Effect of time-of-day nivolumab and stereotactic body radiotherapy in metastatic head and neck squamous cell carcinoma: A secondary analysis of a prospective randomized trial.

BACKGROUND: Prior work documented circadian rhythm impacts on efficacy and toxicity of cancer therapies. METHODS: Secondary analysis of prospective, phase II trial of metastatic HNSCC randomized to nivolumab+/-SBRT. Used cutoffs of 1100 and 1630. Timing classified by first infusion or majority of SBRT (e.g., PM SBRT defined by two or three fractions after 1630). RESULTS: Of 62 patients, there was no significant difference in median PFS between AM nivolumab (n = 7, 175 days), PM nivolumab (n = 21, 58 days), or Mid-Day nivolumab (n = 34, 67 days; p = 0.8). There was no significant difference in median PFS with AM SBRT (n = 4, 78 days), PM SBRT (n = 13, 111 days), or Mid-Day SBRT (n = 15, 63 days; p = 0.8). There was no significant difference in Grade 3-4 toxicity or ORR. Sensitivity analyses with other timepoints were negative. CONCLUSIONS: Further work may elucidate circadian impacts on select patients, tumors, and therapies; however, we found no significant effect in this study.

Osteoradionecrosis Rates After Head and Neck Radiation Therapy: Beyond the Numbers.

PURPOSE: Osteoradionecrosis (ORN) is a severe late complication of head and neck radiation therapy shown to have profound negative effect on the quality of life of cancer survivors. Over the past few decades, improvements in radiation delivery techniques have resulted in a decrease in the incidence of ORN. However, even with modern radiation therapy techniques, ORN remains an important clinical concern. In recent literature, there is a wide range of reported ORN rates from 0% to as high as 20%. With such a high level of variability in the reported incidence of ORN, oncologists often encounter difficulties estimating the risk of this serious radiation therapy toxicity. METHODS AND MATERIALS: In this review, the authors present a summary of the factors that contribute to the high level of variability in the reported incidence of ORN. RESULTS: Variable definition, variable grading, and heterogeneity of both study inclusion criteria and treatment parameters can each significantly influence the reporting of ORN rates. CONCLUSIONS: Given numerous factors can affect the reported incidence of ORN, a thorough understanding of the clinical context behind the reported ORN rates is needed to comprehend the true risk of this important radiation therapy toxicity.

Gender, assigned sex at birth, and gender diversity: Windows into diagnostic timing disparities in autism.

LAY ABSTRACT: Later autism diagnosis is associated with risk for mental health problems. Understanding factors related to later autism diagnosis may help reduce mental health risks for autistic people. One characteristic associated with later autism diagnosis is female sex. However, studies often do not distinguish sex assigned at birth and gender identity. Gender diversity may be more common in autistic relative to neurotypical people, and autism is more common in gender-diverse populations. We studied age at autism diagnosis by sex assigned at birth, gender identity, and gender diversity (gender-diverse vs cisgender) status, separately. We studied three separate autistic samples, each of which differed in how they were diagnosed and how they were recruited. The samples included 193 persons (8.0-18.0 years) from a research-recruited academic medical center sample; 1,550 people (1.3-25.4 years) from a clinic-based sample; and 244 people (18.2-30.0 years) from a community-enriched sample. We found significant differences in the clinic-based and community-enriched samples. People assigned female sex at birth were diagnosed with autism significantly later than people assigned male at birth. People of female gender were diagnosed significantly later than people of male gender. Gender-diverse people were diagnosed significantly later than cisgender people. Sex assigned at birth, gender identity, and gender diversity may each show unique relationships with age of autism diagnosis. Differences in how autistic people are diagnosed and recruited are important to consider in studies that examine sex assigned at birth or gender identity. More research into autism diagnosis in adulthood is needed.

Exploring the sexual experiences and challenges of individuals with cerebral palsy.

PURPOSE: Cerebral palsy (CP) is a prevalent motor disorder affecting children, with evolving demographics indicating an increasing survival into adulthood. This shift necessitates a broader perspective on CP care, particularly in addressing the often overlooked aspect of sexuality. The purpose of this study was to investigate experiences of, challenges with, and related factors of sexuality and intimacy that people with CP are facing. METHODS: This was a descriptive and cross-sectional single institution survey among individuals with CP, ages 18 to 65, who had the ability to independently complete an online survey. RESULTS: A total of 40 respondents participated in the survey (Gross Motor Function Classification System [GMFCS] level I/II, 32.5%; III, 35%; IV, 32.5%). Of those, 45% were partnered, 60% had past sexual experience, 47.5% were currently sexually active at the time of submitting the survey, 80% had masturbation experience, and 45.8% believed it had positive effect on their self-esteem. Only 10% received sex education tailored for people with disability, whereas school (72.5%) and internet (35%) were the most common sources of sex education. Muscle spasms, positioning difficulty, and pain/discomfort were the most common physical challenges experienced during intimate activity amongst all function stratifications. Stratification analysis showed that, compared to higher functioning respondents, a smaller proportion of lower functioning respondents were partnered (GMFCS IV, 23.1%; quadriplegic, 31.6%), had past or current sexual experience (GMFCS IV, 44.4%, 36.4%; quadriplegic, 42.1%, 26.3%, respectively), and had masturbation experience (GMFCS IV, 61.5%); Also, they had worse Quality of Life Scale scores on average (GMFCS IV, 88.4; quadriplegic, 88.3) and a higher rate of reported positive effects of sexual experiences on self-esteem than negative (GMFCS IV, 38.5%; quadriplegic, 35%).

An Analysis of Positron Emission Tomography Maximum Standard Uptake Value Among Patients With Head and Neck Cancer Receiving Photon and Proton Radiation.

PURPOSE: One main advantage of proton therapy versus photon therapy is its precise radiation delivery to targets without exit dose, resulting in lower dose to surrounding healthy tissues. This is critical, given the proximity of head and neck tumors to normal structures. However, proton planning requires careful consideration of factors, including air-tissue interface, anatomic uncertainties, surgical artifacts, weight fluctuations, rapid tumor response, and daily variations in setup and anatomy, as these heterogeneities can lead to inaccuracies in targeting and creating unwarranted hotspots to a greater extent than photon radiation. In addition, the elevated relative biological effectiveness at the Bragg peak's distal end can also increase hot spots within and outside the target area. METHODS AND MATERIALS: The purpose of this study was to evaluate for a difference in positron emission tomography (PET) standard uptake value (SUV) after definitive treatment, between intensity modulated proton therapy (IMPT) and intensity modulated photon therapy (IMRT). In addition, we compared the biologic dose between PET areas of high and low uptake within the clinical target volume-primary of patients treated with IMPT. This work is assuming that the greater SUV may potentially result in greater toxicities. For the purposes of this short communication, we are strictly focusing on the SUV and do not have correlation with toxicity outcomes. To accomplish this, we compared the 3- and 6-month posttreatment fluorodeoxyglucose PET scans for 100 matched patients with oropharyngeal cancer treated definitively without surgery using either IMPT (n = 50) or IMRT (n = 50). RESULTS: Our study found a significant difference in biologic dose between the high- and low-uptake regions on 3-month posttreatment scans of IMPT. However, this difference did not translate to a significant difference in PET uptake in the clinical target volume-primary at 3 and 6 months' follow-up between patients who received IMPT versus IMRT. CONCLUSIONS: Studies have proposed that proton's greater relative biological effectiveness at the Bragg peak could lead to tissue inflammation. Our study did not corroborate these findings. This study's conclusion underscores the need for further investigations with ultimate correlation with clinical toxicity outcomes.

Auto-segmentation of neck nodal metastases using self-distilled masked image transformer on longitudinal MR images.

Objectives: Auto-segmentation promises greater speed and lower inter-reader variability than manual segmentations in radiation oncology clinical practice. This study aims to implement and evaluate the accuracy of the auto-segmentation algorithm, "Masked Image modeling using the vision Transformers (SMIT)," for neck nodal metastases on longitudinal T2-weighted (T2w) MR images in oropharyngeal squamous cell carcinoma (OPSCC) patients. Methods: This prospective clinical trial study included 123 human papillomaviruses (HPV-positive [+]) related OSPCC patients who received concurrent chemoradiotherapy. T2w MR images were acquired on 3 T at pre-treatment (Tx), week 0, and intra-Tx weeks (1-3). Manual delineations of metastatic neck nodes from 123 OPSCC patients were used for the SMIT auto-segmentation, and total tumor volumes were calculated. Standard statistical analyses compared contour volumes from SMIT vs manual segmentation (Wilcoxon signed-rank test [WSRT]), and Spearman's rank correlation coefficients (ρ) were computed. Segmentation accuracy was evaluated on the test data set using the dice similarity coefficient (DSC) metric value. P-values <0.05 were considered significant. Results: No significant difference in manual and SMIT delineated tumor volume at pre-Tx (8.68 ± 7.15 vs 8.38 ± 7.01 cm3, P = 0.26 [WSRT]), and the Bland-Altman method established the limits of agreement as -1.71 to 2.31 cm3, with a mean difference of 0.30 cm3. SMIT model and manually delineated tumor volume estimates were highly correlated (ρ = 0.84-0.96, P < 0.001). The mean DSC metric values were 0.86, 0.85, 0.77, and 0.79 at the pre-Tx and intra-Tx weeks (1-3), respectively. Conclusions: The SMIT algorithm provides sufficient segmentation accuracy for oncological applications in HPV+ OPSCC. Advances in knowledge: First evaluation of auto-segmentation with SMIT using longitudinal T2w MRI in HPV+ OPSCC.

Nomogram to predict risk of early mortality following definitive or adjuvant radiation and systemic therapy for head and neck cancer.

Purpose/Objectives: We sought to create nomograms to predict individual risk of early mortality, which can identify patients who require interventions to prevent early death. Methods: We included patients in the National Cancer Database with non-metastatic squamous cell carcinoma of the head and neck who received radiation and systemic therapy between 2004 and 2017 in the definitive or adjuvant setting. Early mortality was defined as any death less than 90 days after starting radiation. Multivariable logistic regression was used to assess the relationship between covariates and early mortality. Nomograms to predict the risk of early death were created for both the definitive and adjuvant settings. Results: Among 84,563 patients in the definitive group and 18,514 patients in the adjuvant group, rates of early mortality were 3.5 % (95 % CI 3.4-3.7 %) and 2.2 %, (95 % CI 1.9-2.4 %), respectively. Patients above the age of 70 had an early mortality rate of 7.8 % (95 % CI 7.3-8.2 %) in the definitive group and 4.4 % (95 % CI 3.6-5.4 %) in the adjuvant group. In the multivariable analysis, age, comorbidity, T and N category, and tumor site were associated with early mortality in both cohorts (p < 0.05 for all). Nomograms including age, comorbidity, T and N category and tumor site performed better than age alone at predicting early mortality (AUC for definitive group: 0.70 vs 0.66; AUC for adjuvant group: 0.71 vs 0.61). Conclusion: Nomograms including age, comorbidity, T and N category and tumor site were developed to predict the risk of early death following definitive or adjuvant chemoradiation.

Clinical Experience With an Offline Adaptive Radiation Therapy Head and Neck Program: Dosimetric Benefits and Opportunities for Patient Selection.

PURPOSE: The objective of this study was to develop a linear accelerator (LINAC)-based adaptive radiation therapy (ART) workflow for the head and neck that is informed by automated image tracking to identify major anatomic changes warranting adaptation. In this study, we report our initial clinical experience with the program and an investigation into potential trigger signals for ART. METHODS AND MATERIALS: Offline ART was systematically performed on patients receiving radiation therapy for head and neck cancer on C-arm LINACs. Adaptations were performed at a single time point during treatment with resimulation approximately 3 weeks into treatment. Throughout treatment, all patients were tracked using an automated image tracking system called the Automated Watchdog for Adaptive Radiotherapy Environment (AWARE). AWARE measures volumetric changes in gross tumor volumes (GTVs) and selected normal tissues via cone beam computed tomography scans and deformable registration. The benefit of ART was determined by comparing adaptive plan dosimetry and normal tissue complication probabilities against the initial plans recalculated on resimulation computed tomography scans. Dosimetric differences were then correlated with AWARE-measured volume changes to identify patient-specific triggers for ART. Candidate trigger variables were evaluated using receiver operator characteristic analysis. RESULTS: In total, 46 patients received ART in this study. Among these patients, we observed a significant decrease in dose to the submandibular glands (mean ± standard deviation: -219.2 ± 291.2 cGy, P < 10-5), parotids (-68.2 ± 197.7 cGy, P = .001), and oral cavity (-238.7 ± 206.7 cGy, P < 10-5) with the adaptive plan. Normal tissue complication probabilities for xerostomia computed from mean parotid doses also decreased significantly with the adaptive plans (P = .008). We also observed systematic intratreatment volume reductions (ΔV) for GTVs and normal tissues. Candidate triggers were identified that predicted significant improvement with ART, including parotid ΔV = 7%, neck ΔV = 2%, and nodal GTV ΔV = 29%. CONCLUSIONS: Systematic offline head and neck ART was successfully deployed on conventional LINACs and reduced doses to critical salivary structures and the oral cavity. Automated cone beam computed tomography tracking provided information regarding anatomic changes that may aid patient-specific triggering for ART.

Hypoxia-Directed Treatment of Human Papillomavirus-Related Oropharyngeal Carcinoma.

PURPOSE: Standard curative-intent chemoradiotherapy for human papillomavirus (HPV)-related oropharyngeal carcinoma results in significant toxicity. Since hypoxic tumors are radioresistant, we posited that the aerobic state of a tumor could identify patients eligible for de-escalation of chemoradiotherapy while maintaining treatment efficacy. METHODS: We enrolled patients with HPV-related oropharyngeal carcinoma to receive de-escalated definitive chemoradiotherapy in a phase II study (ClinicalTrials.gov identifier: NCT03323463). Patients first underwent surgical removal of disease at their primary site, but not of gross disease in the neck. A baseline 18F-fluoromisonidazole positron emission tomography scan was used to measure tumor hypoxia and was repeated 1-2 weeks intratreatment. Patients with nonhypoxic tumors received 30 Gy (3 weeks) with chemotherapy, whereas those with hypoxic tumors received standard chemoradiotherapy to 70 Gy (7 weeks). The primary objective was achieving a 2-year locoregional control (LRC) of 95% with a 7% noninferiority margin. RESULTS: One hundred fifty-eight patients with T0-2/N1-N2c were enrolled, of which 152 patients were eligible for analyses. Of these, 128 patients met criteria for 30 Gy and 24 patients received 70 Gy. The 2-year LRC was 94.7% (95% CI, 89.8 to 97.7), meeting our primary objective. With a median follow-up time of 38.3 (range, 22.1-58.4) months, the 2-year progression-free survival (PFS) and overall survival (OS) rates were 94% and 100%, respectively, for the 30-Gy cohort. The 70-Gy cohort had similar 2-year PFS and OS rates at 96% and 96%, respectively. Acute grade 3-4 adverse events were more common in 70 Gy versus 30 Gy (58.3% v 32%; P = .02). Late grade 3-4 adverse events only occurred in the 70-Gy cohort, in which 4.5% complained of late dysphagia. CONCLUSION: Tumor hypoxia is a promising approach to direct dosing of curative-intent chemoradiotherapy for HPV-related carcinomas with preserved efficacy and substantially reduced toxicity that requires further investigation.

Higher Rates of Inadequate Adjuvant Radiation Dose Among Older Adults with Head and Neck Cancer.

OBJECTIVE: To determine the rate of inadequate radiotherapy and identify risk factors associated with inadequate adjuvant radiotherapy for head and neck cancer among older adults. METHODS: A retrospective review of the National Cancer Database (NCDB) was performed to identify patients diagnosed with squamous cell cancer of the head and neck between 2004 and 2017. Patients with a single malignancy, negative surgical margins, no extranodal extension, and receipt of adjuvant radiation without systemic therapy were included in the study cohort. The main outcome of interest was the adjuvant radiation dose received. Participant data were compared using univariable, multivariable, and correlation analyses to evaluate risk factors for inadequate radiation therapy (RT) dosing. RESULTS: Among 7608 patients, 1010 patients (13.3%) received an inadequate radiation dose and 6598 (86.7%) received an adequate dose. Patients living in a higher income zip-code, younger age, and those who received intensity-modulated RT (IMRT) were more likely to receive an adequate radiation dose (p < 0.05). Patients older than 70 and 80 years old had a greater likelihood of receiving an inadequate radiation dose (≥70 vs. <70: 16.9% vs. 12.5%; p < 0.05 and ≥80 vs. <80: 20.6% vs. 13.0%%; p < 0.05). Similarly, increasing age was negatively correlated with radiation dose (correlation coefficient: -0.05; p < 0.001). CONCLUSION: A substantial proportion of older patients receiving adjuvant radiation do not complete the full treatment. Older age, year of diagnosis, non-IMRT, and living in a lower-income zip code were associated with early termination of RT. Future studies should examine strategies to improve tolerance of adjuvant RT so that more patients complete the full treatment. LEVEL OF EVIDENCE: 3; Cohort Study Laryngoscope, 134:2206-2211, 2024.

Radiation oncology for the rhinologist.

PURPOSE OF REVIEW: This comprehensive review explores evolving treatment strategies for sinonasal and nasopharyngeal malignancies. It analyzes the role of adjuvant radiotherapy, the potential of intensity-modulated proton therapy (IMPT), and the relevance of de-escalation strategies nasopharyngeal carcinoma (NPC). Additionally, it discusses hyperfractionation in re-irradiation in NPC. RECENT FINDINGS: Adjuvant radiotherapy remains pivotal for sinonasal tumors, improving locoregional control and survival, notably in squamous cell carcinomas, adenocarcinomas, and adenoid cystic carcinomas. IMPT promises enhanced outcomes by sparing healthy tissues, potentially improving patients' quality of life. For select stage II/T3N0 NPC, radiotherapy alone offers comparable outcomes to concurrent chemoradiotherapy, with fewer adverse events and improved quality of life. Selective neck irradiation in NPC patients with uninvolved necks maintains oncologic outcomes while reducing late toxicity. Hyperfractionation in re-irradiation shows promise in lowering late toxicities and improving overall survival, particularly in undifferentiated sinonasal carcinomas. SUMMARY: This review underscores the significance of adjuvant radiotherapy and the potential of advanced radiation techniques in optimizing sinonasal and nasopharyngeal malignancy outcomes. It emphasizes evolving de-escalation methods and individualized, evidence-based approaches. Future research will further refine strategies for these challenging malignancies.

Standard-of-care systemic therapy with or without stereotactic body radiotherapy in patients with oligoprogressive breast cancer or non-small-cell lung cancer (Consolidative Use of Radiotherapy to Block [CURB] oligoprogression): an open-label, randomised, controlled, phase 2 study.

BACKGROUND: Most patients with metastatic cancer eventually develop resistance to systemic therapy, with some having limited disease progression (ie, oligoprogression). We aimed to assess whether stereotactic body radiotherapy (SBRT) targeting oligoprogressive sites could improve patient outcomes. METHODS: We did a phase 2, open-label, randomised controlled trial of SBRT in patients with oligoprogressive metastatic breast cancer or non-small-cell lung cancer (NSCLC) after having received at least first-line systemic therapy, with oligoprogression defined as five or less progressive lesions on PET-CT or CT. Patients aged 18 years or older were enrolled from a tertiary cancer centre in New York, NY, USA, and six affiliated regional centres in the states of New York and New Jersey, with a 1:1 randomisation between standard of care (standard-of-care group) and SBRT plus standard of care (SBRT group). Randomisation was done with a computer-based algorithm with stratification by number of progressive sites of metastasis, receptor or driver genetic alteration status, primary site, and type of systemic therapy previously received. Patients and investigators were not masked to treatment allocation. The primary endpoint was progression-free survival, measured up to 12 months. We did a prespecified subgroup analysis of the primary endpoint by disease site. All analyses were done in the intention-to-treat population. The study is registered with ClinicalTrials.gov, NCT03808662, and is complete. FINDINGS: From Jan 1, 2019, to July 31, 2021, 106 patients were randomly assigned to standard of care (n=51; 23 patients with breast cancer and 28 patients with NSCLC) or SBRT plus standard of care (n=55; 24 patients with breast cancer and 31 patients with NSCLC). 16 (34%) of 47 patients with breast cancer had triple-negative disease, and 51 (86%) of 59 patients with NSCLC had no actionable driver mutation. The study was closed to accrual before reaching the targeted sample size, after the primary efficacy endpoint was met during a preplanned interim analysis. The median follow-up was 11·6 months for patients in the standard-of-care group and 12·1 months for patients in the SBRT group. The median progression-free survival was 3·2 months (95% CI 2·0-4·5) for patients in the standard-of-care group versus 7·2 months (4·5-10·0) for patients in the SBRT group (hazard ratio [HR] 0·53, 95% CI 0·35-0·81; p=0·0035). The median progression-free survival was higher for patients with NSCLC in the SBRT group than for those with NSCLC in the standard-of-care group (10·0 months [7·2-not reached] vs 2·2 months [95% CI 2·0-4·5]; HR 0·41, 95% CI 0·22-0·75; p=0·0039), but no difference was found for patients with breast cancer (4·4 months [2·5-8·7] vs 4·2 months [1·8-5·5]; 0·78, 0·43-1·43; p=0·43). Grade 2 or worse adverse events occurred in 21 (41%) patients in the standard-of-care group and 34 (62%) patients in the SBRT group. Nine (16%) patients in the SBRT group had grade 2 or worse toxicities related to SBRT, including gastrointestinal reflux disease, pain exacerbation, radiation pneumonitis, brachial plexopathy, and low blood counts. INTERPRETATION: The trial showed that progression-free survival was increased in the SBRT plus standard-of-care group compared with standard of care only. Oligoprogression in patients with metastatic NSCLC could be effectively treated with SBRT plus standard of care, leading to more than a four-times increase in progression-free survival compared with standard of care only. By contrast, no benefit was observed in patients with oligoprogressive breast cancer. Further studies to validate these findings and understand the differential benefits are warranted. FUNDING: National Cancer Institute.

Implications of Using the BRIEF-Preschool With School-Age Children With Down Syndrome.

This study evaluated the appropriateness of scoring the Behavior Rating Inventory of Executive Function-Preschool (BRIEF-P) using age-equivalent scores generated from multiple measures of cognition and language among school-age children with Down syndrome (DS). Subscale T scores for 95 children with DS were contrasted using standard scoring on the Behavior Rating Inventory of Executive Function-Second edition (BRIEF-2; based on chronological age) to alternate scoring using the BRIEF-P (based on age-equivalent) for patterns of subscale intercorrelations, differences in mean scores, and agreement on findings from clinical cut-off scores. Results with children with DS suggested using (1) the BRIEF-P for children ages 2-5 years old, (2) the BRIEF-2 with chronological-age scoring or the BRIEF-P with age-equivalent scoring (with some caveats) for research on children ages 5-10 years old, and (3) the BRIEF-2 for children ages 11 and older.

Increased anticholinergic medication use in middle-aged and older autistic adults and its associations with self-reported memory difficulties and cognitive decline.

Many commonly used prescription and over-the-counter medicines have potent anticholinergic (AC) effects. Among older adults, AC medications are associated with cognitive impairment and risk for cognitive disorders, including Alzheimer's disease. Collectively, the impact of AC medications is known as anticholinergic cognitive burden (ACB). Because of the high rates of co-occurring medical and psychiatric conditions, autistic adults may have high AC exposure and, thus, may experience elevated ACB. However, no research has characterized AC exposure or examined its associations with cognitive outcomes in autistic adults. Autistic adults (40-83 years) recruited via Simons Powering Autism Research's (SPARK) Research Match service self-reported their medication use (N = 415) and memory complaints (N = 382) at Time (T)1. At T2, 2 years later, a subset of T1 participants (N = 197) self-reported on decline in cognition. Medications were coded using two scales of AC potency. A high proportion (48.2%-62.9%, depending upon the AC potency scale) of autistic adults reported taking at least one medication with AC effects, and 20.5% to 26.5% of autistic adults reported clinically-relevant levels of AC medication (potency ≥3). After controlling for birth-sex, and age, hierarchical linear regression models showed total ACB scores and AC potency values of ≥3 predicted greater memory complaints. Logistic regression models showed that AC medicines at T1 were associated with self-reported cognitive decline at follow-up 2 years later. Understanding AC medications-including potentially earlier AC polypharmacy-and their impacts on cognition (e.g., dementia risk) in autistic adults is warranted.

Second-trimester Abortion.

In 2019, the US Centers for Disease Control reported that 7% of abortions were performed after 13 weeks of pregnancy, a small proportion of all terminations. However, the need for second-trimester abortions will increase commensurate with restrictions to access nationwide. Second-trimester abortions are performed with medications or through a procedure. Health care practitioners serving persons at risk of pregnancy should understand how abortions are performed and how to deliver evidence-based postabortion care. The purpose of this article is to provide a foundation for caring for individuals before, during, and after second-trimester abortion.

A Quantitative Multiparametric MRI Analysis Platform for Estimation of Robust Imaging Biomarkers in Clinical Oncology.

There is a need to develop user-friendly imaging tools estimating robust quantitative biomarkers (QIBs) from multiparametric (mp)MRI for clinical applications in oncology. Quantitative metrics derived from (mp)MRI can monitor and predict early responses to treatment, often prior to anatomical changes. We have developed a vendor-agnostic, flexible, and user-friendly MATLAB-based toolkit, MRI-Quantitative Analysis and Multiparametric Evaluation Routines ("MRI-QAMPER", current release v3.0), for the estimation of quantitative metrics from dynamic contrast-enhanced (DCE) and multi-b value diffusion-weighted (DW) MR and MR relaxometry. MRI-QAMPER's functionality includes generating numerical parametric maps from these methods reflecting tumor permeability, cellularity, and tissue morphology. MRI-QAMPER routines were validated using digital reference objects (DROs) for DCE and DW MRI, serving as initial approval stages in the National Cancer Institute Quantitative Imaging Network (NCI/QIN) software benchmark. MRI-QAMPER has participated in DCE and DW MRI Collaborative Challenge Projects (CCPs), which are key technical stages in the NCI/QIN benchmark. In a DCE CCP, QAMPER presented the best repeatability coefficient (RC = 0.56) across test-retest brain metastasis data, out of ten participating DCE software packages. In a DW CCP, QAMPER ranked among the top five (out of fourteen) tools with the highest area under the curve (AUC) for prostate cancer detection. This platform can seamlessly process mpMRI data from brain, head and neck, thyroid, prostate, pancreas, and bladder cancer. MRI-QAMPER prospectively analyzes dose de-escalation trial data for oropharyngeal cancer, which has earned it advanced NCI/QIN approval for expanded usage and applications in wider clinical trials.

The Applications and Pitfalls of Cone-Beam Computed Tomography-Based Synthetic Computed Tomography for Adaptive Evaluation in Pencil-Beam Scanning Proton Therapy.

PURPOSE: The study evaluates the efficacy of cone-beam computed tomography (CBCT)-based synthetic CTs (sCT) as a potential alternative to verification CT (vCT) for enhanced treatment monitoring and early adaptation in proton therapy. METHODS: Seven common treatment sites were studied. Two sets of sCT per case were generated: direct-deformed (DD) sCT and image-correction (IC) sCT. The image qualities and dosimetric impact of the sCT were compared to the same-day vCT. RESULTS: The sCT agreed with vCT in regions of homogeneous tissues such as the brain and breast; however, notable discrepancies were observed in the thorax and abdomen. The sCT outliers existed for DD sCT when there was an anatomy change and for IC sCT in low-density regions. The target coverage exhibited less than a 5% variance in most DD and IC sCT cases when compared to vCT. The Dmax of serial organ-at-risk (OAR) in sCT plans shows greater deviation from vCT than small-volume dose metrics (D0.1cc). The parallel OAR volumetric and mean doses remained consistent, with average deviations below 1.5%. CONCLUSION: The use of sCT enables precise treatment and prompt early adaptation for proton therapy. The quality assurance of sCT is mandatory in the early stage of clinical implementation.

Self-reported Prospective and Retrospective Memory Among Middle Aged and Older Autistic and Non-autistic People.

OBJECTIVE: Self-reported memory difficulties are common among older adults, but few studies have examined memory problems among autistic middle-aged and older people. The current study examines self-rated prospective (PM) and retrospective (RM) memory difficulties and their associations with age in middle-aged and older autistic and non-autistic people. METHODS: 350 autistic people (58% assigned-female-at-birth; age-range: 40-83 years) and 350 non-autistic adults matched on age, birth-sex and education level were included in the analysis. Participants completed the Prospective and Retrospective Memory Questionnaire (PRMQ) which includes questions about PM vs. RM (memory type), environment-cued vs. self-cued (cue), and short vs. long delay (delay). RESULTS: Autistic people reported significantly more PM and RM difficulties than the comparison group. Both groups reported more difficulties with PM (vs. RM), self-cued (vs. environment-cued), and short (vs. long) delay. No significant interactions were observed. Among autistic people, younger age was associated with reporting more PM and RM difficulties, but this pattern was not observed among non-autistic people. CONCLUSIONS: Autistic people may be at reduced risk for memory problems as they age, compared to their same-age non-autistic peers. Further studies are required to explore the association between self-reported memory challenges and memory task performance among autistic older people.