ES 09.05 Management of Paraneoplastic Syndromes in SCLC

Abstract

Small cell lung cancer (S.C.L.C.) represents approximately 15% of lung cancers and offers a unique profile of clinical and biological features) S.C.C.L. is a fast growing tumor with are estimated doubling time of 10 days, high propensity to metastatic diffusion since the early beginning of the disease, high sensitivity to chemoradiotherapy but early and common development of pleiotropic drug resistance. Unfortunately in the past 30 years very few advances have been realized in the treatment of S.C.L.C. which in most of the patients is a fatal disease with a median survival of 16-18 months in limited thoracic and 11 months in extensive disease. S.C.L.C. is the most common cancer associated with paraneoplastic syndromes because of its propensity to release endocrine peptides, ectopic hormones and neoantigens that can develop the para neoplastic syndromes. Paraneoplastic syndromes constitutes different and heterogeneous clinical conditions associated with cancer development, affecting various tissues at remote locations from the primary tumor , with an unpredictable clinical behavior. In SCLC, a large number of paraneoplastic syndromes have been reported, involving different organ functions and complicating the clinical course of the disease, including endocrine, neurological and miscellaneous less frequent manifestations. The most common paraneoplastic syndromes in SCLC, can be divided in ectopic hormone-associated syndromes, and immunomediated neurologic syndromes. According to the S.C.L.C. produced hormones we can recognized among the ectopic hormone-associated syndromes, the Hyponatremia (10%) of S.C.L.C., the ectropic Cushing syndrome (5%) Hypertension reninrelated (1%), galactorrhea (1%) and hyperamylasemia (1%). S.C.L.C. has the unique feature to be often heralded or accompanied by a number of immune-mediated neurologic syndromes, the Lambert-Eaton myastemic syndrome 1%, the limbic encephalopaty and the encephalomyelitis, the sensory polyneuropathy, the cerebellar degeneration the opsoclonus myoclonus, all accounting for less than 1%. In most of the cases the neurological symptoms develop before the onset of clinical overt S.C.L.C manifestation and the stage seems not to be related to the presence of paraneoplastic neurological syndrome, whose evolution usually mirrors the behavior and the clinical manifestation. In most of the cases the starting of systemic chemotherapy can induce a dramatic improvement of neurological symptoms in advance to clinical response, and vice versa the worsening of the neurological condition can indicate progressive disease and resistance to the treatment. The study and the improved understanding of pathophisiolgy mechanisms of paraneoplasic syndromes in SCLC can contribute to elucidate the natural history of a fascinating and still largely unknown disease which was erroneously predicted to be a potential curable disease in the eighty years. From that time the treatment strategies and the therapeutic results have been only marginally improved and the undersanding and resolution of paraneoplastic syndromes can contribute substantially to the cure improvement of SCLC.