Tom Wei-Wu Chen

Background:Ultrarare sarcomas (URS) are subtypes of sarcomas with an extremely low incidence (≤1 per 1,000,000), resulting in limited clinical understanding. This study aimed to investigate the clinical characteristics, overall survival (OS) outcomes, and prognostic factors of URS by using a national cancer registry database. Methods:Patients in the Taiwan Cancer Registry, diagnosed between January 2002 and December 2019, were included. Based on the International Classification of Diseases for Oncology, Third Edition, histologic codes and their incidence, patients were categorized into URS, non-URS (NURS), or non-sarcoma solid tumors (NSST). Annual percentage change (APC) and factors associated with OS were analyzed. Results:Among 1,578,049 patients, 0.23% (n = 3,690) were URS, 1.93% (n = 30,503) were NURS, and 97.83% (n = 1,543,856) were NSST. The most common URS histologies were conventional chordoma and extraskeletal Ewing sarcoma. The incidence of URS demonstrated an increase from 2002 to 2019 (APC = 2), without an improvement in OS [2011–2019 vs. 2002–2009 URS: HR, 1.12; 95% confidence interval (CI), 1.02–1.20]. After multivariable adjustment, OS remained worse in URS compared with NURS (HR, 1.86; 95% CI, 1.77–1.96). Across all age groups except 0 to 18 years, patients with URS had inferior OS to those with NURS. Notably, within individual URS histologies, age was independently associated with OS. Conclusions:Despite an increasing incidence, outcomes for URSs remain poor. Age emerges as a major determinant of heterogeneity and prognosis, underscoring the need for age-stratified approaches in future research and clinical management. Impact:Our findings underscore the urgent need for increased awareness of URS and characterize the impact of age on these patients.See related In the Spotlight, p. 1487

Supplementary Figure S1. The age distribution in each URS subtype. Among the five most common URS subtypes, extraskeletal Ewing sarcoma predominantly affects patients under 40 (age 70: 9.4%). Conversely, pleomorphic liposarcoma (age 70: 28.3%) and conventional chordoma (age 70: 15.5%) occur primarily in adult and elderly populations.

Supplementary Figure S2. The overall survival of (A) alveolar soft part sarcoma (ASPS) (B) desmoplastic small round cell tumor (DSRCT) in the four age subgroups. In ASPS, the 5-year OS rates were 93.3% in pediatric and adolescent patients(n=31), 58.6% in young adults (n=84), and 41.5% in adults (n=15) (log-rank test, P<0.05). Corresponding 5-year OS rates for DSRCT were 93.3% (n=31), 58.6% (n=84), and 41.5% (n=15), respectively (log-rank test, P < 0.05).

Supplementary Table S4. Comparison of 5-year overall survival rate between diagnosis periods across tumor subgroups

Supplementary Table S1. List of ultra-rare sarcoma entities according to the CTOS 2021 classification and reasons for exclusion from the analysis

Supplementary Table S3. The top five common subtypes of URS in each age subgroup.

Supplementary Table S2. The 5-year survival rate in each age groups in ascending order (excluding subtypes with patient number less than 5)

Supplementary Table S5. Comparison of 5-year overall survival rate between bone and soft tissue sarcomas among URS patients

Supplementary Table S6. Comparison of 5-year overall survival rate between ultra-rare sarcomas and non-ultra-rare sarcomas across anatomical sites

Background: Ultrarare sarcomas (URS) are subtypes of sarcomas with an extremely low incidence (≤1 per 1,000,000), resulting in limited clinical understanding. This study aimed to investigate the clinical characteristics, overall survival (OS) outcomes, and prognostic factors of URS by using a national cancer registry database. Methods: Patients in the Taiwan Cancer Registry, diagnosed between January 2002 and December 2019, were included. Based on the International Classification of Diseases for Oncology, Third Edition, histologic codes and their incidence, patients were categorized into URS, non-URS (NURS), or non-sarcoma solid tumors (NSST). Annual percentage change (APC) and factors associated with OS were analyzed. Results: Among 1,578,049 patients, 0.23% (n = 3,690) were URS, 1.93% (n = 30,503) were NURS, and 97.83% (n = 1,543,856) were NSST. The most common URS histologies were conventional chordoma and extraskeletal Ewing sarcoma. The incidence of URS demonstrated an increase from 2002 to 2019 (APC = 2), without an improvement in OS [2011–2019 vs. 2002–2009 URS: HR, 1.12; 95% confidence interval (CI), 1.02–1.20]. After multivariable adjustment, OS remained worse in URS compared with NURS (HR, 1.86; 95% CI, 1.77–1.96). Across all age groups except 0 to 18 years, patients with URS had inferior OS to those with NURS. Notably, within individual URS histologies, age was independently associated with OS. Conclusions: Despite an increasing incidence, outcomes for URSs remain poor. Age emerges as a major determinant of heterogeneity and prognosis, underscoring the need for age-stratified approaches in future research and clinical management. Impact: Our findings underscore the urgent need for increased awareness of URS and characterize the impact of age on these patients.