Citations

Radiation-induced brain injury (RIBI) is a debilitating sequela after radiotherapy to treat head and neck cancer, and 20 to 30% of patients with RIBI fail to respond to or have contraindications to the first-line treatments of bevacizumab and corticosteroids. Here, we reported a Simon’s minmax two-stage, single-arm, phase 2 clinical trial (NCT03208413) to assess the efficacy of thalidomide in patients with RIBI who were unresponsive to or had contraindications to bevacizumab and corticosteroid therapies. The trial met its primary endpoint, with 27 of 58 patients enrolled showing ≥25% reduction in the volume of cerebral edema on fluid-attenuated inversion recovery–magnetic resonance imaging (FLAIR-MRI) after treatment (overall response rate, 46.6%; 95% CI, 33.3 to 60.1%). Twenty-five (43.1%) patients demonstrated a clinical improvement based on the Late Effects Normal Tissues–Subjective, Objective, Management, Analytic (LENT/SOMA) scale, and 36 (62.1%) experienced cognitive improvement based on the Montreal Cognitive Assessment (MoCA) scores. In a mouse model of RIBI, thalidomide restored the blood-brain barrier and cerebral perfusion, which were attributed to the functional rescue of pericytes secondary to elevation of platelet-derived growth factor receptor β (PDGFRβ) expression by thalidomide. Our data thus demonstrate the therapeutic potential of thalidomide for the treatment of radiation-induced cerebral vasculature impairment.

AbstractAs we were invited to write an article for celebrating the 50th Anniversary of Medical Physics journal, on something historically significant, commemorative, and exciting happening in the past decades, the first idea came to our mind is the fascinating radiotherapy paradigm shift from conventional fractionation to hypofractionation and stereotactic ablative radiotherapy (SABR). It is historically and clinically significant since as we all know this RT treatment revolution not only reduces treatment duration for patients, but also improves tumor control and cancer treatment outcomes. It is also commemorative and exciting for us medical physicists since the technology development in medical physics has been the main driver for the success of this treatment regimen which requires high precision and accuracy throughout the entire treatment planning and delivery. This article provides an overview of the technological development and clinical trials evolvement in the past 25 years for hypofractionation and SABR, with an outlook to the future improvement.

AbstractObjectiveTo evaluate the effect of a health maintenance reminder (HMR) on human papillomavirus (HPV) vaccine administration and completion across different age, insurance, and race cohorts.Study DesignRetrospective pre‐post analysis.SettingAcademic primary care.MethodsPatients aged 9 to 26 who had initiated the HPV vaccine series from 2016 to 2021 were analyzed, based on current age‐based standards. The cohort was divided based on vaccine uptake before and after the implementation of the HMR program in February 2020. The multivariate analysis estimated the odds of vaccine completion based on sociodemographic factors, and variable interactions were investigated to determine independent associations between sociodemographic factors and HMR implementation.ResultsThere were 7654 individual patients (mean age was 15.8 years; 46.7 were males; and 50.7% were white). HPV vaccine completion rates increased post‐HMR implementation by 59.2% (37% pre‐, and 58.9% post‐HMR; p < .001) in the entire cohort. Overall, black patients (adjusted odds ratio [aOR] = 0.68; 95% confidence interval [CI]: 0.60, 0.70) and patients ≥18 years (aOR = 0.13; 95% CI: 0.11, 0.15) were significantly less likely to complete their vaccine series; however, this improved significantly following HMR in these groups (p < .001). Post‐HMR, race, and insurance status were not independently associated with disparate vaccine completion rates, however, age was, and patients ≤14 or younger had higher odds of vaccine completion (aOR = 3.54; 95% CI: 2.91, 4.32).ConclusionThe implementation of an HMR was associated with increased HPV vaccine uptake across age and race groups in this single‐institution study. Future research should explore barriers to implementing HMRs in different health care settings.

AbstractAcute myeloid leukemia (AML) is a challenging cancer in terms of achieving and maintaining long‐duration remissions. Many novel therapies have been added to the standard regimen (combining cytarabine and anthracycline “7 + 3”) to achieve such goals. Nilotinib is an oral multikinase inhibitor that is active against KIT tyrosine kinase, an important stem cell target. In this trial, we combined nilotinib with 7 + 3 induction (daunorubicin 60 mg/m2), high‐dose cytarabine consolidation, and subsequently, if the patient was a candidate, for 2 years' maintenance therapy in patients with AML and KIT (CD117) expression. Patients were allowed to proceed to allogeneic hematopoietic cell transplantation (HCT) if deemed necessary. Our primary goal was increased complete remission rate with this combination. Thirty‐four patients (with a median age 58.5 years) were enrolled on a single‐arm phase II bi‐institutional study; 21 (62%) patients achieved remission. The complete remission rate was 78% in evaluable patients. Thirteen of 34 (38%) patients had allogeneic HCT, all thirteen of which are still alive (100%). Common (>20%) grade 3 non‐hematological toxicities included febrile neutropenia, hypophosphatemia, elevated liver enzymes, and hypertension. Only one patient (3%) died in induction due to liver failure, which was thought secondary to daunorubicin. Our current study reveals good outcomes in patients who received HCT and may warrant a larger study to confirm our findings in that specific population.

AbstractWaldenström macroglobulinemia (WM) is a rare, indolent lymphoma, that predominately affects the elderly. We report the outcomes of young WM patients, evaluated over five decades, compared to their older counterparts, matched for the time of diagnosis. Between January 1, 1960 and October 31, 2013, 140 (11.8%) WM patients were ≤50 years of age at diagnosis in our database, and their estimated 10‐year overall survival (OS) was 74%, with death attributable to WM in a higher proportion of patients compared to their older (≥65 years) counterparts (91% vs. 58%, p = .0001). Young patients were grouped into three cohorts based on the timing of the initiation of therapy: Group 1 (1960–1977, n = 12), Group 2 (1978–1995, n = 48), and Group 3 (1996–2013, n = 74). Among young patients, there was no disease‐specific survival (DSS) difference across the three periods, [median DSS at 13 years (95% CI 5–23), 16 years (95% CI 14–22), and 15 years (95% CI 10‐NR; p = .41), respectively]. However, DSS for the older cohort incrementally improved (Group 1, median 5.2 years, Group 2: 9.6 years, Group 3: 12 years; p = .05) over these periods. The estimated average years‐of‐life lost for the young cohort was 11.2 years from diagnosis, based on the expected survival for a normal age‐ and sex‐matched population. Despite a protracted disease course, nearly all young patients succumb to their disease. In contrast to the improved survival of the elderly patient population, the evolving treatment strategies in WM have not impacted the outcome of young patients; however, the impact of Bruton tyrosine kinase inhibitors on this unique patient population remains to be determined.

Objective: Sleep fragmentation determined by repetitive arousals from sleep in obstructive sleep apnea (OSA) is associated with hypertension. We aimed to quantify the independent association of arousals during rapid eye movement (REM)/non-rapid eye movement (NREM) sleep with prevalent hypertension. Methods: We included adults with 4 h of total sleep time and at least 30 min of REM sleep obtained from overnight in-laboratory polysomnography. Logistic regression models were fitted to explore the association between arousals during REM/NREM sleep and prevalent hypertension. All models controlled for OSA metrics and arousals during NREM/REM sleep, either by statistical adjustment or by stratification. Results: The sample comprised of 11 643 patients, of which 10 055 were OSA patients. Fully adjusted models demonstrated significant dose-relationships between arousal index during REM sleep (AI-REM) and prevalent hypertension (P trend = 0.002). The higher relative odds of prevalent hypertension were most evident with AI-REM > 40 events/h. In OSA patients with arousal index during NREM sleep (AI-NREM) <15 events/h, every10-unit increase in the AI-REM was associated with 18% higher odds of hypertension (odds ratio, 1.18; 95% confidence interval, 1.11–1.27) in OSA. On the contrary, AI-NREM was not a significant predictor of hypertension in any of the models. Conclusions: Our findings indicate that arousals during REM sleep are associated with prevalent hypertension. This is clinically relevant because treatment of OSA is often limited to the first half of the sleep period leaving most of sleep fragmentation during REM sleep untreated.