This study shows that higher levels of free circulating DNA can be detected in patients with lung cancer compared with disease-free heavy smokers by a PCR assay, and suggests a new, noninvasive approach for early detection of lung cancer. Levels of plasma DNA could also identify higher-risk individuals for lung cancer screening and chemoprevention trials.

Key words: lung cancer; early detection; genetic markers; p53; FHITLung cancer is one of the leading causes of cancer mortality in the world, especially in developed countries. 1 A major problem in lung cancer is the lack of clinically efficient noninvasive methods for early detection and screening of asymptomatic high-risk individuals.In the past, the most common screening techniques, such as chest radiography and sputum cytology, were unable to reduce the mortality. 2 Recent results achieved by spiral CT have opened new prospects for significant reduction of lung cancer mortality but proper selection of high-risk population and differential diagnosis are critical elements. 3 In fact, even though for stage I lung cancer patients surgical resection can achieve a 60 -70% 5-year survival, over 70% of cases are detected in stage II-IV patients where survival is poor. 4 Thus, the development of novel molecular methodologies is needed to facilitate early detection of lung cancer. Lung cancer is associated with a variety of genetic alterations, including p53 5 and K-ras mutations, 6 inactivation of the fragile histidine triad (FHIT) gene, 7,8 allelic imbalances at multiple chromosomal loci 9,10 and aberrant promoter methylation of several genes, mainly p16 INK4a . 11 Most of these changes have also been described in premalignant lesions and early phases of lung carcinogenesis. 12 The use of sensitive molecular techniques has enabled the detection in the plasma of lung cancer patients of the same genetic alterations observed in their tumors. [13][14][15] In addition, several studies have demonstrated the presence of significantly higher concentrations of circulating DNA in the plasma/serum in patients with different types of cancer, 16 -19 including primary or recurrent lung cancer. 20 Thus, quantification of plasma DNA and characterization of specific molecular changes could represent useful biomarkers of lung cancer. In an attempt to validate a grid of molecular genetic markers detectable in plasma DNA of lung cancer patients, we analyzed a series of 64 patients with stage I-III non small cell lung cancer (NSCLC), focusing our attention on 3 very common alterations: p53, FHIT and allelic imbalances affecting other 4 loci on 3p. The ultimate goal of the study was the validation of molecular approaches that might be useful for an effective early detection and monitoring of NSCLC. MATERIAL AND METHODS Pathologic and immunohistochemical methodsClinical and pathologic data are illustrated in Table I. There were 38 squamous cell carcinomas, 19 adenocarcinomas, 5 large cell carcinomas, and 2 non small cell carcinomas not further defined. Stage I accounted for 45%, stage II for 27% and stage III for 28% of the tumors. For immunohistochemical analysis, formalin-fixed and paraffin-embedded samples obtained at surgery were investigated for p53 and Fhit markers according to previously refined methods. 21 All cases were evaluated blindly without knowledge of the patients' identity, pathologic diagnosis, clinical outcome or plasm...

PET scan proved to be a valuable staging procedure in patients with clinically resectable lung metastasis and changed the therapeutic management in a high proportion of cases.

Neoangiogenesis and enhanced glucose metabolism in neoplasms are likely to be activated by the same biochemical stimulus; hypoxia. A correlation between these two parameters has been postulated. The objective of this study was to evaluate the relationship between Fluoro-desoxi-glucose uptake at positron emission tomography scan and angiogenesis in lung metastasis. Fluoro-desoxi-glucose activity, expressed as a standard uptake value, and microvessel intratumoural density, were retrospectively calculated in a series of 43 lung metastasis resected in 19 patients. Primary sites were colorectal cancer in 16 metastases, sarcoma in eight, gynaecological in four and other sites in 15. The correlation between the two parameters was tested by logistic regression and multivariate analysis. Positron emission tomography scan was positive in 17 patients (sensitivity 89%). No correlation was observed between standard uptake value and microvessel intratumoural density in this series of lung metastasis. Positron emission tomography negative and positive nodules presented comparable value of microvessel intratumoural density (12.9 vs 11.3). Standard uptake value was significantly correlated with nodules size and was higher in colon cancer metastasis than in sarcoma ones. Microvessel intratumoural density was independent from nodule size but significantly higher in sarcoma than in colon cancer metastasis. The lack of correlation was confirmed by multivariate analysis after adjustment for tumour type and nodules size. The present study demonstrated that positron emission tomography scan is positive in a high proportion of patients regardless of microvessel density. Glucose uptake and angiogenesis appear to be independent biological features in lung metastasis. This observation may have implications for future antiangiogenic therapies.

e17018 Background: The biochemical recurrence (BCR) criteria are different depending on the primary tumour treatment: PSA ≥0.2 ng/mL after radical prostatectomy (RP) and PSA ≥ 2 ng/mL above the nadir after radiotherapy (RT)[Phoenix criteria]. The latter was established based on the detection of metastasis by conventional imaging tests (CT and bone scanning). Next generation imaging (NGI) techniques (18F-choline PET/CT and specially 18F-PSMA PET/CT), allow detection of metastasis with PSA values much lower than the Phoenix criteria. The purpose of this study is to compare the profile of patients diagnosed with metastatic hormone sensitive prostate cancer (mHSPC) by NGI techniques after BCR according to the primary tumour treatment performed. Methods: Patients diagnosed with mHSPC in our Radiation Oncology Department after BCR between February 2021 and December 2022 were reviewed. All of them underwent NGI: 18F-choline PET/CT if there was BCR following RT or a PSA level > 2 ng/ml after PTR; 18F-PSMA PET/CT if there was BCR after PTR or if 18F-choline PET/CT offered diagnostic uncertainties. Then, were stratified according to primary treatment: PTR (+/- salvage RT to the prostatic bed) vs RT (external or brachytherapy). PSA levels prior to NGI, number of metastases (≤5: oligometastatic vs > 5: polymetastatic) and their location (M1a: exclusive lymph node metastasis, M1b: presence of bone metastasis and M1c: presence of visceral metastasis) were compared. Results: A total of 38 patients were idiagnosed with mHSPC: 42.1% after PTR and 57.9% after RT. PTR group had PSA levels prior to NGI of 1.08 ng/ml, of which 75% were 18F-PSMA PET/CT. Twenty-five per cent of patients in this group were classified as polymetastatic. In RT group the median PSA levels prior to NGI was 3.5 ng/ml, of which 68.2% were 18F-choline PET/CT. The proportion of polymetastatic patients was 50%. The location of metastases in PTR and RT group was: M1a (68.8% vs 59.1%), M1b (31.3% vs 36.4%) and M1c (0% vs 4.5%). Conclusions: The percentage of polymetastatic patients in RT group is double that of PTR group, which is a worse prognostic factor. (4). This difference in the number of metastases is due to the higher PSA levels prior to NGI in RT group, which is directly related to the definition established by the Phoenix criteria(3). Given that NGI techniques can detect metastases with PSA values below the Phoenix criteria, it would be reasonable to redefine it in order to reduce the percentage of polymetastatic patients through earlier detection and thus improve their prognosis.