Comparison of different methods for delineation of 18F-FDG PET-positive tissue for target volume definition in radiotherapy of patients with non-Small cell lung cancer.

PET with (18)F-FDG ((18)F-FDG PET) is increasingly used in the definition of target volumes for radiotherapy, especially in patients with non-small cell lung cancer (NSCLC). In this context, the delineation of tumor contours is crucial and is currently done by different methods. This investigation compared the gross tumor volumes (GTVs) resulting from 4 methods used for this purpose in a set of clinical cases. METHODS: Data on the primary tumors of 25 patients with NSCLC were analyzed. They had (18)F-FDG PET during initial tumor staging. Thereafter, additional PET of the thorax in treatment position was done, followed by planning CT. CT and PET images were coregistered, and the data were then transferred to the treatment planning system (PS). Sets of 4 GTVs were generated for each case by 4 methods: visually (GTV(vis)), applying a threshold of 40% of the maximum standardized uptake value (SUV(max); GTV(40)), and using an isocontour of SUV = 2.5 around the tumor (GTV(2.5)). By phantom measurements we determined an algorithm, which rendered the best fit comparing PET with CT volumes using tumor and background intensities at the PS. Using this method as the fourth approach, GTV(bg) was defined. A subset of the tumors was clearly delimitable by CT. Here, a GTV(CT) was determined. RESULTS: We found substantial differences between the 4 methods of up to 41% of the GTV(vis). The differences correlated with SUV(max), tumor homogeneity, and lesion size. The volumes increased significantly from GTV(40) (mean 53.6 mL) < GTV(bg) (94.7 mL) < GTV(vis) (157.7 mL) and GTV(2.5) (164.6 mL). In inhomogeneous lesions, GTV(40) led to visually inadequate tumor coverage in 3 of 8 patients, whereas GTV(bg) led to intermediate, more satisfactory volumes. In contrast to all other GTVs, GTV(40) did not correlate with the GTV(CT). CONCLUSION: The different techniques of tumor contour definition by (18)F-FDG PET in radiotherapy planning lead to substantially different volumes, especially in patients with inhomogeneous tumors. Here, the GTV(40) does not appear to be suitable for target volume delineation. More complex methods, such as system-specific contrast-oriented algorithms for contour definition, should be further evaluated with special respect to patient data.     

Prospective feasibility trial of radiotherapy target definition for head and neck cancer using 3-dimensional PET and CT imaging.

The aim of this investigation was to evaluate the influence and accuracy of (18)F-FDG PET in target volume definition as a complementary modality to CT for patients with head and neck cancer (HNC) using dedicated PET and CT scanners. METHODS: Six HNC patients were custom fitted with head and neck and upper body immobilization devices, and conventional radiotherapy CT simulation was performed together with (18)F-FDG PET imaging. Gross target volume (GTV) and pathologic nodal volumes were first defined in the conventional manner based on CT. A segmentation and surface-rendering registration technique was then used to coregister the (18)F-FDG PET and CT planning image datasets. (18)F-FDG PET GTVs were determined and displayed simultaneously with the CT contours. CT GTVs were then modified based on the PET data to form final PET/CT treatment volumes. Five-field intensity-modulated radiation therapy (IMRT) was then used to demonstrate dose targeting to the CT GTV or the PET/CT GTV. RESULTS: One patient was PET-negative after induction chemotherapy. The CT GTV was modified in all remaining patients based on (18)F-FDG PET data. The resulting PET/CT GTV was larger than the original CT volume by an average of 15%. In 5 cases, (18)F-FDG PET identified active lymph nodes that corresponded to lymph nodes contoured on CT. The pathologically enlarged CT lymph nodes were modified to create final lymph node volumes in 3 of 5 cases. In 1 of 6 patients, (18)F-FDG-avid lymph nodes were not identified as pathologic on CT. In 2 of 6 patients, registration of the independently acquired PET and CT data using segmentation and surface rendering resulted in a suboptimal alignment and, therefore, had to be repeated. Radiotherapy planning using IMRT demonstrated the capability of this technique to target anatomic or anatomic/physiologic target volumes. In this manner, metabolically active sites can be intensified to greater daily doses. CONCLUSION: Inclusion of (18)F-FDG PET data resulted in modified target volumes in radiotherapy planning for HNC. PET and CT data acquired on separate, dedicated scanners may be coregistered for therapy planning; however, dual-acquisition PET/CT systems may be considered to reduce the need for reregistrations. It is possible to use IMRT to target dose to metabolically active sites based on coregistered PET/CT data.     

The Reasons for Discrepancies in Target Volume Delineation

PURPOSE: To understand the reasons for differences in the delineation of target volumes between physicians. MATERIAL AND METHODS: 18 Swiss radiooncology centers were invited to delineate volumes for one prostate and one head-and-neck case. In addition, a questionnaire was sent to evaluate the differences in the volume definition (GTV [gross tumor volume], CTV [clinical target volume], PTV [planning target volume]), the various estimated margins, and the nodes at risk. Coherence between drawn and stated margins by centers was calculated. The questionnaire also included a nonspecific series of questions regarding planning methods in each institution. RESULTS: Fairly large differences in the drawn volumes were seen between the centers in both cases and also in the definition of volumes. Correlation between drawn and stated margins was fair in the prostate case and poor in the head-and-neck case. The questionnaire revealed important differences in the planning methods between centers. CONCLUSION: These large differences could be explained by (1) a variable knowledge/interpretation of ICRU definitions, (2) variable interpretations of the potential microscopic extent, (3) difficulties in GTV identification, (4) differences in the concept, and (5) incoherence between theory (i.e., stated margins) and practice (i.e., drawn margins).     

PET／CT确定食管癌大体靶区的研究进展

随着功能影像及分子影像的发展,PET／CT逐渐成为辅助制定肿瘤最佳精确放疗计划的成像方式。许多研究支持18F-FDGPET／CT用于精确放疗中食管癌的靶区勾画,然而18F-FDGPET／CT在食管癌靶区勾画中的有效性尚需进一步研究。该文主要对18F—FDGPET／CT用于食管癌原发病灶、区域转移淋巴结GTV勾画的应用价值及有效性等方面的研究进行综述。     

A new role of PET/CT for target delineation for radiotherapy treatment planning for head and neck carcinomas

Fluorine-18-fluorodeoxyglucose- positron emission tomography ((18)F-FDG PET) in head and neck cancer patients is useful for staging, identification of macroscopic disease, detection of invaded lymph nodes and distant metastases, delineation of radiotherapy target volume and assessment of treatment response. This brief review addresses the potential role of PET in radiotherapy planning as compared to MRI and CT scan. Positron emission tomography is considered by radiation oncologists a useful test for the identification of the specific target volume for treatment. In addition, a number of hypoxia-related PET radiopharmaceuticals such as the fluorine-18-fluoromisonidazole ((18)F-FMISO) and the fluorine-18-fluoroazomycin arabinoside ((18)F-FAZA) are now available in order to identify hypoxic tumor subvolumes helping to implement new radiotherapy techniques. Magnetic resonance imaging (MRI) has the advantage to discriminate the soft tissue contrast from the tumor, against computerized tomography (CT), but PET/CT scans have the additional advantage to incorporate the metabolic imaging for improving the delineation of variable and hypoxic tumor tissue in the head and neck region. Regardless of the method used for determining the gross tumor volume, clinical examination remains irreplaceable. In conclusion, PET/CT offers complementary information for the delineation of the primary tumor and the corresponding lymph nodes compared to the use of MRI and CT and can support the use of modern radiotherapy techniques, having fewer toxicities.     

Advances in image-guided radiation therapy--the role of PET-CT.

In the era of image-guided radiation therapy (IGRT), the greatest challenge remains target delineation, as the opportunity to maximize cures while simultaneously decreasing radiation dose to the surrounding normal tissues is to be realized. Over the last 2 decades, technological advances in radiographic imaging, biochemistry, and molecular biology have played an increasing role in radiation treatment planning, delivery, and evaluation of response. Previously, fluoroscopy formed the basis of radiation treatment planning. Beginning in the late 1980s, computed tomography (CT) has become the basis for modern radiation treatment planning and delivery, coincident with the rise of 3-dimensional conformal radiation therapy (3DCRT). Additionally, multi-modality anatomic imaging registration was the solution pursued to augment delineation of tumors and surrounding structures on CT-based treatment planning. Although these imaging modalities provide the customary anatomic details necessary for radiation treatment planning, they have limitations, including difficulty with identification of small tumor deposits, tumor extension, and distinction from scar tissues. To overcome these limitations, PET and, more recently, PET-CT have been innovative regarding the extent of disease appraisal, target delineation in the treatment planning, and assessment of therapy response. We review the role of functional imaging in IGRT as it reassures transformations on the field of radiation oncology. As we move toward the era of IGRT, the use of multi-modality imaging fusion, and the introduction of more sensitive and specific PET-CT tracers may further assist target definition. Furthermore, the potential to predict early outcome or even detect early recurrence of tumor, may allow for the tailoring of intervention in cancer patients. The convergence of a biological target volume, and perhaps multi-tracer tumor, molecular, and genetic profile tumors will probably be vital in cancer treatment selection. Nevertheless, prospective clinical experience with outcome is encouraged and needs to be expanded to entirely exploit the benefits of the IGRT.     

Relevance of Positron Emission Tomography (PET) in Oncology

BACKGROUND: The clinical use of positron emission tomography (PET) for detection and staging of malignant tumors is rapidly increasing. Furthermore, encouraging results for monitoring the effects of radio- and chemotherapy have been reported. METHODS: This review describes the technical principles of PET and the biological characteristics of tracers used in oncological research and patient studies. The results of clinical studies published in peer reviewed journals during the last 5 years are summarized and clinical indications for PET scans in various tumor types are discussed. RESULTS AND CONCLUSIONS: Numerous studies have documented the high diagnostic accuracy of PET studies using the glucose analogue F-18-fluordeoxyglucose (FDG-PET) for detection and staging of malignant tumors. In this field, FDG-PET has been particularly successful in lung cancer, colorectal cancer, malignant lymphoma and melanoma. Furthermore, FDG-PET has often proven to be superior to morphological imaging techniques for differentiation of tumor recurrence from scar tissue. Due to the high glucose utilization of normal gray matter radiolabeled amino-acids like C-11-methionine are superior to FDG for detection and delineation of brain tumors by PET. In the future, more specific markers of tumor cell proliferation and gene expression may allow the application of PET not only for diagnostic imaging also but for non-invasive biological characterization of malignant tumors and early monitoring of therapeutic interventions.     

Radiotherapy planning: PET/CT scanner performances in the definition of gross tumour volume and clinical target volume

Purpose Positron emission tomography is the most advanced scintigraphic imaging technology and can be employed in the planning of radiation therapy (RT). The aim of this study was to evaluate the possible role of fused images (anatomical CT and functional FDG-PET), acquired with a dedicated PET/CT scanner, in delineating gross tumour volume (GTV) and clinical target volume (CTV) in selected patients and thus in facilitating RT planning.Methods Twenty-eight patients were examined, 24 with lung cancer (17 non-small cell and seven small cell) and four with non-Hodgkins lymphoma in the head and neck region. All patients underwent a whole-body PET scan after a CT scan. The CT images provided morphological volumetric information, and in a second step, the corresponding PET images were overlaid to define the effective target volume. The images were exported off-line via an internal network to an RT simulator.Results Three patient were excluded from the study owing to change in the disease stage subsequent to the PET/CT study. Among the remaining 25 patients, PET significantly altered the GTV or CTV in 11 (44%) . In five of these 11 cases there was a reduction in GTV or CTV, while in six there was an increase in GTV or CTV.Conclusion FDG-PET is a highly sensitive imaging modality that offers better visualisation of local and locoregional tumour extension. This study confirmed that co-registration of CT data and FDG-PET images may lead to significant modifications of RT planning and patient management.An erratum to this article can be found at     

Variability of Gross Tumor Volume Delineation in Head-and-Neck Cancer Using PET/CT Fusion,Part II: The Impact of a Contouring Protocol

The purpose of this study was to assess the efficacy of a gross tumor volume (GTV) contouring protocol on interobserver variability between 4 physicians in positron emission therapy/computed tomography (PET/CT) treatment planning of head-and-neck cancer. A GTV contouring protocol for PET/CT treatment planning was developed utilizing 4 stages: Preliminary contouring on CT alone, determination of appropriate PET windowing, accurate image registration, and modification of CT contouring with correctly formatted PET/CT display and rules for modality disagreement. Two neuroradiologists and 2 radiation oncologists (designated as A, B, C, and D, respectively) were given a tutorial of PET/CT coregistered imaging individualized to their skill level, which included a step-by-step explanation of the protocol with clinical examples. Opportunities for questions and hands-on practice were given. The physicians were asked to re-contour 16 head-and-neck patients from Part I on PET/CT fusion imaging. Differences in volume magnitude were analyzed for statistical significance by analysis of variance (ANOVA) and paired t-tests (α < 0.05). Volume overlap was analyzed for statistical significance using Wilcoxon signed-rank tests (α < 0.05). Volume overlap increased significantly from Part I to Part II (p < 0.05). One previously significant difference between physicians disappeared with the protocol in place. The mean fusion volume of Physician C, however, remained significantly larger than that of Physician D (p < 0.01). This result is unchanged from Part I. The multidisciplinary contouring protocol significantly improved the coincidence of GTVs contoured by multiple physicians. The magnitudes of the volumes showed marginal improvement in consistency. Developing an institutional contouring protocol for PET/CT treatment planning is highly recommended to reduce interobserver variability.     

PET/CT scanning guided intensity-modulated radiotherapy in treatment of recurrent ovarian cancer

Objective

This study was undertaken to evaluate the clinical contribution of positron emission tomography using ¹⁸F-fluorodeoxyglucose and integrated computer tomography (FDG-PET/CT) guided intensity-modulated radiotherapy (IMRT) for treatment of recurrent ovarian cancer.

Materials and methods

Fifty-eight patients with recurrent ovarian cancer from 2003 to 2008 were retrospectively studied. In these patients, 28 received PET/CT guided IMRT (PET/CT–IMRT group), and 30 received CT guided IMRT (CT–IMRT group). Treatment plans, tumor response, toxicities and survival were evaluated.

Results

Changes in GTV delineation were found in 10 (35.7%) patients based on PET–CT information compared with CT data, due to the incorporation of additional lymph node metastases and extension of the metastasis tumor. PET/CT guided IMRT improved tumor response compared to CT–IMRT group (CR: 64.3% vs. 46.7%, P = 0.021; PR: 25.0% vs. 13.3%, P = 0.036). The 3-year overall survival was significantly higher in the PET–CT/IMRT group than control (34.1% vs. 13.2%, P = 0.014).

Conclusions

PET/CT guided IMRT in recurrent ovarian cancer patients improved the delineation of GTV and reduce the likelihood of geographic misses and therefore improve the clinical outcome.