RESUMO
OBJECTIVES: The study objectives were to assess the outcomes of lung resection in patients with non-small cell lung cancer previously treated with nonoperative treatment and to identify prognostic factors associated with survival. METHODS: Patients who underwent surgery (2010-2022) after initial nonoperative treatment at a single institution were identified from a prospectively maintained database. Exclusion criteria included metachronous cancer, planned neoadjuvant therapy, and surgery for diagnostic or palliative indications. Cox models were constructed for overall survival and event-free survival. Survival of patients with stage IV disease was compared with survival of a nonstudy cohort who did not undergo surgery. RESULTS: In total, 120 patients met the inclusion criteria. Initial clinical stage was early stage in 16%, locoregionally advanced in 25%, and metastatic in 59% of patients. The indication for surgery was recurrence in 18%, local persistent disease in 23%, oligoprogression in 22%, and local control of oligometastatic disease in 38% of patients. Grade 3 or greater complications occurred in 5% of patients; 90-day mortality was 3%. Three-year event-free survival and overall survival were 39% and 73%, respectively. Male sex and lymphovascular invasion were associated with shorter event-free survival and overall survival; younger age and prior radiation therapy were associated with shorter overall survival. Patients with stage IV disease who received salvage lung resection had better overall survival than similar patients who received subsequent systemic therapy and no surgery. CONCLUSIONS: In this selected, heterogeneous population, lung resection after initial nonoperative treatment for non-small cell lung cancer was safe. Surgery as local consolidative therapy was associated with encouraging outcomes and should be considered for these patients.
RESUMO
PURPOSE: The epidermal growth factor receptor tyrosine kinase inhibitor ZD1839 (Iressa) markedly potentiates the efficacy of many cytotoxic agents against several human cancer xenografts, irrespective of tumor EGFR expression levels. We subsequently investigated the extent to which ZD1839 might improve radiation therapy (RT) in similar animal models of human cancer within the limits of tolerance at a relevant organ site. EXPERIMENTAL DESIGN: We carried out studies of ZD1839 in in vivo models of human non-small cell lung (A549 and SK-LC-16) and breast (MDA-MB468) cancers and human mesothelioma (JMN). The tumors were implanted s.c. over the rib cage or on the most proximate breast and RT given ventral dorsally to the chest only, with mediastinal protection. After the tumor reached a palpable size (0.4-0.6 mm), treatment was initiated with the maximum-tolerated dose (MTD) of ZD1839 (150 mg/kg once daily x 5 for 2 successive weeks), RT (a total of 40 Gy given fractionally at 4 Gy once daily x 5 for 2 successive weeks), or both ZD1839 and RT. RESULTS: This level of RT induced no untoward effects in the mice and was effective (18-72%) in bringing about regression of the tumors with a few complete regressions. ZD1839 alone, given p.o. on the same schedule at its MTD (150 mg/kg), was modestly inhibitory (35-40%) to tumor growth. RT and ZD1839 could be given together at the same doses on the same schedule, resulting in marked regression (50-99%) and a large number of complete regressions of each of the tumors studied. In these studies, the MTD of ZD1839 could be combined with the MTD of RT with no change in schedule or increase toxicity over ZD1839 or RT alone. CONCLUSIONS: ZD1839 significantly enhanced the antitumor action of RT against the test tumors without significant adverse effects, increasing the therapeutic selectively of ionizing radiation in these model systems. These results predict substantial benefits for this multimodality regimen of therapy in patients.
