Outcomes in patients with ETV6::RUNX1 or high-hyperdiploid B-ALL treated in the St. Jude Total Therapy XV/XVI studies.

Children with ETV6::RUNX1 or high-hyperdiploid B-acute lymphoblastic leukemia (B-ALL) have favorable outcomes. The St. Jude (SJ) classification considers these patients low-risk, regardless of their National Cancer Institute (NCI) risk, except when there is slow minimal residual disease (MRD) response or central nervous system/testicular involvement. We analyzed outcomes in children (aged 1-18.99 years) with these genotypes in the SJ Total XV and XVI studies (2000-2017). Patients with ETV6::RUNX1 (n = 222) or high-hyperdiploid (n = 296) B-ALL had 5-year event-free survival (EFS) of 97.7% ± 1.1% and 94.7% ± 1.4%, respectively. For ETV6::RUNX1, EFS was comparable for NCI standard-risk and high-risk patients (97.8% ± 1.2% and 97.5% ± 2.6%, respectively; P = 0.917) and for SJ low-risk and standard-risk patients (97.4% ± 1.2% and 100.0%; P = 0.360). Thirty-seven of 40 NCI high-risk patients who received SJ low-risk therapy had excellent EFS (97.3% ± 2.8%). For high-hyperdiploid B-ALL, EFS was worse for NCI high-risk patients than for standard-risk patients (87.6% ± 4.5% and 96.4% ± 1.3%; P = 0.016). EFS was similar for NCI standard-risk and high-risk patients classified as SJ low-risk (96.0% ± 1.5% and 96.9% ± 3.2%; P = 0.719); however, EFS was worse for NCI high-risk patients than for NCI standard-risk patients receiving SJ standard/high-risk therapy (77.4% ± 8.2% and 98.0% ± 2.2%; P = 0.004). NCI high-risk patients with ETV6::RUNX1 or high-hyperdiploid B-ALL who received SJ low-risk therapy had lower incidences of thrombosis (P = 0.013) and pancreatitis (P = 0.011) than those who received SJ standard/high-risk therapy. Contemporary MRD-directed therapy yielded excellent outcomes, except for NCI high-risk high-hyperdiploid B-ALL patients with slow MRD response, who require new treatment approaches. Among NCI high-risk patients, 93% with ETV6::RUNX1 and 54% with high-hyperdiploid B-ALL experienced excellent outcomes with a low-intensity regimen. These trials were registered at www.clinicaltrials.gov as #NCT00137111 and #NCT00549848.

Patient out-of-pocket costs for cannabis use during cancer treatment.

BACKGROUND: We assessed patient costs associated with cannabis use during cancer treatment. METHODS: Adults treated for cancer at a large, comprehensive center completed an anonymous survey regarding their thoughts and experiences with cannabis and cancer. Bivariate and weighted multivariable logistic regression assessed clinical and sociodemographic factors associated with patient-reported out-of-pocket costs for cannabis products. RESULTS: Overall, 248 cannabis users provided data on cost and were analyzed. Median monthly out-of-pocket cost for cannabis was $80 (interquartile range = $25-$150). On regression analysis, male gender (odds ratio = 2.5, 95% confidence interval = 1.2 to 5.5, P = .026) and being 45 years of age or older (odds ratio = 7.5, 95% confidence interval = 1.9 to 30.0, P = .0042) were associated with spending $100 a month or more on cannabis. Of the 166 patients who stopped using cannabis early or used less than preferred, 28% attributed it to cost and 26% to lack of insurance coverage. CONCLUSION: Cannabis use during cancer treatment may contribute to significant out-of-pocket costs, with men and younger patients more likely to pay higher costs.

Comparing sleep measures in cancer survivors: self-reported sleep diary versus objective wearable sleep tracker.

PURPOSE: Cancer survivors are increasingly using wearable fitness trackers, but it is unclear if they match traditional self-reported sleep diaries. We aimed to compare sleep data from Fitbit and the Consensus Sleep Diary (CSD) in this group. METHODS: We analyzed data from two randomized clinical trials, using both CSD and Fitbit to collect sleep outcomes: total sleep time (TST), wake time after sleep onset (WASO), number of awakenings (NWAK), time in bed (TIB), and sleep efficiency (SE). Insomnia severity was measured by Insomnia Severity Index (ISI). We used the Wilcoxon signed rank test, Spearman's rank correlation coefficients, and the Mann-Whitney test to compare sleep outcomes and assess their ability to distinguish insomnia severity levels between CSD and Fitbit data. RESULTS: Among 62 participants, compared to CSD, Fitbit recorded longer TST by an average of 14.6 (SD = 84.9) minutes, longer WASO by an average of 28.7 (SD = 40.5) minutes, more NWAK by an average of 16.7 (SD = 6.6) times per night, and higher SE by an average of 7.1% (SD = 14.4); but shorter TIB by an average of 24.4 (SD = 71.5) minutes. All the differences were statistically significant (all p < 0.05), except for TST (p = 0.38). Moderate correlations were found for TST (r = 0.41, p = 0.001) and TIB (r = 0.44, p < 0.001). Compared to no/mild insomnia group, participants with clinical insomnia reported more NWAK (p = 0.009) and lower SE (p = 0.029) as measured by CSD, but there were no differences measured by Fitbit. CONCLUSIONS: TST was the only similar outcome between Fitbit and CSD. Our study highlights the advantages, disadvantages, and clinical utilization of sleep trackers in oncology.

Bootstrap Evaluation of Association Matrices (BEAM) for Integrating Multiple Omics Profiles with Multiple Outcomes.

Motivation: Large datasets containing multiple clinical and omics measurements for each subject motivate the development of new statistical methods to integrate these data to advance scientific discovery. Model: We propose bootstrap evaluation of association matrices (BEAM), which integrates multiple omics profiles with multiple clinical endpoints. BEAM associates a set omic features with clinical endpoints via regression models and then uses bootstrap resampling to determine statistical significance of the set. Unlike existing methods, BEAM uniquely accommodates an arbitrary number of omic profiles and endpoints. Results: In simulations, BEAM performed similarly to the theoretically best simple test and outperformed other integrated analysis methods. In an example pediatric leukemia application, BEAM identified several genes with biological relevance established by a CRISPR assay that had been missed by univariate screens and other integrated analysis methods. Thus, BEAM is a powerful, flexible, and robust tool to identify genes for further laboratory and/or clinical research evaluation. Availability: Source code, documentation, and a vignette for BEAM are available on GitHub at: https://github.com/annaSeffernick/BEAMR. The R package is available from CRAN at: https://cran.r-project.org/package=BEAMR. Contact: Stanley.Pounds@stjude.org. Supplementary Information: Supplementary data are available at the journal's website.

Racial differences in treatment adherence and response to acupuncture and cognitive behavioral therapy for insomnia among Black and White cancer survivors.

BACKGROUND: Racial disparities in sleep are well-documented. However, evidence-based options for addressing these disparities are lacking in cancer populations. To inform future research on sleep interventions, this study aims to understand racial differences in treatment responses to acupuncture and cognitive behavioral therapy for insomnia (CBT-I) among Black and White cancer survivors. METHODS: We conducted a secondary analysis of a comparative effectiveness trial evaluating acupuncture versus CBT-I for insomnia in cancer survivors. We compared insomnia severity, sleep characteristics, and co-morbid symptoms, as well as treatment attitudes, adherence, and responses among Black and White participants. RESULTS: Among 156 cancer survivors (28% Black), Black survivors reported poorer sleep quality, longer sleep onset latency, and higher pain at baseline, compared to White survivors (all p < 0.05). Black survivors demonstrated lower adherence to CBT-I than White survivors (61.5% vs. 88.5%, p = 0.006), but their treatment response to CBT-I was similar to white survivors. Black survivors had similar adherence to acupuncture as white survivors (82.3% vs. 93.4%, p = 0.16), but they had greater reduction in insomnia severity with acupuncture (-3.0 points, 95% CI -5.4 to 0.4, p = 0.02). CONCLUSION: This study identified racial differences in sleep characteristics, as well as treatment adherence and responses to CBT-I and acupuncture. To address racial disparities in sleep health, future research should focus on improving CBT-I adherence and confirming the effectiveness of acupuncture in Black cancer survivors.

Impact of Age on Pharmacogenomics and Treatment Outcomes of B-Cell Acute Lymphoblastic Leukemia.

PURPOSE: Acute lymphoblastic leukemia (ALL) can occur across all age groups, with a strikingly higher cure rate in children compared with adults. However, the pharmacological basis of age-related differences in ALL treatment response remains unclear. METHODS: Studying 767 children and 309 adults with newly diagnosed B-cell ALL enrolled on frontline trials at St Jude Children's Research Hospital, MD Anderson Cancer Center, the Alliance for Clinical Trials in Oncology, and the ECOG-ACRIN Cancer Research Group, we determined the ex vivo sensitivity of leukemia cells to 21 drugs. Twenty-three ALL molecular subtypes were identified using RNA sequencing. We systematically characterized the associations between drug response and ALL genomics in children, adolescents and young adults, and elderly adults. We evaluated the effect of age-related gene expression signature on ALL treatment outcomes. RESULTS: Seven ALL drugs (asparaginase, prednisolone, mercaptopurine, dasatinib, nelarabine, daunorubicin, and inotuzumab ozogamicin) showed differential activity between children and adults, of which six were explained by age-related differences in leukemia molecular subtypes. Adolescents and young adults showed similar patterns of drug resistance as older adults, relative to young children. Mercaptopurine exhibited subtype-independent greater sensitivity in children. Transcriptomic profiling uncovered subclusters within CRLF2-, DUX4-, and KMT2A-rearranged ALL that were linked to age and cytotoxic drug resistance. In particular, a subset of children had adult-like ALL on the basis of leukemia gene expression patterns across subtypes, despite their chronological age. Resistant to cytotoxic drugs, children with adult-like ALL exhibited poor prognosis in pediatric ALL trials, even after adjusting for age and minimal residual diseases. CONCLUSION: Our results provide pharmacogenomic insights into age-related disparities in ALL cure rates and identify leukemia prognostic features for treatment individualization across age groups.

The genomic basis of childhood T-lineage acute lymphoblastic leukaemia.

T-lineage acute lymphoblastic leukaemia (T-ALL) is a high-risk tumour1 that has eluded comprehensive genomic characterization, which is partly due to the high frequency of noncoding genomic alterations that result in oncogene deregulation2,3. Here we report an integrated analysis of genome and transcriptome sequencing of tumour and remission samples from more than 1,300 uniformly treated children with T-ALL, coupled with epigenomic and single-cell analyses of malignant and normal T cell precursors. This approach identified 15 subtypes with distinct genomic drivers, gene expression patterns, developmental states and outcomes. Analyses of chromatin topology revealed multiple mechanisms of enhancer deregulation that involve enhancers and genes in a subtype-specific manner, thereby demonstrating widespread involvement of the noncoding genome. We show that the immunophenotypically described, high-risk entity of early T cell precursor ALL is superseded by a broader category of 'early T cell precursor-like' leukaemia. This category has a variable immunophenotype and diverse genomic alterations of a core set of genes that encode regulators of hematopoietic stem cell development. Using multivariable outcome models, we show that genetic subtypes, driver and concomitant genetic alterations independently predict treatment failure and survival. These findings provide a roadmap for the classification, risk stratification and mechanistic understanding of this disease.

Association between Hispanic Ethnicity and Greater Expectation of Benefit from Acupuncture or Massage for Pain in Cancer.

Individuals living with cancer and survivors of cancer who self-identify as Hispanic experience higher pain burden and greater barriers to pain management compared with their non-Hispanic counterparts. The Society for Integrative Oncology-ASCO guideline recommends acupuncture and massage for cancer pain management. However, Hispanic individuals' expectations about these modalities remain under-studied and highlight a potential barrier to treatment utilization in this population. We conducted a subgroup analysis of baseline data from two randomized clinical trials to evaluate ethnic differences in treatment expectations about integrative pain treatment modalities among Hispanic and non-Hispanic cancer patients and survivors of cancer. The Mao Expectancy of Treatment Effects (METE) instrument was used to measure treatment expectancy for electro-acupuncture, auricular acupuncture, and massage therapy. Results of this study demonstrated that Hispanic participants reported greater expectation of benefit from electroacupuncture, auricular acupuncture, and massage (all P < 0.01). After controlling for age, gender, race, and education, Hispanic ethnicity remained significantly associated with greater expectation of benefit from integrative therapies for pain (coef.=1.47, 95% CI, 0.67-2.27). Non-white race (coef.=1.04, 95% CI, 0.42-1.65), no college education (coef.=1.16, 95% CI, 0.59-1.74), and female gender (coef.=0.94, 95% CI, 0.38-1.50) were also associated with a greater expectation of benefit from integrative therapies. Pain management should be informed by a shared decision-making approach that aligns treatment expectancy with treatment selections to optimize outcomes. Compared with non-Hispanic participants, Hispanic individuals reported higher expectation of benefit from acupuncture and massage, highlighting the potential role for integrative therapies in addressing ethnic pain disparities. Trial Registration NCT02979574 NCT04095234.

A transgenic mouse model of Down syndrome acute lymphoblastic leukemia identifies targetable vulnerabilities.

Not available.

Development of an Orally Bioavailable LCK PROTAC Degrader as a Potential Therapeutic Approach to T-Cell Acute Lymphoblastic Leukemia.

Despite significant advances over recent years, the treatment of T cell acute lymphoblastic leukemia (T-ALL) remains challenging. We have recently shown that a subset of T-ALL cases exhibited constitutive activation of the lymphocyte-specific protein tyrosine kinase (LCK) and were consequently responsive to treatments with LCK inhibitors and degraders such as dasatinib and dasatinib-based PROTACs. Here we report the design, synthesis and in vitro/vivo evaluation of SJ45566, a potent and orally bioavailable LCK PROTAC.

Differential symptom cluster responses and predictors to repetitive transcranial magnetic stimulation treatment in Parkinson's disease: A retrospective study.

Background: Repetitive transcranial magnetic stimulation (rTMS) is an effective noninvasive neuromodulation technique for Parkinson's disease (PD). However, the efficacy of rTMS varies widely between individuals. This study aimed to investigate the factors related to the response to rTMS in PD patients. Methods: We retrospectively analyzed the response of 70 idiopathic PD patients who underwent rTMS for 14 consecutive days targeting the supplementary motor area (SMA) in either an open-label trail (n = 31) or a randomized, double-blind, placebo-controlled trial (RCT) (n = 39). The motor symptoms of PD patients were assessed by the United Parkinson's Disease Rating Scale Part III (UPDRSIII). Based on previous studies, the UPDRSIII were divided into six symptom clusters: axial dysfunction, resting tremor, rigidity, bradykinesia affecting right and left extremities, and postural tremor. Subsequently, the efficacy of rTMS to different motor symptom clusters and clinical predictors were analyzed in these two trails. Results: After 14 days of treatment, only the total UPDRSIII scores and rigidity scores improved in both the open-label trial and the RCT. The results of multiple linear regression analysis indicated that baseline rigidity scores (ß = 0.37, p = 0.047) and RMT (ß = 0.30, P = 0.02) positively predicted the improvement of UPDRSIII. The baseline rigidity score (ß = 0.55, P < 0.0001) was identified as an independent factor to predict the improvement of rigidity. Conclusion: This study demonstrated significant improvements in total UPDRSIII scores and rigidity after 14-day treatment, with baseline rigidity scores and RMT identified as predictors of treatment response, underscoring the need for individualized therapy.

Infrared laser moxibustion for cancer-related fatigue in breast cancer survivors: a randomized controlled trial.

BACKGROUND: Cancer-related fatigue (CRF) is a pervasive, persistent, and distressing symptom experienced by cancer patients, for which few treatments are available. We investigated the efficacy and safety of infrared laser moxibustion (ILM) for improving fatigue in breast cancer survivors. METHODS: A three-arm, randomized, sham-controlled clinical trial (6-week intervention plus 12-week observational follow-up) was conducted at a tertiary hospital in Shanghai, China. The female breast cancer survivors with moderate to severe fatigue were randomized 2:2:1 to ILM (n = 56) sham ILM (n = 56), and Waitlist control (WLC)(n = 28) groups. Patients in the ILM and sham ILM (SILM) groups received real or sham ILM treatment, 2 sessions per week for 6 weeks, for a total of 12 sessions. The primary outcome was change in the Brief Fatigue Inventory (BFI) score from baseline to week 6 with follow-up until week 18 assessed in the intention-to-treat population. RESULTS: Between June 2018 and July 2021, 273 patients were assessed for eligibility, and 140 patients were finally enrolled and included in the intention-to-treat analysis. Compared with WLC, ILM reduced the average BFI score by 0.9 points (95% CI, 0.3 to 1.6, P = .007) from baseline to week 6, with a difference between the groups of 1.1 points (95% CI, 0.4 to 1.8, P = .002) at week 18. Compared with SILM, ILM treatment resulted in a non-significant reduction in the BFI score (0.4; 95% CI, -0.2 to 0.9, P = .206) from baseline to week 6, while the between-group difference was significant at week 18 (0.7; 95% CI, 0.2 to 1.3, P = .014). No serious adverse events were reported. CONCLUSION: While ILM was found to be safe and to significantly reduce fatigue compared with WLC, its promising efficacy against the sham control needs to be verified in future adequately powered trials. TRIAL REGISTRATION: Clinicaltrials.gov: NCT04144309. Registered 12 June 2018.

Investigation of inherited noncoding genetic variation impacting the pharmacogenomics of childhood acute lymphoblastic leukemia treatment.

Defining genetic factors impacting chemotherapy failure can help to better predict response and identify drug resistance mechanisms. However, there is limited understanding of the contribution of inherited noncoding genetic variation on inter-individual differences in chemotherapy response in childhood acute lymphoblastic leukemia (ALL). Here we map inherited noncoding variants associated with treatment outcome and/or chemotherapeutic drug resistance to ALL cis-regulatory elements and investigate their gene regulatory potential and target gene connectivity using massively parallel reporter assays and three-dimensional chromatin looping assays, respectively. We identify 54 variants with transcriptional effects and high-confidence gene connectivity. Additionally, functional interrogation of the top variant, rs1247117, reveals changes in chromatin accessibility, PU.1 binding affinity and gene expression, and deletion of the genomic interval containing rs1247117 sensitizes cells to vincristine. Together, these data demonstrate that noncoding regulatory variants associated with diverse pharmacological traits harbor significant effects on allele-specific transcriptional activity and impact sensitivity to antileukemic agents.

How does pretreatment expectancy influence pain outcomes with electroacupuncture and battlefield acupuncture in cancer survivors?: Pretreatment expectancy and pain reduction by acupuncture.

Background: Outcome expectancy is an important component of non-specific effect that may play an important role in pain research and clinical care. We sought to evaluate whether pretreatment expectancy predicts pain reduction in cancer survivors receiving electroacupuncture (EA) or battlefield acupuncture (BFA). Methods: We analyzed data from a randomized clinical trial that compared EA and BFA versus wait list control (WLC) for chronic musculoskeletal pain in cancer survivors. Expectancy was measured by the Acupuncture Expectancy Scale (AES) at baseline. Pain severity was assessed using the Brief Pain Inventory (BPI) at baseline and week 12. For each treatment arm, multivariable regression models were used to evaluate the association between pretreatment expectancy and week 12 pain severity, controlling for baseline pain severity, age, sex, race, and education. Results: Among 360 participants enrolled, the mean age was 62.1 years (SD 12.7), with 251 (69.7 %) women and 88 (24.4 %) non-white survivors. Pretreatment expectancy was similar for all groups at baseline (EA: 13.9 ± 3.6; BFA: 13.2 ± 3.7, WLC:12.8 ± 3.3, p = 0.14). Greater pretreatment expectancy was not significantly associated with greater pain reduction in any group, after adjusting for co-variates (EA: Coef. = -0.05, 95 % CI = -0.14 - 0.04, p = 0.28; BFA: Coef. = -0.07, 95 % CI = -0.16 - 0.02, p = 0.15; WLC: Coef. = -0.09, 95 % CI = -0.25 - 0.06, p = 0.23). Conclusions: Pretreatment expectancy did not predict pain reduction for either EA or BFA in cancer survivors. Our study contributes to the interpretation of analgesic effects of EA or BFA, beyond the notion of a mere 'placebo effect'.

Experiences and perceived benefits of remotely delivered dance/movement therapy for adult cancer patients: a multi-method program evaluation.

BACKGROUND: Dance/movement therapy (DMT) is increasingly used as a complementary treatment to address psychological and physical wellbeing. However, it is unknown how it can be leveraged in adult cancer care. This mixed methods program evaluation aimed to assess patient-reported benefits and satisfaction with the virtual DMT in an academic oncology setting. METHODS: We developed, implemented, and evaluated a 6-week virtual, synchronous DMT program aiming to improve physical health, address mental distress, and foster social connection for cancer patients. We used deidentified program evaluation data to assess impact of DMT on patient-reported outcomes and patients' satisfaction with the DMT program. Pre- and post-session data were analyzed using descriptive statistics and a paired t-test. Qualitative data were captured through semi-structured interviews and analyzed using thematic analysis. RESULTS: Results from 39 participants (mean age 64.7 ± 9.8), majority female (89.7%) with a history of breast cancer (43.6%), showed high satisfaction (100%) and unanimous program recommendation (100%). Significant improvements were noted in anxiety (- 0.42 ± 0.76, p = .009), distress (- 0.35 ± 0.80, p = .036), and sense of joy (0.73 ± 1.18, p = .004), with a non-significant trend in increased physical activity (0.38 ± 0.98, p = .057). Thematic findings indicated that DMT participation (1) facilitated engagement in physical activity for improved physical health, (2) fostered creative expression, (3) improved mental state, and (4) helped build social connections and support. CONCLUSION: Our DMT program shows promise as a component of integrative cancer care. The mixed-method evaluation provides insightful information to generate hypotheses for future RCT studies aiming to evaluate the specific effects of DMT on patient experience and outcomes.

Nocebo expectations rather than placebo expectations affect topical pain relief: A randomized clinical trial.

Patients' expectations and beliefs regarding the potential benefits and harms of medical interventions may induce placebo and nocebo effects, and affect the response to pain therapies. In a randomized clinical trial, we examined the effect of placebo and nocebo expectations on pain relief and adverse events (AEs) in association with a topical treatment among 65 cancer survivors experiencing chronic musculoskeletal pain. Participants received either a 1% camphor-based topical pain patch or a placebo treatment for 14 days. We measured pain severity with the worst pain item of the Brief Pain Inventory (BPI) at baseline and 14 days and treatment expectations at baseline with validated expectation questionnaires. We found that high vs. low nocebo expectations decreased pain severity improvements by 2.5 points (95% confidence interval [CI] -3.8 to -1.2; p<0.001) on a 0-10 numeric rating scale of the BPI and pain response rate by 42.7% (95% CI 0.2-0.6; p<0.001) at day 14, irrespective of placebo expectation status or treatment arms. Patients with high vs. low nocebo expectations in the true arm reported 22.4% more unwanted AEs. High nocebo expectations were associated with increased AEs by 39.5% (odds ratio: 12.0, 95% CI 1.2, 145.5; p=0.029) and decreased pain response in the true arm vs. placebo. Our study demonstrated that nocebo expectations, rather than placebo expectations, elevate the risk of AEs and compromise the effect of topical pain interventions. The findings raise the possibility that nocebo expectations may worsen somatic symptoms through heightening central pain amplification and should be further investigated.

Patient-Reported Outcomes as a Recruitment Strategy for Clinical Trial Enrollment.

Importance: Clinical trials are critical for progress in oncology; however, only 5% of the adult cancer population participates. Harnessing data that are routinely collected (ie, electronic patient-reported outcomes [ePROs]) may serve as a method to promote trial enrollment. Objective: To evaluate if an ePRO-prompted recruitment strategy is associated with increased clinical trial enrollment. Design, Setting, and Participants: A randomized substudy was conducted from September 2022 to March 2023 at a multisite tertiary cancer center as part of an ongoing clinical trial that was testing a symptom-intervention for cancer-related fatigue. Patients with breast cancer who were undergoing radiotherapy who completed at least 1 ePRO questionnaire during the study period were included. Physician-level cluster randomization assigned fatigue-eligible patients to either receive a portal message invitation to a symptom-intervention trial or standard of care (SOC; physician-based referral). Exposure: ePRO questionnaires distributed in routine practice were queried weekly and screened for moderate or greater fatigue, the principle inclusion criterion for the primary trial. To assess the association of the portal message source with response and enrollment, every other patient received a message from the primary radiation oncology team or the referral service. Main Outcomes and Measures: Clinical trial response/referral and enrollment. Results: A total of 1041 patients completed ePRO questionnaires, of whom 394 (38%; 53 Asian [13.6%], 43 Black [11.0%], 29 Hispanic [7.4%], and 262 White individuals [66.5%]; median [IQR] age, 55 [47-65] years) endorsed moderate or greater fatigue while receiving treatment. A total of 210 patients (53.3%) were assigned to receive a portal message and 184 (46.7%) patients, SOC. In the portal message group, 73 patients (35%) responded and 41 (20%) enrolled compared with 1 patient (0.5%) referred and 0 enrolled in the SOC group (P < .001). The response rate to portal messages favored the referral service vs the primary radiation oncology service (44% vs 26%; P = .01), but there was no significant difference in enrollments. Conclusions and Relevance: The study results suggest that use of routine care ePROs was associated with greater enrollment in a symptom-intervention trial compared with physician-based referral. Messaging directly from the referral service may support enrollment and help reduce oncology physician-level barriers to trial enrollment for studies testing symptom interventions.

CD9 shapes glucocorticoid sensitivity in pediatric B-cell precursor acute lymphoblastic leukemia.

Resistance to glucocorticoids (GC), the common agents for remission induction in pediatric B-cell precursor acute lymphoblastic leukemia (BCP-ALL), poses a significant therapeutic hurdle. Therefore, dissecting the mechanisms shaping GC resistance could lead to new treatment modalities. Here, we showed that CD9- BCP-ALL cells were preferentially resistant to prednisone and dexamethasone over other standard cytotoxic agents. Concordantly, we identified significantly more poor responders to the prednisone prephase among BCP-ALL patients with a CD9- phenotype, especially for those with adverse presenting features including older age, higher white cell count and BCR-ABL1. Furthermore, gain- and loss-offunction experiments dictated a definitive functional linkage between CD9 expression and GC susceptibility, as demonstrated by the reversal and acquisition of relative GC resistance in CD9low and CD9high BCP-ALL cells, respectively. Despite physical binding to the GC receptor NR3C1, CD9 did not alter its expression, phosphorylation or nuclear translocation but potentiated the induction of GC-responsive genes in GC-resistant cells. Importantly, the MEK inhibitor trametinib exhibited higher synergy with GC against CD9- than CD9+ lymphoblasts to reverse drug resistance in vitro and in vivo. Collectively, our results elucidate a previously unrecognized regulatory function of CD9 in GC sensitivity, and inform new strategies for management of children with resistant BCP-ALL.

Five Dimensions of Needs for Help: The Efficacy of a Technology-Based Intervention Among Asian American Breast Cancer Survivors.

Cancer survivors including Asian American breast cancer survivors have reported their high needs for help during their survivorship process. With the COVID-19 pandemic, the necessity of technology-based programs to address their needs for help without face-to-face interactions has been highlighted. The purpose of this randomized intervention study was to determine the efficacy of a technology-based program in reducing various types of needs for help among this specific population. This was a randomized clinical trial with repeated measures. A total of 199 participants were included in the data analysis. The recruitment settings included both online and offline communities/groups for Asian Americans. The needs for help were assessed using the Support Care Needs Survey-34 Short Form (SCNS) subscales measuring psychological, information, physical, support, and communication needs. Data analysis was conducted through an intent-to-treat approach. In the mixed effect models, psychological needs, information needs, physical needs, and communication needs decreased over time (P < .001). However, there were no significant group * time effects. Social support significantly mediated the effects of a technology-based intervention on psychological, information, and support needs at the pre-test and the post-1 month. This study supported significant decreases in the needs for help of Asian American breast cancer survivors by a technology-based intervention. Further studies are needed with other racial/ethnic groups of cancer survivors to confirm the efficacy of a technology-based intervention in reducing cancer survivors' needs for help during their survivorship process.