Prognostic Value of 2-[(18)F] Fluoro-2-deoxy-D-glucose Positron Emission Tomography-Computed Tomography Scan Carried out During and After Radiation Therapy for Head and Neck Cancer Using Visual Therapy Response Interpretation Criteria.

AIMS: To evaluate the prognostic utility of 2-[(18)F] fluoro-2-deoxy-d-glucose positron emission tomography-computed tomography (FDG PET-CT) carried out in the third week (iPET) and after completion (pPET) of definitive radiation therapy in patients with mucosal primary head and neck squamous cell carcinoma (MPHNSCC) and to investigate the optimal visual grading criteria for therapy response assessment. MATERIALS AND METHODS: Sixty-nine consecutive patients with newly diagnosed MPHNSCC treated with radical radiation therapy with or without systemic therapy underwent staging. PET-CT, iPET and pPET were included. All PET-CT images were reviewed by using a visual grading system to assess metabolic response for primary tumour: 0 = similar to adjacent background blood pool activity; 1 = more than background but < mediastinal blood pool; 2 ≥ mediastinal blood pool and < liver; 3 ≥ liver; and 4 ≥ brain. The results were correlated with locoregional recurrence-free survival (LRFS), disease-free survival (DFS) and overall survival, using Kaplan-Meier analysis. RESULTS: The median follow-up was 28 months (range 6-62), the median age was 61 years (range 39-81) and AJCC 7th edition clinical stage II, III and IV were six, 18 and 45 patients, respectively. The optimal threshold for non-complete metabolic response (non-CMR) was defined as focal uptake ≥ liver (grade 3) for iPET and focal uptake ≥ mediastinum (grade 2) for pPET. The 2 year Kaplan-Meier LRFS, DFS and overall survival estimates for primary CMR and non-CMR in iPET were 89.8% versus 71.5% (P = 0.062), 80.1% versus 65.3% (P = 0.132), 79.1% versus 72.1% (P = 0.328) and in pPET 86.2% versus 44.6% (P = 0.0005), 77.6% versus 41.2% (P = 0.006), 81.2% versus 40.6% (P = 0.01), respectively. The negative predictive value (NPV) for LRFS for patients achieving both primary and nodal CMR in iPET was 100%. No locoregional failure was observed in patients with both primary and nodal iPET CMR (P = 0.038), whereas those with nodal iPET CMR had no regional failure (P = 0.033). However, the positive predictive values (PPV) for LRFS and DFS for iPET and pPET were found to be poor: 30% and 36% for iPET and 35% and 39% for pPET, respectively. CONCLUSION: Standardised criteria using visual assessment are feasible. The metabolic response using visual assessment with standardised interpretation criteria of iPET and pPET can be useful predictors of tumour control. Dose de-escalation can be considered on the basis of a high NPV for iPET. However, the PPV of iPET is poor, indicating that additional discriminative tools are needed.

Positron emission tomography changes management and prognostic stratification in patients with oesophageal cancer: results of a multicentre prospective study.

OBJECTIVES: The aims of this study were (1) to determine the incremental information provided by (18)F-FDG positron emission tomography (PET) in staging patients with oesophageal cancer, and (2) to determine the impact of PET staging on post-PET clinical management of oesophageal cancer, and on prognosis. METHODS: In a multicentre, single-arm open study, patients with proved oesophageal cancer without definite distant metastases and regarded as suitable for potentially curative treatment were examined by PET. Clinicians were requested to supply a management plan before and another plan after being supplied with the PET scan results. Patients were followed for at least 1 year for outcome analysis. RESULTS: A total of 129 patients (104 men, mean age 67 y) were recruited. PET detected additional sites of disease in 53 patients (41%). Significant changes in management (high or medium impact) were observed in 38% of patients, primarily as a result of identifying additional sites of disease and/or confirming previously equivocal regional and distant metastases. Progression-free survival was significantly shorter in patients found to have additional lesions on PET (p < 0.05), but was not related to SUV(max). CONCLUSION: These findings demonstrate the significant impact of PET on the clinical management of patients with newly diagnosed oesophageal carcinoma, and on prognostic stratification of these patients.

The role of FDG-PET in the management of non-small cell lung carcinoma.

INTRODUCTION: Positron emission tomography (PET) using 18F-2-fluoro-2 deoxy-D-glucose (FDG) has been widely investigated and used in the non-invasive imaging of malignancy. Non-small cell lung carcinoma (NSCLC) is one of the most common and best validated indications for an FDG-PET scan. This review examines the roles of FDG-PET in the management of NSCLC and attempts to identify emerging uses and possible future developments. MATERIALS AND METHODS: Literature review of English language literature indexed on Medline. RESULTS: There is strong evidence to support the clinical efficacy and cost effectiveness of FDG-PET in the characterisation of solitary pulmonary nodules and in the staging of NSCLC. In addition, there are emerging uses in radiotherapy planning, monitoring of treatment response and prognostication. CONCLUSIONS: FDG-PET plays an integral role in the management of NSCLC and it is likely to expand as evidence supporting additional roles in the management of NSCLC becomes available.

Optimal pinhole techniques for preoperative localization with Tc-99m MIBI for primary hyperparathyroidism.

PURPOSE: Technetium-99m-labeled 2-methoxyisobutylisonitrile (Tc-99m MIBI) has been used extensively to localize parathyroid adenomas before operation. Imaging techniques vary widely, and the aim of this study was to determine the optimal time of delayed imaging and the value of routine correlative pertechnetate thyroid imaging. MATERIALS AND METHODS: In this study, preoperative parathyroid localization was performed using pinhole anterior and oblique images (15 minutes and 2 and 4 hours after injection) with correlative pertechnetate thyroid images. Ninety-seven patients underwent dual- or triple-phase Tc-99m MIBI imaging and correlative pertechnetate thyroid imaging before surgery. Two nuclear medicine physicians blinded to the surgical findings interpreted all available images and various Tc-99m MIBI image combinations at 15 minutes alone; 15 minutes and 2 hours, 15 minutes and 4 hours; and 15 minutes and 2 and 4 hours each with and without correlative pertechnetate thyroid imaging. RESULTS: Ninety parathyroid adenomas were detected in 86 patients. The optimal results were achieved with 15-minute and 2- and 4-hour Tc-99m-MIBI images, with correlative thyroid scans resulting in a sensitivity rate of 88%. Fifteen-minute and 2-hour Tc-99m-MIBI images and correlative thyroid scans and 15-minute and 4-hour Tc-99m MIBI images and correlative thyroid scans produced similar results (sensitivity rate, 86% and 83%, respectively; P = not significant). Compared with all Tc-99m MIBI image combinations alone, the addition of the routine correlative thyroid scan significantly improved sensitivity and also improved reporter confidence in 45% of studies. CONCLUSIONS: Of the pinhole techniques compared, 15-minute and 2-hour Tc-99m MIBI images with correlative thyroid scanning may be the preferred imaging protocol, because this yields results similar to imaging for as long as 4 hours after injection in a shorter, more logistically acceptable imaging time.

The value of oblique pinhole images in pre-operative localisation with 99mTc-MIBI for primary hyperparathyroidism.

Technetium-99m labelled 2-methoxyisobutylisonitrile (MIBI) has been extensively utilised for preoperative localisation of parathyroid adenomas. Imaging techniques have varied widely, with many centres not performing routine oblique images; thus this study aimed to examine the value of routine oblique pinhole imaging. Ninety-two patients underwent pre-operative 99mTc-MIBI imaging including early and delayed anterior oblique pinhole images in addition to standard anterior pinhole images and a thyroid study prior to surgery for primary hyperparathyroidism. These studies were reviewed blindly comparing anterior and oblique images and anterior images only in relation to surgical findings. Of the 92 patients, 83 were found to have 86 parathyroid adenomas or parathyroid adenoma/hyperplasia at surgery. When compared to anterior images only, oblique views improved overall sensitivity from 76% to 88% (P<0.05), correctly localised 11 more adenomas than anterior images alone (13%) and improved the confidence of interpretation in 17 patients (20%). In conclusion, routine oblique pinhole views result in greater sensitivity and reporter confidence in pre-operative parathyroid localisation with 99mTc-MIBI.

An empirical method for the prediction of T-cell epitopes.

Identification of T-cell epitopes from foreign proteins is the current focus of much research. Methods using simple two or three position motifs have proved useful in epitope prediction for major histocompatibility complex (MHC) class I, but to date not for MHC class II molecules. We utilized data from pool sequence analysis of peptides eluted from two HLA-DR13 alleles to construct a computer algorithm for predicting the probability that a given sequence will be naturally processed and presented on these alleles. We assessed the ability of this method to predict known self-peptides from these DR-13 alleles, DRB1(*)1301 and *1302, as well as an immunodominant T-cell epitope. We also compared the predictions of this scoring procedure with the measured binding affinities of a panel of overlapping peptides from hepatitis B virus surface antigen. We concluded that this method may have wide application for the prediction of T-cell epitopes for both MHC class I and class II molecules.

Growth and metastasis of human bladder cancer xenografts in the bladder of nude rats. A model for intravesical radioimmunotherapy.

A potentially useful therapeutic approach to the treatment of human bladder cancer is intravesical therapy with radiolabelled monoclonal antibodies (MAbs). We have established an animal model to study this approach. Inoculation of cloned 2B8 cells derived from the human bladder cancer cell line, UCRU-BL-17, into the bladder wall of nude rats pre-irradiated with 900 rads, resulted in local tumour growth in 39/40 (97.5%) animals, with invasion or metastases to distant organs in 25% of cases. Both the bladder tumours and the metastases were morphologically similar to the original biopsy sample from which the cell line, UCRU-BL-17, was established. The cells were of human origin, as shown by expression of HLA antigens, Alu probing, and cytogenetic analysis. Preliminary studies indicated that i.p. injection of anti-human bladder cancer monoclonal antibody (MAb), BLCA-38, radiolabelled with either iodine 131 or samarium 153 (153Sm), resulted in tumour localisation, with tumour-to-blood ratios of 5.04 (131I), and 4.3 and 3.1 (153Sm) respectively. We now aim to examine the efficacy of the intravesical route for radioimmunotherapy in the nude rat model. This model will also serve for preclinical studies on the efficacy of systemically injected radioimmunoconjugates for control of metastatic growth.