Serial Assessment by PET•CT During Radiation Therapy in Non-small Cell Lung Cancer
Assessment of PET•CT-based metabolic tumor volume
Professor Pierre Vera, MD, Agathe Edet-Sanson, MD and Sebastian Hapdey, PhD
Case study data provided by Rouen University Hospital, Mont-Saint-Aignan, France
Fludeoxyglucose F 18* (18F FDG) PET•CT is widely used for initial staging of non-small cell lung carcinoma (NSCLC), as well as for subsequent radiation therapy planning. Early assessment of tumor response to radiation or chemoradiation therapy might lead to adaptive therapy modifications based on individual tumor radiosensitivity. Mid-treatment 18F FDG PET•CT studies aimed at the modification of planning target volume (PTV) for the escalation of radiation dose to metabolically active tumor tissue during radiation therapy has shown promise of improved local control with reduced toxicity.1
*Siemens' PETNET Solutions is a manufacturer of fludeoxyglucose F 18 injection (18F FDG). Indication and important safety information as approved by the US Food and Drug Administration can be found at the bottom of the page for 18F FDG, adult dose 5-10 mCi, administered by intravenous injection.
A 74-year-old male patient with a right upper lobar lung tumor detected on x-ray and confirmed by CT. In view of the localized nature of the tumor (T1N1 stage on CT), the patient was referred for radiation therapy with curative intent. The patient underwent an initial 18F FDG PET•CT study (PET 0) 1 week before initiation of radiation therapy. After the start of radiation therapy, sequential 18F FDG PET•CT studies were performed after every 14 Gy (every 7 fractions up to a total dose of 70 Gy). In total, the patient underwent 5 18F FDG PET•CT studies during the entire course of radiation therapy with a total dose of 70 Gy delivered. All studies were acquired on a Biograph™ 16 PET•CT system 60 minutes after 8 mCi 18F FDG injection. For the first study, whole-body acquisition at 3 minutes per bed position was followed by respiratory gated list mode acquisition of the thorax for 15 minutes. For the subsequent 5 studies performed during radiation therapy, only list mode and static acquisitions limited to the thorax were performed.SUVmax was obtained for all studies using the volume of interest (VOI) created using automatic delineation with a fixed 40% SUVmax threshold. SUVmax was compared for all the sequential studies. The metabolic tumor volume was calculated using VOI with 40% threshold, as well as manual VOI delineation for each time point. The gross tumor volume (GTV) included the primary tumor and adjacent mediastinal node. The clinical target volume (CTV) around the primary tumor was obtained by adding a 5 mm expansion to the GTV with manual correction to exclude vascular structures. An isotropic 1-cm margin was added around the CTV to obtain the planning target volume (PTV). The total dose prescribed at the isocenter was 70 Gy to the PTV. Radiation therapy consisted of 5 fractions per week with 2 Gy per fraction using 18 MV x-ray beams.
Figures 1 and 2 show a progressive decrease in 18F FDG uptake in the right paratracheal mass during the course of radiation therapy with an uptake level similar to the aorta at the end of 70 Gy. The tumor size, however, shows only a slight reduction. This reflects the synergy of metabolic response measured by 18F FDG PET•CT to actual response of tumor to radiation, while the tumor shrinkage measured by CT takes longer to be visible and quantifiable. The absence of a significant inflammatory reaction is also a notable finding in this patient, which may be reflective of the accuracy of GTV delineation and avoidance of normal lung tissue. Quantitative evaluation of sequential PET•CT (Figure 2) acquisition shows high initial SUVmax of 10.69 in the para-tracheal lung mass in the initial study. There is a progressive decrease in SUVmax with near normalization of SUVmax in the fourth and fifth PET•CT study (at 56 Gy and 70 Gy). A decrease in SUVmax by 50% was achieved with 28 Gy dose.
This patient is part of a study involving sequential PET•CT imaging during radiation therapy in 10 NSCLC patients using the above-mentioned protocol of a PET•CT study every 7 fractions.2 SUVmax values decreased in all lesions. A 50% decrease in SUVmax for most lesions was achieved around a dose of 40-50 Gy. The mean relative decrease in functional tumor volume at week 5 was 44% compared to that at baseline. The reduction in functional volume followed in parallel with the decrease in SUVmax. None of the patients showed disturbing radiation inflammation related 18F FDG uptake, which could have complicated interpretation and quantitative evaluation. This study challenges the current approach of performing 18F FDG PET•CT 2 to 3 months after completion of radiation therapy to avoid inflammation related artifacts despite the fact that imaging so late after radiation precludes any possibility of therapy modification or adaptation. In all patients, 18F FDG PET•CT images were acquired during radiation therapy without artifacts that could hamper interpretation.
18F FDG uptake was halved around the fifth week of conventionally fractionated radiation therapy. At this time, 40 Gy on an average had been delivered, and the possibility of adapting the dose and treatment plan based on early tumor response was a possibility. In case of an accelerated schedule, as in stereotactic body radiation therapy (SBRT), such adaptation may not be feasible or may require a higher frequency of PET•CT follow up. In a study from Maastrict,3 23 patients with medically inoperable NSCLC, underwent four repeated PET/CT scans before, during and after accelerated radiotherapy. There was large variation in SUVmax response among patients. Responders showed no change in SUVmax during radiation, while non-responders showed a mean increase in SUVmax of 48% during the first week of therapy and 15% decrease during the second week. Nonresponders also had higher SUVmax in all PET•CT studies compared to responders. Thus, the SUVmax change at mid-therapy at a time when 40-45 Gy has been delivered by conventional fractionated radiation therapy or accelerated SBRT may have prognostic implication as well.
- Feng et al Int J Radiat Oncol Biol Phys. 2009 Mar 15;73(4):1228-34).
- Edet – Sanson et al Serial assessment of FDG –PET FDG uptake and functional volume during ra-diotherapy in patients with non-small cell lung cancer. Radiother Oncol(2011)10.106/j.ra-donc.2011.07.023.
- van Baardwijk et al Radiother Oncol 2007 Feb;82(2):145-52.
*Fludeoxyglucose F 18 Injection
INDICATIONS AND USAGE
Fludeoxyglucose F 18 injection (18F FDG) is indicated for positron emission tomography (PET) imaging in the following setting:
Oncology: For assessment of abnormal glucose metabolism to assist in the evaluation of malignancy in patients with known or suspected abnormalities found by other testing modalities, or in patients with an existing diagnosis of cancer.
IMPORTANT SAFETY INFORMATION
Radiation-emitting products, including fludeoxyglucose F 18 injection, may increase the risk for cancer, especially in pediatric patients. Use the smallest dose necessary for imaging and ensure safe handling to protect the patient and health care worker.
Blood Glucose Abnormalities
In the oncology and neurology setting, suboptimal imaging may occur in patients with inadequately regulated blood glucose levels. In these patients, consider medical therapy and laboratory testing to assure at least two days of normoglycemia prior to fludeoxyglucose F18 injection administration.
Hypersensitivity reactions with pruritus, edema and rash have been reported; have emergency resuscitation equipment and personnel immediately available.
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The statements by Siemens customers described herein are based on results that were achieved in the customer's unique setting. Since there is no "typical" hospital and many variables exist (e.g., hospital size, case mix, level of IT adoption) there can be no guarantee that other customers will achieve the same results.