Prognostic value of the DNA integrity index in patients with malignant lung tumors.

INTRODUCTION: Lung cancer survival remains poor in the western world due to late presentation in most cases, leading to difficulty of treatment in these advanced and metastatic patients. Therefore, the development of a robust biomarker for prognosis and to monitor treatment response and relapse would be of great benefit. The use of Alu repeats and DNA Integrity Index has been shown to hold both diagnostic and prognostic value, and as it is obtained from the plasma of patients, it can serve as a non-invasive tool for routine monitoring. This study evaluates the efficiency of this technique in malignant lung cancer patients. METHODS: Plasma samples were collected from 48 patients, consisting of 29 lung cancer patients and 19 non-cancer controls. Alu repeat ratio and confounders were measured. RESULTS: Observations showed a higher Alu repeat ratio amongst the cancer group compared to controls (p=0.035), mean Alu ratio 0.38 (range 0.01-0.93) and 0.22 (0.007-0.44) respectively, ROC curve analysis AUC 0.61 (p=0.22). Analysis by staging was more promising, whereby a higher DNA Integrity Index was seen in advanced cases compared to both early stage and controls, p<0.0001; AUC: 0.92 (P=0.0002) and p=0.0006, AUC - 0.88 (p=0.0007) respectively, however no significant difference was observed in the early stage compared to controls. Short term survival data also showed a DNA Integrity Index of >0.5 to be associated with poorer overall survival p=0.03. CONCLUSION: The results of this study show a potential use of Alu repeats ratios for prognostic purposes in the advanced setting for lung cancer patients.

Perioperative detection of circulating tumour cells in patients with lung cancer.

Lung cancer is a leading cause of mortality and despite surgical resection a proportion of patients may develop metastatic spread. The detection of circulating tumour cells (CTCs) may allow for improved prediction of metastatic spread and survival. The current study evaluates the efficacy of the ScreenCell® filtration device, to capture, isolate and propagate CTCs in patients with primary lung cancer. Prior to assessment of CTCs, the present study detected cancer cells in a proof-of-principle- experiment using A549 human lung carcinoma cells as a model. Ten patients (five males and five females) with pathologically diagnosed primary non-small cell lung cancer undergoing surgical resection, had their blood tested for CTCs. Samples were taken from a peripheral vessel at the baseline, from the pulmonary vein draining the lobe containing the tumour immediately prior to division, a further central sample was taken following completion of the resection, and a final peripheral sample was taken three days post-resection. A significant increase in CTCs was observed from baseline levels following lung manipulation. No association was able to be made between increased levels of circulating tumour cells and survival or the development of metastatic deposits. Manipulation of the lung during surgical resection for non-small cell lung carcinoma results in a temporarily increased level of CTCs; however, no clinical impact for this increase was observed. Overall, the study suggests the ScreenCell® device has the potential to be used as a CTC isolation tool, following further work, adaptations and improvements to the technology and validation of results.

Detection of Circulating Tumour Cells and Survival of Patients with Non-small Cell Lung Cancer.

BACKGROUND: Detection of circulating tumour cells (CTCs) in the peripheral blood of lung cancer patients may predict survival. Various platforms exist that allow capture of these cells for further analysis; little work however, has been done with the ScreenCell device, an antibody-independent CTC platform. The aim of our study was to evaluate the ScreenCell device for detection of CTCs in lung cancer patients and to establish correlations of these findings with survival. MATERIALS AND METHODS: Twenty-three patients, nine males, and fourteen females, underwent surgical treatment from February to May 2014 for non-small cell lung cancer. Thirteen patients had adenocarcinoma and ten squamous cell carcinoma, while eight were at an early stage (I-II) and five at a later stage (III-IV). Blood samples were obtained prior to surgery and following filtration through the ScreenCell device, were independently reviewed by 2 consultant pathologists. RESULTS: The pathologists were able to independently identify CTCs in 78.3% (N=18) and 73.9% (N=17) of the cases examined, with overall 80.6% in early stages compared to 60.0% in late stages. The median survival times of positive vs. negative for CTC patients were 1011 and 711 days respectively, with a survival percentage rate of 77.8% and 60% in positive and negative CTC cohorts respectively. CONCLUSION: The results of this study suggest that the presence of CTCs analyzed by ScreenCell did not necessarily lead to a poorer prognosis in patients with lung cancer after curative surgery.

Endoluminal cryotherapy in the management of endobronchial metastatic tumors of extrapulmonary origin.

BACKGROUND: Endobronchial metastases from extrapulmonary tumors are rare and often cause significant symptoms particularly when they present within the main bronchial tree. Cryotherapy has been shown to be effective in the treatment of primary malignancies of the endobronchial tree. This is the first detailed analysis of the application of cryotherapy to endobronchial metastatic tumors of extrapulmonary origin. This study assessed the role of endobronchial cryotherapy in the management of these patients, including control of symptoms and improvement in endobronchial patency. METHODS: The details of 35 patients treated over a 17-year period were reviewed. Patients' ages ranged from 22 to 80 years. The primary tumors were mainly colorectal and renal. RESULTS: There were no perioperative or in-patient deaths. Endobronchial cryotherapy was carried out as a day-case procedure in over 80% of cases. Of the 35 patients, 30 (85%) reported a significant improvement in their main presenting symptom. In over half the patients, endoluminal patency was increased by ≥50% following 1 treatment of cryotherapy. Survival ranged from 10 days to 4 years 8 months, with a median survival of 34 weeks. One-year survival was 37.5%. CONCLUSIONS: Endoluminal cryotherapy gives rapid resolution of symptoms and can be carried out as a day-case procedure in the vast majority of patients. We recommend that cryotherapy should be considered as a first-line palliation in patients with symptomatic metastases to the endobronchial tree.