Clinical Significance of Incidental Central Venous Catheter-Related Thrombosis in Children Previously Treated for Cancer

Background: Up to 50% of children with cancer may develop clinically unsuspected venous thrombo-embolisms (VTE), most related to an underlying central venous catheter (CVC). Whether clinically unsuspected and symptomatic VTEs are associated with similar long-term clinical impacts in children with cancer is controversial.

Aims: To describe the proportion of patients with post-thrombotic syndrome (PTS) and with residual vascular occlusion among children previously treated for cancer and who required a CVC.

Methods: This cross-sectional study included 50 consecutive children aged 1-18 years old previously treated for cancer requiring a CVC, following completion of anticancer treatment and CVC removal, whose family provided informed consent. Children with brain tumors were excluded, given the important differences in anticancer treatment.

PTS was evaluated using CAPTSure©, an index validated for diagnosis and grading of pediatric PTS, available in English and in French. Any score > 10 represents PTS, and a score > 30 indicates moderate to severe PTS. Residual vascular occlusion was determined by Doppler ultrasound of the upper limb(s) in which CVC(s) had been placed and classified as patent, partial or complete occlusion. Doppler ultrasounds were performed by experienced radiologists unaware of the clinical assessment. Results of the Doppler ultrasound were blinded to the participants and research team. Obesity was defined as body mass index ≥ 95 percentile for age and sex.

Data are presented descriptively, with median (interquartile range, IQR) and proportions (%). Binomial proportion confidence intervals were estimated using the Clopper-Pearson interval method. Spearman rank correlations were used to determine the association between prior VTE, PTS and residual vascular occlusion.

Results: Fifty patients (median age: at cancer diagnosis: 4.5 years; at PTS assessment: 10.4 years; 52% male) were assessed at a median of 4.1 years (IQR: 2.9-5.3) after cancer diagnosis and 1.6 years (IQR: 0.7-3.4 years) after CVC removal. The most common cancer diagnoses were acute lymphoblastic leukemia (26, 52%), Hodgkin lymphoma (7, 14%) and non-Hodgkin lymphoma (5, 10%). No patient had received primary thromboprophylaxis. Most patients had 1 CVC (median 1, IQR: 1-1, 74% Port-A-Caths and 26% peripherally inserted central catheters), equally distributed between left and right-sided placements. Four CVCs were removed non-electively. Moreover, 11 patients (22%) had sustained a VTE during anticancer treatment, with 7/11 affecting upper limbs and deemed CVC-related. Complete and partial resolution of VTE was documented radiologically in 4/11 and 3/11, respectively.

The median CAPTSure© score was 0 (IQR: 0-5, range: 0-35). Three patients (6%, 95% CI: 2.1-16.2%) showed clinical evidence of PTS, including 1 (2%) with moderate to severe PTS. This patient had sustained a cerebral venous sinus thrombosis during treatment, and showed no upper limb vascular occlusion. Fourteen patients (28%, 95% CI: 18-42%) showed residual vascular occlusion on imaging, including 12 partial and 2 complete occlusions.

Prior VTE was significantly associated with higher CAPTSure© scores (r=0.4091, p=0.003). Conversely, no statistically significant relationship was observed between residual vascular occlusion and PTS (r=0.0581, p=0.688) nor between prior VTE and residual vascular occlusion (r=0.0425, p=0.769). Obesity was seen in 5 patients (10%) at PTS assessment and was more common among children with PTS compared to children without PTS (67% vs 6%, p=0.023).

Conclusion: Residual vascular occlusion, suggesting prior unresolved clinically unsuspected VTE, occurred in approximately 1 out of 4 children previously treated for cancer. PTS was rare and was not associated with residual vascular occlusion. The association between prior VTE and PTS suggests that VTE has long-lasting detrimental effects in children with cancer. Further longitudinal work is necessary to understand the natural history of clinically unsuspected VTE in children with cancer.