Impact of immune reconstitution on outcomes to chemoradiation in cervical cancer

免疫重建对宫颈癌放化疗结果的影响

• 批准号: 9128436
• 负责人: STEPHEN M HAHN
• 金额: $ 1.05万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-01 至 2020-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9128436
• 关键词: Acquired Immunodeficiency Syndrome; Address; Adult; Affect; Africa; Age; Age-Years; Anti-Retroviral Agents; Botswana; CD4 Lymphocyte Count; CD4 Positive T Lymphocytes; Cancer Etiology; Cancer Patient; Cervix carcinoma; Clinical; Communicable Diseases; Comparative Study; Diagnosis; Dose; Future; Goals; HIV; Heterosexuals; Human Papillomavirus; Immune; Immunologic Deficiency Syndromes; Immunologics; Immunosuppression; Inferior; Kaposi Sarcoma; Life; Lymphocyte Count; Malignant Neoplasms; Malignant neoplasm of cervix uteri; Malignant neoplasm of lung; Merkel cell carcinoma; Non-Hodgkin' s Lymphoma; Outcome; Outcome Study; Patient risk; Patients; Pattern; Population; Prevalence; Recovery; Research; Resources; Retrospective Studies; Risk Factors; Shapes; Southern Africa; Time; Toxic effect; Transplant Recipients; Viral; Virus Diseases; Woman; Youth; acute toxicity; cancer therapy; chemoradiation; clinical practice; follow-up; immune activation; improved; low and middle-income countries; men; multidisciplinary; prospective; reconstitution; response; therapy outcome; treatment response; tumor; viral transmission

Cervical cancer is the leading cause of cancer in women living in the developing world, and in the setting of HIV (human immunodeficiency virus), it is an AIDS defining illness. In Botswana, approximately 17% of the population is HIV positive and approximately 60%-80% of cervical cancer patients have concomitant HIV infection. In Southern Africa as in resource-poor settings, women's survival after the onset of invasive cervical cancer is adversely affected by suboptimal diagnosis, treatment response, and follow-up in addition to HIV status. The long-range goals of this project are to improve survival in HIV+ women undergoing chemo-radiotherapy by defining the clinical (tolerability and toxicity) and immunological parameters associated with invasive cervical cancer therapy response. The results of these studies will be used to shape future multi-disciplinary strategies to maximize treatment of HIV positive women with human papillomavirus (HPV) -associated cervical cancer in Botswana. Immunosuppression associated with HIV infection has been established as a risk factor for a variety of malignancies, including non-Hodgkin lymphoma, Kaposi Sarcoma, Merkel cell carcinoma, cervical cancer, and lung cancer. Comparative studies have shown that the pattern of increased cancers in HIV patients was similar to that observed in immunosuppresed transplant patients and that the risk in HIV patients correlates with CD4+ T-lymphocyte count, suggesting that immunodeficiency is likely the underlying cause of increased malignancy observed in HIV patients. Amongst women who are HIV positive with cervical cancer, prospective clinical outcome studies are limited and retrospective studies have demonstrated inferior survival and decreased tolerability to chemo-radiotherapy for unclear reasons. Therefore,' a gap exists in our understanding of the impact of HIV infection and anti-retroviral therapy (ART) on tolerability and the contribution of immune reconstitution on cervical cancer treatment response as none of these studies have yet examined the impact of ART on chemoradiotherapy or how immunologic status affects outcomes. Our proposal will address the relationship between immune reconstitution following ART and cancer therapy outcomes in HIV+ women receiving chemoradiotherapy for HPV-associated invasive cervical carcinoma. This information will impact clinical practice or therapy dosing as the presence of ART or immune reconstitution is not currently considered as a determinant to HPV-associated cervical cancer treatment response.

宫颈癌是居住在发展中国家的妇女癌症的主要原因，在艾滋病毒（人类免疫缺陷病毒）的情况下，它是定义疾病的艾滋病。在博茨瓦纳，大约17％的人口为HIV阳性，大约60％-80％的宫颈癌患者伴有HIV感染。在南部非洲，与资源贫乏的环境一样，侵入性宫颈癌发作后的妇女生存受到次优诊断，治疗反应和HIV状态之外的随访的不利影响。该项目的远距离目标是通过定义与临床（耐受性和毒性）和与侵入性宫颈癌癌症治疗反应相关的临床（耐受性和毒性）和免疫学参数来改善接受化学疗法的HIV+妇女的生存。这些研究的结果将用于塑造未来的多学科策略，以最大程度地利用博茨瓦纳与人乳头瘤病毒（HPV）相关的宫颈癌的艾滋病毒阳性妇女的治疗。与HIV感染相关的免疫抑制已被确定为各种恶性肿瘤的危险因素，包括非霍奇金淋巴瘤，Kaposi肉瘤，默克尔细胞癌，宫颈癌和肺癌。比较研究表明，HIV患者中癌症增加的模式与免疫抑制的移植患者中观察到的模式相似，HIV患者的风险与CD4+ T-淋巴细胞计数相关，这表明免疫缺陷可能是在HIV患者中观察到的恶性肿瘤的潜在原因。在患有宫颈癌阳性的妇女中，前瞻性临床结果研究是有限的，回顾性研究表明，由于不明确的原因，对化学疗法的生存率较低，对化学疗法的耐受性降低。因此，'在我们对HIV感染和抗逆转录病毒疗法（ART）对耐受性的影响以及免疫重建对宫颈癌治疗反应的贡献的理解中存在差距，因为这些研究尚未研究艺术对化学放疗的影响或免疫学状况如何影响出现。我们的建议将解决ART后的ART后免疫重建和癌症治疗结果的关系，以接受HPV相关的浸润性宫颈癌接受化学放射治疗。由于目前尚未将其视为与HPV相关的宫颈癌治疗反应的决定因素，因此此信息将影响临床实践或治疗给药。