Pretreatment minimal staging for non-small cell lung cancer: an updated consensus report

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/31247/1/0000153.pd

Analytical variables influencing the performance of a miRNA based laboratory assay for prediction of relapse in stage I non-small cell lung cancer (NSCLC)

<p>Abstract</p> <p>Background</p> <p>Laboratory assays are needed for early stage non-small lung cancer (NSCLC) that can link molecular and clinical heterogeneity to predict relapse after surgical resection. We technically validated two miRNA assays for prediction of relapse in NSCLC. Total RNA from seventy-five formalin-fixed and paraffin-embedded (FFPE) specimens was extracted, labeled and hybridized to Affymetrix miRNA arrays using different RNA input amounts, ATP-mix dilutions, array lots and RNA extraction- and labeling methods in a total of 166 hybridizations. Two combinations of RNA extraction- and labeling methods (assays I and II) were applied to a cohort of 68 early stage NSCLC patients.</p> <p>Results</p> <p>RNA input amount and RNA extraction- and labeling methods affected signal intensity and the number of detected probes and probe sets, and caused large variation, whereas different ATP-mix dilutions and array lots did not. Leave-one-out accuracies for prediction of relapse were 63% and 73% for the two assays. Prognosticator calls ("no recurrence" or "recurrence") were consistent, independent on RNA amount, ATP-mix dilution, array lots and RNA extraction method. The calls were not robust to changes in labeling method.</p> <p>Conclusions</p> <p>In this study, we demonstrate that some analytical conditions such as RNA extraction- and labeling methods are important for the variation in assay performance whereas others are not. Thus, careful optimization that address all analytical steps and variables can improve the accuracy of prediction and facilitate the introduction of microRNA arrays in the clinic for prediction of relapse in stage I non-small cell lung cancer (NSCLC).</p

Clinical significance in the number of involved lymph nodes in patients that underwent surgery for pathological stage III-N2 non-small cell lung cancer

<p>Abstract</p> <p>Purpose</p> <p>This study investigated whether the number of involved lymph nodes is associated with the prognosis in patients that underwent surgery for pathological stage (p-stage) III/N2 NSCLC.</p> <p>Subjects</p> <p>This study evaluated 121 patients with p-stage III/N2 NSCLC.</p> <p>Results</p> <p>The histological types included 65 adenocarcinomas, 39 squamous cell carcinomas and 17 others. The average number of dissected lymph nodes was 23.8 (range: 6-55). The average number of involved lymph nodes was 5.9 (range: 1-23). The 5-year survival rate of the patients was 51.0% for single lymph node positive, 58.9% for 2 lymph nodes positive, 34.2% for 3 lymph nodes positive, and 30.0% for 4 lymph nodes positive, and 20.4% for more than 5 lymph nodes positive. The patients with either single or 2 lymph nodes positive had a significantly more favorable prognosis than the patients with more than 5 lymph nodes positive. A multivariate analysis revealed that the number of involved lymph nodes was a significant independent prognostic factor.</p> <p>Conclusion</p> <p>Surgery appears to be preferable as a one arm of multimodality therapy in p-stage III/N2 patients with single or 2 involved lymph nodes. The optimal incorporation of surgery into the multimodality approach therefore requires further clinical investigation.</p

KRAS-mutation incidence and prognostic value are metastatic site-specific in lung adenocarcinoma: poor prognosis in patients with KRAS-mutation and bone metastasis

Current guidelines lack comprehensive information on the metastatic site-specific role of KRAS mutation in lung adenocarcinoma (LADC). We investigated the effect of KRAS mutation on overall survival (OS) in this setting. In our retrospective study, 500 consecutive Caucasian metastatic LADC patients with known KRAS mutational status were analyzed after excluding 32 patients with EGFR mutations. KRAS mutation incidence was 28.6%. The most frequent metastatic sites were lung (45.6%), bone (26.2%), adrenal gland (17.4%), brain (16.8%), pleura (15.6%) and liver (11%). Patients with intrapulmonary metastasis had significantly increased KRAS mutation frequency compared to those with extrapulmonary metastases (35% vs 26.5%, p=0.0125). In contrast, pleural dissemination and liver involvement were associated with significantly decreased KRAS mutation incidence (vs all other metastatic sites; 17% (p<0.001) and 16% (p=0.02) vs 33%, respectively). Strikingly, we found a significant prognostic effect of KRAS status only in the bone metastatic subcohort (KRAS-wild-type vs KRAS-mutant; median OS 9.7v 3.7 months; HR, 0.49; 95% CI, 0.31 to 0.79; p =0.003). Our study suggests that KRAS mutation frequency in LADC patients shows a metastatic site dependent variation and, moreover, that the presence of KRAS mutation is associated with significantly worse outcome in bone metastatic cases.(VLID)469049

Vascular phenotype in angiogenic and non-angiogenic lung non-small cell carcinomas

We have previously described a group of non-small cell lung carcinomas without morphological evidence of neo-angiogenesis. In these tumours neoplastic cells fill up the alveoli and the only vessels present appear to belong to the trapped alveolar septa. In the present study we have characterised the phenotype of the vessels present in these non-angiogenic tumours, in normal lung and in angiogenic non-small cell lung carcinomas. The vessels, identified by the expression of CD31, were scored as mature when expressing the epitope LH39 in the basal membrane and as newly formed when expressing αVβ3 on the endothelial cells and/or lacking LH39 expression. In the nine putative non-angiogenic cases examined, the vascular phenotype of all the vessels was the same as that of alveolar vessels in normal lung: LH39 positive and αVβ3 variable or negative. Instead in 104 angiogenic tumours examined, only a minority of vessels (mean 13.1%; range 0–60%) expressed LH39, while αVβ3 (in 45 cases) was strongly expressed on many vessels (mean 55.5%; range 5–90%). We conclude that in putative non-angiogenic tumours the vascular phenotype is that of normal vessels and there is no neo-angiogenesis. This type of cancer may be resistant to some anti-angiogenic therapy and different strategies need to be developed

Increase in perceived case suspiciousness due to local contrast optimisation in digital screening mammography

Item does not contain fulltextOBJECTIVES: To determine the influence of local contrast optimisation on diagnostic accuracy and perceived suspiciousness of digital screening mammograms. METHODS: Data were collected from a screening region in the Netherlands and consisted of 263 digital screening cases (153 recalled,110 normal). Each case was available twice, once processed with a tissue equalisation (TE) algorithm and once with local contrast optimisation (PV). All cases had digitised previous mammograms. For both algorithms, the probability of malignancy of each finding was scored independently by six screening radiologists. Perceived case suspiciousness was defined as the highest probability of malignancy of all findings of a radiologist within a case. Differences in diagnostic accuracy of the processing algorithms were analysed by comparing the areas under the receiver operating characteristic curves (A(z)). Differences in perceived case suspiciousness were analysed using sign tests. RESULTS: There was no significant difference in A(z) (TE: 0.909, PV 0.917, P = 0.46). For all radiologists, perceived case suspiciousness using PV was higher than using TE more often than vice versa (ratio: 1.14-2.12). This was significant (P <0.0083) for four radiologists. CONCLUSIONS: Optimisation of local contrast by image processing may increase perceived case suspiciousness, while diagnostic accuracy may remain similar. KEY POINTS: Variations among different image processing algorithms for digital screening mammography are large. Current algorithms still aim for optimal local contrast with a low dynamic range. Although optimisation of contrast may increase sensitivity, diagnostic accuracy is probably unchanged. Increased local contrast may render both normal and abnormal structures more conspicuous.1 april 201

Pre-operative chemotherapy in early stage resectable non-small-cell lung cancer: a randomized feasibility study justifying a multicentre phase III trial

Surgical resection offers the best chance for cure for early stage non-small-cell lung cancer (NSCLC, stage I, II, IIIA), but the 5-year survival rates are only moderate, with systemic relapse being the major cause of death. Pre-operative (neo-adjuvant) chemotherapy has shown promise in small trials restricted to stage IIIA patients. We believe similar trials are now appropriate in all stages of operable lung cancer. A feasibility study was performed in 22 patients with early stage (IB, II, IIIA) resectable NSCLC; randomized to either three cycles of chemotherapy [mitomycin-C 8 mg m−2, vinblastine 6 mg m−2 and cisplatin 50 mg m−2 (MVP)] followed by surgery (n = 11), or to surgery alone. Of 40 eligible patients, 22 agreed to participate (feasibility 55%) and all complied with the full treatment schedule. All symptomatic patients achieved either complete (50%) or partial (50%) relief of tumour-related symptoms with pre-operative chemotherapy. Fifty-five per cent achieved objective tumour response, and a further 27% minor tumour shrinkage; none had progressive disease. Partial pathological response was seen in 50%. No severe (WHO grade III–IV) toxicities occurred. No significant deterioration in quality of life was detected during chemotherapy. Pre-operative MVP chemotherapy is feasible in early stage NSCLC, and this study has now been initiated as a UK-wide Medical Research Council phase III trial. © 1999 Cancer Research Campaig