From the Stephen E. and Catherine Pappas Center for Neuro-Oncology (K.I.L., V.L.M., R.D.T., J.L.D., C.C.O., H.P.H., S.R.P., J.T.J.), Massachusetts General Hospital; Department of Radiology (W.C., M.A.B., C.Y.C., G.J.H.), Massachusetts General Hospital; Biostatistics Center (A.M.), Massachusetts General Hospital; and Department of Obstetrics and Gynecology (M.E.M.), Massachusetts General Hospital, Boston.
Neurology. 2023 Feb 14;100(7):e661-e670. doi: 10.1212/WNL.0000000000201535. Epub 2022 Nov 4.
Internal neurofibromas, including plexiform neurofibromas (PNF), can cause significant morbidity in patients with neurofibromatosis type 1 (NF1). PNF growth is most pronounced in children and young adults, with more rapid growth thought to occur in a subset of PNF termed distinct nodular lesions (DNL). Growth behavior of internal neurofibromas and DNL in older adults is not well documented; yet knowledge thereof is important for patient risk stratification and clinical trial design. The primary objective of this study was to evaluate the long-term growth behavior of internal neurofibromas in adults with NF1. Secondary objectives were to correlate tumor growth behavior with patient-specific, tumor-specific, and patient-reported variables.
In this prospective cohort study, internal neurofibromas were identified on coronal short TI inversion recovery sequences on baseline and follow-up whole-body MRIs (WBMRIs). Tumor growth and shrinkage were defined as a volume change ≥20%. The association between tumor growth and patient-specific (baseline age, sex, and genotype), tumor-specific (morphology, location, DNL presence on baseline WBMRI, and maximum standardized uptake value on baseline PET imaging), and patient-reported variables (endogenous and exogenous hormone exposure, pain intensity, and quality of life) was assessed using the Spearman correlation coefficient and Kruskal-Wallis test.
Of 106 patients with a baseline WBMRI obtained as part of a previous research study, 44 had a follow-up WBMRI. Three additional patients with WBMRIs acquired for clinical care were included, generating 47 adults for this study. The median age during baseline WBMRI was 42 years (range 18-70). The median time between WBMRIs was 10.4 years. Among 324 internal neurofibromas, 62.8% (56% of PNF and 62.1% of DNL) shrank spontaneously without treatment and 17.1% (17.9% of PNF and 13.8% of DNL) grew. Growth patterns were heterogeneous within participants. Patient-specific, tumor-specific, and patient-reported variables (including endogenous and exogenous hormone exposure) were not strong predictors of tumor growth.
Internal neurofibroma growth behavior in older adults differs fundamentally from that in children and young adults, with most tumors, including DNL, demonstrating spontaneous shrinkage. Better growth models are needed to understand factors that influence tumor growth. These results will inform clinical trial design for internal neurofibromas.
神经纤维瘤病 1 型（NF1）患者的体内神经纤维瘤，包括丛状神经纤维瘤（PNF），可导致显著的发病率。PNF 在儿童和青年中生长最为明显，据认为，在称为明显结节性病变（DNL）的 PNF 亚组中，生长更为迅速。老年人的体内神经纤维瘤和 DNL 的生长行为尚未得到充分记录；然而，了解这一点对于患者的风险分层和临床试验设计非常重要。本研究的主要目的是评估 NF1 成年患者体内神经纤维瘤的长期生长行为。次要目的是将肿瘤生长行为与患者特定、肿瘤特定和患者报告的变量相关联。
在这项前瞻性队列研究中，在基线和随访全身 MRI（WBMRI）的冠状短 TI 反转恢复序列上识别体内神经纤维瘤。肿瘤生长和缩小定义为体积变化≥20%。使用 Spearman 相关系数和 Kruskal-Wallis 检验评估肿瘤生长与患者特定（基线年龄、性别和基因型）、肿瘤特定（形态、位置、基线 WBMRI 上的 DNL 存在以及基线 PET 成像上的最大标准化摄取值）和患者报告变量（内源性和外源性激素暴露、疼痛强度和生活质量）之间的关联。
在之前的研究中，有 106 名患者进行了基线 WBMRI 检查，其中 44 名患者进行了随访 WBMRI 检查。另外 3 名因临床护理进行了 WBMRI 检查的患者也包括在内，共有 47 名成年人参与了这项研究。基线 WBMRI 时的中位年龄为 42 岁（18-70 岁）。两次 WBMRI 之间的中位时间为 10.4 年。在 324 个体内神经纤维瘤中，62.8%（56%的 PNF 和 62.1%的 DNL）自发缩小而无需治疗，17.1%（17.9%的 PNF 和 13.8%的 DNL）生长。参与者内的生长模式存在异质性。患者特定、肿瘤特定和患者报告的变量（包括内源性和外源性激素暴露）并不是肿瘤生长的强预测因素。
老年人体内神经纤维瘤的生长行为与儿童和青年的生长行为有根本的不同，大多数肿瘤，包括 DNL，表现出自发性缩小。需要更好的生长模型来了解影响肿瘤生长的因素。这些结果将为体内神经纤维瘤的临床试验设计提供信息。
