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Racial and ethnic disparities in early treatment with immunotherapy for advanced HCC in the United States
 
 
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Immunotherapy has emerged as an effective treatment for patients with advanced-stage HCC.
 
Immunotherapy was associated with improved OS - overall survival - compared with chemotherapy (adjusted HR: 0.76, 95% CI: 0.65-0.88) after adjusting for covariates.
 
There were racial and ethnic disparities in access to immunotherapy, with Hispanic (adjusted OR [aOR]: 0.63, 95% CI: 0.46-0.83) and Black patients (aOR: 0.71, 95% CI: 0.54-0.89) less likely to receive immunotherapy compared with White patients.
 
Race-ethnicity was one of the strongest predictors of receiving immunotherapy: Hispanic (adjusted OR [aOR]: 0.63, 95% CI: 0.46-0.83) and Black patients (aOR: 0.71, 95% CI: 0.54-0.89) were significantly less likely to receive immunotherapy compared with White patients. In contrast, there were no significant differences in treatment choice by socioeconomic status or education measures.
 
Compared with patients in the chemotherapy group, a higher proportion of the immunotherapy group was treated at academic centers (55.1% vs. 45.8%, p < 0.001) and in the Northeast (29.6% vs. 19.8%, p < 0.001). Patients treated with immunotherapy had larger tumor sizes (median 8.0 cm vs. 7.5 cm, p = 0.012). There were no significant differences in the Charlson Comorbidity Index, diagnosis method, MELD score, cirrhosis, or AFP category between the two groups.
 
Type and region of treatment site showed a strong association with receipt of immunotherapy. Compared with patients treated at academic centers, those treated at community cancer programs (aOR: 0.56, 95% CI: 0.36-0.82), comprehensive community cancer programs (aOR: 0.77, 95% CI: 0.62-0.92), and integrated networks (aOR: 0.62, 95% CI: 0.48-0.80) were significantly less likely to receive immunotherapy. In addition, patients treated in the Midwest (aOR: 0.45, 95% CI: 0.36-0.61) and the South (aOR: 0.67, 95% CI: 0.57-0.87) were less likely to receive immunotherapy compared with patients treated in the Northeast. In terms of clinical variables, patients with Charlson Comorbidity Index of 3 or higher were less likely to receive immunotherapy compared to those with Charlson Comorbidity Index of 0 or 1 (aOR: 0.76, 95% CI: 0.59-0.94). While diagnosis method, MELD score, and AFP were not associated with receipt of immunotherapy, larger tumor size was associated with a higher likelihood of receiving immunotherapy (aOR: 1.01, 95% CI: 1.004-1.03).
 
There were 3,248 (81.4%) patients treated with chemotherapy and 742 (18.6%) patients treated with immunotherapy. During the study period, the annual proportion of patients receiving immunotherapy increased from 14.2% in 2017 to 23.0% in 2018. The two treatment groups had similar age and sex distributions, with median age of 64 years and male predominance. Compared to patients treated with chemotherapy, patients treated with immunotherapy had higher proportions of White (66.6% vs. 61.9%) and Asian (10.3% vs. 7.9%) patients and lower proportions of Hispanic (9.1% vs. 12.4%) and Black patients (14.0% vs. 17.8%) (p < 0.001). In addition, higher proportions of patients treated with immunotherapy belonged to the highest income quartile (34.5% vs. 27.7%, p = 0.001) and lived in neighborhoods with high average education levels (21.2% vs. 14.9%, p = 0.002).
 
Despite the positive results showing the overall efficacy of immunotherapy in patients with advanced HCC, our study also highlights significant racial and ethnic disparities in early access to immunotherapy, more notable in the nonacademic cancer centers. It is known that health care disparities can emerge or worsen with discoveries of more effective approaches to cancer treatment such as immunotherapy.[30] Racial and ethnic minorities experience significant barriers in access to clinical trials and experimental therapies.
 
For example, a study of 310 clinical trials conducted between 2003 and 2016 showed that Black and Hispanic patients were less likely to enroll in clinical trials for breast, colorectal, lung, pancreas, prostate, and renal cell carcinoma and melanoma.[31] A more recent study with the National Cancer Institute’s Clinical Data Update System between 2000 and 2019 showed persistent underrepresentation of Black and Hispanic patients in breast, colorectal, lung, and prostate cancer clinical trials, although disparity has decreased in recent years.[32] The barriers could arise at multiple levels.[15] At a system level, racial and ethnic minorities are more likely to be underinsured and receive their care at underresourced hospital systems with limited offers for clinical trials or experimental drugs.[33] Studies have reported that implicit bias among physicians has an impact on interactions with racial and ethnic minority patients, and that some physicians are hesitant to discuss clinical trials or experimental treatments with Black patients because they believe that Black patients will be resistant or less likely to comply with the recommended treatments.[34, 35] Conversely, racial and ethnic minority patients and their family members may also hold negative attitudes and mistrust toward clinical trials and experimental treatments, which affects their willingness to participate.[36, 37] A recent study among a cohort of patients with HCC highlighted high proportions of medical mistrust, health literacy, and transportation barriers among Black and Hispanic patients compared with White patients.[38] At an interpersonal level, racial and ethnic differences in the quality of communication between health care professionals and patients exist, with or without language barriers. A linguistic analysis of encounters between oncologists and Black patients has shown that the visit times were overall shorter compared to the visits with White patients, the topic of clinical trials was less frequently mentioned, and even when clinical trials were mentioned, less time was spent discussing them.[39]

 
 
 
 
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