Role of FDG-PET in the diagnosis and management of lung cancer

Positron emission tomography (PET) using [¹⁸F]-2-deoxy-2-fluoro-d-glucose (FDG) has emerged as a valuable diagnostic modality in patients with non-small cell lung cancer (NSCLC). Data in the literature show that the addition of FDG-PET definitely alters clinical management in patients with potentially resectable NSCLC by adequately staging the mediastinum and detecting previously unknown distant metastases. Thus, the number of noncurative thoracotomies and unnecessary mediastinoscopies is reduced. Furthermore, there is increasing evidence that FDG-PET will change radiation treatment planning by defining a biologic treatment volume, incorporating unsuspected additional locoregional disease, and avoiding overtreatment by identifying computerized tomography abnormalities as benign. For follow-up during systemic therapy, early FDG-PET appears to be predictive for the response to therapy. However, before FDG-PET-induced changes in patient management can be incorporated into clinical practice both for radiation treatment planning and chemotherapy, technical issues must be resolved, validation studies should be performed and, most importantly, randomized trials are necessary to evaluate the effect of FDG-PET on patient outcome parameters.     

Response to radiation

Computed tomography (CT) has traditionally been the standard radiographic modality for diagnosing and monitoring non-small cell; lung cancer (NSCLC) after treatment. Given the limitations of CT, the utility of 18F-fluoro-2-deoxy-glucose positron emission tomography (FDG-PET) has been investigated for the management of NSCLC, with promising findings. Its adjunctive role with CT in diagnosing and staging disease is well established. FDG-PET also has been found to be a valuable tool for radiation treatment planning because it improves the precision of lesion definition. More recently, its value for determining clinical response both during and after treatment has been explored. This review highlights the various applications of FDG-PET in the diagnosis and management of NSCLC as corroborated by clinical data, with considerations of future directions.     

Impact of FDG-PET on radiation therapy volume delineation in non-small-cell lung cancer

PURPOSE: Locoregional failure remains a significant problem for patients receiving definitive radiation therapy alone or combined with chemotherapy for non-small-cell lung cancer (NSCLC). Positron emission tomography (PET) with [(18)F]fluoro-2-deoxy-d-glucose (FDG) has proven to be a valuable diagnostic and staging tool for NSCLC. This prospective study was performed to determine the impact of treatment simulation with FDG-PET and CT on radiation therapy target volume definition and toxicity profiles by comparison to simulation with computed tomography (CT) scanning alone. METHODS: Twenty-six patients with Stages I-III NSCLC were studied. Each patient underwent sequential CT and FDG-PET simulation on the same day. Immobilization devices used for both simulations included an alpha cradle, a flat tabletop, 6 external fiducial markers, and a laser positioning system. A radiation therapist participated in both simulations to reproduce the treatment setup. Both the CT and fused PET/CT image data sets were transferred to the radiation treatment planning workstation for contouring. Each FDG-PET study was reviewed with the interpreting nuclear radiologist before tumor volumes were contoured. The fused PET/CT images were used to develop the three-dimensional conformal radiation therapy (3DCRT) plan. A second physician, blinded to the results of PET, contoured the gross tumor volumes (GTV) and planning target volumes (PTV) from the CT data sets, and these volumes were used to generate mock 3DCRT plans. The PTV was defined by a 10-mm margin around the GTV. The two 3DCRT plans for each patient were compared with respect to the GTV, PTV, mean lung dose, volume of normal lung receiving > or =20 Gy (V20), and mean esophageal dose. RESULTS: The FDG-PET findings altered the AJCC TNM stage in 8 of 26 (31%) patients; 2 patients were diagnosed with metastatic disease based on FDG-PET and received palliative radiation therapy. Of the 24 patients who were planned with 3DCRT, PET clearly altered the radiation therapy volume in 14 (58%), as follows. PET helped to distinguish tumor from atelectasis in all 3 patients with atelectasis. Unsuspected nodal disease was detected by PET in 10 patients, and 1 patient had a separate tumor focus detected within the same lobe of the lung. Increases in the target volumes led to increases in the mean lung dose, V20, and mean esophageal dose. Decreases in the target volumes in the patients with atelectasis led to decreases in these normal-tissue toxicity parameters. CONCLUSIONS: Radiation targeting with fused FDG-PET and CT images resulted in alterations in radiation therapy planning in over 50% of patients by comparison with CT targeting. The increasing availability of integrated PET/CT units will facilitate the use of this technology for radiation treatment planning. A confirmatory multicenter, cooperative group trial is planned within the Radiation Therapy Oncology Group.     

Intérêt de la tomographie par émission de positons au [18F]-fluoro-2-désoxyglucose dans la détermination des volumes cibles de radiothérapie. Application à l''irradiation conformationnelle des cancers bronchiques non à petites cellules

Traditional radiation treatment planning relies on density imaging such as Computed Tomography for anatomic information of various structures of interest including target and normal tissues. However, the difficulties to distinguish malignant from normal tissue on CT slides often leads to inaccurate outlining of the GTV and/or to geographic misses. 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) has shown an increase in both sensitivity and specificity over CT in locoregional staging of patients with non-small cell lung cancer (NSCLC). The co registration of FDG-PET images to the data of the CT planning offers the radiation oncologist the possibility to include functional information into the target outlining. For the treatment of patients with NSCLC, it has been shown that the use of FDG-PET images: 1) modified the shape and volume of radiation fields in 22-62% of cases, mainly due to a better nodal staging and distinction of atelectasis from tumor and; 2) significatively reduced the interobserver and intraobserver variability. This paper reviews the results reported in the literature. Challenges and proposed solutions are discussed.     

Impact of computed tomography (CT) and 18F-deoxyglucose positron emission tomography (FDG-PET) image fusion for conformal radiotherapy in esophageal carcinoma]

PURPOSE: To study the impact of fused (18)F-fluoro-deoxy-D-glucose (FDG)-hybrid positron emission tomography (PET) and computed tomography (CT) images on conformal radiation therapy (CRT) planning for patients with esophageal carcinoma. PATIENTS AND METHODS: Thirty-four patients with esophageal carcinoma were referred for concomitant radiotherapy and chemotherapy with radical intent. Each patient underwent CT and FDG-hybrid PET for simulation treatment in the same radiation treatment position. PET-images were coregistered using five fiducial markers. Target delineation was initially performed on CT images and the corresponding PET data were subsequently used as an overlay to CT data to define the target volume. RESULTS: FDG-PET identified previously undetected distant metastatic disease in 2 patients, making them ineligible for curative CRT. The Gross Tumor Volume (GTV) was decreased by CT and FDG image fusion in 12 patients (35%) and was increased in 7 patients (20.5%). The GTV reduction was >or=25% in 4 patients due to reduction of the length of the esophageal tumor. The GTV increase was >or=25% with FDG-PET in 2 patients due to the detection of occult mediastinal lymph node involvement in one patient and an increased length of the esophageal tumor in the other patient. Modifications of the GTV affected the planning treatment volume (PTV) in 18 patients. Modifications of delineation of GTV and displacement of the isocenter of PTV by FDG-PET also affected the percentage of total lung volume receiving more than 20 Gy (VL20) in 25 patients (74%), with a dose reduction in 12 patients and a dose increase in 13 patients. CONCLUSION: In our study, CT and FDG-PET image fusion appeared to have an impact on treatment planning and management of patients with esophageal carcinoma related to modifications of GTV. The impact on treatment outcome remains to be demonstrated.     

Impact of computed tomography (CT) and 18F-deoxyglucose-coincidence detection emission tomography (FDG-CDET) image fusion for optimisation of conformal radiotherapy in non-small-cell lung cancers]

To report a retrospective study concerning the impact of fused 18F-fluorodeoxy-D-glucose (FDG)-hybrid positron emission tomography (PET) and computed tomography (CT) images on three-dimensional conformal radiation therapy (3D-CRT) planning for patients with non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: One hundred and one patients consecutively treated for stages I-III NSCLC were studied. Each patient underwent CT and FDG-hybrid PET for simulation treatment in the same radiation treatment position. Images were coregistered using five fiducial markers. Target volume delineation was initially performed on the CT images and the corresponding FDG-PET data were subsequently used as an overlay to the CT data to define target volume. RESULTS: FDG-PET identified previously undetected distant metastatic disease in 8 patients making them ineligible for curative CRT (one patient presented some positive uptakes corresponding to concomitant pulmonary tuberculosis). Another patient was ineligible for curative treatment because fused CT/PET images demonstrated excessively extensive intrathoracic disease. The gross tumor volume (GTV) was decreased by CT/PET image fusion in 21 patients (23%) and was increased in 24 patients (26%). The GTV reduction was > or = 25% in 7 patients because CT/PET image fusion reduced pulmonary GTV in 6 patients (3 patients with atelectasis) and mediastinal nodal GTV in 1 patient. The GTV increase was > or = 25% in 14 patients due to an increase of the pulmonary GTV in 11 patients (4 patients with atelectasis) and detection of occult mediastinal lymph node involvement in 3 patients. Among 81 patients receiving a total dose > or = 60 Gy at ICRU point, after CT/PET image fusion, the percentage of total lung volume receiving more than 20 Gy (VL20) increased in 15 cases and decreased in 22 cases. The percentage of total heart volume receiving more than 36 Gy increased in 8 patients and decreased in 14 patients. The spinal cord volume receiving at least 45 Gy (2 patients) decreased. After multivariate analysis, one single independent factor made significant effect of FDG/PET on the modification of the size of the GTV: tumor with atelectasis (P = 0.0001). Conclusion. - Our study confirms that integrated hybrid PET/CT in the treatment position and coregistered images have an impact on treatment planning and management of patients with NSCLC. FDG images using dedicated PET scanners with modern image fusion techniques and respiration-gated acquisition protocols could improve CT/PET image coregistration. However, prospective studies with histological correlation are necessary and the impact on treatment outcome remains to be demonstrated.     

18F-fluoro-2-deoxy-D-glucose positron emission tomographic imaging: recent developments in head and neck cancer

PURPOSE OF REVIEW: Positron emission tomography using 18F-fluoro-2-deoxy-D-glucose (18FDG-PET) is well established in clinical routine as a metabolism-based whole-body imaging tool for cancer diagnosis and follow-up. Several reports have appeared indicating the potential and limitations of this technique in head and neck cancer (HNC). This review limits its scope to the recent advances using 18FDG-PET in the clinical management of HNC. RECENT FINDINGS: The combination of 18FDG-PET and sentinel node biopsy has been explored for the surgical treatment planning of oral and oropharyngeal cancer. Recent reports indicate that multimodality imaging combining PET with high-end CT scanning increases the diagnostic accuracy. 18FDG-PET has a potential for use in radiation treatment planning and for the prediction of response and early evaluation of treatment efficacy. SUMMARY: Increasingly 18FDG-PET is used as a clinical imaging modality in the different stages of the management of HNC. In particular, its clinical value in initial staging of neck lymph nodes and in the evaluation of recurrent or residual disease is well established. In these settings 18FDG-PET has been shown to be more accurate than conventional imaging. Recent studies indicate that 18FDG-PET could be of additional value in staging the N0 neck, in radiation treatment planning, and in prediction of treatment efficacy.     

Successfully resected stage IIIA non-small cell lung cancer with mediastinal lymphnode metastasis after chemotherapy of cisplatin and docetaxel combined with concurrent radiation

A 47-year-old man with no symptoms was admitted to our hospital for the treatment of NSCLC, which was incidentally detected by an X-ray examination at the mass screening. Computed tomography (CT) of the chest and FDG-PET revealed a 3.6 cm tumor in the right upper lobe with multiple lymphadenopathy in the right mediastinum. Based on these clinical findings, we classified this case as a T2N2M0, stage IIIA NSCLC. The patient consented to and received 2 courses of systemic chemotherapy consisting of cisplatin (CDDP 40 mg/m(2); day 1, 8) and docetaxel (DOC 40 mg/m(2); day 1, 8) combined with concurrent radiation (2 Gy/day; total 46 Gy) with no severe adverse events. His tumors responded well to the treatment, and restaging chest CT showed marked regression of mediastinal lymphadenopathy, and partial response to the lung tumor. Then, acurative surgical resection was performed. Finally, the case was diagnosed as a T1N1M0, stage IIA NSCLC pathologically. Our chemotherapy regimen consisting of CDDP and DOC combined with concurrent radiation might be as potent as neo-adjuvant therapy for clinical stage III NSCLC.     

Impact of fluorine-18 fluorodeoxyglucose positron emission tomography on patient management: first year's experience in a clinical center.

PURPOSE: To measure the impact of whole-body fluorodeoxyglucose (FDG) positron emission tomography (PET) on patient management during its first year of use in a community hospital. MATERIALS AND METHODS: First-year FDG-PET impact was determined from 463 referring physicians' evaluations of their patients' PET imaging results using two surveys. Survey 1 was given to all physicians referring patients to PET to discover whether PET changed patient management or had decision-making value in the patient's clinical algorithm. Survey 2 was given to one surgeon and one pulmonologist after therapy to determine how PET affected the surgical, chemotherapeutic, and/or radiotherapeutic treatment for the 53 cancer patients they referred. RESULTS: The 463 responses to survey 1 described 23 different PET indications. Lung (40%), head and neck (18%), and colorectal cancers (11%) were the three leading causes of referral. PET changed patient management/therapy in 45% of all patients referred and had inferential/decision-making value in another 44%. Overall, PET had some type of positive influence in 412 (89%) of the patients. Survey 2 provided a more detailed assessment of 53 referrals from two specialists. PET positively affected surgery in 31 patients (58%), prompted the addition of chemotherapy or radiation therapy in nine patients (17%), and eliminated chemotherapy or radiation therapy in four cases (8%). Overall, PET affected patient management/therapy in 70% of the cases and had some decision-making value in another 26%, for a combined PET impact on patient management of 96%. CONCLUSION: FDG-PET can be valuable for physicians in clinical practice. Its sensitivity and specificity in metabolic imaging, when combined with complementary anatomic imaging techniques, contribute significantly to the clinical treatment of cancer patients. In addition, the high accuracy of FDG-PET makes it a cost-effective radiologic procedure in the work-up of all suspected and/or recurrent cancer patients. Further research is needed to link this demonstrated impact on patient management to cost-effectiveness.     

Posttreatment assessment of response using FDG-PET/CT for patients treated with definitive radiation therapy for head and neck cancers

PURPOSE: The goal of this study was to evaluate coregistered [18F] fluorodeoxyglucose (FDG)-positron emission tomography (PET)/computed tomography (CT) for the detection of persistent disease after definitive radiation therapy in head and neck cancer. METHODS AND MATERIALS: Posttreatment FDG-PET/CT was performed in 28 patients on average 8 weeks (range, 4 to 15.7 weeks) after completing definitive radiation therapy. FDG-PET/CT was visually analyzed for the entire patient group and at two time points (4-8 and >8 weeks) after treatment. The contrast-enhanced CT portion of PET/CT was separately analyzed blinded to the results of coregistered FDG-PET/CT and classified as negative or positive for residual locoregional disease. Pathologic findings and clinical follow-up served as the reference standard. RESULTS: Follow-up data were available for all 28 patients (median, 17.6 months). Regarding the detection of residual disease, the overall sensitivity and specificity of FDG-PET/CT was 76.9% and 93.3%, respectively, compared with 92.3% and 46.7% for contrast-enhanced CT. The accuracy of FDG-PET/CT was 85.7%, compared with 67.9% for CT alone. All false-negative (n = 3) and false-positive (n = 1) FDG-PET/CT results occurred between 4 and 8 weeks after treatment. At 8 weeks or later after treatment, the specificity of CT was 28%, compared with 100% for FDG-PET/CT. CONCLUSIONS: The metabolic-anatomic information from coregistered FDG-PET/CT provided the most accurate assessment for treatment response when performed later than 8 weeks after the conclusion of radiation therapy. FDG-PET/CT excelled by a higher specificity and overall diagnostic performance than CT imaging alone. These results support a potential clinical role of FDG-PET/CT in the early assessment of therapy response after definitive radiation therapy.     

Impact of hybrid fluorodeoxyglucose positron-emission tomography/computed tomography on radiotherapy planning in esophageal and non-small-cell lung cancer

PURPOSE: The aim of this study was to investigate the impact of a hybrid fluorodeoxyglucose positron-emission tomography/computed tomography (FDG-PET/CT) scanner in radiotherapy planning for esophageal and non-small-cell lung cancer (NSCLC). METHODS AND MATERIALS: A total of 30 patients (16 with esophageal cancer, 14 with NSCLC) underwent an FDG-PET/CT for radiotherapy planning purposes. Noncontrast total-body spiral CT scans were obtained first, followed immediately by FDG-PET imaging which was automatically co-registered to the CT scan. A physician not involved in the patients' original treatment planning designed a gross tumor volume (GTV) based first on the CT dataset alone, while blinded to the FDG-PET dataset. Afterward, the physician designed a GTV based on the fused PET/CT dataset. To standardize PET GTV margin definition, background liver PET activity was standardized in all images. The CT-based and PET/CT-based GTVs were then quantitatively compared by way of an index of conformality, which is the ratio of the intersection of the two GTVs to their union. RESULTS: The mean index of conformality was 0.44 (range, 0.00-0.70) for patients with NSCLC and 0.46 (range, 0.13-0.80) for patients with esophageal cancer. In 10 of the 16 (62.5%) esophageal cancer patients, and in 12 of the 14 (85.7%) NSCLC patients, the addition of the FDG-PET data led to the definition of a smaller GTV. CONCLUSION: The incorporation of a hybrid FDG-PET/CT scanner had an impact on the radiotherapy planning of esophageal cancer and NSCLC. In future studies, we recommend adoption of a conformality index for a more comprehensive comparison of newer treatment planning imaging modalities to conventional options.     

Dosimetric implications of the addition of 18 fluorodeoxyglucose-positron emission tomography in CT-based radiotherapy planning for non-small-cell lung cancer

The aim of this study was to assess the impact of F-18 fluorodeoxyglucose-positron emission tomography (FDG-PET) CT on radiotherapy planning parameters for patients treated curatively with radiotherapy for non-small-cell lung cancer (NSCLC). Five patients with stages I–III NSCLC underwent a diagnostic FDG-PET CT (dPET CT), planning FDG-PET CT (pPET CT) and a simulation CT (RTP CT). For each patient, three radiation oncologists delineated a gross tumour volume based on RTP CT alone, and fused with dPET CT and pPET CT. Standard expansions were used to generate PTVs, and a 3D conformal plan was created. Normal tissue doses were compared between plans. Coverage of pPET CT PTV by the plans based on RTP CT and dPET CT was assessed, and tumour control probabilities were calculated. Mean PTV was similar between RTP CT, dPET CT and pPET CT, although there were significant inter-observer differences in four patients. The plans, however, showed no significant differences in doses to lung, oesophagus, heart or spinal cord. The RTP CT plan and dPET CT plan significantly underdosed the pPET PTV in two patients with minimum doses ranging from 12 to 63% of prescribed dose. Coverage by the 95% isodose was suboptimal in these patients, but this did not translate into poorer tumour control probability. The effect of fused FDG-PET varied between observers. The addition of dPET and pPET did not significantly change the radiotherapy planning parameters. Although FDG-PET is of benefit in tumour delineation, its effect on normal tissue complication probability and tumour control probability cannot be predicted.     

The impact of (18)FDG-PET on target and critical organs in CT-based treatment planning of patients with poorly defined non-small-cell lung carcinoma: a prospective study

PURPOSE: To prospectively study the impact of coregistering (18)F-fluoro-deoxy-2-glucose hybrid positron emission tomographic (FDG-PET) images with CT images on the planning target volume (PTV), target coverage, and critical organ dose in radiation therapy planning of non-small-cell lung carcinoma. METHODS AND MATERIALS: Thirty patients with poorly defined tumors on CT, referred for radical radiation therapy, underwent both FDG-PET and CT simulation procedures on the same day, in radiation treatment position. Image sets were coregistered using external fiducial markers. Three radiation oncologists independently defined the gross tumor volumes, using first CT data alone and then coregistered CT and FDG-PET data. Standard margins were applied to each gross tumor volume to generate a PTV, and standardized treatment plans were designed and calculated for each PTV. Dose-volume histograms were used to evaluate the relative effect of FDG information on target coverage and on normal tissue dose. RESULTS: In 7 of 30 (23%) cases, FDG-PET information changed management strategy from radical to palliative. In 5 of the remaining 23 (22%) cases, new FDG-avid nodes were found within 5 cm of the primary tumor and were included in the PTV. The PTV defined using coregistered CT and FDG-PET would have been poorly covered by the CT-based treatment plan in 17--29% of cases, depending on the physician, implying a geographic miss had only CT information been available. The effect of FDG-PET on target definition varied with the physician, leading to a reduction in PTV in 24-70% of cases and an increase in 30-76% of cases. The relative change in PTV ranged from 0.40 to 1.86. On average, FDG-PET information led to a reduction in spinal cord dose but not in total lung dose, although large differences in dose to the lung were seen for a few individuals. CONCLUSION: The coregistration of planning CT and FDG-PET images made significant alterations to patient management and to the PTV. Ultimately, changes to the PTV resulted in changes to the radiation treatment plans for the majority of cases. Where possible, we would recommend that FDG-PET data be integrated into treatment planning of non-small-cell lung carcinoma, particularly for three-dimensional conformal techniques.     

Increased therapeutic ratio by 18FDG-PET CT planning in patients with clinical CT stage N2-N3M0 non-small-cell lung cancer: a modeling study

PURPOSE: With this modeling study, we wanted to estimate the potential gain from incorporating fluorodeoxyglucose-positron emission tomography (FDG-PET) scanning in the radiotherapy treatment planning of CT Stage N2-N3M0 non-small-cell lung cancer (NSCLC) patients. METHODS AND MATERIALS: Twenty-one consecutive patients with clinical CT Stage N2-N3M0 NSCLC were studied. For each patient, two three-dimensional conformal treatment plans were made: one with a CT-based planning target volume (PTV) and one with a PET-CT-based PTV, both to deliver 60 Gy in 30 fractions. From the dose-volume histograms and dose distributions on each plan, the dosimetric factors predicting esophageal and lung toxicity were analyzed and compared. For each patient, the maximal tolerable prescribed radiation dose for the CT PTV vs. PET-CT PTV was calculated according to the constraints for the lung, esophagus, and spinal cord. From these results, the tumor control probability (TCP) was estimated, assuming a clinical dose-response curve with a median toxic dose of 84.5 Gy and a gamma(50) of 2.0. Dose-response curves were modeled, taking into account geographic misses according to the accuracy of CT and PET in our institutions. RESULTS: The gross tumor volume of the nodes decreased from 13.7 +/- 3.8 cm(3) on the CT scan to 9.9 +/- 4.0 cm(3) on the PET-CT scan (p = 0.011). All dose-volume characteristics for the esophagus and lungs decreased in favor of PET-CT. The esophageal V(45) (the volume of the esophagus receiving 45 Gy) decreased from 45.2% +/- 4.9% to 34.0% +/- 5.8% (p = 0.003), esophageal V(55) (the volume of the esophagus receiving 55 Gy) from 30.6% +/- 3.2% to 21.9% +/- 3.8% (p = 0.004), mean esophageal dose from 29.8 +/- 2.5 Gy to 23.7 +/- 3.1 Gy (p = 0.004), lung V(20) (the volume of the lungs minus the PTV receiving 20 Gy) from 24.9% +/- 2.3% to 22.3% +/- 2.2% (p = 0.012), and mean lung dose from 14.7 +/- 1.3 Gy to 13.6 +/- 1.3 Gy (p = 0.004). For the same toxicity levels of the lung, esophagus, and spinal cord, the dose could be increased from 56.0 +/- 5.4 Gy with CT planning to 71.0 +/- 13.7 Gy with PET planning (p = 0.038). The TCP corresponding to these doses was estimated to be 14.2% +/- 5.6% for CT and 22.8% +/- 7.1% for PET-CT planning (p = 0.026). Adjusting for geographic misses by PET-CT vs. CT planning yielded TCP estimates of 12.5% and 18.3% (p = 0.009) for CT and PET-CT planning, respectively. CONCLUSION: In this group of clinical CT Stage N2-N3 NSCLC patients, use of FDG-PET scanning information in radiotherapy planning reduced the radiation exposure of the esophagus and lung, and thus allowed significant radiation dose escalation while respecting all relevant normal tissue constraints. This, together with a reduced risk of geographic misses using PET-CT, led to an estimated increase in TCP from 13% to 18%. The results of this modeling study support clinical trials investigating incorporation of FDG-PET information in CT-based radiotherapy planning.     

Usefulness of FDG-PET for early prediction of the response to gefitinib in non-small cell lung cancer

Increased tumor uptake of (18)F-fluorodeoxyglucose (FDG) measured by positron emission tomography (PET) reflects glucose metabolism and proliferative activity of tumor cells. We conducted a study to assess the usefulness of FDG-PET for early prediction of the response to gefitinib, an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), in advanced non-small cell lung cancer (NSCLC). Five NSCLC patients underwent FDG-PET to evaluate changes in FDG uptake at day 2 and 4 weeks after the initiation of gefitinib therapy compared with FDG-PET prior to therapy. FDG uptake was evaluated as the maximum standardized uptake value (SUVmax) of the target lesions, which were assessable by conventional CT. Based on the CT evaluation, two patients exhibited a partial response (PR), two patients had stable disease (SD) with a minor response, and one patient had progressive disease (PD). In patients with PR and SD, SUVmax decreased by 61+/-18% (standard deviation) and 59+/-12%, respectively, on day 2, and by 26+/-6 and 43+/-10%, respectively, at 4 weeks after the initiation of gefitinib. Two patients with SD had decreased FDG uptake within 2 days of initiation of therapy, and achieved progression-free survival (PFS) of more than 12 months. In contrast, SUVmax increased up to 153+/-21% at 2 days and 232+/-73% at 4 weeks in a patient with PD. The present preliminary study suggests that FDG-PET may be able to predict response to gefitinib in the early stage of therapy in patients with advanced NSCLC and may have a potential prognostic role.     

Positron emission tomography in limited-stage small-cell lung cancer: a prospective study.

PURPOSE: To determine how often positron emission tomography with [(18)F]fluoro-2-deoxy-D-glucose (FDG-PET) detects extensive-stage small-cell lung cancer (SCLC) in patients considered to have limited-stage disease based on conventional staging procedures, and to determine the impact of PET on treatment planning for presumed limited-stage SCLC. PATIENTS AND METHODS: We prospectively performed pretreatment FDG-PET on 24 patients determined by conventional staging methods to have limited-stage SCLC (defined as disease that could be encompassed within a reasonable radiotherapy portal, excluding bilateral supraclavicular disease). PET images were evaluated for evidence of extensive-stage disease. Tumor-node-metastasis system staging was also assigned for each patient, with and without PET information. RESULTS: FDG-PET demonstrated findings consistent with extensive-stage SCLC in three of 24 patients. FDG-PET correctly upstaged two (8.3%) of 24 patients to extensive-stage disease (95% CI, 1.03% to 27.0%). PET correctly identified tumor in each SCLC mass (primary or nodal) that was suspected on computed tomography (CT) imaging, thus giving a lesion-based sensitivity relative to CT of 100%. PET identified unsuspected regional nodal metastasis in six (25%) of 24 patients, and the radiation therapy plan was significantly altered to include the PET-positive/CT-negative nodes within the high-dose region in each of these patients. Brain PET images in 23 patients disclosed no evidence of brain metastasis. CONCLUSION: FDG-PET has high sensitivity for SCLC and appears to be of value for initial staging and treatment planning of patients with presumed limited-stage disease.     

Megavoltage computed tomography imaging: a potential tool to guide and improve the delivery of thoracic radiation therapy

Helical tomotherapy is an innovative means of delivering intensity-modulated radiation therapy (IMRT) using a device that merges features of a linear accelerator and a helical computed tomography (CT) scanner. The tomotherapy unit can generate CT images from the megavoltage radiation it uses for treatment as often as needed during a course of radiation therapy. These megavoltage CT (MVCT) images offer verification of patient position prior to and potentially during radiation therapy, and provide considerably more anatomical detail than the conventional radiation therapy port films used for patient set-up verification. Also, MVCT imaging may enable reconstruction of the radiation dose delivered, thereby providing unprecedented verification of the actual treatment. These key features of helical tomotherapy distinguish it from other IMRT approaches. We report results from a pilot feasibility trial of 10 patients with non-small-cell lung cancer (NSCLC) on whom we obtained MVCT images using a prototype helical tomotherapy system. All patients underwent conventional CT imaging for radiation therapy treatment planning. Specific aims were to subjectively compare MVCT and conventional CT images and then to objectively compare the 2 modalities by contouring tumors and performing a volumetric comparison. Seven patients had disease located primarily in the lung parenchyma, 2 primarily in the mediastinum, and 1 in both. When evaluated by location, all 7 patients with lesions primarily in the lung parenchyma had subjectively high-quality MVCT images. Objectively, the volumetric agreement between conventional and MVCT for parenchymal lesions was excellent in 5 of the 7 patients. Megavoltage CT imaging via the helical tomotherapy prototype provided adequate information for use in verification of patient position and dose reconstruction for lesions within the pulmonary parenchyma, but presently appears suboptimal for primarily mediastinal disease. Further studies are ongoing to optimize MVCT imaging and better define its utility in patients with NSCLC.     

Impact of CT and 18F-deoxyglucose positron emission tomography image fusion for conformal radiotherapy in esophageal carcinoma

PURPOSE: To study the impact of fused (18)F-fluoro-deoxy-D-glucose (FDG)-hybrid positron emission tomography (PET) and computed tomography (CT) images on conformal radiotherapy planning for esophageal carcinoma patients. METHODS AND MATERIALS: Thirty-four esophageal carcinoma patients were referred for concomitant radiotherapy and chemotherapy with radical intent. Each patient underwent CT and FDG-hybrid PET for simulation treatment in the same treatment position. PET images were coregistered using five fiducial markers. Target delineation was initially performed on CT images, and the corresponding PET data were subsequently used as an overlay to CT data to define the target volume. RESULTS: (18)F-fluorodeoxy-D-glucose-PET identified previously undetected distant metastatic disease in 2 patients, making them ineligible for curative conformal radiotherapy. The gross tumor volume (GTV) was decreased by CT and FDG image fusion in 12 patients (35%) and increased in 7 patients (21%). The GTV reduction was > or =25% in 4 patients owing to a reduction in the length of the esophageal tumor. The GTV increase was > or =25% with FDG-PET in 2 patients owing to the detection of occult mediastinal lymph node involvement in 1 patient and an increased length of the esophageal tumor in 1 patient. Modifications of the GTV affected the planning treatment volume in 18 patients. Modifications of the delineation of the GTV and displacement of the isocenter of the planning treatment volume by FDG-PET also affected the percentage of total lung volume receiving >20 Gy in 25 patients (74%), with a dose reduction in 12 patients and dose increase in 13. CONCLUSION: In our study, CT and FDG-PET image fusion appeared to have an impact on treatment planning and management of esophageal carcinoma. The affect on treatment outcome remains to be demonstrated.     

Practical integration of [18F]-FDG-PET and PET-CT in the planning of radiotherapy for non-small cell lung cancer (NSCLC): the technical basis, ICRU-target volumes, problems, perspectives.

The value of positron emission tomography using [18F]-fluoro-deoxy-glucose (FDG-PET) for pretherapeutic evaluation of patients with non-small cell lung cancer (NSCLC) is beyond doubt. Due to the increasing availability of PET and PET-CT scanners the method is now widely available, and its technical integration has become possible for radiotherapy planning systems. Due to the depiction of malignant tissue with high diagnostic accuracy, the use of FDG-PET in radiotherapy planning of NSCLC is very promising. However, by uncritical application, PET could impair rather than improve the prognosis of patients. Therefore, in the present paper we give an overview of technical factors influencing PET and PET-CT data, and their consequences for radiotherapy planning. We further review the relevant literature concerning the diagnostic value of FDG-PET and on the integration of FDG-PET data in RT planning for NSCLC. We point out the possible impact in gross tumor volume (GTV) definition and describe methods of target volume contouring of the primary tumor, as well as concepts for the integration of diagnostic information on lymph node involvement into the clinical target volume (CTV), and the possible implications of PET data on the definition of the planning target volume (PTV). Finally, we give an idea of the possible future use of tracers other than [18F]-FDG in lung cancer.     

Role of FDG-PET in the diagnosis and treatment of colorectal liver metastases

Positron emission tomography (PET) using [(18)F]-2-deoxy-2-fluoro-d-glucose (FDG) has emerged as a promising diagnostic modality in recurrent colorectal cancer. Data in the literature show that the addition of FDG-PET changes disease management in up to 30% of patients with potentially resectable liver metastases, mainly by detecting previously unknown extrahepatic disease. Furthermore, FDG-PET is useful in the follow-up of patients who underwent surgical procedures of the liver, since it is exquisitely sensitive in detecting residual or relapse malignancy in scarred liver tissue following both resection and local ablative techniques. For follow-up during systemic therapy, early FDG-PET appears predictive for response to therapy. However, at present, the available data are insufficient to justify the FDG-PET-driven management of patients treated with chemotherapy. FDG-PET and computerized tomography are complimentary techniques in staging and restaging patients with advanced colorectal cancer. The combination of these two modalities significantly impacts upon patient management.