伽马射线立体定向放射治疗肺转移瘤42例

目的:回顾性分析了采用伽马射线体部肿瘤立体定向放射治疗（SBRT）的方法治疗肺转移瘤的疗效及毒副反应。方法:对2012年至2014年接受治疗的42例肺转移瘤患者进行回顾性分析。42例肺转移瘤患者共68个肺转移瘤病灶行伽马射线SBRT治疗,其中男性18例,女性24例;年龄45~67岁,中位年龄56岁;病理鳞癌25例,腺癌17例;所有患者之前均接受过多程化疗。采用体位固定床和真空负压袋固定体位,在螺旋CT下行薄层定位扫描,应用OUR-QGD型治疗计划系统,制定治疗计划以50%等剂量曲线为处方剂量线,处方剂量范围:40~54Gy,1次/d、5 次/周、3~8Gy/次,5~18次完成。治疗后定期复查CT。结果:肺转移瘤病灶完全缓解44.1%(30/68),部分缓解38.2%(26/68),稳定14.7%(10/68),进展3%(2/68),总有效率为82.3 %,肿瘤局部控制率为97%(66/68)。1年生存率为97.6%(41/42)。随访时间6~20个月,中位随访时间12个月。全组无严重毒副反应。结论:体部伽马刀治疗化疗无效肺转移瘤,能获得较高的局控率,延长生存期,是一种毒副反应轻、并发症少,且安全有效的治疗方法。     

肺转移瘤的放射治疗

肺转移瘤是最常见的转移性肿瘤之一,手术仅适用于局限性肺转移的治疗,并且大部分患者不适合行手术治疗.化疗是主要治疗方法,但是疗效欠佳.研究证实,随着三维适形放疗、体部立体定向放射治疗等精确放疗的不断发展,放疗对于肺转移患者有效,尤其对于局限性转移,体部立体定向放射治疗可以取得较好的生存期,但仍需大规模前瞻性研究.     

非小细胞肺癌放射治疗研究进展

目的 肺癌是全球男性肿瘤患者首位死亡原因,也是我国发病率、死亡率第1位的恶性肿瘤,约80%~85%肺癌患者是非小细胞肺癌(non-small cell lung cancer,NSCLC).本文对放疗在NSCLC的治疗现状和研究进展进行综述.方法 检索Pubmed和CNKI期刊全文数据库,以"肺癌与放疗、放疗联合靶向治疗、放疗联合免疫治疗"为关键词,检索2005-11-01-2016-11-30关于NSCLC放疗的文献,共检索文献篇653篇.纳入标准:(1)放疗在NSCLC的应用;(2)放疗与靶向治疗的联合;(3)放疗与免疫治疗联合应用的研究.根据纳入标准最后纳入分析44篇文献.结果早期肺癌患者可选择手术或立体定向放射治疗(stereotacticbodyradiationtherapy,SBRT),尤其是高龄、心肺功能不全及不能耐受手术的Ⅰ期肺癌患者,SBRT已经成为标准的治疗手段,不仅靶区小、单次照射剂量高、照射次数少,并且将邻近正常组织剂量控制在可接受范围.对于中晚期失去手术机会的患者,靶向治疗可以通过抑制放疗引起的DNA双链断裂的损伤修复、诱导肿瘤细胞凋亡及影响细胞周期等机制增加放疗敏感性.而免疫治疗与放疗的结合,可以促进机体的免疫反应,增加针对肿瘤细胞的特异性抗体,从而发挥抗肿瘤作用,尤其是放疗与免疫治疗结合后引起的"远位效应".结论放疗在NSCLC的治疗中有独特的优势,与其他治疗方法的结合为肺癌患者提供了新的治疗模式.     

Use of stereotactic body radiation therapy for medically inoperable multiple primary lung cancer

Introduction: To review outcomes of medically inoperable patients treated with stereotactic body radiation therapy (SBRT) for multiple primary lung cancer (MPLC). Methods: We retrospectively reviewed the charts of 10 patients (21 lesions) treated with SBRT for synchronous (seven), metachronous (one) or synchronous/metachronous lung cancers. All patients were male, medically inoperable and had a median age of 66 years. Eight patients had bilateral disease and two had unilateral disease. All patients had a histological diagnosis in at least one of the two lesions and four patients (44.4%) had both lesions biopsied. There were 18 T1 lesions and three T2 lesions. SBRT was in three fractions of 20 Gy or five fractions of 11–12 Gy to each lesion. Results: Mean and median follow up were 18.8 and 15.5 months, respectively. At analysis, six patients (60.0%) are alive, and five of these living patients (83.3%) have no evidence of disease recurrence or progression. Four patients (44.4%) developed distant metastatic disease. Twenty lesions (95.2%) achieved in‐field local control. No patients experienced acute pulmonary complications and only two patients (22.2%) experienced late grade I lung toxicity as per the Radiation Therapy Oncology Group toxicity criteria. Conclusion: SBRT for MPLC in medically inoperable patients is a safe, feasible and effective treatment approach.     

Stereotactic body radiation therapy (SBRT) for early-stage lung cancer in the elderly

Early-stage non-small cell lung cancer (NSCLC) is on the rise due to the implementation of screening guidelines for patients at risk for developing lung cancer. It is anticipated that as the US population continues to age, there will be a higher percentage of medically inoperable early-stage lung cancer patients. For this reason, noninvasive ablative therapies are necessary. Stereotactic body radiation therapy (SBRT) is an effective modality in addressing early-stage NSCLC. SBRT consists of high-dose radiation delivered over 3–5 treatments. Several randomized trials comparing surgery to SBRT in early-stage operable patients have unfortunately closed early due to poor accrual. However, a recent pooled analysis from 2 randomized trials (StereoTActic Radiotherapy and Radiosurgery Or Surgery for operable Early-stage non–small cell Lung cancer) comparing surgery to SBRT did show comparable local control and overall survival rates between surgery and SBRT, offering a very effective, noninvasive modality for older adult patients with early-stage NSCLC. In this review, we summarize the role of SBRT in early-stage NSCLC, in particularly applied to the older adult population.     

Surgery versus stereotactic body radiation therapy for stage I non–small cell lung cancer: A comprehensive review

Non–small cell lung cancer (NSCLC) is the leading cause of cancer‐related death in the United States. With the implementation of lung cancer screening, the number and proportion of patients diagnosed with early‐stage disease are anticipated to increase. Surgery is currently the standard of care for patients with operable stage I NSCLC. However, promising outcomes with stereotactic body radiation therapy (SBRT) in patients with inoperable disease has led to interest in directly comparing SBRT and surgery in operable patients. Unfortunately, early randomized trials comparing surgery and SBRT closed early because of poor accrual. In this article, the nuances of surgery and SBRT for early‐stage NSCLC are reviewed. Furthermore, retrospective and prospective analyses of SBRT in early‐stage NSCLC are discussed, and active randomized trials comparing these 2 approaches are described. Cancer 2018;124:667‐78. © 2017 American Cancer Society.     

Long-term Follow-up and Patterns of Recurrence of Patients With Oligometastatic NSCLC Treated With Pulmonary SBRT

IntroductionThis multicenter study aims to analyze outcome as well as early versus late patterns of recurrence following pulmonary stereotactic body radiotherapy (SBRT) for patients with oligometastatic non–small-cell lung cancer (NSCLC).Materials and MethodsThis analysis included 301 patients with oligometastatic NSCLC treated with SBRT for 336 lung metastases. Although treatment of the primary tumor consisted of surgical resection, radiochemotherapy, and/or systemic therapy, pulmonary oligometastases were treated with SBRT.ResultsThe median follow-up time was 16.1 months, resulting in 2-year overall survival (OS), local control (LC), and distant control (DC) of 62.2%, 82.0%, and 45.2%, respectively. Multivariate analysis identified age (P = .019) and histologic subtype (P = .028), as well as number of metastatic organs (P < .001) as independent prognostic factors for OS. LC was superior for patients with favorable histologic subtype (P = .046) and SBRT with a higher biological effective dose at isocenter (P = .037), whereas DC was inferior for patients with metastases in multiple organs (P < .001) and female gender (P = .027). Early (within 24 months) local or distant progression was observed in 15.3% and 36.5% of the patients. After 24 months, the risk of late local failure was low, with 3- and 4-year local failure rates of only 4.0%, and 7.6%. In contrast, patients remained at a high risk of distant progression with 3- and 4-year failure rates of 13.3% and 24.1%, respectively, with no plateau observed.ConclusionSBRT for pulmonary oligometastatic NSCLC resulted in favorable LC and promising OS. The dominant failure pattern is distant with a continuously high risk of disease progression for many years.     

Current challenges of lung cancer care in an aging population

Local control for advanced non-small cell lung cancer (NSCLC) remains a significant problem with chemoradiation local failure rates in the chest of 30–50%. Despite attempts at dose escalation with conventional radiation therapy techniques, toxicities limit the amount of radiation that can be delivered. For stage I NSCLC, mounting evidence supports the use of hypofractionated radiation therapy (SBRT) to gain high local control rates with acceptable toxicity. For healthy patients with stage II/III NSCLC, the National Comprehensive Cancer Network guidelines suggest surgery is the preferred standard of care for patients with <N2 nodes or T3 tumors. In select patients who are surgical candidates or have more extensive disease, guidelines may include pre-operative chemoradiation followed by surgery, although this remains controversial and is the subject of a current national clinical trial (RTOG 0839). Dose escalation through conventional radiation therapy planning suggests that we can improve outcomes in stage III patients, but toxicity remains problematic. It follows that with improvements in imaging and delivery of radiotherapy, dose escalation with SBRT incorporation may improve local control in stage II/III NSCLC for medically inoperable patients. The rationale for dose escalation and some of the considerations for incorporation of SBRT dose escalation in stage III lung cancer are reviewed here.     

立体定向放疗用于结直肠癌肝与肺寡转移的研究进展

寡转移是肿瘤从局部区域病变进展到远处广泛转移过程中存在的一种中间状态,通过局部治疗有获得长期生存的可能。体部立体定向放疗(SBRT)单次剂量高、分割次数少,是一种高精准的局部消融治疗手段。结直肠癌有近一半患者会发生转移,主要转移部位为肝和肺。本文主要阐述SBRT治疗结直肠癌肝、肺寡转移灶的安全性、近期疗效及其影响因素,同时也总结了SBRT具体实施的要点。SBRT在严格的呼吸运动管理和放疗质控下是治疗结直肠癌寡转移的有效手段。     

Stereotactic Body Radiotherapy Versus Metastasectomy in Patients With Pulmonary Metastases From Soft Tissue Sarcoma

The lung is the preferred site of metastasis from soft tissue sarcoma (STS). This systematic review aims to evaluate the outcomes of stereotactic body radiotherapy (SBRT) and metastasectomy (MTS) for the treatment of lung metastases from STS. A systematic review was carried out according to the PRISMA protocol. PubMed, Medline, EMBASE, Cochrane Library, Ovid and Web of Knowledge databases were searched for English-language articles to December 2018 using a predefined strategy. Retrieved studies were independently screened and rated for relevance. Data were extracted by two researchers. In total, there were 1306 patients with STS: 1104 underwent MTS and 202 had SBRT. The mean age ranged from 40 to 55.8 years in the MTS group and from 47.9 to 64 years in the SBRT group. The cumulative death rate was 72% (95% confidence interval 59–85%) in the MTS group and 56% (38–74%) in the SBRT group. The cumulative mean overall survival time was 46.7 months (36.4–57.0%) in the MTS group and 47.6 months (33.7–61.5%) in the SBRT group. The cumulative rate of patients alive with disease was 5% (2–9%) in the MTS group and 15% (6–36%) in the SBRT group. Finally, the cumulative rate of patients alive without disease in the two groups was 19% (9–29%) and 20% (10–50%), respectively. Our study showed that local treatment of pulmonary metastases from STS with SBRT, compared with surgery, was associated with a lower cumulative overall death rate and similar overall survival time and survival rates without disease. By contrast, SBRT was associated with a higher survival rate with disease than MTS. Large randomised trials are necessary to confirm these findings and to establish whether SBRT may be a reliable option for early stage disease.     

Accreditation and quality assurance for Radiation Therapy Oncology Group: Multicenter clinical trials using Stereotactic Body Radiation Therapy in lung cancer

Starting in 2002, the Radiation Therapy Oncology Group in North America began the process of developing multicenter prospective trials in lung cancer using Stereotactic Body Radiation Therapy (SBRT). Much of the work was based on the prospective single institution trials from Indiana University that had been presented and published. In late 2004, RTOG 0236 using SBRT for medically inoperable patients with clinical stage I non-small cell lung cancer (NSCLC) was activated for accrual. Prior to activation, representatives from the Lung, Image-Guided Therapy, Physics, and Radiobiology Committees met on regular occasions to design the multicenter study and quality assurance measures. SBRT is not a black box, and the essence of the therapy had to be distilled via guidelines. Issues related to patient selection, method of dosimetry construction, equipment requirements, motion assessments and control, site accreditation, data exchange, and follow-up policies were worked out by compromise and consensus. RTOG 0236 has nearly completed its accrual. The Lung Committee has initiated the development of several other trials, each building on the last, to investigate the therapy in central tumors, in combinations with systemic therapy, in operable patients, and in lung metastases patients. The guidelines developed for RTOG 0236 will be refined to take advantage of more modern innovations including heterogeneity corrections and intensity modulation when appropriate. The development of RTOG 0618 using SBRT in operable patients with early stage NSCLC is a testament to both the enthusiasm from already published works and prospective multicenter clinical testing using SBRT techniques.     

Pilot Study of the Safety and Efficacy of Dose Escalation in Stereotactic Body Radiotherapy for Peripheral Lung Tumors

Background

This pilot study aimed to evaluate the safety and efficacy of a dose escalation method for the treatment of peripheral lung tumors by administrating steep dose gradients in the target volumes via stereotactic body radiotherapy (SBRT).

GOECP/SEOR radiotheraphy guidelines for non-small-cell lung cancer

Non-small cell lung cancer (NSCLC) is a heterogeneous disease accounting for approximately 85% of all lung cancers. Only 17% of patients are diagnosed at an early stage. Treatment is multidisciplinary and radiotherapy plays a key role in all stages of the disease. More than 50% of patients with NSCLC are treated with radiotherapy (curative-intent or palliative). Technological advances-including highly conformal radiotherapy techniques, new immobilization and respiratory control systems, and precision image verification systems-allow clinicians to individualize treatment to maximize tumor control while minimizing treatment-related toxicity. Novel therapeutic regimens such as moderate hypofractionation and advanced techniques such as stereotactic body radiotherapy (SBRT) have reduced the number of radiotherapy sessions. The integration of SBRT into routine clinical practice has radically altered treatment of early-stage disease. SBRT also plays an increasingly important role in oligometastatic disease. The aim of the present guidelines is to review the role of radiotherapy in the treatment of localized, locally-advanced, and metastatic NSCLC. We review the main radiotherapy techniques and clarify the role of radiotherapy in routine clinical practice. These guidelines are based on the best available evidence. The level and grade of evidence supporting each recommendation is provided.     

Frequent EGFR mutations in brain metastases of lung adenocarcinoma

Lung adenocarcinomas often metastasize to the brain, and the prognosis of patients with brain metastases is still very poor. The epidermal growth factor receptor (EGFR) gene is mutated in a considerable fraction of primary lung adenocarcinomas, in particular those with drastic response to EGFR tyrosine kinase inhibitors. The present study was designed to elucidate the prevalence of EGFR mutations in brain metastases and the timing of their occurrence during cancer progression. EGFR mutations were detected in 12 of 19 metastatic lung adenocarcinomas to the brain (63%). This frequency was higher than those in previous studies for EGFR mutations at various stages of lung adenocarcinoma in East Asia, including Japan (i.e., 20-55%). In 6 cases with EGFR mutations, the corresponding primary lung tumors were also examined for the mutations, and in all of them, the same types of EGFR mutations were detected also in the primary tumors. In 2 of them, second metastatic brain tumors in addition to the first ones were also available for analysis, and the same types of EGFR mutations were detected in both the first and second ones in both cases. These results indicate that EGFR mutations are present frequently in brain metastases and occur preceding brain metastasis. These findings will be highly informative for treatment of metastatic lung adenocarcinoma to the brain.     

A prospective pilot study of curative-intent stereotactic body radiation therapy in patients with 5 or fewer oligometastatic lesions

BACKGROUND: It is hypothesized that oligometastatic disease represents a state of potentially curable, limited metastases. Stereotactic body radiation therapy (SBRT) is an option for patients who are not amenable to or do not want resection. METHODS: From 2001 to 2006, 121 patients with < or =5 detectable metastases were enrolled in 2 prospective studies that used curative-intent SBRT. Most patients were treated with 10 fractions of 5 Gray. Stereotactic radiosurgery was offered to patients with brain metastases. RESULTS: The 2-year overall survival (OS), progression-free survival (PFS), local control (LC), and distant control (DC) rates were 50%, 26%, 67%, and 34%, respectively; and the respective 4-year rates values were 28%, 20%, 60%, and 25%. A greater net tumor volume predicted significantly worse OS, PFS, LC, and DC. Patients with breast cancer fared significantly better with respect to OS, PFS, LC, and DC; and patients with adrenal metastases had significantly worse OS, PFS, and DC despite the small number of such patients enrolled. Neither the number of metastatic lesions nor the number of organs involved was a significant predictor of outcome. Among 45 patients who remained alive at the last follow-up, 29 patients had no evidence of disease, including 23 patients with > or =2 years of follow-up. CONCLUSIONS: Oligometastatic disease is a potentially curable state of distant cancer spread. In this hypothesis-generating analysis, patients with less volume burden of their metastatic disease and those with primary breast cancer fared better. SBRT delivered with curative intent in patients with limited metastases should be investigated further. The Southwest Oncology Group is developing a prospective protocol to treat women who have limited breast cancer metastases with SBRT.     

Stereotactic body radiotherapy for lung oligometastases impacts on systemic treatment-free survival: a cohort study

To analyze the impact of SBRT on systemic treatment-free survival in patients affected by lung oligometastases. Inclusion criteria of the study were (a) KPS?>?70, (b) 1–5 lung oligometastases underwent SBRT with a BED?≥?100 Gy, (c) absence of extra-thoracic disease, (d) controlled primary tumor, (e) metachronous oligorecurrences for whom SBRT was adopted as primary treatment option, (f) oligoprogressive lung metastases who progressed following a disease remission after a first-line therapy, (g) oligopersistent disease after systemic therapy, and (h) at least 6 months of follow-up post-SBRT. Primary study endpoint was the systemic treatment-free survival for each group, whereas distant progression-free survival (DPFS), local failure-free survival (LFFS), and overall survival (OS) were the secondary endpoints. Seventy-eight patients and 114 lung metastases were analyzed. Of these, 32 patients were treated with SBRT in the oligorecurrence group, whereas the remaining patients underwent SBRT for oligoprogressive disease (n?=?35) oligopersistent disease (n?=?11). In the whole cohort of patients, the median systemic treatment-free survival was 16 months (3–46 months), the median LFFS was 18 months (12–46 months), the median DPFS was 14 months (3–43 months), and the median OS was 19.6 months (12–47 months). Oligorecurrence group had better clinical outcomes in terms of systemic treatment-free survival (log-rank test p?=?0.0035) and DPFS (log-rank test p?=?0.0017) compared to the other groups. In the present experience, SBRT allowed to delay the administration of systemic treatments in several settings of lung oligometastasis.     

局限期小细胞肺癌的放化疗

肺癌是引起肿瘤相关死亡的首要原因之一,其中15%～20%的患者为小细胞肺癌。小细胞肺癌的恶性程度高,易于远处转移,常至骨、肝、脑及肾上腺,并迅速导致患者死亡。目前大约25%～30%的小细胞肺癌患者确诊时尚为局限期,行放疗及化疗的联合治疗是目前此类患者的标准治疗措施。通常所选择的化疗方案为EP或EC,共4个周期,放疗常采取1f/d的胸部放射治疗,范围包括病变区及纵膈,总剂量在50～60Gy之间,并需要早期同步参与化疗。为提高放疗的生物学效应,关于超分割放疗的临床试验正进一步被评价。本文简要的阐述了局限期小细胞肺癌的治疗策略,也会进一步探讨放化疗时序的重要性。     

Bowel perforation due to metastatic lung cancer

Lung cancer infrequently metastasizes to the bowel. When this occurs, the symptoms may vary from mild to emergent in nature. Three patients are presented illustrating the life threatening complications that may occur due to bowel metastases of lung carcinoma. A review of the literature reveals that only four of 24 reported patients have survived bowel perforation due to metastatic lung carcinoma. One of the three patients presented herein survived to be discharged home. Patients with known lung carcinoma who develop abdominal complaints should be investigated aggressively to prevent life-threatening complications by early intervention. © 1992 Wiley-Liss, Inc.     

Decision Regret among Patients with Early-stage Lung Cancer Undergoing Radiation Therapy or Surgical Resection

AimsClinical equipoise exists regarding early-stage lung cancer treatment among patients as trials comparing stereotactic body radiation therapy (SBRT) and surgical resection are unavailable. Given the potential differences in treatment effectiveness and side-effects, we sought to determine the associations between treatment type, decision regret and depression.Materials and methodsA multicentre, prospective study of patients with stage IA–IIA non-small cell lung cancer (NSCLC) with planned treatment with SBRT or surgical resection was conducted. Decision regret and depression were measured using the Decision Regret Scale (DRS) and Patient Health Questionnaire-4 (PHQ-4) at 3, 6 and 12 months post-treatment, respectively. Mixed linear regression modelling examined associations between treatment and decision regret adjusting for patient sociodemographics.ResultsAmong 211 study participants with early-stage lung cancer, 128 (61%) patients received SBRT and 83 (39%) received surgical resection. The mean age was 73 years (standard deviation = 8); 57% were female; 79% were White non-Hispanic. In the entire cohort at 3 months post-treatment, 72 (34%) and 57 (27%) patients had mild and severe decision regret, respectively. Among patients who received SBRT or surgery, 71% and 46% of patients experienced at least mild decision regret at 3 months, respectively. DRS scores increased at 6 months and decreased slightly at 12 months of follow-up in both groups. Higher DRS scores were associated with SBRT treatment (adjusted mean difference = 4.18, 95% confidence interval 0.82 to 7.54) and depression (adjusted mean difference = 3.49, 95% confidence interval 0.52 to 6.47). Neither patient satisfaction with their provider nor decision-making role concordance was associated with DRS scores.ConclusionsMost early-stage lung cancer patients experienced at least mild decision regret, which was associated with SBRT treatment and depression symptoms. Findings suggest patients with early-stage lung cancer may not be receiving optimal treatment decision-making support. Therefore, opportunities for improved patient–clinician communication probably exist.