Infants younger than 1 year with bone and soft tissue tumors had poorer survival than children aged 1 to 10 years despite no greater risk of relapse, a gap largely explained by a 4-fold higher risk of treatment-related mortality (TRM), according to a Canadian population-based study published in Pediatric Blood & Cancer.¹ After accounting for tumor type and metastases, infancy remained independently associated with worse overall survival (OS), with an adjusted HR of 1.61 (95% CI, 1.13-2.31; P = .009).

Infants also developed a different mix of tumors than older children. Malignant rhabdoid tumors (MRT) made up more than a quarter of infant cases vs less than 3% in older children.

These cancers typically require several treatment modalities, but the authors explained that cases arising before a first birthday are uncommon and poorly characterized. An earlier analysis by the same group found that infants with any cancer in Canada had worse outcomes than older children, with the youngest facing the highest TRM.²

The researchers used data from the Cancer in Young People in Canada program, a national surveillance system that tracks treatment, complications, and outcomes for children with cancer at all 16 of the country’s pediatric cancer and transplant centers.³ The retrospective cohort included 1102 children aged 10 years or younger with extracranial bone or soft tissue neoplasms diagnosed from 2001 through 2020, of whom 146 (13.2%) were infants.

Incidence among infants rose from 1.7 per 100,000 infant-years in the first decade to 2.27 per 100,000 in the second (P = .03). Fibrosarcoma (28.8%), MRT (26.7%), and rhabdomyosarcoma (25.3%) were the most frequent infant diagnoses, whereas rhabdomyosarcoma (43.8%), Ewing sarcoma (20.1%), and osteosarcoma (15.6%) were the most common among older children. The share of patients with metastases at diagnosis was similar between age groups (26.6% vs 27.5%; P = .83).

Treatment-Related Mortality Drove the Survival Gap

Of 53 infants (36.3%) who died during follow-up, 12 (22.6%) died from treatment toxicities or other complications. Deaths from treatment toxicity occurred in 4.8% of infants vs 1.5% of older children (HR, 4.03; 95% CI, 1.62-9.99; P = .003), even though grade 3 and 4 treatment-related complications were reported at comparable rates (13.7% vs 14.9%; P = .71).

OS in infants lagged at 1 year (63.7% vs 81.5%) and at 5 years (56.9% vs 62.0%), and the survival curves differed significantly (log-rank P < .001) because infant deaths tended to occur earlier. Relapse by 5 years was less common among infants (26.3% vs 38.4%), but this gap did not reach statistical significance (P = .19).

“Together, these findings suggest that the survival disadvantage observed in infants was driven more by excess treatment-related toxicity rather than by higher relapse risk or intrinsically more aggressive disease,” the authors wrote. They noted that infants process drugs differently, which could make a toxicity of a given grade more dangerous at this age.

Survival at 5 years for infants was lowest with MRT (16.8%) and highest with fibrosarcoma (92.7%). The authors noted that early-phase trials of the EZH2 inhibitor tazemetostat (Tazverik; Ipsen) excluded infants younger than 1 year, whereas larotrectinib (Vitrakvi; Bayer), approved by the FDA for solid tumors harboring NTRK gene fusions, has changed management of NTRK fusion-positive infantile fibrosarcoma.^1,4

Study Limitations and Calls for Age-Adapted Care

The study was limited by its retrospective design, which may lead to incomplete or misclassified data, and the rarity of individual subtypes reduced power for subgroup comparisons. Molecular data were not routinely captured, and the therapy responsible for each treatment-related death could not be identified, the authors explained. Infants were also less likely than older children to be enrolled in a clinical trial (8.4% vs 19.8%; P < .001).

“These findings highlight the unmet need to identify novel treatment approaches that balance toxicity and efficacy, especially for infants with MRT,” the authors concluded. “Future progress will require to leverage biologically informed diagnostics and risk stratification, age-adapted therapeutic drug monitoring and supportive care, and expansion of age limit to include infants in early phase trials to provide access to innovative therapies for high-risk tumors that are prevalent during infancy.”

References

1. Sassine S, Coltin H, Kondyli M, et al. Bone and soft tissue neoplasms in infants versus older children: a report from the Cancer in Young People in Canada program. Pediatr Blood Cancer. Published online 2026:e70753. doi:10.1002/1545-5017.70753

2. Sassine S, Coltin H, Kondyli M, et al. Incidence and outcome of infants with cancer in Canada: a report from Cancer in Young People in Canada database. Pediatr Blood Cancer. 2026;73(2):e70050. doi:10.1002/1545-5017.70050

3. The Cancer in Young People in Canada program. Public Health Agency of Canada. Updated June 9, 2026. Accessed November 6, 2026. https://www.canada.ca/en/public-health/services/chronic-diseases/cancer/cancer-young-people-canada-program.html

4. Laetsch TW, Voss S, Ludwig K, et al. Larotrectinib for newly diagnosed infantile fibrosarcoma and other pediatric NTRK fusion-positive solid tumors (Children’s Oncology Group ADVL1823). J Clin Oncol. 2025;43(10):1188-1197. doi:10.1200/JCO-24-01854