Assessing benefits and harms of cannabis use in patients treated with immunotherapy for cancer: a prospective cohort study

项目摘要 多达40%的患者报告在癌症治疗期间和之后使用大麻来处理症状 尽管我们对其纵向治疗用途和危害的理解存在差距。同时，免疫- 肿瘤学是一个快速发展的癌症治疗领域。近44%的癌症患者横跨20种肿瘤类型 接受免疫治疗，特别是免疫检查点抑制剂(ICIS)，这可能导致 免疫系统会持续几个月甚至几年的变化。鉴于大麻也有免疫调节作用 关于大麻的影响，迫切需要产生关于大麻使用对纵向效益的影响的长期数据 对接受ICIS治疗的癌症患者的伤害、免疫功能和疾病进展。这项建议建立了 在我们现有的研究项目上。我们的团队已经进行了4个由NCI资助的关于大麻使用的项目 在癌症患者中，包括对在3NCI接受治疗的患者进行的3次大型横断面调查 指定的癌症中心。在不同的地点，26%的癌症患者(3169人中有831人)报告在 治疗。然而，在接受免疫治疗的患者中，这一比例要高得多(32%)。这个 这项研究的首要目标是推动关于以下方面的科学研究： 在接受ICIS治疗癌症的人中使用大麻。我们提出了一个多地点、为期12个月的前瞻性队列 对接受ICI治疗的癌症患者进行的研究(N=450；每个站点150人)：225名大麻使用者(定期) 前一个月每周吸食大麻)和225个非吸食大麻者(过去6个月未吸食大麻)。吸食大麻， 效益和危害将通过生态瞬时评估进行评估(收集7天/时间点；49 总天数)，患者报告的结果将通过在线/电话调查进行评估，常规临床数据将 从电子病历中提取。在60名尚未开始ICI的患者中 治疗(30名吸食大麻者，30名非吸毒者)，我们将检测免疫标记物(例如，肿瘤坏死因子-α、IL-6、C反应蛋白) 在基线(开始ICI之前)、2、6和12个月。具体目标是：1)评估收益(疼痛严重程度 &干扰、睡眠障碍、焦虑、生活质量)和伤害(注意力难以集中、记忆力受损、 头晕、疲劳)随时间的推移而使用大麻；2)测试随时间的使用大麻是否缓和了这种联系 目标1中的邻里劣势(面积剥夺指数)与利与害之间的关系； 60例尚未开始ICI的非皮肤实体恶性肿瘤患者的亚组，探讨 大麻的使用与疾病进展和免疫标志物有关。这项及时和全面的研究，在 对RFA-CA-22-052的回应，将填补关于大麻纵向益处和危害的知识的关键空白 用于接受ICIS治疗的人。强大的多学科团队带来了癌症方面的必要专业知识 症状管理、医用大麻、卫生公平、肿瘤学、免疫学和药物滥用。在……里面 与其他资助的U01和U24合作，这项研究将对 癌症症状管理，并最终改善患者护理和安全。

Project Abstract Up to 40% of patients report using cannabis for symptom management during and after cancer treatments despite gaps in our understanding of its longitudinal therapeutic uses and harms. Simultaneously, immuno- oncology is a rapidly advancing field of cancer treatment. Nearly 44% of cancer patients across 20 tumor types receive treatments with immunotherapy, notably Immune Checkpoint Inhibitors (ICIs), which can lead to persistent changes in the immune system for months or even years. Given cannabis also has immunomodulatory effects, there is a critical need to generate long-term data on the impact of cannabis use on longitudinal benefits and harms, immune function, and disease progression in cancer patients treated with ICIs. This proposal builds upon our existing program of research. Our team has conducted 4 NCI-funded projects regarding cannabis use in cancer patients, including 3 large cross-sectional surveys of cannabis use among patients treated at 3 NCI designated cancer centers. Across sites, 26% (n=831 of 3,169) of cancer patients reported using cannabis during treatment. However, the rate was considerably higher among patients treated with immunotherapy (32%). The overarching goal of this study is to advance the science regarding the longitudinal benefits and harms of cannabis use among those treated with ICIs for cancer. We propose a multi-site, 12-month prospective cohort study (N=450; 150 per site) with cancer patients treated with ICI (within 3 months): 225 cannabis users (regular weekly use in the prior month) and 225 cannabis non-users (no use in the past 6 months). Cannabis use, benefits, and harms will be assessed via ecological momentary assessment (collected 7 days/time point; 49 days total), patient reported outcomes will be assessed via online/phone surveys, and routine clinical data will be extracted from electronic medical records. Among a subset of 60 patients who have not yet started ICI treatment (30 cannabis users; 30 non-users), we will examine immunological markers (e.g., TNF-α, IL-6, CRP) at baseline (prior to starting ICI), 2, 6, & 12 months. The Specific Aims are to: 1) assess benefits (pain severity & interference, sleep disturbance, anxiety, quality of life) and harms (difficulty concentrating, impaired memory, dizziness, fatigue) of cannabis use over time; 2) test whether cannabis use over time moderates the associations between neighborhood disadvantage (Area Deprivation Index) and benefits and harms in Aim 1; & 3) among a subset of 60 patients with non-skin solid malignancies who have not yet started ICI, explore the association of cannabis use with disease progression and immunological markers. This timely and comprehensive study, in response to RFA-CA-22-052, will fill critical gaps in knowledge about longitudinal benefits and harms of cannabis use in persons treated with ICIs. The strong multidisciplinary team brings the requisite expertise in cancer symptom management, medical cannabis, health equity, oncology, immunology, and substance misuse. In collaboration with other funded U01s and U24, this research will have a sustained impact on the science of cancer symptom management and ultimately improve patient care and safety.