Anatomic, functional and molecular imaging in lung cancer precision radiation therapy: treatment response assessment and radiation therapy personalization

Abstract

This article reviews key imaging modalities for lung cancer patients treated with radiation therapy (RT) and considers their actual or potential contributions to critical decision-making. An international group of researchers with expertise in imaging in lung cancer patients treated with RT considered the relevant literature on modalities, including computed tomography (CT), magnetic resonance imaging (MRI) and positron emission tomography (PET). These perspectives were coordinated to summarize the current status of imaging in lung cancer and flag developments with future implications. Although there are no useful randomized trials of different imaging modalities in lung cancer, multiple prospective studies indicate that management decisions are frequently impacted by the use of complementary imaging modalities, leading both to more appropriate treatments and better outcomes. This is especially true of 18F-fluoro-deoxyglucose (FDG)-PET/CT which is widely accepted to be the standard imaging modality for staging of lung cancer patients, for selection for potentially curative RT and for treatment planning. PET is also more accurate than CT for predicting survival after RT. PET imaging during RT is also correlated with survival and makes response-adapted therapies possible. PET tracers other than FDG have potential for imaging important biological process in tumors, including hypoxia and proliferation. MRI has superior accuracy in soft tissue imaging and the MRI Linac is a rapidly developing technology with great potential for online monitoring and modification of treatment. The role of imaging in RT-treated lung cancer patients is evolving rapidly and will allow increasing personalization of therapy according to the biology of both the tumor and dose limiting normal tissues.

Keywords: Lung cancer; magnetic resonance imaging (MRI); positron emission tomography (PET); radiation therapy (RT).

Conflict of interest statement

Conflicts of Interest: The authors have no conflicts of interest to declare.

Figures

Figure 1

Value of CT in local assessment of lung cancer. Detailed information obtained in a lung cancer patient from contrast-enhanced CT. This patient has a right hilar NSCLC (T), which has caused thrombosis of the superior vena cava and brachiocephalic vein (arrow) and is associated with extensive collateral vessel dilatation. CT, computed tomography; NSCLC, non-small cell lung cancer.

Figure 2

Detection of nerve root infiltration by MRI. MRI scan showing invasion of the T1 nerve root by a left sided apical lung cancer (arrow). This was not visualized on contemporaneous CT imaging. MRI, magnetic resonance imaging, CT, computed tomography.

Figure 3

Incremental value of FDG-PET added to CT imaging. (A) FDG PET/CT scan of a patient with locoregionally advanced NSCLC being considered for curative intent RT. In addition to the known primary tumor and intrathoracic lymph node involvement, this scan showed unexpected distant bony metastases in the left sacrum (highlighted in cross hairs) and sternum; (B) this patient with stage IIIA NSCLC (SCC) of the left upper lobe was planned for combined chemo-RT. Atelectatic upper lobe was included in the GTV when CT was used for target delineation. When PET information was incorporated, tumor margins were clearly seen and a much smaller (green) GTV was contoured. FDG-PET, 18F-fluoro-deoxyglucose positron emission tomography; CT, computed tomography; NSCLC, non-small cell lung cancer; GTV, gross tumor volume.

Figure 4

Response assessment with PET during therapy. (A) This patient with Stage IIIA NSCLC underwent serial FDG and FLT PET/CT scans prior to and during chemo-radiation therapy comprising baseline (top row), week 2 (middle row) and week 4 (bottom row), with FDG scans (left column) and FLT scans (right column). The FLT scans showed a more rapid and marked therapeutic response and complete disappearance of the bone marrow signal by week 2; (B) this patient had an initial radiation treatment plan using the baseline FDG-PET and CT scans (upper panels) that would deliver 60–66 Gy to FDG-avid tumor with a lung NTCP of 17.2%. Based on interim PET/CT, an adaptive plan was created that delivered 76–80 Gy to residual active tumor whilst maintaining a lung NTCP of 17.2%. PET, positron emission tomography; NSCLC, non-small cell lung cancer; FDG, 18F-fluoro-deoxyglucose; CT, computed tomography; FLT, 18F-fluorothymidine; NTCP, normal tissue complication probability.

Figure 5

Imaging the normal tissue effects of radiation. (A) This patient with stage IIIA adenocarcinoma of the right upper lobe was treated with concomitant chemoRT to 62 Gy. Post treatment PET/CT showed both an excellent therapeutic response and increased FDG uptake in the esophagus. Esophagoscopy revealed ulceration and early stenosis. Yellow arrow indicates linear FDG uptake in the esophagus; (B) serial perfusion imaging with 68Ga PET/CT in a patient treated with 60 Gy of external beam RT. By the mid-point of treatment a substantial reduction of blood flow had occurred in the high-dose volume. The post treatment scan shows extremely poor perfusion in the high-dose volume. PET, positron emission tomography; CT, computed tomography; FDG, 18F-fluoro-deoxyglucose.