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

项目摘要 高达40%的患者报告在癌症治疗期间和之后使用大麻进行症状管理 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- 肿瘤学是癌症治疗的快速发展领域。近44%的20种肿瘤类型的癌症患者 接受免疫治疗，特别是免疫检查点抑制剂（ICI），这可能导致 免疫系统持续数月甚至数年的变化。大麻还具有免疫调节作用， 鉴于大麻使用的影响，迫切需要生成关于大麻使用对纵向效益的影响的长期数据， 和危害，免疫功能和疾病进展的癌症患者接受ICI治疗。这一建议建立 我们现有的研究计划。我们的团队已经进行了4个关于大麻使用的NCI资助的项目 在癌症患者中，包括在3个NCI治疗的患者中进行的3项大麻使用大型横断面调查 指定的癌症中心在各研究中心，26%（3，169例中的831例）的癌症患者报告在治疗期间使用大麻。 治疗然而，在接受免疫治疗的患者中，这一比例要高得多（32%）。的 这项研究的首要目标是推进关于纵向利益和危害的科学， 在接受ICI治疗的癌症患者中使用大麻。我们提出了一个多中心，12个月的前瞻性队列 在接受ICI治疗（3个月内）的癌症患者中开展的研究（N=450;每个研究中心150例）：225名大麻使用者（定期 225名非大麻使用者（过去6个月未使用）。吸食大麻， 将通过生态瞬时评估（收集7天/时间点; 49 总天数），将通过在线/电话调查评估患者报告的结局，常规临床数据将 从电子病历中提取。在60例尚未开始ICI的患者亚组中 治疗（30名大麻使用者; 30名非使用者），我们将检查免疫学标记物（例如，TNF-α、IL-6、CRP） 基线（开始ICI之前）、2、6和12个月。具体目的是：1）评估获益（疼痛严重程度 和干扰，睡眠障碍，焦虑，生活质量）和危害（难以集中注意力，记忆力受损， 头晕，疲劳）大麻使用随着时间的推移; 2）测试大麻使用是否随着时间的推移缓和了相关性 邻里劣势（区域发展指数）与目标1和3中的利益和危害之间的关系 60例尚未开始ICI的非皮肤实体恶性肿瘤患者的亚组，探索 大麻使用与疾病进展和免疫学标志物。这项及时而全面的研究， 对RFA-CA-22-052的回应将填补有关大麻纵向益处和危害的知识方面的关键空白 用于接受ICI治疗的患者。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、健康公平、肿瘤学、免疫学和药物滥用。在 与其他资助的U 01和U24合作，这项研究将对科学产生持续的影响， 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.