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Although adults aged 65 years or older make up a strong majority of cancer patients, their underrepresentation in cancer clinical trials leads to the lack of representative data to guide evidence-based therapeutic decisions in this patient population. The Trial Design Working Group, convened as part of the workshop titled, Engaging Older Adults in the National Cancer Institute Clinical Trials Network: Challenges and Opportunities, recommended study designs and design elements that could improve accrual of older adults in National Cancer Institute–funded clinical trials. These include trials that are specifically designed to enroll older adults, trials that include a cohort of older patients (parallel cohort, stratified cohort, or embedded cohort), and trials with pragmatic design elements to facilitate enrollment of older adults. This manuscript provides brief descriptions of the recommended designs, examples of successful trials, and considerations for implementation of these designs. As with any clinical trial, the scientific questions and trial objectives should drive the study design, the selection of endpoints and intervention, and eligibility criteria. When designing trials that include older adults, the heterogeneity of fitness levels is an important consideration as fitness can influence accrual rates and outcomes. Appropriately incorporating geriatric assessments can help identify the optimal subset of older patients for inclusion and minimize selection bias. Incorporating pragmatic design elements to reduce the burden on trial participants as well as on accruing sites and retaining essential elements to ensure that the main goal of the trial can be accomplished can enhance enrollment without compromising the integrity of trials.

A 39-year-old previously healthy man presented with insidiously progressive paresthesia in his lower extremities and worsening of gait and balance. MRI demonstrated T2-hyperintense signal abnormalities involving the thalami, midbrain, dentate nuclei, and adjacent deep cerebellar white matter, which are characteristic of cerebrotendinous xanthomatosis (CTX) (figure). Magnetic resonance spectroscopy revealed typical lipid peaks at 0.9 and 1.3 ppm,1 and serology analysis indicated sterol 27-hydroxylase deficiency,2 confirming the diagnosis. CTX is a rare lipid storage disease with unique clinical and imaging findings, and effective treatment with positive outcomes if initiated early, raising the importance of awareness and early recognition of this disease.2

SETD2 catalyzes methylation at lysine 36 of histone H3 and it has many disease connections. We investigated the substrate sequence specificity of SETD2 and identified nine additional peptide and one protein (FBN1) substrates. Our data showed that SETD2 strongly prefers amino acids different from those in the H3K36 sequence at several positions of its specificity profile. Based on this, we designed an optimized super-substrate containing four amino acid exchanges and show by quantitative methylation assays with SETD2 that the super-substrate peptide is methylated about 290-fold more efficiently than the H3K36 peptide. Protein methylation studies confirmed very strong SETD2 methylation of the super-substrate in vitro and in cells. We solved the structure of SETD2 with bound super-substrate peptide containing a target lysine to methionine mutation, which revealed better interactions involving three of the substituted residues. Our data illustrate that substrate sequence design can strongly increase the activity of protein lysine methyltransferases., Deutsche Forschungsgemeinschaft (German Research Foundation), German Academic Exchange Service (DAAD), Egyptian Ministry of Higher Education, Projekt DEAL

The H3.3 G34W mutation has been observed in 90% of the patients affected by giant cell tumor of bone (GCTB). It had been shown to reduce the activity of the SETD2 H3K36 protein lysine methyltransferase (PKMT) and lead to genome wide changes in epigenome modifications including a global reduction in DNA methylation. Here, we investigated the effect of the H3.3 G34W mutation on the activity of the H3K36me2 methyltransferase NSD1, because NSD1 is known to play an important role in the differentiation of chondrocytes and osteoblasts. Unexpectedly, we observed that H3.3 G34W has a gain-of-function effect and it stimulates K36 methylation by NSD1 by about 2.3-fold with peptide substrates and 6.3-fold with recombinant nucleosomal substrates. This effect is specific for NSD1, as NSD2 shows only a mild stimulation on G34W substrates. The potential downstream effects of the G34W induced hyperactivity of NSD1 on DNA methylation, H3K27me3, histone acetylation and splicing are discussed.

PURPOSE To assess the prevalence of positive conflict of interest (COI) disclosures in U.S.-based interventional radiology (IR) research as well as the level of agreement between disclosed financial relationships and open payment data for top-cited image-guided procedure research. MATERIALS AND METHODS All publications in volume 30 (2019) of the Journal of Vascular and Interventional Radiology (JVIR) were reviewed to estimate the prevalence of COI disclosures in IR research. Publications were categorized as primary research, systematic review, or other. Prevalence was then compared across JVIR publication subtype, categories, and whether they were device-focused with chi-squared tests. Additionally, the Web of Science database was searched for the top 10 cited studies of 10 common image-guided procedures with available U.S. physician payment data. Payments were categorized as historical (>1 year prior to publication) or active (

Background: Older adults account for 70% of cancer-related deaths, but previous studies have shown that they are underrepresented in cancer clinical trials. We sought to analyze the representation and outcomes of older adults in trials conducted in the era of novel targeted therapy and immunotherapy. Methods: We searched the 2020 NCCN Clinical Practice Guidelines in Oncology and retrieved trials from the past 10 years leading to category 1 recommendations in the first-line metastatic setting for the 5 most common causes of cancer death. We categorized trials by cancer type, single-agent versus multiagent approach, and therapeutic class. We described the percentage of older adults (according to each trial’s definition) and used a Mantel-Haenszel random-effects meta-analysis model to compare overall and progression-free survival by age. Results: We identified 30 trials consisting of 24,416 patients. Across all trials, 44% of enrolled patients were older adults. Representation of older adults by cancer type within trials was 49% prostate cancer, 38% pancreatic cancer, 37% breast cancer, and 34% non–small cell lung cancer. Representation of older adults also varied by therapeutic class: 20% received immunotherapy, 44% received cytotoxic chemotherapy, 54% received targeted/hormonal therapy, and 34% received combination therapy (PConclusions: We found that >40% of patients in practice-changing trials are older adults. Although they remain underrepresented in clinical trials compared with the general population, older adults in practice-changing trials seem to be better represented than in previously reported analyses of cooperative group trials.

PURPOSE This study determined whether an electronic version of the geriatric assessment is feasible in a multi-institutional, diverse setting. METHODs Ten sites within the Alliance for Clinical Trials in Oncology participated. Patients who had active cancer or a history of cancer and were 65 years of age or older were eligible. The geriatric assessment was completed with an electronic data capture system that had been loaded onto iPads. Feasibility was defined a priori as completion in at least 70% of patients either with or without help. To enhance racial diversity, the original sample size was later changed and augmented by 50% with the intention of increasing enrollment of older minority patients. RESULTS A total of one hundred fifty-four patients were registered with a median age of 72 years (range, 65-91 years). Forty-three (28%) identified themselves as African American or Black. One hundred forty-one patients (92%) completed the electronic geriatric assessment. Feasibility was observed across all subgroups, regardless of race, education, performance status, comorbidities, and cognition; 124 patients (81%) completed the geriatric assessment without help. Reasons for not completing the geriatric assessment are as follows: clinic visit did not occur (n = 6), no iPad connection to the Internet (n = 3), patient declined (n = 2), prolonged hospitalization (n = 1), and patient died (n = 1). Reasons for needing help, as reported by study personnel, were as follows: the patient preferred that research personnel ask the questions (n = 9), vision problem (n = 3), lack of comfort with the iPad (n = 2), questions were not clear (n = 1), less proficient in English (n = 1), and challenge in pressing the green button to go to the next question (n = 1). CONCLUSION The electronic geriatric assessment is feasible in a multi-institutional setting that includes a notable proportion of African American or Black patients.

As pegylated interferon alpha (PEG-IFN-α) is increasingly used in combination regimens of novel drugs, we aimed to characterize ALT flares and their relationship with serum HBsAg and HBV RNA kinetics in a large combined cohort of chronic hepatitis B (CHB) patients on PEG-IFN-α-based therapy. In this post hoc analysis of four international randomized trials, 269/130/124/128 patients on PEG-IFN-α monotherapy, PEG-IFN-α plus nucleos(t)ide analogue (NA) de novo combination, PEG-IFN-α add-on to NA or NA monotherapy were included, respectively. A flare was defined as an episode of ALT ≥5 × ULN. The association between flares and HBsAg and HBV RNA changes were examined. On-treatment flares occurred in 83/651 (13%) patients (median timing/magnitude: week 8 [IQR 4–12], 7.6 × ULN [IQR 6.2–10.5]). Flare patients were more often Caucasians with genotype A/D and had higher baseline ALT, HBV DNA, HBV RNA and HBsAg levels than the no-flare group. More flares were observed on PEG-IFN-α monotherapy (18%) and PEG-IFN+NA de novo combination (24%) vs. PEG-IFN-α add-on (2%) or NA monotherapy (1%) (p 10 at the final visit declines started shortly before the flare, progressing towards 24 weeks thereafter. On-treatment flares were seen in 16/22 (73%) patients who achieved HBsAg loss. In conclusion, ALT flares during PEG-IFN-α treatment are associated with subsequent HBsAg and HBV RNA decline and predict subsequent HBsAg loss. Flares rarely occurred during PEG-IFN-α add-on therapy and associated with low HBsAg loss rates. Combination regimens targeting the window of heightened response could be promising.

Hepatocellular carcinoma (HCC) is the most common primary cancer of the liver and has an overall five-year survival rate of less than twenty percent. For patients with unresectable disease, evolving liver-directed locoregional therapies provide efficacious treatment across the spectrum of disease stages and via a variety of catheter-directed and percutaneous techniques. Goals of locoregional therapies in HCC may include curative intent in early-stage disease, bridging or downstaging to surgical resection or transplantation for early or intermediate-stage disease, and local disease control and palliation in advanced-stage disease. This review explores the outcomes of chemoembolization, bland embolization, radioembolization, and percutaneous ablative therapies. Attention is also given to prognostic factors related to each of the respective techniques, as well as future directions of locoregional therapies for HCC.

Evidence has begun to emerge indicating that cancer survivors experience accelerated aging. This study examines this phenomenon by evaluating trajectories of functional decline in older adults with a history of a cancer diagnosis relative to those without a history of cancer.Community dwelling healthy volunteers in the Baltimore Longitudinal Study of Aging were evaluated in the Clinical Research Unit of the National Institute on Aging Intramural Research Program. Between 2006 and 2019, 1728 men and women (aged 22-100) underwent clinical evaluation of functional status; 359 reported having a history of cancer. Longitudinal associations between self-reported cancer history and measures of functional decline were examined using generalized estimating equations. Additionally, time-to-event and Cox proportional hazards models were used to examine trajectories of decline. Where appropriate, age-stratified associations were examined, and models were adjusted for sex, body mass index, race, smoking status, education, and number of comorbid conditions.Among all participants, a history of cancer was associated with 1.42 (95% CI 1.11-1.81) greater odds of weak grip strength. Among older participants (65 years of age), those with a history of cancer had 1.61 (95% CI 1.28, 2.02) greater odds of slow gait speed and a 0.11 unit (95% CI 0.19-0.03) lower physical performance score than those with no cancer history. Time-to-event analysis showed that older individuals with a history of cancer experienced steeper decline in grip strength and gait speed than older adults with no history of cancer (p 0.01).Cancer survivors, especially older individuals, demonstrate greater odds of and accelerated functional decline, suggesting that cancer and/or its treatment may alter aging trajectories. Observational and intervention studies are needed for prevention, mitigation, and/or reversal of aging-related effects of cancer and its treatment.

Purpose To evaluate national trends in tube-related genitourinary interventions, with specific attention to primary operator specialty. Methods Using a 5% national sample of Medicare claims data from 2005 to 2015, all claims associated with nephrostomy tube, nephro-ureteral tube, and ureteral stent placement and exchange were identified. The annual volume of the nine billable procedures were analyzed to evaluate trends in the number of procedures performed and primary operator specialty over time. The Charleston Comorbidity Index (CCI) was used to evaluate patient comorbidities and to determine differences in patient populations treated by interventional radiologists and urologists. Results The total volume of tube-related genitourinary interventions has increased over the course of the study period, representing 455.0 services per 100,000 Medicare Fee-for-Service beneficiaries in 2005 to 607.2 services in 2015, an increase of 33.4%. Interventional radiologists performed the majority of all procedures in all procedure types and for each year (>90%) with the exception of nephro-ureteral catheter placement or ureteral stent placement, for which urologists performed the overwhelming majority of procedures each year (>85%). Interventional radiologists performed 63% of their total number of procedures on patients with a CCI = 3 or higher, and urologists performed 42% of their total number of procedures on patients with a CCI = 3 or higher (P Conclusion Tube-related genitourinary interventions have demonstrated persistent growth over the 2005 to 2015 decade. Interventional radiologists are the dominant providers for the majority of these interventions compared with urologists while delivering care to a patient population with a higher number of comorbidities.

This cross-sectional study assesses differences in clinical trial participation among older vs younger adults with cancer.

Transdermal measurement of glomerular filtration rate (GFR) has been used to evaluate kidney function in conscious animals. This technique is well established in rodents to study acute kidney injury and chronic kidney disease. However, GFR measurement using the transdermal system has not been validated in pigs, a species with a similar renal system to humans. Hence, we investigated the effect of sepsis on transdermal GFR in anesthetized and mechanically ventilated neonatal pigs. Polymicrobial sepsis was induced by cecal ligation and puncture (CLP). The transdermal GFR measurement system consisting of a miniaturized fluorescence sensor was attached to the pig's shaved skin to determine the clearance of fluorescein-isothiocyanate (FITC) conjugated sinistrin, an intravenously injected GFR tracer. Our results show that at 12 h post-CLP, serum creatinine increased with a decrease in GFR. This study demonstrates, for the first time, the utility of the transdermal GFR approach in determining renal function in mechanically ventilated, neonatal pigs.

OBJECTIVE. The purpose of this study was to report national utilization trends and outcomes after percutaneous cholecystostomy, cholecystectomy, or no intervention among patients admitted to hospitals with acute cholecystitis. MATERIALS AND METHODS. The Nationwide Inpatient Sample was queried from 2005 to 2014. Admissions were identified and stratified into treatment groups of percutaneous cholecystostomy, cholecystectomy, and no intervention on the basis of International Classification of Diseases, 9th revision, codes. Outcomes, including length of stay, inpatient mortality, and complications including hemorrhage and bile peritonitis, were identified. Multivariate analysis was performed to identify mortality risk by treatment type after adjustment for baseline comorbidities and risk of mortality. RESULTS. Among 2,550,013 patients (58.6% women, 41.4% men; mean age, 55.9 years) admitted for acute cholecystitis over the study duration, 73,841 (2.9%) patients underwent percutaneous cholecystostomy, 2,005,728 (78.7%) underwent cholecystectomy, and 459,585 (18.0%) did not undergo either procedure. Use of percutaneous cholecystostomy increased from 2985 procedures in 2005 to 12,650 in 2014. The percutaneous cholecystostomy cohort had a higher mean age (70.6 years) than the other two groups (cholecystectomy, 53.8 years; no intervention, 62.5 years), a higher mean comorbidity index (cholecystostomy, 3.74; cholecystectomy, 1.77; no intervention, 2.65), and a higher mean risk of mortality index (cholecystostomy, 2.88; cholecystectomy, 1.45; no intervention, 2.07) (p < .05). Unadjusted inpatient all-cause mortality was 10.1% in the percutaneous cholecystostomy, 0.8% in the cholecystectomy, and 5.2% in the no intervention cohorts. After adjustment for baseline mortality risk, percutaneous cholecystostomy (odds ratio, 0.78; 95% CI, 0.76-0.81) and cholecystectomy (odds ratio, 0.42; 95% CI, 0.41-0.43) were associated with reduced mortality compared with no intervention. CONCLUSION. Use of percutaneous cholecystostomy is increasing among patients admitted with acute cholecystitis. After adjustment for baseline comorbidities, percutaneous cholecystostomy is associated with improved odds of survival compared with no intervention.

Chemotherapy may impair cognition and contribute to accelerated aging. The purpose of this study was to assess the effects of chemotherapy on the connectivity of the default mode network (DMN) in older women with breast cancer. This prospective longitudinal study enrolled women aged ≥ 60 years with stage I–III breast cancer (CTx group) and matched healthy controls (HC group). Study assessments, consisting of resting-state functional MRI (rs-fMRI) and the Picture Sequence Memory (psm) test for episodic memory from the NIH Toolbox for Cognition, were obtained at baseline and within one month after the completion of chemotherapy for the CTx group and at matched intervals for the HC group. Two-sample t-test and FDR multiple comparison were used for statistical inference. Our analysis of the CTx group (N = 19; 60–82 years of age, mean = 66.6, SD = 5.24) compared to the HC group (N = 14; 60–78 years of age, mean = 68.1, SD = 5.69) revealed weaker DMN subnetwork connectivity in the anterior brain but stronger connectivity in the posterior brain at baseline. After chemotherapy, this pattern was reversed, with stronger anterior connectivity and weaker posterior connectivity. In addition, the meta-level functional network connectivity (FNC) among the DMN subnetworks after chemotherapy was consistently weaker than the baseline FNC as seen in the couplings between anterior cingulate cortex (ACC) and retrosplenial (rSplenia) region, with ΔFNC(‘ACC’,’rSplenia’)=-0.14, t value=-2.44, 95 %CI=[-0.27,-0.10], pFDR

Purpose Twitter is an increasingly popular social media platform within the health care community. The objective of this analysis is to characterize the profile of radiation oncology–related tweets and Twitter users over the past 6 years. Methods and Materials Using the web-based social media analytics platform Symplur Signals, we filtered tweets containing at least 1 of the following hashtags or key words: #radonc, #radiationoncology, "rad onc," or "radiation oncology." We evaluated radiation oncology–related Twitter activity between October 2014 and March 2020 for tweet frequency, tweet content, and individuals or groups posting tweets. We identified the most influential Twitter users contributing to radiation oncology–related tweets. Results From 2014 to 2020, the quarterly volume of radiation oncology–related tweets increased from 5027 to 29,763. Physicians contributed the largest growth in tweet volume. Academic radiation oncologists comprise 60% of the most influential Twitter accounts responsible for radiation oncology–related content. The number of radiation-oncology resident physicians on Twitter increased from 25 to 328 over the past 6 years, and 20% of radiation-oncology residency programs have a Twitter account. Seventy-one percent of radiation oncology–related tweets generated direct communication via mentions, and 59% of tweets contain links to external sources, including scientific articles. Conclusions The number of physicians contributing radiation oncology–related Twitter content has increased significantly in recent years. Academic radiation oncologists are the primary influencers of radiation oncology–related Twitter activity. Twitter is used by radiation oncologists to both professionally network and discuss findings related to the field. There remains the opportunity for radiation oncologists to broaden their audience on Twitter to encompass a more diverse community, including patients.

As part of ongoing efforts to meaningfully improve recruitment, enrollment, and accrual of older adults into cancer clinical trials, the National Cancer Institute (NCI) sponsored a workshop with experts across the country entitled Engaging Older Adults in the NCI Clinical Trials Network: Challenges and Opportunities. Three working groups, including Study Design, Infrastructure, and Stakeholders, were formed, who worked together to offer synergistic improvements in the system. Here, we summarize the workshop discussions of the Infrastructure Working Group, whose goal was to address infrastructural challenges, identify underlying resources, and offer solutions to facilitate accrual of older adults into cancer clinical trials. Based on preconference work and workshop discussions, four key recommendations to strengthen NCI infrastructure were proposed: 1) further centralize resources and expertise; 2) provide training for clinical research staff; (3) develop common data elements; and 4) evaluate what works and does not work. These recommendations provide a strategy to improve the infrastructure to enroll more older adults in cancer clinical trials.

PURPOSE Limited tools exist to predict the risk of chemotherapy toxicity in older adults with early-stage breast cancer. METHODS Patients of age ≥ 65 years with stage I-III breast cancer from 16 institutions treated with neoadjuvant or adjuvant chemotherapy were prospectively evaluated for geriatric and clinical features predictive of grade 3-5 chemotherapy toxicity. Logistic regression with best-subsets selection was used to identify and incorporate independent predictors of toxicity into a model with weighted variable scoring. Model performance was evaluated using area under the ROC curve (AUC) and goodness-of-fit statistics. The model was internally and externally validated. RESULTS In 473 patients (283 in development and 190 in validation cohort), 46% developed grade 3-5 chemotherapy toxicities. Eight independent predictors were identified (each assigned weighted points): anthracycline use (1 point), stage II or III (3 points), planned treatment duration > 3 months (4 points), abnormal liver function (3 points), low hemoglobin (3 points), falls (4 points), limited walking (3 points), and lack of social support (3 points). We calculated risk scores for each patient and defined three risk groups: low (0-5 points), intermediate (6-11 points), or high (≥ 12 points). In the development cohort, the rates of grade 3-5 chemotherapy toxicity for these three groups were 19%, 54%, and 87%, respectively ( P < .01). In the validation cohort, the corresponding toxicity rates were 27%, 45%, and 76%. The AUC was 0.75 (95% CI, 0.70 to 0.81) in the development cohort and 0.69 (95% CI, 0.62 to 0.77) in the validation cohort. Risk groups were also associated with hospitalizations and reduced dose intensity ( P < .01). CONCLUSION The Cancer and Aging Research Group-Breast Cancer (CARG-BC) score was developed and validated to predict grade 3-5 chemotherapy toxicity in older adults with early-stage breast cancer.

Background The leadless Micra transcatheter-pacing system (Micra-TPS) is implanted via a femoral approach using a 27-French introducer sheath. The Micra Transcutaneous Pacing Study excluded patients with inferior vena cava (IVC) filters. Objective To examine the feasibility and safety of Micra-TPS implantation through an IVC filter. Methods This multicenter retrospective study included patients with an IVC filter who underwent a Micra-TPS implantation. Data for clinical and IVC filter characteristics, preprocedure imaging, and procedural interventions were collected. The primary outcome was a successful leadless pacemaker (LP) implantation via a femoral approach in the presence of an IVC filter. Periprocedural and delayed clinical complications were also evaluated. Results Of the 1528 Micra-TPS implants attempted, 23 patients (1.5%) had IVC filters. The majority (69.6%) of IVC filters were permanent. Six (26.1%) patients underwent preprocedural imaging to assess for filter patency. One patient's filter was retrieved before LP implantation. The primary outcome was achieved in 21 of 22 patients (95.5%) with an existing IVC filter. An occluded IVC precluded LP implantation in one patient. Difficulty advancing the stiff guidewire or the 27-Fr sheath was encountered in five patients. These cases required repositioning of the wire (n = 2), gradual sheath upsizing (n = 2), or balloon dilation of the filter (n = 1). Postprocedure fluoroscopy revealed intact filters in all cases. During a median 6-month follow-up, there were no clinical complications related to the filter or the Micra-TPS. Conclusion This multicenter experience demonstrates the feasibility and safety of Micra-TPS implantation via an IVC filter without acute procedural or delayed clinical complications.

Cancer is a disease of aging and, as the world's population ages, the number of older persons with cancer is increasing and will make up a growing share of the oncology population in virtually every country. Despite this, older patients remain vastly underrepresented in research that sets the standards for cancer treatments. Consequently, most of what we know about cancer therapeutics is based on clinical trials conducted in younger, healthier patients, and effective strategies to improve clinical trial participation of older adults with cancer remain sparse. For this systematic review, the authors evaluated published studies regarding barriers to participation and interventions to improve participation of older adults in cancer trials. The quality of the available evidence was low and, despite a literature describing multifaceted barriers, only one intervention study aimed to increase enrollment of older adults in trials. The findings starkly amplify the paucity of evidence-based, effective strategies to improve participation of this underrepresented population in cancer trials. Within these limitations, the authors provide their opinion on how the current cancer research infrastructure must be modified to accommodate the needs of older patients. Several underused solutions are offered to expand clinical trials to include older adults with cancer. However, as currently constructed, these recommendations alone will not solve the evidence gap in geriatric oncology, and efforts are needed to meet older and frail adults where they are by expanding clinical trials designed specifically for this population and leveraging real-world data.

PURPOSE: Despite considerable research on the barriers to enrollment in cancer therapeutic trials, few studies have elicited barriers from the perspective of community physicians, who provide the majority of cancer care. The purpose of this study was to characterize barriers to and facilitators of cancer therapeutic trials as perceived by oncologists in community practices. METHODS: Twenty semistructured interviews were conducted with oncologists at six community sites affiliated with City of Hope National Medical Center from March to June 2018. Responses were recorded digitally and transcribed. Data were analyzed using qualitative content analysis. RESULTS: Of the 20 participants, 4 (20%) were women, 13 (65%) had > 10 years of practice experience, and 16 (80%) reported that < 5% of their patients were enrolled in a therapeutic trial. Participants identified four system-level barriers: lack of appropriate trials for community-based settings, insufficient infrastructure support, restrictive eligibility criteria, and financial limitations; three physician-level barriers: lack of awareness of available trials, lack of knowledge of trial details, and lack of time; and two patient-level barriers: patient burden and negative beliefs/attitudes toward research. Efforts aimed to increase trial availability, clinical trial support personnel, and physician knowledge were identified as major facilitators. CONCLUSION: Community oncologists face numerous complex, multifaceted barriers to cancer therapeutic trial enrollment. Although expanding clinical research beyond the academic setting allows access to a larger and more diverse patient population, increasing generalizability and relevance of trial findings, there remains a substantial need for new strategies to improve cancer research delivery in the community.

High metabolic tumor volume (MTV) predicts worse outcomes in lymphoma treated with chemotherapy. However, it is unknown if this holds for patients treated with axicabtagene ciloleucel (axi-cel), an anti-CD19 targeted chimeric antigen receptor T-cell therapy. The primary objective of this retrospective study was to investigate the relationship between MTV and survival (overall survival [OS] and progression-free survival [PFS]) in patients with relapsed/refractory large B-cell lymphoma (LBCL) treated with axi-cel. Secondary objectives included finding the association of MTV with response rates and toxicity. The MTV values on baseline positron emission tomography of 96 patients were calculated via manual methodology using commercial software. Based on a median MTV cutoff value of 147.5 mL in the first cohort (n = 48), patients were divided into high and low MTV groups. Median follow-up for survivors was 24.98 months (range, 10.59-51.02 months). Patients with low MTV had significantly superior OS (hazard ratio [HR], 0.25; 95% confidence interval [CI], 0.10-0.66) and PFS (HR, 0.40; 95% CI, 0.18-0.89). Results were successfully validated in a second cohort of 48 patients with a median follow-up for survivors of 12.03 months (range, 0.89-25.74 months). Patients with low MTV were found to have superior OS (HR, 0.14; 95% CI, 0.05-0.42) and PFS (HR, 0.29; 95% CI, 0.12-0.69). In conclusion, baseline MTV is associated with OS and PFS in axi-cel recipients with LBCL.

Patients undergoing MRI may experience fear, claustrophobia, or other anxiety manifestations due to the typically lengthy, spatially constrictive, and noisy MRI acquisition process and in some cases are not able to tolerate completion of the study. This article discusses several patient-centered aspects of radiology practice that emphasize interpersonal interactions. Patient education and prescan communication represent 1 way to increase patients' awareness of what to expect during MRI and therefore mitigate anticipatory anxiety. Some patient interaction strategies to promote relaxation or calming effects are also discussed. Staff teamwork and staff training in communication and interpersonal skills are also described, along with literature evidence of effectiveness with respect to patient satisfaction and productivity endpoints. Attention to how radiologists, nurses, technologists, and other members of the radiology team interact with patients before or during the MRI scan could improve patients' motivation and ability to cooperate with the MRI scanning process as well as their subjective perceptions of the quality of their care. The topics discussed in this article are relevant not only to MRI operations but also to other clinical settings in which patient anxiety or motion represent impediments to optimal workflow.

Objectives Oncologists can be one of the major barriers to older adult's participation in research. Multiple studies have described academic clinicians' concerns for not enrolling older adults onto trials. Although the majority of older adults receive their cancer care in the community, few studies have examined the unique challenges that community oncologists face and how they differ from oncologist-related barriers in academia. Methods Semi-structured interviews were conducted by telephone or face-to-face with 44 medical oncologists (24 academic-based and 20 community-based) at City of Hope from March to June 2018. Interviews explored oncologists' perceptions of barriers to clinical trial enrollment of older adults with cancer. Data were analyzed using qualitative content analysis. Results Of the 44 participants, 36% were women and 68% were in practice for >10 years. Among the entire sample, stringent eligibility criteria (n = 20) and oncologist concerns for treatment toxicities (n = 15) were the most commonly cited barriers. Compared to academic oncologists, community oncologists more often cited patient attitudes, beliefs, and understanding (n = 9 vs. n = 2) and caregiver burden (n = 6 vs. n = 0). In contrast, compared to community oncologists, academic oncologists more often cited oncologist bias (n = 10 vs. n = 3) and insufficient time/support (n = 4 vs. n = 1). Conclusions Differences in perceptions among academic and community oncologists about trials suggest that barriers are multifaceted, complex, and vary by practice setting. Interventions to increase trial accrual among older adults with cancer may benefit from being tailored to address the unique barriers of different practice settings.

With the aging of the US population, the number of individuals age 65 or older who will be diagnosed with breast cancer is expected to rise. Despite this, older adults with breast cancer remain severely under-represented in cancer clinical trials. Numerous studies have highlighted disparites in care experienced by older patients with breast cancer. Dr. Arti Hurria was one of the most influential leaders in oncology to shed light on this vunerable and growing population. By uniting the fields of geriatrics and oncology, she brought together a powerful community of like-minded individuals and, through collaborative research, pioneered the current day approach and care of older patients with cancer. In this review, we highlight Dr. Hurria's contribution in breast oncology. Specifically, we describe her work on functional and cognitive effects of breast cancer therapy, shared-decision making, toxicity risk prediction, and breast cancer therapeutics.

PURPOSE To evaluate ultrasound-accelerated, catheter-directed thrombolysis (CDT) for treatment of acute submassive pulmonary embolism (PE). MATERIALS AND METHODS This single-center, retrospective study included patients who underwent CDT for acute submassive PE (N = 113, 52% men/48% women) from 2013 to 2017. Baseline characteristics included history of deep venous thrombosis (12%), history of PE (6%), and history of cancer (18%). Of cohort patients, 88% (n=99) had a simplified PE severity index score of ≥ 1 indicating a high risk of mortality. RESULTS A technical success rate of 100% was achieved with 84% of patients having bilateral catheter placements. Average tissue plasminogen activator (tPA) therapy duration was 20.7 hours ± 1.5, and median tPA dose was 21.5 mg. Three patients (2.6%) experienced minor hemorrhagic complications. Mean hospital length of stay was 6 days. Mean pulmonary arterial pressure decreased from 55 mm Hg on presentation to 37 mm Hg (P < .01) 1 day following initiation of thrombolytic therapy. All-cause mortality rate of 4% (n = 4) was noted on discharge, which increased to 6% (n = 7) at 6 months. At 6-month follow-up compared with initial presentation, symptom improvements (93%), physiologic improvements (heart rate 72 beats/min vs 106 beats/min, P < .01), oxygen requirement improvements (fraction of inspired oxygen 20% vs 28%, P < .01), and right ventricular systolic pressure improvements by echocardiography (30 mm Hg vs 47 mm Hg, P < .01) were observed. CONCLUSIONS CDT for acute submassive PE was associated with low complications and mortality, decreased right ventricular systolic pressure, high rates of clinical improvement, and improved intermediate-term clinical outcomes.

The combination of immunotherapy and radiotherapy/chemoradiation has demonstrated promising results in some disease sites for cancer patients. However, translation to real-world practice is complicated by limited representation in clinical trials of older adults with comorbidities who comprise a significant percentage of patients treated in the clinic. The purpose of this review is to outline the current evidence for multimodality treatment in the older adult population including extrapolation from single modality therapies and the rationale for combinatorial treatment. Although few in number, ongoing trials specifically targeting older cancer patients are highlighted. Looking toward the future, current gaps in the field are identified with recommendations to consider both in the preclinical setting and when designing clinical trials in order to better inform the use of multimodality therapy in the clinic as this data evolves.

Women with triple negative breast cancer (TNBC) have a high prevalence of BRCA1 mutations, and current clinical guidelines recommend genetic testing for patients with TNBC aged ≤60 years. However, studies supporting this recommendation have included few older women with TNBC. Methods Genetic testing results from women aged >60 years with TNBC enrolled in the Clinical Cancer Genomics Community Research Network (CCGCRN) registry were included in this analysis. Prevalence of breast cancer-associated pathogenic variants (PVs) was compared across age groups. Results We identified 151 women with TNBC aged >60 years (median 65 years; SD 5.3). Of these, 130 (86%) underwent genetic testing, and a breast cancer–associated PV was identified in 16 (12.3%; 95% CI 7–19): BRCA1 (n = 6), BRCA2 (n = 5), PALB2 (n = 2), ATM (n = 1) and RAD51C (n = 2). We found no differences in the proportion of patients with close blood relatives with breast (≤50 years) or ovarian cancer (any age) between PV carriers (37.5%) and non-carriers (34.2%) (p = 0.79). Among PV's carriers, the proportion of older women with a BRCA1 PV was lower when compared to younger women (37.5% vs 77.2%; p Conclusion Breast cancer-associated PVs were found in an important proportion of women aged >60 years with TNBC undergoing genetic testing, including greater representation of BRCA2. These results suggest that older women with TNBC should be offered genetic testing, and that their exclusion based on chronologic age alone may not be appropriate.

While surveillance biopsies play a critical role in management of patients with muscle invasive bladder cancer (MIBC) treated with trimodal therapy (TMT), their assessment is often confounded by pronounced post-treatment changes. The aim of this study was to characterize these morphologic alterations and their clinical implications. A single-center retrospective analysis of surveillance transurethral resection of bladder tumor (TURBT) samples was undertaken, assessing for post-treatment morphologic changes in non-neoplastic and neoplastic tissue, as well as the correlation between these changes and cancer recurrence and cancer-specific survival. The cohort consisted of 73 patients with 56 males (76.7%), with a median age of 72 years and stage cT2 in 84.9%. The median follow-up was 28 months (4-207 months), with 34 patients (46.6%) dead during follow-up. A wide spectrum of morphologic characteristics was documented in all post-TMT TURBTs, with most common features including fibrosis (63.0%), inflammation (56.2%), and epithelial denudation (45.2%). Presence of fibrosis inversely correlated with cancer-specific death (n = 68, p = 0.027). Among the 18 cases with residual MIBC, 12 cases (66.7%) showed morphologic changes in the neoplastic cells that deviated from usual morphology of urothelial carcinoma. Presence of these changes was enriched in patients with subsequent disease recurrence (n = 18, p = 0.05). Secondary pathology review identified two cases (2.7%) with diagnostic discrepancy, both due to omission of in situ component. Post-treatment changes in post-TMT TURBTs must be recognized to avoid diagnostic misinterpretation and accurately guide patient management. Also, poor cellular preservation and severe cytologic changes in the residual carcinoma are not associated with a better prognosis.

Evaluate trends and demographic predictors of imaging utilization at a university-affiliated health system.In this single-institution retrospective study, per capita estimates of imaging utilization among patients active in the health system were computed by cross-referencing all clinical encounters (2004-2016) for 1,628,980 unique patients with a listing of 6,157,303 diagnostic radiology encounters. Time trends in imaging utilization and effects of gender, race/ethnicity, and age were assessed, with subgroup analyses performed by imaging modality. Utilization was analyzed as both a continuous and binary outcome variable.Over 13 years, total diagnostic exams rose 6.8% a year (285,947-622,196 exams per annum), while the active population size grew 7.0% a year (244,238-543,290 active patients per annum). Per capita utilization peaked in 2007 at 1.33 studies/patient/year before dropping to 1.06 from 2011 to 2015. Latest per capita utilization was 0.22 for computed tomography, 0.10 for MR, 0.20 for US, 0.03 for NM, 0.51 for radiography, and 0.07 for mammography. Over the study period, ultrasound utilization doubled, whereas NM and radiography utilization decreased. computed tomography, MR, and mammography showed no significant net change. Univariate analysis of utilization as a continuous variable showed statistically significant effects of gender, race/ethnicity, and age (P0.0001), with utilization higher in males and Blacks and lower in Asian/Pacific Islanders and Hispanics. Utilization increased with age, except for a decline after age 75. Many of the effects of age, gender, and race/ethnicity were also found when analyzing the binarized utilization variable.Although absolute counts of imaging studies more than doubled, the net change in per capita utilization over the study period was minimal. Variations in utilization across age, gender, and race/ethnicity may reflect differential health needs and/or access disparities, warranting future studies.

IMPORTANCE: Although geriatric assessment–driven intervention improves patient-centered outcomes, its influence on chemotherapy-related toxic effects remains unknown. OBJECTIVE: To assess whether specific geriatric assessment–driven intervention (GAIN) can reduce chemotherapy-related toxic effects in older adults with cancer. DESIGN, SETTING, AND PARTICIPANTS: A randomized clinical trial enrolled 613 participants from a National Cancer Institute–designated cancer center between 2015 and 2019. Patients were 65 years and older with a solid malignant neoplasm, were starting a new chemotherapy regimen, and completed a geriatric assessment. Patients were followed up until chemotherapy completion or 6 months after initiation, whichever occurred first. Data analysis was done by intention-to-treat principle. INTERVENTIONS: Patients were randomized (2:1) to either the GAIN (intervention) or standard of care (SOC) arm. In the GAIN arm, a geriatrics-trained multidisciplinary team composed of an oncologist, nurse practitioner, social worker, physical/occupation therapist, nutritionist, and pharmacist reviewed geriatric assessment results and implemented interventions based on prespecified thresholds built into the geriatric assessment’s domains. In the SOC arm, geriatric assessment results were sent to treating oncologists for consideration. MAIN OUTCOMES AND MEASURES: The primary outcome was incidence of grade 3 or higher chemotherapy-related toxic effects (graded using National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0). Secondary outcomes included advance directive completion, emergency department visits, unplanned hospitalizations, average length of stay, unplanned hospital readmissions, chemotherapy dose modifications, and early discontinuation. Overall survival analysis was performed up to 12 months after chemotherapy initiation. RESULTS: Among the 605 eligible participants for analysis, median (range) age was 71 (65-91) years, 357 (59.0%) were women, and 432 (71.4%) had stage IV disease. Cancer types included gastrointestinal (202 [33.4%]), breast (136 [22.5%]), lung (97 [16.0%]), genitourinary (91 [15.0%]), gynecologic (54 [8.9%]), and other (25 [4.1%]). Incidence of grade 3 or higher chemotherapy-related toxic effects was 50.5% (95% CI, 45.6% to 55.4%) in the GAIN arm and 60.6% (95% CI, 53.9% to 67.3%) in the SOC arm, resulting in a significant 10.1% reduction (95% CI, −1.5 to −18.2%; P = .02). A significant absolute increase in advance directive completion of 28.4% with GAIN vs 13.3% with SOC (P

Intravascular ultrasound (IVUS) is a proven and rapidly developing imaging modality that can be used for a multitude of both diagnostic and interventional purposes. By allowing for superior intraluminal characterization, compared with angiography, IVUS has emerged as a technically valuable tool in interventional procedures such as transjugular intrahepatic portosystemic shunt/direct intrahepatic portosystemic shunt, venous interventions (May Thurner stenting, inferior vena cava filter placement, recanalization in the setting of chronic venous thrombosis/insufficiency), percutaneous fenestration in the setting of aortic dissection and angioplasty. Additional applications evaluating coronary arteries and plaque morphology have been described, but are outside the scope of this review. In addition to IVUS's merit as a pre- and intra-procedural guidance modality, there are also several advantages compared to the gold standard of angiography which include decreased need for iodinated contrast, decreased radiation exposure and decreased procedural times in certain cases. With current research, such as that aimed at supraharmonic imaging, further improvements in imaging depth, resolution and contrast to noise ratio are on the horizon.

Background Hepatitis B virus RNA (HBV-RNA) is a novel serum biomarker that correlates with transcription of intrahepatic covalently closed circular (cccDNA), which is an important target for pegylated interferon (PEG-IFN) and novel therapies for functional cure. We studied HBV-RNA kinetics following PEG-IFN treatment and its potential role as a predictor to response in HBeAg-negative chronic hepatitis B (CHB) patients. Methods HBV-RNA levels were measured in 133 HBeAg-negative CHB patients treated in an international randomized controlled trial (PARC study). Patients received PEG-IFN α-2a for 48 weeks. HBV-RNA was measured from baseline through week 144. Response was defined as HBV-DNA Results Mean HBV-RNA at baseline was 4.4 (standard deviation [SD] 1.2) log10 c/mL. At week 12, HBV-RNA declined by −1.6 (1.1) log10 c/mL. HBV-RNA showed a greater decline in responders compared to nonresponders early at week 12 (−2.0 [1.2] vs −1.5 [1.1] log10 c/mL, P = .04). HBV-RNA level above 1700 c/mL (3.2 log10 c/mL) had a negative predictive value of 91% at week 12 and 93% at week 24 (P = .01) for response. Overall, HBV-RNA showed a stronger correlation with HBV-DNA and HBcrAg (.82 and .80, P Conclusions During PEG-IFN treatment for HBeAg-negative CHB, HBV-RNA showed a fast and significant decline that correlates with treatment response and HBsAg loss at long-term follow-up. Clinical Trials Registration NCT00114361

Objective Interventional radiology/diagnostic radiology (IR/DR) is the newest primary specialties offered to trainees, one that medical students can now apply to directly out of medical school. However, medical students are disadvantaged in that the integrated IR/DR pathway requires early decision when often radiology rotations are not part of the core clerkship curriculum. Based upon results from a survey to Integrated IR/DR Program Directors, we report strategies being used by programs to introduce and attract medical students to IR. Materials and Methods A questionnaire was written touching on various aspects of medical student engagement. The questionnaire was sent out electronically to 51 IR/DR Program Directors and answers were collated by the Society of Interventional Radiology Resident Fellow Student Section, IR Residency Training Committee. Results Eighteen responses were recorded from programs across the country. All programs encouraged applying to both DR and IR programs. All except one offered research opportunities (94%). The majority offered shadowing opportunities, had dedicated IR interest groups, and invited medical students to device workshops (78%). Planned informal opportunities for medical students to meet faculty and a dedicated department website were made available by most (67%). Little more than half invited medical students to journal clubs (59%). Formal medical student-faculty mentorship program and social media outreach initiatives like Facebook, Student Doctor Network, Twitter, LikedIn, Youtube, and podcasts rounded out the bottom two (50%). Importantly, respondents indicated that they were interested in hearing the results of the survey. Conclusion Our survey offers a snapshot of exactly what program directors are doing to address the issue of medical student recruitment.

To assess and raise medical student interest in interventional radiology (IR); and to evaluate student response across gender, level of training, and surgical vs nonsurgical specialty interest.All Ohio medical students were invited to an IR Symposium held by a large academic medical center in central Ohio. The program encompassed didactic lectures, hands-on simulation models, and a networking luncheon with faculty, trainees, and industry partners. All attendees completed an anonymous, 5-point Likert scaled survey preattending and postattending the event to assess their awareness of IR as a specialty, understanding of the current training pathways, and level of interest.A total of 46 participants (M:F 60%:40%, MS1-53%, MS2-36%, and MS3-11%) attended the symposium. The cohort demonstrated increased interest in pursuing a career in IR following the symposium (4.12 vs 3.70, P0.001). Students with an interest in a nonsurgical specialty showed an increased interest in IR (4.20 vs 3.68, P0.001), whereas surgically oriented students did not demonstrate a significant increase (4.00 vs 3.71, P = 0.375). No statistically significant differences were noted across gender or level of training. The symposium experience significantly increased understanding of the IR training pathways (4.51 vs 2.94, P0.001). Students rated lectures (57%) and endovascular simulators (41%) as the most useful experiences.This study demonstrated the role of symposia in improving medical student awareness of IR and training pathways. Findings were validated across gender and training level, and identified the subset of students with nonsurgical interests as most responsive to such intervention and potential recruitment.

Purpose To evaluate changes in the use of catheter-directed therapy (CDT) for pulmonary embolism (PE) treatment with attention to primary operator specialty in the Medicare population. Methods Using a 5% national sample of Medicare claims data from 2004 to 2016, all claims associated with PE were identified. The annual volume of 2 billable CDT services—arterial mechanical thrombectomy and transcatheter arterial infusion for thrombolysis—were determined to evaluate changes in CDT use and primary CDT operator specialty over time. Results The total number of CDT procedures increased over the course of the study period, representing 0.457 and 5.057 service counts per 100,000 Medicare beneficiaries in 2004 and 2016, respectively. The proportion of PEs treated with CDT increased 10-fold from 2004 to 2016, increasing from 0.1% to 1.0%. Interventional radiologists performed most CDT therapies each year, with the exception of 2010 when vascular surgeons performed more. In 2016, interventional radiologists performed 3.54 CDT services for PE per 100,000 Medicare beneficiaries, which was 70% of total CDT for PE procedures, followed by interventional cardiologists and vascular surgeons performing 0.92 services (18%) and 0.60 services (12%), respectively. Conclusions CDT is an increasingly used treatment for PE, with a 10-fold increase from 2004 to 2016. Interventional radiologists are the dominant providers of these services, followed by interventional cardiologists and vascular surgeons.

There is a gap in current medical student education pertaining to procedural skills' exposure and acquisition. The aim of this study is to evaluate the institutional experience of a novel medical student procedural course and its impact on procedural confidence.This is a single-center prospective study performed at a public medical school and its associated tertiary care medical center between June 2020 and January 2021. This study was deemed exempt by our Institutional Review Board and was performed with participant consent. The multimodal course developed by the radiology department consisted of four didactic lectures, four simulation sessions, and a minimum of 16 clinical rotation hours with the department's vascular access team. Primary outcomes were assessed by comparing participant pre and post course surveys including twenty-five 5-point Likert scaled questions.Twenty-five self-selected students completed the course in its entirety. The curriculum and the corresponding survey analysis were stratified into sections by procedure modality. An increase in participant confidence to a moderate or greater level was observed when comparing pre and post course survey data for each procedure: vascular access (4% vs 52%, p0.01), thoracentesis (8% vs 48%, p0.01), paracentesis (8% vs 72%, p0.01), lumbar puncture (4% vs 44%, p0.01), and bone marrow biopsy (0% vs 48%, p0.01).The creation of a medical-student-centric procedural course is feasible and fills a potential gap in undergraduate medical education. This study demonstrated that a comprehensive multimodal course, designed to include didactic, simulation and clinical experiences, increases participant exposure to, participation with, and confidence in bedside procedural performance abilities.