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Background: Chemotherapy in combination with radiotherapy (RT) is the standard for early-stage (ES) Hodgkin lymphoma (cHL). Despite high cure rates (12-year overall survival (OS) >93%), there is room to improve short and long-term outcomes for children and adults with ES cHL. Incorporation of immunotherapy (IO) into front line treatment of ES cHL is an opportunity to both improve progression-free survival (PFS) and maintain OS, while minimizing long-term morbidity and mortality by reducing exposure to RT and high-dose chemotherapy. Study Design and Methods: HL leaders of the NCTN groups, expert HL researchers and physicians, and representatives from the Cancer Therapy Evaluation Program (CTEP) formed a working group in April 2020 with the goals of harmonizing treatment approaches for ES cHL across pediatric and adult patients and reaching consensus regarding the optimal study design for incorporating IO therapy into frontline treatment. Study champions identified from each of the North American cooperative groups [Children's Oncology Group (COG), SWOG, ECOG-ACRIN, Alliance, NRG] and experts in imaging, radiation oncology, lymphoma biology and patient-reported outcomes (PROs) were included. The resulting COG-led clinical trial, AHOD2131, represents the largest ES cHL trial in the history of North American cooperative groups and the first to enroll patients across the age continuum. AHOD2131 (NCT05675410; Figure) is a randomized, phase 3 trial enrolling patients ages 5 to 60 years with newly diagnosed, previously untreated stage I and II cHL and will investigate the addition of the CD30-antibody drug conjugate brentuximab vedotin (Bv) with PD-1 blockade (nivolumab) compared to standard chemotherapy +/- RT. Since the April 2023 activation, 97 North American sites have activated the trial, and 21 participants have enrolled. Target enrollment is 1875 patients over 5 years of accrual, for an estimated 1782 eligible and evaluable patients. The primary objective is to compare the 3-year PFS of patients with ES cHL treated through a response-adapted, superiority design with either standard therapy or with an IO approach (BV + nivolumab). All patients will be stratified as favorable or unfavorable based on disease risk features at enrollment. Based on initial response assessment by PET/CT (via central review) after 2 cycles of ABVD, patients were classified to PET2 positive (SER, defined as 5 Point Score 4 or 5, ~15% of patients) and PET negative (RER). Those who are PET positive will receive involved site RT (ISRT). The SER and RER patients will be randomized to standard chemotherapy vs. IO therapy respectively. In addition to the primary outcome of PFS, there are 11 secondary and 10 exploratory aims. The secondary aims focus on OS, PFS of subgroups, and event-free survival at 12 years, physician-reported treatment-related adverse event (AE) rates, patient-reported AE using pediatric and adult versions of Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE), and the capture of representation by self-report and the use of electronic PRO data collections. The exploratory aims include the assessment of imaging central review as compared to local institutional review and the use of convolutional neural networks through artificial-intelligence machine learning. The study will examine the effect of therapy on acute and long-term adverse effects including health-related quality of life (HRQoL) and OS for up to 12 years. The study will compare patient self-report and provider AE reports and evaluate the associations of self-reported race/ethnicity and social determinants of health (SDOH)and post-progression/post-relapse OS. AHOD2131 strengthens the effort between the North American cooperative groups to conduct collaborative clinical trials and aims to harmonize an improved standard of care for ES cHL across the age continuum.

Healthcare inequities are often attributed to large-scale structural barriers for access to medical care or patient-medical staff interactions. However, the role of the electronic medical record (EMR) in perpetuating hidden biases has been poorly characterized. This passive form of sharing implicit biases with unknown readers may have profound ripple effects asynchronous in place and time from the note writer. This study aims to illustrate racial imbalances in ad hominem patient characterizations as documented by medical staff, regardless of role, in a large metro healthcare system. The use of certain potentially stigmatizing language in emergency department (ED) and inpatient notes for hematology/oncology patients was investigated. Retrospective chart review of four hospitals within a university network in a major metro area between 1/1/2019 - 6/30/2021 was undertaken. Patients ≥22 years old were included with two primary hypotheses in mind: 1) Negative terms are used more frequently for underrepresented minorities, and 2) words with shock value (i.e. curse words) are used more often than more general descriptors of these terms (e.g. “cursing” or “profanity”). Nine positive and twelve negative terms were evaluated, based on the authors' observations of their use in the EMR in past encounters (Table 1). Some were personal descriptors in which the ED or inpatient note writer would be less likely than outpatient providers to have a full sense of outpatient care or social determinants of health (e.g. compliant). Others were behavioral descriptions (e.g. hostile) or words with minimal medical relevance (e.g. curse words). If multiple notes in an encounter included the same word(s), the encounter was only analyzed once for each word to avoid word count inflation, though re-occurrences for the same patient in subsequent encounters were counted. Authors' manual data review using natural language processing software confirmed appropriate use of terms. Generalized estimating equations were used for race-based comparisons to account for same-patient clustered encounters. Odds ratios (OR) and 95% confidence intervals (CI) were calculated for self-reported demographic comparisons with White as the reference category. P≤0.05 was considered significant. A total of 1,059 encounters for 889 hematology/oncology patients were analyzed. Mean age was 61 years (standard deviation 16.7) and 49.4% were female. White race was reported for 80.2% of patients (72% system-wide prevalence during same timeframe) and Black for 11.4% (15.2% system-wide); all others were ≤4% so only White/Black comparisons were included. Positive terms were more prevalent than negative ones (n=535 vs 459). However, negative terms were found more often for Black individuals (OR 2.24, CI 1.41 - 3.56, P<0.001), while the positive terms were less frequently documented in Black patients relative to White patients (OR 0.51, CI 0.33 - 0.77, P=0.001), and neither category was concordant with the overall patient racial demographics. Other significant racial differences existed for the terms “Argumentative”, “Disrespectful”, “Noncompliant”, and “Polite”, all discrepancies which favored White patients (Table 2). Specific curse words were documented nearly as often as “cursing”, “swearing”, or “profanity”, but no racial differences were observed. Some words in the initial search (“Brave”, “Courageous”, “Empathetic”, and “Ambitious”) were not found in hematology/oncology notes in this timeframe. EMR documentation in hospital-based hematology/oncology care demonstrated evidence of racial discrepancies in language that may carry stigma, positively or negatively. Importantly, many of these terms have questionable, if any, medical relevance. The use of stigmatizing terminology in the EMR may reflect implicit biases that extend past the direct patient encounter, passively and subconsciously prejudicing future care from other staff members. Time-saving heuristics and documentation shortcuts like copy-forwarding may further ossify healthcare inequities. This phenomenon is undoubtedly not limited to this hospital system or the hematology/oncology field, but quantitative real-world evidence has been scant. Improved awareness of stigmatizing language in documentation may be one step towards mitigating this contributor to unequal care for hematology/oncology providers and their patients.