Longevity after radiotherapy of stage III lung cancer: superior vena cava obstruction is associated with early mortality.

BACKGROUND: People with locally advanced lung cancer have a poor prognosis. Physicians are unable to accurately predict life expectancy of patients. The aims of this retrospective study were to identify the life spans of individuals after radiotherapy of stage III carcinoma of the lung and to determine whether potential prognostic factors could identify people with distinct life spans. METHODS: Between September 1981 and August 2010, 133 consecutive individuals underwent definitive or palliative radiotherapy (with or without chemotherapy) for stage IIIA/IIIB disease. Analysis of the survival data revealed that 14 patients experienced long-term survival, exceeding 36 months; 94 patients had a short-term life span (STLS), extending between 4 and 36 months, and 25 patients were in the end-of-life (EOL) period, referring to the last 3 months of life. Recognized pre-treatment clinicopathological features were tested for their impact on prognosis. RESULTS: The largest proportion of patients presenting with superior vena cava obstruction (SVCO) (P<0.001) and receiving palliative radiotherapy (P=0.009) were from the EOL group. Most of the individuals with inadequate or no health insurance belonged to the STLS and EOL cohorts (P=0.001). Multivariate analysis revealed that the presence of SVCO was an independent factor predictive of shortened survival/EOL status (P=0.001). CONCLUSIONS: Our study showed that a particular disease characteristic, health insurance status and provision of contemporary therapy can influence individual longevity. Selection and prioritization of health care resources remain important; therefore, identification of influential prognostic factors in lung cancer patients deserves further scrutiny.

The green tea polyphenol EGCG potentiates the antiproliferative activity of c-Met and epidermal growth factor receptor inhibitors in non-small cell lung cancer cells.

PURPOSE: Activation of the c-Met and epidermal growth factor receptors (EGFR) promotes the growth and survival of non-small cell lung cancer (NSCLC). Specific receptor antagonists have shown efficacy in the clinic, but tumors often become resistant to these therapies. We investigated the ability of (-)-epigallocatechin-3-gallate (EGCG) to inhibit cell proliferation, and c-Met receptor and EGFR kinase activation in several NSCLC cell lines. EXPERIMENTAL DESIGN: NSCLC cell lines with variable sensitivity to the EGFR antagonist erlotinib were studied. Cell growth was evaluated using proliferation and colony formation assays. Kinase activation was assessed via Western blot analysis. Experiments were conducted with EGCG, the EGFR antagonist erlotinib, and the c-Met inhibitor SU11274. The antagonists were also tested in a xenograft model using SCID mice. RESULTS: EGCG inhibited cell proliferation in erlotinib-sensitive and -resistant cell lines, including those with c-Met overexpression, and acquired resistance to erlotinib. The combination of erlotinib and EGCG resulted in greater inhibition of cell proliferation and colony formation than either agent alone. EGCG also completely inhibited ligand-induced c-Met phosphorylation and partially inhibited EGFR phosphorylation. The triple combination of EGCG/erlotinib/SU11274 resulted in a greater inhibition of proliferation than EGCG with erlotinib. Finally, the combination of EGCG and erlotinib significantly slowed the growth rate of H460 xenografts. CONCLUSION: EGCG is a potent inhibitor of cell proliferation, independent of EGFR inhibition, in several NSCLC cell lines, including those resistant to both EGFR kinase inhibitors and those overexpressing c-Met. Therefore, EGCG might be a useful agent to study as an adjunct to other anticancer agents.

The elderly with synchronous non-small cell lung cancer and solitary brain metastasis: does palliative thoracic radiotherapy have a useful role?

We evaluated the prognosis associated with advanced age by comparing the clinical features of individuals 65 years of age and older to those of younger patients with single metastasis to the brain alone (SMBA) and simultaneous non-small cell lung cancer (NSCLC), and the potential role of palliative thoracic radiotherapy in this cohort of patients. Our 23-year experience included 72 consecutive (22 elderly and 50 non-elderly) people. Older patients predominantly presented with N0-N1 stage disease and coexisting illness. Univariate analysis showed that younger age (p=0.04) and operative removal of SMBA (p=0.01) were predictive of better survival. However, with multivariate analysis, resection of SMBA remained the sole predictor of prognosis. The application of NSCLC radiotherapy for palliation did not favorably alter outcome. In conclusion, elderly patients with simultaneous NSCLC and SMBA seem to fare less well than their younger counterparts. Moreover, the concurrent application of radiotherapy for palliation of the lung neoplasm was not prognostically advantageous.

Restless legs syndrome in the older adult: diagnosis and management.

Restless legs syndrome (RLS) is common in the elderly, with an estimated prevalence of 10 to 35% in individuals over 65 years of age. RLS is characterised by paraesthesias and dysaesthesias of the legs, typically occurring in the evening. The symptoms occur at rest and result in motor restlessness; movement often temporarily relieves the symptoms. Patients with poorly controlled RLS may develop related problems including insomnia (due to sleep-onset restlessness or periodic limb movements or related sleep fragmentation) and depression. RLS can be a primary disorder that develops in the young and includes familial cases. Secondary RLS occurs in association with iron-deficiency anaemia, uraemia and polyneuropathies. Typically, RLS is misdiagnosed or undiagnosed for years. In the elderly, both primary and secondary types of the disorder are common. It is thought that RLS represents lower CNS levels of, or reduced responsiveness to, dopamine. The symptoms improve with dopaminergic therapy. Ergotamine dopamine-receptor agonists such as pergolide, and the non-ergotamine dopamine-receptor agonists pramipexole and ropinirole, are becoming more commonly used to treat RLS. The dopamine precursor levodopa, in combination with carbidopa, is another effective therapeutic agent. An advantage of levodopa is lower cost than non-ergotamine and ergotamine dopamine-receptor agonists. However, the adverse effect of symptom augmentation appears to develop more frequently with levodopa than dopamine-receptor agonists; therefore, levodopa may currently be used somewhat less often as first-line therapy. Patients with painful symptoms may respond favourably to the anticonvulsants gabapentin and carbamazepine. Opioids and hypnosedatives are helpful in selected patients; however, these agents may have troubling adverse effects in the elderly. Correction of iron deficiency improves symptoms in patients with low ferritin levels. Lifestyle modification may also be helpful. Therapy is directed at symptoms, and most symptomatic patients benefit from treatment. It is important to consider RLS in the differential diagnosis of any patient with paraesthesias of the limbs.