The Laboratory of Symptom Management incorporates the Mucosal Injury Unit (MIU) and the Patient Reported Outcomes Core (PRO). Evaluations of novel interventions for the management of symptoms associated with cancer-therapy and GVHD are described in Mucosal Injury Unit summary. Current and planned studies of quality of life and the development of patient-reported outcomes are described for the Patient Reported Outcomes Core.
Mucosal Injury Unit
The Mucosal Injury Unit is focused on clinical research designed to elucidate the underlying molecular mechanisms of and evaluate the efficacy of novel interventions for symptoms associated with cancer treatment in order to provide the basis for evidence-based nursing practice. Specifically, the Mucosal Injury Unit focuses on clinically significant side effects related to chemotherapy stomatitis, mucositis, and associated oropharyngeal pain.
Cancer treatment-induced oral complications such as stomatitis and mucositis, are biologically complex conditions that often lead to a cascade of negative sequelae that present clinical treatment challenges. Oncology treatments designed to maximize clinical and survival outcomes, or provide palliative treatment, may be compromised when dose reduction or treatment cessation is necessary because of treatment related complications such as stomatitis.
Patient outcomes from these cancer treatment-induced conditions range from severe oral pain to life-threatening medical emergencies such as sepsis. The underlying principals of this clinical research are that the human model is the most appropriate for clinical research, and that the etiology, progression, and resolution of these symptoms have a multifactorial nature (Peterson and Sonis, 2001). Synergizing the expertise of clinical researchers and basic scientists promotes formulation of novel hypotheses regarding the contributions of potential mechanism such as inflammation and sustained cytokine dysregulation, that underlie the tissue injury and repair mechanisms associated with cancer treatment-induced symptoms.
Clinical Research Protocols
The MIU is directing two randomized controlled clinical trials to elucidate the role of inflammation in stomatitis and related oropharyngeal pain seen in the HCT and the cGVHD populations.
- The first study (02-NR-0133) is designed to test the effects of a novel tumor necrosis factor (TNF) fusion protein etanercept, (Enbrel, Immunex Corporation, Seattle, WA) on the incidence and severity of stomatitis.
- The second clinical trial (04-NR-0069) is designed to elucidate the role of inflammation in cGVHD-related ulcerative stomatitis by testing the efficacy of topical thalidomide on the resolution of this condition and the related oropharyngeal pain.
Patient Reported Outcomes Core
Patient reported outcomes are used increasingly to broaden the assessment of the impact of medical treatment modalities beyond traditional indicators such as survival. The view that what patients experience as a result of their medical care can only be known by them has gained recognition (FDA, 2006). Patients may have the same disease but their response to the disease and medical treatment may be different (Parmenter, 1994; Schipper, Clinch, & Olweny, 1996). Therefore, there is a need and a desire to know the diverse and subjective experiences of patients as it relates to their health, illness and the effects of treatment. An integrated HRQL and symptoms research portfolio provides a systematic assessment of patients unique perspective in an effort to provide direction in the development and implementation of interventions that may have potential to alleviate symptom burden and improve HRQL.
The focus of the Patient Reported Outcomes Core is to develop a health-related quality of life (HRQL) research portfolio that evaluates the impact of various diseases and novel treatment modalities from the viewpoint of the patient. Data are generated on how diverse patient populations view the burden of their illness and which treatments they perceive to provide optimal beneficial effects.
One focus of the PRO initiative is the development of intramural collaborative studies that examine whether novel treatments improve HRQL and symptom experience in patients with chronic and terminal illnesses undergoing novel therapies. The following clinical studies exemplify this initiative.
- The first study (00-CC-0052) is examining HRQL and symptoms in patients with metastatic melanoma enrolled in intramural National Cancer Institute (NCI) Surgery Branch immunotherapy protocols and receiving vaccine alone or in conjunction with high dose bolus intravenous interleukin-2 (IL2) or subcutaneous.
- The second collaborative study (00-CC-002) focused on the effect of reduced intensity conditioning (RIC) and myeloablative (MT) peripheral blood stem cell transplant (PBSCT) on HRQL and symptom distress. RIC has less regimen-related morbidity and mortality than MT offering allogeneic transplantation to patients otherwise excluded, however, it remains unclear whether these advantages improve HRQL.
- Surgical resection and continuous hyperthermic intraperitoneal perfusion with chemotherapy is an intensive therapy for peritoneal carcinomatosis. The purpose of this third intramural, collaborative study (00-C-0069) was to examine the impact of this therapy on HRQL in patients with peritoneal surface malignancies over a 1 year trajectory.
A second PRO research initiative focuses on the use of advanced modeling techniques to discern mediating relationships among latent constructs that elucidate how patients feel, function and interpret their illness. Specifically, theoretical model testing is applied to examine how modifiable factors such as symptom distress, illness representations, and attitudes towards technology dependency influence HRQL in patients who are dependent on therapeutic health care technology. The influence of antecedent clinical and demographic factors is also considered.
A third PRO initiative will be to determine the impact of the relative burden of disease conditions and treatments on HRQL and symptom experience. This project involves secondary analyses of baseline data of HRQL and symptom experiences from three prospective studies: a) HRQL, fatigue, and symptom distress in patients with advanced melanoma: Comparison to the General U.S. population and cancer population, b) HRQL and Symptom Distress In Patients Prior To Allogeneic Stem-Cell Transplant, and c) Assessing the Relationship between Symptom Distress and HRQL in Patients with HIV Infection.