11548 Background: Sarcomas are a rare and heterogenous group of cancers that arise from bone or soft tissue, and two thirds have poorly defined mutational profiles. Given their rarity, few comprehensive studies have fully characterized mutations and gene expression across sarcoma histologies correlated with clinical outcomes. Further studies are needed to determine the presence of targetable mutations that may improve patient outcomes. In this study, we explored the genomic landscape and clinical actionability of sarcoma mutations from patients enrolled in our CAUSAL (Cohort to Augment the Understanding of Sarcoma survivorship Across the Lifespan) study. Methods: Between 04/01/2022 and 01/01/2023, 481 participants, treated from 2012 – present with multiple sarcoma histologies were enrolled on CAUSAL. Next Generation Sequencing (NGS) was performed on primary or metastatic tumors from 76 patients to determine DNA mutations within a 648 gene panel. Whole transcriptome RNA sequencing (seq) provided expression profiles and RNA fusion products. Further analysis was performed using principal components analysis of RNA seq data to explore correlates amongst sarcoma subtypes. Tumor mutations were queried in ClinVar for relevance to known variants and were assigned to tiers I-IV based on the ESMO scale for clinical actionability of molecular targets (ESCAT). Tier I mutations have drug-mutation matched evidence of actionability while tier IV have only pre-clinical evidence. Results: NGS has been completed on 76 tumor samples. Sequenced tumors represented 19 histologies, with the most common ones as follows: undifferentiated pleomorphic sarcoma (15.8%), liposarcoma (9.2%), gastrointestinal stromal tumor (9.2%), osteosarcoma (7.9%), and leiomyosarcoma (7.9%). Of 76 patients, 66 (87%) had at least one mutation detected with an mean frequency of 2.74. TP53 (20/66), RB1 (14/66), and ATRX (9/66) were most commonly mutated genes. Mean (std) tumor mutation burden (TMB) was 3.4 m/MB (3.5m/MB) and one tumor had TMB of 25.3 m/MB. Of the 76 samples, 68 had RNA expression and fusion data available, of which 42 (62%) had anomalous expression changes and 11 had RNA fusions. The most overexpressed genes were NY-ESO-1 (13), LAGE-1 (9), and RET (7); the most under-expressed genes were SMARCB1 (9) and MGMT (6). 30.2% (23 of 76) of patients had potentially actionable DNA mutations, 9 had ESCAT tier I DNA mutations, 3 had tier II, 10 had tier III, and 1 had tier IV. 29.4% (20/68) of patients had potential targets based on RNA expression. 51.3% (39/76) patients had either a potential DNA or RNA target, and 6.6% (5/76) had multiple RNA or DNA targets. Conclusions: NGS revealed potentially actionable targets in over half of sarcoma patients based on ESCAT criteria. With ongoing accrual and sequencing of additional tumor specimens future analysis of CAUSAL will focus on assessing the correlation between targetable mutations and clinical outcomes.
e24165 Background: A cancer diagnosis is stressful for both patients and caregivers, and there may be interdependence of mental health. Integration of caregivers into support for AYAO patients may improve outcomes. Methods: We enrolled dyads of AYAO patients (age 15-39) and their caregivers within the first month of treatment. Eligible patients were treated with curative intent or expected remission of at least 5 years. We assessed participants at baseline using validated self-reported survey methods, including the COmprehensive Score for financial Toxicity (COST), Impacts of Events Scale-Revised (IES-R), Adult Self-Report (ASR), NCCN Distress Thermometer and Problem List, and FACT-G and FACT-GP instruments. Results: We enrolled 13 dyads with patient age range 22 to 39 (median 29) years with 60% male patients and 30% male caregivers. Median scores for the NCCN Distress Thermometer were 5.0 for patients (sd 2.9) and caregivers (sd 2.4), with a score of 3 consistent with significant distress. On the Problem List, greater than half of both patients and caregivers reported “yes” to problems with “insurance/financial,” “work/school,” “treatment decisions,” “fears,” “sadness,” “worry,” and “fatigue,” and independently with “family health issues” and “work/school,” respectively. Median patient FACT-G summary score was 78, with median sub-scale scores (27.5 social, 19.5 functional, 17.5 emotional, 15.5 physical). Likewise, median caregiver FACT-GP score was 58 with sub-scale scores (20 physical, 20 functional, 15 social, 10 emotional), with higher scores indicating better quality of life. COST median scores were 12 for patients (sd 9) and caregivers (sd 7), where max score 44 indicates least financial toxicity. IES-R median patient and caregiver scores were 16 (sd 16) and 46 (sd 26), respectively, with scores >24 concerning for PTSS. In contrast, median patient and caregiver ASR depression and anxiety sub-scales were not in the range for concern. Conclusions: Diagnosis is a critical moment of distress for caregivers and patients alike. Effective interventions are needed to alleviate acute suffering and to improve short-term psychological and financial wellbeing for both caregivers and patients. Such outcomes may translate to longer-term benefit. As we continue to accrue dyads, we will follow them over 6 months to assess changes in distress pattern over time and identify the critical time periods for intervention.
Abstract Moon snail predation on clams is a common model system of predator–prey interactions. In this system, the predator bores through the shell of its prey, leaving a distinct and identifiable hole. Some paleoecological and behavioral research on moon snails suggests a trend in predation preference directed toward clams with small shells. Rarely, however, have studies tested relative drilling frequencies across species and size ranges in natural assemblages of clam communities. We examined the clam community composition at two beaches in South Carolina, USA, and we then tested moon snail predator preferences for (a) clam prey species and (b) whether their selection is related to prey shell size. We collected a total of 1,879 clam shells, identified each shell to species and recorded their anteroposterior length. The species composition of clams differed significantly between the two beaches; Anadara ovalis was dominant at both sites, but three of ten total species were only collected at one beach. Folly Beach had nearly a 60% higher the overall drilling frequency (34.6%) versus Edisto Beach (21.8%), and this may be linked to the differences in clam community compositions at the sites. For A. ovalis and Mulinia lateralis , shells with larger lengths have lower probabilities of being bored by a moon snail. Anadara brasiliana , which generally is a thinner‐shelled clam species, had the highest total drilling frequency (77.2%), and Noetia ponderosa , a thicker‐shelled clam, had a considerably lower drilling frequency (12.0%). We conclude that both community level factors (species composition) and population characteristics (shell size distributions) may influence the local drilling frequency by moon snails.
12085 Background: Sarcomas are a rare heterogeneous malignancy group affecting both sexes and all ages. Treatment is often intensive, resulting in long-term toxicities. Given the rarity of sarcoma, there is a paucity of data defining physical and emotional outcomes. The Cohort to Augment the Understanding of Sarcoma Survivorship Across the Lifespan (CAUSAL) was constructed at Vanderbilt University Medical Center (VUMC) to evaluate health-related outcomes. Methods: Sarcoma patients treated at VUMC from 2012 – present are enrolled into CAUSAL. Patient demographics, tumor and treatment data are abstracted from the electronic medical record. Participants complete surveys including PROMIS-57 consisting of seven domains including physical function, sleep disturbance, fatigue, and satisfaction with participation in social roles, which are reported here. Participants who have completed treatment are given a FitBit to track activity level and sleep over 12 weeks. Data are synced to an online platform, Fitabase. Body mass index (BMI) is assessed at study entry. For each participant, FitBit data were summarized using medians. To estimate the association between PROMIS-57 scores and activity and sleep data (FitBit), linear regression models were fit controlling for age, sex, and BMI of participants. Results: Of 306 CAUSAL participants who completed the PROMIS-57, 193 were post completion of sarcoma therapy. Of these, 76 also had FitBit data and are included in this analysis. Median step count was 5826 (quartiles: 3668, 7967), which was lower than average Fit Bit step count data for the US population (8170). Median daily active minutes was 252 minutes (quartiles: 174, 307). Median duration of sleep was 447 minutes (quartiles:381, 474) which was greater than the average reported by FitBit for the general US population (436 min). Step count was correlated with higher physical function score (p < 0.001). A 10-point increase in physical function led to an average increase of 1291 (95% CI: 609,1973) steps when adjusting for age and sex. Compared with participants receiving treatment within 30 days prior to CAUSAL enrollment, participants not receiving treatment had 4.50 (95% CI: 1.53, 7.47) higher physical function score and 6.26 (95% CI: 1.87, 10.65) higher satisfaction in their social roles. There was no correlation between minutes of sleep recorded by FitBit and PROMIS responses. Conclusions: Using PROMIS-57, and FitBits, we demonstrated an association between higher step counts and self-reported higher physical function but did not find a correlation between FitBit recorded activity level/sleep and self-reported sleep disturbance or fatigue scores. Further, our data suggests patients with sarcoma sleep more and walk less than the general US population. As enrollment continues in CAUSAL, we will focus on PROMIS scores over time and their association with activity level and sleep.
10046 Background: Retinoblastoma (RB) is the most common tumor of the eye in childhood. Intraocular RB cure rates approach 100%. Therefore, treatment now focuses on globe salvage preserving functional vision. The Research Into Visual Endpoints and RB Health Outcomes After Treatment (RIVERBOAT) consortium was established to examine patient health outcomes, including vision, in the contemporary therapy era. Methods: Patients with RB treated at consortium centers from 2007 to present were identified. Medical record abstraction was performed for disease presentation, treatment, and outcomes. A subset of the patients returned to centers and completed functional vision questionnaires (Child Vision Function Questionnaire - ages 0 – 7 and Cardiff Visual Ability Questionnaire for Children - ages > 8) and had visual acuity assessed. For participants who could not yet return for a study evaluation, medical record abstraction alone was performed. Results: Among 463 participants enrolled to date, 270 (58%) had unilateral disease. One patient with metastatic RB did not survive, resulting in overall survival of 99.6. There was one case of secondary leukemia. The eye group distribution (International Intraocular Retinoblastoma Classification) was 0.4% A, 5.6% B, 7.0% C, 36.0% D, 49.0% E and 2.0% not classified. 131 (49%) patients underwent primary enucleation and are not included in further analyses. Among the remaining 139 patients, 3% were treated with local ophthalmic therapy only, 22% with intravenous chemotherapy (IV) only, 53% with intra-arterial chemotherapy (IAC) only, 22% with IV and IAC, and 35% required secondary enucleation. Globe salvage after chemotherapy was successful in 100% A, 93% B, 82% C, 72% D, and 48% E eyes. This salvage was achieved with IV only, IAC only, or both in 22%, 58% and 20% respectively. The mean percentage of patients receiving IAC per year increased from 13% (2008 – 2013) to 21% (2014 – 2017) to 28% (2018 – 2022). In 29 patients without enucleation who reported functional vision to date, the mean scores (survey theoretical ranges) were 0.72 for < 3 years (0.57 to 0.87), 0.82 for 3 -7 years (0.56 to 0.94) and -2.72 for > 8 years (-2.53 to -0.51), all considered good functional vision. In 20 of these 29 patients, 4 eyes had normal vision (20/20-20/40) across A to D groups. Moderate vision loss (> 20/40 – 20/70) was noted in 3 D eyes and low vision (> 20/70 - < 20/200) in 1 D eye. Twelve B through E eyes met criteria for a legally blind eye (>20/200). Conclusions: In this cohort of RB patients with unilateral disease treated from 2007 - 2022, 66% required primary or secondary enucleation. Among 29 patients with globe salvage, self-reported functional vision was good, but 12 eyes in 20 of the patients were legally blind. IAC only or IV plus IAC was most used in those who avoided secondary enucleation. With ongoing cohort accrual and increased IAC use, it will remain to be determined if globe salvage with functional vision will improve.
