Byron Sigel

Multiple myeloma (MM) is the most common plasma cell dyscrasia in the United States with tremendously high burden. MM is preceded by a premalignant condition, monoclonal gammopathy of undetermined significance (MGUS). Although several risk factors for progression have been identified (e.g., older age, male sex, black race, obesity, chemical exposure), their relative contributions remain unclear. Unlike other malignancies, such evidence is lacking for MM despite its high burden. To identify potential intervention strategies that can effectively prevent progression in patients with MGUS, we quantified contributions of the identified modifiable risk factors in the United States Veteran population with MGUS. Compared to the general population, this population is particularly vulnerable to MM as its higher proportions of male and older age as well as the potential prior Agent Orange exposure. We conducted a retrospective cohort study in the Veterans Health Administration and calculated multivariable‐adjusted population attributable fractions (aPAFs) of progression accounting for competing risk of death. The aPAF estimates the proportion of progression burden in the population with MGUS that is statistically attributable to a specific risk factor, independent of other factors. In the cohort of 35,073 Veterans with MGUS, among all evaluated risk factors (both modifiable and non‐modifiable), excess body mass index (BMI ≥25 kg/m ² ) was the leading factor (Black: aPAF = 27.1%, 95% CI 19.5%–34.0%; White: 27.2%, 95% CI 20.3%–33.4%; All: aPAF = 27.1%, 95% CI 22.1%–31.9%). Our study highlights the potential of weight management and lifestyle modification for informing the design of targeted MM prevention strategies for Veterans diagnosed with MGUS.

Adult primary brain and central nervous system (CNS) cancers, though comprising only about 4% of new cancer diagnoses, significantly impact morbidity and mortality due to their low survival rates. Globally, brain and CNS tumor incidence varies considerably, with the United States exhibiting one of the highest rates and Japan among the lowest worldwide. In the United States, incidence rates differ by race, with higher rates in non‐Hispanic whites (NHW) and lower rates in Asian Americans and Pacific Islanders (AAPI). This study examines the incidence of malignant CNS tumors in Japan and Japanese Americans, comparing these groups to NHW and AAPI populations in the United States. We estimated age‐standardized incidence rates (ASR) of brain and CNS tumors among adults using data from the Monitoring of Cancer Incidence in Japan (MCIJ) and the U.S. Surveillance, Epidemiology, and End Results (SEER)‐9 registries from 2007 to 2014. Incidence rates were stratified by age, sex, and specific CNS tumor subtypes. Incidence rates of CNS tumors among Japanese (ASR: 3.66, 95% CI: 3.56–3.76) and Japanese Americans (ASR: 2.5, 95% CI: 2.13–3.05) were lower than among NHW (9.43, 95% CI, 9.31–9.56) and AAPI populations (ASR: 4.13, 95% CI: 3.94–4.33) in the United States. The same pattern was observed for CNS tumor subtypes and across age groups and sex. This study supports a genetic component in the risk of brain and CNS tumors, a cancer type with largely unknown etiology. By comparing incidence rates across populations, it contributes to understanding the balance of genetic and environmental risk factors in the development of these cancers.

PURPOSE: Survivors of hereditary retinoblastoma have excellent survival but substantially increased risks of subsequent bone and soft-tissue sarcomas, particularly after radiotherapy. Comprehensive investigation of sarcoma risk patterns would inform clinical surveillance for survivors. PATIENTS AND METHODS: In a cohort of 952 irradiated survivors of hereditary retinoblastoma who were originally diagnosed during 1914 to 2006, we quantified sarcoma risk with standardized incidence ratios (SIRs) and cumulative incidence analyses. We conducted analyses separately for bone and soft-tissue sarcomas occurring in the head and neck (in/near the radiotherapy field) versus body and extremities (out of field). RESULTS: Of 105 bone and 124 soft-tissue sarcomas, more than one half occurred in the head and neck (bone, 53.3%; soft tissue, 51.6%), one quarter in the body and extremities (bone, 29.5%; soft tissue, 25.0%), and approximately one fifth in unknown/unspecified locations (bone, 17.1%; soft tissue, 23.4%). We noted substantially higher risks compared with the general population for head and neck versus body and extremity tumors for both bone (SIR, 2,213; 95% CI, 1,671 to 2,873 v SIR, 169; 95% CI, 115 to 239) and soft-tissue sarcomas (SIR, 542; 95% CI, 418 to 692 v SIR, 45.7; 95% CI, 31.1 to 64.9). Head and neck bone and soft-tissue sarcomas were diagnosed beginning in early childhood and continued well into adulthood, reaching a 60-year cumulative incidence of 6.8% (95% CI, 5.0% to 8.7%) and 9.3% (95% CI, 7.0% to 11.7%), respectively. In contrast, body and extremity bone sarcoma incidence flattened after adolescence (3.5%; 95% CI, 2.3% to 4.8%), whereas body and extremity soft-tissue sarcoma incidence was rare until age 30, when incidence rose steeply (60-year cumulative incidence, 6.6%; 95% CI, 4.1% to 9.2%), particularly for females (9.4%; 95% CI, 5.1% to 13.8%). CONCLUSION: Strikingly elevated bone and soft-tissue sarcoma risks differ by age, location, and sex, highlighting important contributions of both radiotherapy and genetic susceptibility. These data provide guidance for the development of a risk-based screening protocol that focuses on the highest sarcoma risks by age, location, and sex.