Korean J Radiol.  2017 Feb;18(1):28-41. 10.3348/kjr.2017.18.1.28.

Molecular Targeted Therapy in Modern Oncology: Imaging Assessment of Treatment Response and Toxicities

• Krajewski
• Braschi-Amirfarzan M
• DiPiro PJ
• Jagannathan JP
• Shinagare

• KMID: 2468120
• DOI: http://doi.org/10.3348/kjr.2017.18.1.28

Abstract

Oncology is a rapidly evolving field with a shift toward personalized cancer treatment. The use of therapies targeted to the molecular features of individual tumors and the tumor microenvironment has become much more common. In this review, anti-angiogenic and other molecular targeted therapies are discussed, with a focus on typical and atypical response patterns and imaging manifestations of drug toxicities.

Keyword

Vascular endothelial growth factor; Response Evaluation Criteria in Solid Tumors; Epidermal growth factor receptor; Anaplastic lymphoma kinase; Mammalian target of rapamycin; Human epidermal growth factor receptor 2

MeSH Terms

Angiogenesis Inhibitors/adverse effects/therapeutic use
Antineoplastic Agents/adverse effects/therapeutic use
Humans
Molecular Targeted Therapy/adverse effects/*methods
Neoplasms/*diagnostic imaging/*drug therapy/genetics
Tomography, X-Ray Computed
Treatment Outcome
Angiogenesis Inhibitors
Antineoplastic Agents

Figure

• 

  Fig. 1 Typical response of metastatic clear cell renal cell carcinoma to VEGF-targeted therapy and subsequent tumor growth off of treatment. In this 55-year-old woman, baseline contrast-enhanced CT prior to start of treatment demonstrates vascularized right hilar metastasis (arrow, A), pelvic serosal deposit (arrow, B) and left iliac bone metastasis (arrowhead, B). After 10 weeks of axitinib treatment, each metastasis is decreased in size and density (C, D). Patient subsequently developed wound infection in her right lower extremity, resulting in hold in axitinib treatment. After 6 weeks of holding treatment (and 18 weeks from first follow-up CT), right hilar mass (E), and pelvic serosal metastasis (arrow, F) are increased in size and enhancement, representing tumor growth. In addition, rim enhancement is newly seen involving left iliac bone lesion (arrowhead), also representing increasing tumor at site. VEGF = vascular endothelial growth factor

• 

  Fig. 2 Atypical response to VEGF-targeted therapy in colon cancer. In this 57-year-old woman with metastatic colon cancer, baseline contrast-enhanced CT (A) demonstrates multiple heterogeneous liver metastases. Serum CEA at baseline measured 2049. After 12 weeks of therapy with folinic acid, fluorouracil, oxaliplatin (FOLFOX) and avastin, multiple liver metastases have increased in size but have decreased in density (B), showing greater homogeneity and better defined margins. Serum CEA at time of 12 week follow-up CT measured 1126. Findings at follow-up CT represent response according to CT-morphologic criteria. CEA = carcinoembryonic antigen, VEGF = vascular endothelial growth factor

• 

  Fig. 3 Hepatocellular cancer (HCC) with response to VEGF-targeted therapy according to mRECIST. Baseline contrast-enhanced CT (A) demonstrates vascularized, enhancing tumor thrombus in right anterior and posterior portal vein branches (arrows) in this 59-year-old man with multifocal HCC. Follow-up contrast-enhanced CT after 2 months of VEGF-targeted therapy shows loss of hypervascularity of tumor thrombus (B), in keeping with response to therapy according to mRECIST. mRECIST = modified Response Evaluation Criteria in Solid Tumors, VEGF = vascular endothelial growth factor

• 

  Fig. 4 Gastrointestinal stromal tumor with response to sunitinib and tumor bowel fistula development. In this 76-year-old woman, baseline axial contrast-enhanced CT (A) demonstrates mass adjacent to small bowel in left lower quadrant (white arrow). Follow-up contrast-enhanced CT (B) demonstrates new oral contrast within tumor lesion, contiguous with small bowel lumen (black arrow).

• 

  Fig. 5 EGFR-mutant lung cancer with response to treatment, development of resistant disease, flare off of therapy and subsequent response to second-line treatment. Baseline CT in this 62-year-old never smoker demonstrates large left upper lobe perihilar mass with interlobular septal thickening emanating from mass (A), multistation lymphadenopathy is not shown. CT follow-up 5 months after erlotinib treatment shows dramatic shrinkage of left perihilar mass (B). Subsequent follow-up CT 8 months after start of treatment shows mild increase in left perihilar tumor indicative of resistant disease (not shown). Lymph node biopsy confirmed T790M secondary resistance mutation. Erlotinib therapy was discontinued in anticipation of clinical trial participation. One month after erlotinib discontinuation, patient presented with shortness of breath, cough and chest pain. CT chest revealed flare phenomenon, represented by marked increase in tumor burden in both lungs (C, D). Erlotinib was re-initiated with carboplatin and pemetrexed chemotherapy, and tumor burden significantly decreased 8 weeks later (E, F). EGFR = epidermal growth factor receptor

• 

  Fig. 6 EMF4-ALK rearranged lung cancer response to crizotinib and associated toxicity. Baseline contrast-enhanced CT in this 50-year-old man demonstrates large right lateral chest wall mass (arrow, A) which responded dramatically to crizotinib therapy, with little if any residual mass after 3 months of treatment (B). Thoracic vertebral bodies were normal in height at baseline (C). Demineralization and compression deformities developed during course of treatment (arrow, D), known toxicity of crizotinib related to rapid onset hypogonadism and low testosterone. ALK = anaplastic lymphoma kinase, EMF4= echinoderm microtubule-associated protein-like 4

• 

  Fig. 7 Response to mTOR-inhibitor treatment in Waldenstrom's macroglobulinemia and lung toxicity. Baseline contrast-enhanced coronal CT images in 59-year-old woman show retroperitoneal lymphadenopathy (black arrows) and mild splenomegaly (A). Five months after start of treatment, coronal contrast-enhanced CT shows decreased adenopathy and splenomegaly (B). At baseline, clear lung bases were present (C). On five month follow-up CT (D), new ground-glass and reticular opacities developed in lung bases (white arrows), in keeping with mTOR-associated pneumonitis. Patient was asymptomatic. mTOR = mammalian target of rapamycin

• 

  Fig. 8 Response to aromatase inhibitor and cyclin dependent kinase inhibitor in metastatic hormone receptor+, HER2 negative breast cancer. In this 29-year-old woman, baseline coronal CT (A) demonstrates multiple liver metastases (arrow). Follow-up coronal contrast-enhanced CT (B) demonstrates decreased size of multiple liver lesions (arrow) representing response to treatment. HER2 = human epidermal growth factor receptor 2

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