Korean J Radiol.  2017 Feb;18(1):6-17. 10.3348/kjr.2017.18.1.6.

Evolving Cancer Classification in the Era of Personalized Medicine: A Primer for Radiologists

• O'Neill AC
• Jagannathan JP
• Ramaiya NH

• KMID: 2468118
• DOI: http://doi.org/10.3348/kjr.2017.18.1.6

Abstract

Traditionally tumors were classified based on anatomic location but now specific genetic mutations in cancers are leading to treatment of tumors with molecular targeted therapies. This has led to a paradigm shift in the classification and treatment of cancer. Tumors treated with molecular targeted therapies often show morphological changes rather than change in size and are associated with class specific and drug specific toxicities, different from those encountered with conventional chemotherapeutic agents. It is important for the radiologists to be familiar with the new cancer classification and the various treatment strategies employed, in order to effectively communicate and participate in the multi-disciplinary care. In this paper we will focus on lung cancer as a prototype of the new molecular classification.

Keyword

Lung cancer; NSCLC; Adenocarcinoma; EGFR mutation; ALK rearrangement

MeSH Terms

Antineoplastic Agents/therapeutic use
Carcinoma, Non-Small-Cell Lung/*classification/diagnostic imaging/drug therapy/genetics
Humans
Lung Neoplasms/*classification/diagnostic imaging/drug therapy/genetics
Molecular Targeted Therapy/methods
Mutation
Precision Medicine/*methods
Receptor Protein-Tyrosine Kinases/genetics
Receptor, Epidermal Growth Factor/genetics
Tomography, X-Ray Computed
Antineoplastic Agents
Receptor Protein-Tyrosine Kinases
Receptor, Epidermal Growth Factor

Figure

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  Fig. 1 Timeline of events in lung cancer molecular targeted therapies. ALK = anaplastic lymphoma kinase, EGFR = epidermal growth factor receptor, FDA = Food and Drug Administration

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  Fig. 2 Pie chart demonstrating percentage of driver alterations in lung adenocarcinoma. Adapted from Sholl et al. J Thorac Oncol 2015;10:768-777 (2). ALK = anaplastic lymphoma kinase, EGFR = epidermal growth factor receptor

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  Fig. 3 Axial contrast enhanced CT on soft tissue windows at four different time points in 57-year-old woman with EGFR exon 19 deletion lung adenocarcinoma. A. Initial image demonstrates large right upper lobe mass (arrow). B. Second image demonstrates response to first generation EGFR TKI (erlotinib) after 3 months with significant decrease in size of mass (arrow). C. Third image was performed 6 months later demonstrates further decrease in size of right upper lobe mass (arrow). D. Final image demonstrates gradual increase in size (arrow). Biopsy demonstrated T790M mutation that has known resistance to EGFR TKI (erlotinib) therapy. EGFR = epidermal growth factor receptor, TKI = tyrosine kinase inhibitor

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  Fig. 4 Axial CECT on lung windows in 53-year-old woman with L8585R point mutation in exon 21 adenocarcinoma. Patient had been treated with EGFR tyrosine kinase inhibitor (erlotinib) for 11 months but was progressing on serial CT studies. Initial CT (A) demonstrates multiple small right-sided pulmonary metastases and almost confluent opacification in left lung. Patient was taken off therapy and CT performed two weeks later due to patients dyspnea demonstrates now complete opacification in left hemithorax and interval increase in size in right sided pulmonary metastases, several had doubled in size (B). Appearances and clinical presentation were consistent with ‘flare’ phenomenon. CECT = contrast enhanced CT, EGFR = epidermal growth factor receptor

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  Fig. 5 Axial CECT on lung windows in 68-year-old woman with exon 19 EGFR mutant adenocarcinoma. A. Patient had dominant masses in right and left lower lobes (arrows) on initial CT. Patient was treated with EGFR tyrosine kinase inhibitor (erlotinib) and follow up CT performed 2 months later (B) demonstrates decrease in size of lower lobe masses (arrows). C. Patient also had developed multifocal faint bilateral subpleural ground glass changes (arrowheads) consistent with pneumonitis. Patient was asymptomatic and remained on treatment with changes on pneumonitis resolving on follow up studies. CECT = contrast enhanced CT, EGFR = epidermal growth factor receptor

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  Fig. 6 Axial contrast enhanced CT of thorax on lung windows (A, B) and axial T1 post gadolinium contrast MRI of brain (C) in 40-year-old man with metastatic lung adenocarcinoma with ALK rearrangement. On initial CT (A) patient has 2.5 × 2.3 cm mass in left upper lobe (arrow). Patient was treated with first generation ALK tyrosine kinase inhibitor (crizotinib) and had durable response in his lungs with second CT (B) post 5 year of treatment demonstrating small 1.2 × 0.6 cm ill-defined nodule at site of primary dominant mass (arrow). Patient unfortunately developed brain metastases due to poor blood brain barrier penetration with ALK inhibitor (crizotinib) and MRI (C) demonstrates ring enhancing 1.0 cm metastasis in right occipital lobe (arrowhead). ALK = anaplastic lymphoma kinase

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  Fig. 7 Axial contrast enhanced CT on soft tissue (A, B) and lung windows (C) in 38-year-old man lifelong non smoker with metastatic ALK rearranged lung adenocarcinoma. A, B. Initial CT demonstrates extensive left pleural nodularity and circumferential thickening with example of pleural thickening in left lower lobe included (arrows). C. Follow up performed 8 weeks after treatment with alectinib (second generation ALK inhibitor) demonstrated decrease in left pleural metastatic disease but interval development of new right lower lobe ground glass changes (arrowheads) consistent with pneumonitis. Patient was not symptomatic and therapy was continued. ALK = anaplastic lymphoma kinase

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  Fig. 8 Axial (A–D) and coronal enhanced (E, F) CT in 58-year-old woman with metastatic lung adenocarcinoma with ALK rearrangement. A, B. Initial CT demonstrates post obstructive atelectasis in left upper lobe from left hilar lymphadenopathy (not shown) and bilateral lung metastases, largest in left upper lobe measuring 1.3 x 1.3 cm (arrow) and in right lower lobe (arrow) measuring 1.6 × 1.4 cm. Patient was treated with crizotinib and follow up CT performed after 8 weeks of therapy (C, D) demonstrates response with resolution of metastases with only mild ground glass changes at site of dominant masses. E, F. Coronal CT demonstrates complication of crizotinib therapy with development of osteopenia best seen on CT as decreased sclerosis after 2 years of therapy within blastic bone metastasis (arrow). ALK = anaplastic lymphoma kinase

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  Fig. 9 Axial CECT at floor of mouth in 58-year-old man with EGFR mutant squamous cell carcinoma of tongue. A. Patient had been treated with right sided hemiglossectomy but developed large enhancing mass in surgical site on right (arrow) and level IIa low density left cervical chain lymph node (arrowhead) on CT. B. Patient was treated with EGFR monoclonal antibody (cetuximab) and follow up CT performed 2 months later demonstrates resolution of mass on right and significant decrease in left cervical lymph node. CECT = contrast enhanced CT, EGFR = epidermal growth factor receptor

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  Fig. 10 MIP (A, C) and axial non contrast fused 18F-FDG PET/CT (B) in 20-year-old man with ALK positive anaplastic large cell lymphoma. A. Patient had been diagnosed one year earlier and treated with brentuximab but had relapsed 6 months after completing treatment. New baseline PET/CT demonstrated residual lymphadenopathy in right external iliac and inguinal lymph nodes (arrows). B. Axial fused PET/CT demonstrates FDG avid right inguinal lymph node (arrow) with SUVmax 5.5. C. Patient was treated with salvage chemotherapy (gemcitabine, vinorelbine and doxil) with response to treatment and resolution of right pelvic lymphadenopathy on PET/CT performed 8 weeks later. ALK = anaplastic lymphoma kinase, MIP = maximum intensity projection, PET = positron emission tomography

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