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。这种改善伴随着急性和晚期治疗效果的显著增加。[晚期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。了解晚期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。纤维化和淋巴水肿继发于肿瘤或治疗引起的组织损伤的基质反应，这是导致治疗后期效应的研究不足和理解不足的机制。我们假设[迟发性纤维化和淋巴水肿代表了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，纤维化和淋巴水肿都可能与慢性炎症有关，导致一个活跃的、持续的过程。因此，淋巴水肿和纤维化可能在治疗完成后发生；随着时间的推移而进步；自我延续]。国家癌症研究所的战略计划指出，需要“扩大努力，了解影响癌症患者对疾病、治疗和康复反应的生物、物理、心理和社会机制及其相互作用”，并“支持对当前和新的癌症治疗的不良慢性和晚期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/淋巴水肿连续体。具体目的是：1)确定HNC患者晚期效应（治疗后3个月）纤维化和/或淋巴水肿的患病率和性质；2)探讨HNC患者炎症反应的生物学机制、遗传多态性、[治疗因素]与晚期纤维化和/或淋巴水肿的关系；3)探讨HNC患者晚期纤维化和/或淋巴水肿与社会心理应激源（抑郁和社交退缩）之间的关系。数据收集，采用选择性重复测量，将在治疗结束后，治疗后6周至48周间隔，治疗后15和18个月间隔进行。Nagin的基于群体的轨迹模型将用于评估我们的发现。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)[为未来在其他具有纤维化和/或淋巴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）中的研究奠定基础；2)协助开发预测风险模型；3)激发新的预防途径。介入性研究（如抗炎药）；4)帮助医生和其他医疗保健专业人员更好地诊断、降低风险和治疗迟发性纤维化和/或淋巴水肿。

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.