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David Binns

Publications and source records attributed to David Binns.

18 recordsLinked to original sources
PubMed2007

New developments in the InterPro database.

InterPro is an integrated resource for protein families, domains and functional sites, which integrates the following protein signature databases: PROSITE, PRINTS, ProDom, Pfam, SMART, TIGRFAMs, PIRSF, SUPERFAMILY, Gene3D and PANTHER. The latter two new member databases have been integrated since the last publication in this journal. There have been several new developments in InterPro, including an additional reading field, new database links, extensions to the web interface and additional match XML files. InterPro has always provided matches to UniProtKB proteins on the website and in the match XML file on the FTP site. Additional matches to proteins in UniParc (UniProt archive) are now available for download in the new match XML files only. The latest InterPro release (13.0) contains more than 13 000 entries, covering over 78% of all proteins in UniProtKB. The database is available for text- and sequence-based searches via a webserver (http://www.ebi.ac.uk/interpro), and for download by anonymous FTP (ftp://ftp.ebi.ac.uk/pub/databases/interpro). The InterProScan search tool is now also available via a web service at http://www.ebi.ac.uk/Tools/webservices/WSInterProScan.html.

Databases, Protein↗
PubMed2006

Prognostic significance of [18F]-misonidazole positron emission tomography-detected tumor hypoxia in patients with advanced head and neck cancer randomly assigned to chemoradiation with or without tirapazamine: a substudy of Trans-Tasman Radiation Oncology Group Study 98.02.

PURPOSE: To determine the association between tumor hypoxia, treatment regimen, and locoregional failure (LRF) in patients with stage III or IV squamous cell carcinoma of the head and neck randomly assigned to radiotherapy (70 Gy in 35 fractions over 7 weeks) plus either tirapazamine and cisplatin in weeks 1, 4, and 7 and tirapazamine alone in weeks 2 and 3 (TPZ/CIS) or cisplatin and infusional fluorouracil during weeks 6 and 7 (chemoboost). PATIENTS AND METHODS: Forty-five patients were enrolled onto a hypoxic imaging substudy of a larger randomized trial. Pretreatment and midtreatment [18F]-fluoromisonidazole positron emission tomography scans (FMISO-PET) were performed 2 hours after tracer administration, with qualitative scoring of uptake in both primary tumors and nodes. RESULTS: Thirty-two patients (71%) had detectable hypoxia in either or both primary and nodal disease. In patients who received chemoboost, one of 10 patients without hypoxia had LRF compared with eight of 13 patients with hypoxia; the risk of LRF was significantly higher in hypoxic patients (exact log-rank, P = .038; hazard ratio [HR] = 7.1). By contrast, in patients who received the TPZ/CIS regimen, only one of 19 patients with hypoxic tumors had LRF; risk of LRF was significantly higher in chemoboost patients (P = .001; HR = 15). Similarly, looking at the primary site alone, in patients with hypoxic primaries, zero of eight patients treated with TPZ/CIS experienced failure locally compared with six of nine patients treated with chemoboost (P = .011; HR = 0). CONCLUSION: Hypoxia on FMISO-PET imaging, in patients receiving a nontirapazamine-containing chemoradiotherapy regimen, is associated with a high risk of LRF. Our data provide the first clinical evidence to support the experimental observation that tirapazamine acts by specifically targeting hypoxic tumor cells.

Cell Hypoxia↗
PubMed2006

A prospective study to evaluate the impact of FDG-PET on CT-based radiotherapy treatment planning for oesophageal cancer.

BACKGROUND AND PURPOSE: This prospective study sought to determine how the use of combined PET/CT for radiotherapy treatment planning of oesophageal cancer would alter the delineation of tumour volumes compared to CT alone if PET/CT is assumed to more accurately represent true disease extent. PATIENTS AND METHODS: All patients underwent FDG-PET/CT scanning in the radiotherapy treatment position. For each patient, two separate gross tumour volumes (GTV) were defined, one based on CT images alone (GTV-CT) and another based on combined PET/CT data (GTV-PET). Corresponding planning target volumes (PTV) were generated, and separate treatment plans were then produced. For each patient, volumetric analysis of GTV-CT, PTV-CT and GTV-PET was performed to quantify the proportion of PET-avid disease that was not included in the GTV and PTV (geographic miss) if CT data alone were used for radiotherapy planning. Assessment of the cranial and caudal extent of the primary oesophageal tumour as defined by CT alone vs PET/CT was also compared. RESULTS: The addition of PET information altered the clinical stage in 8 of 21 eligible patients enrolled on the study (38%); 4 patients had distant metastatic disease and 4 had unsuspected regional nodal disease. Sixteen patients proceeded to the radiotherapy planning phase of the study and received definitive chemoradiation planned with the PET/CT data set. The GTV based on CT information alone excluded PET-avid disease in 11 patients (69%), and in five patients (31%) this would have resulted in a geographic miss of gross tumour. The discordance between CT and PET/CT was due mainly to differences in defining the longitudinal extent of disease in the oesophagus. The cranial extent of the primary tumour as defined by CT vs PET/CT differed in 75% of cases, while the caudal extent differed in 81%. CONCLUSIONS: This study demonstrates that if combined PET/CT is used for radiotherapy treatment planning, there may be alterations to the delineation of tumour volumes when compared to CT alone, with the potential to avoid a geographic miss of tumour.

Esophageal Neoplasms↗
PubMed2006

Multi-tracer small animal PET imaging of the tumour response to the novel pan-Erb-B inhibitor CI-1033.

PURPOSE: This study was designed as "proof of concept" for a drug development model utilising multi-tracer serial small animal PET imaging to characterise tumour responses to molecularly targeted therapy. METHODS: Mice bearing subcutaneous A431 human squamous carcinoma xenografts (n=6-8) were treated with the pan-Erb-B inhibitor CI-1033 or vehicle and imaged serially (days 0, 3 and 6 or 7) with [(18)F]fluorodeoxyglucose, [(18)F]fluoro-L: -thymidine, [(18)F]fluoro-azoazomycinarabinoside or [(18)F]fluoromisonidazole. Separate cohorts (n=3) were treated identically and tumours were assessed ex vivo for markers of glucose metabolism, proliferation and hypoxia. RESULTS: During the study period, mean uptake of all PET tracers generally increased for control tumours compared to baseline. In contrast, tracer uptake into CI-1033-treated tumours decreased by 20-60% during treatment. Expression of the glucose transporter Glut-1 and cell cycle markers was unchanged or increased in control tumours and generally decreased with CI-1033 treatment, compared to baseline. Thymidine kinase activity was reduced in all tumours compared to baseline at day 3 but was sevenfold higher in control versus CI-1033-treated tumours by day 6 of treatment. Uptake of the hypoxia marker pimonidazole was stable in control tumours but was severely reduced following 7 days of CI-1033 treatment. CONCLUSION: CI-1033 treatment significantly affects tumour metabolism, proliferation and hypoxia as determined by PET. The PET findings correlated well with ex vivo biomarkers for each of the cellular processes studied. These results confirm the utility of small animal PET for evaluation of the effectiveness of molecularly targeted therapies and simultaneously definition of specific cellular processes involved in the therapeutic response.

Adenocarcinoma↗
PubMed2005

An in vivo tumor model exploiting metabolic response as a biomarker for targeted drug development.

In vivo models that recapitulate oncogene-dependent tumorigenesis will greatly facilitate development of molecularly targeted anticancer therapies. We have developed a model based on activating mutations in c-KIT in gastrointestinal stromal tumors (GISTs). This model comprises murine tumors of FDC-P1 cell lines expressing c-KIT mutations that render the tumors either responsive (V560G) or resistant (D816V) to the small-molecule c-KIT inhibitor, imatinib. Clinically, GIST response to imatinib is associated with rapid reduction in fluorodeoxyglucose (FDG) uptake on positron emission tomography (PET), preceding changes in conventional response criteria by several weeks. Using the FDC-P1 model in small animal PET, FDG uptake into tumors expressing the c-KIT V560G mutation was significantly reduced as early as 4 hours after imatinib treatment. In contrast, no change in FDG uptake was observed in resistant c-KIT D816V-expressing tumors after 48 hours of imatinib treatment. Consistent with the PET results, expression of the glucose transporter, GLUT1, was significantly reduced in V560G tumors at 4 hours, preceding changes in markers of proliferation by several hours. In vitro, imatinib treatment of V560G cells resulted in a reduction of glucose transporter numbers at the cell surface and decreased glucose uptake well before changes in cell viability. Notably, decreased ambient glucose concentrations enhanced the cytotoxic effect of imatinib. Taken together, these data account for the rapidity and significance of the PET response to imatinib and suggest that metabolic effects may contribute to imatinib cytotoxicity. Further, the FDC-P1 model represents a very useful paradigm for molecularly targeted drug development.

Animals↗
PubMed2005

Utility of FMISO PET in advanced head and neck cancer treated with chemoradiation incorporating a hypoxia-targeting chemotherapy agent.

PURPOSE: The purpose of the study was to evaluate [(18)F]fluoromisonidazole (FMISO) PET in advanced head and neck cancer during hypoxia-targeting therapy. METHODS: Fifteen of 16 patients in a phase I trial of chemoradiation plus tirapazamine (specific cytotoxin for hypoxic cells) in advanced (T3/4 and/or N2/3) head and neck cancer underwent serial [(18)F]fluorodeoxyglucose (FDG) and FMISO PET. We have previously reported excellent early clinical outcome of these patients and now review FMISO PET results in the context of longer follow-up of this patient cohort. RESULTS: Based on blinded qualitative scoring by two readers, FMISO PET was positive in 13/15 patients at baseline: 12/15 of primary sites and 8/13 neck nodes were scored as positive. All sites of corresponding FDG and FMISO abnormality at baseline showed marked qualitative reduction of uptake within 4 weeks of commencing therapy, consistent with effective hypoxia-targeted therapy. With a median follow-up of 6.9 years, there have been only four locoregional failures, while three other patients have died of metachronous lung cancer. The 5-year overall survival was 50% (95% CI 27-73%), the 5-year failure-free survival was 44% (95% CI 22-68%) and the 5-year freedom from locoregional failure was 68% (95% CI 38-88%). CONCLUSION: The high prevalence of hypoxia demonstrated on FMISO PET imaging is consistent with the advanced disease stage of these patients and would be expected to predict an adverse prognosis. Evidence of the early resolution of FMISO abnormality during treatment, associated with excellent locoregional control in this patient cohort, supports further investigation of hypoxia-targeting agents in advanced head and neck cancer.

Adult↗
PubMed2005

An evaluation of GO annotation retrieval for BioCreAtIvE and GOA.

BACKGROUND: The Gene Ontology Annotation (GOA) database http://www.ebi.ac.uk/GOA aims to provide high-quality supplementary GO annotation to proteins in the UniProt Knowledgebase. Like many other biological databases, GOA gathers much of its content from the careful manual curation of literature. However, as both the volume of literature and of proteins requiring characterization increases, the manual processing capability can become overloaded. Consequently, semi-automated aids are often employed to expedite the curation process. Traditionally, electronic techniques in GOA depend largely on exploiting the knowledge in existing resources such as InterPro. However, in recent years, text mining has been hailed as a potentially useful tool to aid the curation process. To encourage the development of such tools, the GOA team at EBI agreed to take part in the functional annotation task of the BioCreAtIvE (Critical Assessment of Information Extraction systems in Biology) challenge. BioCreAtIvE task 2 was an experiment to test if automatically derived classification using information retrieval and extraction could assist expert biologists in the annotation of the GO vocabulary to the proteins in the UniProt Knowledgebase. GOA provided the training corpus of over 9000 manual GO annotations extracted from the literature. For the test set, we provided a corpus of 200 new Journal of Biological Chemistry articles used to annotate 286 human proteins with GO terms. A team of experts manually evaluated the results of 9 participating groups, each of which provided highlighted sentences to support their GO and protein annotation predictions. Here, we give a biological perspective on the evaluation, explain how we annotate GO using literature and offer some suggestions to improve the precision of future text-retrieval and extraction techniques. Finally, we provide the results of the first inter-annotator agreement study for manual GO curation, as well as an assessment of our current electronic GO annotation strategies. RESULTS: The GOA database currently extracts GO annotation from the literature with 91 to 100% precision, and at least 72% recall. This creates a particularly high threshold for text mining systems which in BioCreAtIvE task 2 (GO annotation extraction and retrieval) initial results precisely predicted GO terms only 10 to 20% of the time. CONCLUSION: Improvements in the performance and accuracy of text mining for GO terms should be expected in the next BioCreAtIvE challenge. In the meantime the manual and electronic GO annotation strategies already employed by GOA will provide high quality annotations.

Animals↗
PubMed2005

InterPro, progress and status in 2005.

InterPro, an integrated documentation resource of protein families, domains and functional sites, was created to integrate the major protein signature databases. Currently, it includes PROSITE, Pfam, PRINTS, ProDom, SMART, TIGRFAMs, PIRSF and SUPERFAMILY. Signatures are manually integrated into InterPro entries that are curated to provide biological and functional information. Annotation is provided in an abstract, Gene Ontology mapping and links to specialized databases. New features of InterPro include extended protein match views, taxonomic range information and protein 3D structure data. One of the new match views is the InterPro Domain Architecture view, which shows the domain composition of protein matches. Two new entry types were introduced to better describe InterPro entries: these are active site and binding site. PIRSF and the structure-based SUPERFAMILY are the latest member databases to join InterPro, and CATH and PANTHER are soon to be integrated. InterPro release 8.0 contains 11 007 entries, representing 2573 domains, 8166 families, 201 repeats, 26 active sites, 21 binding sites and 20 post-translational modification sites. InterPro covers over 78% of all proteins in the Swiss-Prot and TrEMBL components of UniProt. The database is available for text- and sequence-based searches via a webserver (http://www.ebi.ac.uk/interpro), and for download by anonymous FTP (ftp://ftp.ebi.ac.uk/pub/databases/interpro).

Databases, Protein↗
PubMed2005

Modulation of intratumoral hypoxia by the epidermal growth factor receptor inhibitor gefitinib detected using small animal PET imaging.

Blockade of signaling through the epidermal growth factor receptor (EGFR) tyrosine kinase by inhibitors such as gefitinib (Iressa) can inhibit tumor angiogenesis and enhance responses to ionizing radiation. In this study, the ability of gefitinib to modulate intratumoral oxygenation was evaluated in human EGFR-expressing A431 squamous cell carcinoma xenografts using in vivo small animal positron emission tomography (PET) imaging with the hypoxia marker [(18)F]fluoroazomycin arabinoside (FAZA) and by the immunohistochemical detection of hypoxia-induced adducts of the 2-nitroimidazole, pimonidazole. Serial noninvasive PET imaging of A431 xenografts showed a significant reduction in FAZA uptake following treatment with 75 mg/kg/d of gefitinib [tumor to background ratio, 6.1 +/- 1.0 (pretreatment) versus 2.3 +/- 0.6 (posttreatment); P = 0.0004]. Similarly, ex vivo quantitation of FAZA uptake showed significantly reduced FAZA uptake in established A431 xenografts treated with gefitinib compared with vehicle control (tumor to blood ratio for controls versus gefitinib, 8.0 +/- 3.0 versus 2.7 +/- 0.8; P = 0.007; or tumor to muscle ratio controls versus gefitinib, 8.6 +/- 2.8 versus 2.6 +/- 1.0; P = 0.002). The effect of gefitinib treatment seemed to be independent of tumor size. In addition, gefitinib treatment reduced pimonidazole-binding in A431 xenografts measured after 5 and 8 days of gefitinib treatment compared with baseline and with tumors treated with vehicle alone. A strong correlation was observed between pimonidazole binding and FAZA uptake. Together, these findings show that gefitinib reduces intratumoral hypoxia.

Animals↗
PubMed2004

Early FDG-PET imaging after radical radiotherapy for non-small-cell lung cancer: inflammatory changes in normal tissues correlate with tumor response and do not confound therapeutic response evaluation.

PURPOSE: To investigate the relationship between positron emission tomography (PET) detected inflammatory changes in irradiated normal tissues and metabolic response at tumor sites in patients receiving radical radiotherapy for non-small-cell lung cancer. The prognostic significance of these changes was also studied. METHODS: In 73 consecutive patients, (18)F-fluorodeoxyglucose (FDG) PET was performed at a median of 70 days after completion of radical radiotherapy. Radiation-induced inflammatory change was scored for normal tissues within the radiation treatment volume using a 0-3 grading scale. Metabolic tumor response was assessed using a pattern-recognition algorithm comparing pre- and posttreatment scans. Prognostic significance of inflammatory changes was tested using the Cox proportional hazards regression model. RESULTS: Increased FDG uptake in normal tissues (radiotoxicity) was associated with a greater likelihood of complete or partial tumor response on both PET (p = 0.0044) and computed tomography (p = 0.029). Prognostic stratification provided by PET response was both significant and of a similar magnitude in patients with low- and high-grade radiotoxicity. CONCLUSION: Postradiotherapy inflammatory changes detected by FDG-PET are positively correlated with tumor response, suggesting that tumor radioresponsiveness and normal tissue radiosensitivity may be linked. Prognostic stratification provided by PET is not compromised by inflammatory changes if a meticulous visual response assessment technique is used.

Adenocarcinoma↗
PubMed2004

UniProt archive.

UniProt Archive (UniParc) is the most comprehensive, non-redundant protein sequence database available. Its protein sequences are retrieved from predominant, publicly accessible resources. All new and updated protein sequences are collected and loaded daily into UniParc for full coverage. To avoid redundancy, each unique sequence is stored only once with a stable protein identifier, which can be used later in UniParc to identify the same protein in all source databases. When proteins are loaded into the database, database cross-references are created to link them to the origins of the sequences. As a result, performing a sequence search against UniParc is equivalent to performing the same search against all databases cross-referenced by UniParc. UniParc contains only protein sequences and database cross-references; all other information must be retrieved from the source databases.

Amino Acid Sequence↗
PubMed2004

The Gene Ontology Annotation (GOA) Database: sharing knowledge in Uniprot with Gene Ontology.

The Gene Ontology Annotation (GOA) database (http://www.ebi.ac.uk/GOA) aims to provide high-quality electronic and manual annotations to the UniProt Knowledgebase (Swiss-Prot, TrEMBL and PIR-PSD) using the standardized vocabulary of the Gene Ontology (GO). As a supplementary archive of GO annotation, GOA promotes a high level of integration of the knowledge represented in UniProt with other databases. This is achieved by converting UniProt annotation into a recognized computational format. GOA provides annotated entries for nearly 60,000 species (GOA-SPTr) and is the largest and most comprehensive open-source contributor of annotations to the GO Consortium annotation effort. By integrating GO annotations from other model organism groups, GOA consolidates specialized knowledge and expertise to ensure the data remain a key reference for up-to-date biological information. Furthermore, the GOA database fully endorses the Human Proteomics Initiative by prioritizing the annotation of proteins likely to benefit human health and disease. In addition to a non-redundant set of annotations to the human proteome (GOA-Human) and monthly releases of its GO annotation for all species (GOA-SPTr), a series of GO mapping files and specific cross-references in other databases are also regularly distributed. GOA can be queried through a simple user-friendly web interface or downloaded in a parsable format via the EBI and GO FTP websites. The GOA data set can be used to enhance the annotation of particular model organism or gene expression data sets, although increasingly it has been used to evaluate GO predictions generated from text mining or protein interaction experiments. In 2004, the GOA team will build on its success and will continue to supplement the functional annotation of UniProt and work towards enhancing the ability of scientists to access all available biological information. Researchers wishing to query or contribute to the GOA project are encouraged to email: goa@ebi.ac.uk.

Animals↗
PubMed2003

The Gene Ontology Annotation (GOA) project: implementation of GO in SWISS-PROT, TrEMBL, and InterPro.

Gene Ontology Annotation (GOA) is a project run by the European Bioinformatics Institute (EBI) that aims to provide assignments of terms from the Gene Ontology (GO) resource to gene products in a number of its databases (http://www.ebi.ac.uk/GOA). In the first stage of this project, GO assignments have been applied to a data set representing the complete human proteome by a combination of electronic mappings and manual curation. This vocabulary has also been applied to the nonredundant proteome sets for all other completely sequenced organisms as well as to proteins from a wide range of organisms where the proteome is not yet complete.

Computational Biology↗
PubMed2003

The InterPro Database, 2003 brings increased coverage and new features.

InterPro, an integrated documentation resource of protein families, domains and functional sites, was created in 1999 as a means of amalgamating the major protein signature databases into one comprehensive resource. PROSITE, Pfam, PRINTS, ProDom, SMART and TIGRFAMs have been manually integrated and curated and are available in InterPro for text- and sequence-based searching. The results are provided in a single format that rationalises the results that would be obtained by searching the member databases individually. The latest release of InterPro contains 5629 entries describing 4280 families, 1239 domains, 95 repeats and 15 post-translational modifications. Currently, the combined signatures in InterPro cover more than 74% of all proteins in SWISS-PROT and TrEMBL, an increase of nearly 15% since the inception of InterPro. New features of the database include improved searching capabilities and enhanced graphical user interfaces for visualisation of the data. The database is available via a webserver (http://www.ebi.ac.uk/interpro) and anonymous FTP (ftp://ftp.ebi.ac.uk/pub/databases/interpro).

Animals↗
PubMed2002

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 18F 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 clinician's 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.

Adenocarcinoma↗
PubMed2002

InterPro: an integrated documentation resource for protein families, domains and functional sites.

The exponential increase in the submission of nucleotide sequences to the nucleotide sequence database by genome sequencing centres has resulted in a need for rapid, automatic methods for classification of the resulting protein sequences. There are several signature and sequence cluster-based methods for protein classification, each resource having distinct areas of optimum application owing to the differences in the underlying analysis methods. In recognition of this, InterPro was developed as an integrated documentation resource for protein families, domains and functional sites, to rationalise the complementary efforts of the individual protein signature database projects. The member databases - PRINTS, PROSITE, Pfam, ProDom, SMART and TIGRFAMs - form the InterPro core. Related signatures from each member database are unified into single InterPro entries. Each InterPro entry includes a unique accession number, functional descriptions and literature references, and links are made back to the relevant member database(s). Release 4.0 of InterPro (November 2001) contains 4,691 entries, representing 3,532 families, 1,068 domains, 74 repeats and 15 sites of post-translational modification (PTMs) encoded by different regular expressions, profiles, fingerprints and hidden Markov models (HMMs). Each InterPro entry lists all the matches against SWISS-PROT and TrEMBL (2,141,621 InterPro hits from 586,124 SWISS-PROT and TrEMBL protein sequences). The database is freely accessible for text- and sequence-based searches.

Algorithms↗
PubMed2002

The clinical impact of (18)F-FDG PET in patients with suspected or confirmed recurrence of colorectal cancer: a prospective study.

UNLABELLED: This prospective study aimed to confirm, in a clinical setting, the benefits suggested by earlier retrospective studies of (18)F-FDG PET scanning for the evaluation of patients with suspected recurrence of colorectal cancer. METHODS: The referring oncologist was asked to prospectively assign a treatment plan for 102 consecutive patients being evaluated by (18)F-FDG PET for suspected or confirmed recurrence of colorectal cancer and without evidence of unresectable disease on conventional staging investigations, including CT. This treatment plan was then compared with that based on incremental information supplied by PET. Management changes were validated by follow-up. RESULTS: For 6 patients, the oncologist would not commit to a management plan without access to PET information, and for all these patients, PET correctly guided management. Of the remaining 96 patients, the management plan for 54 (56%) was altered as a direct result of unexpected PET findings. Thus, PET directly influenced management in 60 (59%) of 102 patients. The discrepant PET results could be validated in 57 patients and were correct for both the presence and the extent of malignant disease in 52 (91%) of these patients but were false-positive in 1 patient because of a pelvic abscess and underestimated the extent of metastatic disease in 4 (7%). Relapse was confirmed in 49 (98%) of 50 evaluable patients with positive PET findings. Significantly, planned surgery was abandoned in 26 (60%) of 43 patients because of incremental PET findings. Of the 42 patients for whom management was not changed by PET findings, false-negative PET findings were documented for 5 (4 with metastases < 1 cm), and the PET findings for 1 were presumed to be false-positive because of sarcoidosis. CONCLUSION: This prospective study confirms the high impact, suggested by previous retrospective analyses, of (18)F-FDG PET on management of patients with suspected recurrent colorectal cancer. The major benefit of PET is avoidance of inappropriate local therapies by documentation of widespread disease.

Adult↗