Node-positive Non-small Cell Lung Research Articles

Treating Locally Advanced Disease: An Analysis of Very Large, Hilar Lymph Node Positive Non-Small Cell Lung Cancer Using the National Cancer Data Base

Very large, locally advanced non-small cell lung cancers (NSCLC) remain a therapeutic challenge. This retrospective study compares the effect of treatment modalities on survival of patients with large NSCLC with hilar lymph node involvement (T3>7 cmN1). The National Cancer Data Base was used to identify adult patients who were diagnosed with T3>7 cmN1 NSCLC from 1999 to 2005 (n=642). Nonsurgical treatments included chemoradiation, chemotherapy, radiation therapy, or no treatment, whereas primary surgical treatments included surgery, chemoradiation or chemotherapy prior to surgery, chemoradiation or chemotherapy after surgery, or postoperative radiotherapy. Five-year overall survival (OS) was estimated by the Kaplan-Meier method and comparisons made using log-rank tests and Cox regression models. A total of 642 patients were evaluated; 425 nonsurgical (66%) and 217 surgical (34%). Primary surgical therapy was associated with improved 5-year OS; 28% versus 8% and 4% for nonsurgical and no treatment, respectively (p<0.001). The 5-year OS were 11%, 5%, 2%, and 4% for chemoradiation, chemotherapy, radiation therapy, and no treatment, respectively (p<0.001). The 5-year OS were 16% for surgery only, 40% and 44% for neoadjuvant chemoradiation or chemotherapy with surgery, respectively, 40% and 38% for adjuvant chemoradiation or chemotherapy with surgery, respectively, and 18% for postoperative radiotherapy (p<0.001). On multivariate analysis, surgery and chemotherapy in most combinations were associated with significantly improved OS compared with chemoradiation only. Surgery with systemic therapy delivered in a neoadjuvant or adjuvant fashion for patients with T3>7 cmN1 NSCLCs is associated with improvements in OS.

High tumor cell expression of microRNA-21 in node positive non-small cell lung cancer predicts a favorable clinical outcome

BackgroundMicroRNA (miR)-21 has been revealed as an oncogene in cancer development, and is one of the miRNAs closely connected to angiogenesis. We aimed to explore the impact of miR-21 expression in both tumor and stromal compartments of non-small cell lung cancer (NSCLC), and correlations between miR-21 and angiogenic protein markers.MethodsFrom 335 unselected stage I to IIIA NSCLC carcinomas, duplicate tumor and tumor-associated stromal cores were collected in tissue microarrays (TMAs). In situ hybridization (ISH) was used to detect the expression of miR-21 separately in tumor cells and stromal cells of the tumor, and immunohistochemistry (IHC) was used to detect the expression of the protein markers protein kinase B (Akt), phosphatidylinositol-3-kinase (PI3K), hypoxia induced factor 1 (HIF1α) and vascular endothelial growth factor-A (VEGF-A).ResultsIn univariate analyses, high tumor cell expression of miR-21 in patients with lymph node metastasis was a positive prognostic factor (P = 0.024). High stromal miR-21 expression had a negative prognostic impact (P = 0.022). In the multivariate analysis, low tumor mir-21 expression in node positive patients was an independent adverse prognostic factor (HR 2.03, CI 95% 1.09-3.78, P = 0.027).ConclusionsIn patients with lymph node metastasis, miR-21 expression in tumor cells is an independent positive prognostic factor. High stromal miR-21 expression is a negative prognostic factor.

Fluorodeoxyglucose positron-emission tomography ratio in non-small cell lung cancer patients treated with definitive radiotherapy

PurposeTo determine whether the maximum standardized uptake value (SUV) of [18F] fluorodeoxyglucose uptake by positron emission tomography (FDG PET) ratio of lymph node to primary tumor (mSUVR) could be a prognostic factor for node positive non-small cell lung cancer (NSCLC) patients treated with definitive radiotherapy (RT).Materials and MethodsA total of 68 NSCLC T1-4, N1-3, M0 patients underwent FDG PET before RT. Optimal cutoff values of mSUVR were chosen based on overall survival (OS). Independent prognosticators were identified by Cox regression analysis.ResultsThe most significant cutoff value for mSUVR was 0.9 with respect to OS. Two-year OS was 17% for patients with mSUVR > 0.9 and 49% for those with mSUVR ≤ 0.9 (p = 0.01). In a multivariate analysis, including age, performance status, stage, use of chemotherapy, and mSUVR, only performance status (p = 0.05) and mSUVR > 0.9 (p = 0.05) were significant predictors of OS. Two-year OS for patients with both good performance (Eastern Cooperative Oncology Group [ECOG] ≤ 1) and mSUVR ≤ 0.9 was significantly better than that for patients with either poor performance (ECOG > 1) or mSUVR > 0.9, 23% (71% vs. 23%, p = 0.04).ConclusionOur results suggested that the mSUVR was a strong prognostic factor among patients with lymph node positive NSCLC following RT. Addition of mSUVR to performance status identifies a subgroup at highest risk for death after RT.

The lymphatic pathways of non-small cell lung cancer and their implication in curative irradiation treatment

Using the pre-therapy CT scans of 266 node positive non-small cell lung cancer patients, we analysed the lymphatic pathways and the incidence of lymph node metastases in regional lymph nodes (as described by CT criteria corresponding to the modified mapping scheme of the American Thoracic Society), in order to develop the target volume for curative irradiation treatment. Among the 105 patients with node positive left sided primaries, the incidence of involvement of the ipsilateral supraclavicular lymph nodes was 9.5%, and the incidence of involvement of the contralateral lymph nodes was 3.8%. The incidence of involvement of the contralateral hilar lymph nodes was 4.8%. Among the 161 patients with nodal positive right sided primaries, the incidence of involvement of the ipsilateral supraclavicular lymph nodes was 8.7% and the incidence of involvement of the contralateral lymph nodes was 1.8%. For this group of patients, the incidence of involvement of the contralateral hilar lymph nodes was 3.7%. All patients with involvement of the contralateral hilar lymph nodes died within 2.5 years of diagnosis. In the cases where there was involvement of the supraclavicular lymph nodes, the patients died within 1.6 years. Involvement of the ipsilateral and/or contralateral supraclavicular lymph nodes, and/or the contralateral hilar lymph nodes, is defined as N3 disease, and is included in Stage IIIb. No curative surgery is indicated for these patients. Why therefore should this group of patients be treated with curative intent by irradiation of the primary, ipsilateral and contralateral hilar lymph nodes, as well as mediastinal, ipsilateral and contralateral supraclavicular lymph nodes? The curative radiation treatment volume for lung cancer has to include the primary tumor and the ipsilateral hilar, and the low and high mediastinal lymph nodes, as is indicated for Stage I, II and IIIa disease.