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Tobacco control- What is important for oncologists to know?

Although there is often little cross-talk between advocacy based tobacco control and the basic and clinical science of the treatment of lung cancer, it is critical that both are aware of developments in each other’s area of expertise, said Carolyn Dresler of the Tobacco Prevention and Cessation Program, Arkansas Department of Health, Little Rock/USA during the Keynote lecture. As various countries implement regulations that limit or eliminate certain constituents, such as nitrosamines, there will be changes in the epidemiology of the growing proportion of adenocarcinomas and related biomarkers associated with adenocarcinomas. Similarly, knowledge of such changes may impact both treatment and the studies performed to determine appropriate treatment for the potentially shifting proportions of histologic types of lung cancer.

Novel therapeutic agents

Today, a specific session focused on the determination of new pathways in the pathogenesis of lung cancer as therapeutic targets and detailed mechanisms of action for new agents. The first presentation featured targeting the M-phase with particular emphasis on PLK-1 and Aurora B inhibitors presented by Flavio Solca of the Department of Pharmacology, Boehringer-Ingelheim, Vienna, Austria; the program then focused on Gli inhibitors/Hedgehog pathway inhibitors presented by David Jablons of the Thoracic Surgery, UCSF Helen Diller Family, San Francisco, USA; foretinib - a multikinase AXL/MET inhibitor was covered by Li Liu of the Translational Research, GlaxoSmithKline, King of Prussia, USA; and targeting ALK-rearranged non-small cell lung carcinoma by John Lafrate of the Department of Pathology, Massachusetts General Hospital, Boston, USA.

Consequences of the new staging system

The new system proposed by the IASLC staging project has introduced multiple changes in the TNM classification of lung cancer, taking into account tumour size in the T descriptors, site of other lung nodules, introduction of a new M1 category and a better grouping of the TNM subsets, proposing a new thoracic lymph node map, extending its application to histological types other than non-small cell lung cancer (small cell lung cancer, carcinoid tumours). All those changes have practical operational and prognostic consequences, about which Jean-Paul Sculier of the Institut Jules Bordet, Brussels, Belgium spoke today.

CXCR4 over-expression by immunohistochemistry heralds poor outcome in metastatic NSCLC

Between 2003-2006, Gwyn Bebb and colleagues of the Tom Baker Cancer Centre and University of Calgary, Canada, identified 832 patients diagnosed with stage IV NSCLC, and with 303 tissue samples available, 200 suitable for tissue array generation. Automated immunohistochemistry for CXCR4 was successfully completed on the tester cohort of 103 patients. High expressers (10.7% of the tested stage IV patients) had a significantly poorer clinical outcome with a median overall survival of 2.7 months vs. 6.1 months for the low expressers (P=0.0001). CXCR4 over-expression was associated with squamous histology, smoking history and a higher rate of brain metastases. These results suggest that novel therapeutic strategies, possibly involving anti-CXCR4 drugs, should be tested in CXCR4 over-expressers.

Lung volume reduction surgery in patients with lung carcinoma

Lung cancer surgery in selected high-risk patients with very severe emphysema and impaired lung function is feasible and safe in an experienced centre. The in hospital mortality is low, the postoperative lung function may be improved and the 5-years survival is acceptable, according to multi-institutional Swiss experience in patients with marginal lung function who underwent resection of preoperatively detected lesions. Results were presented today by Michaela Tutic of the Department of Thoracic Surgery, University Hospital Zurich, Switzerland.

Radiological and clinical pneumonitis after stereotactic lung radiotherapy

Lung fibrosis is common after stereotactic body radiotherapy (SBRT) for lung tumours, but the influence of treatment technique on rates of clinical and radiological pneumonitis is not well-described. After implementing volumetric modulated arc therapy for SBRT, David Palma of the Radiation Oncology, VU University Medical Center, Amsterdam, Netherlands compared the early pulmonary changes seen with arc vs. conventional 3-dimensional SBRT (3D-CRT). Twenty-five SBRT patients treated with volumetric modulated arc therapy were matched with fifty SBRT patients treated with 3D-CRT. The investigators did not observe differences in clinical or radiological findings 3 months after therapy and data with longer follow-up is awaited to exclude late changes.

Advantages and limitations of different imaging techniques used in chest imaging

There is a growing body of knowledge that practising oncologists should know about regarding imaging. Measurement of lung tumours is important for staging and follow-up. Especially in the new lung cancer system, tumour size has become a major descriptor in T staging. During the state-of-the-art session on imaging, Walter De Wever of the Department of Radiology, University Hospitals Leuven, Belgium spoke about how to measure T status from the perspective of different imaging techniques and methods. Oliver Lucidarme of the Service de Radiologie Centrale, Groupe Hospitalier Pitié Salpêtrière, Paris, France featured new non-invasive imaging techniques in lung cancer and Johan Vansteenkiste of the Respiratory Oncology Unit, University Hospital Gasthuisberg, Leuven, Belgium discussed how PET–CT should influence decision making.

Serum proteomic prediction of outcomes in advanced NSCLC patients treated with erlotinib/placebo in the NCIC Clinical Trials Group BR.21 trial

The study team led by David Carbone of the Vanderbilt-Ingram Comprehensive Cancer Center, Nashville, USA analysed blinded baseline plasma samples available from 441 patients included in the BR.21 study. This trial has demonstrated survival benefit of erlotinib compared to placebo in previously treated patients with NSCLC. Results of the serum proteomic study are presented at the Proffered Papers Session today; proteomics ‘good’ patients achieved a significantly higher response rate than proteomics ‘poor’ patients (P=0.002). Importantly, with the serum test, 99% of patients had a successful determination of proteomic status, while only about 28% had successful EGFR sequencing, and 22% had successful FISH determinations. FISH overall was a better predictor of benefit, but can only be done with adequate biopsy tissue, so this proteomic test may be of particular value for those in whom tumour tissue is inadequate or unavailable.

Different KRAS mutations may predict a different impact on drug activity in NSCLC

Marina Garassino of the Department of Oncology, Fatebenefratelli and Ophtalmic Hospital, Milano, Italy presented results of the TAILOR (NCT00637910), a multicenter Italian phase III trial powered to evaluate a differential effect of all biological markers in selecting patients for erlotinib and docetaxel as second line therapy in patients with NSCLC. KRAS and EGFR mutational status were available from 161 of 256 patients registered into the trial. The investigators found six types of KRAS mutation in 35 patients (20%). Specific mutational status of KRAS gene in NSCLC seems to differ from that reported for colorectal cancer; this clinical observation, together with in vitro results which suggest different patterns of sensitivity/resistance to EGFR inhibition in transfected cell lines, might explain the ambiguous role of KRAS as a predictor to anti-EGFR therapy in NSCLC.

Analysis of biomarkers in the AVAiL phase III randomised study of first-line bevacizumab with cisplatin-gemcitabine in NSCLC patients

The exploratory analysis conducted by Martin Reck of the Department of Thoracic Oncology, Hospital Grosshansdorf, Germany as lead investigator shows that biomarkers involved in angiogenic pathways may play a prognostic role in patients with advanced NSCLC. Baseline plasma samples of patients included in the AVAiL trial were collected and analysed for vascular endothelial growth factor (VEGF), intracellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), E-selectin and basic fibroblast growth factor (bFGF). Samples were available for 358 patients. High baseline levels of these markers were associated with a shorter overall survival (OS) compared with low levels. When comparing progression-free survival between the 15mg/kg of bevacizumab and placebo arms, a trend towards a larger treatment effect was observed in patients with low ICAM-1 levels; comparing OS between the 7.5mg/kg of bevacizumab and placebo arms, a trend towards a larger treatment effect was observed in patients with high bFGF levels.

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