【文献摘要】放射治疗在治疗成年新近诊断的多形性胶质母细胞瘤中的作用:系统综述和基于证据的临床实践指南更新。
《Journal of Neurooncology 》杂志2020年11月刊载[ Nov;150(2):215-267.]美国 Mateo Ziu, Betty Y S Kim, Wen Jiang,的等撰写的《放射治疗在治疗成年新近诊断的多形性胶质母细胞瘤中的作用:系统综述和基于证据的临床实践指南更新。The role of radiation therapy in treatment of adults with newly diagnosed glioblastoma multiforme: a systematic review and evidence-based clinical practice guideline update 》（doi: 10.1007/s11060-020-03612-7. ）。
目标人群
这些建议适用于新近诊断为胶质母细胞瘤的成年患者。
问题1
在提高新诊断为胶质母细胞瘤的成年(65岁及以下)患者的生存率方面，增加放疗(RT)是否比不放疗的管理更为有益?
建议
I级:推荐放射治疗(RT)作为成人新诊断的恶性胶质瘤的治疗。
问题2
对于新诊断的胶质母细胞瘤成年(65岁及以下)患者，每天分割2Gy，照射60Gy的放射治疗（RT）方案是否比其他方案更有利于生存，同时使毒性最小化?
建议
一级:对包括的增强区域，治疗方案应包括每天2Gy的剂量，最高为60G 。
问题3
对于新近诊断为胶质母细胞瘤的成年患者(65岁及以下)，在降低辐射诱导毒性并保持疗效的同时，定制的靶区体积（tailored target volume）是否优于区域性放疗（regional RT ）?
建议
II级:建议放射治疗计划包括在放射影像T1加权增强肿瘤体积或MRI T2加权异常周围1-2厘米的边缘。
III级:在长期放疗过程中，由于手术缺损的体积会发生变化，为了减少正常脑的照射体积（the radiation volume），可能需要重新计算放疗期间的照射体积。
问题4
新近诊断为胶质母细胞瘤的成年(65岁及以下)患者，在标准肿瘤体积治疗中增加脑室下区放疗（the subventricular zone RT）是否能改善肿瘤控制率和总体生存率?
建议
支持和反对有意地对脑室下区(SVZ)进行照射的证据相互矛盾，无法作出任何建议。
问题5
对于老年(>65岁)和/或虚弱的新诊断为胶质母细胞瘤的患者，在手术干预中加入放疗（RT）是否能改善疾病控制率和总体生存率?
建议
I级:建议对老年和体弱的新诊断胶质母细胞瘤患者进行放射治疗，以提高总体生存率。
问题6
在新近诊断的胶质母细胞瘤老年(>65岁)和/或虚弱的患者中，调整标准方案的放疗（RT）剂量和分割方案是否能降低毒性、改善疾病控制率和生存率?
建议
II级:因为总体生存率没有差异，而短期放疗（RT）方案的放射治疗（RT）风险较佳，相对于每日分割2Gy，常规的60Gy，建议虚弱和老年患者采用短期放疗（RT）治疗方案。
II级:老年人和/或虚弱患者短时间放疗时，应考虑以15次分割照射40.05Gy或5次分割照射25Gy,或10次分割照射34Gy的剂量。
问题7
对于新近诊断为胶质母细胞瘤的成年患者，延迟开始放疗（RT）而不是在手术干预后2周开始放疗（RT），在降低辐射诱发毒性、改善疾病控制和生存方面是否有优势?
建议
III级:建议新近诊断的胶质母细胞瘤（GBM）患者在手术干预后6周内开始放疗（RT），而不是更晚。对于新诊断为胶质母细胞瘤并已行手术切除的成年患者，在6周的间隔内，没有足够的证据推荐最佳的术后特定某天开始RT。
问题8
对于新近诊断的幕上胶质母细胞瘤成年患者，影像调强放疗 (IMRT)或类似技术在提供肿瘤控制率和提高生存率方面是否与标准区域放疗（RT）一样有效?
建议
III级:没有证据表明，在改善新近诊断为胶质母细胞瘤的成年患者的总生存率方面，调强放疗比常规放疗更好。因此，不应偏向调强放疗，而非常规放疗作为照射模式。
问题9
在新近诊断的胶质母细胞瘤成年患者中，使用放疗增敏剂是否会提高由疾病控制和总生存率决定的放疗的疗效?
建议
III级:不建议将碘苷（Iododeoxyuridine）作为放射增敏剂用于新诊断的GBM患者的放疗（RT）治疗
问题10
在新近诊断为胶质母细胞瘤的成年患者中，超分割（Ultrafractionated ）放疗在改善疾病控制率和生存率方面是否优于标准分割治疗?
建议
目前还没有足够的证据来制定关于使用超分割放疗方案和关于可从中获益的患者群体的建议。
问题11
在预后不良的新诊断的胶质母细胞瘤患者中，大分割放疗（RT）是否可以替代以毒性程度、疾病控制率和生存率来衡量的标准分割方案?
建议
I级:大分割放疗（RT）方案可用于预后差、生存率有限且无折中反应（compromising response）的患者。文献中没有足够的证据使我们能够推荐最佳的有最长的总体生存期和/或在毒性最少和治疗时间较短的情况下给予相同的总体生存率的大分割放疗方案。
问题12
对于新近诊断为胶质母细胞瘤的成年患者，在标准分割放疗基础上加用近距离放射治疗（brachytherapy）是否可以改善疾病控制率和生存率?
建议
I级:近距离放射治疗作为外放射放疗的强化并没有被证明是有益的，也不推荐用于新诊断的胶质母细胞瘤（GBM）患者的常规治疗。
问题13
在新近诊断为胶质母细胞瘤的老年患者(>65岁)中，以毒性程度、疾病控制率 和生存率来衡量，在什么情况下加速超分割放疗有指证代替标准分割治疗方案?
建议
III级:与常规外放疗相比加速超分割放疗的总放疗剂量为45 Gy或48 Gy，可以缩短治疗的时间而不损害生存率,应被视为新诊断的GBM老年患者的治疗选项。
问题14
对于新近诊断为胶质母细胞瘤的成年患者，在常规标准分割放疗的基础上增加立体定向放射外科治疗(SRS)是否可以改善疾病控制率和生存率?
建议
I级:外放射治疗外推量立体定向放射外科治疗并没有被证明是有益的，也不推荐对新近诊断为恶性胶质瘤的患者进行常规治疗。
Target population
These recommendations apply to adult patients diagnosed with newly diagnosed glioblastoma.
Question 1
In adult patients (aged 65 and under) with newly diagnosed glioblastoma, is the addition of radiation therapy (RT) more beneficial than management without RT in improving survival?
Recommendations
Level I: Radiation therapy (RT) is recommended for the treatment of newly diagnosed malignant glioblastoma in adults.
Question 2
In adult patients (aged 65 and under) with newly diagnosed glioblastoma, is the RT regimen of 60 Gy given in 2 Gy daily fractions more beneficial than alternative regimens in providing survival benefit while minimizing toxicity?
Recommendations
Level I: Treatment schemes should include dosage of up to 60 Gy given in 2 Gy daily fractions that includes the enhancing area.
Question 3
In adult patients (aged 65 and under) with newly diagnosed glioblastoma, is a tailored target volume superior to regional RT for reduction of radiation-induced toxicity while maintaining efficacy?
Recommendation
Level II: It is recommended that radiation therapy planning include 1–2 cm margin around the radiographically T1 weighted contrast-enhancing tumor volume or the T2 weighted abnormality on MRI.
Level III: Recalculation of the radiation volume during RT treatment may be necessary to reduce the radiated volume of normal brain since the volume of surgical defect will change during the long period of RT.
Question 4
In adult patients (aged 65 and under) with newly diagnosed glioblastoma, does the addition of RT of the subventricular zone to standard tumor volume treatment improve tumor control and overall survival?
Recommendation
No recommendation can be formulated as there is contradictory evidence in favor of and against intentional radiation of the subventricular zone (SVZ)
Question 5
In elderly (age > 65 years) and/or frail patients with newly diagnosed glioblastoma, does the addition of RT to surgical intervention improve disease control and overall survival?
Recommendation
Level I: Radiation therapy is recommended for treatment of elderly and frail patients with newly diagnosed glioblastoma to improve overall survival.
Question 6
In elderly (age > 65 years) and/or frail patients with newly diagnosed glioblastoma, does modification of RT dose and fractionation scheme from standard regimens decrease toxicity and improve disease control and survival?
Recommendation
Level II: Short RT treatment schemes are recommended in frail and elderly patients as compared to conventional 60 Gy given in 2 daily fractions because overall survival is not different while RT risk profile is better for the short RT scheme.
Level II: The 40.05 Gy dose given in 15 fractions or 25 Gy dose given in 5 fractions or 34 Gy dose given in 10 fractions should be considered as appropriate doses for Short RT treatments in elderly and/or frail patients.
Question 7
In adult patients with newly diagnosed glioblastoma is there advantage to delaying the initiation of RT instead of starting it 2 weeks after surgical intervention in decreasing radiation-induced toxicity and improving disease control and survival?
Recommendation
Level III: It is suggested that RT for patients with newly diagnosed GBM starts within 6 weeks of surgical intervention as compared to later times. There is insufficient evidence to recommend the optimal specific post-operative day within the 6 weeks interval to start RT for adult patients with newly diagnosed glioblastoma that have undergone surgical resection.
Question 8
In adult patients with newly diagnosed supratentorial glioblastoma is Image-Modulated RT (IMRT) or similar techniques as effective as standard regional RT in providing tumor control and improve survival?
Recommendation
Level III: There is no evidence that IMRT is a better RT delivering modality when compared to conventional RT in improving overall survival in adult patients with newly diagnosed glioblastoma. Hence, IMRT should not be preferred over the Conventional RT delivery modality.
Question 9
In adult patients with newly diagnosed glioblastoma does the use of radiosensitizers with RT improve the efficacy of RT as determined by disease control and overall survival?
Recommendation
Level III: Iododeoxyuridine is not recommended to be used as radiosensitizer during RT treatment for patients with newly diagnosed GBM
Question 10
In adult patients with newly diagnosed glioblastoma is the use of Ultrafractionated RT superior to standard fractionation regimens in improving disease control and survival?
Recommendation
There is insufficient evidence to formulate a recommendation regarding the use of ultrafractionated RT schemes and patient population that could benefit from it.
Question 11
In patients with poor prognosis with newly diagnosed glioblastoma is hypofractionated RT indicated instead of a standard fractionation regimen as measured by extent of toxicity, disease control and survival?
Recommendation
Level I: Hypofractionated RT schemes may be used for patients with poor prognosis and limited survival without compromising response. There is insufficient evidence in the literature for us to be able to recommend the optimal hypofractionated RT scheme that will confer longest overall survival and/or confer the same overall survival with less toxicities and shorter treatment time.
Question 12
In adult patients with newly diagnosed glioblastoma is the addition of brachytherapy to standard fractionated RT indicated to improve disease control and survival?
Recommendation
Level I: Brachytherapy as a boost to external beam RT has not been shown to be beneficial and is not recommended in the routine management of patients with newly diagnosed GBM.
Question 13
In elderly patients (> 65 year old) with newly diagnosed glioblastoma under what circumstances is accelerated hyperfractionated RT indicated instead of a standard fractionation regimen as measured by extent of toxicity, disease control and survival?
Recommendation
Level III: Accelerated Hyperfractionated RT with a total RT dose of 45 Gy or 48 Gy has been shown to shorten the treatment time without detriment in survival when compared to conventional external beam RT and should be considered as an option for treatment of elderly patients with newly diagnosed GBM.
Question 14
In adult patients with newly diagnosed glioblastoma is the addition of Stereotactic Radiosurgery (SRS) boost to conventional standard fractionated RT indicated to improve disease control and survival?
Recommendation
Level I: Stereotactic Radiosurgery boost to external beam RT has not been shown to be beneficial and is not recommended in patients undergoing routine management of newly diagnosed malignant glioma.