Citations

ABSTRACTBackgroundComplementary and alternative medicine (CAM) usage among childhood cancer patients remains understudied. Factors associated with CAM use and motivations of caregivers for using CAM remain poorly understood.MethodsThis cross‐sectional mixed‐methods study was conducted among caregivers of patients aged ≤18 years with confirmed cancer diagnoses. Caregivers were interviewed regarding CAM use, reasons for using/non‐using CAM, and views on CAM. Logistic regression identified factors associated with CAM use, whereas qualitative interviews explored motivations and barriers. The impact of CAM usage on 2‐year overall survival was explored.ResultsOut of 450 respondents, CAM usage was reported by 35.78% (n = 161), with home remedies (28.44%, n = 128) and AYUSH (Ayurveda, Unani, Siddha, Yoga, Homeopathy) therapies (13.56%, n = 61) being most common. CAM use was associated with symptom duration ≥30 days (adjusted odds ratio [aOR]: 1.71; 95% CI: 1.09–2.67; p = 0·019) and hematological malignancies (aOR: 2.05; 95% CI: 1.33–3.17; p = 0·001). Major motivations for CAM use included belief in effectiveness (44.72%, n = 72) and family recommendations (34.16%, n = 55). Qualitative interviews highlighted cost, accessibility issues, and diagnostic delays as key drivers of CAM adoption. The 2‐year survival probabilities of CAM users and nonusers were comparable (0.88 [95% CI: 0.83–0.94] vs. 0.87 [95% CI: 0.83–0.92], log‐rank p = 0.75).ConclusionCAM is frequently used by pediatric cancer patients, driven by caregiver beliefs, family influence, and access barriers. Addressing caregiver practices and integrating CAM discussions into care may enhance supportive strategies without impacting survival outcomes.

Context Adolescence is a critical period for bone development. Due to an elevated risk for low body mass index (BMI) and/or low energy availability, certain adolescent athletes are at increased risk of bone stress injury (BSI) and eating disorders (EDs). Despite this risk, the incidence of EDs in patients with BSI is unclear. Objective To compare the incidence of a premorbid drop in BMI percentile in a sample of adolescent athletes diagnosed with a BSI between 2005 and 2016. We also evaluated the relative risk of developing an ED for this sample, compared with a sex-matched, age-matched (±6 months), and time-matched (±2 years) sample of active adolescents with knee pain. Design Retrospective cohort study. Setting Data collected through the Rochester Epidemiology Project. Patients or Other Participants One hundred eighty-seven adolescent (aged 13–18) athletes with BSI and 187 active adolescents with knee pain. Main Outcome Measure(s) Conditional logistic regression was used to assess whether premorbid weight loss was a risk factor for BSI. A stratified log-rank test was used to evaluate the association between ED diagnosis and case-control status up to 5 years postinjury. Results Patients with a BSI had 1.53 times the odds of premorbid BMI percentile drop compared with controls (95% CI = 0.83, 2.12; P = .17). A total of 14 patients with a BSI had ED diagnoses after injury compared with 8 controls ( P = .13). Patients from weight-based or aesthetic sports had 1.93 times the odds of a BSI compared with controls (95% CI = 1.23, 3.02; P = .0040). The Kaplan-Meier estimates indicate that the case group had a greater risk of ED diagnosis. Conclusions Results suggest a trend toward a greater drop in BMI percentile and increased frequency of ED diagnoses in the BSI group compared with controls. The documented co-occurrence of weight loss, stress fractures, and EDs in adolescent athletes should inform guidelines for screening and treatment of adolescent athletes with BSIs.

Abstract Background Cabozantinib is indicated for hepatocellular carcinoma (HCC) following first-line (1L) sorafenib, but the 1L standard has shifted to immuno-oncology (IO)-based regimens. This study evaluated real-world outcomes among patients with advanced HCC receiving second-line (2L) cabozantinib following 1L therapies, including newer regimens. Patients and Methods US claims data were used to identify adults with advanced HCC initiating 2L cabozantinib monotherapy (index date). Patients were stratified into three 1L treatment cohorts: IO monotherapy/IO + IO combination therapy; IO + non–IO combination therapy; or tyrosine kinase inhibitor (TKI) monotherapy. Real-world time to treatment discontinuation (rwTTD), real-world time to next treatment or death (rwTNTD), real-world overall survival (rwOS), and cabozantinib dosing were assessed collectively and by cohort. Adverse events were assessed before/after cabozantinib initiation. Results Among 148 patients who received 2L cabozantinib, 28 were in the IO monotherapy/IO + IO combination therapy cohort, 54 in the IO + non–IO combination therapy cohort, and 66 in the TKI monotherapy cohort. Median rwTTD among all patients was 3.2 months; median rwTNTD was 7.6 months; 12-month rwOS rate was 61.6%. There were no significant differences in these outcomes among the three cohorts. Overall, 44.6% of patients initiated 2L cabozantinib at 60 mg/day, of whom 39.4% required a dose reduction; 37.8% initiated at 40 mg/day, of whom 16.1% had a dose reduction. Adverse event rates were similar before/after cabozantinib initiation. Conclusions Cabozantinib shows consistent effectiveness and safety in the 2L HCC setting following prior TKIs or IO-based regimens in real-world clinical practice. These findings may inform 2L treatment decisions.

Abstract The aim of this international meta-analysis was to quantify the predictive value of BMI for incident fracture and relationship of this risk with age, sex, follow-up time, and BMD. A total of 1 667 922 men and women from 32 countries (63 cohorts), followed for a total of 16.0 million person-years were studied. 293 325 had FN BMD measured (2.2 million person-years follow-up). An extended Poisson model in each cohort was used to investigate relationships between WHO-defined BMI categories (Underweight: <18.5 kg/m2; Normal: 18.5-24.9 kg/m2; Overweight: 25.0-29.9 kg/m2; Obese I: 30.0-34.9 kg/m2; Obese II: ≥35.0 kg/m2) and risk of incident osteoporotic, major osteoporotic and hip fracture (HF). Inverse-variance weighted β-coefficients were used to merge the cohort-specific results. For the subset with BMD available, in models adjusted for age and follow-up time, the hazard ratio (95% CI) for HF comparing underweight with normal weight was 2.35 (2.10-2.60) in women and for men was 2.45 (1.90-3.17). Hip fracture risk was lower in overweight and obese categories compared to normal weight [obese II vs normal: women 0.66 (0.55-0.80); men 0.91 (0.66-1.26)]. Further adjustment for FN BMD T-score attenuated the increased risk associated with underweight [underweight vs normal: women 1.69 (1.47-1.96); men 1.46 (1.00-2.13)]. In these models, the protective effects of overweight and obesity were attenuated, and in both sexes, the direction of association reversed to higher fracture risk in Obese II category [Obese II vs Normal: women 1.24 (0.97-1.58); men 1.70 (1.06-2.75)]. Results were similar for other fracture outcomes. Underweight is a risk factor for fracture in both men and women regardless of adjustment for BMD. However, while overweight/obesity appeared protective in base models, they became risk factors after additional adjustment for FN BMD, particularly in the Obese II category. This effect in the highest BMI categories was of greater magnitude in men than women. These results will inform the second iteration of FRAX®.

Abstract Intracranial hemorrhage (ICH) and resulting neurologic disability are severe complications for a subset of infants with severe hemophilia A (HA). Although prophylactic factor replacement reduces bleeding risk, it is typically delayed until after age 1 year due to risks associated with central venous access placement. Emicizumab, a subcutaneous activated factor VIII (FVIII) mimetic, has demonstrated safety and efficacy in preventing ICH in infants aged <12 months in the HAVEN 7 trial. Despite its high cost, the cost-effectiveness of emicizumab prophylaxis initiated during the first year of life for infants with severe HA is not known. We developed a Markov cohort model to compare emicizumab prophylaxis to standard care (no prophylaxis) in infants aged 0 to 1 year with severe HA without FVIII inhibitors. The analysis was conducted from a US societal perspective over a lifetime horizon across all accepted willingness-to-pay (WTP) thresholds. The primary outcome was the incremental cost-effectiveness ratio (ICER) in US dollar per quality-adjusted life-year (QALY). Emicizumab prophylaxis and standard care accrued 25.6 and 25.1 QALYs at costs of $13.12 million and $13.07 million, respectively, resulting in an ICER of $99 900 per QALY (95% credible interval [CI], 84 000-120 000). Scenario analysis examining prophylaxis with low-dose emicizumab resulted in an ICER of $19 600 per QALY (95% CI, 12 000-29 000). Probabilistic sensitivity analyses showed that standard-dose emicizumab is the cost-effective strategy in 100%, 66%, and 0% of 10 000 Monte Carlo iterations at WTP thresholds of $150 000, $104 000, and $50 000 per QALY, respectively, and in 100% across all WTP thresholds for low-dose emicizumab.

Background: Transfusion has a persistent low risk of transfusion-transmitted infection and transfusion-associated graft- versus -host disease that may be addressed using pathogen reduction. The Red Cell Pathogen Inactivation (ReCePI) trial tested whether amustaline/glutathione pathogen-reduced red cells are noninferior to conventional transfusions for support of acute surgical blood loss. Methods: A phase 3, double-blinded, noninferiority trial randomized cardiac or thoracic–aorta surgery patients with increased risk of red cell transfusion to receive pathogen-reduced or conventional red cells during and for 7 days postsurgery. The primary endpoint was the proportion of patients with acute kidney injury (AKI), which is defined as an increase from baseline of greater than or equal to 0.3 mg/dl serum creatinine within 48 h of surgery. Noninferiority was claimed if the upper bound 95% CI of the treatment difference was less than half (50%) of the observed conventional arm incidence. Adverse events and treatment-emergent red cell antibodies were assessed for 28 and 75 days, respectively. Results: A total of 581 subjects were randomized, and 321 (55%) were transfused with study red cells. Transfused subjects in both arms had similar baseline demographics, medical histories, hemoglobin levels, and surgical procedures. Hemoglobin day 3 nadir levels (8.6 g/dl [7.8 to 9.2] in the pathogen-reduced arm; 8.4 g/dl [7.8 to 9.3] in the conventional arm; P = 0.52) were comparable. Incidence of AKI by 48 h was 46 of 157 (29.3%) in the pathogen-reduced arm and 45 of 161 (28.0%) in the conventional arm (treatment difference, 0.7%; 95% CI, −8.9 to 10.4%; noninferiority margin, 14.0%; P = 0.001 for noninferiority). AKI within 7 days by Kidney Disease Improving Global Outcomes staging criteria was not different (59 of 159 [37.1%] in the pathogen-reduced arm; 55 of 162 [34.0%] in the conventional arm; P = 0.53), but stage III was more common in the pathogen-reduced arm (pathogen-reduced arm, 15 of 159 [9.4%]; conventional arm, 7 of 162 [4.3%]; P = 0.075). Of 159 pathogen-reduced red cell recipients, 5 (3.1%) developed specific, low-titer antibodies without evidence of hemolysis. Conclusions: The incidence of AKI in recipients of pathogen-reduced red cells was noninferior to conventional red cell transfusion. Treatment-emergent antibodies were uncommon and not clinically significant.

Abstract Purpose: R,R-1,2 cyclohexanediamine-pyrophosphato-platinum(II) (PT-112) is a novel immunogenic cell death–inducing small molecule under phase II development in several cancer types. It inhibits ribosome biogenesis and causes organelle stresses, leading to selective immunogenic cell death in cancer cells. The possibility of PT-112’s pyrophosphate moiety driving high drug concentrations to bone sites of disease has led to an interest in PT-112’s use in multiple myeloma. In this study, we present findings from phase I and in vivo studies for PT-112 in relapsed or refractory multiple myeloma. Experimental Design: PT-112 biodistribution was analyzed in mice via laser ablation inductively coupled plasma mass spectrometry. The activity of PT-112 was assessed in de novo and transplantable Tg(Igkv3-5*-MYC)#Plbe (Vk*MYC) multiple myeloma mouse models as monotherapy or combination therapies. M-spike levels and survival were measured. A phase I dose escalation study of PT-112 monotherapy was conducted using a 3 + 3 design in patients with heavily pretreated relapsed or refractory multiple myeloma with exhausted available therapies. Results: In vivo biodistribution imaging revealed high concentrations in the bone, kidney, lung, skin, and liver. PT-112 was active in Vk*MYC multiple myeloma mouse models, both alone and in combination. Phase I data showed that PT-112 monotherapy was safe and well-tolerated, establishing a recommended phase II dose of 360 mg/m2 on days 1, 8, and 15 of a 28-day cycle. Confirmed responses and other signals of activity were observed. Conclusions: These results suggest a lack of cross-resistance with the standard of care and support the translational value of the Vk*MYC model system. Further clinical investigation of PT-112 is warranted in multiple myeloma.