体部立体定向放疗在寡转移NSCLC的临床应用和前景北大核心CSCD

免疫治疗及靶向治疗等药物的快速进展,为局部晚期非小细胞肺癌(NSCLC)带来了长期生存获益。尤其是针对转移病灶少的晚期肺癌,通过积极的局部治疗手段,可进一步提高患者的生存率,甚至达到临床治愈的可能。近年来,随着放射技术的进步,体部立体定向放射治疗(SBRT)实现了对小靶区肿瘤的精准高剂量放射治疗,目前已被广泛应用于不可手术的早期肺癌,而其在晚期肺癌患者中的应用价值和安全性也正被积极探索。本文就SBRT在晚期寡转移肺癌的研究现状、进展及未来发展方向进行讨论。     

体部立体定向放疗在寡转移NSCLC的临床应用和前景

免疫治疗及靶向治疗等药物的快速进展, 为局部晚期非小细胞肺癌(NSCLC)带来了长期生存获益。尤其是针对转移病灶少的晚期肺癌, 通过积极的局部治疗手段, 可进一步提高患者的生存率, 甚至达到临床治愈的可能。近年来, 随着放射技术的进步, 体部立体定向放射治疗(SBRT)实现了对小靶区肿瘤的精准高剂量放射治疗, 目前已被广泛应用于不可手术的早期肺癌, 而其在晚期肺癌患者中的应用价值和安全性也正被积极探索。本文就SBRT在晚期寡转移肺癌的研究现状、进展及未来发展方向进行讨论。     

血脑屏障在非小细胞肺癌脑转移治疗中的意义

目前,肺癌的发病率居中国恶性肿瘤首位,且其病死率也较高,是导致肿瘤患者死亡的最主要的原因,其中非小细胞肺癌(NSCLC)约占肺癌的85%。局部复发及远处转移是肺癌病死率较高的主要原因,而颅脑是肺癌远处转移的常见部位。随着脑磁共振成像技术的普遍应用和肺癌患者生存率的提高,肺癌脑转移的发生率呈上升趋势。一旦发生肺癌脑转移,将会严重影响患者的生活质量,且预后极差。血脑屏障(BBB)的存在一直被认为是限制药物成功治疗肺癌脑转移的重要原因,故本文将针对BBB在NSCLC脑转移治疗中的意义进行阐述,以期为提高NSCLC脑转移患者的疗效提供依据。     

53例非小细胞肺癌伴脑转移的外科治疗及预后因素分析

脑转移是非小细胞肺癌(non small cell lung cancer．NSCLC)常见的远处转移。1／3的非小细胞肺癌伴脑转移患者是单发病灶的脑转移(single brain metastasis．SBM)，而不伴其它远处转移。许多研究表明．在延长非小细胞肺癌伴单发脑转移患者生存时间方面，外科治疗优于其它任何治疗。本文对     

Ⅳ期非小细胞肺癌寡转移放射治疗的理论及研究现状

目的 以铂类为基础的系统化疗一直以来被当做Ⅳ期非小细胞肺癌(non-small cell lung cancer,NSCLC)主要的治疗方式,放疗只起姑息减症作用.近年来越来越多的临床研究指出对转移灶和转移器官数目有限的“寡转移”患者,其生物学行为不同于广泛转移的患者,预后相对较好.因此,加强原发病灶的局部治疗来提高局控率进而改善生存的研究也逐步凸显其必要性和重要性.本文主要探讨放射治疗在Ⅳ期寡转移NSCLC治疗中的理论及应用.方法 应用Science Direct、CNKI期刊全文数据库检索系统,以“非小细胞肺癌,寡转移,治疗”为关键词检索2005-01-2015-12年的相关文献,共131篇,其中英文文献72篇,中文文献59篇.纳入标准:(1)Ⅳ期NSCLC;(2)寡转移;(3)局部治疗.排除标准:(1)广泛转移NSCLC;(2)合并其他原发性癌.根据标准分析文献33篇.结果 针对局部病灶的治疗可将寡转移患者的中位生存期提高到13.5个月.近年来随着放射治疗技术与设备的不断发展,放射治疗已经与提高寡转移患者的局部控制率息息相关,也有越来越多的寡转移患者接受了局部病灶放疗.结论 放射治疗对提高寡转移患者的局部控制率与整体生存率起着确切的作用.为了提出更有说服力的循证医学证据,相关的临床试验也还在不断地进行中.     

非小细胞肺癌放疗靶区研究进展

肺癌是最常见的恶性肿瘤之一,近年来其发病率和死亡率都有逐年增加的趋势,其中非小细胞肺癌(NSCLC)大约占肺癌总数的70%～80%.由于难以早期诊断,确诊时只有15%的患者能够手术治疗.因此放射治疗就成为局部晚期NSCLC的主要治疗手段;对不能手术的Ⅰ期和Ⅱ期NSCLC放疗是唯一可能治愈的治疗手段;对可以手术治疗的Ⅲa期NSCLC病人,作为术前放疗常常和化疗联合应用配合手术治疗;也常常和化疗联合应用于不能手术治疗的Ⅲa和Ⅲb期NSCLC病人.NSCLC治疗失败的主要原因为局部未控、复发和远处转移,远处转移也与局部治疗失败有关.     

伴远处孤立转移的非小细胞肺癌治疗进展

肺癌是严重威胁人类健康及生命的恶性肿瘤之一,发病率逐年上升.非小细胞肺癌(NSCLC)中Ⅳ期患者可达40%左右.而其中一小部分Ⅳ期NSCLC患者呈单脏器孤立转移,且原发灶亦为早期.对此部分患者,其治疗方式同初治时即有多部位远处转移者有所不同;同样,其预后同初治时即有多部位远处转移者亦不相同.对于孤立脑转移患者.在原发NSCLC能够完全切除或已经得到良好控制的情况下,切除同时性或异时性孤立脑转移的5年生存率高达10%～30%,目前的标准治疗推荐手术切除原发灶及孤立脑转移灶或立体定向放疗联合全脑放疗.而孤立肾上腺转移发生率大约在1.62%～3.5%.通过积极的外科切除及联合化疗,NSCLC同时或异时性孤立肾上腺转移患者能延长生存并可获长期生存,5年生存率可达25%～40%.查阅大量相关文献,得出结论认为:对于伴有不同部位的远处孤立转移非小细胞肺癌患者,在原发灶完全切除基础上,进行积极的转移灶局部手术治疗,生存期明显优于其它Ⅳ期患者.     

糖酵解与肺癌相关研究进展

肺癌是全球发病率和病死率最高的恶性肿瘤。男性中肺癌占新发肿瘤病例的17%以上,约占癌症死亡总数的23%,且发病率呈上升趋势。肺癌患者中约80%为非小细胞肺癌(non-small cell lung cancer,NSCLc)。NSCLC预后较差,主要与局部复发及远处转移有关,而较多患者就诊时已经发生局部侵润(37%)和远处转移(38%)。在NSCLC等实体肿瘤的生长过程中,癌细胞增殖迅速     

非小细胞肺癌“寡转移”的概念及治疗策略

非小细胞肺癌是发病率及致死率最高的恶性肿瘤之一。约20%-50%会发生远处转移,最常见的转移部位为脑、骨、肝及肾上腺。寡转移状态是一段肿瘤生物侵袭性较温和的时期,存在于局限性原发灶与广泛性转移之间的过渡阶段,转移瘤数目有限并且转移器官具有特异性。"寡转移"来源于微转移,肿瘤细胞已具有器官特异性,但尚不具备全身播散的遗传倾向。治疗寡转移状态的关键是局部控制,需要兼顾预防远处转移、治疗隐匿性转移灶、治疗寡转移灶和全身治疗结束后清除残留癌灶四个方面。本文旨在对"寡转移"概念在非小细胞肺癌常见转移脏器治疗中的应用作一综述。     

放疗联合免疫治疗非小细胞肺癌脑转移研究进展

肺癌是最常见的恶性肿瘤之一, 非小细胞肺癌(NSCLC)约占80%, 其中20%～40%晚期NSCLC患者会发生脑转移。脑转移生存效益极低, 脑转移患者的中位生存期仅4～6个月。对于NSCLC脑转移的治疗, 目前推荐全脑放疗、立体定向放射外科等。近年来, 免疫治疗对NSCLC脑转移的独特疗效也逐渐被重视。放疗可改变肿瘤微环境, 与免疫治疗联合应用可逆转免疫抑制为免疫活化状态, 实现更好的抗肿瘤作用。本文主要对放疗联合免疫抑制剂治疗NSCLC脑转移的研究进行综述, 为今后研究及临床实践提供参考。     

Local thermal ablative therapies for extracranial oligometastatic disease of non-small-cell lung cancer

Non-small cell lung cancer (NSCLC) is the most common type of lung cancer. Clinically, 40–50% of patients with NSCLC are found to have systemic metastasis at the initial diagnosis. Meanwhile, 30–75% of patients with lung cancer who have undergone radical surgical resection have local recurrence and distant metastases. However, not all distant metastases are multiple, and some are potentially curable. In this study, among the patients with NSCLC having distant organ metastasis, approximately 7% showed extrapulmonary solitary metastasis and remained in this relatively stable state for a long time. This form of metastasis is known as NSCLC oligometastases. This review describes the concept and classification of oligometastases, as well as the local treatment and prognosis of extracranial oligometastases.     

Local treatment of oligometastatic recurrence in patients with resected non-small cell lung cancer

Objectives

We previously reported a retrospective study indicating the prognostic impact of the local treatment of oligometastatic recurrence after a complete resection for non-small cell lung cancer (NSCLC). In the present study, we prospectively observed postoperative oligometastatic patients and investigated the effects of local treatment on progression-free survival (PFS).

Methods

Using a prospectively maintained database of patients with completely resected NSCLC treated between October 2007 and December 2011, we identified 52 consecutive patients with postoperative recurrence, excluding second primary lung cancer. Of these patients, 31 suffering from distant metastases alone without primary site recurrence were included in this study. According to the definition of ‘oligometastases’ as a limited number of distant metastases ranging from one to three, 17 patients had oligometastatic disease. Of those 17 patients, four patients with only brain metastasis were excluded from the analysis.

Results

The oligometastatic sites included the lungs in five patients, bone in four patients, the lungs and brain in two patients, the adrenal glands in one patient and soft tissue in one patient. Eleven of the 13 patients first received local treatment. Three patients (lung, adrenal gland, soft tissue) underwent surgical resection, and the remaining eight patients received radiotherapy. The median PFS was 20 months in the oligometastatic patients who received local treatment. There were five patients with a PFS of longer than two years. The metastatic sites in these patients varied, and one patient had three lesions. On the other hand, the two remaining patients first received a systemic chemotherapy of their own selection. The PFS of these two patients was five and 15 months, respectively.

Conclusion

Local therapy is a choice for first-line treatment in patients with postoperative oligometastatic recurrence.     

Ablative Therapy for Oligometastatic Non–Small Cell Lung Cancer

The oligometastatic state represents a distinct entity among those with metastatic disease and consists of patients with metastases limited in number and location, representing an intermediate state between locally confined and widely metastatic cancer. Although similar, “oligorecurrence” (limited number of metachronous metastases under conditions of a controlled primary lesion) and “oligoprogressive” (disease progression at a limited number of sites with disease controlled at other disease sites) states are distinct entities. In non–small cell lung cancer (NSCLC), the oligometastatic state is relatively common, with 20% to 50% of patients having oligometastatic disease at diagnosis. This subgroup of patients when receiving ablative therapy, such as surgery or stereotactic body radiation radiotherapy, can obtain markedly long progression-free and overall survival. The role of radical treatment for intracranial oligometastases is well established. Fewer data exist regarding radical treatment of extracranial metastases in lung cancer; however, retrospective series using surgery or stereotactic body radiotherapy for extracranial oligometastatic disease in NSCLC have shown excellent local control, with a suggestion of improvement in progression-free survival. In the present report, we have reviewed the data on the treatment of brain metastases in oligometastatic NSCLC and the results of ablative treatment of extracranial sites. Recently, the first randomized trial comparing ablative treatment versus control in oligometastatic disease was reported, and those data are reviewed in the context of smaller series. Finally, areas of controversy are discussed and a therapeutic approach for patients with oligometastatic disease is proposed.     

Proposing synchronous oligometastatic non–small‐cell lung cancer based on progression after first‐line systemic therapy

Despite the importance of accurate disease definitions for effective management and treatment decisions, there is currently no consensus on what constitutes oligometastatic non–small‐cell lung cancer (NSCLC). Predominant patterns of initial progressive disease (PD) after first‐line systemic therapy have been shown to be a substantial basis for local ablative therapy (LAT) for all disease sites in patients with oligometastatic NSCLC, suggesting that these patterns could be helpful in defining synchronous oligometastatic NSCLC. Therefore, this retrospective study aimed to propose a threshold number of metastases for synchronous oligometastatic NSCLC, based on the pattern of initial PD after first‐line systemic therapy. The cut‐off threshold number of metastases compatible with synchronous oligometastatic NSCLC was determined using receiver operating characteristic (ROC) curve analyses of PD at the initially involved sites alone. ROC analysis of 175 patients revealed that the presence of 1‐3 metastases before first‐line treatment (sensitivity, 85.9%; specificity, 97.3%; area under the curve, 0.91) was compatible with oligometastatic NSCLC, therefore we divided patients into oligometastatic NSCLC and non‐oligometastatic NSCLC groups. Multivariate logistic regression analyses revealed oligometastatic NSCLC to be the only independent predictor of PD at initially involved sites alone (odds ratio 165.7; P < .001). The median survival times in patients with oligometastatic or non‐oligometastatic NSCLC were 23.0 and 10.9 mo (hazard ratio, 0.51; P = .002), respectively. Based on these findings, we propose synchronous oligometastatic NSCLC as 1‐3 metastases in accordance with patterns of initial progression. The result of our study might be contributory to provide a common definition of synchronous oligometastatic NSCLC.     

Results of a surgical resection for patients with stage IV non--small-cell lung cancer

PurposeThis study retrospectively investigated the clinical significance of surgical treatment for stage IV non–small-cell lung cancer (NSCLC).SubjectsThere were 36 patients who underwent surgical resection for stage IV NSCLC between 1999 and 2008.ResultsThe patients included 22 males and 14 females. All patients had either synchronous distant metastasis or pleural dissemination. The mean age of the patients was 65.8 years (range, 18 to 90 years). The histological types included 29 adenocarcinomas, 5 squamous-cell carcinomas and 2 large-cell carcinomas. The organs of metastasis were bone in 5 patients, brain in 4, adrenal gland in 4, axillary lymph nodes in 3, liver in 2, and 1 patient had a contralateral pulmonary metastasis. The number of metastases was one site in 13, two sites in 3, three sites in 1, and five sites in 2 patients. The patients with bone metastasis were treated with radiation, and the patients with brain metastasis underwent stereotaxic radiosurgery. The patients with either adrenal metastasis, axillary lymph node metastasis, or contralateral lung metastasis underwent surgical resection. Among the patients with distant metastasis, the 5-year survival rate was 30.1 %. There were 17 patients with pleural dissemination. The 5-year survival rate in these patients was 25.3%. The overall 5-year survival rate after surgery in the patients with stage IV disease was 26.8%.ConclusionSelected patients who can undergo surgical resection for the primary tumor and effective local therapy for metastatic lesions still have a chance to obtain long-term survival. Surgical treatment for NSCLC with oligometastatic disease can be considered as one arm of multidisciplinary treatment.     

Therapeutic strategy for postoperative recurrence in patients with non-small cell lung cancer

Postoperative recurrence occurs in approximately half of patients with non-small cell lung cancer (NSCLC), even after complete resection. Disease recurrence after surgical resection reduces the patient’s life expectancy sharply. The prognosis after postoperative recurrence is considered to largely depend on both the mode of first recurrence (distant, locoregional or combined) and the treatment modality: (1) The majority of cases of postoperative recurrence involve distant metastasis with or without locoregional recurrence. Platinum-based systemic chemotherapy is practically accepted as the treatment for these diseases on the basis of evidence for original stage IV disease. The advent of both pemetrexed and molecular-targeted drugs has improved the survival of nonsquamous NSCLC and changed the chemotherapeutic algorithm for NSCLC; (2) Among patients with distant metastatic recurrence without locoregional recurrence at the primary tumor site, the metastasis is often limited in both organ and number. Such metastases are referred to as oligometastases. Local therapy, such as surgical resection and radiotherapy, has been suggested to be the first-line treatment of choice for oligometastatic recurrence; and (3) While locoregional recurrence is likely to cause troublesome symptoms, it is a potentially limited disease. Therefore, providing local control is important, and radiation is usually beneficial for treating local recurrence. In order to obtain better control of the disease and provide treatment with curative intent in patients with limited disease, the administration of concurrent platinum-based chemoradiotherapy is recommended according to the results of originally nonresectable stage IIIA and IIIB disease.     

非小细胞肺癌脑转移治疗的研究进展

肺癌是全球范围内发病率和死亡率最高的恶性肿瘤,非小细胞肺癌（non-small cell lung cancer,NSCLC）约占肺癌的80%,其中超过40%的晚期NSCLC患者在疾病病程中会发生脑转移,导致预后不良。传统的治疗方法如单纯放疗,化疗,外科手术对于改善肺癌脑转移的预后非常有限。近些年来随着立体定向放射治疗、靶向治疗的发展,尤其是化疗联合靶向,放疗联合靶向等交叉领域的联合治疗,NSCLC脑转移患者的生存质量得到提高,中位总生存期（median overall survival,mOS）得以延长。然而对于NSCLC脑转移的最佳治疗方案,仍然存在争议,本文将针对NSCLC脑转移领域的最新研究进展进行阐述,以期对肺癌脑转移患者选择合理治疗方案提供理论依据。      

The evolving role of radiotherapy in treatment of oligometastatic NSCLC

Non-small cell lung cancer (NSCLC) patients with metastases limited in site and number, termed oligometastases, may represent a unique subpopulation of advanced NSCLC with improved prognosis. The optimal management of these patients remains unclear with the treatment approach currently undergoing a paradigm shift. The potential benefit of aggressive metastasis directed local treatment with surgery and/or radiotherapy (RT) in combination with systemic therapy is bolstered predominantly by retrospective analyses but also by a growing number of non-randomized prospective studies regarding the use of ablative RT techniques including stereotactic body radiotherapy (SBRT), alternatively termed stereotactic ablative radiotherapy (SABR), directed at the primary tumor (if present) and all metastatic sites. Long-term survival is possible in a subset of patients treated aggressively in this manner. The challenge for the clinical oncology community moving forward is appropriately selecting patients for this treatment approach based on clinical, imaging, and molecular features and increasing enrollment of patients to prospective clinical trials to more definitively determine the added benefit and appropriate timing of aggressive metastasis directed therapy in the oligometastatic setting.     

Prevalence of bone pain decreases as lymph node stage increases in nonsmall cell lung cancer patients

According to lung cancer guidelines, positron emission tomography scan is recommended for initial evaluation of bone metastasis. However, guidelines differ in their recommendations for when it should be used. We investigated the appropriate use of bone imaging in nonsmall cell lung cancer (NSCLC) patients.One hundred seventy-seven consecutive NSCLC patients who had distant metastases at presentation and were admitted between January 2012 and April 2016 were retrospectively reviewed. Among patients with bone metastases, we explored bone pain, number of bone metastases, location of bone metastases, and clinical tumor (T) and lymph node (N) classification.Sixty-three patients had bone metastases. There was a trend toward an increase in prevalence of bone metastases as lymph node stage increased. The prevalence of bone pain significantly decreased as N stage increased (p?=?0.017). N0 and N2-3 patients were more likely to have multiple bone metastases (p?=?0.038). Compared with patients who had a single bone metastasis, patients with multiple metastases had a significantly higher probability of having at least 1 bone metastasis located in the thorax or upper abdomen. All N0 patients have at least 1 bone metastasis in the thorax or upper abdomen.Clinical N0 NSCLC patients with bone metastasis are likely to have bone pain and have multiple bone metastases. N2-3 patients are more likely to have bone metastases but less likely to have bone pain. If NSCLC patients do not have bone pain, and CT of the chest and upper abdomen does not reveal any lymph node or bone metastasis, further survey for bone metastases may be omitted; bone imaging should be performed in N2 and N3 patients regardless of symptoms.