Purpose: Vincristine (VCR) is a chemotherapeutic agent used in the treatment of pediatric oncology patients, but its main toxicity is VCR‐induced peripheral neuropathy (VIPN). However, whether VIPN has an effect on health‐related quality of life (HR‐QoL) in children during treatment is unknown. Therefore, the aim of our study was to investigate the association between VIPN and HR‐QoL in children starting treatment for cancer.Methods: Measurements of VIPN were performed using two tools: Common Terminology Criteria for Adverse Events (CTCAE) and pediatric‐modified Total Neuropathy Score (ped‐mTNS). Assessment of HR‐QoL was done with self‐ and proxy assessment of the Cancer and Generic module of the Pediatric Cancer Quality of Life Inventory™ (PedsQL).Results: In total, N = 86 children were included. HR‐QoL of children with VIPN (n = 67%, 76%) was significantly lower in comparison with children without VIPN: estimated Total score of PedsQL Generic (proxy) 84.57; β = −8.96 and 95% confidence interval (CI) −14.48 to −3.43; p = 0.002, estimated PedsQL Generic Total score (self‐reported): 85.16, β = −8.38 (95% CI: −13.76 to −3.00); p = 0.003. Similar results were found in the Pain and Hurt domain of the PedsQL Cancer (pain: estimated score [proxy]: 85.28, β = −9.94 [95%CI: −16.44 to −3.45], p = 0.003; hurt: estimated score [self‐report] 97.57, β = −19.15 [95%CI: −26.82 to −11.48], p < 0.001).Conclusion: VIPN results in a significant reduction of HR‐QoL in children under treatment for a malignancy, which means that VIPN is important for the well‐being of pediatric oncology patients. Therefore, this study underlines the importance of optimizing treatment with VCR, thereby aiming to reduce VIPN while maintaining efficacy.

Vincristine (VCR) is frequently used in pediatric oncology and can be administered intravenously through push injections or 1 h infusions. The effects of administration duration on population pharmacokinetics (PK) are unknown. We described PK differences related to administration duration and the relation between PK and VCR-induced peripheral neuropathy (VIPN). PK was assessed in 1–5 occasions (1–8 samples in 24 h per occasion). Samples were analyzed using high-performance liquid chromatography/tandem mass spectrometry. Population PK of VCR and its relationship with administration duration was determined using a non-linear mixed effect. We estimated individual post-hoc parameters: area under the concentration time curve (AUC) and maximum concentration (C_max) in the plasma and peripheral compartment. VIPN was assessed using Common Terminology Criteria for Adverse Events (CTCAE) and the pediatric-modified total neuropathy score (ped-mTNS). Overall, 70 PK assessments in 35 children were evaluated. The population estimated that the intercompartmental clearance (IC-Cl), volume of the peripheral compartment (V₂), and C_max were significantly higher in the push group. Furthermore, higher IC-Cl was significantly correlated with VIPN development. Administration of VCR by push led to increased IC-Cl, V₂, and C_max, but were similar to AUC, compared to 1 h infusions. Administration of VCR by 1 h infusions led to similar or higher exposure of VCR without increasing VIPN.

Vincristine (VCR) is a frequently used chemotherapeutic agent. However, it can lead to VCR-induced peripheral neuropathy (VIPN). In this study we investigated if one-hour infusions of VCR instead of push-injections reduces VIPN in pediatric oncology patients. We conducted a multicenter randomized controlled trial in which participants received all VCR administrations through push injections or one-hour infusions. VIPN was measured at baseline and 1–5 times during treatment using Common Terminology Criteria of Adverse Events (CTCAE) and pediatric-modified Total Neuropathy Score. Moreover, data on co-medication, such as azole antifungals, were collected. Overall, results showed no effect of administration duration on total CTCAE score or ped-mTNS score. However, total CTCAE score was significantly lower in patients receiving one-hour infusions concurrently treated with azole antifungal therapy (β = -1.58; p = 0.04). In conclusion, generally VCR administration through one-hour infusions does not lead to less VIPN compared to VCR push injections in pediatric oncology patients. However, one-hour infusions lead to less severe VIPN compared to push-injections when azole therapy is administered concurrently with VCR. These results indicate that in children treated with VCR and requiring concurrent azole therapy, one-hour infusions might be beneficial over push injections, although larger trials are needed to confirm this association.

Vincristine (VCR) is an important component of curative chemotherapy for many childhood cancers. Its main side effect is VCR-induced peripheral neuropathy (VIPN), a dose limiting toxicity. Some children are more susceptible to VIPN, which is at least partially dependent on genetic factors and pharmacokinetics (PK). In this study, we identify and replicate genetic variants associated with VCR PK and VIPN. Patient samples from a randomized clinical trial studying the effect of administration duration of VCR on VIPN in 90 patients were used. PK sampling was conducted on between one and five occasions at multiple time points. A linear two-compartment model with first-order elimination was used, and targeted next-generation DNA sequencing was performed. Genotype–trait associations were analyzed using mixed-effect models or logistic regression analysis for repeated measures, or Poisson regression analysis in which the highest VIPN score per patient was included. Nine single-nucleotide polymorphisms (SNPs) in seven genes (NDRG1, GARS, FIG4, FGD4, SEPTIN9, CEP72, and ETAA1) were associated with VIPN. Furthermore, three SNPs in three genes (MTNR1B, RAB7A and SNU13) were associated with PK of VCR. In conclusion, PK of VCR and VIPN are influenced by SNPs; upfront identification of those that lead to an altered susceptibility to VIPN or VCR exposure could help individualize VCR treatment.

We report the clinical history of 2 female patients with Ewing sarcoma and microscopic ovarian infiltration. In both cases, the initial workup found no metastasis. However, the examination of cryopreserved ovarian tissues revealed the presence of CD99 positive tumor cells with rearrangement of EWS gene confirmed by FISH. Both children were treated as patients with localized tumor and are currently in remission. These reports underline that, in Ewing sarcoma patients, retransplantation of cryopreserved ovarian tissue is not harmless and could lead to cancer relapse. These observations question also on the significance of ovarian dissemination on Ewing sarcoma prognosis and therapy.