Non-small Cell Lung Cancer: PET/CT Provides Superior Pre-Radiotherapy Treatment Planning
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PET/CT bests CT
Each year, 1.3 million new cases of lung cancer are diagnosed across the globe. It is the leading cause of death in men and women in most countries—with a five-year survival rate of just 15 percent. Non-small cell lung cancer accounts for 80 percent of all lung cancers, according to SNM. Staging for NSCLC is based upon tumor size and location (T-stage), nodal involvement (N-stage) and the presence or absence of metastases (M-stage). While multidetector CT has served as the gold standard for providing data on transfissural tumor growth, pleural involvement and mediastinal and chest wall invasion, FDG-PET has proved valuable for assessing nodal and extrathoracic disease (Eur Respir J 2009;33:201-212).FDG-PET should be introduced into the planning process for all NSCLC patients who cannot be treated surgically, such as those with stage IIIB-IV of the disease, says Arturo Chiti, MD, chair of the European Association of Nuclear Medicine’s Oncology Committee and director of nuclear medicine at Istituto Clinico Humanitas in Rozzano Milano, Italy.
The American Society of Clinical Oncology guideline update on the treatment of unresectable NSCLC notes the importance of FDG-PET when choosing between radiotherapy of palliative or curative intent (J Clin Oncol 2004;22:330-353).
“FDG-PET is superior to CT for identifying the boundaries of the tumor, because CT might miss areas with lung collapse [atelectasis],” says Issam M. El Naqa, PhD, assistant professor of radiation oncology at McGill University in Montreal, Quebec, Canada. In fact, he references a typical case of a lack of ability to identify lung collapse on a CT image of a lung cancer patient because it has similar density to the tumor itself.
Due to this higher sensitivity and specificity of PET/CT, compared with the morphologic imaging of CT, imaging a patient prior to radiotherapy can bring about a change in the patient’s treatment plan. Pommier et al, sponsored by the French National Cancer Institute, sought to quantify the impact of pre-radiotherapy 18F-FDG PET when deciding whether radiotherapy should be curative or palliative and defining detailed planning in patients with NSCLC referred for 3D conformal radical radiotherapy in a prospective multicenter study of 134 patients (79 percent with stage III disease).
Pommier et al found that knowledge of pre-radiotherapy PET/CT data caused treatment to be cancelled or changed from curative to palliative intent in 11 percent of patients. Of the 119 patients in whom radical radiotherapy was confirmed, the treatment plan was modified in 31 percent of the cases (AJR 2010; 195:350-355).
In a review of the current clinical literature, PET/CT specifically led to a modification of clinical target volume (CTV) in between 34 and 65 percent of cases, according to Pommier et al, who concluded that “pre-radiotherapy FDG-PET probably led to better selection of those patients likely to benefit from conformal radiotherapy.”
For treatment planning purposes, “FDG-PET [also] is beneficial in discovering if the cancer has begun to metastasize, and a particularly high SUV [standardized uptake value] suggests a poor prognosis,” says El Naqa. This is important because, as SNM recommends, patients usually are not surgical candidates if they have metastases to ipsilateral supraclavicular or contralateral medisatinal nodes, pulmonary metastases to another lobe or lung, or distant metastatic disease.
In fact, the American College of Chest Surgeons recommends PET/CT should be considered for mediastinal and extra thoracic staging in patients with clinical IA lung cancer and should be performed in patients with clinical IB-IIIB lung cancer being treated with curative intent (Cancer Chest 2007;132:1-19).
PET/CT bests PET
“Since the state of the art is FDG PET/CT, FDG-PET alone should not be used for pre-radiotherapy planning, if a facility has access to the hybrid scanner,” Chiti says.“While PET reveals areas [of cancer] that are very active, it is affected by motion artifacts that are very common in lung cancer cases, which can cause the reader to underestimate the tumor extent,” El Naqa concurs. “As a result, the combination of the anatomical information from the CT, along with PET that better identifies the boundaries of the tumor, results in PET/CT being a superior modality for this patient population.”
In a review that assessed PET/CT in the staging of NCSLC, De Wever et al wrote: “Integrated PET/CT is the best imaging technique for T-staging … For N-(re)staging, integrated PET/CT increases the specificity and positive predictive value, owing to the combination of metabolic and anatomic information. For M-staging, the additional value of integrated PET/CT is related to the fact that a CT of the whole body becomes available and to the fact that FDG hotspots can be better located” (ERJ 2009;33(1):201-212).
“If you extract certain image-based features from PET, like SUV measurements, and combine these with other image features from CT, that combination provides better prediction of response to radiotherapy,” El Naqa says. “Specifically, you can better predict local control if you take data from both CT and PET.”
In 2009, the U.S. National Comprehensive Cancer Network recommended PET/CT as part of the 3D conformal radiotherapy techniques because PET/CT is preferable to CT alone for the gross tumor volume delineation in cases with significant atelectasis.
In fact, Messa et al found that 18F-FDG PET/CT images co-registration in radiotherapy treatment planning led to a change in CTV definition in the majority of the study participants, which may “significantly modify management and radiation treatment modality” (Q J Nucl Med Mol Imaging 2005;49(3):259-266).
CT has a greater role than just attenuation correction, because it provides better delineation of the tumor, says El Naqa. “While PET provides the metabolic activity of the tumor, the addition of CT reveals how dense the tumor is,” he adds. “There are two conflicting objectives: You want to radiate the tumor, without radiating normal tissue—which could be very detrimental to the patient, such as radiation fibrosis.”
“In an ideal world, the oncologist should have as much anatomical detail as possible,” Chiti says. “However, in the practical world, where radiation dose needs to be a consideration, we tend to use a very low dose PET/CT scan because most of these patients have already undergone a diagnostic CT.” He adds that while radiation burden to the lung cancer patient is always a concern, this patient population is at a high risk of dying, so survival should take precedence.
Also, compared with the radiotherapy, the radiation dose exposure emitted from an FDG-PET or PET/CT exam is “relatively small, but these tests should be limited for the necessary patients only,” says El Naqa.
Both El Naqa and Chiti suggest that the trends are indicating an increase in the utilization of PET/CT for NSCLC patients. “PET/CT will become the gold standard for pre-radiotherapy treatment planning for this patient population,” Chiti says.
While FDG-PET or PET/CT are not yet embraced by all professional society guidelines, these modalities for pre-radiotherapy treatment planning for this patient population are gaining traction in real-life clinical practice due to reimbursement in the U.S., Canada and Europe. In the U.S., where reimbursement tends to be the most stringent, the Centers for Medicare & Medicaid Services approves PET and PET/CT for diagnosis, staging and restaging of NSCLC, but monitoring response during treatment is only covered by the agency when patients are participants in a clinical research trial or have been registered with the U.S. National Oncologic PET Registry (NOPR).