The Fibrosis-Lymphedema Continuum in Head and Neck Cancer

描述（由申请人提供）：头颈癌（HNC）的积极治疗提高了生存率。这种改善伴随着治疗的急性和迟发效应的显著增加。[迟发效应可能继发于治疗]（手术、放疗和化疗）或肿瘤本身的影响。它们对幸存者的长期症状负担、功能和整体生活质量（QOL）有深远的影响。了解迟发效应的机制和表现对于设计改善HNC患者生存质量的干预措施至关重要。]继发于间质对[肿瘤或治疗引起的组织损伤未得到充分研究且对导致治疗晚期效应的机制了解甚少]的反应的纤维化和水肿。我们假设迟发性纤维化和水肿是存在于生物学和临床连续体上的相互关联的过程。此外，最近的数据表明，纤维化和水肿可能与慢性炎症有关，导致[一个活跃的，持续的过程。因此，水肿和纤维化可能：在治疗完成后发展;随时间进展;并且自我延续]。国家癌症研究所的战略计划解决了需要“扩大努力，了解生物，物理，心理和社会机制及其相互作用，影响癌症患者对疾病，治疗和恢复的反应”，并“支持对当前和新的癌症治疗的不良慢性和迟发效应所涉及的生物和生理机制的研究。“这项纵向描述性研究的目的是研究[HNC患者]的纤维化/水肿连续体。具体目标是：1）确定迟发效应的发生率和性质（e治疗后3个月）HNC患者中的纤维化和/或水肿; 2）探索HNC患者中炎症反应的生物学机制、遗传多态性、[治疗因素]和迟发性纤维化和/或水肿之间的关系;和3）[探索HNC患者中迟发性纤维化和/或水肿与心理社会应激源（抑郁和社交退缩）之间的关系。将在治疗结束时、治疗后6周至治疗后48周以及治疗后15个月和18个月间隔时使用选定的重复测量进行数据收集。]纳金的基于组的轨迹模型将被用来评估我们的研究结果。如果目标得以实现，信息得以传播，重要的新信息将可用于：1）[作为未来在其他具有发生纤维化和/或水肿高风险的癌症人群（如乳腺癌、卵巢癌、前列腺癌和黑色素瘤患者）中进行研究的基础; 2）帮助开发预测风险模型; 3）刺激新的预防途径。介入性研究（例如抗炎剂）;]和4）帮助医生和其他医疗保健专业人员更好地诊断、降低迟发性纤维化和/或水肿的风险并治疗迟发性纤维化和/或水肿。 公共卫生相关性：头颈部癌症患者的寿命更长，许多人在治疗后头部和颈部出现硬度和肿胀。我们不知道为什么有些人遇到这些问题，而另一些人没有。这项研究将提供信息，使医疗保健提供者可以更好地治疗这些患者。

DESCRIPTION (provided by applicant): Aggressive treatment for head and neck cancer (HNC) has improved survival rates. This improvement comes with a marked increase in acute and late-effects of treatment. [Late-effects may be secondary to treatment] (surgery, radiation, and chemotherapy) or effects of the tumor itself. They have a profound impact on [survivor's long-term symptom burden, functionality, and overall quality of life (QOL). Under- standing the mechanisms and manifestations of late-effects is critical to the design of interventions for improvement of quality of survivorship in HNC patients.] Fibrosis and lymphedema secondary to the stromal response to [tissue damage from tumor or treatment are understudied and poorly understood mechanisms that contribute to late-effects of therapy.] We hypothesize [that late-effect fibrosis and lymphedema represent inter-related processes that exist on biological and clinical continuums. Further- more, recent data indicates that both] fibrosis and lymphedema may be associated [with chronic] inflammation resulting in [an active, ongoing process. Thus, lymphedema and fibrosis may: develop after treatment is completed; progress over time; and be self perpetuating]. The National Cancer Institute's strategic plan addresses the need to "expand efforts to understand biologic, physical, psychological, and social mechanisms and their interactions that affect a cancer patient's response to disease, treatment, and recovery," and to "support research on the biologic and physiological mechanisms involved in adverse chronic and late-effects of both current and new cancer treatment." The objective of this longitudinal, descriptive study is to investigate the fibrosis/ lymphedema continuum [in HNC patients]. Specific Aims are to: 1) determine prevalence and nature of late-effect (e 3 months post-treatment) fibrosis and/or lymphe- dema in HNC patients; 2) explore relationships among biological mechanisms of inflammatory response, genetic polymorphisms, [treatment factors], and late-effect fibrosis and/or lymphedema in HNC patients; and 3) [explore relationships among late-effect fibrosis and/or lymphedema and psychosocial stressors (depression and social withdrawal) in HNC patients. Data collection, using select repeated measures, will take place at end of treatment, six week intervals after treatment through 48 weeks post-treatment, and 15 and 18 month intervals post-treatment.] Nagin's group-based trajectory modeling will be used to evaluate our findings. If the aims are achieved and information is disseminated, important new information will be available to: 1) [serve as underpinnings for future studies in other cancer populations at high risk for development of fibrosis and/or lymphedema, such as those with breast, ovarian, prostate cancers, and melanoma; 2) aid in development of predictive risk models; 3) stimulate new avenues of preventive. interventional research (e.g. anti-inflammatory agents);] and 4) assist physicians and other healthcare professionals to better diagnose, reduce risk for, and treat late-effect fibrosis and/or lymphedema. PUBLIC HEALTH RELEVANCE: Head and neck cancer patients are living longer, and many suffer hardness and swelling in the head and neck post-treatment. We do not know why some experience these problems and others do not. This study will provide information so healthcare providers can better treat these patients.