Citations

Abstract Advances in the treatment of Langerhans cell histiocytosis (LCH) have resulted in a growing survivor population. There is a lack of data on long-term outcomes among adults with LCH. We conducted a retrospective record review of 219 adults (aged ≥18 years) with LCH. Most common presentation was multisystem (34.2%), followed by single-system pulmonary (32%), unifocal (28.3%), and single-system multifocal (5.5%) LCH. Risk organ involvement (the liver, spleen, or bone marrow) was seen in 8.7% of cases, and 40 of 88 (45.5%) tested cases were BRAFV600E. At a median follow-up of 74 months, 5-year progression-free survival (PFS) was 58.3% and estimated median PFS was 83 months. Median overall survival (OS) was not reached; 5- and 10-year OS rates were 88.7% and 74.5%, respectively. Risk organ involvement was associated with worse PFS (hazard ratio [HR], 4.5) and OS (HR, 10.8). BRAFV600E was not associated with risk organ involvement or survival. When compared with matched unaffected US population, individuals with LCH had a significantly higher risk of overall mortality (standardized mortality ratio [SMR], 2.66), specifically among those aged <55 years at diagnosis (SMR, 5.94) and those with multisystem disease (SMR, 4.12). Second cancers occurred in 16.4% cases, including diverse hematologic and solid organ malignancies. LCH-associated deaths constituted 36.1% of deaths and occurred within 5 years of diagnosis. After 5 years, non-LCH causes of death, including second cancers, chronic obstructive pulmonary disease, and cardiovascular diseases, predominated. Our study highlights, to our knowledge, for the first time, that adults with LCH experience early and late mortality from non-LCH causes and the need for development of targeted survivorship programs to improve outcomes.

Abstract Introduction The CYP2D6 enzyme metabolizes opioids commonly prescribed for cancer‐related pain, and CYP2D6 polymorphisms may contribute to variability in opioid response. We evaluated the feasibility of implementing CYP2D6 ‐guided opioid prescribing for patients with cancer and reported pilot outcome data. Methods Adult patients from two cancer centers were prospectively enrolled into a hybrid implementation‐effectiveness clinical trial and randomized to CYP2D6 ‐genotype‐guided opioid selection, with clinical recommendations, or usual care. Implementation metrics, including provider response, medication changes consistent with recommendations, and patient‐reported pain and symptom scores at baseline and up to 8 weeks, were assessed. Results Most (87/114, 76%) patients approached for the study agreed to participate. Of 85 patients randomized, 71% were prescribed oxycodone at baseline. The median (range) time to receive CYP2D6 test results was 10 (3–37) days; 24% of patients had physicians acknowledge genotype results in a clinic note. Among patients with CYP2D6 ‐genotype‐guided recommendations to change therapy ( n = 11), 18% had a change congruent with recommendations. Among patients who completed baseline and follow‐up questionnaires ( n = 48), there was no difference in change in mean composite pain score (−1.01 ± 2.1 vs. −0.41 ± 2.5; p = 0.19) or symptom severity at last follow‐up (3.96 ± 2.18 vs. 3.47 ± 1.78; p = 0.63) between the usual care arm ( n = 26) and genotype‐guided arm ( n = 22), respectively. Conclusion Our study revealed high acceptance of pharmacogenetic testing as part of a clinical trial among patients with cancer pain. However, provider response to genotype‐guided recommendations was low, impacting assessment of pain‐related outcomes. Addressing barriers to utility of pharmacogenetics results and clinical recommendations will be critical for implementation success.

Introduction: Using a digital process that leverages electronic health records (EHRs) can ease many of the challenges presented by the traditional enrollment process for clinical trials. We tested if automated batch enrollment using a technology-enabled subject recruitment system (TESRS) enhances recruitment while preserving representation of research subjects for the study population in our study setting. Methods: An ongoing community-based prospective adult cohort study was used to randomize 600 subjects who were eligible by age and residential address to TESRS (n = 300) and standard mailing method (n = 300), respectively, for 3 months. Then, TESRS was initiated and included automatic identification of patients’ preference for being contacted (online patient portal vs postal mail) from EHRs and automatic sending out of invitation letters followed by completion of a short online survey for checking eligibility and the digital consent process if eligible. We compared (1) median time to consent from invitation sent out per subject and total subjects recruited after a 3-month recruitment period, (2) the estimated study staff’s time, and (3) representation of sociodemographic characteristics (e.g., age, sex, race, SES measured by HOUSES index, and rural residence) between subjects recruited via TESRS and those via traditional mailing methods. Results: Median age of randomized subjects (n = 600) was 63 years with 52.0% female and 89.2% non-Hispanic White. Over a 3-month period, results showed consent rate via TESRS was 13% (39/297) similar to 11% (31/295) via standard mailing. However, recruitment was significantly faster with the TESRS approach (median 7 vs 26 days) given the study staff’s effort. Study staff’s time saved by using TESRS compared to standard mailing approach was estimated at 40 min per subject (equivalent to 200 h for 300 subjects). No significant differences in characteristics of research subjects from the study population were found. Conclusion: Our study demonstrated the utility of TESRS as a subject recruitment digital technology which significantly enhanced the recruitment effort while reducing the study staff burden of recruitment while maintaining the consistency of characteristics of recruited subjects. The strategy and support for implementing and testing TESRS in other study settings should be considered.

Background: Adolescent and young adult cancer patients are at high risk of developing radiation-associated side effects after treatment. Proton beam radiation therapy might reduce the risk of these side effects for this population without compromising treatment efficacy. Methods: We review the current literature describing the utility of proton beam radiation therapy in the treatment of central nervous system tumors, sarcomas, breast cancer and Hodgkin lymphoma for the adolescent and young adult cancer population. Results: Proton beam radiation therapy has utility for the treatment of certain cancers in the young adult population. Preliminary data suggest reduced radiation dose to normal tissues, which might reduce radiation-associated toxicities. Research is ongoing to further establish the role of proton therapy in this population. Conclusion: This report highlights the potential utility of proton beam radiation for certain adolescent young adult cancers, especially with reducing radiation doses to organs at risk and thereby potentially lowering risks of certain treatment-associated toxicities.

Small-for-size syndrome (SFSS) is a well-recognized complication following liver transplantation (LT), with up to 20% developing this following living donor LT (LDLT). Preventing SFSS involves consideration of factors before the surgical procedure, including donor and recipient selection, and factors during the surgical procedure, including adequate outflow reconstruction, graft portal inflow modulation, and management of portosystemic shunts. International Liver Transplantation Society, International Living Donor Liver Transplantation Group, and Liver Transplant Society of India Consensus Conference was convened in January 2023 to develop recommendations for the prediction and management of SFSS in LDLT. The format of the conference was based on the Grading of Recommendations, Assessment, Development, and Evaluation system. International experts in this field were allocated to 4 working groups (diagnosis, prevention, anesthesia, and critical care considerations, and management of established SFSS). The working groups prepared evidence-based recommendations to answer-specific questions considering the currently available literature. The working group members, independent panel, and conference attendees served as jury to edit and confirm the final recommendations presented at the end of the conference by each working group separately. This report presents the final statements and evidence-based recommendations provided by working group 2 that can be implemented to prevent SFSS in LDLT patients.

AbstractYoung adults have increasing genomic testing opportunities; however, little is known about how equipped they feel about making decisions to learn personal genomic information. We conducted qualitative interviews with 19 young adults, ages 18–21 years old, enrolled in a research study where they made decisions about learning personal genomic risk for developing preventable, treatable, and adult‐onset conditions and carrier status for autosomal recessive conditions. Participants had the option to include a parent in their study visit and the decision‐making process. The goal of this project was to explore young adults' reasons for involving or not involving a parent in the study and to assess young adults' perspectives about parental roles in their healthcare. Nine participants included a parent in the study and ten did not include a parent. Eleven participants received genomic test results before the interview, while eight participants had not yet received their results at the time of the interview. The study team developed a coding guide and coded interview transcripts inductively and deductively using an interpretive descriptive‐analytic approach. Logistical issues dominated solo participants' reasons for not involving a parent in the study, whereas those who involved a parent often cited a close relationship with the parent and the parent's previous involvement in the participant's healthcare as reasons for involving them. Both groups of participants described gradually transitioning to independent healthcare decision‐making with age and felt their comfort in medical decision‐making depends on the severity of and their familiarity with the situation. Participants recommended that future genomic researchers or clinicians give young adults the option to involve a parent or friend as a support person in research or clinical visits. Although young adults may have different journeys toward independent healthcare decision‐making, some may benefit from continued parental or peer involvement after reaching the age of legal adulthood.

AbstractAdolescents and young adults (AYA) with lymphoma experience treatment‐related effects in the short and long term that impact their quality of life and survivorship experience. The effort to improve outcomes for AYA lymphoma survivors requires understanding the available literature, identifying current knowledge deficits, designing better clinical trials incorporating the patient perspective, using novel tools to bridge data gaps and building survivorship guidelines that translate research to clinical practice. This review article summarizes the current state of lymphoma treatment‐related outcomes in AYAs and provides future direction.

Purpose: Magnetic resonance elastography (MRE) has been established as the most accurate noninvasive technique for diagnosing liver fibrosis. Recent publications have suggested that the measurement of splenic stiffness is useful in setting where portal hypertension may be present. The goal of the current study was to compile normative data for MRE-assessed stiffness measurements of the spleen in young adults. Materials and Methods: A total of 100 healthy young Caucasian volunteers (65 females and 35 males) in the age range of 20 to 32 years were enrolled in this study. The participants reported no history of chronic spleen and liver disease, normal alcohol consumption, and a normal diet. The MRE data were acquired by using a 1.5 T whole-body scanner and a 2D GRE pulse sequence with 60 Hz excitation. Spleen stiffness was calculated as a weighted mean of stiffness values in the regions of interest manually drawn by the radiologist on three to five spleen slices. Results: Mean spleen stiffness was 5.09 ± 0.65 kPa for the whole group. Male volunteers had slightly higher splenic stiffness compared to females: 5.28 ± 0.78 vs. 4.98 ± 0.51 kPa, however, this difference was not statistically significant (p = 0.12). Spleen stiffness did not correlate with spleen fat content and liver stiffness but a statistically significant correlation with spleen volume was found. Conclusions: The findings of this study provide normative values for 2D MRE-based measurement of spleen stiffness in young adults, a basis for assessing the value of this biomarker in young patients with portal system pathologies.