Department of Radiation Oncology, Lausanne University Hospital and University of Lausanne, Switzerland; Radiation Oncology Laboratory, Department of Radiation Oncology. Lausanne University Hospital and University of Lausanne, Switzerland.
Department of Radiation Oncology, Lausanne University Hospital and University of Lausanne, Switzerland.
Radiother Oncol. 2019 Oct;139:18-22. doi: 10.1016/j.radonc.2019.06.019. Epub 2019 Jul 11.
When compared to conventional radiotherapy (RT) in pre-clinical studies, FLASH-RT was shown to reproducibly spare normal tissues, while preserving the anti-tumor activity. This marked increase of the differential effect between normal tissues and tumors prompted its clinical translation. In this context, we present here the treatment of a first patient with FLASH-RT.
MATERIAL & METHODS: A 75-year-old patient presented with a multiresistant CD30+ T-cell cutaneous lymphoma disseminated throughout the whole skin surface. Localized skin RT has been previously used over 110 times for various ulcerative and/or painful cutaneous lesions progressing despite systemic treatments. However, the tolerance of these RT was generally poor, and it was hypothesized that FLASH-RT could offer an equivalent tumor control probability, while being less toxic for the skin. This treatment was given to a 3.5-cm diameter skin tumor with a 5.6-MeV linac specifically designed for FLASH-RT. The prescribed dose to the PTV was 15 Gy, in 90 ms. Redundant dosimetric measurements were performed with GafChromic films and alanine, to check the consistency between the prescribed and the delivered doses.
At 3 weeks, i.e. at the peak of the reactions, a grade 1 epithelitis (CTCAE v 5.0) along with a transient grade 1 oedema (CTCAE v5.0) in soft tissues surrounding the tumor were observed. Clinical examination was consistent with the optical coherence tomography showing no decrease of the thickness of the epidermis and no disruption at the basal membrane with limited increase of the vascularization. In parallel, the tumor response was rapid, complete, and durable with a short follow-up of 5 months. These observations, both on normal skin and on the tumor, were promising and prompt to further clinical evaluation of FLASH-RT.
This first FLASH-RT treatment was feasible and safe with a favorable outcome both on normal skin and the tumor.
在临床前研究中，与传统放射治疗（RT）相比，FLASH-RT 能够重复地保护正常组织，同时保留抗肿瘤活性。这种正常组织与肿瘤之间差异效应的显著增加促使其进行临床转化。在这种情况下，我们在此介绍首例接受 FLASH-RT 治疗的患者。
一名 75 岁的患者患有多耐药 CD30+T 细胞皮肤淋巴瘤，全身皮肤均有扩散。局部皮肤 RT 以前曾用于 110 多次治疗各种溃疡性和/或疼痛性皮肤病变，但尽管进行了全身治疗，这些 RT 的疗效仍然较差，有人假设 FLASH-RT 可以提供等效的肿瘤控制概率，同时对皮肤的毒性更小。该治疗用于一个直径为 3.5 厘米的皮肤肿瘤，使用专门设计用于 FLASH-RT 的 5.6-MeV 直线加速器。将 15Gy 的处方剂量施用于 PTV，照射时间为 90ms。使用 GafChromic 胶片和丙氨酸进行冗余剂量测量，以检查规定剂量与实际剂量之间的一致性。
在 3 周时，即反应高峰期，观察到肿瘤周围软组织的 1 级上皮炎（CTCAE v5.0）和短暂的 1 级水肿（CTCAE v5.0）。临床检查与光学相干断层扫描结果一致，表皮厚度无减少，基膜无破坏，血管化程度有限增加。同时，肿瘤反应迅速、完全且持久，随访时间仅为 5 个月。这些观察结果无论是在正常皮肤还是肿瘤上都很有希望，并促使对 FLASH-RT 进行进一步的临床评估。
首例 FLASH-RT 治疗是可行且安全的，对正常皮肤和肿瘤均有良好的效果。
