ABSTRACT
PURPOSE: To define symptoms and therapeutic requirements for patients with metastatic or locally recurrent lung cancer. METHODS AND MATERIALS: Data were collected from 69 consecutive patients with locally advanced lung cancer seen in consultation at a radiation oncology facility serving a community hospital in Virginia. The Lung Cancer Symptom Scale, a validated quality of life instrument, measured the incidence of symptoms in this group. RESULTS: Average survival for the entire group was 7 months. Fifty-seven patients received 81 courses of radiation therapy, 33 directed at thoracic disease and 48 delivered to sites of metastasis. Thirty-three percent of those who received radiation therapy required treatment to more than one anatomic site. Every patient was symptomatic at the time of consultation, with the number (p = 0.001) and severity (p = 0.001) of symptoms they suffered worse in the patient group seen 0 to 3 months prior to death rather than 4 to 6 months prior to death. With the exception of cough, symptoms were marked in their severity. CONCLUSIONS: Patients with advanced lung cancer suffer frequent and severe symptoms that worsen in the final months of life. The appropriate timing and combination of radiotherapy and chemotherapy are yet to be resolved. Future studies will require use of validated quality of life instruments to better catalogue palliation and treatment toxicity.
Subject(s)
Anorexia/classification , Anorexia/etiology , Bone Neoplasms/complications , Bone Neoplasms/secondary , Brain Neoplasms/complications , Brain Neoplasms/secondary , Chest Pain/classification , Chest Pain/etiology , Cough/classification , Cough/etiology , Dyspnea/classification , Dyspnea/etiology , Fatigue/classification , Fatigue/etiology , Hemoptysis/classification , Hemoptysis/etiology , Lung Neoplasms/pathology , Neoplasm Recurrence, Local/complications , Quality of Life , Severity of Illness Index , Aged , Anorexia/psychology , Bone Neoplasms/mortality , Bone Neoplasms/therapy , Brain Neoplasms/mortality , Brain Neoplasms/therapy , Chest Pain/psychology , Combined Modality Therapy , Cough/psychology , Cross-Sectional Studies , Dyspnea/psychology , Fatigue/psychology , Female , Hemoptysis/psychology , Hospitals, Community , Humans , Incidence , Male , Palliative Care/methods , Prospective Studies , Survival Analysis , Time Factors , Treatment Outcome , Virginia/epidemiologyABSTRACT
Mature T cells initially respond to Ag by activation and expansion, but high and repeated doses of Ag cause programmed cell death and can suppress T cell-mediated diseases in rodents. We evaluated repeated systemic Ag administration in a marmoset model of experimental allergic encephalomyelitis that closely resembles the human disease multiple sclerosis. We found that treatment with MP4, a chimeric, recombinant polypeptide containing human myelin basic protein and human proteolipid protein epitopes, prevented clinical symptoms and did not exacerbate disease. CNS lesions were also reduced as assessed in vivo by magnetic resonance imaging. Thus, specific Ag-directed therapy can be effective and nontoxic in primates.
Subject(s)
Callithrix/immunology , Immunodominant Epitopes/immunology , Immunotherapy, Active/methods , Multiple Sclerosis/immunology , Multiple Sclerosis/therapy , Myelin Basic Protein/immunology , Myelin Proteolipid Protein/immunology , Animals , Autoantibodies/biosynthesis , Brain/pathology , Cytokines/biosynthesis , Disease Models, Animal , Dose-Response Relationship, Immunologic , Drug Administration Schedule , Immunodominant Epitopes/administration & dosage , Immunosuppressive Agents/administration & dosage , Immunosuppressive Agents/immunology , Injections, Intravenous , Lymphocyte Activation/immunology , Magnetic Resonance Imaging , Male , Multiple Sclerosis/pathology , Myelin Basic Protein/administration & dosage , Myelin Proteolipid Protein/administration & dosage , Recombinant Fusion Proteins/administration & dosage , Recombinant Fusion Proteins/immunology , Th1 Cells/immunology , Th1 Cells/metabolism , Th2 Cells/immunology , Th2 Cells/metabolismABSTRACT
Definition of the immune process that causes demyelination in multiple sclerosis is essential to determine the feasibility of Ag-directed immunotherapy. Using the nonhuman primate, Callithrix jacchus jacchus (common marmoset), we show that immunization with myelin basic protein and proteolipid protein determinants results in clinical disease with significant demyelination. Demyelination was associated with spreading to myelin oligodendrocyte glycoprotein (MOG) determinants that generated anti-MOG serum Abs and Ig deposition in central nervous system white matter lesions. These data associate intermolecular "determinant spreading" with clinical autoimmune disease in primates and raise important issues for the pathogenesis and treatment of multiple sclerosis.
