Turner J Harvey
School of Medicine and Pharmacology, The University of Western Australia , Perth , Australia.
Br J Radiol. 2018 Nov;91(1091):20180440. doi: 10.1259/bjr.20180440. Epub 2018 Sep 4.
"Those who cannot remember the past are condemned to repeat it." George Santayana 1905 "If men could learn from history, what lessons it might teach us! But passion and party blind our eyes, and the light which experience gives is a lantern on the stern, which shines only on the waves behind us!" Samuel Taylor Coleridge 1835 The medical speciality of theranostic nuclear oncology has taken three-quarters of a century to move the stern light cast retrospectively by single-centre clinical reports, to the forepeak in the bow of our theranostic craft, where prospective randomised controlled multicentre clinical trials now illuminate the way forward. This recent reorientation of nuclear medicine clinical research practice to align with that of standard medical and radiation oncology protocols, reflects the paradigm shift toward individualised molecular oncology and precision medicine. Theranostics is the epitome of personalised medicine. The specific tumour biomarker is quantitatively imaged on positron emission tomography (PET)/CT or single photon emission computed tomography (SPECT)/CT. If it is clearly demonstrated that a tumoricidal radiation absorbed dose can be delivered, the theranostic beta or alpha-emitting radionuclide pair, coupled to the same targeted molecule, is then administered, to control advanced metastatic cancer in that individual patient. This prior selection of patients who may benefit from theranostic treatment is in direct contrast to the evolving oncological indirect treatments using immune-check point inhibitors, where there is an urgent need to define biomarkers which can reliably predict response, and thus avoid the high cost and toxicity of these agents in patients who are unlikely to benefit. The immune and molecular treatment approaches of oncology are a recent phenomenon and the efficacy and safety of immune-check point blockade and chimeric antigen receptor T-cell therapies are currently under evaluation in multicentre randomised controlled trials. Such objective evaluation is compromised by the inadequacy of conventional response evaluation criteria in solid tumour (RECIST) CT/MR anatomical/functional imaging to define tumour response, in both immune-oncology and theranostic nuclear oncology. This introduction to the clinical practice of theranostics explores ways in which nuclear physicians can learn from the lessons of history, and join with their medical, surgical and radiation oncology colleagues to establish a symbiotic collaboration to realise the potential of personalised molecular medicine to control advanced cancer and actually enhance quality of life whilst prolonging survival.
“那些无法铭记过去的人注定要重蹈覆辙。” 乔治·桑塔亚那,1905年
“如果人们能从历史中汲取教训,那它会教给我们多少东西啊!但激情和党派偏见蒙蔽了我们的双眼,经验给予的光芒就像船尾的一盏灯笼,只照亮我们身后的波浪!” 塞缪尔·泰勒·柯勒律治,1835年
核诊疗肿瘤学这一医学专业用了四分之三个世纪,才将单中心临床报告回顾性投下的船尾灯,移至我们核诊疗之船船头的前峰位置,如今前瞻性随机对照多中心临床试验正在此照亮前行的道路。核医学临床研究实践最近重新定位,以与标准医学和放射肿瘤学方案保持一致,这反映了向个体化分子肿瘤学和精准医学的范式转变。核诊疗是精准医学的典范。特定肿瘤生物标志物在正电子发射断层扫描(PET)/CT 或单光子发射计算机断层扫描(SPECT)/CT 上进行定量成像。如果能明确证明可以给予杀肿瘤辐射吸收剂量,那么就会施用与同一靶向分子偶联的核诊疗β或α发射放射性核素对,以控制该个体患者的晚期转移性癌症。这种对可能从核诊疗治疗中受益的患者的预先选择,与使用免疫检查点抑制剂的不断发展的肿瘤学间接治疗形成直接对比,在后者中,迫切需要确定能够可靠预测反应的生物标志物,从而避免这些药物在不太可能受益的患者中产生高昂成本和毒性。肿瘤学的免疫和分子治疗方法是最近才出现的现象,免疫检查点阻断和嵌合抗原受体T细胞疗法的疗效和安全性目前正在多中心随机对照试验中进行评估。在免疫肿瘤学和核诊疗肿瘤学中,传统的实体瘤疗效评价标准(RECIST)CT/MR解剖/功能成像在定义肿瘤反应方面的不足,损害了这种客观评价。这篇核诊疗临床实践介绍探讨了核医学医师可以从历史教训中学到什么,以及如何与医学、外科和放射肿瘤学同事建立共生合作关系,以实现个体化分子医学控制晚期癌症、切实提高生活质量同时延长生存期的潜力。