Efficacy and Safety of Apatinib for Radiation-induced Brain Injury Among Patients With Head and Neck Cancer: An Open-Label, Single-Arm, Phase 2 Study

He, Lei; Pi, Yaxuan; Li, Yang; Wu, Ying; Jiang, Jingru; Rong, Xiaoming; Cai, Jinhua; Yue, Zhihui; Cheng, Jinping; Li, Honghong; Chua, Melvin Lee Kiang; Simone, Charles B.; Aronow, Wilbert S.; Lattanzi, Simona; Palmer, Joshua D.; Gaertner, Jan; Glass, Jon; Chen, Pingyan; Tang, Yamei

doi:10.1016/j.ijrobp.2022.03.027

Cited by 6 publications

(5 citation statements)

References 35 publications

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“…A recent guideline recommended clinical intervention if conventional MRI indicated RT‐related brain injury 36 . Although novel therapies such as bevacizumab 37 and apatinib 38 ameliorate RT‐related brain necrosis, cognitive impairment after RT has remained a challenging side effect 39 . However, there is still a dearth of prevention strategies or early intervention therapy supported by sufficient clinical evidence.…”

Section: Discussionmentioning

confidence: 99%

Disparate Radiation‐Induced Microstructural Injuries in Whole‐Brain White Matter of Patients With Nasopharyngeal Carcinoma: A Longitudinal Study Using Multishell Diffusion MRI

Liang

Zhang

Lin

et al. 2023

Magnetic Resonance Imaging

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BackgroundEvidence for prevention strategies of radiotherapy (RT)‐related injury in patients with nasopharyngeal carcinoma (NPC) was lacking. Understanding the dynamic alterations in the cerebral white matter (WM) microstructure after RT may be helpful.PurposeTo investigate the dynamic alterations in the whole brain WM microstructure in patients with NPC in the 12 months after RT using multishell diffusion MRI (MS‐dMRI).Study TypeSingle‐center longitudinal study.PopulationA total of 28 treatment‐naïve patients with pathologically confirmed NPC (age: 39.68 ± 8.93 years, 11 female) and 20 healthy controls (age: 40.65 ± 9.76 years, 7 female).Field Strength/SequencesA 3 T, MS‐dMRI using a single‐shot echo planar imaging sequence.AssessmentMS‐dMRI was acquired at baseline for the NPC patients and healthy controls, at 0–3 (acute, AC), 6 (early delayed, ED) and 12 months (late delayed, LD) after RT for the NPC patients. The mean and maximum radiation doses to the temporal lobe were acquired. The quality of images was reviewed. MS‐dMRI was analyzed using tract‐based spatial statistics (TBSS). The presentations of injury were defined by the findings of TBSS.Statistical TestsChi‐square, t tests, repeated ANOVA, and Spearman‐rank correlation analysis were used. P < 0.05 was considered to be statistically significant.ResultsTBSS showed two WM injuries (injuries 1 and 2). Injury 1 emerged in the ED phase in the bilateral temporal poles and persisted throughout the ED and LD phases. Injury 2 developed from the AC to ED phase in the bilateral hemisphere and partially recovered in the LD phase. In the ED and LD phases, the multiple diffusion metrics were well correlated (r > 0.5 or <−0.5) with the RT dose, especially in the WM tracts in the temporal lobes.Data ConclusionDisparate WM injuries were observed in NPC patients after RT. The injuries may be primarily or secondarily induced by radiation. Injury 1 may be irreversible, while injury 2 seems to partially recover.Evidence Level2.Technical EfficacyStage 4.

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Section: Discussionmentioning

confidence: 99%

Disparate Radiation‐Induced Microstructural Injuries in Whole‐Brain White Matter of Patients With Nasopharyngeal Carcinoma: A Longitudinal Study Using Multishell Diffusion MRI

Liang

Zhang

Lin

et al. 2023

Magnetic Resonance Imaging

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“…Apatinib monotherapy has been investigated in multiple subsequent studies on nasopharyngeal and non-nasopharyngeal SCCHN with encouraging results ( 76 – 78 ). Apatinib has also been shown to be efficacious in ameliorating radiation-induced brain injury amongst patients with head and neck cancer ( 79 ). Table 1 summarizes the aforementioned studies on VEGF-TKI monotherapy in SCCHN.…”

Section: Vegf-tkis In Scchnmentioning

confidence: 99%

Critical review of the current and future prospects of VEGF-TKIs in the management of squamous cell carcinoma of head and neck

Puttagunta,

Pamulapati,

Bates

et al. 2023

Front. Oncol.

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As the prognosis for squamous cell carcinoma of the head and neck remains unsatisfactory when compared to other malignancies, novel therapies targeting specific biomarkers are a critical emerging area of great promise. One particular class of drugs that has been developed to impede tumor angiogenesis is vascular endothelial growth factor-tyrosine kinase inhibitors. As current data is primarily limited to preclinical and phase I/II trials, this review summarizes the current and future prospects of these agents in squamous cell carcinoma of the head and neck. In particular, the combination of these agents with immunotherapy is an exciting area that may be a promising option for patients with recurrent or metastatic disease, evidenced in recent trials such as the combination immune checkpoint inhibitors with lenvatinib and cabozantinib. In addition, the use of such combination therapy preoperatively in locally advanced disease is another area of interest.

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“… 4 Clinically, glucocorticoids and bevacizumab are used as first‐line medicines, 5 , 6 and thalidomide and apatinib have passed phase II clinical trials according to previous researches. 7 , 8 However, current therapeutic approaches fall short of satisfaction due to a lack of knowledge regarding the pathogenesis. Although accumulating evidence has involved DNA damage, neuron death, glial activation, blood–brain barrier (BBB) disruption, and oxide stress response in the development of RIBI, the specific mechanisms remain unclear.…”

Section: Introductionmentioning

confidence: 99%

“…It dramatically affects the life quality of more than 50% of patients who undergo radiotherapy and survive 4 . Clinically, glucocorticoids and bevacizumab are used as first‐line medicines, 5,6 and thalidomide and apatinib have passed phase II clinical trials according to previous researches 7,8 . However, current therapeutic approaches fall short of satisfaction due to a lack of knowledge regarding the pathogenesis.…”

Section: Introductionmentioning

confidence: 99%

Terminally differentiated cytotoxic CD4⁺ T cells were clonally expanded in the brain lesion of radiation‐induced brain injury

Ma,

Zuo,

et al. 2024

CNS Neurosci Ther

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BackgroundAccumulating evidence supports the involvement of adaptive immunity in the development of radiation‐induced brain injury (RIBI). Our previous work has emphasized the cytotoxic function of CD8+ T cells in RIBI. In this study, we aimed to investigate the presence and potential roles of cytotoxic CD4+ T cells (CD4+ CTLs) in RIBI to gain a more comprehensive understanding of adaptive immunity in this context.Main TextUtilizing single‐cell RNA sequencing (scRNA‐seq), we analyzed 3934 CD4+ T cells from the brain lesions of four RIBI patients and identified six subclusters within this population. A notable subset, the cytotoxic CD4+ T cells (CD4+ CTLs), was marked with high expression of cytotoxicity‐related genes (NKG7, GZMH, GNLY, FGFBP2, and GZMB) and several chemokine and chemokine receptors (CCL5, CX3CR1, and CCL4L2). Through in‐depth pseudotime analysis, which simulates the development of CD4+ T cells, we observed that the CD4+ CTLs exhibited signatures of terminal differentiation. Their functions were enriched in protein serine/threonine kinase activity, GTPase regulator activity, phosphoprotein phosphatase activity, and cysteine‐type endopeptidase activity involved in the apoptotic signaling pathway. Correspondingly, mice subjected to gamma knife irradiation on the brain showed a time‐dependent infiltration of CD4+ T cells, an increase of MHCII+ cells, and the existence of CD4+ CTLs in lesions, along with an elevation of apoptotic‐related proteins. Finally, and most crucially, single‐cell T‐cell receptor sequencing (scTCR‐seq) analysis at the patient level determined a large clonal expansion of CD4+ CTLs in lesion tissues of RIBI. Transcriptional factor‐encoding genes TBX21, RORB, and EOMES showed positive correlations with the cytotoxic functions of CD4+ T cells, suggesting their potential to distinguish RIBI‐related CD4+ CTLs from other subsets.ConclusionThe present study enriches the understanding of the transcriptional landscape of adaptive immune cells in RIBI patients. It provides the first description of a clonally expanded CD4+ CTL subset in RIBI lesions, which may illuminate new mechanisms in the development of RIBI and offer potential biomarkers or therapeutic targets for the disease.

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Efficacy and Safety of Apatinib for Radiation-induced Brain Injury Among Patients With Head and Neck Cancer: An Open-Label, Single-Arm, Phase 2 Study

Cited by 6 publications

References 35 publications

Disparate Radiation‐Induced Microstructural Injuries in Whole‐Brain White Matter of Patients With Nasopharyngeal Carcinoma: A Longitudinal Study Using Multishell Diffusion MRI

Disparate Radiation‐Induced Microstructural Injuries in Whole‐Brain White Matter of Patients With Nasopharyngeal Carcinoma: A Longitudinal Study Using Multishell Diffusion MRI

Critical review of the current and future prospects of VEGF-TKIs in the management of squamous cell carcinoma of head and neck

Terminally differentiated cytotoxic CD4⁺ T cells were clonally expanded in the brain lesion of radiation‐induced brain injury

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Efficacy and Safety of Apatinib for Radiation-induced Brain Injury Among Patients With Head and Neck Cancer: An Open-Label, Single-Arm, Phase 2 Study

Cited by 6 publications

References 35 publications

Disparate Radiation‐Induced Microstructural Injuries in Whole‐Brain White Matter of Patients With Nasopharyngeal Carcinoma: A Longitudinal Study Using Multishell Diffusion MRI

Disparate Radiation‐Induced Microstructural Injuries in Whole‐Brain White Matter of Patients With Nasopharyngeal Carcinoma: A Longitudinal Study Using Multishell Diffusion MRI

Critical review of the current and future prospects of VEGF-TKIs in the management of squamous cell carcinoma of head and neck

Terminally differentiated cytotoxic CD4+ T cells were clonally expanded in the brain lesion of radiation‐induced brain injury

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Terminally differentiated cytotoxic CD4⁺ T cells were clonally expanded in the brain lesion of radiation‐induced brain injury