Improved Survival Outcomes for Kidney Cancer Patients With Brain Metastases

Background

Brain metastases (BM) occur frequently in patients with metastatic kidney cancer and are a significant source of morbidity and mortality. Although historically associated with a poor prognosis, survival outcomes for patients in the modern era are incompletely characterized. In particular, outcomes after adjusting for systemic therapy administration and International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk factors are not well-known.

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

背景与目的：立体定向放疗（stereotacticradiotherapv,SRT）与全脑放疗（wholebrainradiationtherapy’WBRT）是治疗脑转移瘤的主要手段。本文旨在探讨伽玛射线大分割SRT加或不加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,SRT＋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1313个月,二者无显著性差异（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＋SRT相似的生存期．     

External Validation of the Graded Prognostic Assessment in Patients with Brain Metastases from Small Cell Lung Cancer

Background: Recently, graded prognostic assessment (GPA) for small cell lung cancer (SCLC) patients with brain metastases has been developed. This includes age, performance status, number of brain metastases and presence of extracranial metastases. The aim of the present study was to validate this four-tiered prognostic score in a European cohort of patients. Methods: The retrospective validation study included 180 patients from two centers in Germany and Norway. Results: Median survival from radiological diagnosis of brain metastases was 7 months. The GPA point sum as continuous variable (0–4 points) was significantly associated with survival (p < 0.001). However, no significant survival difference was observed between patients in the two strata with better survival (3.5–4 and 2.5–3 points, respectively). Long-term survival in the poor prognosis group (0–1 points) was better than expected. Conclusion: This study supports the prognostic impact of all four parameters contributing to the GPA. The original way of grouping the parameters and breaking the final strata did not give optimal results in this cohort. Therefore, additional validation databases from different countries should be created and evaluated.     

Brain Metastases in Patients with Cancer of Unknown Primary

Between January 1985 and December 2000, 916 patients with brain metastases were treated with whole brain radiation therapy (WBRT) at the Department of Radiotherapy, University Hospital Freiburg. In 47 patients, a primary tumor could not be identified (cancer of unknown primary (CUP)). Sixteen patients had a solitary brain metastasis, 31 patients presented with multiple brain metastases. Surgical resection was performed in 15 patients, biopsy alone in 12 patients. WBRT was applied with daily fractions of 2 or 3Gy to a total dose of 50 or 30Gy, respectively. According to the recursive partitioning analysis (RPA) classes of the Radiation Therapy Oncology Group for patients with brain metastases none of the patients met the criteria for Class I, 23 for Class II, and 24 for Class III.The median overall survival (OS) for all patients with brain metastases (n = 916) was 3.4 and 4.8 months for patients with CUP (p = 0.45). In patients with CUP (n = 47) the median OS for patients with a single brain metastasis was 7.3 versus 3.9 months for patients with multiple brain metastases (p = 0.05). Median OS for patients with a Karnofsky performance status (KPS) 70 was 6.3 months versus 3.2 months for KPS <70 (p = 0.01).At multivariate analysis performance status and resection status could be identified as independent prognostic factors for the OS.     

The Rationale for Targeted Therapies and Stereotactic Radiosurgery in the Treatment of Brain Metastases

Brain metastases are the most common intracranial malignancy. Many approaches, including radiation therapy, surgery, and cytotoxic chemotherapy, have been used to treat patients with brain metastases depending on the patient’s disease burden and symptoms. However, stereotactic surgery (SRS) has revolutionized local treatment of brain metastases. Likewise, targeted therapies, including small-molecule inhibitors and monoclonal antibodies that target cancer cell metabolism or angiogenesis, have transformed managing systemic disease. Prospective data on combining these treatments for synergistic effect are limited, but early data show favorable safety and efficacy profiles. The combination of SRS and targeted therapy will further individualize treatment, potentially obviating the need for cytotoxic chemotherapy or whole-brain radiation. There is a great need to pursue research into these exciting modalities and novel combinations to further improve the treatment of patients with brain metastases. This article discusses reported and ongoing clinical trials assessing the safety and efficacy of targeted therapy during SRS.

Implications for Practice:

Treatment of patients with brain metastases requires a multidisciplinary approach. Stereotactic radiosurgery is increasingly used in the upfront setting to treat new brain metastasis. Targeted therapies have revolutionized systemic treatment of many malignancies and may sometimes be used as initial treatment in metastatic patients. There is sparse literature regarding safety and efficacy of combining these two treatment modalities. This article summarizes the supporting literature and highlights ongoing clinical trials in combining radiosurgery with targeted therapy.     

Biologically Effective Dose in Stereotactic Body Radiotherapy and Survival for Patients With Early-Stage NSCLC

IntroductionStereotactic body radiotherapy (SBRT) results in excellent local control of stage I NSCLC. Radiobiology models predict greater tumor response when higher biologically effective doses (BED₁₀) are given. Prior studies support a BED₁₀ greater than or equal to 100 Gy with SBRT; however, data are limited comparing outcomes after various SBRT regimens. We therefore sought to evaluate national trends and the effect of using “low” versus “high” BED₁₀ SBRT courses on overall survival (OS).MethodsThis retrospective study used the National Cancer Data Base to identify patients diagnosed with clinical stage I (cT1-2aN0M0) NSCLC from 2004 to 2014 treated with SBRT. Patients were categorized into LowBED (100-129 Gy) or HighBED (≥130 Gy) groups. A 1:1 matched analysis based on patient and tumor characteristics was used to compare OS by BED₁₀ group. Tumor centrality was not assessed.ResultsO 25,039 patients treated with LowBED (n = 14,756; 59%) or HighBED (n = 10,283; 41%) SBRT, 20,542 were matched. Shifts in HighBED to LowBED SBRT regimen use correlated with key publications in the literature. In the matched cohort, 5-year OS rates were 26% for LowBED and 34% for HighBED groups (p = 0.039). On multivariate analysis, receipt of LowBED was associated with significantly worse survival (hazard ratio = 1.046, 95% confidence interval: 1.004–1.090, p = 0.032).ConclusionsLowBED SBRT for treating stage I NSCLC is becoming more common. However, our findings suggest SBRT regimens with BED₁₀ greater than or equal to 130 Gy may confer an additional survival benefit. Additional studies are required to evaluate the dose-response relationship and toxicities associated with modern HighBED SBRT.     

吉非替尼联合全脑放疗治疗非小细胞肺癌脑转移的疗效分析

目的 采用吉非替尼联合全脑放疗治疗非小细胞肺癌脑转移患者,分析其治疗效果.方法 选取非小细胞肺癌发生脑转移的患者,实验组患者行吉非替尼联合全脑放疗,对照组仅进行全脑放疗,于治疗前、放疗结束、放疗结束后3个月行头MRI、胸部CT明确肿瘤情况,进行疗效评价,比较其生活质量评分(KPS)、中位生存时间、1年生存率、不良反应.结果 实验组完全缓解(CR)5例,部分缓解(PR) 18例,稳定(SD)6例,进展(PD)1例,有效率(RR)为76.7％,疾病控制率(DCR)为96.7％,高于对照组,差异有统计学意义(P＜0.05);治疗后实验组KPS评分达(74.5±7.1)分,KPS≥10分占63.3％,中位生存时间为12.2个月,1年生存率为43.3％,均明显高于对照组,差异有统计学意义(P＜0.05).2组患者均出现皮疹、恶心、呕吐、腹泻、白细胞下降、转氨酶升高、骨髓抑制等不良反应,实验组的皮疹、恶心、呕吐、骨髓抑制发生率与对照组比较,差异有统计学意义(P＜0.05).实验组1个月生存率93.3％,3个月生存率76.7％,6个月生存率66.7％,1年生存率50.0％,均明显高于对照组,差异有统计学意义(P＜0.05).结论 吉非替尼联合全脑放疗治疗非小细胞肺癌脑转移患者能够明显提高治疗效果,提高患者的生活质量及生存质量,延长生存期,提高生存率,且不良反应较少.     

肺癌脑转移治疗研究进展

肺癌是中国发病率和死亡率最高的恶性肿瘤,而且在疾病发展过程中易发生脑转移,严重影响患者的生存质量以及生存期。肺癌脑转移的治疗方法包括外科手术、化疗、全脑放射治疗、立体定向放射外科治疗、分子靶向治疗、免疫治疗以及抗血管生成治疗等。对于不同患者如何选择合理且有效的治疗方案是目前研究的热点之一。本文将对肺癌脑转移治疗相关研究进展进行综述,以期为肺癌脑转移患者选择更合理的临床治疗方案提供参考。     

Group and Individual Change in Cognitive Functioning in Patients With 1 to 10 Brain Metastases Following Gamma Knife Radiosurgery

AimsStereotactic radiosurgery is increasingly used to treat multiple (four or more) brain metastases. Preserving cognitive functions is a highly relevant treatment goal because cognitive deteriorations may negatively affect a patient's quality of life. The aim of this study was to assess cognitive change, at the group and individual level, in patients with 1 to 10 brain metastases up to 9 months after Gamma Knife radiosurgery (GKRS).Materials and methodsNinety-two patients with 1 to 10 newly diagnosed brain metastases, expected survival >3 months and Karnofsky Performance Status (KPS) ≥70 and 104 non-cancer controls were included. A neuropsychological test battery was administered before GKRS (n = 92) and at 3 (n = 66), 6 (n = 52) and 9 (n = 41) months after GKRS. The course of test performances, while taking into account practice effects, was analysed using linear mixed models. Pre-GKRS predictors of cognitive trajectories were analysed. To determine proportions of individuals with cognitive changes, reliable change indices, with correction for practice effects, were calculated.ResultsAt the group level, immediate memory, working memory and information processing speed significantly improved over 9 months after GKRS. There were no cognitive declines. Neither number nor volume of brain metastases influenced cognitive change over time. At the individual level, proportions of patients with stable, improved or declined performances were comparable with controls, except for information processing speed (more individuals with improvements in patients) and motor dexterity (more improvements and declines in patients).ConclusionsCognitive functioning in patients with 1 to 10 brain metastases was preserved, or improved, up to 9 months after GKRS. Neither number nor volume of brain metastases influenced cognitive performance.     

130例脑转移瘤常规放疗和调强放疗的疗效分析

目的 评价调强放射治疗在脑转移瘤治疗中的疗效.方法 将130例脑转移瘤患者随机分成常规放疗组和调强放射治疗组.常规放疗组64例,先行全脑放射治疗(WBRT)36～40 Gy后,局部缩野加量,总剂量到50～60 Gy,每次2 Gy,5次/周.调强放射治疗组66例,全脑放射治疗剂量39.2～39.6Gy,脑转移灶剂量54～60 Gy,5次周,共23次.结果 治疗结束后3月、6月复查,对1～3个脑转移灶患者,常规放疗组和调强放疗组的中位生存期、有效率(CR+ PR)和1年生存率分别为13月、82％、59％和14月、88％、61％.对于脑转移灶数目大于3个的患者,常规放疗组和调强放疗组的中位生存期、有效率(CR+ PR)和1年生存率分别为9月、73％、47％和13月、87.5％、59％.结论 调强放射治疗可能是多发脑转移瘤患者的一种较常规全脑放疗更有效的治疗手段.     

Pulmonary Resection after Radiosurgery and Neoadjuvant Immunochemotherapy for NSCLC Patients with Synchronous Brain Metastasis—A Case Series of Three Patients

Simple SummaryIn this short communication, we present three cases of patients with symptomatic, synchronous brain metastases of otherwise locally limited non-small cell lung cancer. The patients received local ablative treatment of the brain metastases followed by neoadjuvant immunochemotherapy with pemetrexed, cisplatin, and pembrolizumab, and resection of the pulmonary lesion with curative intent. With two of the patients still alive and maintaining a good quality of life with a progression-free survival and overall survival of 28 and 35 months, respectively, this case series illustrates the potential of novel combinatorial treatment approaches.AbstractBrain metastases are a common finding upon initial diagnosis of otherwise locally limited non-small cell lung cancer. We present a retrospective case series describing three cases of patients with symptomatic, synchronous brain metastases and resectable lung tumors. The patients received local ablative treatment of the brain metastases followed by neoadjuvant immunochemotherapy with pemetrexed, cisplatin, and pembrolizumab. Afterwards, resection of the pulmonary lesion with curative intent was performed. One patient showed progressive disease 12 months after initial diagnosis, and passed away 31 months after initial diagnosis. Two of the patients are still alive and maintain a good quality of life with a progression-free survival and overall survival of 28 and 35 months, respectively, illustrating the potential of novel combinatorial treatment approaches.     

Peripheral Blood Lymphocyte-to-Monocyte Ratio at Relapse Predicts Outcome for Patients With Relapsed or Refractory Diffuse Large B-cell Lymphoma in the Rituximab Era

BackgroundPatients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) have a poor prognosis, even in the rituximab era. Several studies have reported the clinical importance of the peripheral blood lymphocyte-to-monocyte ratio (LMR) in various malignancies, including lymphoma. However, the prognostic value of the LMR in relapsed/refractory DLBCL has not been well evaluated. The purpose of the present study was to investigate whether the LMR at relapse can predict clinical outcomes for relapsed/refractory DLBCL patients treated with rituximab.Patients and MethodsWe analyzed data on 74 patients with relapsed/refractory DLBCL, who were initially treated with R-CHOP (rituximab and cyclophosphamide, doxorubicin, vincristine, and prednisone) or an R–CHOP-like regimen.ResultsThere was a significant association between a low LMR (≤ 2.6) and shorter overall survival (OS; P < .001) and progression-free survival (PFS; P < .001) compared with the high LMR group (> 2.6). Multivariate analysis showed that LMR was an independent prognostic factor for OS (P < .001) and PFS (P < .001), as was the international prognostic index (IPI) at relapse for OS. In addition, the LMR had an incremental value for OS and PFS compared with the IPI at relapse.ConclusionThe LMR predicts OS and PFS outcomes in relapsed/refractory DLBCL patients treated with rituximab, and might facilitate better stratification among patients in low- and intermediate-risk IPI groups.     

第15届世界肺癌大会非小细胞肺癌放疗研究进展

第15届世界肺癌大会（WCLC）共收到约210篇放疗相关研究的摘要。内容涉及早期非小细胞肺癌（NSCLC）应用体部立体定向放疗（SBRT）的疗效和安全性、评价手段和剂量分割探讨;局部晚期NSCLC同步放化疗中高剂量与标准放疗剂量、不同化疗方案以及是否联合西妥昔单抗的对照研究;经全切的ⅢA～N2期NSCLC患者术后采用三维适行放疗（3D-CRT）的临床意义;NSCLC多发脑转移行全脑放疗（WBRT）同步联合酪氨酸激酶抑制剂（TKI）的疗效和安全性以及表皮生长因子受体（EGFR）突变状态对疗效的影响。另外关于放疗的防护、毒性、疗效、预后及生活质量评估也多有报告。     

Generation of a New Disease-specific Prognostic Score for Patients With Brain Metastases From Small-cell Lung Cancer Treated With Whole Brain Radiotherapy (BMS-Score) and Validation of Two Other Indices

Introduction

Patients with small-cell lung cancer (SCLC) demonstrate an exception in the treatment of brain metastases (BM), because in patients with SCLC whole brain radiotherapy (WBRT) only is the preferred treatment modality. The purpose of this study was to develop a prognostic score for patients with brain metastases from SCLC treated with WBRT.

三维适形放疗与立体定向放射外科治疗脑胶质瘤初步临床分析

目的分析三维适形放疗(3DCRT)与立体定向放射外科(SRS)对于不能手术切除或拒绝手术治疗的脑胶质瘤的疗效。方法对46例不能手术或拒绝接受手术治疗的脑胶质瘤患者随机分为两组,3DCRT组24例,SRS组22例。3DCRT组施行三维适形放疗,SRS组施行立体定向放射外科治疗。结果3DCRT组患者1、2、3年生存率分别是91.7%、54.2%和8.3%,SRS组分别是80.9%、47.6%、4.8%,两组间比较无显著性差异(P=0.6487)。3DCRT组放射性脑水肿发生率为66.7%,SRS组为95.5%,两组间差异有显著性(P<0.05)。结论3DCRT与SRS放射治疗脑胶质瘤生存率相似。SRS放射性脑水肿反应明显高于3DCRT,3DCRT较SRS易为患者耐受。采用非手术疗法治疗脑胶质瘤,3DCRT可能是一种适宜的放射治疗方法。