Prakash Manoharan

Excess adiposity and survival in patients with colorectal cancer: a systematic review.

Excess adiposity is an established risk factor for incident colorectal cancer (CRC) but whether this association extrapolates to poorer survival is unclear. We undertook a systematic review to examine relationships between measures of adiposity and survival in patients with CRC. For distinction, we included pre‐diagnosis exposure and CRC‐related mortality. We performed dose‐response meta‐analyses and assessed study quality using eight domains of bias. Six study categories were identified based on (i) timing of adiposity measurement relative to survival analysis time zero and (ii) clinical setting. Several types of adiposity measurements were reported; body mass index (BMI) was the commonest. For pre‐diagnosis cohorts, baseline BMI negatively impacted on CRC‐related mortality in men only (risk estimate per 5 kg m−2 = 1.19, 95% confidence intervals: 1.14–1.25). The other groups were pre‐diagnosis BMI but diagnosis as time zero; population‐based cohorts; treatment cohorts; observational analyses within adjuvant chemotherapy trials; patients with metastatic CRC – each had several biases (e.g. treatment selection, reverse causality) and sources of confounding (e.g. chemotherapy ‘capping’). Overall, there was insufficient evidence for a strong link between adiposity and survival. These findings demonstrate an important principle: an established link between an exposure (here, adiposity) and increased cancer incidence does not necessarily extrapolate into an inferior post‐treatment outcome.

Role of FDG PET/CT in imaging of renal lesions.

Focal incidental renal lesions are commonly encountered on positron emission tomography (PET)/computed tomography (CT) imaging. The vast majority of these lesions are benign. However, the interpretation of renal lesions can be problematic if the imaging criteria of simple cysts are not met. Limited literature exists on the characterisation of renal masses with metabolic imaging. The purpose of this article is to focus on the imaging features of benign and malignant renal masses with PET/CT. The lesions discussed include renal cyst, angiomyolipoma, oncocytoma, renal cell carcinoma, renal metastases and other infiltrating neoplastic processes affecting the kidney. Both the anatomical and metabolic features which characterise these benign and malignant entities are described. We emphasise the importance of viewing the CT component to identify the typical morphological features and discuss how to best use hybrid imaging for management of renal lesions. Metabolic imaging has a promising role in the imaging of renal lesions and can help prevent unnecessary biopsies and ensure optimal management of suspicious lesions.

Imaging in gastrointestinal stromal tumours: current status and future directions

Gastrointestinal stromal tumours (GISTs) have distinct biological and treatment-related features posing challenges for imaging. In this review the importance of imaging in different stages of patient management is discussed, emphasizing the unique characteristics of GISTs. Potential pitfalls of using the standard response criteria on conventional imaging have been highlighted. These include size measurements, which may not adequately reflect response rates, pseudo-progression, and spurious new lesions. Furthermore, the role of positron emission tomography/computed tomography (PET/CT) in early response evaluation and in the detection of both primary and acquired resistance is explored. The current role and future directions of use of both conventional and metabolic imaging in the management of GISTs are discussed.

The role of FDG PET/CT in patients with colorectal cancer metastases.

INTRODUCTION Growing subsets of patients with metastatic colorectal cancer (CRC) are being considered for treatment with curative intent. Accurate restaging of patients with potentially resectable hepatic or pulmonary metastases is therefore crucial for optimal management. This article presents data to assess the role of 18-fluoro-deoxyglucose ((18)FDG) positron emission tomography/computed tomography (PET/CT) in metastatic CRC. MATERIALS AND METHODS A total of 341 patients with potentially resectable liver and/or pulmonary CRC metastases underwent (18)FDG PET/CT between 1st April 2007 and 31st August 2008 at our unit. Of these, 157 patients fulfilled the inclusion criteria and were included in this retrospective assessment. Imaging and clinical histories of these patients were evaluated. Findings on PET/CT were compared with pre-PET/CT conventional imaging and overall impact on patient management was assessed. The PET/CT results were confirmed either with histological comparison where available or with serial imaging follow up. RESULTS On a lesion to lesion basis, PET/CT when compared with pre-PET/CT conventional imaging in patients with metastatic liver and lung lesions had a Spearman correlation coefficient of 0.8 and P value < 0.0001 in both subgroups. PET/CT upstaged disease in 33.1% (52/157), down staged disease in 24.9% (39/157) and was in agreement with pre-PET/CT conventional imaging in the remaining 42% of patients (66/157). Based on PET/CT results surgery was averted in 33.8% patients (53/157). PET/CT had a sensitivity of 87.1%, specificity of 88.0%, positive predictive value of 97.4%, negative predictive value of 56.4% and an overall accuracy of 87.3% in assessing metastatic disease. CONCLUSION Assessment with (18)FDG PET/CT has a significant impact on the management of CRC patients with hepatic and pulmonary metastases.

Metastatic cutaneous malignant melanoma: Spectrum of imaging findings and the role of multimodality imaging

Cutaneous malignant melanoma is one of the most lethal and widely metastasising cancers with unpredictable pathways of spread. One of the most significant factors associated with survival in patients who have distant metastases is the number of organ sites involved. Innovative treatment options are now available for metastatic melanoma, and diagnostic imaging has become crucial for accurate staging and restaging of disease. The objective of this pictorial review is to illustrate the imaging spectrum of metastatic cutaneous malignant melanoma including both the common and the relatively ubiquitous sites of involvement using both conventional cross‐sectional and metabolic molecular imaging. This review also highlights the importance of combining multiple imaging methods for accurate staging of metastatic melanoma.

Utility of 18-fluorodeoxyglucose positron emission/computed tomography in the management of recurrent colorectal cancer.

This study aimed to evaluate the utility of 18‐fluorodeoxyglucose positron emission/computed tomography (PET/CT) in the management of colorectal cancer (CRC) patients with suspected recurrence.

68Gallium DOTANOC-PET Imaging in Lung Carcinoids: Impact on Patients' Management

Background:68Gallium DOTA-PET imaging is preferable to standard somatostatin receptor scintigraphy where available; however, its role in the management of lung carcinoid tumours (LC) remains unclear. Methods: All consecutive patients with histologically confirmed LC from two ENETS Centres of Excellence were identified retrospectively. The primary objective was to assess the impact of 68Ga-DOTANOC-PET on clinical management in patients with LC. Results: Of 166 patients screened, 46 were eligible: 52% female, median age 57 years (range 21-86); type of LC: diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (4%), typical (44%), atypical (35%), not reported (17%); stage: localised (63%), locally advanced (13%), and metastatic (17%) (7% unknown). A total of 47 68Ga-DOTANOCs were performed with the following rationale: LC diagnosis confirmation (4; 9%), primary tumour identification (2; 4%), post-surgical assessment (19; 40%), staging (patients with known LC present at time of 68Ga-DOTANOC) (19; 40%), and consideration of peptide receptor radionuclide therapy (3; 7%). Twenty-seven (57%) scans showed evidence of non-physiological uptake: median maximum standardised uptake value 7.2 (range 1.42-53). 68Ga-DOTANOC provided additional information in 37% (95% CI 22-51) of patients and impacted on management in 26% (95% CI 12-41); 9 patients (21%) were identified to have occult sites of metastases. Out of the 19 patients with post-surgical 68Ga-DOTANOC, 3 (16%) were identified to have distant metastases. There were no differences in the rate of practice changing 68Ga-DOTANOC results by type of LC (p value 0.5). Conclusions: Our results support the role of 68Ga-DOTANOC for optimising the management of patients with LC, including post-surgical re-staging due to the potential for identifying occult metastases.

Update on Treatment Options for Advanced Bile Duct Tumours: Radioembolisation for Advanced Cholangiocarcinoma

Cholangiocarcinoma is a rare form of gastrointestinal cancer with a poor prognosis. Patients often present with biliary obstruction or non-specific abdominal pain, and a high proportion of patients have advanced disease at initial diagnosis. The goal of this review is to discuss treatment options for patients with advanced bile duct tumours focusing on radioembolisation (RE) and its impact on overall survival. RE provides a therapeutic option for patients with unresectable cholangiocarcinoma. However, although systemic chemotherapy has demonstrated a survival benefit in randomised controlled trials, there is limited supporting evidence for the use of RE in this setting. Studies are mostly limited to single-centre, small cohorts with variable outcome measures. Additionally, patients included in these studies received a variety of previous therapies including chemotherapy, surgery or alternative intra-arterial therapy; therefore, a true assessment of overall survival benefit is difficult.

Digital histology quantification of intra-hepatic fat in patients undergoing liver resection

BACKGROUND High intra-hepatic fat (IHF) content is associated with insulin resistance, visceral adiposity, and increased morbidity and mortality following liver resection. However, in clinical practice, IHF is assessed indirectly by pre-operative imaging [for example, chemical-shift magnetic resonance (CS-MR)]. We used the opportunity in patients undergoing liver resection to quantify IHF by digital histology (D-IHF) and relate this to CT-derived anthropometrics, insulin-related serum biomarkers, and IHF estimated by CS-MR. METHODS A reproducible method for quantification of D-IHF using 7 histology slides (inter- and intra-rater concordance: 0.97 and 0.98) was developed. In 35 patients undergoing resection for colorectal cancer metastases, we measured: CT-derived subcutaneous and visceral adipose tissue volumes, Homeostasis Model Assessment of Insulin Resistance (HOMA-IR), fasting serum adiponectin, leptin and fetuin-A. We estimated relative IHF using CS-MR and developed prediction models for IHF using a factor-clustered approach. RESULTS The multivariate linear regression models showed that D-IHF was best predicted by HOMA-IR (Beta coefficient(per doubling): 2.410, 95% CI: 1.093, 5.313) and adiponectin (β(per doubling): 0.197, 95% CI: 0.058, 0.667), but not by anthropometrics. MR-derived IHF correlated with D-IHF (rho: 0.626; p = 0.0001), but levels of agreement deviated in upper range values (CS-MR over-estimated IHF: regression versus zero, p = 0.009); this could be adjusted for by a correction factor (CF: 0.7816). CONCLUSIONS Our findings show IHF is associated with measures of insulin resistance, but not measures of visceral adiposity. CS-MR over-estimated IHF in the upper range. Larger studies are indicated to test whether a correction of imaging-derived IHF estimates is valid.

Inter-tumor validation, through advanced MRI and circulating biomarkers, of plasma Tie2 as the vascular response biomarker for bevacizumab.

11521Background: VEGF inhibitor (VEGFi) use is compromised by lack of predictive/ response biomarkers. Previously, we identified plasma Tie2 (pTie2) as a vascular response biomarker (VRB) for bevacizumab (bev) in ovarian cancer (OC). Here, we applied dynamic contrast-enhanced MRI (DCE-MRI) and circulating biomarkers in colorectal cancer (CRC), to validate pTie2 as the first tumor VRB. Methods: Seventy patients were recruited, with untreated, mCRC and ≥1 lesion of 3-10cm diameter for DCE-MRI. Patients received bev 10mg/kg for 2 weeks to elicit a biomarker response and then FOLFOX6/bev until progressive disease (PD) Thirteen circulating and 6 imaging biomarkers were measured before and during treatment and at PD. Unsupervised correlation analysis identified bev-induced biomarker correlations. Biomarkers were evaluated by clustered parameter-time course studies to determine their epithelial or vascular origin. Clinical significance was determined by relating the biomarker data to tumor 3D volumetric change a...