Citations

Background and Aims: Accumulating data related to prevention, surveillance and treatment of chronic hepatitis B (CHB) provided the impetus for this updated guideline, using the Grading of Recommendation Assessment, Development and Evaluation (GRADE) approach. Methods: The guideline was developed in compliance with the National Academy of Medicine standards. The guideline panel developed structured questions following the Population, Intervention Comparison, Outcomes (PICO) framework. The panel addressed 6 PICO questions covering prevention (maternal to infant transmission and horizontal transmission), surveillance for liver cancer (among hepatitis B surface antigen positive (HBsAg) persons co-infected with hepatitis C virus, hepatitis D virus and/or human immunodeficiency viruses and after HBsAg loss) and treatment (HBsAg positive persons in immune-tolerant or indeterminate phases as well as withdrawal of antiviral therapy), providing evidence-based recommendations on these topics. Four systematic reviews of the literature were conducted, and two existing systematic reviews were utilized to support the recommendations in this practice guideline. Conclusions: This evidence-based guideline provides updated recommendations to optimize the care of persons with CHB.

Background: Aging increases the risk of resistant hypertension which is associated with an increased risk of mortality and cardiovascular events. Here, we examined the characteristics, blood pressure (BP) trajectories, and treatment patterns of older patients with apparent treatment resistant hypertension (aTRH). Hypothesis: We hypothesized aTRH would be undertreated, especially in octogenarians. Methods: We conducted a retrospective study of all patients with two available ambulatory BP measurements separated by at least 3 months in a community-based teaching hospital. aTRH was defined as BP above goal despite the use of ≥3 antihypertensive medication classes or controlled BP on ≥4 antihypertensive medication classes. Results: Of the 71,470 patients with available data, 7308 (10.2%) met criteria for aTRH with a mean follow-up length of 18.9 months. Compared to patients with normal BP, patients with aTRH were older with a mean age of 74 years versus 65 years (p<0.001). Patients with aTRH were more likely to be males (58.3%) compared to the normal BP groups (40.6%, p<0.001) (Figure 1). Compared to patients with normal BP, patients with aTRH were more likely to be obese and have a higher prevalence of smoking history, diabetes, coronary artery disease, heart failure, peripheral arterial disease, atrial fibrillation, and chronic kidney disease (Figure 1). Amongst those with aTRH, 1566 (5.3%) were aged 18-65, 3763 (13.2%) were aged 66-79, and 2623 (19.7%) were ≥80 years old. At follow-up, among those with aTRH at baseline, 5773 (72.6%) remained with aTRH, 896 (11.3%) improved to non-aTRH, 1270 (16.0%) improved to controlled BP, and 13 (0.2%) improved to normal BP (Figure 2). Most patients irrespective of age had no change in the number of medications at follow-up; only 15.5% of octogenarians with aTRH had an increase in antihypertensives (Figure 3). Between baseline and follow up, octogenarians as a whole had a systolic BP drop of -2.34 (p<0.001), and diastolic BP drop of -0.56 (p=0.061), whereas octogenarians with aTRH had a systolic BP drop of -3.7 (p<0.001) and diastolic BP drop of -0.55 (p=0.050). Conclusion: In an ambulatory population of patients at a community hospital, the prevalence of aTRH was high among patients ≥80 years and associated with established cardiovascular risk factors. Most patients with aTRH do not have a change in BP status over time. Anti-hypertensive medication escalation is infrequent among patients with aTRH irrespective of age.

Immune checkpoint inhibitors (ICIs) are an important class of cancer treatment. Endocrine immune-related adverse events (E-irAEs) account for a significant proportion of irAEs in ICI-treated patients. Diagnosing E-irAEs accurately and timely can be challenging in the absence of clear categorization and standardization across oncology, endocrinology and other specialties. While existing guidelines provide some broad directions to diagnosis and management, they lack clarity on irAE-specific symptom evaluation and work-up, as well as assessment of severity. These limitations can then impact triage, time-sensitive management and care escalation to specialists such as oncoendocrinologists. The objective of this study was to develop consensus-based statements on disease definitions for E-irAEs. A core working group of endocrinologists with expertise in the oncoendocrinology field drafted a survey with statements outlining the general approach to E-irAEs, disease definition and management approach of six specific diagnoses: ir-thyroiditis thyrotoxic phase, ir-thyroiditis hypothyroidism, ir-Graves’ disease, ir-hypophysitis, ir-adrenalitis and ir-type 1 diabetes mellitus. Severity grading tables were drafted for three disease categories—“thyroid”, “pituitary and adrenal”, and “diabetes mellitus”. A two-round modified Delphi process, using the RAND/University of California Los Angeles (RAND/UCLA) Appropriateness Method, was employed. In this process, a 25-member voting panel consisting of endocrinologists, oncologists and other specialists and healthcare providers with experience in management of ICI-treated patients and irAEs was recruited. The panel rated anonymously on usability, accuracy, appropriateness or agreement of 41 items on a 9-point scale in Survey 1, after which a meeting was convened. Statements were modified based on voting results from Survey 1 and Meeting 1, and the process was repeated in Survey 2 and Meeting 2. At the end of this process, consensus was achieved for all statements. Our study findings address the gap in standardized nomenclature, clinical, laboratory and radiological evaluations, and management principles of E-irAEs. With consensus achieved from a panel of experts from a variety of disciplines, we anticipate that the statements can form the basis for standardization of the diagnostic process and improvement of patient care.

The treatment landscape of B-cell lymphomas has significantly evolved in recent years with approval of novel targeted therapies. CD3 × CD20 bispecific antibodies and CD19-directed monoclonal antibodies and antibody–drug conjugates have demonstrated efficacy in relapsed/refractory follicular lymphoma (FL). Bruton tyrosine kinase (BTK) inhibitor–based regimens are emerging as effective treatment options for patients with TP53-mutated classical mantle cell lymphoma (MCL). Results from ongoing clinical trials suggest that the addition of CD3 × CD20 bispecific antibodies to chemoimmunotherapy improves outcomes in patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL). These NCCN Guideline Insights highlight significant updates to the NCCN Guidelines for B-Cell Lymphomas for the treatment of FL, MCL, and DLBCL.

501 Background: Targeted treatment options have significantly improved outcomes for patients with chronic lymphocytic leukemia (CLL), but oncology healthcare professionals (HCPs) who provide care for fewer numbers of patients with CLL are challenged to remain current with continuously changing treatment paradigms. To assess ongoing educational needs, we analyzed the treatment choices made by HCPs in an online survey for select cases of poor-prognosis CLL and compared these with the choices of experts in CLL treatment for the same clinical scenarios. Methods: As part of a CME program, HCPs could access an online algorithm to enter specific characteristics of a CLL case scenario and receive treatment recommendations from 5 US-based CLL experts. Experts made recommendations in July 2024 for 146 possible case patients built into the algorithm. After entering their case characteristics, HCPs were asked to enter their planned treatment prior to viewing the expert recommendations. We compared expert and HCP treatment choices across various case scenarios that were entered into the algorithm, with a focus on previously untreated CLL with del(17p)/mutated TP53 or R/R CLL. Results: Between August 2024 and February 2025, 346 cases were entered into the algorithm by 174 HCPs. Among responding HCPs, 38% were based in the UK/EU, 24% in the US, and 10% in Asia; 62% treated ≤10 patients with CLL per month and 49% sought recommendations for a specific patient in their practice. Among 231 cases of previously untreated CLL entered, 91 (39%) sought recommendations for del(17p)/mutated TP53 disease. For cases with no major comorbidities and previously untreated CLL with del(17p)/mutated TP53 , all experts recommended acalabrutinib or zanubrutinib; in 19 cases submitted by HCPs practicing in locations where second-generation BTK inhibitors (BTKi) are approved for CLL (including the US, EU, and Japan), 58% planned 1 of these treatments for this case scenario, 17% planned ibrutinib-based therapy, and 11% planned venetoclax-based therapy. Among case scenarios requiring third-line therapy after progressing with 2 regimens including a covalent BTKi and venetoclax plus an anti-CD20 Ab (with progression <2 years after completing treatment), all experts would recommend a noncovalent BTKi (eg, pirtobrutinib), with 1 expert indicating they would also consider CAR T-cell therapy. For the same case scenario among 6 US-based HCPs, 1 planned pirtobrutinib and 3 planned CAR T-cell therapy. Overall, after reviewing expert recommendations, 61% of HCP respondents whose planned treatment differed from the experts indicated that they would change their approach, and 20% indicated barriers to implementing the recommendations. Conclusions: Our findings provide insight into potential educational needs among HCPs who manage patients with CLL, suggesting that targeted expert-led education could benefit these HCPs.

98 Background: Prior authorization (PA) purports to control costs and ensure adherence to evidence-based guidelines but negatively impacts cancer care. Radiation oncology (RO) represents a minority of overall cancer spending yet bears a disproportionately high PA burden. Limited research exists on the effects of PA on patient outcomes and administrative workload within RO clinics. Methods: From 9/2024 to 10/2024, an online survey was open to U.S. members of the American Society for Radiation Oncology assessing experiences with PA including disposition (approval/denial/appeal including peer-to-peer [P2P] review) and perceived impact on patient care and administrative workload. Outcomes included treatment delays, changes from recommended treatment, and patient event including hospitalization, ED visits, permanent disability, or death. Descriptive statistics evaluated responses. Results: Of 736 responding radiation oncologists (16% response rate), 83% reported a rise in PA over the past three years, with 58% noting the burden has increased greatly. In the past year, 50% reported that more than half of their cases required PA, with a median approval rate of 75% and median overturn rate of 82% for denials. For more than half of their cases, nearly half of physicians (43%) noted that P2P was a futile effort to overturn PA denials due to insurance policies. Most (75%) reported that PA resulted in their practice needing to reallocate staff; 91% reported worsening burnout due to PA. P2P reviews were particularly burdensome, averaging 1.65 hours per week. A third (30%) reported that PA requirements had caused serious complications for their patients, including 7% who reported PA had contributed to patient death. Almost all (91%) reported PA-related treatment delays for some of their patients, with 58% indicating average delays of ≥5 days. Most (81%) reported that at times they had to use radiation techniques they considered less optimal due to PA, including 58% who were forced to deviate from national guidelines. The most common reasons for not appealing a PA denial were anticipated delays (73%), perceived futility based on prior PA experiences (62%), and administrative burden (45%). Conclusions: The administrative and clinical burdens associated with PA have significant implications for patient care, physician well-being, and healthcare resource allocation in RO. Treatment delays, compromised therapies, and adverse patient outcomes are commonly reported and underscore the need for PA reform to improve patient outcomes, reduce physician burnout, and improve efficiency.

Abstract Objective This study aimed to understand the factors limiting access to medications for the preventive treatment of migraine and to improve access to evidence‐based preventive care. Background For decades, the effective use of medication for the preventive treatment of migraine was limited by slow onset, slow and complex dose titration schedules, modest benefits, drug interactions, frequent side effects, and very low long‐term adherence. The calcitonin gene‐related peptide (CGRP) targeted preventive medications mitigate some of these limitations and demonstrated substantial therapeutic benefits in a significant proportion of adults with migraine. The American Headache Society considers these medications among the first‐line options for migraine prevention, although access to them remains limited. The American Migraine Foundation hosted a single‐day, multidisciplinary expert panel discussion to identify barriers to optimal preventive care and developed recommendations to address them. Methods Participants identified and prioritized barriers and used a modified nominal group technique to achieve consensus on them. A series of moderated discussions in plenary and breakout sessions was used to create possible solutions. Modified nominal group technique was also employed to achieve consensus on the priorities among these barriers and to achieve whole‐group consensus on the recommendations. Ethical issues that inform access were discussed. Results Participants included eight neurologists and board‐certified headache specialists, six representatives of reimbursement decision‐makers, six employees of life sciences companies, four patient advocates with lived experience with migraine, and a medical ethicist. Among those who have consulted healthcare professionals and received a diagnosis of migraine, we identified four main barriers to accessing preventive treatment: restrictive prior authorization requirements, the perceived lack of real‐world evidence and treatment guidelines, the need for clinician education, and the need for patient education. Consensus recommendations for eliminating barriers centered on using new evidence to evaluate policies that restrict the selection of first‐line therapies, initiating/improving collaboration among stakeholders, sharing of data and best practices, and increased training. Participants agreed to explore novel definitions of the value of preventive treatment and to establish the Migraine Prevention Network to facilitate ongoing cooperation and collective action. However, due to financial limitations, staffing changes, and time constraints, post‐meeting discussions led to a shift from establishing a broad Migraine Prevention Network to forming smaller task forces focused on the top‐priority barriers (real‐world evidence and The Patient Playbook ) identified through collaborative voting among American Headache Society, American Migraine Foundation, and industry stakeholders. Conclusions Adults with migraine face multiple barriers in accessing novel migraine‐specific, CGRP‐targeted preventive treatment. Stakeholders in the delivery of care, including clinicians, reimbursement decision‐makers, life sciences companies, and patient and clinician advocates, may be able to overcome many of these barriers and improve access by working with and on behalf of patients.

Importance The definition of cure in stage II to III colon cancer (CC) remains unclear due to limitations in conventional end points, which include deaths and second primary tumors as events. These can complicate communication with patients regarding long-term outcomes. Objective To distinguish relapses from competing health-related events to classify long-term outcomes years after surgery and explore when the incidence of true relapses of the initial CC approaches 0% to define cure in this disease. Design, Setting, and Participants This pooled analysis of individual patient–level data from 15 phase 3 randomized clinical trials assessed time to CC-related relapse using Kaplan-Meier and Aalen-Johansen methods, with death and second primary tumors treated as competing risks. Cox regression models evaluated prognostic associations, stratified by sex, stage, and tumor. Patients with stage II to III CC who underwent adjuvant chemotherapy were included. All patients had undergone radical surgery for CC and received adjuvant chemotherapy with a median follow-up of at least 6 years. The Adjuvant Colon Cancer Endpoints (ACCENT) and the International Duration Evaluation of Adjuvant Chemotherapy (IDEA) databases included adjuvant studies conducted between 1996 and 2015. Data were analyzed from February 2022 to June 2025. Exposures Adjuvant chemotherapy regimens varied across trials, including fluoropyrimidines alone or in combination with oxaliplatin or biologic agents. Main Outcomes and Measures The primary outcome was time to CC-related recurrence. The predefined threshold for cure was a recurrence risk below 0.5%. Results Of 35 213 included patients, 19 346 (54.9%) were male, and the mean (SD) age was 60.2 (10.8) years. The incidence rate of recurrence peaked at 6.4% (1993 of 31 373) between month 6 and month 12 and decreased continuously until year 10 of follow-up never exceeding 0.5%. Recurrence rate appeared to increase again after year 10 and peaked at 2.0% during year 12.5 to year 13, a pattern observed exclusively in the MOSAIC trial. Competing-event analysis revealed that death and second primary tumors inflated the apparent recurrence rate, especially for older patients. The overall cumulative incidence of relapse with death as competing risk was lower among female patients (hazard ratio, 0.58; 95% CI, 0.45-0.76; P &amp;lt; .001). Conclusions and Relevance In this pooled analysis of phase 3 randomized clinical trials, a recurrence rate less than 0.5% occurred after 6 years from surgery, supporting a practical definition of cure. Recognizing this milestone may improve patient communication, guide follow-up duration, and reduce unnecessary long-term surveillance.