Late-toxicity burden high among survivors of high-risk neuroblastoma

CHICAGO — Survivors of high-risk neuroblastoma face a substantial burden of late toxicity, according to study results presented at ASCO Annual Meeting.

Prevalence of some late effects vary by treatment received, findings showed.

Background

Survival in high-risk neuroblastoma has improved due to use of aggressive therapies; however, the late toxicities associated with use of these approaches have not been clearly established, according to study background.

Tara O. Henderson, MD, FASCO, MPH,director of the Childhood, Adolescent and Young Adult Survivorship Center at University of Chicago, and colleagues used medical conducted a comprehensive cross-sectional evaluation of outcomes among high-risk neuroblastoma survivors who had enrolled in the Chidlren’s Oncology Group ALTE15N2 — LEAHRN study.

Researchers used in-person clinical assessments and medical record abstraction to evaluate patients who enrolled in the study after Jan. 1, 2000, and were at least 5 years beyond primary diagnosis. They performed descriptive and multivariable analyses to evaluate extent of and risk factors for late toxicity.

The analysis included 375 participants (55% male; 74% white; 13% Hispanic) from 88 centers.

Median age at diagnosis was 2.5 years (range, 0.2-15.8). Median age at enrolment was 12 years (range, 5-24).

All received chemotherapy and 94% had received cisplatin (median dose, 398 mg/m²). Other treatments included radiation (95%), isotretinoin (91%), anti-GD2 antibody therapy (64%), metaiodobenzylguanidine (7%), single autologous transplantation (79%) and tandem autologous transplantation (20%).

Transplantation conditioning regimens included busulfan/melphalan (18%), carboplatin/etoposide/melphalan (73%), thiotepa/cytoxan (19%) and total body irradiation (5%).

Results

绝大多数(88%)的幸存者经历ototoxicity, with 58% reporting severe cases — defined as requiring hearing aids.

Nearly one-quarter (24%) exhibited growth failure (defined as > – 2 Height Z score), and an analysis of 142 girls aged 8 years or older showed 24% had premature ovarian failure.

Eight percent exhibited restrictive lung disease, defined as total lung capacity less than 70% of expected.

Other physician-reported late effects included hypothyroidism (17%), pulmonary hypertension (4%) and congestive heart failure (2%).

Fifteen (4%) study participants developed subsequent malignant neoplasms. These included sarcoma (n = 4), myelodysplasia (n = 2) and one case each of four with sarcoma and three with myelodysplastic syndrome/therapy-related acute myeloid leukemia, as well as one case each of eight other cancers.

Multivariable analyses showed higher risk for growth failure (OR = 3.4; 95% CI, 1.8-7) and restrictive lung disease (OR = 6.8; 95% CI, 1.4-33.9) among patients who underwent tandem vs. single transplant with carboplatin/etoposide/melphalan conditioning.

Researchers reported lower risk for restrictive lung disease among those who received anti-GD2 antibody therapy vs. those who did not (OR = 0.2; 95% CI, .04-0.9).

Multivariable analysis identified multiple factors associated with severe hearing loss, including exposure to higher-dose cisplatin (P= .04), carboplatin in transplant (P= .02) and age at diagnosis (more than 547 days or younger than 5 years,P= .01).

Results also showed a significant interaction between cisplatin and carboplatin, indicating a fourfold increase in hearing loss among patients who received high-dose vs. low-dose cisplatin in the setting of no carboplatin-based stem cell transplant. In contrast, results showed no significant effect of high-dose vs. low-dose induction cisplatin in the setting of carboplatin-based stem cell transplant.

Henderson and colleagues acknowledged limitations, including the potential that enrollment bias may have influenced measures of prevalence, and the limited generalizability in the setting of Children’s Oncology Group-based treatment regimens.

额外的分析将执行检查cardiopulmonary, renal and endocrine outcomes, as well as quality of life and educational outcomes.

In addition, investigators will perform whole-genome sequencing of collected germline DNA from members of the cohort to determine whether associations exist between late toxicity and genetic correlates or variants.