Robert E. Ware

Utility of positron emission tomography for the detection of disease in residual neck nodes after (chemo)radiotherapy in head and neck cancer.

This study evaluates the utility of fluorine‐18 fluorodeoxyglucose positron emission tomography (FDG PET) in patients with a node‐positive mucosal head and neck squamous cell carcinoma who achieved a complete response at the primary site but had a residual mass in the neck 8 weeks or more after definitive (chemo)radiotherapy.

Fluorine-18 fluorodeoxyglucose Positron emission tomography, Gallium-67 scintigraphy, and conventional staging for Hodgkin's disease and non-Hodgkin's lymphoma

PURPOSE To compare fluorine-18 fluorodeoxyglucose positron emission tomography (PET) and gallium scanning with each other and with conventional staging, for patients with Hodgkins disease or non-Hodgkins lymphoma. SUBJECTS AND METHODS Fifty patients had PET, gallium scanning, and conventional staging of newly diagnosed or progressive Hodgkins disease or non-Hodgkins lymphoma. Disease sites, stage, and treatment plans were assessed retrospectively. RESULTS Positron emission tomography and gallium scanning each upstaged 14% of patients (n = 7). Management was altered by PET in 9 cases (18%) and by gallium scanning in 7 (14%, P = 0.6). Disease was evident in 117 sites in 42 patients. The case positivity rate for conventional assessment was 90%; for PET, 95%; for gallium scanning, 88%; for conventional assessment plus PET, 100%; and for conventional assessment plus gallium scanning, 98%. Site positivity rates for conventional assessment were 68%; for PET, 82%; for gallium scanning, 69% (conventional vs. PET, P = 0.01; conventional vs. gallium scanning, P = 0.9; PET vs. gallium scanning, P = 0.01); for conventional assessment plus PET, 96%; and for conventional assessment plus gallium scanning, 94%. Positron emission tomography and gallium scanning were entirely concordant in 31 patients; in the other 19 patients, PET identified 25 sites missed by gallium scanning, whereas gallium scanning identified 10 sites missed by PET. CONCLUSION In this retrospective study, PET demonstrated a higher site positivity rate than did gallium scanning, with similar case positivity rates. These data support the use of PET in place of gallium scanning for the staging of patients with Hodgkins disease or non-Hodgkins lymphoma.

Clinical Impact of 18F Fluorodeoxyglucose Positron Emission Tomography in Patients With Non–Small-Cell Lung Cancer: A Prospective Study

PURPOSE To prospectively study the impact of (18)F fluorodeoxyglucose (FDG) positron emission tomography (PET) on clinical management of patients with non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS One hundred five consecutive patients with NSCLC undergoing (18)F FDG PET were analyzed. Before PET, referring physicians recorded scan indication, conventional clinical stage, and proposed treatment plan. PET scan results were reported in conjunction with available clinical and imaging data, including results of computed tomography (CT). Subsequent management and appropriateness of PET-induced changes were assessed by follow-up for at least 6 months or until the patients death. RESULTS Indications for PET were primary staging (n = 59), restaging (n = 34), and suspected malignancy subsequently proven to be NSCLC (n = 12). In 27 (26%) of 105 of cases, PET results led to a change from curative to palliative therapy by upstaging disease extent. Validity of the PET result was established in all but one case. PET appropriately downstaged 10 of 16 patients initially planned for palliative therapy, allowing either potentially curative treatment (four patients) or no treatment (six patients). PET influenced the radiation delivery in 22 (65%) of 34 patients who subsequently received radical radiotherapy. Twelve patients considered probably inoperable on conventional imaging studies were downstaged by PET and underwent potentially curative surgery. PET missed only one primary tumor (5-mm scar carcinoma). CT and PET understaged three of 20 surgical patients (two with N1 lesions < 5 mm and one with unrecognized atrial involvement), and PET missed one small intrapulmonary metastasis apparent on CT. No pathological N2 disease was missed on PET. CONCLUSION FDG PET scanning changed or influenced management decisions in 70 patients (67%) with NSCLC. Patients were frequently spared unnecessary treatment, and management was more appropriately targeted.

Powerful Prognostic Stratification By [18F]Fluorodeoxyglucose Positron Emission Tomography in Patients With Metastatic Breast Cancer Treated With High-Dose Chemotherapy

PURPOSE This study examines the use of [(18)F]fluorodeoxyglucose positron emission tomography (FDG-PET) for the evaluation of the therapeutic response for patients treated with high-dose chemotherapy (HDC) with autologous stem cell transplantation for metastatic breast cancer (MBC) focusing on prognostic stratification. PATIENTS AND METHODS Forty-seven patients with MBC were treated with a maximum of three cycles of HDC. Therapeutic response was assessed with conventional imaging (CImg; including a computed tomography in all cases and ultrasound, mammography, and bone scanning as clinically indicated) and by FDG-PET study performed after the last cycle of HDC. Parameters analyzed for predicting survival were FDG-PET and CImg results, pattern of disease, prior treatment, and HDC regimen. RESULTS Complete responses were observed in 16 patients (37%) with CImg and 34 patients (72%) with FDG-PET. The FDG-PET result was the most powerful and independent predictor of survival; patients with a negative post-treatment FDG-PET had a longer median survival than patients with a positive FDG-PET (24 months v 10 months; P < .001). By multivariate analysis the relative risk (RR) of death was higher in patients with FDG-PET-positive disease (RR, 5.3), prior anthracycline treatment (RR, 3.3), or with visceral metastasis (RR, 2.4). CONCLUSION A single FDG-PET study performed after completion of HDC for MBC can powerfully stratify for survival. This may have implications for how we should assess outcome after conventional-dose therapy for MBC and warrants additional study.

USEFULNESS OF FLUORINE-18 FLUORODEOXYGLUCOSE POSITRON EMISSION TOMOGRAPHY IN PATIENTS WITH A RESIDUAL STRUCTURAL ABNORMALITY AFTER DEFINITIVE TREATMENT FOR SQUAMOUS CELL CARCINOMA OF THE HEAD AND NECK

Residual structural abnormalities after definitive treatment of head and neck squamous cell carcinoma (HNSCC) are common and pose difficult management problems. The usefulness of fluorine‐18 fluorodeoxyglucose positron emission tomography (FDG PET) to supplement conventional evaluation with clinical and standard radiologic examination (CE) in such patients was assessed.

How do oncologists deal with incidental abnormalities on whole-body fluorine-18 fluorodeoxyglucose PET/CT?

Combined positron emission tomography (PET)/computed tomography (CT) using fluorine‐18 fluorodeoxyglucose (FDG) is an exciting technique for cancer evaluation, but false‐positive results are a recognized limitation. The aim of the study was to evaluate how oncologists deal with focal extrathyroidal FDG abnormalities considered by imaging specialists to be unrelated to the referral indication.

Comparative PET study using F-18 FET and F-18 FDG for the evaluation of patients with suspected brain tumour

The aim of this prospective pilot study in patients with suspected or known brain tumour was to establish the diagnostic value of O-(2-[(18)F]-fluoroethyl)-L-tyrosine (FET) positron emission tomography (PET) when compared to fluorine-18 fluorodeoxyglucose (FDG) PET. Twenty-five FET PET and FDG PET scans were performed on 21 consecutive patients within 24 months. Final malignant pathology included 11 glioma (eight low-grade, three high grade), two lymphoma, one olfactory ganglioneuroblastoma, one anaplastic meningioma. Benign pathology included two encephalitis and one cortical dysplasia. Definitive pathology was not available in three patients. The accuracy of PET was determined by subsequent surgical histopathology in 12 and clinical/imaging course in nine patients. Median follow-up period was 20 months. FET sensitivity was 93%, specificity 100%, accuracy 96%, positive predictive value (PPV) 100% and negative predictive value (NPV) 91%. FDG sensitivity was 27%, specificity 90%, accuracy 52%, PPV 80% and NPV 45%. FET PET is more accurate than FDG PET for detecting malignant brain lesions, especially low-grade gliomas.

The Cost-Effective Use of 18F-FDG PET in the Presurgical Evaluation of Medically Refractory Focal Epilepsy

This study applied decision tree analysis to evaluate the sensitivity, specificity, and cost-effectiveness of clinical algorithms that incorporate 18F-FDG PET. Methods: A cohort of 176 patients was studied. The localization rate, accuracy, therapeutic impact on the presurgical decision-making process, and correlation with the postsurgical outcome were assessed for the tests commonly performed for seizure localization. Decision tree sensitivity analysis compared 3 imaging strategies with a baseline strategy of medical therapy for all: video-electroencephalography monitoring (VEM)/MRI strategy, in which patients underwent VEM and brain MRI only, and +SPECT and +PET strategies, in which patients with an indeterminate VEM/MRI result underwent ictal SPECT or interictal 18F-FDG PET, respectively. Results: The localization rates for VEM, MRI, 18F-FDG PET, ictal SPECT, and intracranial electroencephalography (EEG) were 62.2%, 35.8%, 75.0%, 60.0%, and 93.8%. The VEM/MRI strategy had the lowest cost per class I/II outcome, but the additional costs per class I/II outcome for the +PET and +SPECT strategies were always below the minimum reported cost savings for a class I/II outcome. There were no valid conditions in which the +SPECT strategy had a lower cost per class I/II outcome than the +PET strategy. Within the range of cost savings estimated to be associated with a class I/II outcome, all decision strategies produced net cost savings; however, these were significantly higher for the +PET and the +SPECT strategies. Conclusion: 18F-FDG PET is cost-effective in the presurgical evaluation, particularly when used in patients with a nonlocalizing or nonconcordant VEM or MRI result.

RADIATION CHANGES DO NOT INTERFERE WITH POSTCHEMORADIATION RESTAGING OF PATIENTS WITH RECTAL CANCER BY FDG PET/CT BEFORE CURATIVE SURGICAL THERAPY

PURPOSE Changes in F-18 fluorodeoxyglucose (FDG) uptake in normal tissues after chemoradiation therapy (CRT) potentially limit the ability of positron emission tomography (PET) to provide early assessment of therapeutic response. This study evaluated whether such changes negatively impact interpretation of posttherapy PET performed within 6 weeks of CRT completion and before definitive surgery in patients with locally advanced rectal cancer. The positive predictive value (PPV) and specificity of post-CRT PET, read clinically, was determined in 63 consecutive rectal cancer patients who had undergone preoperative CRT. METHODS AND MATERIALS A schema for identifying and scoring postradiation effects on PET was prospectively defined and applied in a blinded manner. This was compared with initial clinical reporting of response. Histologic assessment of the operative specimens was used as the reference standard. Correlation between clinical proctitis during CRT and radiation changes on subsequent PET was also assessed. RESULTS Clinical reporting of post-CRT PET yielded a high PPV (94%; 95% confidence interval, 89--100%) but may have been exaggerated by the low prevalence of complete tumor clearance (16%). The specificity was 80% with only two false-positive results. On blinded reading, significant post-CRT effects on PET were recorded in 4 of 63 patients (6% 95% confidence interval, 0-13%), but pattern recognition converted both false-positive PET results to a complete metabolic response. Clinical CRT proctitis was not correlated with PET findings. CONCLUSION Postradiation effects do not appear to significantly compromise the interpretation of PET for therapeutic response assessment. The proposed PET pattern of response may further improve the specificity of PET.

PET/CT: will it change the way that we use CT in cancer imaging?

Accurate staging of cancer is of fundamental importance to treatment selection and planning. Current staging paradigms focus, first, on a detailed delineation of the primary tumour in order to determine its suitability for resection, and, thereafter, on assessment of the presence of metastatic spread that would alter the surgical approach, or mandate non-surgical therapies. This approach has, at its core, the assumption that the best, and sometimes the only, way to cure a patient of cancer is by surgical resection. Unfortunately, all non-invasive techniques in current use have imperfect ability to identify those primary tumours that are able to be completely excised, and even worse ability to define the extent of metastatic spread. Nevertheless, because of relatively low cost and widespread availability, computed tomography (CT) scanning is the preferred methodology for tumour, nodal and systemic metastasis (TNM) staging. This is often supplemented by other tests that have improved performance in particular staging domains. For example, magnetic resonance imaging (MRI), mammography, or endoscopic ultrasound may be used as complementary tests for T-staging; surgical nodal sampling for N-staging; and bone scanning, MRI or ultrasound for M-staging. Accordingly, many patients undergo a battery of investigations but, even then, are found to have been incorrectly staged based on subsequent outcomes. Even for those staged surgically, pathology can only identify metastases within the resection specimens and has no capability for detecting remote disease. As a result of this, many patients undergo futile operations for disease that could never have been cured by surgery. In the case of restaging, the situation is even worse. The sequelae of prior treatment can be difficult to differentiate from residual cancer and the likelihood of successful salvage therapy is even less than at presentation. More deleteriously, patients may be subjected to additional morbid treatments when cure has already been achieved. Thus, in post-treatment follow-up, the presence and extent of disease is equally critical to treatment selection and patient outcome as it is in primary staging. One of the major strengths of positron emission tomography (PET)/CT as a cancer staging modality is its ability to identify systemic metastases. At any phase of cancer evaluation, demonstration of systemic metastasis has profound therapeutic and prognostic implications. Only in the absence of systemic metastasis does nodal status become important, and only when unresectable nodal metastasis has been excluded does T-stage become important. There are now accumulating data that PET/CT could be used as the first, rather than the last test to assess M- and N-stage for evaluating cancers with an intermediate to high pre-test likelihood of metastatic disease based on poor long-term survival. In this scenario, there is great opportunity for subsequently selecting and tailoring the performance of anatomically based imaging modalities to define the structural relations of abnormalities identified by PET, when this information would be of relevance to management planning. Primary staging of oesophageal cancer and restaging of colorectal cancer are illustrative examples of a new paradigm for cancer imaging.