AR: Lung cancer imaging in the era of molecular medicine
Molecular imaging will play a key role in the evaluation and assessment of patients with lung cancer, and radiologists need to be familiar with the molecular elements of the disease, according to a review published in the April issue of Academic Radiology.

The authors reviewed molecular mechanisms of lung cancer, beginning with the role of epidermal growth factor receptor (EGFR) in non-small-cell lung cancer (NSCLC). Specifically, “overexpression of EGFR is frequently noted in the development and progression of NSCLC, and its presence is associated with shortened survival,” wrote Mizuki Nishino, MD, from the department of imaging at Dana-Farber Cancer Institute in Boston. The researchers pointed to the link between sensitizing mutation in EGFR and clinical response and prolonged time to progression among NSCLC patients treated with gefitinib and erlotinib.

They also considered rat sarcoma (RAS) mutations; KRAS mutations, which are smoking related, are associated with poor prognosis among lung anedocarcinomas, wrote Nishino.

The authors pointed out that most NSCLC patients with EGFR mutations who initially respond to gefitinib (Iressa, AstraZeneca) and erlotinib (Tarceva, Genentech) develop tumor progession because of acquired resistance, with molecular mechanisms playing a part in the development of resistance. “An accurate radiologic method for response assessment and definition of radiographic criteria for clinical response are needed to define the correct time for therapy change,” according to Nishino and colleagues.

The role of histology is likely to evolve in the molecular medicine era with conventional classifications of patients with NSCLC and small cell lung cancer being stratified into subgroups based on genomic mutation testing and genomic characterization. Histology, posed the authors, will be employed to select genomic testing and treatments.

In fact, a recent study conducted by Ding et al identified more than 1,000 somatic mutations and hinted at the potential of new molecular targets for treatment. “With extensive genomic analysis and the identification of more targetable genomic abnormalities in lung cancer and the concordant development of agents directed against these changes, more patients will likely be treated by agents targeting the abnormalities specific to the tumor,” according to Nishino and colleagues.

Similarly, conventional methods of assessing response to therapy based on size measurement and an assumption of uniform or symmetrical changes in tumor volume need to be refined. For example, computer-assisted volume measurement may offer a more precise method for calculating tumor burden and further defining patients’ response to therapy.

Nishino and colleagues referred to promising early studies of DCE MRI in lung cancer imaging, indicating its potential for response assessment to chemotherapy and targeted therapy. Similarly, 18F-FDG PET could allow physicians to predict response to therapy at one and three weeks following chemotherapy initiation, offered the researchers. This has led at least one expert to propose a revised monitoring criteria, Positron Emission Tomography Response Criteria in Solid Tumors (PERCIST), which bolsters anatomic therapy response platforms.  Moreover, newer tracers like fluoride-18-fluorothymidine (FLT) also may play a role in response assessment, offered Nishino and colleagues.

Finally, the authors noted the potential of multiparametric quantitative and functional imaging techniques for assessing response to therapy.

Nishino and colleagues concluded by stressing the importance of developing an understanding of the molecular basis of lung cancer and the critical role of advanced imaging in the characterization of lung cancer and assessment of the disease before, during and after treatment.