Overall survival, disease-free survival, local control and distant metastasis-free survival were calculated using the Kaplan-Meier method. The complications of radiotherapy were also compared between the two groups. The median follow-up duration was 36 months in the CV group while 24 months in the CF group. Results： No statistically significant differences were found in terms of disease-free survival, local-regional control and distant metastasis-free survival in the two treatment groups. However, the overall survival was found statistically significant different in the two groups （P = 0.014）. Postoperative radiotherapy complications such as weight loss, skin reaction, dysphagia, and cardiac related complication were similar in the two groups although the lung fibrosis, cardiac complications and hematologic complications were significantly different, and 8 cases of death in the CV group associated with cardiac complications while none was observed in the CF group. Conclusion： The treatment of stage IliA NSCLC using either CV or CF postoperative radiotherapy resulted in similar outcomes in terms of local control, disease-free survival and most of complications. However, CF could achieve better overall survival and less complications such as lung fibrosis, cardiac complications and hematologic complications. The advantage is worth further observation.

Investigation of Target Minimum and Maximum Dosimetric Criteria for the Evaluation of Standardized Radiotherapy Plan <br/>—Target Minimum and Maximum Evaluation

Purpose: Standardization of tumor dosimetric coverage is essential for the evaluation of radiotherapy treatment plan quality. National clinical trials network RTOG protocols include tumor target dosimetric criteria that specify the prescription dose and minimum and maximum dose (Dmin and Dmax) coverages. This study investigated the impact of various minimum and maximum dose definitions using tumor control probability (TCP) models. Methods and Materials: Three disease sites (head and neck, lung, and prostate) were studied using target volume dosimetric criteria from the RTOG 0920, 1308, and 0938 protocols. Simulated target dose-volume histograms (DVHs) of Dmin and Dmax were modeled using the protocol specifications. Published TCP models for the three disease sites were applied to the DVH curves. The effects of various dose definitions on TCP were studied. Results: While the prescription dose coverage was maintained, a -3.7% TCP difference was observed for head and neck cancer when the target doses varied by 3.5% of the tumor volume from the point dose. For prostate and lung cancers, -3.3% and -2.2% TCP differences were observed, respectively. The TCPs for head and neck and prostate cancers were more negatively affected by deviations in the Dmin than the TCP for lung cancer. The lung TCP increased to a greater extent with a change in the Dmax compared with the head and neck and prostate TCPs. Conclusions: These results can be used to evaluate plan quality when the target dose only slightly deviates from the dosimetric criteria. When the overall target prescription dose coverage is maintained, the Dmax is recommended to be within 3% of the target volume: 98% (for head and neck and prostate) and 97% (for lung) of the target volume, satisfying the Dmin needed to maintain TCP variations at less than 2.1%. Using 0.03 cc instead of a point dose for Dmin and Dmax criteria minimally impacts TCPs.

Extra-pleural pneumonectomy in the setting of tri-modality therapy for patients with malignant pleural mesothelioma

Although declining in the US due to restrictions of asbestos exposure, malignant pleura/mesothelioma （MPP） remains a very serious thoracic malignancy that is rising in incidence worldwide （1）. Trirnodality therapy with chemotherapy and radiotherapy combined with extrapleural pneumonectomy （EPP） has gained acceptance given the acceptable mortality rate （〈5%） and long term survival reported in patients with epithelial histology, negative margins, and no extrapleural lymph node involvement after trimodalitv treatment （2）.

Integrated circulating tumor DNA and T cell repertoire predict radiotherapeutic response and outcome in non-small cell lung cancer patients with brain metastasis

Dear editor,The scarcity of routinemetastatic biopsies or resection limits the finding of biomarkers of diagnosis and prognosis in patients with brain metastases.Derived from necrosis,apoptosis,and secretion of tumor cells,circulating tumor DNA(ctDNA)is widely distributed in various body fluids,including peripheral blood and cerebrospinal fluid(CSF),as an alternative biomarker for tumor-associated analysis[1].Fortunately,genomic alterations of blood ctDNA and CSF ctDNA have been proven as prognostic markers in non-small cell lung cancer(NSCLC)patients with brain metastasis[2,3].

Functional promoter rs189037 variant of ATM is associated with decrease in lung diffusing capacity after irradiation for nonesmall-cell lung cancer

Objective: Single-nucleotide polymorphisms (SNPs) in the ataxia telangiectasiaemutated gene ATM have been linked with pneumonitis after radiotherapy for lung cancer but have not been evaluated in terms of pulmonary function impairment. Here we investigated potential associations between SNPs in ATM and changes in diffusing capacity of the lung for carbon monoxide (DLCO) in patients with nonesmall-cell lung cancer (NSCLC) after radiotherapy. Methods: From November 1998 through June 2009, 448 consecutive patients with inoperable primary NSCLC underwent definitive (≥60 Gy) radiotherapy, with or without chemotherapy. After excluding patients with a history of thoracic surgery, ra-diation, or lung cancer; without DNA samples available for analysis; or without pulmonary function testing within the 12 months before and the 12 months after radiotherapy, 100 patients were identified who are the subjects of this study. We genotyped two SNPs of ATM previously found to be associated with radiation-induced pneumonitis (rs189037 and rs228590) and evaluated potential correlations between these SNPs and impairment (decreases) in DLCO by using logistic regression analysis. Results: Univariate and multivariate analyses showed that the AA genotype of ATM rs189037 was associated with decreased DLCO after definitive radiotherapy than the GG/AG genotypes (univariate coefficient, -0.122; 95％ confidence interval (CI),-0.236 to -0.008; P = 0.037; and multivariate coefficient, -0.102; 95％ CI, -0.198 to -0.005; P = 0.038)No such correlations were found for rs228590 (univariate coefficient, -0.096; 95％ CI, -0.208 to 0.017; P = 0.096). Conclusions: The AA genotype of ATM rs189037 was associated with higher risk of lung injury than were the GG/AG genotypes in patients with NSCLC treated with radiotherapy. This finding should be validated prospectively with other patient populations.

DNA repair capacity correlates with standardized uptake values from 18F-fluorodeoxyglucose positron emission tomography/CT in patients with advanced non-small-cell lung cancer

Objective: The DNA repair capacity (DRC) of tumor cells is an important contributor to resistance to radiation and platinum-based drugs. Because DRC may be affected by tumor cell metabolism, we measured DRC in lymphocytes from patients with non-small-cell lung cancer (NSCLC) and compared the findings with the maximum standardized uptake value (SUVmax) on 18 F-fluorodeoxyglucose positron emission tomography (FDG PET) after (chemo)radiation therapy. Methods: This study included 151 patients with stage IA-IV NSCLC who had FDG PET at a single institution and donated blood samples before chemotherapy. We assessed the correlation of DRC, measured in peripheral T lymphocytes by a host-cell reac-tivation assay with SUVmax and their associations with overall survival (OS) time by hazards ratios calculated with a Cox pro-portional hazards regression model. Results: SUVmax of the primary tumor at diagnosis was inversely associated with lymphocyte DRC (r＝－0.175, P＝0.032), particularly among patients with advanced disease (r ＝ －0.218, P ＝ 0.015). However, △SUVmax of primary tumor was not significantly associated with DRC (r＝0.005, P＝0.968). SUVmax of regional lymph nodes at diagnosis (r＝－0.307, P＝0.0008) and after (chemo)radiation treatment (r＝－0.329, P＝0.034) and SUVmax of the primary tumor after (chemo)radiation treatment (r＝－0.253, P＝0.045) were also inversely associated with OS time. Conclusion: DRC was inversely associated with primary tumor SUVmax before treatment but not with △SUVmax after (chemo)radiation.