Protective Effects of Shikonin on Brain Injury Induced by Carbon Ion Beam Irradiation in Mice

Radiation encephalopathy is the main complication of cranial radiotherapy. It can cause necrosis of brain tissue and cognitive dysfunction. Our previous work had proved that a natural antioxidant shikonin possessed protective effect on cerebral ischemic injury. Here we investigated the effects of shikonin on carbon ion beam induced radiation brain injury in mice. Pretreatment with shikonin significantly increased the SOD and CAT activities and the ratio of GSH/GSSG in mouse brain tissues compared with irradiated group （P〈0.01）, while obviously reduced the MDA and PCO contents and the RO$ levels derived from of the brain mitochondria.

Is There Any Indication for Prophylactic Brain Irradiation in the Management of Small Cell Prostate Cancer?

Small cell prostate carcinoma (SCPC) is an extremely rare pathology with an aggressive behavior, characterized by early brain metastases. We describe three cases of SCPC where brain metastases occurred despite response to chemotherapy. The benefit of prophylactic brain irradiation (PBI), as part of the management of SCPC, is discussed and compared to its indications in small cell lung cancer.

The effects of three-dimensional conformal radiotherapy combined with whole brain irradiation on brain metastases

Objective： To observe the recently therapeutic effects and toxicity of three-dimensional conformal radiotherapy combined with whole brain irradiation for patients with brain metastasis. Methods： 33 cases were treated by whole brain irradiation at first, the dose of which was 36-40 Gy （18-20 f）. Then three-dimensional conformal radiotherapy was added to the focus with a total dose of 20-25 Gy, whose fractionated dose was 2-5 Gy/time, 5 times/week or 3 times/week. Results： Within 1 month after radiotherapy, according to imaging of the brain, the CR of all patients was 45.5%, PR 36.4%, NC 15.1%, and PD 3%. For the 32 cases with neural symptoms before radiation, the CR of the symptoms was 40.6% and PR 59.4%. All patients gained different increases in KPS grade. By the end of the follow-up period, there were 22 deaths with the mean survival time up to 9.3 months. Conclusion： Three-dimensional conformal radiotherapy combined with whole brain irradiation can not only effectively control brain metastases and improve life quality, but also tends to prolong survival time.

Advance of prophylactic cranial irradiation in lung cancer

Brain metastases in patients with lung cancer are a devastating problem with profound impact on survival. Prophylactic cranial irradiation has been discussed as an option to reduce the risk of brain metastases. This report provides an extensive review of the current evidence from non-randomized and randomized trials regarding the use of prophylactic cranial irradiation in lung cancer.

均整器对海马规避全脑非均分调强放射治疗的剂量学影响

目的:研究非均分9野调强放疗均整过滤器(9F-IMRT-FF)和9野调强放疗非均整过滤器(9F-IMRT-FFF)两种模式下海马规避全脑放疗的剂量学差异。方法:选取2023年1-12月在承德市中心医院已完成全脑放疗的20例颅内转移患者的模拟定位CT图像,在计划系统中重新设计全新9F-IMRT-FF和9F-IMRT-FFF两种模式放疗计划。在两种模式优化参数保持一致的条件下进行放疗计划优化。比较两种模式计划的剂量学参数差异,以及加速器照射效率差异。结果:9F-IMRTFFF模式计划靶体积(PTV)的2%靶区体积的受照剂量(D_(2%))为(33.36±0.79)Gy,低于9F-IMRT-FF的(36.44±0.36)Gy,差异有统计学意义(t=-2.496,P<0.05)。9F-IMRT-FFF模式计划左侧海马的100%靶区体积的受照剂量(D_(100%))、最大剂量(D_(max))和平均剂量(D_(mean))均低于9F-IMRT-FF模式计划,差异有统计学意义(Z=-3.179、-3.018、-2.145,P<0.05)。9F-IMRT-FFF模式计划右侧海马D_(100%)、D_(max)低于9F-IMRT-FF模式计划,差异有统计学意义(Z=-3.099、-3.260,P<0.05)。9F-IMRT-FFF模式计划机器总跳数(MU)比9F-IMRT-FF模式计划增加25%,而治疗时间比9F-IMRT-FF模式缩短38%,差异有统计学意义(t=-9.664、-13.312,P<0.05)。结论:9F-IMRT-FF和9F-IMRT-FFF两种模式均能满足临床要求。9F-IMRT-FFF模式具备更佳的束流调制能力,对于降低海马放疗剂量、减少治疗时间和提高治疗效率更具有优势。

BRAIN研究:EGFR-TKI首次挑战全脑放疗

众所周知，脑转移在晚期非小细胞肺癌（non-small cell lung cancer，NSCLC）中较常见，约20%~25%的初诊晚期肺癌患者会发生脑转移。近30%的晚期肺癌最终会发生脑转移，预后较差［1］。脑转移患者的治疗比较棘手，全脑放疗（whole brain irradiation，WBI）是脑转移患者的传统标准治疗方案，但其会增加患者认知功能下降的风险。Ⅱ期CTONG0803研究结果显示［2］，对于EGFR突变阳性NSCLC脑转移患者，单药使用厄洛替尼治疗脑转移病灶的有效率很不错，患者的中位生存时间数据非常好。吴一龙等教授看到了此临床现状，牵头启动了BRAIN研究（CTONG1201）［3］。

Whole-brain radiation therapy alone vs. combined therapy with stereotactic radiosurgery for the treatment of limited brain metastases: A systematic review

Objective The aim of the study was to compare the efficacy and safety of whole brain radiotherapy(WBRT) used alone and combined with stereotactic radiosurgery(SRS) in the treatment of limited(1–4)brain metastases. Methods We searched for randomized controlled and matched-pair analysis trials comparing WBRT plus SRS versus WBRT alone for brain metastases. The primary outcomes were the overall survival(OS), intracranial control(IC), and localcontrol(LC). The secondary outcome was radiation toxicity. The log hazard ratios(lnHRs) and their variances were extracted from published Kaplan-Meier curves and pooled using the generic inverse variance method in the RevMan 5.3 software. The non-pooled outcome measures were evaluated using descriptive analysis. Results Three randomized controlled trials and two matched-pair analysis studies were included. There was no difference in the OS for limited brain metastases between the two groups [lnHR 0.91(95% CI 0.76–1.09, P = 0.32) vs. 0.72(95% CI 0.44–1.19, P = 0.20)]. The LC and IC were significantly higher in the combined treatment group [lnHR 0.69(95% CI 0.55–0.86, P = 0.001) vs. 0.41(95% CI 0.29–0.58, P < 0.0001)]. For patients with a single lesion, one trial showed a higher survival in the combined treatment group(median OS: 6.5 months vs. 4.9 months, P = 0.04). The combined treatment was not associated with significantly higher incidence of radiation toxicity. Conclusion Combined treatment with WBRT plus SRS should be recommended for patients with limited brain metastases based on the better LC and IC without increased toxicity. It should also be considered a routine treatment option for patients with solitary brain metastases based on the prolonged OS.

A Single Institutional Phase II Randomized Trial of Whole Brain Radiation Therapy with or without Irinotecan for the Treatment of Brain Metastases from Solid Tumours

Background: The relatively suboptimal results of whole brain radiation therapy (WBRT) alone in eradication of brain metastases and an attempt to improve outcomes with WBRT have led to studies combining radiotherapy with chemotherapy drugs that could act as radiosensitizers with a rationale of improving local tumor control. Materials and Methods: This randomized phase II study evaluated the use of Irinotecan concomitant with 37.5 Gray (Gy) of WBRT in 2.5 Gy daily fractions × 5 days each week for 3 weeks versus Whole WBRT alone in patients with brain metastasis (BM) from solid tumors. Fifty patients were randomized to receive either WBRT alone or concomitant with three irinotecan IV infusions 80 mg/m2, 2 hrs before RT on days 1, 8, and 15. Results: The objective response rate (ORR) was significantly improved in patients receiving Irinotecan with radiotherapy versus radiotherapy alone (48% vs. 28%;p = 0.048). The median time to progression of brain metastasis was significantly longer in the irinotecan and WBRT arm as compared to the WBRT arm (8 vs. 5 months;p < 0.001). There was no significant difference in survival between treatment arms (p = 0.361). Irinotecan with radiotherapy was generally well tolerated and did not interfere with the delivery of WBRT. Conclusions: Irinotecan concomitant with WBRT was well tolerated and significantly improved local control of BM compared with WBRT alone. These findings require confirmation in a phase III trial with addition of quality of life assessment.

局限期小细胞肺癌预防性脑照射后脑转移相关危险因素分析

目的:明确局限期小细胞肺癌患者行预防性脑照射(prophylactic cranial irradiation, PCI)后发生脑转移的危险因素,并对相关因素进行分析。以筛选出不能从PCI中获益的人群,为PCI的临床应用提供参考。方法:回顾性分析2011年08月至2019年12月在我院接受过PCI的167例局限期小细胞肺癌患者的病历资料。采用SPSS 26.0统计软件对病历资料进行统计分析。用Kaplan-Meier法计算脑转移发生率及总生存率,并用Log-rank法进行检验。采用Cox回归对影响脑转移及总生存的危险因素进行单因素及多因素分析。结果:局限期小细胞肺癌患者PCI后1、2、3年脑转移率分别为3.8%、12.7%、18.9%。单因素及多因素分析结果显示原发肿瘤为T_(4)期(P=0.004,HR=7.06,95%CI:1.86~26.82)是影响患者PCI后脑转移的危险因素,T_(2)期(P=0.008,HR=2.48,95%CI:1.26~4.89)、T_(3)期(P=0.003,HR=3.38,95%CI:1.49~7.47)、T_(4)期(P=0.001,HR=3.87,95%CI:1.79~8.35)是影响患者总生存的危险因素。结论:较高的T分期是局限期小细胞肺癌患者PCI后脑转移及总生存的独立危险因素。即使T_(4)期患者PCI后脑转移发生率高于其他期别,但仍能够从PCI中获益。

糖原合酶激酶-3β与颅脑照射后认知障碍的相关性研究进展

近年来,随着医疗技术的不断进步,接受颅脑照射治疗的肿瘤患者的长期生存率大幅提升。因此,颅脑照射的远期并发症,如智力下降、记忆力减退、甚至是痴呆等问题愈来愈受到人们的重视。糖原合酶激酶-3(glycogen synthase kinase-3,GSK-3)是一种高度保守的丝氨酸/苏氨酸蛋白激酶,广泛存在于真核生物的细胞质中,目前已发现有GSK-3α和GSK-3β两种亚型。GSK-3β在脑组织尤其是海马区域中高表达,广泛参与各种神经退行性疾病、神经精神类疾病和癌症等多种重大疾病的发病过程。研究显示GSK-3β参与细胞炎症反应、糖原代谢、神经系统功能等的调控,激活GSK-3β的活性会影响整个生命周期中的细胞增殖、衰老、凋亡及突触的可塑性,进而导致神经系统认知功能的障碍。目前,GSK-3β与颅脑照射后认知障碍的相关性研究较少,该文结合国内外近年来的研究成果对GSK-3β在颅脑照射后认知功能障碍中的作用展开综述。

Relief Effect of Bevacizumab on Severe Edema Induced by Re-irradiation in Brain Tumor Patients

INTRODUCTION Brain edema is a serious clinical event and could cause various neurological symptoms such as dizziness and headache.Drugs frequently used to relieve brain edema include steroid,dehydrant （e.g.,mannitol）,and diuretics.But the effects of these drugs were limited in patients with severe edema.Bevacizumab has been applied in the treatment of cerebral radiation necrosis. Case studies have reported on the application of bevacizumab in the treatment of severe brain edema. In the present study,we describe significant effects of bevacizumab on severe brain edema in patients with re-irradiation.

Are memantine, methylphenidate and donepezil effective in sparing cognitive functioning after brain irradiation?

One strategy to reduce neurocognitive deterioration in patients after brain irradiation is the use of neuroprotective medication.To generate up-to date knowledge regarding neuroprotective agents we performed a systematic review on the clinical effectiveness of three agents that were reported to have neuroprotective characteristics:memantine,methylphenidate and donepezil.The use of memantine after brain irradiation showed a delay in cognitive deterioration,although at 24 weeks this did not reach significance(P=0.059).Lack of significance is likely to be the result of the limited statistical power of 35%and memantine did show significant differences in secondary outcomes.The study on methylphenidate was not conclusive.Donepezil revealed significant differences in a few cognitive tests however no difference in global cognition was found.In addition,larger effects were observed in individuals with greater cognitive dysfunction prior to treatment.

复发/难治性原发性中枢神经系统淋巴瘤挽救性全颅放疗和化疗的疗效比较及预后因素分析

目的比较全颅放疗(whole brain radiotherapy,WBRT)与其他挽救性治疗方案在复发/难治性原发性中枢神经系统淋巴瘤(relapsed/refractory primary central nervous system lymphoma,R/R PCNSL)中的疗效,并进行预后因素分析。方法采用回顾性队列研究,统计2016年1月至2020年12月复旦大学附属华山医院收治的初次R/R PCNSL患者相关资料,对接受含或不含WBRT挽救治疗的患者进行生存与预后相关因素的统计学分析。结果共纳入104例患者,37例接受WBRT治疗(WBRT组),67例仅接受单纯化疗(非WBRT组)。WBRT组与非WBRT组的客观反应率(objective response rate,ORR)分别为70.6%和29.2%,差异有统计学意义(P<0.01)。WBRT组中位无进展生存期(progression-free survival,PFS)6.1个月,非WBRT组中位PFS 2.0个月,差异有统计学意义(P<0.01)。WBRT组中位总生存期(overall survival,OS)28.8个月,非WBRT组中位OS 30.2个月,差异无统计学意义(P>0.05)。预后单因素与多因素分析显示,脑脊液(cerebral spinal fluid,CSF)蛋白水平和挽救治疗反应与PFS有关,KPS评分和挽救治疗反应与OS有关。结论可以推荐WBRT作为初次R/R PCNSL的早期挽救治疗方法,相比化疗能获得更佳的PFS和应答率,但未见OS的明显获益。脑脊液蛋白>0.45 g/L、挽救治疗3个疗程内未达到部分缓解(partial remission,PR)是对预后不利的独立危险因素。

111例非小细胞肺癌脑转移的治疗与预后

背景与目的 肺癌脑转移临床表现各异，尚无标准治疗方案。本研究的目的是回顾性分析非小细胞肺癌（NSCLC）脑转移的个体化治疗策略以及全身化疗与全脑放疗的时序对生存期的影响。方法 纳入111例1995年9月至2004年5月伴脑转移的NSCLC患者，根据确诊时有无中枢神经系统（CNS）症状归纳为有症状组（37例）和无症状组（74例）：前者首选全脑放疗（WBRT）继之全身化疗；后者以全身化疗为主，择期行WBRT。化疗主要为含铂方案。WBRT：DT30～40Gy／20次。治疗过程中49例曾用卡莫司汀（BCNU）或鬼臼噻吩甙（VM-26）治疗。结果 全组中位生存11个月，1年生存率为40．79％，2年生存率为13．26％，有症状组与无症状组生存期差异无统计学意义。无症状组WBRT前中位化疗3周期（1～6周期），WBRT前接受3或4周期化疗者有预后意义（P=0．0188，P=0．0035）。无症状组治疗中并用BCNU或VM=26者生存期明显优于未用者（P=0．0219）。两组患者Ⅲ／Ⅳ度血液学毒性差异无统计学意义。COX多因素回归分析结果显示，脑转移灶数目（P=0．000）、脑外病灶数目（P=0．022）及ECOG状态（P=0．001）为独立预后因素。结论=无症状脑转移者WBRT前化疗3或4周期为宜，化疗可部分控制脑转移病灶，治疗中并用BCNU或VM-26可能有延长生存的优势。

序贯化疗联合脑放射治疗非小细胞肺癌脑转移

背景与目的脑放疗是非小细胞肺癌脑转移的传统治疗,化疗与脑放疗的联合是近年的研究方向。鉴于序贯/维持化疗近年来在晚期非小细胞肺癌显示较好前景,我们对非小细胞肺癌脑转移患者进行序贯化疗联合脑放射的治疗探索。方法对确诊的非小细胞肺癌脑转移患者采用TP-NP-GP三个方案序贯化疗联合同期的脑放射进行治疗。TP方案:TXT175mg/m2d1,DDP20mg/m2d1-5,每3周重复;NP方案:NVB25mg/m2d1、8,DDP20mg/m2d1-5,每3周重复;GP方案:GEM1g/m2d1、8,DDP20mg/m2d1-5,每3周重复。每个化疗方案至少使用2疗程,有效的患者继续原方案至4疗程后行下一个方案的序贯化疗。结果51例患者使用TP-NP-GP方案序贯化疗在外周病灶的有效率分别为41.2%、35.6%及27.8%,联合同期的脑放射治疗在脑转移灶的有效率达到60.8%。中位生存期14.7个月。1年、2年及3年生存率分别为67.8%、20.6%及1.3%。结论第三代新药方案序贯化疗联合脑放射治疗非小细胞肺癌脑转移可以取得较好疗效,总体耐受性良好。

厄洛替尼联合全脑放疗治疗肺腺癌伴脑转移的临床观察

目的探讨厄洛替尼联合全脑放疗（WBRT）治疗肺腺癌伴脑转移的临床疗效及不良反应。方法选取2011年1月至2012年6月我院收治的肺腺癌伴脑转移患者42例,随机分为治疗组（n=22）和对照组（n=20）。治疗组患者给予厄洛替尼150mg口服,每日1次;同时行WBRT,总剂量为30~36Gy/10~12次,3Gy/次,5次/周,若脑转移病灶为1~2个,WBRT 30~36Gy后,缩野脑转移灶加量16~20Gy/8~10次/2周。对照组患者先行全身化疗2个周期,然后行WBRT,放疗方法同治疗组。ECOG评分为0~1分患者采用AP方案（培美曲塞500mg/m2,第1天;顺铂25mg/m2,静脉滴注,第1~3天）或DP方案（多西他赛75mg/m2,第1天;顺铂25mg/m2,静脉滴注,第1~3天）,ECOG评分2分患者给予单药培美曲塞化疗,21天为1个周期。观察两组患者的近期疗效、不良反应及生存情况。结果 42例患者均可评价疗效。治疗组和对照组脑转移灶的RR分别为86.4%、70.0%,差异无统计学意义（P〉0.05）。治疗组和对照组肺癌原发灶的RR分别为40.9%、35.0%,差异无统计学意义（P〉0.05）。治疗组和对照组的中位TTP分别为8.5个月和4.5个月,差异无统计学意义（P〉0.05）。治疗组和对照组的中位OS分别为14.0个月和9.8个月,差异无统计学意义（P〉0.05）。治疗组和对照组的1年生存率分别为59.1%和45.0%,2年生存率分别为27.3%和15.0%,差异均无统计学意义（P〉0.05）。治疗组不良反应仅为皮疹和腹泻,多数为1~2级,患者可耐受,无明显骨髓抑制或消化道反应;对照组主要为骨髓抑制、恶心和呕吐等消化道反应,经对症处理后好转。结论厄洛替尼联合WBRT治疗肺腺癌伴脑转移能延长患者的生存时间,且患者耐受性良好。

立体定向放射治疗和全脑放射治疗脑转移瘤对患者神经认知功能和健康相关生活质量的影响分析

目的探讨立体定向放射治疗(SRT)和全脑放射治疗(WBRT)对脑转移瘤患者神经认知功能和健康相关生活质量的影响。方法对收集的192例脑转移瘤患者,分别进行单纯WBRT、单纯SRT以及SRT+WBRT治疗,每组随机分为64例患者,分别进行神经认知功能和健康相关生活质量(HRQo L)的评价,神经认知功能共评价6个功能部分,HRQoL用QLQ-C30和BN20表进行共6个方面的评价。结果在神经认知功能方面,患者在WBRT、SRT、SRT+WBRT之后在视觉记忆、工作记忆、注意力、视觉构象能力方面均无显著性差异(P均>0.05),而在信息处理速度和执行功能方面SRT+WBRT优于单纯WBRT组和单纯SRT组,差异均有统计学意义(P均<0.05);KPS<90分患者与KPS≥90分患者在信息处理速度(P=0.0036)和执行功能(P=0.0024)方面差异具有统计学意义(P均<0.05),其他方面差异无统计学意义。在健康相关生活质量方面,患者在WBRT、SRT、SRT+WBRT之后在情感功能、角色功能、交流障碍、运动功能障碍方面均无显著性差异(P均>0.05),而在物理功能和认知功能方面SRT+WBRT优于单纯WBRT组和SRT组,差异均有统计学意义(P均<0.05);KPS<90分患者与KPS≥90分患者在物理功能(P=0.0016)和认知功能(P=0.0048)方面,差异具有统计学意义(P均<0.05),其他方面差异无统计学意义。结论立体定向放射治疗加全脑放射治疗对于提高患者的神经认知功能和生活质量方面有一定效果,可作为更好的治疗脑转移瘤的方式。

全脑放射促进顺铂通过血脑屏障的研究

目的：通过检测顺铂 (cis-diamminedichloroplatinum,DDP)在脑脊液中的浓度变化，定量观察脑放射促进 DDP透过血脑屏障的作用。方法： 20例非小细胞肺癌 (non-small cell lung cancer,NSCLC)脑转移患者接受脑放射， DDP 20mg/m2分别于脑放射前、脑放射 10 Gy、 20 Gy、 30 Gy及 40 Gy时静滴，于之后 3h采集脑脊液与血标本。 10例 NSCLC无脑转移者于首次用 DDP后 3h采集脑脊液与血标本。采用石墨炉原子吸收光谱法检测 DDP浓度。结果：脑转移可评价者 20例，无脑转移者 10例。脑转移者放疗前脑脊液中 DDP浓度平均 1.02mg/L，明显高于无脑转移者脑脊液中 DDP浓度 (平均 0.33mg/L)；脑转移者全脑放疗 10～ 30Gy，脑脊液中 DDP浓度随脑放射剂量的增加而增加，全脑照射 30Gy时浓度最高，平均 2.36mg/L。结论： DDP可透过脑转移者受损的血脑屏障进入脑脊液中，并可以达到治疗浓度；全脑放射可以促进 DDP透过血脑屏障，全脑放疗 10～ 30Gy时 DDP进入脑脊液中的浓度随放射剂量的增加而增加， 30Gy时浓度最高； DDP可少量通过正常的血脑屏障，但未达有效治疗浓度。

伽玛刀照射正常大鼠后急性期血脑屏障通透性的改变

目的 :观察伽玛刀照射正常大鼠后急性期血脑屏障 (blood brainbarrier,BBB)通透性的改变。 方法 :选择正常大鼠右侧尾状核头部为照射靶点 ,动物按伽玛刀最大照射剂量分为 2 0、5 0、75、16 0Gy 4组 ,准直器直径为 4mm。于伽玛刀照射后12h至 14d内应用兔多抗清蛋白抗体行免疫组化染色半定量分析 ;并以硝酸镧作为示踪剂 ,应用透射电镜观察BBB的超微结构改变。 结果 :免疫组化法显示 16 0Gy和 75Gy剂量组于照射后 12h ,5 0Gy和 2 0Gy剂量组于照射后 1d靶区内出现血浆蛋白外渗 ;硝酸镧示踪电镜显示 16 0Gy、75Gy和 5 0Gy组于照射后 12h、2 0Gy组于照射后 1dBBB内皮细胞间的紧密连接开放。 75Gy、5 0Gy、2 0Gy组变化高峰期出现在照射后 3d ,而 7d后开始消散 ,16 0Gy组靶区阳性反应持续至照射后 14d。结论 :大鼠在伽玛刀照射后急性期存在BBB通透性改变 ,这种改变在 2 0～ 75Gy范围内具有自限性。

食管癌术后脑转移17例临床分析

目的探讨食管癌术后脑转移的临床特点及治疗方法。方法对1993年4月-2005年6月收治的17例食管癌术后脑转移患者的临床特点和治疗方法进行回顾性分析。结果全组平均生存时间为26.3个月,7例单纯脑转移切除平均生存时间为17.7个月,3例手术切除联合放疗平均生存时间为65.5个月。结论食管癌术后脑转移预后不良,治疗原则上应采用以手术切除联合放疗为主的综合治疗。