A Prospective Study of The Prevalence and Significance of Paraneoplastic Autoantibodies in Small Cell Lung Cancer and Cancer of The Breast, Ovary, Hodgkin's Disease, Neuroblastoma and Other Cancers
To determine prospectively the prevalence and specificity of anti-Hu and other
paraneoplastic antibodies in patients with small cell lung cancer (SCLC) and other cancers
including, but not limited to, ovarian cancer, breast cancer and Hodgkin's disease / the
prevalence of other autoimmune antibodies in patients with SCLC and other cancers including
but not limited to anti-nuclear antibodies, anti-P53 antibodies, rheumatoid factor and
anti-calcium channel antibodies /the prevalence and significance of antibodies against a
LEMS-related antigen (MysB)/whether the production of autoantibodies including anti-Hu
antibodies is related to patient MHC phenotype.
- To examine tumor specimens and other available tissues (sputum and bone marrow, if
possible) for the presence of Hu antigen-expressing cells, and/or cells expressing
other paraneoplastic antigens/patients with SCLC and other cancers for the development
of neurologic signs, paraneoplastic or otherwise.
- Attempts will be made to evaluate all patients at the time of initial consultation by
the primary oncologist. If this is not possible, attempts will be made to obtain the
neurological evaluation at the time of the next visit with the oncologist, or in case
of inpatients, during the patient's admission. A complete history and neurologic
examination will be performed at that time by the neurologist with documentation of
signs and symptoms. The patient will be given the Memorial Symptom Assessment Scale to
complete (see attached).
- At initial evaluation, blood will be obtained for the following laboratory studies
including but not limited to (for children the amount of blood drawn will be no more
than 5 cc per Kg for each visit): A) Rheumatoid Factor and Anti-nuclear,
anti-thyroglobulin, anti-microsomal, anti-Ro, and antip53 antibodies. B) HLA Typing
(HLA-ABC, IEF, Class II DNA) and lymphocyte analysis C) Anti-neuronal antibodies,
including HuD, HuC and HeI-N1, anti-Yo, anti-Ri, anti-Tr antibodies D) LEMS-associated
antibodies (MysB antibodies)
- At follow-up (approximately every 4 months) appointments, blood samples will be
obtained for the following studies, including but not limited to, anti-neuronal
antibodies HuC and HeI-N1) and LEMS-associated antibodies (MysB antibodies).
- Tissue samples obtained at diagnosis or during the course of treatment (tumor resection
or biopsy, sputum collections or bone marrow aspirations) will be evaluated for the
expression of Hu and other paraneoplastic antigens.
- As part of the study, patients with positive paraneoplastic antibody serology will be
requested to undergo a lumbar puncture for antibody determination of these antibodies,
cellcount, and chemistry (proteins, glucose, and IgG index) in CSF. In pediatric
neuroblastoma patients with stage 4 neuroblastoma the lumbar puncture will be avoided,
since there is preliminary evidence suggesting increased risk for leptomeningeal
dissemination. Antibody positive patients will be offered quantitative sensory testing
for evaluation of subclinical sensory neuronopathy. This test analyzes the minimum
increments of sensory stimuli (cold, hot and vibration) required to be noticed by the
patient, and compares these results with known normal standard values. The test is
given by the clinical neurologist, and does not cause any discomfort.
Conventional nerve conduction studies or EMG are not required, unless the patient has
symptoms and signs of neuropathy, or the patient is asymptomatic but the quantitative
sensory test is abnormal. In these situations nerve conduction and EMG studies of upper and
lower extremities will be obtained. All patients who undergo CSF analysis, will be required
to have a blood test (glucose, proteins, and IgG) to be compared with the CSF values and to
obtain the IgG index (a measurement of intrathecal synthesis of IgG).
- Patients with positive anti-Mys B antibody serology, or with symptoms suggesting LEMS
(proximal weakness, decreased or absent reflexes) will be offered EMG, nerve conduction
studies, and repetitive stimulation.
- A random sample of 20% of patients not presenting with positive anti-Hu serology will
be offered quantitative sensory testing for evaluation of subclinical sensory
neuropathy in order to serve as a control group. Spinal fluid from patients who undergo
lumbar puncture for reasons unrelated to anti-Hu serology results (approximately 10-15%
of patients) will serve as a control for the spinal fluids obtained from seropositive
patients. In these patients a sample of blood will be obtained to measure glucose,
proteins, IgG, and IgG index
Observational Model: Case-Only, Time Perspective: Prospective
Blood samples for autoantibody determinations and HLA typing and clinical evaluations via Symptom Assessment Scale
Jerome Posner, MD
Memorial Sloan-Kettering Cancer Center
United States: Institutional Review Board
|Memorial Sloan Kettering Cancer Center||New York, New York 10021|