Evaluation of FLT-PET-CT as an imaging biomarker of proliferation in primary breast cancer.

BACKGROUND: [(18)F]fluorothymidine (FLT) has been proposed as a positron emission tomography (PET)-imaging biomarker of proliferation for breast cancer. The aim of this prospective study was to assess the feasibility of FLT-PET-CT as a technique for predicting the response to neoadjuvant chemotherapy (NAC) in primary breast cancer and to compare baseline FLT with Ki-67. METHODS: Twenty women with primary breast cancer had a baseline FLT-PET-CT scan that was repeated before the second cycle of chemotherapy. Expression of Ki-67 in the diagnostic biopsy was quantified. From the FLT-PET-CT scans lesion maximum and mean standardised uptake values (SUVmax, SUVmean) were calculated. RESULTS: Mean baseline SUVmax was 7.3, and 4.62 post one cycle of NAC, representing a drop of 2.68 (36.3%). There was no significant association between baseline, post chemotherapy, or change in SUVmax and pathological response to NAC. There was a significant correlation between pre-chemotherapy Ki-67 and SUVmax of 0.604 (P=0.006). CONCLUSIONS: Baseline SUVmax measurements of FLT-PET-CT were significantly related to Ki-67 suggesting that it is a proliferation biomarker. However, in this series neither the baseline value nor the change in SUVmax after one cycle of NAC were able to predict response as most patients had a sizeable SUVmax reduction.

Can combined 18F-FDG-PET and dynamic contrast-enhanced MRI predict behavior of desmoid tumors in patients with familial adenomatous polyposis?

BACKGROUND: Desmoid tumors associated with familial adenomatous polyposis show variable behavior; about 10% grow relentlessly, resulting in severe morbidity or mortality. Investigations that could identify the minority of desmoid tumors that behave aggressively would allow these tumors to be treated early and spare the majority of patients who have more benign disease from unnecessary intervention. OBJECTIVE: The aim of this study was to investigate whether imaging the tumor metabolic-vascular phenotype by modern methods predicts growth. DESIGN: This is a prospective case series study. SETTINGS: The study was conducted at a tertiary center specializing in familial adenomatous polyposis and desmoid disease. PATIENTS: Nine patients with familial adenomatous polyposis (4 male, mean age 39 years) with desmoid tumor underwent 18F-FDG-PET and dynamic contrast-enhanced MRI. Standard MRI was repeated a year later to assess tumor growth. MAIN OUTCOME MEASURES: The primary outcome measured was the correlation between 18F-FDG-PET and dynamic contrast-enhanced MRI parameters and subsequent desmoid growth. RESULTS: Failed intravenous access precluded dynamic contrast-enhanced MRI in 1 female patient. Thirteen desmoid tumors (4 intra-abdominal, 2 extra-abdominal, 7 abdominal wall; mean area, 68 cm) were analyzed in the remaining 8 patients. Two patients died before follow-up MRI. Five tumors decreased in size, 3 increased in size, and 3 remained stable after a year. Significant correlation (Spearman rank correlation, significance at 5%) existed between maximum standardized uptake value and k(ep) (r = -0.56, p = 0.04), but not with other vascular parameters (K(trans) (r = -0.47, p = 0.09); v(e) (r = -0.11, p = 0.72); integrated area under the gadolinium-time curve at 60 seconds (r = -0.47, p = 0.10)). There was no significant difference in the maximum standardized uptake value or dynamic contrast-enhanced MRI parameters (K(trans), v(e), k(ep), integrated area under the gadolinium-time curve at 60 seconds) between the tumors that grew or decreased in size or between the tumor sites. However, vascular metabolic ratio (maximum standardized uptake value/K(trans)) was significantly different for tumor site (p = 0.001) and size (p = 0.001, 1-way ANOVA). LIMITATIONS: This investigation is limited because of its exploratory nature and small patient numbers. CONCLUSIONS: Although not predictive for tumor behavior, some correlations existed between dynamic contrast-enhanced MRI and 18F-FDG-PET parameters. Vascular metabolic ratio may provide further information on tumor behavior; however, this needs to be evaluated with further larger studies.

Investigation of dose minimisation protocol for 18F-FDG PET-CT in the management of lymphoma postchemotherapy followup.

INTRODUCTION: (18)F-FDG-PET-CT plays an important role in the management of lymphoma postchemotherapy followup. Some centres perform prechemotherapy baseline CT and postchemotherapy PETCT. With a concern of radiation burden, especially in young patients, this study aimed to assess if PETCT radiation dose could be reduced. METHODS: Retrospective analysis of 100 lymphoma patients was performed to record sites of disease on prechemotherapy CT and postchemotherapy PETCT. The potential reduction in radiation and time achieved with PETCT limited to sites of known disease identified on prechemotherapy CT was calculated. RESULTS: No FDG-uptake was seen in 72 cases. FDG uptake at known disease sites was seen in 24. Of the remaining 4, one had clinically significant pathology, a rectal adenocarcinoma. PETCT did not reveal any unexpected sites of lymphoma. Limiting PETCT to sites of known disease would have saved a mean radiation dose of 4 mSv (27.3%), with a mean time of 16 minutes. CONCLUSION: Our study suggests that young patients may benefit from reduced radiation by limiting PETCT to sites of known disease with low risk of missing significant pathology. However, in older patients, with increased incidence of asymptomatic synchronous malignancies, whole-body PETCT is advisable unless prechemotherapy PETCT has been performed.

Superiority of 18F-FDG PET compared to 111In-labelled leucocyte scintigraphy in the evaluation of fever of unknown origin.

AIM: To compare the accuracy of positron emission tomography (PET) using (18)F-FDG (Fluorodeoxyglucose) PET with (111)In-labelled leucocytes scintigraphy (LS) in patients with fever of unknown origin (FUO). METHODS: Twenty-three consecutive patients with FUO were prospectively studied using whole-body LS and PET. Performance of the two modalities for identifying a cause of FUO was evaluated. Final diagnosis was based on biopsy, microbiological tests, clinical and imaging follow-up. RESULTS: Abnormal tracer uptake was seen in 3/23(13%) and 14/23(61%) patients on LS and PET respectively, suggesting a higher sensitivity (p < 0.01) for the latter. All LS positive cases were identified on PET and confirmed as infection. The causes of FUO in the other PET positive patients were: infection (n = 3), vasculitis (n = 3), non-infectious inflammatory conditions (n = 2) and cancer (n = 1). No specific diagnosis was reached in 2 patients. Of 13 patients without a definite diagnosis following PET and LS, 10 made a spontaneous recovery during the follow-up period and no definite cause for FUO was found on investigation. Still's disease, Polymyalgia rheumatica and Chronic fatigue syndrome/Myalgic encephalomyelitis were diagnosed in the remaining three patients during follow-up. The results thus showed an overall sensitivity of 86% for PET and 20% for LS (p < 0.01). The overall specificity for FDG PET was 78% as against 100% for LS. PET had a PPV of 86% and a NPV of 78% whereas LS had a PPV of 100% and a NPV of 40%. CONCLUSION: PET has a higher sensitivity than LS in identifying the aetiology of FUO. PET/PET-CT, where available, should be used as the non-invasive investigation of choice in the assessment of patients with FUO.

To PET or not to PET? That is the question. Staging in anal cancer.

BACKGROUND: Anal cancer is a rare tumour accounting for ∼2% of all colorectal cancers between 1997 and 2000 in the UK. Staging is still dominated by DRE (digital rectal examination), computed tomography (CT) and magnetic resonance imaging (MRI) imaging. The role of PET as a definitive modality is still emerging and there are relatively few adequate studies in the literature. METHODS: We looked at patients treated radically for anal cancer at Mount Vernon Cancer Centre (UK) between 2009 and 2010. Eighty-eight patients underwent treatment according to data-based coding records of which 46 had positron emission tomography (PET)/CT scans. Notes were unavailable for three patients. We compared staging following conventional modalities (DRE, MRI and CT) and PET/CT scans for these 43 patients. RESULTS: In 18 patients, the PET/CT stage differed from MRI. PET/CT altered the stage in 42% of patients but changes in subsequent management were not implemented. CONCLUSIONS: Our data show that PET/CT does alter staging in a significant number of cases although it did not lead to change in management under the current guidelines. Furthermore, there is agreement that PET/CT shows greater sensitivity for detection of lymph nodes and our study has demonstrated a distinct trend towards upstaging of anal cancer with PET/CT.

Age and dose-limited PET-CT scan regime in lymphoma: between the devil and the deep blue sea?

In this study the authors speculate about hypothetical effective-dose (E) reduction through limiting post-chemotherapy PET-CT scanning to lymphoma sites previously identified on pre-treatment CT. E reductions/scan time savings are compared between post-treatment standard and theoretically limited PET-CT scans. The influence of patient age with E savings and associated clinical implication for 100 subjects are discussed. The greatest E theoretical savings of 52 and 32% for the CT contribution and combined PET-CT, respectively, were seen in patients <18 y old using limited scans in this study, with a potential mean time saving of 16 min per patient across the entire cohort. However, the limited PET-CT regime here missed a 1% rate of unexpected cancer that standard PET-CT recorded. The authors recommend performing larger scale multi-centre studies comparing PET-CT pre- and post-chemotherapy to establish full clinical efficacy of this method.

18F-fluorodeoxyglucose positron emission tomography/computed tomography in the assessment of occult primary head and neck cancers--an audit and review of published studies.

AIMS: To assess the value of 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) in patients with squamous cell and undifferentiated cancer neck nodes and no primary site on conventional assessment. MATERIALS AND METHODS: Seventy-eight patients with neck nodal metastases from an unknown primary cancer were studied. PET/CT was carried out in all patients, 1h after FDG injection. RESULTS: Uptake suspicious of an occult primary cancer was found in 46/78 (59.0%) patients. Subsequent investigations confirmed a primary site in the base of the tongue in 14, pharyngeal palatine tonsil in 14, post cricoid in one, lung in one. PET/CT diagnosed primary cancers in 30/78 patients (38.5%); sensitivity, specificity, positive predictive value, negative predictive value: 30/30 (100.0%), 32/48 (66.7%), 30/46 (65.2%), 32/32 (100.0%), respectively. PET/CT detected additional disease in four patients: contralateral nodal disease in two, mediastinal nodal disease in one and liver metastases in one. CONCLUSIONS: FDG PET/CT is of value in the assessment of patients with occult head and neck primary cancers. However, false-positive results remain a limitation of the investigation.

Breast surgical specimen radiographs: how reliable are they?

Radiography of the excised surgical specimen following wire guided localisation of impalpable breast lesions is standard surgical practice. The aims of the study were to establish the reliability of the breast specimen radiograph (SR) in determining lesion excision and to determine whether the radiographic margin correlated with the histological margin. The clinical, imaging, SR and pathological details of 106 patients with a pre-operative diagnosis of breast cancer were retrospectively reviewed. The reliability of orientation was estimated and the appearance and distance from the mammographic abnormality to each radial margin were measured and correlated with surgical histological findings. The overall accuracy of the specimen radiograph in determining whether the mammographic lesion was present was 99%. The SR could be orientated "very reliably" or "reliably" in 80% of patients however in only 48% of patients did the closest margin on the SR correspond with the same nearest margin at final histology. A maximum measurement of 11 mm or more from the lesion to the specimen edge was associated with a 77% likelihood of having a clear final histological margin (taken as 5mm or more) and if <11 mm a 58% chance of having involved final histological margins. There was however a wide overlap in the results with patients having an apparently wide SR margin but histologically involved margins and vice versa. The SR is reliable at determining whether the target lesion has been removed. The correlation of SR margin orientation and measurement with final histological measurement is however far less reliable.

Incidental breast lesions detected on CT: what is their significance?

An increasing number of breast lesions are being detected incidentally on CT. The aim of this study was to investigate the rate of referrals to the breast unit for assessment of lesions identified on CT and the resulting yield of previously undiagnosed breast malignancies from this pathway. A retrospective review was undertaken of CT examinations conducted over a period of 14 years. All patients (with no previous history of breast cancer) whose report contained the keyword "breast" and who were referred to a specialist breast unit for assessment were reviewed. CT lesion morphology and enhancement pattern were identified and compared with the final diagnostic outcome. 70 patients were identified by retrospective analysis, yielding 78 incidental breast lesions, of which 22 (28.2%) were malignant (category B5). This gave a positive predictive value (PPV) for malignancy of 28.2%. The best morphological predictor of malignancy was spiculation (PPV, 76%) and irregularity (PPV, 58%), whereas calcification patterns (PPV, 36%) were diagnostically unhelpful. Malignant lesions were likely to be larger (mean, 28.5 mm) than benign lesions (mean, 20.2 mm; p<0.05). In conclusion, 30% of incidental breast lesions in this large series of patients proved to be unsuspected breast cancers, particularly irregular spiculated masses. Referral for formal triple assessment of CT-diagnosed breast lesions is worthwhile, and careful examination of the breast should be a routine part of CT examinations.

Nonrigid registration using free-form deformations: application to breast MR images.

In this paper we present a new approach for the nonrigid registration of contrast-enhanced breast MRI. A hierarchical transformation model of the motion of the breast has been developed. The global motion of the breast is modeled by an affine transformation while the local breast motion is described by a free-form deformation (FFD) based on B-splines. Normalized mutual information is used as a voxel-based similarity measure which is insensitive to intensity changes as a result of the contrast enhancement. Registration is achieved by minimizing a cost function, which represents a combination of the cost associated with the smoothness of the transformation and the cost associated with the image similarity. The algorithm has been applied to the fully automated registration of three-dimensional (3-D) breast MRI in volunteers and patients. In particular, we have compared the results of the proposed nonrigid registration algorithm to those obtained using rigid and affine registration techniques. The results clearly indicate that the nonrigid registration algorithm is much better able to recover the motion and deformation of the breast than rigid or affine registration algorithms.

Comparison and evaluation of rigid, affine, and nonrigid registration of breast MR images.

PURPOSE: A new nonrigid registration method, designed to reduce the effect of movement artifact in subtraction images from breast MR, is compared with existing rigid and affine registration methods. METHOD: Nonrigid registration was compared with rigid and affine registration methods and unregistered images using 54 gadolinium-enhanced 3D breast MR data sets. Twenty-seven data sets had been previously reported normal, and 27 contained a histologically proven carcinoma. The comparison was based on visual assessment and ranking by two radiologists. RESULTS: When analyzed by two radiologists independently, all three registration methods gave better-quality subtraction images than unregistered images (p < 0.01), but nonrigid registration gave significantly better results than the rigid and affine registration methods (p < 0.01). There was no significant difference between rigid and affine registration methods. CONCLUSION: Nonrigid registration significantly reduces the effects of movement artifact in subtracted contrast-enhanced breast MRI. This may enable better visualization of small tumors and those within a glandular breast.

Midline extraperitoneal approach for elective abdominal aortic aneurysm repair.

The incidence of abdominal aortic aneurysms (AAA) is rising and elective repair is becoming more commonplace. We describe a new, simple midline extraperitoneal approach for AAA repair. It is particularly suitable for patients who have an inflammatory AAA, abdominal adhesions or a horseshoe kidney. This approach provides excellent exposure to the whole aortoiliac system without the need for separate incisions, whilst retaining the potential advantages of the extraperitoneal approach.

CT identification of ascaris in the biliary tract.

Ascariasis is one of the most common helminthic diseases worldwide. The presence of this worm in the biliary tree causes biliary colic, recurrent pyogenic cholangitis, pancreatitis, hepatic abscesses, and septicemia. The diagnosis of biliary ascariasis is usually made by ultrasound (US). We report the computerized-tomography (CT) aspects that allowed the identification of ascaris in the biliary tract in two patients.