Today, children are surviving pediatric cancer at unprecedented rates, making it one of modern medicine’s true success stories. However, we are increasingly becoming aware of several deleterious effects of cancer and the subsequent “cure” that extend beyond physical sequelae. Indeed, survivors of childhood cancer commonly report cognitive, emotional, and psychological difficulties, including attentional difficulties, anxiety, and posttraumatic stress symptoms (PTSS). Cognitive late- and long-term effects have been largely attributed to neurotoxic effects of cancer treatments (e.g., chemotherapy, cranial irradiation, surgery) on brain development. The role of childhood adversity in pediatric cancer – namely, the presence of a life-threatening disease and endurance of invasive medical procedures – has been largely ignored in the existing neuroscientific literature, despite compelling research by our group and others showing that exposure to more commonly studied adverse childhood experiences (i.e., domestic and community violence, physical, sexual, and emotional abuse) strongly imprints on neural development. While these adverse childhood experiences are different in many ways from the experience of childhood cancer (e.g., context, nature, source), they do share a common element of exposure to threat (i.e., threat to life or physical integrity). Therefore, we argue that the double hit of early threat and cancer treatments likely alters neural development, and ultimately, cognitive, behavioral, and emotional outcomes. In this paper, we (1) review the existing neuroimaging research on child, adolescent, and adult survivors of childhood cancer, (2) summarize gaps in our current understanding, (3) propose a novel neurobiological framework that characterizes childhood cancer as a type of childhood adversity, particularly a form of early threat, focusing on development of the hippocampus and the salience and emotion network (SEN), and (4) outline future directions for research.

中文翻译：

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儿科癌症及其治疗的神经发育后果：应用早期逆境框架来理解认知、行为和情感结果

如今，儿童以前所未有的速度从儿科癌症中存活下来，这使其成为现代医学真正的成功故事之一。然而，我们越来越意识到癌症的一些有害影响以及随后超越身体后遗症的“治愈”。事实上，儿童癌症幸存者通常会出现认知、情感和心理困难，包括注意力困难、焦虑和创伤后应激症状 (PTSS)。认知的晚期和长期影响很大程度上归因于癌症治疗（例如化疗、颅脑照射、手术）对大脑发育的神经毒性作用。儿童期逆境在儿科癌症中的作用，即危及生命的疾病的存在和侵入性医疗程序的耐受性，在现有的神经科学文献中基本上被忽视了，尽管我们小组和其他人的令人信服的研究表明，接触更常见的研究了不良的童年经历（即家庭和社区暴力、身体、性和情感虐待）对神经发育的强烈影响。虽然这些不利的童年经历在很多方面与儿童癌症的经历不同（例如背景、性质、来源），但它们确实有一个共同的暴露威胁因素（即对生命或身体完整性的威胁）。因此，我们认为早期威胁和癌症治疗的双重打击可能会改变神经发育，并最终改变认知、行为和情感结果。在本文中，我们（1）回顾了针对儿童癌症的儿童、青少年和成人幸存者的现有神经影像学研究，（2）总结了我们目前理解中的差距，（3）提出了一种新的神经生物学框架，将儿童癌症描述为一种类型童年逆境的影响，特别是一种早期威胁，重点关注海马体以及显着性和情感网络（SEN）的发育，（4）概述未来的研究方向。