放疗机制与副作用防控(专业版)
放疗是指利用放射线(辐射)治疗肿瘤的一种局部治疗方法。放射线包括同位素产生的α、β、γ射线和各类x射线治疗机或加速器产生的x射线、电子线、质子束及其他粒子束等。
英文名称:Cancer Radiation Therapy
然而,放疗的主要挑战之一是很难仅对癌细胞进行治疗。辐射还会损害肿瘤附近的健康细胞,并引起副作用,因而限制患者可以耐受的放射量。随着新兴技术发展,质子疗法和射波刀疗法可提高治疗精度、最大限度地减少对健康细胞组织损害。此外,研究人员也在开发诸如治疗性高温的方法,以使癌细胞对放射线更加敏感。
研究表明,结合放射疗法几种自然干预措施可以抵消某些副作用,包括益生菌可以缓解辐射引起的腹泻,乳香有助于改善脑水肿,蔓越莓则可减轻膀胱炎症,金盏花局部使用可以缓解皮肤灼伤等。此外,姜黄素、金雀异黄酮(染料木素)和白藜芦醇等一些天然产物可能促进癌细胞对辐射的敏感度。
1.外束放射疗法
外部束放射疗法(EBRT)是最广泛使用的放疗方法。使用线性加速器(LINAC)的机器将辐射束传递到肿瘤。随着时间推移,专门针对肿瘤和相关健康组织的技术得到了改善。不过,对健康组织的损伤仍然是存在的。
EBRT可以通过多种方式交付:
质子束放疗或“质子疗法”是最精确和复杂的外部束放射疗法之一。质子是亚原子粒子,由于其物理特性,它们以独特的方式与人体组织相互作用。与标准放射疗法相比,质子束的物理性质使技术人员可以更好地瞄准肿瘤并将高强度放射线选择性地传递到肿瘤组织。质子疗法可以最大程度地减少对肿瘤外部健康组织的损害。
标准的外束放疗穿透包括健康组织在内的身体,高剂量进入人体,然后在穿过和离开人体时消散。相反,当一束质子进入人体时,质子在接近目标时会释放能量,然后停止移动。因此,对健康组织的辐射剂量被最小化,副作用得以减少。质子治疗由于其靶向递送而使其总辐射剂量比其他形式的外部束光子辐射低约60%。
质子治疗适用于边界明确的实体瘤患者,因为它以精确的光束传输到特定区域。根据美国临床肿瘤学会的资料,目前接受质子治疗的癌症包括如下:
2.近距离放疗或内部放射
近距离放射疗法涉及将放射性物质插入肿瘤周围或内部的体内。临时或永久插入诸如放射状的小颗粒、金属丝、胶囊或试管之类的设备,使辐射能传递到肿瘤内部。在某些情况下,影像技术可用于指导近距离放射治疗设备的放置。
近距离放射疗法越来越多地用于治疗前列腺癌(Heysek 2007),但也用于宫颈癌、子宫癌、乳腺癌、头颈癌、皮肤癌以及其他几种癌症。放射栓塞术是一种用于肝癌的技术,其中将称为微球体的放射性珠粒注入喂养肿瘤的动脉中。
近距离放射治疗植入物可能会保留数分钟至数天,或者在某些情况下会永久保留。植入设备发出的辐射强度还可以根据每个患者的需求而变化。
3.全身放疗
放射性药物是含有放射性同位素的药物。它们口服或静脉内给药。放射性药物可用于治疗癌症,还能用作成像检查的示踪剂以确定肿瘤的位置。例如;锶89(Metastron)、铊153(Quadramet)和镭223(Xofigo)用于治疗骨转移包括乳腺癌和前列腺癌的骨转移,碘131用于治疗甲状腺癌。
放射免疫疗法使用放射性同位素的单克隆抗体。这些抗体靶向癌细胞表面上的分子,将其放射性有效载荷传递给恶性细胞。放射免疫疗法在治疗非霍奇金B细胞淋巴瘤方面显示出希望,但尚未证明对实体瘤有效。在某些放射免疫疗法产品中观察到的一个重要的副作用包括白细胞和血小板计数的下降。
附:批准的放射防护药物
已有两种药物被美国FDA批准用于防止辐射损伤和最小化放疗的副作用。
在放疗中使用具有中和自由基能力的营养素(即抗氧化剂)是有争议的1。放射肿瘤学研究人员和从业人员提出的主要担忧是,抗氧化剂可以保护癌症细胞免受活性氧的破坏作用,活性氧是由辐射形成的,是放疗对癌症抑制作用的组成部分2。这可能是由于抗氧化剂直接清除活性氧或修复肿瘤细胞中的细胞损伤3,4。虽然这在理论上可能是正确的,但生物化学要复杂得多。如多项研究所示,维生素和被归类为抗氧化剂的天然化合物也具有额外的生化和药理学作用,可能有益于放射治疗5。一些作者采取保守的方法,建议接受癌症治疗的患者避免使用高剂量抗氧化剂3,6,并进行更多的人体临床试验,以确定单独和联合抗氧化剂剂量的安全性和有效性7,8。然而,文献综述发现,在绝大多数研究中,没有证据表明癌症患者使用膳食抗氧化剂会降低生存率或治疗反应。相反,这些相同的综述确定了放疗和化疗减少治疗相关副作用的实质性证据6,9,10,11,12。
合成处方抗氧化剂,如阿米福汀、甲磺酸钠(如Mesnex)和右唑烷(Zinecard)已用于各种化疗和放疗方案,具有有益效果,但在临床研究中没有证据表明它们对肿瘤存在保护作用1,13,14。多种常用的常规药物具有抗氧化能力,但缺乏对干扰治疗风险的大规模研究。其中一些药物,包括皮质类固醇,与化疗一起服用,以抵消治疗的副作用15,16。
2.具有抗氧化特性的天然化合物
补充抗氧化剂可能有助于保护正常细胞免受放疗引起的损伤和副作用的增加17,2。此外,抗氧化剂水平在癌症治疗后下降6,18。补充膳食抗氧化剂,如维生素C和E,可以通过增加肿瘤反应和降低对正常细胞的辐射毒性来提高放射治疗的疗效19。膳食抗氧化剂,包括维生素C和E、硒(抗氧化剂硒蛋白的一种成分),以及细胞内发现的抗氧化酶,如超氧化物歧化酶和谷胱甘肽过氧化物酶,可以帮助在活性氧的理想和不理想影响之间保持适当的平衡20。
尽管人们担心在放疗中使用抗氧化剂,但研究表明,补充抗氧化剂可以与放射治疗相结合安全使用。例如,在一项对134名患有早期前列腺癌症的男性进行的回顾性研究中,各种抗氧化剂并没有干扰放射治疗。高剂量抗氧化剂不会干扰辐射的证据是基于五年或五年以上前列腺特异性抗原(PSA)的随访测量。抗氧化剂组和未接受抗氧化剂治疗的组的PSA水平相似21。在383名接受前列腺癌症放射治疗的男性的试验中,β-胡萝卜素不干扰治疗。长期随访未显示使用β-胡萝卜素增加前列腺癌症或转移的死亡风险22。
辐射对正常组织的影响通常分为两类:“早期”和“晚期”反应。早期或急性影响在放射治疗的90天内发展,并在治疗完成后持续2-3周。晚期效应在几个月或几年后出现,通常在90天后,并可能持续一生。早期影响主要发生在高周转组织中,如皮肤、胃肠道、泌尿道和骨髓。晚期效应主要发生在缓慢生长的组织中,如肺、心脏、肝脏和神经系统。这些影响受到几个因素的影响,包括总辐射剂量、照射场、分次大小、分次间隔时间、同时给予化疗、诊断时的年龄、组织愈合能力和遗传学55,56,57。
1.头、颈部放疗副作用
1). 脑水肿:辐射可能导致脑水肿,症状通常包括头痛、恶心和呕吐58。脑水肿的典型治疗方法包括皮质类固醇如地塞米松58,59,但皮质类固醇的副作用可能会限制其使用。此外,已提出了其他疗法包括贝伐单抗(Avastin),它是一种用于治疗多种癌症的抗血管生成剂。然而,贝伐单抗具有很高的潜在严重并发症发生率60。
可能采用的自然干预策略如下:
可能采用的自然干预措施如下:
3).口腔粘膜炎:根据治疗方案,60%至100%接受头颈部癌症放疗的患者会出现口腔粘膜炎。其症状包括溃疡、发红、口腔疼痛和吞咽疼痛74。粘膜炎通常在放疗的第二周后出现,并可能在治疗结束后持续数周75。口腔粘膜炎可导致继发性并发症,包括感染、营养摄入不足和口干等。保持良好的口腔卫生,包括刷牙、使用牙线和漱口,对预防口腔粘膜炎很重要74。
可能采用的营养干预策略如下:
2.胸部放疗副作用
1). 食道炎: 放疗结束后,急性放射性食管炎可持续一至三周,并可导致吞咽困难、吞咽疼痛和胸痛。粘膜炎和溃疡可引起明显症状;食管狭窄是一种晚期并发症,可在放疗后三到八个月发生。同时化疗可能会增加患急性食管炎的风险。严重的食管炎可能导致住院、管饲和治疗中断92。
研究用于治疗心脏纤维化的化合物可以减少心血管并发症:
3). 肺毒性:肺部是放射最敏感的器官之一,相关的副作用严重影响治疗结果104。放射性肺炎或肺部炎症是放疗后前六个月常见的急性副作用,发生在13-37%的患者中105。放射治疗诱导的纤维化通常发生在放射治疗后六个多月,并与肺部瘢痕形成有关。皮质类固醇和抗生素是缓解这些晚期副作用的主要治疗方法105。
贫血是指红细胞或血红蛋白不足,无法向组织充分输送氧气的状况。研究表明,接受治疗的癌症患者中有40-64%患有贫血122。血红蛋白水平低的癌症患者对放疗的反应不如非癌症患者,因为肿瘤细胞没有接受足够的氧气123。低肿瘤氧和低血氧可增强肿瘤生长并产生治疗耐药性122。治疗期间测量的血红蛋白值可以预测患者对治疗的反应。吸烟会导致血红蛋白下降和治疗效果较差,应避免吸烟以提高放射治疗的疗效123。
严重的贫血可以通过输血或药物红细胞生成素(Procrit)进行治疗,这是一种能使血红蛋白水平稳定、持续升高的生长因子。然而,尽管这些方法可能会改善贫血,但研究尚未表明它们能改善与肿瘤控制相关的结果123。
一项对103名癌症宫颈癌患者的研究表明,在顺铂(化疗药)和放疗期间补充抗氧化剂可以减少氧化应激,提高血红蛋白水平和生活质量。使用的抗氧化剂剂量包括每天4.8mgβ-胡萝卜素、10 mg维生素C、200 IU维生素E和15mcg硒124。
4.腹部辐射及相关副作用
1). 胃肠道粘膜炎: 胃肠道、泌尿系统和妇科癌症的腹部或骨盆辐射可导致急性或慢性胃肠道副作用。急性肠炎(肠道炎症)的特征是在放疗期间或放疗后不久出现腹泻、腹痛、腹胀、食欲不振、恶心和大便紧迫感。这些症状通常在放射治疗的第二周开始,并在完成治疗后的三个月内消退。大约15-20%的患者需要改变治疗方案以降低症状的严重程度。慢性小肠放射病可在放射治疗后18个月至6年发展,包括进食后疼痛、急性或间歇性小肠梗阻、恶心、体重减轻、食欲不振、腹胀、腹泻、脂肪便和营养吸收不良等症状。胆汁盐吸收不良、小肠细菌过度生长(SIBO)和乳糖不耐受也可能发生126。
可能采取的自然干预措施如下:
一项针对206名接受腹部和骨盆癌症放射治疗的患者的随机、双盲、安慰剂对照研究表明,与服用安慰剂的患者相比,每天三次服用15亿CFU鼠李糖乳杆菌的患者腹泻减少,所需的抗腹泻药物更少、更晚135。
2017年一项对六项试验的荟萃分析证实了益生菌对腹部或骨盆区域癌症患者的益处136。一般来说,指南建议含有乳酸杆菌的益生菌用于预防盆腔癌放射性腹泻74。
立体定向身体放射治疗是一种相对较新的放射技术,为脑外肿瘤提供高效的放射剂量145。当机器人立体定向身体放射治疗用于治疗某些不可切除(无法通过手术完全切除)的肝脏肿瘤时,放射性肝病的发生率较低,症状自行消退147。
1).盆腔辐射病:也称为胃肠道辐射引起的毒性,可造成短暂或长期的问题。即使使用辐射技术来保护健康组织,如强度调节放射治疗(IMRT),损伤仍然可能发生;此外,损伤可能在几十年后发生157。有关的自然干预措施,请参阅上述“胃肠道粘膜炎”一节内容。
2). 放射性直肠病:这是一种并发症,表现为直肠粘膜损伤、疤痕和组织死亡,有时被称为放射性直肠炎158。在接受前列腺癌、直肠癌、膀胱癌、睾丸癌、宫颈癌和子宫癌盆腔放射治疗的患者中,有5-20%会发生这种并发症。虽然它可以自发愈合,但慢性辐射性直肠病会导致慢性问题,如里急后重(粪便紧迫感伴痉挛样直肠疼痛)、腹泻和直肠出血159。
可能采取的营养干预措施如下:
1).急性放射性皮炎:皮炎是放射治疗的常见副作用,严重程度取决于许多因素,包括更大的治疗范围、更多的总辐射剂量和更长的治疗时间。皮炎症状包括发红(红斑)、疼痛和皮肤剥落(脱屑)。接受放射治疗的患者中,高达95%的患者会出现皮肤变化,这可能会限制患者后续治疗173。可能采用的自然疗法包括如下:
2). 辐射诱发的纤维化: 纤维化或结缔组织增厚是放疗的一种严重晚期影响,可影响皮肤186(Bray 2016)。在乳腺癌患者放疗后出现放射性纤维化的22名患者每天口服800mg己酮可可碱和1000IU维生素E。六个月后,辐射诱导的纤维化面积显著减少,未发现不良反应187。有关纤维化的更多信息,可参阅本文的“肺毒性”部分。
3). 淋巴水肿:淋巴水肿是富含蛋白质的淋巴液的积聚,导致下层皮肤肿胀189。例如,在乳腺癌放疗后,如果淋巴引流被无意中堵塞或切断,手臂可能会出现肿胀。淋巴水肿会导致疼痛、感染风险增加和患肢体积增加190。开始治疗前的肥胖会增加患淋巴水肿的几率191。可能采用的自然干预措施包括如下:
4). 疲劳:高达80%的患者在接受放射治疗时会出现疲劳。在完成放疗后,疲劳会持续存在。据报道,30%的患者在随访期间会出现疲劳。辐射诱发疲劳的机制尚不清楚194。放疗过程中的疲劳被描述为感觉疲劳、虚弱和疲惫。在某些情况下,疲劳可能是贫血、焦虑或抑郁、缺乏活动、药物副作用或感染的下游影响195。
可能采取的自然疗法如下:
5). 恶心和呕吐:放疗引起的恶心和呕吐大多数发生在对上腹部、肝脏和大脑的辐射中,尽管也可能发生在身体其他部位的辐射。同时接受化疗的患者,放疗引起的恶心和呕吐加重199。如果不加以治疗,恶心和呕吐会导致生理变化,包括脱水、电解质失衡、营养不良和恶病质。
可能采取的自然干预措施包括如下:
7.恶病质和食欲不振
恶病质是指脂肪和肌肉组织的快速流失,可能会对患者的生活质量和对治疗的反应产生负面影响203。癌症恶病质是由涉及分子TNF-α和IL-6的炎性反应引起的,它们在辐射抗性中起作用。因此,抑制恶病质的治疗还可以增加肿瘤的放射敏感性,从而提高生存率204。
接受放化疗的、无法手术的头颈癌和食道癌患者容易出现体重减轻和恶病质,有时会在治疗开始前出现205。辐射引起的副作用,如恶心、呕吐、食道炎、粘膜炎和腹泻,会限制患者的进食或吸收营养的能力,从而加重恶病质203。
可能采取的自然干预措施包括如下:
低血细胞计数通常与辐射无关,除非出血过多或辐射影响到产生血细胞的骨髓。贫血在上述内容中已有讨论。可能采用的自然干预措施包括如下:
尽管近年来,原发性癌治疗后的长期生存率显著增加,但癌症治疗最严重的副作用之一是新肿瘤的发展208。在美国,继发性癌症占所有癌症的18%,其中8%是放射治疗引起的。其他被认为是遗传因素、衰老和生活方式结果209。
继发恶性肿瘤的风险可能直接发生在辐射区域或身体其他部位210。该风险是剂量依赖性的,当辐射暴露发生在较年轻的年龄时,风险似乎更高211;潜伏期长,例如,放射治疗后5至9年患白血病的风险通常最高,实体瘤的间隔时间超过10年,通常为几十年212。
总体而言,继发性癌症的风险通常较低,放疗对患者的益处大于发展为继发肿瘤的风险212。由于一些研究已经确定了某些类型原发性癌症的继发性癌症的常见部位,在某些情况下,这为医生提供了加强监测并尝试在早期发现继发性癌的机会213。
一般来说,戒烟、控制体重和身体运动有助于预防继发性癌症的发展209。事实上,一项针对癌症头部和颈部患者的大型研究表明,吸烟会显著增加患继发性癌症和死亡的风险214。
许多实验室或临床试验表明,一些天然化合物可以增强肿瘤对放疗的敏感性。自然干预措施与放疗一起使用可改善治疗效果,包括如下:
了解癌症更多的治疗及防控方法,可参考本网如下专文:
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概述
放疗是指利用放射线(辐射)治疗肿瘤的一种局部治疗方法。放射线包括同位素产生的α、β、γ射线和各类x射线治疗机或加速器产生的x射线、电子线、质子束及其他粒子束等。它能精确地传递高能放射,以杀死癌细胞并缩小肿瘤。放疗、化疗、手术治疗以及免疫疗法组成癌症的主要治疗方法,超过50%的癌症患者需要接受放射治疗。然而,放疗的主要挑战之一是很难仅对癌细胞进行治疗。辐射还会损害肿瘤附近的健康细胞,并引起副作用,因而限制患者可以耐受的放射量。随着新兴技术发展,质子疗法和射波刀疗法可提高治疗精度、最大限度地减少对健康细胞组织损害。此外,研究人员也在开发诸如治疗性高温的方法,以使癌细胞对放射线更加敏感。
研究表明,结合放射疗法几种自然干预措施可以抵消某些副作用,包括益生菌可以缓解辐射引起的腹泻,乳香有助于改善脑水肿,蔓越莓则可减轻膀胱炎症,金盏花局部使用可以缓解皮肤灼伤等。此外,姜黄素、金雀异黄酮(染料木素)和白藜芦醇等一些天然产物可能促进癌细胞对辐射的敏感度。
放疗简介
放疗可实现癌症治疗的多个目标,包括缩小早期肿瘤、预防特定部位的癌症复发以及最大程度地减少症状等。尽管放射线对准肿瘤治疗,但是其周围的健康组织也将不可避免地受到影响。放疗旨在最大程度地增加对肿瘤细胞的辐射剂量,同时对健康细胞的剂量最小化,从而减少副作用。多数情况下,放疗需要与手术、化疗或免疫疗法相结合以治疗癌症。- 辐射如何杀死癌细胞和影响健康组织:
- 糖尿病放疗通常使用高能辐射(X射线)来破坏癌细胞,它能产生高反应性的自由基而损毁DNA、阻止癌细胞分裂。癌细胞通常比健康细胞分裂更快,因此更容易受到辐射的影响。健康细胞通常可以比癌细胞更快地修复辐射诱发的损伤。
- 放疗不会立即杀死癌细胞。癌细胞开始死亡需要数小时、数天甚至数周的时间。放疗结束后,癌细胞继续死亡数周至数月。这种延迟的作用也适用于健康细胞,这可以解释为什么某些副作用需要时间才能显现出来。快速分裂的细胞,例如皮肤、骨髓和肠壁细胞,通常最快显示出损伤迹象。更新较慢的细胞,例如来自大脑和脊髓的细胞,影响则在后来才能表现出来。
- 放疗剂量分割与治疗周期
随着时间进展,放射治疗通常需要分阶段进行。治疗疗程称为“分割(Fraction)”,这种治疗策略对于最大化有效性和最小化对正常组织的损害是必需的。分割放疗使正常细胞有时间在每次放疗之间从辐射诱发的损伤中恢复,同时分割增加了癌细胞在最容易受到DNA损伤的细胞周期中暴露于辐射的可能性。此外,可能已经缺氧(低氧状态)的肿瘤组织可以在分割之间重新充氧。因为氧气的存在可增加杀灭癌细胞的自由基产生,因此这可能会增加辐射在下一个治疗阶段杀死肿瘤细胞的可能性。
在大多数患者中,分割治疗通常需要每周五天、五到八周的周期,当然治疗方案取决于每位患者的独特情况。
在大多数患者中,分割治疗通常需要每周五天、五到八周的周期,当然治疗方案取决于每位患者的独特情况。
- 放疗涉及的5个关键因素:
许多因素可影响肿瘤对放疗的反应。为了尽可能达到放疗治疗目的,需要综合考虑到5个关键因素—即放射肿瘤学的5R概念,它能更好地理解影响肿瘤反应的细胞特征:
- 修复(Repair)):健康细胞和癌细胞都具有修复辐射造成的损伤的机制。这既有利于健康细胞,却可能导致癌症治疗失败。已被破坏的癌细胞DNA修复机制可能更容易受到辐射的影响,这就是在某些情况下用于癌症治疗的DNA修复抑制剂的基础。
- 重新分配(Redistribution):包括癌细胞的大多数细胞都需要经历细胞周期的复制过程。当细胞为新细胞复制其DNA时,其对辐射的敏感性最低(S期),而当它们分裂为两个细胞时,其敏感性则最高(有丝分裂期)。由于细胞处于细胞复制周期的所有阶段中,因此给予分割剂量放射可增加在一个放射治疗阶段中处于放射抗性S期的癌细胞在随后阶段中处于敏感阶段(有丝分裂期)的可能性。
- 重新繁殖(Repopulation):在施行放疗剂量之间,健康和恶性的活细胞分裂并重新繁殖。健康的细胞重新繁殖是可取的,但是新繁殖的癌细胞会导致治疗失败。放疗之间的长时间停顿可导致癌细胞重新聚集。这就是为什么坚持按计划的放疗分割是如此重要的原因之一。
- 复氧(Reoxygenation):肿瘤细胞中氧的存在增加了对放射的敏感性,因为氧分子与辐射反应生成可杀死细胞的自由基。肿瘤细胞缺氧(或低氧)与不良的治疗预后有关。放疗(尤其是大剂量)会导致肿瘤缺氧,因此必须允许肿瘤在化疗分割之间重新充氧,以避免抗辐射的低氧细胞。复氧可能需要数小时至数天。
- 放射敏感性(Radiosensitivity):某些癌症自然地比其他癌症更容易受到辐射的影响。例如,肾细胞癌和黑色素瘤通常比其他癌症更耐放射,而霍奇金淋巴瘤和头颈癌则对辐射具有高度敏感性。
放疗实施方法
放疗可以通过多种方法进行,包括外束放射、近距离放射或内部放射治疗,以及放射性药物或全身放射治疗。1.外束放射疗法
外部束放射疗法(EBRT)是最广泛使用的放疗方法。使用线性加速器(LINAC)的机器将辐射束传递到肿瘤。随着时间推移,专门针对肿瘤和相关健康组织的技术得到了改善。不过,对健康组织的损伤仍然是存在的。
EBRT可以通过多种方式交付:
- 三维适形放射治疗(3D-CRT):使用成像计算机在三个维度上精确绘制肿瘤的位置,目前是全世界诊所使用的EBRT的主要形式。通过将辐射精确地对准肿瘤,可以减少对正常组织的辐射损害。
- 调强放射治疗(IMRT):与3D-CRT类似。但是,IMRT可在某些区域改变辐射束的强度,从而在肿瘤的某些区域增加辐射束的强度,以免对健康组织造成不必要的损伤。
- 影像引导放射疗法(IGRT):将放射线与成像扫描仪结合在一起,使医生可以在施行放射线之前查看是否需要进行细微调整。
- 术中放射疗法(IORT):在外科手术过程中传递给肿瘤的外部放射,尤其适用于体内深处的癌症。
- 立体定向放射外科(SRS):向小肿瘤(通常在大脑或颅骨内)提供大剂量的放射,并且不涉及任何手术。立体定向放疗(SBRT)在人体的某些部位使用此技术,包括脊柱、肝脏和肺部。SRS和SBRT使用伽马刀的机器,该机器可以从许多不同的角度发射多束光束。其他机器,包括射波刀(CyberKnife)或X刀(X-Knife),都结合了先进的摄像头来定位肿瘤在人体中的位置,并结合了机器人技术以在肿瘤处提供高度集中的辐射束。所有这些技术都旨在避免正常组织受损。
质子束放疗或“质子疗法”是最精确和复杂的外部束放射疗法之一。质子是亚原子粒子,由于其物理特性,它们以独特的方式与人体组织相互作用。与标准放射疗法相比,质子束的物理性质使技术人员可以更好地瞄准肿瘤并将高强度放射线选择性地传递到肿瘤组织。质子疗法可以最大程度地减少对肿瘤外部健康组织的损害。
标准的外束放疗穿透包括健康组织在内的身体,高剂量进入人体,然后在穿过和离开人体时消散。相反,当一束质子进入人体时,质子在接近目标时会释放能量,然后停止移动。因此,对健康组织的辐射剂量被最小化,副作用得以减少。质子治疗由于其靶向递送而使其总辐射剂量比其他形式的外部束光子辐射低约60%。
质子治疗适用于边界明确的实体瘤患者,因为它以精确的光束传输到特定区域。根据美国临床肿瘤学会的资料,目前接受质子治疗的癌症包括如下:
- 某些脑癌
- 眼黑素瘤
- 头颈癌
- 肺癌
- 肝癌
- 前列腺癌
- 脊柱和盆腔肉瘤
2.近距离放疗或内部放射
近距离放射疗法涉及将放射性物质插入肿瘤周围或内部的体内。临时或永久插入诸如放射状的小颗粒、金属丝、胶囊或试管之类的设备,使辐射能传递到肿瘤内部。在某些情况下,影像技术可用于指导近距离放射治疗设备的放置。
近距离放射疗法越来越多地用于治疗前列腺癌(Heysek 2007),但也用于宫颈癌、子宫癌、乳腺癌、头颈癌、皮肤癌以及其他几种癌症。放射栓塞术是一种用于肝癌的技术,其中将称为微球体的放射性珠粒注入喂养肿瘤的动脉中。
近距离放射治疗植入物可能会保留数分钟至数天,或者在某些情况下会永久保留。植入设备发出的辐射强度还可以根据每个患者的需求而变化。
3.全身放疗
放射性药物是含有放射性同位素的药物。它们口服或静脉内给药。放射性药物可用于治疗癌症,还能用作成像检查的示踪剂以确定肿瘤的位置。例如;锶89(Metastron)、铊153(Quadramet)和镭223(Xofigo)用于治疗骨转移包括乳腺癌和前列腺癌的骨转移,碘131用于治疗甲状腺癌。
放射免疫疗法使用放射性同位素的单克隆抗体。这些抗体靶向癌细胞表面上的分子,将其放射性有效载荷传递给恶性细胞。放射免疫疗法在治疗非霍奇金B细胞淋巴瘤方面显示出希望,但尚未证明对实体瘤有效。在某些放射免疫疗法产品中观察到的一个重要的副作用包括白细胞和血小板计数的下降。
附:批准的放射防护药物
已有两种药物被美国FDA批准用于防止辐射损伤和最小化放疗的副作用。
- 氨磷汀(Ethyol):一种合成抗氧化剂,最初用于在发生核战争时防止辐射。这种药物可降低接受放射治疗的头颈癌患者中度至重度口腔干燥症(口干)的发生率。氨磷汀还可以减少口疮和吞咽困难的发生率。此外,还可降低放射治疗患者的皮炎、消化道粘膜炎和肺炎等副作用。重要的是,氨磷汀不能保护肿瘤免受放射疗法的毒性影响,也不会降低生存率。氨磷汀可能引起恶心、呕吐、短暂性低血压或过敏反应,从而限制了其使用。
- 帕利夫明(Kepivance)是可注射的重组人类生长因子。 帕利夫明于2004年被FDA批准用于某些因放疗或化学疗法而导致严重口腔粘膜炎的癌症患者。在临床试验中,其最重要的不良反应包括皮疹、瘙痒和与皮肤相关的肿胀。
降低辐射损伤的抗氧化剂
1.放疗与抗氧化剂和放疗:持续的争议在放疗中使用具有中和自由基能力的营养素(即抗氧化剂)是有争议的1。放射肿瘤学研究人员和从业人员提出的主要担忧是,抗氧化剂可以保护癌症细胞免受活性氧的破坏作用,活性氧是由辐射形成的,是放疗对癌症抑制作用的组成部分2。这可能是由于抗氧化剂直接清除活性氧或修复肿瘤细胞中的细胞损伤3,4。虽然这在理论上可能是正确的,但生物化学要复杂得多。如多项研究所示,维生素和被归类为抗氧化剂的天然化合物也具有额外的生化和药理学作用,可能有益于放射治疗5。一些作者采取保守的方法,建议接受癌症治疗的患者避免使用高剂量抗氧化剂3,6,并进行更多的人体临床试验,以确定单独和联合抗氧化剂剂量的安全性和有效性7,8。然而,文献综述发现,在绝大多数研究中,没有证据表明癌症患者使用膳食抗氧化剂会降低生存率或治疗反应。相反,这些相同的综述确定了放疗和化疗减少治疗相关副作用的实质性证据6,9,10,11,12。
合成处方抗氧化剂,如阿米福汀、甲磺酸钠(如Mesnex)和右唑烷(Zinecard)已用于各种化疗和放疗方案,具有有益效果,但在临床研究中没有证据表明它们对肿瘤存在保护作用1,13,14。多种常用的常规药物具有抗氧化能力,但缺乏对干扰治疗风险的大规模研究。其中一些药物,包括皮质类固醇,与化疗一起服用,以抵消治疗的副作用15,16。
2.具有抗氧化特性的天然化合物
补充抗氧化剂可能有助于保护正常细胞免受放疗引起的损伤和副作用的增加17,2。此外,抗氧化剂水平在癌症治疗后下降6,18。补充膳食抗氧化剂,如维生素C和E,可以通过增加肿瘤反应和降低对正常细胞的辐射毒性来提高放射治疗的疗效19。膳食抗氧化剂,包括维生素C和E、硒(抗氧化剂硒蛋白的一种成分),以及细胞内发现的抗氧化酶,如超氧化物歧化酶和谷胱甘肽过氧化物酶,可以帮助在活性氧的理想和不理想影响之间保持适当的平衡20。
尽管人们担心在放疗中使用抗氧化剂,但研究表明,补充抗氧化剂可以与放射治疗相结合安全使用。例如,在一项对134名患有早期前列腺癌症的男性进行的回顾性研究中,各种抗氧化剂并没有干扰放射治疗。高剂量抗氧化剂不会干扰辐射的证据是基于五年或五年以上前列腺特异性抗原(PSA)的随访测量。抗氧化剂组和未接受抗氧化剂治疗的组的PSA水平相似21。在383名接受前列腺癌症放射治疗的男性的试验中,β-胡萝卜素不干扰治疗。长期随访未显示使用β-胡萝卜素增加前列腺癌症或转移的死亡风险22。
- β-胡萝卜素、维生素E与吸烟:接受放射治疗的吸烟者应避免使用β-胡萝卜素和α-生育酚,因为放射治疗的有效性降低,结果更糟23。对540名癌症头颈部患者进行了一项研究,他们接受放射治疗,同时每天服用400IU的dl-α-生育酚(维生素E的一种形式)和30mg的β-胡萝卜素。结果显示,在接受抗氧化剂的组中,辐射的副作用和有效性降低24。对相同数据的重新评估显示,只有在放射治疗期间吸烟的参与者才会发现辐射有效性降低,最终结论是吸烟者在接受放射治疗时不应服用抗氧化剂23,11。
- 锌:对于伴有化疗和放疗的鼻咽癌患者,锌可以提高五年总生存率并减少局部复发。34名癌症III或IV期患者接受了放化疗和75mg锌或安慰剂治疗,为期两个月。锌组的五年无病生存率高于安慰剂组。然而,两组之间的五年无转移生存率没有显著差异,这可能是由于疾病的晚期性质25。
- 硒:硒的放疗增敏和放疗防护特性已得到研究26。对硒和放疗临床研究的文献分析表明,放疗后血硒水平下降,补充硒可能会升高。研究中用于补充的剂量范围包括每天口服200至500mcg的亚硒酸钠或每天静脉注射1000mcg的亚硒酸钠。大多数补充硒研究报告称,在放疗期间服用时,生活质量有所提高,没有一项研究显示补充后的辐射有效性或毒性降低27。一项研究的作者主张在妇科癌症放射治疗之前和期间测量血清硒水平。硒缺乏的患者可以在放射治疗期间得到安全的补充28,29。一项针对在放疗期间服用硒的宫颈癌或子宫癌患者的10年随访研究表明,硒不会对放疗的有效性或长期生存产生负面影响。此外,补充硒可以减少硒缺乏患者的放射治疗引起的腹泻29。
从头颈部鳞状细胞癌标准治疗(手术和/或放疗)的第一天开始,每天补充200mcg的亚硒酸钠,持续八周,在治疗期间和治疗后,细胞介导的免疫反应显著增强30。
- 番茄红素:类胡萝卜素中最有效的自由基清除剂之一。一般来说,摄入与多种癌症风险的降低有关31。多项临床前研究表明,番茄红素对胃肠道细胞32、白细胞33和肝细胞34等具有放射性保护作用。
- 辅酶Q10:已被证明在癌症放射治疗中提供益处35,36。一项针对32名乳腺癌患者的研究,她们接受了不同的标准治疗,其中一些包括放射治疗,以及综合营养素,其中含有90mg辅酶Q10、2850mg维生素C、2500IU维生素E、32.5IUβ-胡萝卜素、387mcg硒、1.2gγ-亚麻酸、3.5gω-3脂肪酸,以及其他维生素和矿物质,发现远处转移减少,长期生存率增加。此外,参与者的生活质量有所提高。根据统计模型,预计有4人死亡,但在18个月的随访期内没有死亡37。在一项针对大鼠的研究中,相对低剂量的辅酶Q10显著降低了辐射后肾脏损伤的标志物38。
- 褪黑素:褪黑激素在夜间达到最高水平,并在24小时周期中由亮/暗阶段引导的昼夜节律中发挥作用39。褪黑素通常用于治疗失眠,它可以改善睡眠质量,减少与睡眠障碍相关的疲劳40。夜班工人的褪黑激素分泌可能会受到干扰,这与乳腺癌和其他癌症的风险增加有关41。
褪黑素通过清除自由基直接减少氧化损伤,并通过刺激抗氧化酶和抑制促氧化酶间接减少氧化损伤42,43。研究表明,在暴露于辐射的大鼠中,褪黑素是一种比维生素E更有效的抗氧化剂42。几项研究表明,褪黑素具有辐射保护作用43,44,45,减少辐射对哺乳动物细胞的毒性作用46。在细胞培养和动物模型中,单独施用褪黑激素抑制了几种类型的癌症细胞的生长和分裂,包括乳腺癌、结肠癌和癌症细胞41,43。除了辐射保护和抗癌作用外,褪黑激素还被证明能使乳腺癌细胞对辐射敏感47。
褪黑素可以缓解辐射诱导的器官损伤引起的症状,包括脾脏、肝脏、肺部、结肠、小肠、晶状体、脊髓和大脑42,以及肾脏48的损伤。尽管与辐射一起使用的最佳剂量尚未确定,但较高剂量的褪黑素通常具有良好的耐受性41,42,43,49。临床研究的文献综述表明,褪黑素可以提高肿瘤缓解率,延长生存期,并减少副作用,包括疲劳、神经毒性和低血小板计数。研究中最常用的剂量是20mg49,41。
胶质母细胞瘤患者通常预后不佳。一项针对无法治疗的胶质母细胞瘤患者的小型研究表明,与单独接受放射治疗的患者相比,口服褪黑素(20mg/天)并接受放射治疗患者一年生存的可能性明显更大。褪黑素治疗组也观察到辐射诱导的毒性降低,包括脱发和感染。大多数接受褪黑素治疗的患者焦虑减轻,睡眠改善,做梦更好50。
胶质母细胞瘤患者通常预后不佳。一项针对无法治疗的胶质母细胞瘤患者的小型研究表明,与单独接受放射治疗的患者相比,口服褪黑素(20mg/天)并接受放射治疗患者一年生存的可能性明显更大。褪黑素治疗组也观察到辐射诱导的毒性降低,包括脱发和感染。大多数接受褪黑素治疗的患者焦虑减轻,睡眠改善,做梦更好50。
- 黑籽油:黑孜然(Nigella sativa)原产于亚洲西南部的开花植物,是传统的药食同源植物51。其种子提取的油(黑籽油)及其活性成分胸腺醌(Thymoquinone),已在动物研究中证明可以保护健康组织免受辐射损伤52,53。此外,黑籽油本身已被证明具有抗癌特性,因此可能补充其他治疗方式54。
降低放疗副作用与自然干预
放射治疗的目标是将精确测量的辐射剂量输送到指定的肿瘤区域,对周围健康组织的损伤尽可能小。然而,放疗的一个常见副作用是对健康组织的损伤,这可能会限制患者的放射耐受量。辐射对正常组织的影响通常分为两类:“早期”和“晚期”反应。早期或急性影响在放射治疗的90天内发展,并在治疗完成后持续2-3周。晚期效应在几个月或几年后出现,通常在90天后,并可能持续一生。早期影响主要发生在高周转组织中,如皮肤、胃肠道、泌尿道和骨髓。晚期效应主要发生在缓慢生长的组织中,如肺、心脏、肝脏和神经系统。这些影响受到几个因素的影响,包括总辐射剂量、照射场、分次大小、分次间隔时间、同时给予化疗、诊断时的年龄、组织愈合能力和遗传学55,56,57。
1.头、颈部放疗副作用
1). 脑水肿:辐射可能导致脑水肿,症状通常包括头痛、恶心和呕吐58。脑水肿的典型治疗方法包括皮质类固醇如地塞米松58,59,但皮质类固醇的副作用可能会限制其使用。此外,已提出了其他疗法包括贝伐单抗(Avastin),它是一种用于治疗多种癌症的抗血管生成剂。然而,贝伐单抗具有很高的潜在严重并发症发生率60。
可能采用的自然干预策略如下:
- 乳香:已知具有多种抗炎特性的化合物。一项针对44名接受脑癌或转移放射治疗的患者的随机安慰剂对照试验显示,服用乳香提取物的患者脑水肿减轻。在治疗组中,患者从辐射的第一天开始,到最后一天结束,每天分剂量接受4200mg的乳香提取物。在MRI检查中,乳香组60%的患者水肿量仅为基线的25%,甚至没有可检测到的水肿。安慰剂组中只有26%的患者达到了最佳效果。作者评论说,水肿的减轻不仅可能是由于乳香的抗炎特性,还可能是由于抗肿瘤和放射增敏作用。作者建议对乳香的这些可能特性进行进一步的研究。乳香提取物无严重副作用;放疗疗程和地塞米松治疗剂量没有统计学差异,作者表示,乳香提取物治疗对患者没有风险61。
可能采用的自然干预措施如下:
- 褪黑素:可预防伽马射线对大鼠脑损伤的某些方面65。其他研究表明,褪黑激素可以防止辐射引起的神经生长和认知能力下降66。
- 鱼油:其中EPA等Omega-3脂肪酸具有抗炎和神经保护作用,已被证明可降低大鼠大脑中的炎症性白细胞介素-1β(IL-1β)并增加抗炎性白细胞素-10(IL-10)67。在一项临床研究中,400多名接受脑转移立体定向放疗的患者补充了ω-3脂肪酸和黄酮类化合物。患者生存时间增加,放射性坏死率降低68。
- L肉碱和维生素E:一项针对每天接受L-肉碱、维生素E或两者结合辐射的大鼠的研究表明,接受维生素E或L-肉碱的大鼠大脑和眼睛损伤减少69。L-肉碱减少了辐射对豚鼠大脑诱发的耳蜗(内耳)损伤70。
- 其他:辐射引起的大脑变化的其他有益营养素可能包括:银杏叶提取物71,72。在一项针对34名接受放射治疗的脑瘤患者的试验中,银杏叶与认知功能、注意力、注意力、记忆力和情绪的改善有关73。有关保护脑神经组织和预防认知能力下降的更多信息,可参阅本网站专文:轻度认知障碍 >>;健忘症 >>
3).口腔粘膜炎:根据治疗方案,60%至100%接受头颈部癌症放疗的患者会出现口腔粘膜炎。其症状包括溃疡、发红、口腔疼痛和吞咽疼痛74。粘膜炎通常在放疗的第二周后出现,并可能在治疗结束后持续数周75。口腔粘膜炎可导致继发性并发症,包括感染、营养摄入不足和口干等。保持良好的口腔卫生,包括刷牙、使用牙线和漱口,对预防口腔粘膜炎很重要74。
可能采用的营养干预策略如下:
- 谷氨酰胺:肠道细胞的主要能量来源,并对癌症恶病质有益76。谷氨酰胺是正常免疫功能所必需的,许多接受过大量治疗的癌症患者都缺乏谷氨酰胺77。一项针对头颈部癌症患者治疗的试验发现,口服谷氨酰胺(16g,溶于240ml生理盐水,在放射治疗期间每日四次含服)可减少放射治疗期间口腔粘膜炎的持续时间和严重程度78。另一项针对接受化疗和放疗的患者的研究发现,虽然所有患者都出现了粘膜炎,但每天三次服用10g谷氨酰胺的患者症状明显减轻79。2016年一项针对接受放射治疗的癌症头颈部患者的研究测试了每天两次使用的谷氨酰胺和精氨酸溶液。使用该溶液的组口腔粘膜炎症状有显著改善,包括口干、食欲、疼痛和吞咽问题80。
- 锌:锌是许多酶的构成成分,在抗氧化防御、组织修复和基因表达中发挥重要作用。在一项针对35名接受头颈癌放射治疗患者的随机安慰剂对照试验中,在放疗开始时,每天三次,每次50 mg硫酸锌,无论是否化疗,并在放疗后持续一个月,结果显示可以改善味觉81。一项双盲随机研究报告,在接受放射治疗的患者中,锌有利于延缓口腔粘膜炎并减轻其严重程度74。另一项研究表明,锌在预防口腔癌症患者粘膜炎方面比接受鼻咽癌放疗的患者更有益82。研究了肌肽锌作为口腔冲洗液,与不服用锌的患者相比,服用锌溶液的患者出现的粘膜炎、疼痛、口干和味觉障碍更少83。另一种形式的锌是在含片中制备的,用于接受高剂量化疗的患者,2级或更严重的口腔粘膜炎影响了74%未使用含片的患者,而使用锌含片患者仅为13%84。
- 蜂蜜:天然蜂蜜可减轻口腔粘膜炎症状。40名被诊断为头颈癌的患者被分为两组,建议一组在放疗前15分钟、放疗后15分钟和放疗后6小时用20mL纯蜂蜜漱口。受试者被要求用蜂蜜冲洗,然后慢慢吞咽,覆盖喉咙的粘膜表面。在蜂蜜治疗组中,症状性3/4级粘膜炎显著减轻,与对照组相比,体重没有变化或体重增加85。多项研究综述显示,使用蜂蜜可降低80%的口腔粘膜炎风险86。
- 蛋白酶:在一项针对头颈癌患者的临床研究中,53名患者从放射治疗前三天开始,每天服用三次蛋白水解酶片,直到治疗结束后五天。与对照组相比,蛋白酶治疗组的粘膜炎、吞咽困难和皮肤反应的严重程度显著降低87。
- 姜黄根:一项关于印度香料姜黄的研究表明,将其作为口腔粘膜炎的漱口水饮用有益。在这项随机对照试验中,80名头部和颈部癌症患者接受了为期7周的放化疗,并接受了姜黄或聚维酮碘含漱液。与聚维酮碘组相比,姜黄组的口腔粘膜炎水平显著降低。姜黄组的治疗中断发生率也有所降低,体重得到了更好的维持88。
- 绿茶:其提取物是在白血病、淋巴瘤和多发性骨髓瘤患者身上测试的漱口水中的活性成分。82%的未使用漱口水组出现口腔粘膜炎,而使用漱口水的组仅为50%89。
- 肌肽锌:使用肌肽锌溶液口服有利于缓解口干症(见上述“口腔粘膜炎”部分)83
2.胸部放疗副作用
1). 食道炎: 放疗结束后,急性放射性食管炎可持续一至三周,并可导致吞咽困难、吞咽疼痛和胸痛。粘膜炎和溃疡可引起明显症状;食管狭窄是一种晚期并发症,可在放疗后三到八个月发生。同时化疗可能会增加患急性食管炎的风险。严重的食管炎可能导致住院、管饲和治疗中断92。
- 谷氨酰胺:在三项独立的研究中,诊断为肺癌的患者每八小时服用10g谷氨酰胺粉末或不服用谷氨酰胺并结合放射治疗。谷氨酰胺治疗组食管炎病例显著减少93,94。
- 绿茶多酚:儿茶素(EGCG)是一种绿茶提取物,在放疗期间出现急性放射性食管炎时,以液体形式(440 mmol/L)口服给37名肺癌症患者,并在放疗后持续两周。EGCG降低了与食管炎相关的疼痛95。另一项研究指出,在接受EGCG(440mmol/L)治疗的24名患者中,有22名患者的食管炎严重程度显著降低96。
研究用于治疗心脏纤维化的化合物可以减少心血管并发症:
- 葡萄籽: 一项关于葡萄籽提取物作用的大鼠研究显示出对辐射引起的心脏损伤的保护作用。与未接受葡萄籽提取物的大鼠相比,在全身照射前14天每天接受葡萄籽提取液的大鼠的心脏损伤较小101。
- 橙皮苷:一种柑橘类黄酮。在全身照射后给大鼠服用7天,在用橙皮苷处理的大鼠中观察到对心脏、肝脏和肾脏的最小损伤。其他参数,包括血清酶和自由基损伤,在治疗组中也以剂量依赖的方式得到改善102。
- 黄芪:黄芪逆转了一些与辐射引起的纤维化相关的分子变化103。
3). 肺毒性:肺部是放射最敏感的器官之一,相关的副作用严重影响治疗结果104。放射性肺炎或肺部炎症是放疗后前六个月常见的急性副作用,发生在13-37%的患者中105。放射治疗诱导的纤维化通常发生在放射治疗后六个多月,并与肺部瘢痕形成有关。皮质类固醇和抗生素是缓解这些晚期副作用的主要治疗方法105。
- 亚麻籽:小鼠研究表明,亚麻籽粉有助于预防辐射引起的肺损伤106和辐射相关的死亡107。亚麻籽含有ω-3脂肪酸和木脂素。亚麻籽减少了氧化损伤,减少了肺部炎症细胞的数量,从而减少了肺组织的纤维化。亚麻籽不会降低小鼠的辐射效果107。14名III期和IV期非小细胞肺癌患者在放疗期间每天食用亚麻籽松饼使肺炎发病率较低108。
- 姜黄素:姜黄素可减少炎性细胞因子并清除自由基109。在大鼠中,姜黄素在辐射前(每周5天)给药,辐射后给药8周。用姜黄素治疗的大鼠减少了肺部炎症和纤维化110。在小鼠中,在放疗前后每天作为饮食的一部分给予姜黄素也可以减少纤维化111。
- 金雀异黄酮:又称染料木素,大豆异黄酮中的一种主要成分。在大鼠和小鼠研究中,它被证明可以减少辐射诱导的肺纤维化104。给大鼠喂食含有染料木素的饮食28周,观察到呼吸频率改善,炎性细胞因子和纤维化减少112。一般来说,大豆异黄酮(包括染料木素和其他异黄酮)已被发现可以减轻肺损伤并使肿瘤组织对辐射敏感113。
- 褪黑素:褪黑素已显示出与放射治疗一起使用的广泛益处。在动物研究中,褪黑素减轻了早期和晚期辐射诱导的肺损伤114,115。对褪黑激素的人体研究表明,在癌症治疗过程中,每天高达20mg的剂量可能是有益的41,49。
- 葡萄籽:一项针对小鼠的研究发现,在辐射前一小时和辐射后四周服用葡萄籽提取物原花青素可以减轻辐射诱导的肺损伤116。葡萄籽原花青素可以减少辐射引起的DNA断裂,保护白细胞和增加体重117。
- 牛磺酸和精氨酸: 二者可以通过减少胶原蛋白的产生来预防辐射诱导的肺纤维化,胶原蛋白是一种参与纤维化过程的蛋白质118。牛磺酸降低了接受胸部放射治疗的小鼠中诱导纤维化的炎性细胞因子TGF-β1的水平119。
- 黄芪:在一篇文献综述中,黄芪被发现可以提高非小细胞肺癌癌症放疗的疗效并降低其毒性。研究表明,一年、二年和三年的死亡风险都有所降低。在服用黄芪的患者中,放射性肺炎(辐射治疗肺癌癌症的早期副作用)的发病率较低,白细胞计数较高120。从黄芪中提取黄酮类化合物并给小鼠服用,可以减轻放射性肺损伤121。
贫血是指红细胞或血红蛋白不足,无法向组织充分输送氧气的状况。研究表明,接受治疗的癌症患者中有40-64%患有贫血122。血红蛋白水平低的癌症患者对放疗的反应不如非癌症患者,因为肿瘤细胞没有接受足够的氧气123。低肿瘤氧和低血氧可增强肿瘤生长并产生治疗耐药性122。治疗期间测量的血红蛋白值可以预测患者对治疗的反应。吸烟会导致血红蛋白下降和治疗效果较差,应避免吸烟以提高放射治疗的疗效123。
严重的贫血可以通过输血或药物红细胞生成素(Procrit)进行治疗,这是一种能使血红蛋白水平稳定、持续升高的生长因子。然而,尽管这些方法可能会改善贫血,但研究尚未表明它们能改善与肿瘤控制相关的结果123。
一项对103名癌症宫颈癌患者的研究表明,在顺铂(化疗药)和放疗期间补充抗氧化剂可以减少氧化应激,提高血红蛋白水平和生活质量。使用的抗氧化剂剂量包括每天4.8mgβ-胡萝卜素、10 mg维生素C、200 IU维生素E和15mcg硒124。
- 黄芪是一种常用中草药,已被证明可以促进小鼠的骨髓功能和血细胞的形成。在放射治疗和/或化疗前注射黄芪的小鼠的红细胞、血红蛋白、血小板和骨髓细胞水平高于对照组动物125。
4.腹部辐射及相关副作用
1). 胃肠道粘膜炎: 胃肠道、泌尿系统和妇科癌症的腹部或骨盆辐射可导致急性或慢性胃肠道副作用。急性肠炎(肠道炎症)的特征是在放疗期间或放疗后不久出现腹泻、腹痛、腹胀、食欲不振、恶心和大便紧迫感。这些症状通常在放射治疗的第二周开始,并在完成治疗后的三个月内消退。大约15-20%的患者需要改变治疗方案以降低症状的严重程度。慢性小肠放射病可在放射治疗后18个月至6年发展,包括进食后疼痛、急性或间歇性小肠梗阻、恶心、体重减轻、食欲不振、腹胀、腹泻、脂肪便和营养吸收不良等症状。胆汁盐吸收不良、小肠细菌过度生长(SIBO)和乳糖不耐受也可能发生126。
可能采取的自然干预措施如下:
- 谷氨酰胺:可维持粘膜生长和功能。谷氨酰胺被广泛用于接受各种化学疗法的患者,以改善包括粘膜炎和腹泻在内的治疗副作用127。多项人体研究表明,谷氨酰胺对辐射诱发的食道粘膜炎和口腔粘膜炎有益128。然而,有的研究未能确定谷氨酰胺对接受放疗患者的下肠道有明显的益处129,130。
- 益生菌:益生菌是一种有益于胃肠道健康的细菌,对胃肠道毒性有积极影响。益生菌维持促炎分子和抗炎分子之间的平衡,调节免疫活性,有利于受损粘膜组织的愈合,并减少有害细菌132,133。一项科学文献综述显示,接受放疗和化疗的患者肠道中的细菌发生了显著变化。细菌的这种转变可能会产生问题,并被认为会导致腹泻等与治疗相关的症状。该综述的作者指出,“肠道微生物群可能通过改变肠道屏障功能、先天免疫和肠道修复机制在粘膜炎的发病机制中发挥重要作用”134。
一项针对206名接受腹部和骨盆癌症放射治疗的患者的随机、双盲、安慰剂对照研究表明,与服用安慰剂的患者相比,每天三次服用15亿CFU鼠李糖乳杆菌的患者腹泻减少,所需的抗腹泻药物更少、更晚135。
2017年一项对六项试验的荟萃分析证实了益生菌对腹部或骨盆区域癌症患者的益处136。一般来说,指南建议含有乳酸杆菌的益生菌用于预防盆腔癌放射性腹泻74。
- 益生元:益生元可以刺激肠道中有益细菌的生长。一项针对38名接受妇科癌症腹部放射治疗的女性的随机试验发现,菊粉和低聚果糖改善了大便的稠度137。
- 硒:可降低因宫颈癌或子宫癌症放射治疗引起的腹泻的严重程度。在一项针对癌症或子宫颈癌患者的研究中,81名血硒水平低的患者被随机分为接受硒加放疗或单独放疗。接受硒治疗的患者在放射治疗的几天内给予500mcg亚硒酸钠,在不治疗的几天后给予300mcg。严重腹泻发生在硒组的20.5%和对照组的44.5%。到放射治疗结束时,补充组的血硒水平显著恢复28,29,138。一项为期10年的随访研究表明,硒不会降低放射治疗的有效性或长期存活率,使硒成为治疗宫颈或子宫癌症硒缺乏患者腹泻的有益药物29,139。
- 车前籽:在接受为期四周骨盆放射治疗的60名癌症患者中,每天服用车前籽纤维可显著降低放射性腹泻的发生率和严重程度。抗腹泻药物的使用也有所减少140。实践指南得出结论,可溶性纤维可能减少化疗和放疗引起的腹泻;然而,尚未确定纤维的剂量和最佳类型141。逐渐增加纤维摄入量可以最大限度地减少快速摄入纤维时出现的腹胀、胀气的影响142。
- 姜黄素:80名参与研究并接受各种癌症放疗的患者,包括结肠癌、直肠癌、肝癌、肾癌、胃癌和肺癌患者,在接受含有100 mg姜黄素与200mg大豆卵磷脂加上辐射或单独辐射。患者在放疗第一天的第二天开始服用姜黄素,并持续服用四个月。姜黄素组的恶心、呕吐、腹泻、便秘、疲劳、营养不良、体重减轻、记忆力、认知障碍以及局部疼痛和肿胀较少143。
立体定向身体放射治疗是一种相对较新的放射技术,为脑外肿瘤提供高效的放射剂量145。当机器人立体定向身体放射治疗用于治疗某些不可切除(无法通过手术完全切除)的肝脏肿瘤时,放射性肝病的发生率较低,症状自行消退147。
- 水飞蓟:从水飞蓟植物中提取的类黄酮复合物(水飞蓟素),在肝病患者中越来越受欢迎148。水飞蓟素可减少炎症,清除自由基149,保持细胞谷胱甘肽含量150,并可能预防或治疗接受抗癌治疗的患者的肝功能障碍151。一项针对大鼠的研究发现,静脉注射水飞蓟素可以预防放射性肝病152。水飞蓟素具有良好的耐受性,并导致某些患者外周血细胞中谷胱甘肽的小幅增加和脂质过氧化的减少153。
- 限制蛋白摄入:饮食调整可能有助于肾毒性患者。过多的蛋白质会给肾脏带来负担,建议一些慢性肾脏疾病患者的饮食蛋白质限制为每天0.6-0.8 g/kg体重156。
1).盆腔辐射病:也称为胃肠道辐射引起的毒性,可造成短暂或长期的问题。即使使用辐射技术来保护健康组织,如强度调节放射治疗(IMRT),损伤仍然可能发生;此外,损伤可能在几十年后发生157。有关的自然干预措施,请参阅上述“胃肠道粘膜炎”一节内容。
2). 放射性直肠病:这是一种并发症,表现为直肠粘膜损伤、疤痕和组织死亡,有时被称为放射性直肠炎158。在接受前列腺癌、直肠癌、膀胱癌、睾丸癌、宫颈癌和子宫癌盆腔放射治疗的患者中,有5-20%会发生这种并发症。虽然它可以自发愈合,但慢性辐射性直肠病会导致慢性问题,如里急后重(粪便紧迫感伴痉挛样直肠疼痛)、腹泻和直肠出血159。
可能采取的营养干预措施如下:
- 合生元:接受前列腺癌症放射治疗的男性,服用含有1亿CFUs罗伊氏乳杆菌和4.3g可溶性纤维的粉末或安慰剂,可减轻原发性疾病症状,改善生活质量160。
- 维生素A:在一项随机双盲试验中,将棕榈酸视黄醇(维生素a,口服10000 IU,90天)与安慰剂进行比较,在骨盆放射治疗后6个月,口服棕榈酸视黄醇显著降低了受试者的直肠辐射副作用161。
- 维生素E和维生素C:在一项试点研究中,20名既往骨盆照射引起的慢性放射性直肠炎患者服用了维生素E(400 IU,每日三次)和维生素C(500 mg,每日三次元)。据报道,出血和腹泻有显著改善,但直肠疼痛没有改善162。
- 异黄酮:从放射治疗的第一天开始,将42名前列腺癌患者随机分为每日200mg大豆异黄酮或安慰剂组,为期6个月。与安慰剂组相比,大豆治疗组的总体勃起能力更高(77%对57.1%),漏尿、直肠痉挛、腹泻和排便疼痛更少165。
- 蛋白酶:在一项针对120名宫颈癌患者的随机开放标签试验中,在放射治疗期间给予包括胰蛋白酶、胰凝乳蛋白酶和木瓜蛋白酶在内的口服酶改善了与辐射诱导的组织损伤相关的症状。在服用蛋白酶的组中,皮肤、阴道粘膜、尿液和胃肠道症状较少167。
- 姜黄素:在一项针对40位前列腺癌患者的初步研究中研究了姜黄素。随机分配到姜黄素组的患者在前1周开始并在完成八周的外部放射治疗后,每天服用高活性的3g姜黄素。要求患者填写与尿、性和肠症状有关的生活质量调查表。治疗20周后,姜黄素组的尿路症状较安慰剂组轻,表明姜黄素对健康组织具有放射防护作用169。
- 蔓越莓:在一项随机、双盲、安慰剂对照试验中,患有急性放射性膀胱炎的前列腺癌症患者服用蔓越莓胶囊(含72 mg原花青素)或安慰剂。在整个放射治疗过程中,患者每天服用一粒胶囊,治疗结束后服用两周。服用蔓越莓胶囊的男性中有65%发生膀胱炎,而服用安慰剂的患者中这一比例为90%。服用蔓越莓的患者疼痛和灼烧的发生率显著降低170。
另一项针对370名接受IMRT治疗6至7周的男性的研究发现,服用200mg蔓越莓片(30%原花青素)的患者下尿路感染率降低。在服用蔓越莓片的组中,184名参与者中只有16人(8.7%)在整个治疗过程中出现了较低的尿路感染;在接受放射治疗的组中,186名参与者中仅有45人(24.2%)出现了较低的尿路感染。此外,排尿疼痛、夜间排尿、尿频和尿急都有所减少171。最后,在一项针对924名接受放射治疗的前列腺癌患者的大型研究中,在放射治疗期间服用蔓越莓提取物六到七周,可将尿路感染的数量减少约50%172。
6.皮肤、全身性等辐射副作用1).急性放射性皮炎:皮炎是放射治疗的常见副作用,严重程度取决于许多因素,包括更大的治疗范围、更多的总辐射剂量和更长的治疗时间。皮炎症状包括发红(红斑)、疼痛和皮肤剥落(脱屑)。接受放射治疗的患者中,高达95%的患者会出现皮肤变化,这可能会限制患者后续治疗173。可能采用的自然疗法包括如下:
- 乳香(局部使用):在一项随机对照试验中,对114名手术后接受放射治疗的乳腺癌女性进行了一项含有乳香提取物的局部使用乳膏的研究,以预防放射性皮炎。该乳膏在放射治疗后立即使用,并在接受放射治疗的当天睡前使用。乳香组的皮肤发红程度明显减轻。乳香组只有25%的女性不得不使用可的松乳膏治疗皮肤反应,而安慰剂组有63%。安慰剂组因放射治疗引起的浅表皮肤不良反应发生率高于乳香组174。
- 金盏花(局部使用):金盏花具有抗炎特性,有助于伤口愈合175。一项随机试验将含有金盏花提取物的乳膏与处方药曲拉明(用于预防癌症患者急性放射性皮炎)进行了比较。从放射治疗的第一天开始,乳腺癌患者每天至少两次将该制剂涂抹在受照射的皮肤上,并持续到治疗结束。金盏花治疗的患者2级或以上急性皮炎的发生率明显较低176。
- 芦荟(局部使用):在临床试验中,添加到肥皂中的芦荟凝胶对接受更高累积辐射剂量的患者具有抗辐射诱发皮炎的保护作用,将可检测到皮肤损伤的时间从三周延长到五周177。
- 水飞蓟(局部使用):在一项针对乳腺癌症患者的研究中,水飞蓟素乳膏减少了放射性皮炎。在接受水飞蓟素乳膏治疗的患者中,只有76.5%的患者出现皮肤反应,而对照组的这一比例为98%178。
- 姜黄素(口服):在一项随机、双盲、安慰剂对照试验中,对30名接受放射治疗的乳腺癌患者进行了姜黄素研究。患者从治疗的第一天开始,在放射治疗的四到七周内,每天三次口服2g姜黄素胶囊或安慰剂。姜黄素显著降低了放射性皮炎和潮湿脱屑的严重程度179。
- 植物化学素等抗氧化剂:一项针对71名接受乳腺癌症放射治疗的患者的研究表明,与未服用该产品的患者相比,在治疗期间口服含有白藜芦醇、番茄红素、维生素C和花青素的产品可降低皮肤毒性。两组均接受了含有透明质酸和类固醇的预防性局部治疗。治疗在放射治疗开始前10天开始,一直持续到放射治疗结束后10天180。
- 蛋白酶(口服):对共219名头颈癌或宫颈癌患者的两项试验的回顾显示,一种名为Wobe-Mugos E的蛋白水解酶制剂(100 mg木瓜蛋白酶、40 mg胰蛋白酶和40 mg胰凝乳蛋白酶)可将放射性皮肤反应的发生率降低87%181。
- 绿茶(局部使用):在乳腺癌患者术后接受放疗的1期试验中,8名女性出现2级皮炎,但绿茶多酚(EGCG)局部治疗后严重程度下降182。同年发表的第二项试验证实,EGCG减轻了类似组患者的疼痛、烧伤和瘙痒182.183。
- 褪黑素(局部使用):在乳腺癌患者术后接受放射治疗的2期随机试验中,褪黑激素霜显著降低了皮炎的发病率184。
- 谷氨酰胺(口服):40名接受放射治疗的乳癌患者被随机分为口服谷氨酰胺(15g)治疗组或对照组。谷氨酰胺组11.1%的患者出现2级皮肤反应,而对照组为80%,这一差异具有统计学意义185。
2). 辐射诱发的纤维化: 纤维化或结缔组织增厚是放疗的一种严重晚期影响,可影响皮肤186(Bray 2016)。在乳腺癌患者放疗后出现放射性纤维化的22名患者每天口服800mg己酮可可碱和1000IU维生素E。六个月后,辐射诱导的纤维化面积显著减少,未发现不良反应187。有关纤维化的更多信息,可参阅本文的“肺毒性”部分。
- 槲皮素:一种植物来源的黄酮醇,可减少辐射诱导的小鼠皮肤纤维化。槲皮素降低了TNF-α和TGF-β,增加了MMP-1活性,并降低了氧化应激—所有这些都与纤维化的发展有关。小鼠在辐射前一周以及整个辐射和随访期间食用含有槲皮素的食物188。
3). 淋巴水肿:淋巴水肿是富含蛋白质的淋巴液的积聚,导致下层皮肤肿胀189。例如,在乳腺癌放疗后,如果淋巴引流被无意中堵塞或切断,手臂可能会出现肿胀。淋巴水肿会导致疼痛、感染风险增加和患肢体积增加190。开始治疗前的肥胖会增加患淋巴水肿的几率191。可能采用的自然干预措施包括如下:
- 硒:研究表明,硒(亚硒酸钠)在放疗后4-6周内以每天300-500mcg的剂量减少多个部位的淋巴水肿有好处192(Bruns 2003)。在一项探索性研究中,48名上肢水肿或头颈部水肿患者在完成放疗后接受了评估。患者在四至六周内每天接受500mcg亚硒酸钠治疗。大多数患者水肿特征减轻,能够避免重大手术干预192,193。
4). 疲劳:高达80%的患者在接受放射治疗时会出现疲劳。在完成放疗后,疲劳会持续存在。据报道,30%的患者在随访期间会出现疲劳。辐射诱发疲劳的机制尚不清楚194。放疗过程中的疲劳被描述为感觉疲劳、虚弱和疲惫。在某些情况下,疲劳可能是贫血、焦虑或抑郁、缺乏活动、药物副作用或感染的下游影响195。
可能采取的自然疗法如下:
- 花旗参:在一项为期八周的随机、双盲、安慰剂对照研究中,2000mg西洋参减轻了364名接受放疗和/或化疗的癌症患者的疲劳。8周时,人参组的疲劳评分与安慰剂组相比有显著改善。人参组接受积极癌症治疗的参与者比那些已经完成癌症治疗的参与者表现出更大的改善。无不良副作用报告196。
- L肉碱:12名接受放疗和/或化疗的晚期癌症患者在四周内每天服用6g L-肉碱。补充L-肉碱后,疲劳显著减少,瘦体重和食欲显著增加197。
- 褪黑素:已在前文的抗氧化部分中描述过,具有对抗辐射诱导疲劳的有益作用41,49。
- 运动锻炼:一项科学文献综述发现,癌症患者在接受治疗时锻炼,疲劳、抑郁和整体生活质量都有所改善。每周进行90-120分钟的适度体育活动对改善疲劳最有效198。
5). 恶心和呕吐:放疗引起的恶心和呕吐大多数发生在对上腹部、肝脏和大脑的辐射中,尽管也可能发生在身体其他部位的辐射。同时接受化疗的患者,放疗引起的恶心和呕吐加重199。如果不加以治疗,恶心和呕吐会导致生理变化,包括脱水、电解质失衡、营养不良和恶病质。
可能采取的自然干预措施包括如下:
- 姜根:通常用于减轻恶心和呕吐。但是,生姜与放疗的结合尚未得到广泛研究,并且在化疗诱发的恶心和呕吐的研究中疗效参差不齐200。
- 维生素B6:在104名接受放射治疗的患者中测试了维生素B6对放射病的影响。52名患者在放射治疗前一小时每天接受100mg维生素B6,持续7天,对照组单独接受放射治疗。与对照组(48.1%)相比,维生素B6组的辐射病(32.6%)减少,恶心和呕吐减少,食欲改善201。
- 绿茶和锌:前述文中关于“胃肠道粘膜炎”内容中描述的其他减少恶心和呕吐的措施包括绿茶和锌。
- 物理方法:事实证明,使用指压带可以成功治疗化疗和放疗引起的恶心和呕吐。这些非处方指压带具有成本效益且安全。特别是,它们刺激手腕上的“P6”穴位,这与恶心有关。在一项针对88名因不同癌症接受放射治疗的恶心患者的随机研究中,指压带加标准护理可使恶心平均减少23.8%。仅标准护理可减少4.8%202。
7.恶病质和食欲不振
恶病质是指脂肪和肌肉组织的快速流失,可能会对患者的生活质量和对治疗的反应产生负面影响203。癌症恶病质是由涉及分子TNF-α和IL-6的炎性反应引起的,它们在辐射抗性中起作用。因此,抑制恶病质的治疗还可以增加肿瘤的放射敏感性,从而提高生存率204。
接受放化疗的、无法手术的头颈癌和食道癌患者容易出现体重减轻和恶病质,有时会在治疗开始前出现205。辐射引起的副作用,如恶心、呕吐、食道炎、粘膜炎和腹泻,会限制患者的进食或吸收营养的能力,从而加重恶病质203。
可能采取的自然干预措施包括如下:
- 鱼油:Omega-3脂肪酸调节炎症途径206。一项随机对照试验发现,与仅接受标准营养的患者相比,111名接受添加EPA和DHA的头颈部和食管癌放化疗的患者的营养和功能状况有所改善。营养配方中的脂肪酸含量包括2g EPA和0.85g DHA。该营养配方在治疗的14周内每天服用。体重下降有较小的趋势。实验组平均减少0.82 kg,对照组减少2.82 kg。两组的炎症细胞因子IL-6均增加,但脂肪酸组的增加幅度要小得多,这支持了EPA和DHA的抗炎作用205。
- L肉碱:如疲劳部分所述,L-肉碱可能会增加瘦体重和食欲197。
更多有关的营养干预措施可参考本网有关专文:癌症恶病质 >>
8.低血细胞计数低血细胞计数通常与辐射无关,除非出血过多或辐射影响到产生血细胞的骨髓。贫血在上述内容中已有讨论。可能采用的自然干预措施包括如下:
- 黄芪:文献综述表明,包括14项不同研究中的1427名患者,发现黄芪在放疗期间可改善白细胞计数120。
- 褪黑素:如上述“抗氧化剂”部分,褪黑素已在多项研究中表明可改善血小板和白细胞计数41,49。许多白细胞在其表面均具有褪黑素受体,褪黑素可以结合这些细胞并保护它们免受辐射的影响207。
尽管近年来,原发性癌治疗后的长期生存率显著增加,但癌症治疗最严重的副作用之一是新肿瘤的发展208。在美国,继发性癌症占所有癌症的18%,其中8%是放射治疗引起的。其他被认为是遗传因素、衰老和生活方式结果209。
继发恶性肿瘤的风险可能直接发生在辐射区域或身体其他部位210。该风险是剂量依赖性的,当辐射暴露发生在较年轻的年龄时,风险似乎更高211;潜伏期长,例如,放射治疗后5至9年患白血病的风险通常最高,实体瘤的间隔时间超过10年,通常为几十年212。
总体而言,继发性癌症的风险通常较低,放疗对患者的益处大于发展为继发肿瘤的风险212。由于一些研究已经确定了某些类型原发性癌症的继发性癌症的常见部位,在某些情况下,这为医生提供了加强监测并尝试在早期发现继发性癌的机会213。
一般来说,戒烟、控制体重和身体运动有助于预防继发性癌症的发展209。事实上,一项针对癌症头部和颈部患者的大型研究表明,吸烟会显著增加患继发性癌症和死亡的风险214。
- 白藜芦醇:一项针对在全身辐射过程中接受白藜芦醇治疗的无癌小鼠的研究发现,与未接受白藜芦酸治疗的小鼠相比,骨髓中的染色体异常更少,这表明其对骨髓具有辐射保护作用。白藜芦醇在全身照射(3 Gy)前两天给药。之后将白藜芦醇添加到饮用水中30天215。
一些自然干预措施(包括抗氧化剂)有助于防止DNA突变和癌症复发,更多内容可参阅本网站专文:癌症辅助疗法 >>
放疗增敏与自然疗法
许多实验室或临床试验表明,一些天然化合物可以增强肿瘤对放疗的敏感性。自然干预措施与放疗一起使用可改善治疗效果,包括如下:- 姜黄素:其放射增敏特性已被广泛研究216。在实验室研究中,姜黄素使多种类型的癌症细胞对辐射敏感217。在前列腺癌症细胞系中,姜黄素是一种有效的放射增敏剂,可克服辐射诱导的促生存基因表达的影响218。在头部和颈部鳞状细胞癌症细胞系中,姜黄素在细胞分裂的有丝分裂阶段阻止细胞,这是细胞最容易受到辐射影响的阶段219。在结直肠癌癌症细胞系中,姜黄素通过阻断可能导致放射性耐药的促存活蛋白复合物核因子κB(NF-κB),提高了抗肿瘤效果220。同样,在乳腺癌症细胞系中,姜黄素阻断NF-κB并能够克服缺氧,从而使乳腺癌细胞对辐射的抗肿瘤作用敏感221。
- 白藜芦醇:存在于葡萄、蓝莓、红酒和日本虎杖等植物中,具有抗炎、抗氧化特性。白藜芦醇已被证明可控制细胞增殖、血管生成和癌症细胞死亡222,223。在一项针对抗辐射黑色素瘤细胞的细胞系研究中,白藜芦醇增强了放射敏感性,减少了增殖,并增加了细胞死亡224。在用白藜芦醇和放射线治疗的抗辐射前列腺癌症细胞系的研究中观察到了类似的效果225。其他类似的细胞系研究已经证实,添加白藜芦醇具有良好的放射增敏作用223,226。
一项研究向小鼠注射多形性胶质母细胞瘤细胞。这种类型的脑癌天生对辐射有抵抗力。结果表明,白藜芦醇预处理的胶质母细胞瘤细胞对辐射更敏感。形成的肿瘤比未经预处理的细胞形成的肿瘤小。接受用白藜芦醇预处理的细胞的小鼠存活时间更长226。这一结果在最近的一项研究中得到了证实227。
标志物CD133已被广泛用于鉴定癌症干细胞,这些干细胞对放射疗法的治疗非常耐受228。一项研究将白藜芦醇处理的CD133阳性非典型畸胎瘤/横纹肌样细胞(一种罕见的肿瘤)与辐射联合注射给小鼠,结果显示小鼠的存活率提高。研究人员得出结论,白藜芦醇是这种抗辐射形式的癌症的有效放射增敏剂229。在另一项研究中,研究人员发现用白藜芦醇治疗的抗辐射胶质母细胞瘤细胞中CD133的表达降低227。
- 精氨酸:是一氧化氮(NO)前体,已研究其在癌症生物学和治疗中的作用230。NO是体内普遍存在的信号分子,以前与肿瘤的发生和生长有关,但研究表明,根据其浓度,它也具有抗肿瘤作用231,232。L-精氨酸的给药能够将NO增加到临床相关水平,有证据表明NO可以通过增加肿瘤血流量和降低肿瘤耗氧量来诱导化疗和放射敏感性。L-精氨酸被认为通过抑制癌细胞中的DNA修复机制,至少部分通过抑制肿瘤代谢来诱导放射敏感性230。
在一项评估L-精氨酸给药对放射治疗影响的临床试验中,63名患者被随机分组,在每次放射治疗前一小时接受10g口服L-精氨碱或安慰剂。在对放疗的反应中,与安慰剂相比,L-精氨酸治疗组表现出明显更好的总体有效率、症状有效率、完全的神经系统反应以及无神经系统进展的患者比例。L-精氨酸不会增加短期或长期不良事件,耐受性良好。这些结果表明,口服L-精氨酸可能是通过诱导癌症细胞的放射敏感性来改善放射治疗的有效方法。有趣的是,L-精氨酸似乎不会伤害免疫细胞,因为肿瘤浸润淋巴细胞中辐射诱导的DNA损伤量没有改变230。
- 槲皮素:槲皮素是一种来自植物的黄酮类化合物,对髓母细胞瘤、乳腺癌、宫颈癌和结直肠癌癌症细胞系具有放射增敏作用233,234。在一项关于癌症的小鼠研究中,用槲皮素治疗的小鼠的肿瘤生长显著减慢,肿瘤细胞的DNA修复机制受到损害235。
- 金雀异黄酮(染料木素):大豆异黄酮的主要成分,可增强辐射对前列腺、宫颈和雌激素受体阳性和雌激素受体阴性乳腺癌细胞系研究的影响236,234。染料木素通过降低表皮生长因子受体(EGFR)的激活来抑制结肠癌细胞的生长。EGFR激活导致与癌症细胞生长和转移相关的多个信号级联,过度活跃的EGFR与更差的预后相关237。
- 亚洲参:使非小细胞肺癌细胞对辐射敏感238,而人参提取物对辐射诱导的肝损伤具有保护作用239
- 姜根:生姜中的活性成分Zerumbone(球姜酮)可以使结肠癌细胞对辐射敏感240。
- 南非醉茄:一种具有抗炎、免疫调节、抗应激和抗肿瘤特性的阿育吠陀医学重要的草药(又称印度人参)241。在癌症、黑色素瘤和淋巴瘤细胞系的研究中起到放射增敏作用242,243,244。在一项对患有黑色素瘤的小鼠的研究中,62.5%的动物在接受放射治疗、南非醉茄(15mg/kg,每周注射5天,持续3周)和局部热疗后,肿瘤大小至少减少了50%244。在另一项啮齿动物研究中,将抗辐射的小鼠黑色素瘤细胞或辐射敏感的纤维肉瘤细胞植入小鼠体内。然后在辐射前一小时用辐射、热疗和南非醉茄(40mg/kg)的组合治疗小鼠。37%的黑色素瘤小鼠和64%的纤维肉瘤小鼠出现完全反应。完全反应被定义为肿瘤消退,在原发肿瘤部位120天内没有再生245。这些结果尤其令人鼓舞,因为黑色素瘤的放射抵抗率很高244。
- 维生素D:越来越多的研究调查了维生素D3水平和维生素D受体基因异常与某些癌症之间的关系,包括结直肠癌、乳腺癌和其他癌症246。维生素D3的放射增敏特性也已得到研究。维生素D3放射增敏的乳腺癌症细胞对辐射具有内在抗性247、非小细胞肺癌癌症细胞和结直肠癌癌症细胞248。这种效应的一种机制是自噬的过程,其中细胞降解自身的内容物,以产生能量和代谢前体来应对压力247,248。在侵袭性乳腺249和前列腺肿瘤细胞系250中,维生素D3通过降低RELB的基因表达来提高放射敏感性,RELB是一种通过保护肿瘤细胞免受辐射而促进肿瘤细胞存活的基因。
- 绿茶:绿茶多酚(EGCG)是绿茶中的一种主要活性成分。对10例局部晚期乳癌患者进行了EGCG辐射治疗效果的研究。5名患者接受400mg EGCG,每日3次,加放疗,5名患者单独接受放疗。服用EGCG的患者血清VEGF、肝细胞生长因子(HGF)和金属蛋白酶2和9(MMP-2/MMP-9)水平较低,所有这些因素都与肿瘤进展和转移有关。将服用EGCG的患者的血清应用于高转移性乳腺癌细胞系的细胞。血清减少了癌症细胞的增殖,增加了细胞凋亡,并减少了参与抗辐射的蛋白质的激活251。另一项研究检测了EGCG对人脑微血管内皮细胞放射增敏的影响。血管内皮细胞在肿瘤形成血管中起着重要作用。在用EGCG和放射线处理的细胞中,细胞死亡是单独用放射线处理细胞的5倍252。
- 萝卜硫素:一种植物化学物质,存在于西兰花和其他十字花科蔬菜(如甘蓝、卷心菜和花椰菜)中253。当头部和颈部癌症细胞用萝卜硫素治疗,然后照射时,研究人员观察到,联合治疗比单独治疗对细胞增殖的抑制更强253。此外,萝卜硫素增强了小鼠骨肉瘤细胞的放射敏感性254。
- 鱼油:细胞系研究发现,EPA(二十碳五烯酸,来自鱼油)可使结直肠癌和胶质母细胞瘤细胞对辐射敏感255。Omega-3脂肪酸,特别是EPA和二十二碳六烯酸(DHA),已被证明主要通过保留身体成分对接受放疗或化疗的人有益256。
- 乳香:一项对44名接受脑肿瘤放射治疗的患者进行的乳香提取物随机对照试验发现,在MRI检查中,乳香组中最大的肿瘤在放射治疗后缩小了88%,而安慰剂组中最大的瘤只缩小了19%61。
- 云芝蘑菇(PSK):从云芝蘑菇中提取的云芝多糖K(PSK)在东亚已经使用了数百年257。一项科学研究综述表明,PSK与肺癌标准放疗和化疗相结合延长了生存期,减少了肿瘤相关症状,并改善了免疫功能258。在一项对187名食管鳞状细胞癌患者的研究中,评估了不同治疗方案的5年生存率:放疗(40%生存率)、PSK和放疗(42%)、化疗放疗(29%)或化疗和PSK放疗(37%)259。在另一项研究中,90名宫颈癌患者接受了放疗和3g PSK或单独放疗。PSK组60%的患者的反应被评为“良好”,但对照组只有32%的患者反应良好。此外,PSK组在整个治疗过程中具有更好的免疫系统反应260。
- 维生素B6(吡哆醇):辐射会消耗吡哆醇(维生素B6)等营养物质,服用吡哆醇可以在没有副作用的情况下逆转这种缺乏。一项对210名患有II期子宫内膜癌症的女性进行的研究显示,在接受放疗期间,每天接受300mg吡多醇或不接受吡多醇治疗,5年生存率提高15%,对放射的耐受性提高15%。恶心、呕吐和腹泻也有所改善261。
营养与草本综合干预方案
基于循证医学和循证营养学有关文献综合,可点击其综合干预方案如下:- 放疗管理(放疗增敏)
- 放疗管理(抗辐射损伤)
- 放疗管理(抗脑水肿)
- 放疗管理(防脑部损伤)
- 放疗管理(防口腔粘膜炎)
- 放疗管理(抗口干症)
- 放疗管理(防食道炎)
- 放疗管理(抗心脏损伤)
- 放疗管理(抗肺脏损伤)
- 放疗管理(防胃肠炎)
- 放疗管理(防肝损伤)
- 放疗管理(防直肠炎)
- 放疗管理(防男性功能障碍)
- 放疗管理(抗女性盆腔损伤)
- 放疗管理(防尿路症状)
- 放疗管理(防止贫血)
- 放疗管理(抗急性皮炎)
- 放疗管理(抗皮肤纤维化)
- 放疗管理(抗淋巴水肿)
- 放疗管理(防疲劳症状)
- 放疗管理(改善恶心、呕吐)
- 放疗管理(防恶病质)
- 放疗管理(改善营养状况)
- 放疗管理(防继发性癌症)
了解癌症更多的治疗及防控方法,可参考本网如下专文:
参考文献:
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参考来源:
美国癌症学会
http://www.cancer.org
美国国立补充整体医学中心
https://nccih.nih.gov/
美国化疗网
http://www.chemotherapy.com
加拿大癌症学会
http://www.cancer.ca
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