胸中下段食管癌三维适形放疗所致放射性肺损伤相关因素分析

目的分析胸中下段食管癌患者三维适形放疗后导致放射性肺损伤的临床、物理因素。方法选取56例接受根治性放疗的食管癌患者密切随访。以患者临床症状、胸部X线片、CT、薄层CT了解患者有无急性放射性肺炎及晚期放射性肺损伤发生,对患者临床资料和治疗计划等指标进行单因素及多因素分析,评价放射性肺损伤。结果单因素分析显示X线片食管病变长度、处方剂量、肺V_5～V_(25)、肺D_(mean)、食管PTVD_(90)、食管PTVV_(50)及总射野数等11个因素与急性放射性肺炎发生相关,且其数值在有无发生急性放射性肺炎两组中有差异;X线片食管病变长度、肺V_5～V_(40)、肺D_(mean)及合并化疗与晚期放射性肺损伤相关,且其数值在有无发生晚期肺损伤的两组患者中亦有差异。Logistic多元回归分析显示肺V_(25)、总射野数和X线片病变长度为急性放射性肺炎发生的独立影响因素,而肺V_(30)和合并化疗为晚期放射性肺损伤发生的独立影响因素。急性放射性肺炎与晚期放射性肺损伤发生未见明显相关性。急性放射性肺炎、晚期放射性肺损伤对近期生存率未见明显影响。结论食管癌患者肺V_(25)、总射野数及X线片食管病变长度可预测急性放射性肺炎的发生,肺V_(30)和合并化疗为影响晚期放射性肺损伤发生的主要因素。     

Large cell neuroendocrine carcinoma of the lung: pathological study and clinical outcome of 18 resected cases

We investigated a risk of developing radiation myelitis during four prospective studies using hyperfractionated radiation therapy (HFX RT) with and without concurrent chemotherapy (CHT) during which a portion of thoracic spinal cord received a dose > or = 50.4 Gy given via 1.2 Gy b.i.d. fractionation. Of 536 patients with Stage III non-small cell lung cancer (NSCLC) which were treated on three prospective randomised Phase III studies and one Phase II study, 336 patients received irradiation dose > or = 50.4 Gy to a portion of their spinal cord and survived >1 year after the beginning of therapy. None of these 336 patients developed thoracic radiation myelitis. Therefore, the influence of potentially contributing factors on the occurrence of radiation myelitis, such as cord length, interfraction interval, or administration of concurrent CHT was not possible to investigate. These results give new insight about the influence of total dose/dose per fraction/interfraction interval with or without concurrent CHT on the thoracic spinal cord toxicity.     

Limited small cell lung cancer: possible prognostic impact of initial chemotherapy doses

While the effect of chemotherapy dose on tumor response in small cell lung cancer has been fairly well established, the effect on survival has been retrospectively analyzed only in some series. This particular point was studied in a series of 52 consecutive patients with limited small cell lung cancer treated by an alternating radiotherapy-chemotherapy schedule. The induction treatment consisted of 6 chemotherapy cycles (the planned doses were: doxorubicin 40 mg/m2 day 1, VP16213 75 mg/m2 days 1-3, cyclophosphamide 300 mg/m2 days 3-6, and cisplatinum 100 mg/m2 day 2) alternated after the first 2 cycles with 3 courses of thoracic radiotherapy delivering a total dose of 55 Gy. Eighty-one percent of patients went into complete remission and the 3-year relapse-free survival was 24%. A multivariate analysis of prognostic factors took into account age, sex, T stage, performance status, delayed hematological toxicity to the first course of chemotherapy, actual dose/m2 of each drug during the first course and mean dose/course delivered during the induction treatment after the first cycle of chemotherapy. It was possible to identify 3 independent factors influencing overall survival and relapse-free survival: actual initial dose of cisplatinum, actual initial dose of cyclophosphamide and the T stage. The effect of the initial dose of cisplatinum and cyclophosphamide proved to be linear on relapse-free survival. The results of this analysis show a possible effect of initial doses of chemotherapy in the management of limited small cell lung cancer in terms of both distant metastasis and overall survival rates.     

局限期小细胞肺癌胸部放疗及放射损伤的研究现状

目的:总结国内外局限期小细胞肺癌(LSCLC)胸部放疗研究的现状。方法:应用PubMed和CHKD期刊全文数据库检索系统,以"局限期小细胞肺癌、胸部放疗和放射损伤"为关键词,检索1986-01-2008-04相关LSCLC胸部放疗的文献,共检索到英文文献430篇和中文文献187篇。纳入标准:1)LSCLC胸部放疗的疗效评价;2)LSCLC胸部放疗的方法;3)LSCLC胸部放疗与化疗结合的研究;4)LSCLC胸部放疗损伤的研究。根据纳入标准,精选82篇,最后纳入分析29篇。结果:配合胸部放疗可以提高LSCLC生存期,虽然胸部放疗的剂量、照射范围、分割方式、放化疗的顺序和最佳时机的选择等一直存有争议,但多数专家认为胸部放疗更为合理的方式为早期配合化疗(3个周期内)常规的累及野照射,剂量45～55Gy为宜。这几个热点问题也是引起胸部放疗损伤的重要因素。结论:胸部放疗在LSCLC的治疗中占重要地位,应选择适宜的放疗时机、合理的照射靶区和剂量,给予个体化治疗,以最小的放疗损伤获得最佳的治疗效果。     

Chemotherapy response as a prognosticator for survival in patients with limited squamous cell lung cancer treated with combined chemotherapy and radiotherapy

Twenty-two patients with limited unresectable squamous cell lung cancer were treated with 6 courses of combination chemotherapy consisting of cyclophosphamide, adriamycin, cisplatin, and bleomycin (CAP-Bleo) and short-course thoracic irradiation started after the first 4 weeks of chemotherapy. Of 20 patients with visible tumor who were treated with 4 weeks of chemotherapy alone, 10 (50 %) had a tumor regression in that 4 week period and 10 did not. Those patients with tumor regression had significantly better progression free and overall survivals than did patients with no chemotherapy regressions (medians of 258 days vs. 136 days and 356 days vs. 150 days respectively). The original bleomycin dose had to be reduced by 50 % primarily because of excessive radiation esophagitis that has not been reported with use of either the CAP regimen or bleomycin along in conjunction with thoracic irradiation. An initial chemotherapy regression seems to be a good prognosticator for progression-free and overall survival in patients with limited squamous cell lung cancer treated with combined chemotherapy and radiotherapy.     

肺癌放射治疗致放射性肺炎的临床分析

目的：观察肺癌患者临床情况与放射性肺炎的（RP）关系。方法：总结419例需行放射治疗的Ⅱ-Ⅲb期肺癌患者的治疗情况，分析年龄、性别、病检、临床分期、肿瘤位置、化疗、手术、肺部疾病、吸烟指数、放疗剂量及放疗机类型对RP发生率的影响。结果：本组RP发生率为29．6％，女性高于男性；中心型高于周围型；单纯放疗者高于术后放疗者；合并有慢支、肺气肿的患者高于肺部无基础疾病者；采用18MV加速器放疗者低于^60Co机治疗者；放疗剂量与RP发生率相关。而患者年龄、临床分期、病理类型、是否合并化疗以及吸烟指数与RP的发生无明显关系。结论：性别、肿瘤位置、手术、肺部并发症、放疗剂量及放疗机类型明显影响RP的发生。     

Risk factors for interstitial lung disease and predictive factors for tumor response in patients with advanced non-small cell lung cancer treated with gefitinib

A high incidence of interstitial lung disease (ILD) has been reported in patients with non-small cell lung cancer (NSCLC) treated with gefitinib in Japan. We retrospectively analyzed 112 patients with advanced NSCLC who received gefitinib monotherapy. Univariate and multivariate analyses were used to identify risk factors for gefitinib-related ILD and predictive factors for tumor response to gefitinib. The incidence of ILD was 5.4%, and it was higher in the patients with pre-existing pulmonary fibrosis (33% versus 2%; P < 0.001). The results of a multivariate analysis showed that pulmonary fibrosis was a significant risk factor for ILD (odds ratio: 177, 95% confidence interval: 4.53-6927, P = 0.006). The response rate was 33% in the 98 evaluable patients and higher in women (53% versus 23%; P = 0.003), patients with adenocarcinoma (38% versus 6%; P = 0.010), never-smokers (63% versus 18%; P < 0.001), and the patients with no history of thoracic radiotherapy (39% versus 13%; P = 0.015). The results of a multivariate analysis showed that the predictors of tumor response were "no history of smoking" and "no history of thoracic radiotherapy". Never-smokers had a significantly longer survival time than smokers (P = 0.007). Although gefitinib therapy confers a clinical benefit on patients with advanced NSCLC, especially on women, patients with adenocarcinoma, never-smokers, and patients with no history of thoracic radiotherapy, it also poses a high risk of ILD, especially to patients with pulmonary fibrosis. The risk-benefit ratio must be carefully considered.     

肺低剂量区体积预测胸中下段食管癌放射性肺炎的价值

目的 明确肺低剂量区体积在预测接受放射治疗的胸中下段食管癌患者出现急性放射性肺炎（radiation pneumonitis, RP）的价值。方法 对205例接受放射治疗并符合入组条件的胸中下段食管癌患者发生RP的情况进行分析,对患者临床资料和治疗计划等指标进行单因素及多因素分析,评价肺低剂量区体积指标的价值。结果 全组患者出现≥2级RP的患者为60例占29.27%（60/205）,其中2级48例（23.41%）,3级10例（4.88%）,4级2例（0.98%）。单因素分析结果显示食管癌病变X 线长度、GTV最大横径、GTV长度、射野数、肺MLD、GTV体积、PTV体积、肺V5、肺V10和肺V15均影响患者≥2级RP的发生。多因素分析结果显示射野数、肺MLD及肺V5为患者≥2级RP发生的独立预测影响因素。ROC曲线分析结果显示本组患者肺V5取值为51.17%为预测放射性肺炎的效能值。结论 肺低剂量区体积V5为接受放疗的胸中下段食管癌患者发生≥2级RP的重要预测因素,建议在以后制定胸中下段食管癌的放射治疗计划时应该予以重视,取值应≤51.17%。     

Radiation pneumonitis and pulmonary fibrosis in non-small-cell lung cancer: pulmonary function, prediction, and prevention

Although radiotherapy improves locoregional control and survival in patients with non-small-cell lung cancer, radiation pneumonitis is a common treatment-related toxicity. Many pulmonary function tests are not significantly altered by pulmonary toxicity of irradiation, but reductions in D(L(CO)), the diffusing capacity of carbon monoxide, are more commonly associated with pneumonitis. Several patient-specific factors (e.g. age, smoking history, tumor location, performance score, gender) and treatment-specific factors (e.g. chemotherapy regimen and dose) have been proposed as potential predictors of the risk of radiation pneumonitis, but these have not been consistently demonstrated across different studies. The risk of radiation pneumonitis also seems to increase as the cumulative dose of radiation to normal lung tissue increases, as measured by dose-volume histograms. However, controversy persists about which dosimetric parameter optimally predicts the risk of radiation pneumonitis, and whether the volume of lung or the dose of radiation is more important. Radiation oncologists ought to consider these dosimetric factors when designing radiation treatment plans for all patients who receive thoracic radiotherapy. Newer radiotherapy techniques and technologies may reduce the exposure of normal lung to irradiation. Several medications have also been evaluated for their ability to reduce radiation pneumonitis in animals and humans, including corticosteroids, amifostine, ACE inhibitors or angiotensin II type 1 receptor blockers, pentoxifylline, melatonin, carvedilol, and manganese superoxide dismutase-plasmid/liposome. Additional research is warranted to determine the efficacy of these medications and identify nonpharmacologic strategies to predict and prevent radiation pneumonitis.     

Serum creatinine level during chemotherapy for testicular cancer as a possible predictor of bleomycin-induced pulmonary toxicity

BACKGROUND: Bleomycin is one of the key drugs used in induction chemotherapy for testicular cancer. Pulmonary toxicity is the major and potentially fatal adverse side-effect of this drug. METHODS: To evaluate the risk factors for bleomycin pulmonary toxicity, we retrospectively analyzed the cases of 20 men treated for metastatic testicular cancer at Tsukuba University Hospital between 1990 and 1996. All patients were treated with two to four cycles of a PVB regimen or BEP regimen. Recombinant human granulocyte colony-stimulating factor was used in all but one case. With a logistic procedure, we evaluated the age, total bleomycin dose, total cisplatin dose, renal injury, leukocytosis, smoking history, lung metastases and drug regimen as risk factors for a decrease in the diffusing capacity. RESULTS: Diffusing capacity was decreased to below 75% of the predicted values in nine patients. Elevation of the serum creatinine level was the most significant risk factor (P = 0.018) by the chi-squared test. A logistic regression analysis also indicated that the elevation of serum creatinine level was an independent risk factor for a decrease in the diffusing capacity (odds ratio 22.3, 95% Cl 1.02-487.3, P = 0.049). CONCLUSIONS: We recommend a pulmonary function assessment of patients receiving a relatively low dose of bleomycin, especially when an elevated serum creatinine level is seen during chemotherapy.      

Ⅳ期非小细胞肺癌预后因素分析及胸部放疗的潜在意义

目的:分析Ⅳ期非小细胞肺癌（NSCLC）患者的疗效和预后因素,探讨胸部放疗在Ⅳ期NSCLC治疗中的意义。方法:回顾性分析79例有远处转移并行胸部放疗的Ⅳ期NSCLC患者的临床资料,采用Kaplan-Meier法计算其生存率,并采用Log-rank检验和单因素预后分析进行分析,对统计学有意义的因素进一步用Cox模型行多因素预后分析。结果:1、2年生存率分别为34.2%、12.3%,中位生存期为10个月。单因素分析结果显示影响Ⅳ期NSCLC预后的因素有是否吸烟、转移灶数、胸部放疗剂量（P=0.021、0.000 1、0.002）。多因素分析显示,转移灶数、胸部放疗剂量是系统化疗并行胸部三维适形放疗（3D-CRT）的Ⅳ期NSCLC的独立预后因素（P=0.002、0.045）。结论:Ⅳ期NSCLC行胸部放疗有潜在的临床意义,并且转移灶数目、胸部放疗剂量是影响其生存的显著预后因素。     

如何减少非小细胞肺癌放疗中的肺损伤

放疗是肺癌的主要治疗方式之一,但所致肺损伤也制约生存质量和疗效;如何提高疗效又减少损伤是必须面临的挑战。然而,根据经验采取一些措施可以更好的减少胸部肿瘤放疗肺损伤。首先较全面了解病情和合并症,以及放化疗协同损伤的影响来制定个体化方案。把掌握或精通的诊断技能和肿瘤生物学特性、以及肿瘤扩散和转移复发和淋巴引流规律等用于治疗靶区的制定中,以每1 mm必争来减少不必要照射。制定和评价放疗计划时,要了解肺和肺损伤修复的生物学特性,遵循宁愿小体积肺高剂量,不要大体积肺低剂量照射的原则;用胸部肿瘤放疗思维做到每1%肺DVH相争来减少肺照射,即使牺牲一些适形度。用肿瘤同步加量技术和二程治疗计划,对正常组织以及亚临床和肿瘤从剂量和分割剂量区别,可进一步增加肿瘤控制和减少损伤。肺失去通气功能剂量在20 Gy或稍多,而且为非功能性纤维化修复,要特别注意降低低剂量肺的照射。艺术性的个体化应用精准放疗技术,点滴积累减少不必要的范围和保护肺组织功能,才能有更好疗后生存质量和肿瘤疗效。     

^125I粒子植入治疗外照射后肺癌残存病灶的可行性分析（附18例）

目的：探讨和评估放射性^125I粒子植入治疗肺癌外照射（适形放疗,伽玛刀）后局部残存病灶的疗效。方法：依据TPS计划系统预先计算出18例肺癌患者外照射后局部残存病灶处所需植入的粒子数目,活度和处方剂量;在手术植入过程中再次通过TPS计划系统做粒子植入剂量验证报告,同时分析危及器官心包、食道、脊髓等组织的受量,以达到与治疗计划相符的处方剂量;粒子植入后2个月再行TPS剂量验证,评估实际肿瘤包块粒子治疗的剂量。结果：18例患者瘤体最小周边剂量（mPD）为80—120Gy,靶区90％体积的吸收剂量（D90）为103．6—137．6Gy;肿瘤距离心包,脊髓组织最近的在1—2cm处,吸收剂量迅速衰减到20％到5％左右,为24和6Gy;18例患者2个月内瘤体达到CR＋PR者17例（94％）,瘤体缩小明显,无明显变化（NC）1例（6％）。并发症：气胸6例,喀血0例,18例患者未发现放射性损伤。结论：放射性^125I粒子植入治疗可有效控制外照射后肺癌局部残存病灶,是一种安全,有效的方法。     

125Ⅰ粒子植入治疗外照射后肺癌残存病灶的可行性分析（附18例）

目的:探讨和评估放射性125I粒子植入治疗肺癌外照射(适形放疗,伽玛刀)后局部残存病灶的疗效。方法:依据TPS计划系统预先计算出18例肺癌患者外照射后局部残存病灶处所需植入的粒子数目,活度和处方剂量;在手术植入过程中再次通过TPS计划系统做粒子植入剂量验证报告,同时分析危及器官心包、食道、脊髓等组织的受量,以达到与治疗计划相符的处方剂量;粒子植入后2个月再行TPS剂量验证,评估实际肿瘤包块粒子治疗的剂量。结果:18例患者瘤体最小周边剂量(mPD)为80-120Gy,靶区90%体积的吸收剂量(D90)为103.6-137.6Gy;肿瘤距离心包,脊髓组织最近的在1-2cm处,吸收剂量迅速衰减到20%到5%左右,为24和6Gy;18例患者2个月内瘤体达到CR+PR者17例(94%),瘤体缩小明显,无明显变化(NC)1例(6%)。并发症:气胸6例,喀血0例,18例患者未发现放射性损伤。结论:放射性125I粒子植入治疗可有效控制外照射后肺癌局部残存病灶,是一种安全,有效的方法。     

Evaluation of the Radiation Pneumonia Development Risk in Lung Cancer Cases

Background: Concurrent chemo-radiotherapy is the recommended standard treatment modality for patients with locally advanced lung cancer. The purpose of three-dimensional conformal radiotherapy (3DCRT) is to minimize normal tissue damage while a high dose can be delivered to the tumor. The most common dose limiting side effect of thoracic RT is radiation pneumonia (RP). In this study we evaluated the relationship between dose-volume histogram parameters and radiation pneumonitis. This study targeted prediction of the possible development of RP and evaluation of the relationship between dose-volume histogram (DVH) parameters and RP in patients undergoing 3DCRT. Materials and Methods: DVHs of 41 lung cancer patients treated with 3DCRT were evaluated with respect to the development of grade ≥ 2 RP by excluding gross tumor volume (GTV) and planned target volume (PTV) from total (TL) and ipsilateral (IPSI) lung volume. Results: Were admitted statistically significant for p<0.05. Conclusions: The cut-off values for V5, V13, V20, V30, V45 and the mean dose of TL-GTV; and V13, V20,V30 and the mean dose of TL-PTV were statistically significant for the development of Grade ≥2 RP. No statistically significant results related to the development of Grade ≥2 RP were observed for the ipsilateral lung and the evaluation of PTV volume. A controlled and careful evaluation of the dose-volumehistograms is important to assess Grade ≥2 RP development of the lung cancer patients treated with concurrent chemo-radiotherapy. In the light of the obtained data it can be said that RP development may be avoided by the proper analysis of the dose volume histograms and the application of optimal treatment plans.     

Cerebral metastases as first symptom of bronchogenic carcinoma. A prospective study of 37 cases

Among the patients showing evidence of cerebral metastases without previously known cancer history, lung cancer has been found 37 times as the primary tumor in our institution. There were 34 men and three women and all but two were heavy smokers. Only one presented at diagnosis with thoracic symptoms but the chest radiograph was abnormal in 34. The histologic type of the primary tumor was obtained in 32 cases as a result of thoracic investigations and in five cases from metastatic tumor tissue. The primary tumor appeared to be non-small cell lung carcinoma in 26 cases and small cell lung carcinoma in 11 cases. These results show that patients treated with surgery (20 cases) have a better survival (median 10 months versus 4.5) than the others, and among surgically treated patients only those treated with bifocal resection (eight patients) are long-term survivors. Also, in four of six patients, objective regression of the neurologic symptoms was seen after radiation therapy alone. Central nervous system relapse was seen in 12 patients, but in none of the patients treated with postoperative radiation therapy. Conventional chemotherapy (11 patients) induced objective responses only in the small cell type and proved to be too toxic when used simultaneously with radiation therapy in inoperable patients.     

Radiotherapy-Related Lymphopenia Affects Overall Survival in Patients With Lung Cancer

IntroductionLymphopenia after radiotherapy has an adverse effect on the patient’s outcome. However, the relationship between radiotherapy dose delivery and lymphopenia is not fully understood. This work used image-based data mining to identify anatomical regions where the received dose is correlated with severe lymphopenia.MethodsA total of 901 patients with lung cancer were analyzed. A Cox model was used to assess prognostic factors of overall survival (OS). Two matched groups were defined—patients with lymphopenia of grade 3 or higher and patients without lymphopenia of grade 3—based on tumor volume, baseline lymphocytes, and prescribed dose. Then, data mining was used to identify regions where dose correlates significantly with lymphopenia of grade 3 or higher. For this, dose matrices were aligned using registration of the computed tomography images to one reference patient. Mean dose distributions were obtained for the two groups, and organs of significance were detected. Dosimetric parameters from the identified organs that had the highest correlation with lymphocytes at nadir were selected. Multivariable analysis was conducted for lymphopenia of grade 3 or higher on the full lung cohort, and the model was tested on 305 patients with esophageal cancer.ResultsAdjusted Cox regression revealed that lymphopenia of grade 3 or higher is an independent factor of OS. The anatomical regions identified were the heart, lung, and thoracic vertebrae. Dosimetric parameters for lymphopenia included thoracic vertebrae V₂₀, mean lung dose, and mean heart dose, which were further validated in the esophageal cancer cohort.ConclusionsWe report that severe lymphopenia during radiotherapy is a poor prognostic factor for OS in patients with lung cancer and could be mitigated by minimizing thoracic vertebrae V₂₀, mean lung dose, and mean heart dose to limit the irradiation of stem cells and blood pool.     

Radiation recall pneumonitis induced by erlotinib after palliative thoracic radiotherapy for lung cancer: Case report and literature review

Radiation lung injury usually develops 1–6 months after cessation of radiation therapy to the lung. Acute change in the previously irradiated lung after administration of antineoplastic agent is known as radiation recall pneumonitis. Erlotinib is a reversible epidemal growth factor receptor tyrosine kinase inhibitor, which is effective for patients with advanced lung cancer with epidermal growth factor receptor mutations. Here we report a rare case of radiation recall pneumonitis following treatment with erlotinib 4 months after palliative radiotherapy to the lung. A 76‐year‐old man with non–small cell lung cancer was treated with polychemotherapy, palliative thoracic irradiation (30 Gy in 12 fractions) and erlotinib thereafter. Two months after administration of erlotinib he developed of severe dyspnea, cough, anorexia and lack of energy. CT chest revealed extensive radiation pneumonitis. Erlotinib was ceased and high‐dose steroids were started. The symptoms ultimately resolved and erlotinib was resumed cautiously after 11 weeks. On dosimetric analysis, lung V20 and the mean lung dose were 20.33% and 10.7 Gy, respectively, and hence, the risk of radiation pneumonitis is very low. These data indicate that systemic administration of erlotinib after low‐dose palliative radiation therapy can be associated with unexpected toxicity when visceral organs are within the radiation field.     

Aggressive Treatment of Primary Tumor in Patients With Non–Small-Cell Lung Cancer and Exclusively Brain Metastases

Between 30% and 50% of patients with non–small-cell lung cancer (NSCLC) will develop cerebral metastases in the course of their illness. As improvements are made in the local brain treatment, the question arises on how to manage patients with NSCLC who have solely stable brain metastatic disease and if treatment should be considered for the primary lung lesion. The present article will review published series of patients with NSCLC and with brain metastases treated with aggressive thoracic management, with either lung tumor resection or thoracic radiation with or without chemotherapy as definitive treatment. We will also assess which prognostic factors may be useful in the identification of the subset of patients who could benefit from this more aggressive approach. For patients treated with surgical resection for the primary lung tumor, median survival ranged from 19 to 27 months, and the 1-, 2-, and 5-year survival reached 56%-69%, 28%-54%, and 11%-24%, respectively. Patients treated with aggressive radiotherapy with or without chemotherapy, achieved a median survival of 15.5-31.8 months, with a 1-year survival of 50%-71%, and a 2-year survival of 16%-60%. Well-selected patients with NSCLC and with exclusively oligometastatic cerebral disease represent a subgroup of patients with stage IV NSCLC that might achieve long-term survival after treatment directed to the brain and lung tumor lesions. Patients with N0 or N1 disease may be selected for surgical thoracic treatment, whereas those with N2 or N3 disease may benefit from combined chemoradiotherapy in the absence of progression after induction chemotherapy.