American Cancer Society; Centers for Disease Control and Prevention; Swiss Re; Swiss Cancer Research foundation; Swiss Cancer League; Institut National du Cancer; La Ligue Contre le Cancer; Rossy Family Foundation; US National Cancer Institute; and the Susan G Komen Foundation.

The distribution of ovarian cancer histology varies widely worldwide. Type I epithelial, germ cell and sex cord-stromal tumours are generally associated with higher survival than type II tumours, so the proportion of these tumours may influence survival estimates for all ovarian cancers combined. The distribution of histological groups should be considered when comparing survival between countries and regions.

Large-scale EGFR testing in the blood of unselected advanced NSCLC patients is feasible and can be used to select patients for targeted therapy when testing cannot be done in tissue. The characteristics and clinical outcomes to TKI treatment of the EGFR-mutated patients identified are undistinguishable from those positive in tumor.

Liquid biopsy analyses are already incorporated in the routine clinical practice in many hospitals and oncology departments worldwide, improving the selection of treatments and monitoring of lung cancer patients. Although they have not yet reached its full potential, liquid biopsy-based tests will soon be as widespread as “standard” biopsies and imaging techniques, offering invaluable diagnostic, prognostic, and predictive information. This review summarizes the techniques available for the isolation and analysis of circulating free DNA and RNA, exosomes, tumor-educated platelets, and circulating tumor cells from the blood of cancer patients, presents the methodological challenges associated with each of these materials, and discusses the clinical applications of liquid biopsy testing in lung cancer.

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Fusion of the anaplastic lymphoma receptor tyrosine kinase gene (ALK) with the echinoderm microtubule-associated protein 4 gene (EML4) is the second most common actionable alteration in non-small-cell lung cancer, with a frequency of 5%. Here, we present a case of an EML4-ALK-positive patient with an atypical in-frame insertion from the LTBP1 gene in the canonical junction of variant 1. The patient was a 39-year-old never-smoker female diagnosed with Stage IV lung adenocarcinoma. A core biopsy was negative for EGFR and KRAS mutations but positive for ALK immunohistochemistry and fluorescence in situ hybridization. When submitted to nCounter, the sample showed a 3′/5′ imbalance indicative of an ALK rearrangement, but failed to give a positive signal for any of the variants tested. Finally, a band with a molecular weight higher than expected appeared after reverse transcriptase-polymerase chain reaction analysis. When Sanger sequencing was performed, the band revealed an atypical EML4-ALK fusion gene with an in-frame 129 bp insertion. A 115 bp segment of the insertion corresponded to an intronic region of LTBP1, a gene located in the short arm of chromosome 2, between ALK and EML4. The patient received crizotinib and showed a good therapeutic response that is still ongoing after 12 months. Our result suggests that short in-frame insertions of other genes in the EML4-ALK junction do not affect the sensitivity of the EML4-ALK fusion protein to crizotinib.

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Background: Circulating epithelial tumor cells (CTCs) in peripheral blood are an ideal source for the detection of disseminated tumor cells of an easy sampling procedure. Their prognosis significance has been demonstrated in metastasic breast carcinoma and have potencial to influence the clinical management for pts. with breast cancer (Cristofanilli, NEJM 2004). The antiangiogenic agent bevacizumab (Bev.), in combination with CT, improves progression free survival (PFS) of first line treatments, may modify tumor cell intravasation and CTC count, and may change CEC levels. Aims of this study are the evaluation of the prevalence and kinetics of CTCs and CECs before and after antiangiogenic treatment with Bev in pts with metastatic breast cancer. Methods: Eligible pts. received Bev (10mg/kg q2w) combined with paclitaxel 150 mg/m2 and gemcitabine 2000mg/m2 d 1 y 15 q28d as first line therapy, until disease progression, unacceptable toxicity or withdrawal. For pts. participating in the sub-study, CTC and CEC were measured in 7.5ml of blood at baseline and after the first cycle of treatment. Samples were subjected to imnumomagnetic enrichment with an anti-EpCAM antibody and fluorescence labelled. CTCs were defined as nucleated cells (DAPI+) expressing cytokeratin 8, 18 and 19 but CD45 negative phenotype. CECs were defined as nuclear cells (DAPI+) expressing CD105 PE and CD45 negative phenotype. A sample was considered positive when 1 or more cells were detected. Results: Data are available for 37 pts. We found ≥1 CTCs before first cycle of treatment with bev in 73% of the patients (N=27). After first treatment, reduction of CTCs was found in 57% of the patients (N=16). The median number of CTCs was 34 cells/7.5 ml (min 0-max 845) of blood in the first determination and 4.79 cells/7.5 ml (min 0-max 99) in the second determination, p=0.0075. In 38% of the pts (N=14) we found ≥5 baseline CTCs and after treatment <5 CTCs were found in 89% of the pts (N=25). In 70% of pts with baseline ≥5 CTCs count, a reduction to < 5CTCs was observed in the second determination (N=10), p=0.20 (IC 34.15-93.33). In 10 pts we found CTCs=0 baseline value (35%) and in the second determination after treatment CTCs=0 cells/7.5 ml was observed in 53%, p=0.058. Baseline CECs ≥1 was observed in 100% of the pts (N=31). After first cycle of treatment with bev plus CT CECs=0 was found in 1 patient (3.4%). In 70% of pts (N=14) there was a reduction of baseline CECs count, p=0.3. The median value of baseline CECs was 123 cells/7.5 ml (min 4- max 1407) and the median value in second determination was 54 cells/7.5 ml (min 0-max 349). The median of reduction of CECs after treatment was 70 CECs, p=0.02. Conclusions: The addiction of bev to 1st line CT was related with high reduction of the value of baseline CTCs and CECs count, statistically significant correlation. Reduction to < 5 CTCs of patients with baseline ≥5 CTCs (unfavourable prognosis) was observed in 70% of patients. The results of this explorative study are preliminary and a large number of pts and follow-up is required. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P3-02-11.