3 research outputs found
Neuroblastoma between 1990 and 2014 in the Netherlands: Increased incidence and improved survival of high-risk neuroblastoma
Purpose: Long-term trends in neuroblastoma incidence and survival in unscreened populations are unknown. We explored trends in incidence, stage at diagnosis, treatment and survival of neuroblastoma in the Netherlands from 1990 to 2014. Methods: The Netherlands Cancer Registry provided data on all patients aged <18 years diagnosed with a neuroblastoma. Trends in incidence and stage were evaluated by calculating the average annual percentage change (AAPC). Univariate and multivariable survival analyses were performed for stage 4 disease to test whether changes in treatment are associated with survival. Results: Of the 593 newly diagnosed neuroblastoma cases, 45% was <18 months of age at diagnosis and 52% had stage 4 disease. The age-standardized incidence rate for stage 4 disease increased at all ages from 3.2 to 5.3 per million children per year (AAPC + 2.9%, p <. 01). This increase was solely for patients ≥18 months old (3.0–5.4; AAPC +3.3%, p =. 01). Five-year OS of all patients increased from 44 ± 5% to 61 ± 4% from 1990 to 2014 (p <. 01) and from 19 ± 6% to 44 ± 6% (p <. 01) for patients with stage 4 disease. Multivariable analysis revealed that high-dose chemotherapy followed by autologous stem cell rescue and anti-GD2-based immunotherapy were associated with this survival increase (HR 0.46, p <. 01 and HR 0.37, p <. 01, respectively). Conclusion: Incidence of stage 4 neuroblastoma increased exclusively in patients aged ≥18 months since 1990, whereas the incidence of other stages remained stable. The 5-year OS of stage 4 patients improved, mostly due to the introduction of high-dose chemotherapy followed by stem cell rescue and immunotherapy
Age does matter in adolescents and young adults versus older adults with advanced melanoma; a national cohort study comparing tumor characteristics, treatment pattern, toxicity and response
Cutaneous melanoma is a common type of cancer in Adolescents and Young Adults
(AYAs, 15–39 years of age). However, AYAs are underrepresented in clinical trials investigating new
therapies and the outcomes from these therapies for AYAs are therefore unclear. Using prospectively
collected nation-wide data from the Dutch Melanoma Treatment Registry (DMTR), we compared
baseline characteristics, mutational profiles, treatment strategies, grade 3–4 adverse events (AEs),
responses and outcomes in AYAs (n = 210) and older adults (n = 3775) who were diagnosed with
advanced melanoma between July 2013 and July 2018. Compared to older adults, AYAs were more
frequently female (51% versus 40%, p = 0.001), and had a better Eastern Cooperative Oncology Group
performance status (ECOG 0 in 54% versus 45%, p = 0.004). BRAF and NRAS mutations were age
dependent, with more BRAF V600 mutations in AYAs (68% versus 46%) and more NRAS mutations in
older adults (13% versus 21%), p < 0.001. This finding translated in distinct first-line treatment patterns,
where AYAs received more initial targeted therapy. Overall, grade 3–4 AE percentages following
first-line systemic treatment were similar for AYAs and older adults; anti-PD-1 (7% versus 14%,
p = 0.25), anti-CTLA-4 (16% versus 33%, p = 0.12), anti-PD-1 + anti-CTLA-4 (67% versus 56%, p = 0.34)
and BRAF/MEK-inhibition (14% versus 23%, p = 0.06). Following anti-CTLA-4 treatment, no AYAs
experienced a grade 3–4 colitis, while 17% of the older adults did (p = 0.046). There was no difference
in response to treatment between AYAs and older adults. The longer overall survival observed in
AYAs (hazard ratio (HR) 0.7; 95% CI 0.6–0.8) was explained by the increased cumulative incidence of
non-melanoma related deaths in older adults (sub-distribution HR 2.8; 95% CI 1.5–4.9), calculated by
competing risk analysis. The results of our national cohort study show that baseline characteristics
and mutational profiles differ between AYAs and older adults with advanced melanoma, leading to
different treatment choices made in daily practice. Once treatment is initiated, AYAs and older adults
show similar tumor responses and melanoma-specific survival