Walter Taal

Background: Plexiform neurofibromas (PNs) and malignant peripheral nerve sheath tumors (MPNSTs) are major complications in adults with neurofibromatosis type 1; we analyzed their clinical features and management in a large cohort of 1,067 adults. Methods: Clinical data from all adults seen at the Dutch NF1 expertise center (2004–2025) were retrospectively collected, including NF1 diagnostic features, genetic data and details on PNs and MPNSTs. Detailed information was recorded on up to three largest or most symptomatic PNs per patient. Five-year survival after MPNST and risk factors for MPNST were analyzed. Known genotype-phenotype associations were evaluated. Results: Among 1,067 adult patients with NF1 (1,019 generalized, 48 mosaic), PNs were present in 47%. Surgical management was frequently limited by regrowth and complications. Overall, 5% of patients were deceased; the median age of death was 48 years, most commonly due to MPNST. MPNST occurred in 4% of the patients, predominantly in proximal body regions. The presence of nodular PNs was an independent risk factor for MPNST. Five-year survival after MPNST was 54.5%. 17q11.2 microdeletion was associated with a higher risk for MPNST. Conclusions: This large cohort study highlights that PNs and the associated risk of malignant transformation represent a significant burden for individuals with NF1. The limitations of surgical management of PNs underscore the need for effective systemic therapies. The prognosis for MPNST remains poor. Regular follow-up is essential for all patients with NF1, particularly those in high-risk subgroups.

Background/Objectives High-resolution nerve ultrasound (HRUS) is a promising imaging modality in patients with neurofibromatosis type 1 (NF1). The aim of this study was to evaluate the use of HRUS in adults with NF1 by assessing changes in HRUS findings over a two-year follow-up time and reporting interobserver variability. Methods Sixty adult patients with NF1 were invited for a study visit including a clinical examination, nerve conduction studies (NCSs) and HRUS, at baseline and after two-years follow-up. The nerve cross-sectional area (CSA) was measured at standard anatomical sites and at additional sites in cases of nerve enlargements. In 16 patients, the CSA measurements of the median nerve on one side were performed by two observers to assess interobserver variability. Results Fifty-two patients participated in the follow-up visit. During follow-up, 40% of nerve enlargements increased, 46% decreased and 14% remained stable. Especially larger CSA measurements at baseline showed substantial increases and decreases at follow-up. The presence or absence of plexiform neurofibromas remained the same. Interobserver agreement of median nerve CSA measurements with HRUS was 0.982 (95% CI: 0.969–0.99). Conclusions HRUS can be an important additional imaging tool in patients with NF1. It is helpful to distinguish between patients with and without plexiform neurofibromas, which is relevant for estimating the risk of developing malignant peripheral nerve sheath tumors (MPNSTs). The good interobserver agreement supports the use of HRUS in clinical practice. The majority of nerve enlargements decreased spontaneously in size within two years, which limits the reliability of tumor volume as sole marker for treatment response.

Background: Limited information exists regarding the impact of neurofibromatosis type 1 (NF1) on patients’ sexuality, despite its significance for Quality of Life. We therefore explored how adult patients with NF1 experienced their sexuality. Methods: A cross-sectional study was conducted among adult patients with NF1. Sex life was ranked on a self-report scale ranging from 0 (very unhappy) up to 10 (very happy). Male sexual function was measured by the International Index of Erectile Function. Female sexual function was measured by the Female Sexual Function Index (FSFI). Differences between variables were analyzed using parametric tests. Results: Out of 568 patients, 294 respondents (52%) started the questionnaire, with 202/294 (69%) completing it. The mean age of respondents was 37 years (range 18-75 years), and 63% were female. Self-reported sex life was rated 4.9 (SD 3.1) for the total group. About 48% scored their sex life ≤ 5. Men with erectile problems (67%) scored their sex life significantly lower than men without erectile problems (4.0 vs 7.2, P < .001). Women with sexual problems (64%) on the FSFI scored their sex life significantly lower than women without sexual problems (3.8 vs 7.5, P < .001). Conclusion: Half the respondents scored their sex life as inadequate, with about two-thirds experiencing sexual problems. This research seems important to better address sexual health in a clinical setting.

We read with great interest the recent study by Iasella et al

Purpose: Pilocytic astrocytomas are circumscribed WHO grade I gliomas that predominantly affect children, although they also occur in adults. While maximal safe resection is standard treatment, until recently chemotherapy was often used in pediatrics with irresectable symptomatic tumors to delay radiotherapy. As evidence for this approach in adults is limited, we performed a multicenter retrospective cohort study on this subject. Methods: Adult patients (≥ 16 years) treated with chemotherapy between 2006 and 2020 across eight Dutch medical centers were included. Treatment response was centrally assessed using RAPNO criteria and survival outcomes were analyzed using the Kaplan–Meier method. Results: Thirty-one patients with pilocytic astrocytoma were included (median age 27 years). Most patients had received prior treatments, including radiotherapy ( n = 19) and/or surgery ( n = 17), with a median interval of over five years from histopathological diagnosis to the start of chemotherapy. Temozolomide was most frequently used (64.5%). The objective response rate for all types of chemotherapy was 42%, with a median progression-free survival of 20 months and a median overall survival of 49 months. Adolescents and young adults (< 40 years) showed significantly better survival outcomes. Conclusion: Chemotherapy offers meaningful disease control in adolescents and young adults with irresectable symptomatic pilocytic astrocytoma, after prior treatments. However, with the improved efficacy and tolerability of targeted treatments, such as BRAF/MEK inhibitors, treatment is shifting away from traditional chemotherapy and radiotherapy. Nevertheless, chemotherapy may still represent a viable treatment option in adolescent and young adults when no actionable molecular targets are identified or when targeted therapies have failed.

Background: Malignant peripheral nerve sheath tumors (MPNSTs) are rare, aggressive sarcomas, with 40% associated with neurofibromatosis type 1 (NF1). Surgical excision is the main treatment for localized disease; however, local recurrence (LR) remains high. Radiotherapy (RTx) is increasingly used to enhance local control in STS, but its use remains controversial due to the potential for increased major wound complications and an increased risk of secondary malignancies in NF1 patients. This study investigated the use and impact of RTx on local control in MPNSTs, particularly in the NF1 setting. Methods: Surgically treated primary MPNSTs from 1988 to 2019 in the MONACO multicenter cohort were included. Differences in demographics, treatment, and RTx use between NF1 and non-NF1 cases were examined. Factors influencing RTx administration and LR were assessed via multivariable analyses. Results: Among 499 patients (33.1% NF1), 143 (28.7%) experienced LRs. Radiotherapy was administered to 56.3% of patients (57.0% in the NF1 group), with 27.3% receiving neoadjuvant and 72.7% adjuvant RTx. RTx was administered significantly more often to high-grade and extremity tumors. While RTx did not affect overall survival, it reduced LR risk in sporadic cases (hazard ratio [HR] 0.530; 95% confidence interval [CI], 0.354–0.793) but not in the NF1 subgroup (HR 1.00; 95% CI, 0.545–1.85). In NF1 patients, a microscopically positive margin (R1) was the only risk factor for LR development (HR 2.1; 95% CI, 1.19–3.79). Conclusions: RTx is frequently used in the treatment of MPNSTs, regardless of NF1 status. While it may affect the LR rate in sporadic cases, its impact on NF1 patients is less clear.

Background/Objectives: Physicians face clinical dilemmas in the diagnosis of non-optic intraparenchymal lesions on MRI brain scans of patients with neurofibromatosis type 1. As the incidence and evolution of these lesions into adulthood remain unclear, we conducted a retrospective study on this topic. Methods: All adult neurofibromatosis type 1 patients who had at least one MRI brain scan in our center were selected for this study. Brain lesions with contrast enhancement after gadolinium administration and/or mass effect were named “glioma-like lesions”. Results: In our cohort of 396 adult neurofibromatosis type 1 patients, 182 had at least one MRI scan of the brain. A total of 48 glioma-like lesions were found in 38/182 patients. The majority of glioma-like lesions remained stable, decreased in size or even disappeared during a median follow-up time of 8.5 years. Twelve glioma-like lesions in 11/182 patients were resected or biopsied, and histology showed gliomas of astrocytic origin (WHO grade 1–4). Conclusions: It was concluded from these data that asymptomatic glioma-like lesions on MRI brain scans in neurofibromatosis type 1 patients, either with contrast enhancement and/or mass effect, had an indolent nature. Mildly symptomatic or asymptomatic patients can therefore be followed without invasive diagnostic and therapeutic procedures.

Background: Almost all patients with Neurofibromatosis type 1 (NF1) develop cutaneous neurofibroma (cNF), benign dermal tumours that have a large impact on the patient’s Quality of Life (QoL). The French cNF-Skindex is the first questionnaire to specifically assess cNF-related QoL in patients with NF1. We aimed to adapt and validate a Dutch version of the cNF-Skindex. Methods: The questionnaire was translated using forward and backwards translation, and subsequently administered to a sample of 59 patients on two separate occasions. Feasibility was evaluated by the presence of floor/ceiling effects. Reliability was assessed by evaluating internal consistency and test-retest reliability, by calculating Cronbach’s alpha and Spearman’s rank correlation coefficients. The EQ-5D-5L and SF-36 were used to evaluate convergent validity, using Spearman’s rank correlation coefficients. An exploratory factor analysis was performed to study the data’s internal structure. Multivariable linear regression was used to model the relationship between patient characteristics and the cNF-Skindex. Results: The Dutch cNF-Skindex demonstrated excellent feasibility and reliability (Cronbach’s alpha 0.96, test-retest correlation coefficient 0.88). Convergent validity was confirmed for the EQ-5D-5L and relevant SF-36 scales. All items and subdomains from the original questionnaire were confirmed following exploratory factor analysis. The patient characteristics included in the multivariable linear regression were not significantly associated with the cNF-Skindex score. Conclusions: The Dutch cNF-Skindex displayed excellent psychometric properties, enabling use in the Netherlands.