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New Radiation Oncology Optimization Principles Based On In-Vivo Predictive Assay and Recent Developments in Molecular Radiation Biology 基于体内预测分析和分子放射生物学最新进展的新放射肿瘤学优化原则
Pub Date : 2024-02-07 DOI: 10.29011/2574-7754.101625
Anders Brahme, Brahme A. Ann Case
The recent understanding that most TP53-intact normal tissues are Low-Dose Hypersensitive (LDHS) and Low-Dose Apoptotic (LDA) implies that the well-known fractionation window at ≈ 2 Gy/Fr defines the optimal tolerance level for most organs at risk and not at all the tumor dose as still is customary today when using IMRT. This necessitates new approaches to biologically optimized radiation therapy, requiring that the maximum dose to organs at risk should be ≤2.3 Gy/Fr, and especially that it should be of low ionization density and LET . Today we know that the fractionation window is due to a low-dose initiation of full DNA repair capability in normal tissues first after ≈½ Gy, and we should use this acquired repair advantage to its full extent up to ≈2.3 Gy where the High Dose Apoptosis (HDA) may set in. Thus biologically optimized treatments should be focused on the application of a low number of high tumor-dose intensity-and/or radiation quality-modulated photon, electron or lower LET light ion beams. Doing so, reduces the integral dose delivery and the risk for secondary cancers and generates a real tumor cure without risk for caspase-3-induced accelerated tumor cell repopulation. The light ions should truly have the lowest possible LET in normal tissues to retain the fractionation window property but still have a high LET only in the gross tumor region to simultaneously maximize tumor cell inactivation. This necessitates the use of the lightest ions, from helium to ≈boron, as this fractionation advantage is practically lost for carbon and heavier ions. This unique property of the lightest ions is combined with the highest possible apoptosis and senescence in front of the Bragg peak and can best be characterized as allowing molecular radiation therapy since surrounding normal tissues are only exposed to a low dose and LET that causes easily repairable damage. Many other new associated ideas are also discussed, such as optimal use of IMRT, molecular tumor imaging with MRSI, PET-CT and phase contrast X-rays, TP53 cell survival radiation biology, biologically optimized radiation therapy: BIOART, quantum biology of curative radiation therapy, 4D-space-time radiation therapy optimization, influence of microdosimetric heterogeneity on the dose response relation, optimal time dose fractionation, accounting for tumor hypoxia, biologically optimal radiation quality, secondary cancer risks, mutant TP53 reactivation, and optimal dose delivery techniques since they are all involved directly or indirectly in these new principles for true optimization of radiation therapy.
最近,人们认识到大多数与 TP53 接触的正常组织对低剂量超敏感(LDHS)和低剂量凋亡(LDA),这意味着众所周知的≈2 Gy/Fr 的分次窗口定义了大多数危险器官的最佳耐受水平,而不是目前使用 IMRT 时所习惯的肿瘤剂量。这就需要采用新的生物优化放射治疗方法,要求对危险器官的最大剂量应≤2.3 Gy/Fr,尤其是应具有较低的电离密度和LET。如今我们知道,分化窗口是由于正常组织在≈½ Gy后首先开始低剂量全面修复DNA的能力,我们应该充分利用这种已获得的修复优势,直到≈2.3 Gy时,高剂量凋亡(HDA)才可能出现。因此,生物优化治疗应侧重于应用少量高肿瘤剂量强度和/或辐射质量调制的光子、电子或低 LET 光离子束。这样做可以减少整体剂量传递,降低继发癌症的风险,并真正治愈肿瘤,而不会有因 Caspase-3 引发的肿瘤细胞加速再增殖的风险。光离子在正常组织中应具有尽可能低的 LET,以保留分馏窗口特性,但在肿瘤区域仍应具有较高的 LET,以同时最大限度地灭活肿瘤细胞。这就需要使用从氦到≈硼的最轻离子,因为碳和较重的离子实际上已经失去了这种分馏优势。最轻离子的这一独特特性与布拉格峰前最高可能的凋亡和衰老相结合,可以说是分子放射治疗的最佳特征,因为周围正常组织只受到低剂量和低辐射的照射,造成的损伤很容易修复。此外还讨论了许多其他相关的新观点,如 IMRT 的最佳使用、利用 MRSI、PET-CT 和相衬 X 射线进行肿瘤分子成像、TP53 细胞存活辐射生物学、生物优化放射治疗:BIOART、治疗性放射治疗的量子生物学、4D-时空放射治疗优化、微剂量异质性对剂量反应关系的影响、最佳时间剂量分次、肿瘤缺氧考虑、生物学最佳放射质量、继发性癌症风险、突变 TP53 再激活以及最佳剂量输送技术,因为它们都直接或间接地涉及到这些真正优化放射治疗的新原则。
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引用次数: 0
Exploring the Prevalence of Low Antithrombin III Level among Post-cardiac Surgery Patients and its Impact on Heparin Efficacy 探讨心脏手术后患者抗凝血酶 III 水平低的普遍性及其对肝素疗效的影响
Pub Date : 2024-02-07 DOI: 10.29011/2574-7754.101627
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引用次数: 0
Oritavancin-Induced Toxic Epidermal Necrolysis (TEN): A Case Report 奥立万星诱发的中毒性表皮坏死(TEN):病例报告
Pub Date : 2024-02-05 DOI: 10.29011/2574-7754.101603
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引用次数: 0
Oritavancin-Induced Toxic Epidermal Necrolysis (TEN): A Case Report 奥立万星诱发的中毒性表皮坏死(TEN):病例报告
Pub Date : 2024-02-05 DOI: 10.29011/2574-7754.101603
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引用次数: 0
Effect of Stem Cell Injections in an Acute Anterior Cruciate Ligament Injury 干细胞注射对急性前十字韧带损伤的影响
Pub Date : 2024-01-30 DOI: 10.29011/2574-7754.101612
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引用次数: 0
Important Connection Between Pregnancy and Desmoid Tumors 怀孕与蝶形肿瘤之间的重要联系
Pub Date : 2024-01-29 DOI: 10.29011/2574-7754.101610
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引用次数: 0
Prohibitin Expression in Antigen-Presenting Cells: Implications for Inciting Trigger in CNS IgG4-Related Disease 抗原递呈细胞中抑制素的表达:中枢神经系统 IgG4 相关疾病的诱发因素
Pub Date : 2024-01-25 DOI: 10.29011/2574-7754.101607
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引用次数: 0
Rare Case of Wide Spread Fungal Spinal Osteomyelitis with Severe Back Pain under Conservative Treatment. Case Report and Review of the Literature 罕见的大范围真菌性脊髓骨髓炎病例,在保守治疗的同时伴有严重的背部疼痛。病例报告和文献综述
Pub Date : 2024-01-25 DOI: 10.29011/2574-7754.101608
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引用次数: 0
Uncommon Presentation of Pyogenic Granuloma in the Small Intestine: A Rare Case Report 小肠化脓性肉芽肿的罕见表现:罕见病例报告
Pub Date : 2024-01-24 DOI: 10.29011/2574-7754.101605
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引用次数: 0
Pulmonary Lymphoepithelioma-Like Carcinoma (PLELC) With a Completed Metabolic Response after Chemoradiotherapy: A Case Report and Review of the Literature 化疗后代谢反应完全的肺淋巴上皮细胞瘤样癌 (PLELC):病例报告与文献综述
Pub Date : 2024-01-22 DOI: 10.29011/2574-7754.101600
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引用次数: 0
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