Angela M. Riddell

Analysis of the efficacy and toxicity of sorafenib in thyroid cancer: a phase II study in a UK based population.

AIM To evaluate the tolerability and efficacy of sorafenib in patients with thyroid carcinoma. METHODS Patients with progressive locally advanced/metastatic medullary thyroid carcinoma (MTC), or differentiated thyroid carcinoma (DTC) with non-radioiodine-avid disease, were treated with sorafenib 400 mg twice daily until disease progression. The primary endpoint was the radiological response rate (RR) at 6 months. Secondary endpoints were RR at 3, 9 and 12 months, biochemical responses, toxicity, biomarker analyses and progression free and overall survival (OS). RESULTS A total of 34 patients were recruited to the study (15 medullary and 19 differentiated). After 6 months, the RR rate was 15% and a further 74% of patients achieved stable disease in the first 6 months. After 12 months of treatment, the RR was 21%. In the MTC patients, the RR at 12 months was 25% and OS was 100%. In DTC patients corresponding rates were 18 and 79% respectively. Median overall and progression-free survival points were not reached at 19 months. Commonest adverse events included hand-foot syndrome, other skin toxicities, diarrhoea and alopecia. Dose reduction was required in 79% patients. Median time on treatment was 16.5 months. CONCLUSION This study demonstrates that sorafenib is tolerable at reduced doses over prolonged periods of time in patients with thyroid cancer. Sorafenib leads to radiological and biochemical stabilisation of disease in the majority of these patients despite dose reductions.

Detection of colorectal hepatic metastases using MnDPDP MR imaging and diffusion-weighted imaging (DWI) alone and in combination

To compare the diagnostic accuracy of MnDPDP MR imaging and diffusion-weighted imaging (DWI), alone and in combination, for detecting colorectal liver metastases in patients with suspected metastatic disease. Thirty-three consecutive patients with suspected colorectal liver metastases underwent MR imaging. Three image sets (MnDPDP, DWI and combined MnDPDP and DWI) were reviewed independently by two observers. Lesions were scored on a five-point scale for malignancy and the areas (Az) under the receiver operating characteristic curves were calculated for each observer and image set. The sensitivity and specificity for lesion detection were calculated for each image set and compared. There were 83 metastases, 49 cysts and 1 haemangioma. Using the combined set resulted in the highest diagnostic accuracy for both observers (Az = 0.94 and 0.96), with improved averaged sensitivity of lesion detection compared with the DWI set (p = 0.01), and a trend towards improved sensitivity compared with the MnDPDP set (p = 0.06). There was no difference in the averaged specificity using any of the three image sets (p > 0.5). Combination of MnDPDP MR imaging and DWI resulted in the highest diagnostic accuracy and can increase sensitivity without loss in specificity.

Combining diffusion-weighted MRI with Gd-EOB-DTPA-enhanced MRI improves the detection of colorectal liver metastases

OBJECTIVES To compare the diagnostic accuracy of gadolinium-ethoxybenzyl-diethylenetriaminepentaacetic acid (Gd-EOB-DTPA)-enhanced MRI, diffusion-weighted MRI (DW-MRI) and a combination of both techniques for the detection of colorectal hepatic metastases. METHODS 72 patients with suspected colorectal liver metastases underwent Gd-EOB-DTPA MRI and DW-MRI. Images were retrospectively reviewed with unenhanced T(1) and T(2) weighted images as Gd-EOB-DTPA image set, DW-MRI image set and combined image set by two independent radiologists. Each lesion detected was scored for size, location and likelihood of metastasis, and compared with surgery and follow-up imaging. Diagnostic accuracy was compared using receiver operating characteristics and interobserver agreement by kappa statistics. RESULTS 417 lesions (310 metastases, 107 benign) were found in 72 patients. For both readers, diagnostic accuracy using the combined image set was higher [area under the curve (Az)=0.96, 0.97] than Gd-EOB-DTPA image set (Az=0.86, 0.89) or DW-MRI image set (Az=0.93, 0.92). Using combined image set improved identification of liver metastases compared with Gd-EOB-DTPA image set (p<0.001) or DW-MRI image set (p<0.001). There was very good interobserver agreement for lesion classification (κ=0.81-0.88). CONCLUSIONS Combining DW-MRI with Gd-EOB-DTPA-enhanced T(1) weighted MRI significantly improved the detection of colorectal liver metastases.

The value of magnetic resonance imaging in target volume delineation of base of tongue tumours--a study using flexible surface coils.

INTRODUCTION Magnetic resonance imaging (MRI) provides superior diagnostic accuracy over computed tomography (CT) in oropharyngeal tumours. Precise delineation of the gross tumour volume (GTV) is mandatory in radiotherapy planning when a GTV boost is required. CT volume definition in this regard is poor. We studied the feasibility of using flexible surface (flex-L) coils to obtain MR images for MR-CT fusion to assess the benefit of MRI over CT alone in planning base of tongue tumours. METHODS Eight patients underwent CT and MRI radiotherapy planning scans with an immobilisation device. Distortion-corrected T1-weighted post-contrast MR scans were fused to contrast-enhanced planning CT scans. GTV, clinical target and planning target volumes (CTV, PTV) and organs at risk (OAR) were delineated on CT, then on MRI with blinding to the CT images. The volumetric and spatial differences between MRI and CT volumes for GTV, CTV, PTV and OAR were compared. MR image distortions due to field inhomogeneity and non-linear gradients were corrected and the need for such correction was evaluated. RESULTS The mean primary GTV was larger on MRI (22.2 vs. 9.5 cm(3), p=0.05) than CT. The mean primary and nodal GTV (i.e. BOT and macroscopic nodes) was significantly larger on MRI (27.2 vs. 14.4 cm(3), p=0.05). The volume overlap index (VOI) between MRI and CT for the primary was 0.34 suggesting that MRI depicts parts of the primary tumour not detected by CT. There was no significant difference in volume delineation between MR and CT for CTV, PTV, nodal CTV and nodal PTV. MRI volumes for brainstem and spinal cord were significantly smaller due to improved organ definition (p=0.002). Susceptibility and gradient-related distortions were not found to be clinically significant. CONCLUSION MRI improves the definition of tongue base tumours and neurological structures. The use of MRI is recommended for GTV dose-escalation techniques to provide precise depiction of GTV and improved sparing of spinal cord and brainstem.

Changes in functional imaging parameters following induction chemotherapy have important implications for individualised patient-based treatment regimens for advanced head and neck cancer

BACKGROUND When induction chemotherapy (IC) is used prior to chemoradiotherapy (CRT) in head and neck cancer (HNC), functional imaging (FI) may inform adaptation of treatment plans with the aim of optimising outcomes. Understanding the impact of IC on FI parameters is, therefore, essential. PURPOSE To prospectively evaluate the feasibility of acquiring serial FI ((18)F-FDG-PET, diffusion-weighted (DW) and dynamic contrast-enhanced (DCE) MRI) and its role in defining individualised treatment regimens following IC in HNC. METHODS AND MATERIALS Ten patients with stage III and IV HNC underwent conventional (CT and MRI) and functional (DW, DCE-MRI and (18)F-FDG-PET/CT) imaging at baseline and following two cycles of IC prior to definitive CRT. RESULTS One patient withdrew due to claustrophobia. Seven out of nine patients had a complete metabolic response to IC on (18)F-FDG-PET imaging. DCE-MRI showed a significant fall in transfer constant (K(trans)) (0.209 vs 0.129 min(-1)P<0.01) and integrated area under gadolinium curve at 60s (IAUGC6O) (18.4 vs 11.9 mmol/min, P<0.01) and DW-MRI a rise in ADC (0.89 vs 1.06 × 10(-3) mm(2)/s, P<0.01) following IC. CONCLUSIONS Acquiring FI sequences is feasible in HNC. There are marked changes in FI parameters following IC which may guide adaptation of individualised treatment regimens.

Whole-body diffusion-weighted MRI: a new gold standard for assessing disease burden in patients with multiple myeloma?

Whole-body diffusion-weighted MRI: a new gold standard for assessing disease burden in patients with multiple myeloma?

A phase II trial of preoperative chemotherapy with epirubicin, cisplatin and capecitabine for patients with localised gastro-oesophageal junctional adenocarcinoma.

Preoperative cisplatin/fluorouracil is used for the treatment of localised oesophageal carcinoma. This phase II study aimed to assess the efficacy and safety of administering preoperative epirubicin/cisplatin/capecitabine (ECX). Patients with stage II or III oesophageal/gastro-oesophageal junctional adenocarcinoma from one institution received 4 cycles of ECX (epirubicin 50 mg m−2 day 1, cisplatin 60 mg m−2 day 1, capecitabine 625 mg m−2 b.i.d. daily) followed by surgery. The primary end point was the pathological complete response (pCR) rate based on a Simon two-stage design. Secondary end points included overall and progression-free survival (OS/PFS). Thirty-four patients were recruited: median age 60 years (range 41–81), 91% male, 97% PS 0/1, 80% T3, 68% N1. Thirty-one patients completed four ECX cycles. Grade 3/4 toxicities ⩾5% included neutropenia (62%), hand–foot syndrome (15%) and nausea/vomiting (9%). Thirteen out of 28 (46%) evaluable patients responded to chemotherapy by EUS (⩾30% reduction in maximal tumour thickness). Twenty-six out of 34 (76%) patients underwent resection (R0=73%, R1=27%). Post-operatively, two patients died within 60 days of surgery. The pCR rate was 5.9% (95% CI 0–14%) in the intent-to-treat population. According to the statistical design, this prompted early study termination. However, with a median follow-up of 34 months the median OS and 1- and 2-year survival rates were 17 months, 67 and 39% respectively. Median PFS was 13 months. Of the 14 relapsed patients, 10 presented with distant metastases. Preoperative ECX is feasible and well tolerated. Although associated with a low pCR rate, survival with ECX was comparable with published studies suggesting that pCR may not correlate with satisfactory outcome from preoperative chemotherapy for localised oesophageal adenocarcinoma.

The predictive value of early assessment after one cycle of induction chemotherapy with 18F-FDG-PET/CT and DW-MRI for response to radical chemoradiotherapy in head and neck squamous cell carcinoma

The objective of this study was to assess the predictive value of early assessment (after 1 cycle of induction chemotherapy [IC]) with 18F-FDG PET/CT and diffusion-weighted (DW) MRI for subsequent response to radical chemoradiotherapy in locally advanced head and neck squamous cell carcinoma (HNSCC). Methods: Twenty patients with stage III–IVa HNSCC prospectively underwent 18F-FDG PET/CT and DW MRI before and 2 wk after each cycle of IC (first cycle, IC1; second cycle, IC2). Response was assessed 3 mo after completion of chemoradiotherapy with clinical examination, MRI, and 18F-FDG PET/CT. Patients with persistent disease were classed as nonresponders. Changes in functional and molecular imaging parameters after IC1 were compared between responders and nonresponders with the Mann–Whitney U test. The significance threshold was set at a P value of less than 0.05. Results: Responders showed a significantly greater reduction in metabolic tumor volume (P = 0.03) and total lesion glycolysis (P = 0.04) after IC1 than nonresponders. Responders also showed a tendency toward a larger but statistically nonsignificant increase in apparent diffusion coefficient after IC1. There was no significant difference in the changes from baseline between the IC1 and IC2 for all functional and molecular imaging parameters, indicating that most biologic response to IC measured by 18F-FDG PET/CT and DW MRI was observed early after the first cycle of IC. Conclusion: Our preliminary data indicate that the 18F-FDG PET/CT–derived metabolic tumor volume or total lesion glycolysis, acquired after IC1, are early predictive biomarkers for ultimate response to subsequent chemoradiotherapy. These early biomarkers enable identification of patients at risk of treatment failure at an early time point, permitting treatment individualization and consideration of alternative strategies such as radiotherapy dose escalation or surgery.

Repeatability and sensitivity of T2* measurements in patients with head and neck squamous cell carcinoma at 3T

To determine whether quantitation of T2* is sufficiently repeatable and sensitive to detect clinically relevant oxygenation levels in head and neck squamous cell carcinoma (HNSCC) at 3T.

Segmental liver hyperintensity in malignant biliary obstruction on diffusion weighted MRI: associated MRI findings and relationship with serum alanine aminotransferase levels.

OBJECTIVES Segmental liver hyperintensity can be observed in malignant biliary obstruction on diffusion weighted MRI (DW-MRI). We describe MRI findings associated with this sign and evaluate whether DW-MRI segmental hyperintensity has any relationship with serum alanine aminotransferase (ALT) levels. METHODS The DW-MRI T(1) weighted, T(2) weighted and gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced T(1) weighted images obtained in 21 patients with hepatic malignancy, who demonstrated biliary obstruction and segmental hyperintensity on DW-MRI (b=0-750 s mm(-2)), were retrospectively reviewed by 2 readers blinded to clinical results. DW-MRI hyperintense liver segments were recorded as hypointense, isointense or hyperintense relative to normal liver on T(1)/T(2) weighted imaging. It was also noted whether contrast enhancement was similar to that observed in normal liver or diminished in the hepatocellular phase. The mean apparent diffusion coefficient (ADC) value (×10(-3) s mm(-2)) of DW-MRI hyperintense segments, normal liver and tumour were compared using Students t-test. The frequency of MRI findings was corroborated with serum ALT levels, which reflect hepatocyte injury. RESULTS DW-MRI hyperintense segments frequently showed T(1) hyperintensity (10/21), T(2) hyperintensity (19/21) and/or diminished contrast enhancement (15/21). Tumours showed significantly lower mean ADC values than liver (1.23 ± 0.08 vs 1.43 ± 0.05; p=0.013). Segments showing concomitant T(1) hyperintensity had lower mean ADC values than liver (1.30 ± 0.05 vs 1.43 ± 0.05; p=0.023). The patients (8/10) with concomitant T(1) and DW-MRI segmental hyperintensity showed elevated ALT levels (p=0.030, Fishers exact test). CONCLUSION Concomitantly high T(1) weighted and DW-MRI signal in liver segments was associated with lower ADC values and abnormal liver function tests, which could reflect underlying cellular swelling and damage.