Osteosarcoma and Ewing sarcoma are bone tumors mostly diagnosed in children, adolescents, and young adults. Despite multimodal therapy, morbidity is high and survival rates remain low, especially in the metastatic disease setting. Trials investigating targeted therapies and immunotherapies have not been groundbreaking. Better understanding of biological subgroups, the role of the tumor immune microenvironment, factors that promote metastasis, and clinical biomarkers of prognosis and drug response are required to make progress. A prerequisite to achieve desired success is a thorough, systematic, and clinically linked biological analysis of patient samples, but disease rarity and tissue processing challenges such as logistics and infrastructure have contributed to a lack of relevant samples for clinical care and research. There is a need for a Europe-wide framework to be implemented for the adequate and minimal sampling, processing, storage, and analysis of patient samples. Two international panels of scientists, clinicians, and patient and parent advocates have formed the Fight Osteosarcoma Through European Research consortium and the Euro Ewing Consortium. The consortia shared their expertise and institutional practices to formulate new guidelines. We report new reference standards for adequate and minimally required sampling (time points, diagnostic samples, and liquid biopsy tubes), handling, and biobanking to enable advanced biological studies in bone sarcoma. We describe standards for analysis and annotation to drive collaboration and data harmonization with practical, legal, and ethical considerations. This position paper provides comprehensive guidelines that should become the new standards of care that will accelerate scientific progress, promote collaboration, and improve outcomes.

Survival in follicular lymphoma (FL) is highly variable, even within prognostic groups defined by tumor grade and the Follicular Lymphoma International Prognostic Index. Studies suggest that germline single nucleotide polymorphisms (SNPs) may hold prognostic information but further investigation is needed. We explored the association between SNPs and FL outcome using two approaches: 1) Two independent genome-wide association studies (GWAS) of ~300.000 SNPs followed by a meta-analysis encompassing 586 FL patients diagnosed in Denmark/Sweden 1999-2002 and in the United States 2001-2006; and 2) Investigation of 22 candidate-gene variants previously associated with FL outcome in the Danish/Swedish cohort (N = 373). We estimated time to lymphoma-specific death (approach 1 and 2) and lymphoma progression (approach 2) with hazard ratios (HR) and 95% confidence intervals (CI) in a multivariable Cox regression model. In the GWAS meta-analysis, using a random effects model, no variants were associated with lymphoma-specific death at a genome-wide significant level (p < 5.0 ×10-8). The strongest association was observed for tightly linked SNPs on 17q24 near the ABCA10 and ABCA6 genes (rs10491178 HRrandom = 3.17, 95% CI 2.09-4.79, prandom = 5.24 ×10-8). The ABCA10 and ABCA6 genes belong to a family of genes encoding for ABC transporter proteins, implicated in multidrug resistance. In line with a previous study, rs2466571 in CD46 (HR = 0.73, 95% CI 0.58-0.91, p = 0.006) showed nominal association with lymphoma progression, as did two highly linked SNPs in IL8 (rs4073 HR = 0.78, 95% CI 0.62-0.97, p = 0.02; rs2227307 HR = 0.75, 95% CI 0.60-0.94, p = 0.01) previously associated with overall survival. The results suggest a possible role for multidrug resistance in FL survival and add to the evidence that genetic variation in CD46 and IL8 may have prognostic implications in FL. Our findings need further confirmation in other independent populations or in a larger multicenter GWAS.

Introduction: Pretreatment prognostic factors in newly diagnosed osteosarcoma are important for clinical management and stratifying patients in clinical trials. Such factors include the presence of metastases, primary tumor size, and site. Factors surrounded by controversy include pathological fracture, histologic subtype, and P‐glycoprotein expression. No prognostic tumor biomarker has been established. We performed a systematic review with the aim to compile available evidence for pretreatment prognostic factors and define optimal cut‐off values for patient stratification or further validation in the upcoming European FOSTER‐CabOS trial.Methods: Predefined search terms were used to search PubMed, Web‐of‐science, and Embase for all studies investigating pretreatment prognostic factors in newly diagnosed osteosarcoma patients published 2000–2023. After applying strict inclusion and exclusion criteria, 49 papers were included.Results: We found 14 factors investigated in at least two separate studies or in a single study using one discovery and at least one validation cohort.Conclusions: We confirmed the prognostic value of patient age, presence of metastasis, tumor size, and site (axial vs. appendicular). Future studies of these factors should focus on specific patient populations and defining optimal cut‐off values. Although serum level of alkaline phosphatase and lactate dehydrogenase were associated with outcome, it remains unclear if they are independent of other prognostic factors. The prognostic value remains unclear for sex, pathological fracture, histologic subtype, and P‐glycoprotein expression. We could not establish any new prognostic biomarker. However, circulating tumor DNA in plasma and the G1/G2 RNA signature in diagnostic tumor biopsies show promise and will be further validated in the upcoming FOSTER‐CabOS trial.

Follicular lymphoma (FL) risk is strongly associated with germline genetic variation in human leukocyte antigen (HLA) class II. Cigarette smoking has been suggested to increase FL risk, primarily among women. We hypothesized that amino acids in HLA–antigen D–related β1 subunit (DRB1) interact with smoking in FL risk, as shown for rheumatoid arthritis. We analyzed 373 patients with FL and 818 controls from 2 population-based case-control studies in Sweden and Denmark (1999–2003). Haplotypes in HLA-DRB1 were imputed at amino acid positions 11, 13, 28, 30, and 70–74 (shared epitope). We estimated the relative risk of FL as odds ratios with 95% confidence intervals for different smoking status/haplotype combinations. Interaction was defined as departure from additivity of effects and quantified by the attributable proportion (AP). Relative to never-smokers carrying no shared epitope alleles, smoking was associated with the risk of FL among all subjects (for former smokers, odds ratio (OR) = 2.20, 95% confidence interval (CI): 1.10, 4.41; OR_current = 3.56, 95% CI: 1.60, 7.92) and women (OR_former = 2.95, 95% CI: 1.18, 7.37; OR_current = 5.63, 95% CI: 2.07, 15.3) carrying 2 shared epitope alleles but not among those carrying zero or 1 shared epitope allele. Smoking and shared epitope status interacted significantly as measured by AP (overall, AP = 0.6, 95% CI: 0.15, 1.0; for women, AP = 0.5, 95% CI: 0.005, 1.0). These results suggest a possible interaction between smoking and HLA-DRB1-associated antigen presentation in FL risk and provide a model to further unravel FL etiology.

Background: Childhood cancer survivors (CCS) are at high risk of chronic health conditions. We aimed to explore young adult CCS’ and matched references’ future diagnoses-specific healthcare use, sickness absence (SA), and disability pension (DP). Methods: We performed a prospective cohort study with microdata from seven nationwide Swedish registers. We included 1305 young adult CCS born 1983–1988 and living in Sweden in 2008 and 6430 matched references and followed them for ten years (2009–2018) regarding mean annual specialized outpatient visits, inpatient days, and SA (spells >14 days) and/or DP (SADP) days, overall and by eight diagnostic groups. Risk factors for >90 SADP days in 2018 were explored as odds ratios (OR) with 95% confidence intervals (CI) by adjusted logistic regression. Results: Approximately 80% of CCS and 90% of references did not have SADP in the ten-year follow-up. Mean SADP days/year was higher among CCS (40–50 days/year), particularly in CNS tumor survivors (76–83 days/year), compared to references (12–18 days/year). Most SADP days were DP days. CCS had more mean outpatient visits (1.6–1.8 visits/year) and inpatient days (0.8–1.7 days/year) than references (0.8–1.2 visits/year and 0.6–0.75 days/year, respectively). The main healthcare use and SADP diagnoses were neoplasms and psychiatric disorders among all CCS, along with nervous system and endocrine conditions among CNS tumor survivors. The risk of SADP >90 days in 2018 was higher among female compared to male CCS (OR = 2.34, 95% CI 1.67–3.32), those with elementary schooling compared to high school/university education (OR = 6.52, 95% CI 4.49–9.49), and survivors of CNS tumors compared to other malignancies (OR hematological versus CNS = 2.88, 95% CI 1.95–4.28; OR hematological versus non-CNS solid tumors = 0.71, 95% CI 0.45–1.09). Conclusions: Most CCS did not have SADP as young adults; nevertheless, their risk of SADP was higher than among matched references. CNS tumor survivors were at particularly high risk of SADP.