Prognostic index to identify patients who may not benefit from whole brain radiotherapy for multiple brain metastases from lung cancer

Palliative whole brain radiotherapy (WBRT) is often recommended in the management of multiple brain metastases. Allowing for WBRT waiting time, duration of the WBRT course and time to clinical response, it may take 6 weeks from the point of initial assessment for a benefit from WBRT to manifest. Patients who die within 6 weeks (‘early death’) may not benefit from WBRT and may instead experience a decline in quality of life. This study aimed to develop a prognostic index (PI) that identifies the subset of patients with lung cancer with multiple brain metastases who may not benefit from WBRT because of ‘early death’. The medical records of patients with lung cancer who had WBRT recommended for multiple brain metastases over a 10-year period were retrospectively reviewed. Patients were classified as either having died within 6 weeks or having lived beyond 6 weeks. Potential prognostic indicators were evaluated for correlation with ‘early death’. A PI was constructed by modelling the survival classification to determine the contribution of these factors towards shortened survival. Of the 275 patients recommended WBRT, 64 (23.22%) died within 6 weeks. The main prognostic factor predicting early death was Eastern Cooperative Oncology Group (ECOG) status >2. Patients with a high PI score (>13) were at higher risk of ‘early death’. Twenty-three per cent of patients died prior to benefit from WBRT. ECOG status was the most predictive for ‘early death’. Other factors may also contribute towards a poor outcome. With further refinement and validation, the PI could be a valuable clinical decision tool.     

3种全脑放疗技术对中耳剂量学研究

目的 比较脑转移瘤全脑放射治疗（WBRT）3种放疗技术对中耳的剂量学差异,对比3种放疗技术在改善靶区剂量和保护中耳腔和咽鼓管峡部的优劣势。方法 选取2018年7月1日—2019年8月1日我院收治的30例脑转移瘤患者,分别设计固定野调强放疗（ff-IMRT）计划、容积旋转调强放疗（VMAT）和三维适形放疗（3DCRT）计划,要求处方剂量（40 Gy）覆盖95%的计划靶区（PTV）。对比分析3组计划的靶区和危及器官剂量学参数、机器跳数等差异。结果 ff-IMRT计划的适形指数（0.93 ±0.02）优于VMAT计划（0.89 ±0.01）和3DCRT计划（0.73 ±0.03）,差异有统计学意义（P < 0.05）;ff-IMRT、VMAT和3DCRT 3种计划的均匀指数分别为（0.05 ±0.01）、（0.08 ±0.1）、（0.08 ±0.01）,差异无统计学意义（P > 0.05）;梯度指数分别为（1.77 ±0.1）、（1.61 ±0.07）、（1.39 ±0.08）,差异有统计学意义（P < 0.05）;机器跳数分别为（1551.97 ±85.05）、（303.7 ±24.28）、（226.2 ±2.5）,差异有统计学意义（P < 0.05）。ff-IMRT、VMAT和3DCRT 3种计划中耳腔最大剂量点（D_max）分别为ff-IMRT（2557.54 ±477.39）cGy、VMAT（3107.9 ±362.28）cGy、3DCRT（4055.37 ±71.45）cGy;咽鼓管峡部D_max分别为ff-IMRT（2425 ±380.4）cGy、VMAT（2902.4 ±526.3）cGy、3DCRT（3862.7 ±135.9）cGy,差异均有统计学意义（P < 0.05）。结论 在全脑放射治疗中,ff-IMRT和VMAT与3DCRT相比明显减少了双侧中耳腔和咽鼓管峡部的照射剂量;而VMAT与ff-IMRT相比,明显减少机器跳数、降低了机器损耗,WBRT时推荐使用VMAT技术。     

HTP方案联合全脑放疗治疗非小细胞肺癌脑转移疗效评价

目的:评价HTP方案联合全脑放疗治疗非小细胞肺癌脑转移的疗效及不良反应。方法:我院2006年10月～2008年10月收治的NSCLC脑转移患者50例,随机分为两组,每组25例,一组(联合治疗组)给予HTP方案同步联合WBRT治疗,一组(对照组)单纯给予WBRT治疗,观察两组患者临床疗效及不良反应的发生情况。结果:治疗后,联合治疗组脑转移灶和肺部原发灶的客观有效率、疾病控制率为64.0%、88.0%明显高于对照组(P<0.05);联合治疗组的1年生存率、3年生存率以及中位生存时间分别为48.0%、24.0%和13个月明显高于对照组的28.0%、8.0%和10个月(P<0.05);对照组I级和II级胃肠道不良反应发生率明显低于联合治疗组(P<0.05)。结论:HTP方案联合全脑放疗治疗NSCLC脑转移患者,具有较高的有效率及生存率,毒性可耐受。     

WBRT for brain metastases from non-small cell lung cancer: for whom and when?—Contemporary point of view

The incidence of brain metastases (BM) is estimated between 20% and 40% of patients with solid cancer. The most common cause of this failure is lung cancer, and in locally advanced non-small cell lung cancer (NSCLC) BM represent a common site of relapse in 30–55% cases. The basic criteria of therapeutic decision-making are based on the significant prognostic factors which are components of prognostic scores. The standard approach to treatment of BM from NSCLC include whole brain radiotherapy (WBRT) which is used as adjuvant modality after local therapy (surgery or stereotactic radiosurgery) or as primary treatment and it remains the primary modality of treatment for patients with multiple metastases. WBRT is also used in combination with systemic therapy. The aim of presented review of literature is trying to answer which patients with BM from NSCLC should receive WBRT and when it could be omitted. There were presented the aspects of application of WBRT in relation to (I) choice between WBRT or the best supportive care and (II) employment of WBRT in combination with local treatment modalities [surgical resection or stereotactic radio-surgery (SRS)] and/or with systemic therapy. According to data from literature we concluded that the most important factor that needs to be considered when assessing the suitability of a patient for WBRT is the patient’s prognosis based on the Lung-molGPA score. WBRT should be applied in treatment of multiple BM from lung cancer in patients with favourable prognosis and in in patients with presence of EML4-ALK translocation before therapy with crizotinib. Whereas WBRT could be omitted in patients with poor prognosis and after primary SRS.     

Factors affecting the outcome after treatment for metastatic melanoma to the brain

Background

Because of the difficulties inherent to the treatment of metastatic melanoma to the brain including high rates of disease progression and local treatment failure, we attempted to determine the prognostic factors that impacted the outcome of these patients, and reviewed patient outcome based on primary treatment with either surgical resection or SRS.

Methods

A retrospective review identified 37 patients treated for metastatic melanoma between July 2002 and April 2007. Information was obtained documenting systemic disease, preoperative symptoms, tumor size and location, disease recurrence, primary and secondary treatments, and survival time.

Results

Two patients were alive as of March 2008. The median survival time for patients primarily treated with surgical resection was 9.7 months compared to 7.9 months for patients initially treated with SRS. Solitary brain metastases and the absence of both preoperative hemorrhage and lung metastases served as prognostic factors increasing survival in both groups. Four patients undergoing primary treatment with SRS required subsequent surgical intervention secondary to radiation necrosis (3 patients) or local recurrence (1 patient). All 4 had lesions greater than 1.5 cm. For surgical patients, planned postoperative treatment with either radiosurgery or radiation therapy increased survival time to 12.3 months vs 7.3 months.

Conclusions

Patients with positive prognostic factors including solitary brain lesions, absence of hemorrhage preoperatively, and absence of lung disease are viable candidates for aggressive, surgical intervention followed by adjuvant therapy with radiosurgery or conventional radiation therapy. Other patients should be considered for more conservative treatment with radiosurgery or other palliative treatments.     

非小细胞肺癌脑转移的治疗

目的在原发病得到控制的情况下,比较单发的非小细胞肺癌脑转移瘤治疗方法的效果。方法1990年1月~2004年12月对125例单发的非小细胞肺癌脑转移瘤的患者实施单纯放疗及手术切除加放疗,全脑照射30~40Gy/2~3周后,再缩野局部追加15~20Gy/1.5~2周。立体定向放疗应用γ-刀治疗。结果手术切除加放疗的中位生存期10.5个月和一年生存率64.5%显著优于单放组的6.3个月和14.9%(P<0.05)。单纯的立体定向放疗中位生存期9.6个月和一年生存率61.8%显著优于单纯的全脑照射组的6.3个月和14.9%(P<0.05)。但这组资料分析结果不能表明手术和立体定向放疗那一种更好。结论单发的非小细胞肺癌脑转移采用手术加放疗比单纯放疗效果好。单纯的立体定向放疗优于单纯的全脑照射。立体定向放疗和传统的外科手术切除的结果相同。     

大分割立体定向放射治疗对非小细胞肺癌脑转移瘤的疗效评估

目的探讨伽玛射线大分割立体定向放疗（SRT）加或不加全脑放疗（WBRT）对肺癌有限脑转移瘤治疗的疗效。方法回顾性分析非小细胞肺癌多发脑转移瘤（1～4枚）患者66例,其中单纯SRT30例,SlIT＋WBRT36例。分析两组患者的临床特征并应用Kaplan--Meier法计算生存率,用Logrank法对各因素进行预后分析。结果两组患者的临床特点无明显区别;SRT组与WBRT＋SRT组的中位生存期（MST）分别为12．1与13．3个月,两者无显著性差异（P=0．216）。Logrank分析显示卡氏评分（P=0．017）和颅外病变的控制情况（P=0．032）是影响预后的主要因素。结论SRT是非小细胞肺癌有限脑转移瘤患者有效治疗手段,单纯SRT可取得与WBRT加SRT相似的生存期。     

A systematic review of trastuzumab and lapatinib in the treatment of women with brain metastases from HER2-positive breast cancer

Patients with HER2-positive breast cancer are living still longer and increasingly experiencing brain metastases. Current HER2-targeted therapies have limited potential to cross the blood–brain-barrier. We performed a systematic review to investigate data on HER2-targeting therapies in the treatment of brain metastases in breast cancer. We searched PUBMED for all human studies published 1998–2012 using the following search terms: breast neoplasm/cancer, human epidermal growth factor receptor 2/HER2, ErbB2, trastuzumab, lapatinib, brain/cerebral neoplasm/metastases and blood–brain barrier. We identified few and mostly small clinical studies. Study designs were very heterogeneous making comparisons on endpoints difficult. Overall survival for patients treated with trastuzumab varied from 8 to 25 months and 5.5 to 11 months for patients receiving lapatinib. The majority of studies were retrospective thus possibly biasing data. Only three studies were identified comparing trastuzumab to lapatinib. Conclusively, no solid data exist on how to treat patients with HER2-positive disease and brain metastases. Although continuous HER2-blockade is recommended by international consensus guidelines, it is still not evident which HER2-targeting agent should be preferred when brain metastases occur. The choice of chemotherapy to accompany the blockade is not obvious and we do not know if dual is better than single blockade. Further clinical trials are urgently needed.