Radiotherapy treatment planning for patients with non-small cell lung cancer using positron emission tomography (PET)

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Abstract

Purpose: Many patients with non-small cell lung cancer (NSCLC) receive external beam radiation therapy as part of their treatment. Three-dimensional conformal radiation therapy (3DCRT) commonly uses computed tomography (CT) to accurately delineate the target lesion and normal tissues. Clinical studies, however, indicate that positron emission tomography (PET) has higher sensitivity than CT in detecting and staging of mediastinal metastases. Imaging with fluoro-2-deoxyglucose (FDG) PET in conjunction with CT, therefore, can improve the accuracy of lesion definition. In this pilot study, we investigated the potential benefits of incorporating PET data into the conventional treatment planning of NSCLC. Case-by-case, we prospectively analyzed planning target volume (PTV) and lung toxicity changes for a cohort of patients.

Materials and methods: We have included 11 patients in this study. They were immobilized in the treatment position and CT simulation was performed. Following CT simulation, PET scanning was performed in the treatment position using the same body cast that was produced for CT simulation and treatment. The PTV, along with the gross target volume (GTV) and normal organs, was first delineated using the CT data set. The CT and PET transmission images were then registered in the treatment planning system using either manual or automated methods, leading to consequent registration of the CT and emission images. The PTV was then modified using the registered PET emission images. The modified PTV is seen simultaneously on both CT and PET images, allowing the physician to define the PTV utilizing the information from both data sets. Dose–volume histograms (DVHs) for lesion and normal organs were generated using both CT-based and PET+CT-based treatment plans.

Results: For all patients, there was a change in PTV outline based on CT images versus CT/PET fused images. In seven out of 11 cases, we found an increase in PTV volume (average increase of 19%) to incorporate distant nodal disease. Among these patients, the highest normal-tissue complication probability (NTCP) for lung was 22% with combined PET/CT plan and 21% with CT-only plan. In other four patients PTV was decreased an average of 18%. The reduction of PTV in two of these patients was due to excluding atelectasis and trimming the target volume to avoid delivering higher radiation doses to nearby spinal cord or heart.

Conclusions: The incorporation of PET data improves definition of the primary lesion by including positive lymph nodes into the PTV. Thus, the PET data reduces the likelihood of geographic misses and hopefully improves the chance of achieving local control.

Introduction

Lung cancer is the most deadly form of cancer in the United States [21]. The outcome of conventional external beam treatment is poor partly because the radiosensitivity of the surrounding normal tissues limit the dose to the target and partly because of difficulty in delineating the extent of lesion in conventional imaging studies. Three-dimensional conformal radiation therapy (3DCRT) is able to accurately conform the dose distribution to the planning target volume (PTV) [2], [10], [14], [35]. This often results in reduced radiation dose to normal tissues and allows dose escalation for some patients. Recent clinical data with 3DCRT for lung treatments has been promising and justifies further clinical efforts [17]. For non-small cell lung carcinoma, Armstrong et al. [1] delivered 70.2 Gy radiation dose to gross disease with 9% of the patients developing radiation pneumonitis but none developing any significant hematologic toxicity. Rosenzweig et al. [32] also reported that, of ten patients receiving 70.2 Gy and ten patients receiving 75.6 Gy, zero patients in the lower and only one patient in the higher dose group experienced grade 3 or higher pulmonary toxicity. A recent report from the same institution [33] indicated only one grade 3 or higher lung toxicity among 11 patients treated to 81 Gy. However, five of these 11 patients were treated with deep-inspiration breath-hold (DIBH) technique [16] to reduce the normal-tissue complication probability (NTCP).

The conventional imaging modality for 3DCRT planning is computed tomography (CT). However, the sensitivity of CT imaging is low for determining the extent of the nodal disease [5], [34], [35]. CT also does not provide information about lesion viability, which may be an important prognostic factor for therapy management. Therefore, it is desirable to supplement CT in the definition of the gross lesion volume gross target volume (GTV) and its subsequent expansion to the PTV. Preliminary studies show increased sensitivity of fluoro-2-deoxyglucose (FDG) positron emission tomography (PET) imaging over CT for detecting solitary pulmonary nodules (SPNs) and for the staging of lung cancer [5], [11], [15], [29], [34]. With the approval of FDG-PET scanning for staging lung cancer by the Food and Drug Administration (FDA) [6], the role of PET in cancer detection has increased dramatically. It has been estimated that 85,000 lung cancer patients who undergo staging procedures will benefit from a FDG-PET scan [12]. Lung cancer staging and the evaluation of SPNs could lead to annual demand of 190,000 FDG-PET scans excluding other malignancies. Assuming that 10% of these patients require curative external beam therapy for disease management, approximately 20,000 patients may receive PET-guided radiotherapy each year.

In a study by Hebert et al. [18], PET identified a smaller metabolically active area than radiographically suspected in 23% of poorly demarcated lesions. Munley et al. [25] showed that pre-radiotherapy PET images would have influenced target volume localization in 15% of the patients. Kiffer et al. reported that the PTVs of four out of 15 lung cancer patients analyzed would have been influenced by PET findings [20]. However, these studies were performed retrospectively, so there was no immediate benefit to the patients.

Inoperable lung lesions are often large (PTV volumes exceeding 100 cm3). It has been theorized that doses as high as 100 Gy might be needed to provide adequate control of the disease [33]. These doses cannot be given safely with conventional methods. Incorporation of 3DCRT, DIBH, or PET based GTV delineation may be necessary to escalate dose without increasing NTCP. Additionally, the high sensitivity of PET in lung cancer (91 versus 75% of CT) [28], can detect distant metastases, so that, target definition and/or overall disease management may be improved. We have investigated the feasibility of prospectively using PET data in the radiation therapy planning of patients with non-small cell lung cancer (NSCLC). We developed software tools and clinical procedures to facilitate the use of FDG-PET images for target definition. The PET images were imported into the treatment planning system and registered with the CT planning scans. Too few patients are included in this feasibility study to allow analysis of the survival outcome of PET based treatment planning. However, the inclusion of PET data into treatment planning should provide greater accuracy in the definition of the treatment volume, leading to better design of the radiation portals and more effective treatment.

Section snippets

Patient population

Eleven patients (eight females, three males) planned for radiation therapy with expectation of nodal disease involvement were included in the study (Table 1). The mean patient age was 72 years (range 39–84). Three of the patients had prior chemotherapy. Based on the PET findings, staging of the disease changed in three patients from IA to IIA, IA to IIIA, and IIIB to IV.

CT simulation

Immobilization and CT simulation were performed, as is routine for lung cancer patients receiving 3DCRT in our department.

Results

Even though the main focus of this work is not image registration, we analyzed the image registration results for both manual and automated methods. Regional-intensity dependent mutual information-based automated image registration converges to a solution in seconds, the whole image registration process takes about 20 min, which includes loading the images, checking and adjusting the registration results. The agreement between manual and automated image registration ranged between 2.2 and 11.0 

Discussion

The successful incorporation of functional nuclear medicine information into RTP requires accurate registration of this imaging data to the planning CT scan. To achieve this goal, PET scans were performed with the patient placed in the patient-specific cast as used during the CT simulation. This reduces registration errors by ensuring that the PET scan, the CT scan, and the treatment are performed with the patient's internal anatomy in the same position. The mold also provides support for the

Conclusions

This study investigated the integration of PET image data during 3DCRT planning for patients with NSCLC. The PET imaging data appear to complement CT information and hopefully combination with CT will result improved local control and reduce geographic misses. Based on our experience, we think that PET should be a part of treatment planning in patients with a risk for mediastinal disease. However, outcome analysis in survival, disease free survival, morbidity, and secondary effects of radiation

Acknowledgements

This work was supported by a NIH Program Project Grant (P01-CA-59017).

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