Annette Hogg

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.

CLINICAL IMPACT OF, AND PROGNOSTIC STRATIFICATION BY, F-18 FDG PET/CT IN HEAD AND NECK MUCOSAL SQUAMOUS CELL CARCINOMA

The aim of this study was to determine prospectively the incremental value of positron emission tomography/computed tomography (PET/CT) over conventional assessment (clinical examination and CT/MRI imaging).

Investigations with FDG-PET scanning in prostate cancer show limited value for clinical practice.

The aim of this study was to investigate FDG-PET (fluorodeoxyglucose positron emission tomography) imaging in the management of prostate cancer. Twenty-two patients were studied during different disease phases of prostate cancer, for staging or restaging to clarify specific clinical questions. FDG-PET was performed encompassing the thorax, abdomen and pelvis using the Penn PET 300H scanner. Scanning was begun 60 min after 18 F fluorodeoxyglucose marker. Patients were catheterized and administered diuretics to minimize urinary activity. Information obtained with FDG-PET was concordant with findings from other investigations in 7/22 (32%) patients, discordant in 15/22 (68%) patients and equivalent in one patient (4%). PET indicated progressive disease in five patients with prostate-specific antigen (PSA) <4 ng/L. The impact on management of the patients was high in 46% of cases, low in 41% and for 14% there was no impact on management. The accuracy of FDG-PET was 72% (95% CI 50-89) as confirmed by invasive diagnostics/follow-up. FDG-PET can provide useful information and improve the clinicians decision on further management procedures in selected patients with low PSA and bone or lymph node changes. A negative PET scan in prostate cancer should be interpreted with caution.

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.

Inactivation of a c-Myb/estrogen receptor fusion protein in transformed primary cells leads to granulocyte/macrophage differentiation and down regulation of c- kit but not c- myc or cdc2

Primary murine fetal hemopoietic cells were transformed with a fusion protein consisting of the ligand-binding domain of the estrogen receptor and a carboxyl-terminally truncated c-Myb protein (ERMYB). The ERMYB-transformed hemopoietic cells exhibit an immature myeloid phenotype when grown in the presence of β-estradiol. Upon removal of β-estradiol, the ERMYB cells display increased adherence, decreased clonogenicity and differentiate to cells exhibiting granulocyte or macrophage morphology. The expression of the c-myc, c-kit, cdc2 and bcl-2 genes, which are putatively regulated by Myb, was investigated in ERMYB cells grown in the presence or absence of β-estradiol. Neither c-myc nor cdc2 expression was down-regulated after removal of β-estradiol demonstrating that differentiation is not a consequence of decreased transactivation of these genes by ERMYB. While bcl-2 expression was reduced by 50% in ERMYB cells grown in the absence of β-estradiol, there was no increase in DNA laddering, suggesting that Myb was not protecting ERMYB cells from apoptosis. In contrast, a substantial (200-fold) decrease in c-kit mRNA level was observed following differentiation of ERMYB cells, and c-kit mRNA could be partially re-induced by the re-addition of β-estradiol. Furthermore, a reporter construct containing the c-kit promoter was activated when cotransfected with a Myb expression vector, providing further evidence of a role for Myb in the regulation of c-kit.

The impact of 18-fluorodeoxyglucose positron emission tomography on the staging, management and outcome of anal cancer.

Accurate inguinal and pelvic nodal staging in anal cancer is important for the prognosis and planning of radiation fields. There is evidence for the role of 18-fluorodeoxyglucose positron emission tomography (FDG-PET) in the staging and management of cancer, with early reports of an increasing role in outcome prognostication in a number of tumours. We aimed to determine the effect of FDG-PET on the nodal staging, radiotherapy planning and prognostication of patients with primary anal cancer. Sixty-one consecutive patients with anal cancer who were referred to a tertiary centre between August 1997 and November 2005 were staged with conventional imaging (CIm) (including computed tomography (CT), magnetic resonance imaging, endoscopic ultrasound and chest X-ray) and by FDG-PET. The stage determined by CIm and the proposed management plan were prospectively recorded and changes in stage and management as a result of FDG-PET assessed. Patients were treated with a uniform radiotherapy technique and dose. The accuracy of changes and prognostication of FDG-PET were validated by subsequent clinical follow-up. Kaplan–Meier survival analysis was used to estimate survival for the whole cohort and by FDG-PET and CIm stage. The tumour-stage group was changed in 23% (14 out of 61) as a result of FDG-PET (15% up-staged, 8% down-staged). Fourteen percent of T1 patients (3 out of 22), 42% of T2 patients (10 out of 24) and 40% of T3–4 patients (6 out of 15) assessed using CIm, had a change in their nodal or metastatic stage following FDG-PET. Sensitivity for nodal regional disease by FDG-PET and CIm was 89% and 62%, respectively. The staging FDG-PET scan altered management intent in 3% (2 out of 61) and radiotherapy fields in 13% (8 out of 61). The estimated 5-year overall survival (OS) and progression-free survival (PFS) for the cohort were 77.3% (95% confidence interval (CI): 55.3–90.4%) and 72.2% (95% CI: 51.5–86.4%), respectively. The estimated 5-year PFS for FDG-PET and CIm staged N2-3 disease was 70% (95% CI: 42.8–87.9%) and 55.3% (95% CI: 23.3–83.4%), respectively. FDG-PET shows increased sensitivity over CIm for staging nodal disease in anal cancer and changes treatment intent or radiotherapy prescription in a significant proportion of patients.

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.

The Impact of 18-Fluorodeoxyglucose Positron Emission Tomography-Computed Tomography on the Staging and Management of Primary Rectal Cancer

Purpose18-fluorodeoxyglucose positron emission tomography-computed tomography (FDG PET-CT) has a role in recurrent colorectal cancer. This study was designed to assess the impact of PET-CT on management of primary rectal cancer.MethodsEighty-three patients with rectal cancer underwent PET-CT scan between 2002 and 2005. Referring physicians prospectively recorded stage and management plan after conventional imaging before PET-CT scan, which were compared to subsequent stage and management after PET-CT.ResultsStaging PET-CT caused a change in stage from conventional imaging in 26 patients (31 percent). Twelve (14 percent) were upstaged (7 change in N stage; 4 change in M stage; 1 change in N and M stage), and 14 (17 percent) were downstaged (10 change in N stage; 3 change in M stage; 1 change in N and M stage). PET-CT scan altered management intent in seven patients (8 percent) (curative to palliative 6 patients; palliative to curative 1 patient). Management was altered in ten patients (12 percent). There was no difference in impact with respect to tumor height.ConclusionsPET-CT scan impacts the management of patients with primary rectal cancer and influences staging/therapy in a third of patients and should be a component of rectal cancer workup.

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.