Search

Introduction: As tumour response rates are increasingly demonstrated in early-phase cancer trials (EPCT), optimal patient selection and accurate prognostication are paramount. Hammersmith Score (HS), a simple prognostic index derived on routine biochemical measures (albumin <35 g/L, lactate dehydrogenase >450 IU/L, sodium <135 mmol/L), is a validated predictor of response and survival in EPCT participants. HS has not been validated in the cancer immunotherapy era., Methods: We retrospectively analysed characteristics and outcomes of unselected referrals to our early-phase unit (12/2019-12/2022). Independent predictors for overall survival (OS) were identified from univariable and multivariable models. HS was calculated for 66 eligible trial participants and compared with the Royal Marsden Score (RMS) to predict OS. Multivariable logistic regression and C-index was used to compare predictive ability of prognostic models., Results: Of 212 referrals, 147 patients were screened and 82 patients treated in EPCT. Prognostic stratification by HS identifies significant difference in median OS, and HS was confirmed as a multivariable predictor for OS (HR: HS 1 vs. 0 2.51, 95% CI: 1.01-6.24, p = 0.049; HS 2/3 vs. 0: 10.32, 95% CI: 2.15-49.62, p = 0.004; C-index 0.771) with superior multivariable predictive ability than RMS (HR: RMS 2 vs. 0/1 5.46, 95% CI: 1.12-26.57, p = 0.036; RMS 3 vs. 0/1 6.83, 95% CI: 1.15-40.53, p < 0.001; C-index 0.743)., Conclusions: HS is a validated prognostic index for patients with advanced cancer treated in the context of modern EPCTs, independent of tumour burden. HS is a simple, inexpensive prognostic tool to optimise referral for EPCT., (© 2024 The Author(s). Published by S. Karger AG, Basel.)

Importance: Patients with head and neck squamous cell carcinoma (HNSCC) have a significant risk of locoregional recurrence within the first 2 years, with approximately two-thirds of patients experiencing such recurrence. While early recurrence detection may be associated with improved patient outcomes, the association of such detection with survival remains uncertain., Objective: To investigate the association of an intensive posttreatment follow-up strategy using 18F-fludeoxyglucose-positron emission tomography with computed tomography (18FDG-PET/CT) with survival among patients with HNSCC., Design, Setting, and Participants: This case-control study was conducted among patients treated at 1 of 3 locations in Brest, France (University Hospital, Military Hospital, or Pasteur Clinic). The statistical analysis was conducted from January to June 2023. All adults with histologically proven HNSCC who were treated with curative intent between January 1, 2006, and December 31, 2019, and achieved a complete response on imaging at 3 to 6 months were included. They had a minimum of 3 years of follow-up., Exposures: Patients undergoing an intensive posttreatment follow-up strategy had 18FDG-PET/CT (PET/CT group) at months 12, 24, and 36, chosen at the discretion of ear, nose, and throat surgeons., Main Outcomes and Measures: Overall survival (OS) at 3 years., Results: Among 782 patients with HNSCC (642 males [82.1%]; median [IQR] age, 61 [56-68] years), 497 patients had 18FDG-PET/CT during follow-up and 285 patients had conventional follow-up (CFU group). Cox regression analysis showed an association between undergoing 18FDG-PET/CT and lower risk of death (odds ratio, 0.71; 95% CI, 0.57-0.88; P = .002) after adjustment for covariates (age, sex, comorbidities, primary location, stage, surgeon, year of treatment, and treatment). The mean (SD) 3-year OS was significantly better in the PET/CT vs CFU group (72.5% [2.0%] vs 64.3% [2.9%]; P = .002). Analysis based on American Joint Committee on Cancer stage showed significantly better mean (SD) 3-year OS for advanced stages III and IV in the PET/CT group (373 patients) vs CFU group (180 patients; 68.5% [2.4%] vs 55.4% [3.8%]; P < .001), while no significant difference was observed between patients with stage I or II HNSCC. Analysis based on primary tumor site revealed significantly longer mean (SD) 3-year OS for oropharyngeal tumor in the PET/CT group (176 patients) than the CFU group (100 patients; 69.9% [3.5%] vs 60.5% [5.0%]; P = .04)., Conclusions and Relevance: This case-control study found that use of 18FDG-PET/CT in the standard annual CFU of HNSCC was associated with a 3-year survival benefit, with a larger benefit for patients with advanced initial tumor stage (III-IV) and oropharyngeal disease.

Background: The use of 18FDG-PET/CT for delineating a gross tumor volume (GTV, also called MTV metabolic tumor volume) in radiotherapy (RT) planning of head neck squamous cell carcinomas (HNSCC) is not included in current recommendations, although its interest for the radiotherapist is of evidence. Because pre-RT PET scans are rarely done simultaneously with dosimetry CT, the validation of a robust image registration tool and of a reproducible MTV delineation method is still required., Objective: Our objective was to study a CT-based elastic registration method on dual-time pre-RT 18FDG-PET/CT images to assess the feasibility of PET-based RT planning in patients with HNSCC., Methods: Dual-time 18FDG-PET/CT [whole-body examination (wbPET) + 1 dedicated step (headPET)] were selected to simulate a 2-times scenario of pre-RT PET images deformation on dosimetry CT. ER-headPET and RR-headPET images were, respectively, reconstructed after CT-to-CT rigid (RR) and elastic (ER) registrations of the headPET on the wbPET. The MTVs delineation was performed using two methods (40%SUVmax, PET-Edge). The percentage variations of several PET parameters (SUVmax, SUVmean, SUVpeak, MTV, TLG) were calculated between wbPET, ER-headPET, and RR-headPET. Correlation between MTV values was calculated (Deming linear regression). MTVs intersections were assessed by two indices (OF, DICE) and compared together (Wilcoxon test). Additional per-volume analysis was evaluated (Mann-Whitney test). Inter- and intra-observer reproducibilities were evaluated (ICC = intra-class coefficient)., Results: 36 patients (30M/6F; median age = 65 y) were retrospectively included. The changes in SUVmax, SUVmean and SUVpeak values between ER-headPET and RR-headPET images were <5%. The variations in MTV values between ER-headPET and wbPET images were -6 and -3% with 40%SUVmax and PET Edge, respectively. Their correlations were excellent whatever the delineation method (R 2 > 0.99). The ER-headPET MTVs had significant higher mean OF and DICE with the wbPET MTVs, for both delineation methods ( p ≤ 0.002); and also when lesions had a volume > 5cc (excellent OF = 0.80 with 40%SUVmax). The inter- and intra-observer reproducibilities for MTV delineation were excellent (ICC ≥ 0.8, close to 1 with PET-Edge)., Conclusion: Our study demonstrated no significant changes in MTV after an elastic deformation of pre-RT 18FDG-PET/CT images acquired in dual-time mode. This opens possibilities for HNSCC radiotherapy planning improvement by transferring GTV-PET on dosimetry CT., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Maajem, Leclère, Bourhis, Tissot, Icard, Arnaud, Le Pennec, Dissaux, Gujral, Salaün, Schick and Abgral.)

Standard treatment for locally advanced cervical cancer (LACC) is chemoradiotherapy followed by brachytherapy. Despite radiation therapy advances, the toxicity rate remains significant. In this study, we compared the prediction of toxicity events after radiotherapy for locally advanced cervical cancer (LACC), based on either dose-volume histogram (DVH) parameters or the use of a radiomics approach applied to dose maps at the voxel level. Toxicity scores using the Common Terminology Criteria for Adverse Events (CTCAE v4), spatial dose distributions, and usual clinical predictors for the toxicity of 102 patients treated with chemoradiotherapy followed by brachytherapy for LACC were used in this study. In addition to usual DVH parameters, 91 radiomic features were extracted from rectum, bladder and vaginal 3D dose distributions, after discretization into a fixed bin width of 1 Gy. They were evaluated for predictive modelling of rectal, genitourinary (GU) and vaginal toxicities (grade ≥ 2). Logistic Normal Tissue Complication Probability (NTCP) models were derived using clinical parameters only or combinations of clinical, DVH and radiomics. For rectal acute/late toxicities, the area under the curve (AUC) using clinical parameters was 0.53/0.65, which increased to 0.66/0.63, and 0.76/0.87, with the addition of DVH or radiomics parameters, respectively. For GU acute/late toxicities, the AUC increased from 0.55/0.56 (clinical only) to 0.84/0.90 (+DVH) and 0.83/0.96 (clinical + DVH + radiomics). For vaginal acute/late toxicities, the AUC increased from 0.51/0.57 (clinical only) to 0.58/0.72 (+DVH) and 0.82/0.89 (clinical + DVH + radiomics). The predictive performance of NTCP models based on radiomics features was higher than the commonly used clinical and DVH parameters. Dosimetric radiomics analysis is a promising tool for NTCP modelling in radiotherapy.

Purpose: The aim of this study was to prospectively investigate tumor volume delineation by amino acid PET and multiparametric perfusion magnetic resonance imaging (MRI) in patients with newly diagnosed, untreated high grade glioma (HGG)., Materials and Methods: Thirty patients with histologically confirmed HGG underwent O-(2-[ 18 F]-fluoroethyl)-l-tyrosine ( 18 F-FET) positron emission tomography (PET), conventional Magnetic Resonance Imaging (MRI) as contrast-enhanced (CE) and fluid-attenuated inversion recovery (FLAIR) and multiparametric MRI as relative cerebral blood volume (rCBV) and permeability estimation map (K2). Areas of MRI volumes were semi-automatically segmented. The percentage overlap volumes, Dice and Jaccard spatial similarity coefficients (OV, DSC, JSC) were calculated., Results: The 18 F-FET tumor volume was significantly larger than the CE volume (median 43.5 mL (2.5-124.9) vs. 23.8 mL (1.4-80.3), p = 0.005). The OV between 18 F-FET uptake and CE volume was low (median OV 0.59 (0.10-1)), as well as spatial similarity (median DSC 0.52 (0.07-0.78); median JSC 0.35 (0.03-0.64)). Twenty-five patients demonstrated both rCBV and CE on MRI: The median rCBV tumor volume was significantly smaller than the median CE volume (p < 0.001). The OV was high (median 0.83 (0.54-1)), but the spatial similarity was low (median DSC 0.45 (0.04-0.83); median JSC 0.29 (0.07-0.71)). Twenty-eight patients demonstrated both K2 and CE on MRI. The median K2 tumor volume was not significantly larger than the median CE volume. The OV was high (median OV 0.90 (0.61-1)), and the spatial similarity was moderate (median DSC 0.75 (0.01-0.83); median JSC 0.60 (0.11-0.89))., Conclusion: We demonstrated that multiparametric perfusion MRI volumes (rCBV, K2) were highly correlated with CE T1 gadolinium volumes whereas 18 F-FET PET provided complementary information, suggesting that the metabolically active tumor volume in patients with newly diagnosed untreated HGG is critically underestimated by contrast enhanced MRI. 18 F-FET PET imaging may help to improve target volume delineation accuracy for radiotherapy planning., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: The objective of this study was to assess the therapeutic and prognostic impact of integrating18F-fluorodeoxyglucose (18-FDG) positron emission tomography (PET)/computed tomography (CT) into work-up (WU) at initial staging of patients with head and neck squamous cell carcinoma (HNSCC). Method: 477 consecutive patients (414M/63F, mean age 62.3 ± 9.7 years) with newly diagnosed HNSCC who underwent pre-treatment 18-FDG PET/CT were retrospectively included. The 18-FDG PET/CT stage (sPET) was compared to the conventional work-up stage (sCWU). A group of cancer specialists determined whether integrating PET/CT into WU at initial staging had an impact on the therapeutic decision, classifying the clinical impact as high (change in therapeutic modality), medium (change in the radiotherapy or surgical procedure), or low (modification of TNM staging and/or detection of synchronous cancer without high or medium impact). Three-year overall survival (OS) was considered as primary endpoint of the prognostic analysis. Results: 18-FDG PET/CT had a clinical impact in 221 patients (46.3%) with a medium or high impact on management in 94 (19.5%) patients. Medium and high impact of 18-FDG PET/CT was statistically equivalent between sCWU-stage I/II and III/IV subgroups ( p = 0.02). 42 patients were PET/CT-upstaged from early stage I/II to advanced stage III/IV and had a significantly lower 3-year OS than those with concordant CWU and 18-FDG PET/CT early stage (54.8 vs. 82.6%, p = 0.001). Conclusion: This study demonstrated that implementing 18-FDG PET/CT in the initial WU of HNSCC provides valuable staging information with a better prognostic stratification. Patient management was modified for any disease stage, even for early stage I-II, with consequences on survival., (Copyright © 2020 Leclere, Delcroix, Rousset, Valette, Robin, Guezennec, Le Pennec, Gujral, Abgral, Ollivier, Marianowski, Salaun, Schick and Abgral.)

Aim: Several series have already demonstrated that intratumoral subvolumes with high tracer avidity (hotspots) in 18F-flurodesoxyglucose positron-emission tomography (FDG-PET/CT) are preferential sites of local recurrence (LR) in various solid cancers after radiotherapy (RT), becoming potential targets for dose escalation. However, studies conducted on head and neck squamous cell carcinoma (HNSCC) found only a moderate overlap between pre- and post-treatment subvolumes. A limitation of these studies was that scans were not performed in RT treatment position (TP) and were coregistred using a rigid registration (RR) method. We sought to study (i) the influence of FDG-PET/CT acquisition in TP and (ii) the impact of using an elastic registration (ER) method to improve the localization of hotpots in HNSCC. Methods: Consecutive patients with HNSCC treated by RT between March 2015 and September 2017 who underwent FDG-PET/CT in TP at initial staging (PET A ) and during follow-up (PET R ) were prospectively included. We utilized a control group scanned in non treatment position (NTP) from our previous retrospective study. Scans were registered with both RR and ER methods. Various sub-volumes (A X ; x = 30, 40, 50, 60, 70, 80, and 90%SUVmax) within the initial tumor and in the subsequent LR (R X ; x = 40 and 70%SUVmax) were overlaid on the initial PET/CT for comparison [Dice, Jaccard, overlap fraction = OF, common volume/baseline volume = A X nR X /A X , common volume/recurrent volume = A X nR X /R X ]. Results: Of 199 patients included, 43 (21.6%) had LR (TP = 15; NTP = 28). The overlap between A 30 , A 40 , and A 50 sub-volumes on PET A and the whole metabolic volume of recurrence R 40 and R 70 on PET R showed moderate to good agreements (0.41-0.64) with OF and A X nR X /R X index, regardless of registration method or patient position. Comparison of registration method demonstrated OF and A X nR X /R X indices (x = 30% to 50%SUVmax) were significantly higher with ER vs. RR in NTP ( p < 0.03), but not in TP. For patient position, the OF and A X nR X /R X indices were higher in TP than in NTP when RR was used with a trend toward significance, particularly for x=40%SUVmax (0.50±0.22 vs. 0.31 ± 0.13, p = 0.094). Conclusion: Our study suggested that PET/CT acquired in TP improves results in the localization of FDG hotspots in HNSCC. If TP is not possible, using an ER method is significantly more accurate than RR for overlap estimation., (Copyright © 2020 Truffault, Bourhis, Chaput, Calais, Robin, Le Pennec, Lucia, Leclère, Gujral, Vera, Salaün, Schick and Abgral.)

Background: Management of metastatic N3 nodal disease from primary head and neck squamous cell carcinoma (HNSCC) is controversial. Recently, there has been a move to observation of the neck for those who achieve complete response (CR) after chemoradiotherapy (CRT). We sought to determine survival outcomes for N3 nodal disease, particularly for patients with human papilloma virus (HPV)-positive HNSCC., Methods: We carried out a systematic search of MEDLINE and Embase for articles between 01/2008 and 12/2017. Articles on N3 nodal disease in HNSCC patients treated with CRT or surgery + adjuvant RT/CRT were included if they reported on oropharyngeal or HPV+ subgroups. Local control (LC), nodal control (NC), distant metastasis-free survival (DMFS), disease-free survival (DFS) or overall survival (OS) was assessed., Results: Nine studies met the inclusion criteria. Eight of these studies (N = 5304) allowed further comparison: 4 were on CRT, 2 on surgery + RT/CRT and 2 on both. Four of these eight studies and the remaining included study reported on residual nodal disease on histology after neck dissection (ND) following CRT. Patients treated with CRT achieved LC rates of 77%-94% at 2-3 years; those who had a CR had LC of >90%. Better NC was noted in patients who achieved a CR. Three-year OS was better for HPV+ HNSCC (range, 55.2%-81%). Patients with CR had better survival outcomes (DMFS 77% at 3 years vs 69.8% for HPV+; OS 68.9% at 3 years vs 55.2% for HPV+). Primary surgery demonstrated similar survival for HPV+ vs HPV- and better survival in oropharyngeal cancers. Five-year DFS rates varied from 30% to 87%, and OS from 26.6% to 84%. For patients with non-CR, positive histology rates varied from 27.3% to 100%, with average positive histology rates of 27.3% in HPV+ patients with non-CR vs 60% for HPV- patients with non-CR., Conclusion: The current literature does not support the de-escalation of treatment with HPV- N3 disease. Observation of HPV+ patients who achieve a CR post-CRT is reasonable but further prospective studies are required given the heterogeneity and risk of bias within these current studies. Planned ND should remain standard of care for non-CR cohort., (© 2019 John Wiley & Sons Ltd.)

The improved survival in patients with HPV-positive (human papilloma virus) oropharyngeal squamous cell carcinoma as compared with HPV-negative disease calls for treatment that preserves quality of life, particularly a functional swallow. There are several trials currently assessing treatment de-escalation in terms of less invasive transoral robotic surgery, reduced-dose radiotherapy, and omission of chemotherapy in this disease cohort. It is important for head and neck oncology surgeons to stay abreast of developments in this area to offer their patients the most up-to-date treatment and consider recruiting patients to trials at their institutions. For this purpose, we provide a summary of current trials and associated challenges in managing a disease with fast-evolving treatment algorithms.

Aims: Management of the clinically node-negative (cN0) neck for parotid tumours remains controversial. Options include observation, elective neck dissection (END) or elective nodal irradiation (ENI). We reviewed the evidence for ENI on a background of current practice among UK clinical oncologists., Materials and Methods: We carried out a systematic search of PubMed between 1 January 1980 and 31 December 2016. Articles on patients treated with parotidectomy and either END or ENI, and studies on nodal patterns of disease, were included. UK clinical oncologists were asked to complete an online questionnaire regarding their use of neck radiotherapy in this setting., Results: From 96 references, 20 studies met the inclusion criteria: 11 reported on END, five on ENI and two on both. Eight studies reported on nodal patterns of disease. The prevalence of occult nodal metastases after END ranged from 0 to 45%. Five year locoregional control was variable (range 64-100%). For ENI, 5 year locoregional control varied from 74 to 100%. High-grade and T3/T4 tumours were factors for nodal relapse after END or ENI, which most commonly occurred in levels I-III. For the survey, 33/50 (66%) of cancer centres responded. Fourteen (42%) centres had guidelines for ENI. Most centres considered high-grade tumours (96%), T3/T4 disease (80%) and lymphovascular invasion (88%) as indications for ENI. Twelve centres (36%) irradiated levels Ib-IV electively; the remaining centres treated other various combinations of nodal levels., Conclusion: There is heterogeneity in the use and indications for ENI in the UK. ENI is a reasonable alternative to END as elective management for the cN0 neck in patients with high-grade tumours or T3/T4 disease. The elective clinical target volume should at least encompass nodal levels I-III., (Copyright © 2018 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.)

Intensity modulated radiotherapy (IMRT) in head and neck cancer allows sculpting of radiation dose to conform closely to target volumes and spare organs at risk. However, this may be offset by an increased risk of a geographical miss and reduction in survival outcomes. We reviewed the data from 5 prospective randomized controlled trials, one prospective phase II trial and 10 retrospective comparative series in terms of patterns of failure, treatment outcomes and late toxicities to determine any compromise in survival outcomes in favour of reduced late toxicity. Whilst there was some variablility in target volume delineation, radiation dose and technique, the published data consistently show reduced long term xerostomia (ranging from 0.5 to 87%) with IMRT compared to older radiation techniques. Some studies showed reduced incidence of >10% weight loss and grade ≥2 dysphagia with IMRT, and 2 studies reported higher rates of dysphagia with IMRT. Most studies demonstrated better, though non-significant, locoregional, disease-free and overall survival. The 4 studies that did demonstrate significantly better overall survival with IMRT were the largest cohorts with around 250 patients or greater. Standardization of target volume delineation, treatment verification protocols and outcome reporting will reduce heterogeneity and allow data to be pooled in order to be adequately powered for survival analyses., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Identification and quantification of the cardiac adverse effects of new cancer therapeutics is important when comparing treatment arms in clinical trials. Heart failure and left ventricular dysfunction are some of the most common adverse cardiac effects of a range of cancer treatments, including anthracyclines, trastuzumab and other targeted agents. Using the example of trastuzumab-induced cardiac dysfunction, we evaluated phase III clinical trials performed over the past decade to establish the methods used to identify heart failure and impairment of left ventricular function. Both these adverse events are difficult to accurately quantify. A clinical diagnosis of heart failure is subjective, and measurement of left ventricular ejection fraction has high interobserver variability depending on the method used to measure it. We found there was heterogeneity in methods used to diagnose both these adverse events. In addition, the use of quality assurance techniques to reduce measurement variability was low. We discuss and propose methods to standardise and reduce variability of cardiac event assessment in cancer clinical trials. This will allow true comparison of cardiac events between arms and trials with the aim of ensuring cardiac safety data are accurate., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: Administration of anthracycline chemotherapy ± trastuzumab is associated with cardiac dysfunction. We sought to identify whether prophylactic administration of angiotensin converting enzyme (ACE) inhibitor or beta-blocker attenuates subsequent left ventricular dysfunction and heart failure., Methods: Electronic databases were searched for studies examining the effect of beta-blockers or ACE inhibitors on left ventricular ejection fraction (LVEF) and heart failure in patients receiving anthracycline chemotherapy ± trastuzumab. The end-point was change in LVEF or development of heart failure., Results: Eight studies (1048 patients) were identified. There was no difference in the change in LVEF (weighted mean difference (MWD) - 4.74 (95% confidence interval (CI): -12.6 to 3.1), p = 0.24) or risk of new heart failure diagnosis (Odds ratio (OR) 0.24 (95% CI: 0.03-1.73), p = 0.16) between patients receiving ACE inhibitor or control. Betablocker use was associated with a significant smaller drop in LVEF compared to control (MWD -3.28 (95% CI: -6.1 to -0.51), p = 0.02) but not in patients who received anthracycline chemotherapy alone (MWD - 3.05 (95% CI -7.22 to 1.12), p = 0.15). There was a significant reduction in new heart failure diagnosis in those receiving beta-blocker compared to those not (OR 0.33 (95% CI: 0.14-0.80), p = 0.01)., Conclusions: Prophylactic ACE inhibitor does not attenuate development of LV dysfunction or heart failure in patients receiving anthracycline chemotherapy ± trastuzumab. Beta-blocker attenuated reduction in LVEF and new heart failure diagnosis. However, the effect in patients only receiving anthracycline is less certain. Studies examining the effect on mortality are required., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Background: Metastases to the thyroid are rare. The most common primary cancer to metastasize to the thyroid is renal cell carcinoma, followed by malignancies of the gastrointestinal tract, lungs, and skin, with breast cancer metastases to the thyroid being rare. Overall, the outcomes in malignancies that have metastasized to the thyroid are poor. There are no prospective studies addressing the role of surgery in metastatic disease of the thyroid. Isolated thyroidectomy has been proposed as a local disease control option to palliate and prevent the potential morbidity of tumor extension related to the airway. Here, we present a case of a patient with breast cancer metastases to the thyroid gland and discuss the role of thyroidectomy in the context of the current literature., Case Presentation: A 62-year-old Afro-Caribbean woman was diagnosed as having bilateral breast carcinoma in 2004, for which she underwent bilateral mastectomy. The pathology revealed multifocal disease on the right, T2N0(0/20)M0 grade 1 and 2 invasive ductal carcinoma, and on the left side, T3N1(2/18)M0 grade 1 invasive ductal carcinoma. Surgery was followed by adjuvant chemotherapy and regional radiotherapy. The disease was under control on hormonal therapy until 2016, when she developed cervical lymphadenopathy. The fine-needle aspiration cytology of the thyroid was reported as papillary thyroid cancer; and the fine-needle biopsy of the left lateral nodal disease was more suggestive of breast malignancy. She underwent a total thyroidectomy and a clearance of the central compartment lymph nodes and a biopsy of the lateral nodal disease. The histopathological analysis was consistent with metastatic breast cancer in the thyroid and lymph nodes with no evidence of a primary thyroid malignancy., Conclusions: A past history of a malignancy elsewhere should raise the index of suspicion of metastatic disease in patients presenting with thyroid lumps with or without cervical lymphadenopathy. Detection of metastases to the thyroid generally indicates poor prognosis, obviating the need of surgery in an already compromised patient. An empirical thyroidectomy should be considered in select patients for local disease control.

Aims: Deep inspiratory breath-hold (DIBH) techniques for left breast and chest wall radiotherapy can reduce cardiac dose. We investigated the use of 'upfront selection' criteria for DIBH based on tumour bed position and whether cardiac shielding was used., Materials and Methods: Four methods of selecting patients for DIBH were assessed retrospectively in a cohort of left breast and chest wall treatments. These were: (1) free breathing scan on all patients, selecting DIBH treatment for those with a predicted mean heart dose ≥3 Gy; (2) selective DIBH for those with maximum heart depth (MHD) on free breathing scan ≥1 cm; (3) use of an 'upfront selection process' using tumour bed position as initial selection and measurement of MHD on those not selected upfront; (4) DIBH on all. The methods were assessed on predicted mean heart dose, proportion needing two scans, sensitivity, specificity and the positive and negative predictive values. These were compared with method (1) as the gold standard., Results: In total 134 cases were analysed. The predicted mean heart dose in free breathing was ≥3 Gy in 28 (20.9%). Therefore, applying method (1), 28/134 (20.9%) would be selected for DIBH treatment. Applying method (2), 66/134 (49.2%) would be selected for DIBH treatment, all requiring two scans. Of these, 40/66 (60.6%) would receive < 3 Gy in free breathing so are over-selected; 2/68 (2.9%) would have received >3 Gy in free breathing so failed to be selected. Selection using method (3) was similar to method (2), but only five patients required two planning scans; 61/134 (45.5%) cases would be selected for DIBH upfront and 5/134 (3.7%) after initial free breathing scan; 42/66 (63.6%) of those selected for DIBH treatment would receive <3 Gy in free breathing and 4/68 not selected (6%) would receive >3 Gy in free breathing. For methods (2) and (3) most patients not selected for DIBH would have had a mean heart dose of ≤3 Gy (64/68, 90%). Using method (3), 86% (95% confidence interval 67-96%) of patients with a mean heart dose >3 Gy would be selected for DIBH treatment. The estimated mean and standard error for the area under the receiver operator characteristic curve for MHD as a predictor for mean heart dose was 0.85 (0.03)., Conclusion: This study supports the use of proposed an 'upfront selection process' as a means of selecting patients for treatment with DIBH and avoiding two radiotherapy planning scans. Calculation of MHD can be used as a surrogate for mean heart dose in the selection of cases for DIBH., (Copyright © 2017 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.)

Studies have reported that intraplaque neovascularisation (IPN) is closely correlated with plaque vulnerability. In this study, a new image processing approach, differential intensity projection (DIP), was developed to visualise and quantify IPN in contrast-enhanced non-linear ultrasound image sequences of carotid arteries. DIP used the difference between the local temporal maximum and the local temporal average signals to identify bubbles against tissue non-linear artefact and noise. The total absolute and relative areas occupied by bubbles within each plaque were calculated to quantify IPN. In vitro measurements on a laboratory phantom were made, followed by in vivo measurements in which 24 contrast-enhanced non-linear ultrasound image sequences of carotid arteries from 48 patients were selected and motion corrected. The results using DIP were compared with those obtained by maximum intensity projection (MIP) and visual assessment. The results indicated that DIP can significantly reduce non-linear propagation tissue artefacts and is much more specific in detecting bubble signals than MIP, being able to reveal microbubble signals that are buried in tissue artefacts in the corresponding MIP image. A good correlation was found between microvascular area (MVA) (r = 0.83, p < 0.001)/microvascular density (r = 0.77, p < 0.001) obtained using DIP and the corresponding expert visual grades, comparing favourably to r = 0.26 and 0.23 obtained using MIP on the same data. In conclusion, the proposed method exhibits great potential in quantification of IPN in contrast-enhanced ultrasound images of carotid arteries., (Copyright © 2016 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.)

Aims: Recently, carotid-sparing intensity-modulated radiotherapy (IMRT) for early laryngeal glottis (T1/T2N0M0) cancer has generated interest in the hope of avoiding long-term carotid toxicity, as well as concerns relating to geographical misses and long-term normal tissue toxicity. The aim of this review was to summarise the current literature on carotid-sparing IMRT for early glottis cancer, with particular focus on definitions of target volumes and the carotid arteries as organs at risk. In addition, we make suggestions for standardisation of these structures, dose constraints and dose reporting., Materials and Methods: From 73 references, 16 articles met the criteria for inclusion in this systematic review. These papers described two case reports, 11 planning studies and three prospective studies., Results: There was variation in all target volume definitions with no clear consensus. The greatest variability was in clinical target volume definition. Carotid artery and spinal cord delineation were not always defined and most studies did not use a carotid artery constraint. Of the eight studies that reported carotid artery delineation, no two studies delineated the same length of carotid artery, yet most studies reported mean doses. Most studies used IMRT with three to seven fields. Five studies used arc therapy and two studies used tomotherapy., Conclusion: This review highlights a lack of consensus in target volume definitions in carotid-sparing IMRT. Ultimately, long-term prospective data are required to show the benefit of carotid-sparing IMRT. Pooled data will prove useful as most studies will report on small numbers of patients. Therefore, adopting a consensus now on target volume definition, dose constraints and dose reporting will be crucial., (Copyright © 2016. Published by Elsevier Ltd.)

Aims: To determine the clinical outcomes of an intensity-modulated radiotherapy technique for total mucosal irradiation (TM-IMRT) in patients with head and neck carcinoma of unknown primary (HNCUP)., Materials and Methods: A single-centre prospective phase II trial design was used in two sequential studies to evaluate TM-IMRT for HNCUP. Patients were investigated for primary tumour site using examination under anaesthetic and biopsies, computed tomography ± magnetic resonance imaging (MRI) or 18-fluorodeoxyglucose positron emission tomography-computed tomography (PET-CT). Patients received IMRT to the potential primary tumour sites and elective cervical nodes. Concomitant chemotherapy was used in patients who received primary radiotherapy or those with nodal extracapsular extension., Results: Thirty-six patients with HNCUP were recruited; 72% male. Twenty-five patients (69.4%) had p16-positive disease. Two year mucosal and local nodal control rates were 97.1% (95% confidence interval 91.4-100) and 89.8% (78.4-100), respectively. One mucosal primary was detected 7.3 months after TM-IMRT and three patients died from recurrent/metastatic squamous cell carcinoma of the head and neck. Twelve patients (33%) developed grade 3 (Late Effects in Normal Tissue-Subjective, Objective, Management and Analytical; LENT-SOMA) dysphagia with a 1 year enteric tube feeding rate of 2.7%. The high-grade subjective xerostomia rate (LENT-SOMA) at 24 months after IMRT was 15%., Conclusions: At a median follow-up of 36.1 months, the use of TM-IMRT was associated with good local control. Toxicity was comparable with previously reported TM-IMRT regimens encompassing similar mucosal volumes., (Copyright © 2016 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.)

Purpose: Abnormal proliferation of adventitial vasa vasorum (vv) occurs early at sites of atherosclerosis and is thought to be an early biomarker of vascular damage. Contrast-enhanced ultrasound (CEUS) can detect this process. Its usefulness in irradiated arteries as a measure of accelerated atherosclerosis is unknown. This study investigates contrast intensity in carotid adventitia as an early marker of radiation-induced damage in head and neck cancer (HNC) patients., Materials/methods: Patients with HNC treated with a wedged-pair and matched neck technique or hemi-neck radiotherapy (RT) (unirradiated side as control) at least 2years previously were included. Patients had been prescribed a dose of at least 50Gy to the neck. CEUS was performed on both carotid arteries and a region of interest was selected in the adventitia of the far wall of both left and right distal common carotid arteries. Novel quantification software was used to compare the average intensity per pixel between irradiated and unirradiated arteries., Results: 48 patients (34 males) with median age of 59.2years (interquartile range (IQR) 49.2-64.2) were included. The mean maximum point dose to the irradiated artery was 61.2Gy (IQR 52.6-61.8) and 1.1Gy (IQR 1.0-1.8Gy) to the unirradiated side. The median interval from RT was 59.4months (IQR 41-88.7). There was a significant difference in the mean (SD) contrast intensity per pixel on the irradiated side (1.1 (0.4)) versus 0.96 (0.34) on the unirradiated side (p=0.01). After attenuation correction, the difference in mean contrast intensity per pixel was still significant (1.4 (0.58) versus 1.2 (0.47) (p=0.02). Previous surgery or chemotherapy had no effect on the difference in contrast intensity between the 2 sides of the neck. Mean intensity per pixel did not correlate to traditional risk prediction models (carotid intima-medial thickness, QSTROKE score)., Conclusions: Proliferation of vv is demonstrated by increased contrast intensity in irradiated carotid arteries. This may be a useful, independent biomarker of radiation-induced carotid atherosclerosis when used as a tool to quantify neovascularization., (Crown Copyright © 2016. Published by Elsevier Ireland Ltd. All rights reserved.)

Background: Primary radical radiotherapy (RT) for head and neck cancer (HNC) often results in significant radiation dose to the carotid arteries., Aim: We assessed whether HNC patients are at increased risk of a cerebrovascular event primarily due to RT or other risk factors for atherosclerosis by (i) risk-stratifying patients according to validated QRISK-2 and QSTROKE scores and (ii) comparing the prevalence of carotid artery stenosis (CAS) in irradiated and unirradiated carotid arteries., Design: HNC patients treated with an RT dose >50 Gy to one side of the neck ≥2 years previously were included., Methods: QRISK-2 (2014) and Q-STROKE (2014) scores were calculated. We compared the prevalence of CAS in segments of the common carotid artery on the irradiated and unirradiated sides of the neck., Results: Fifty patients (median age of 58 years (interquartile range (IQR) 50-62)) were included. The median QRISK-2 score was 10% (IQR 4.4-15%) and the median QSTROKE score was 3.4% (IQR 1.4-5.3%). For both scores, no patient was classified as high risk. Thirty-eight patients (76%) had CAS in one or both arteries. There was a significant difference in the number of irradiated arteries with stenosis (N = 37) compared with unirradiated arteries (N = 16) (P < 0.0001). There were more plaques on the irradiated artery compared with the unirradiated side - 64/87 (73.6%) versus 23/87 (26.4%), respectively (P < 0.001). , Conclusions: Traditional vascular risk factors do not play a role in radiation-induced carotid atherosclerosis. Clinicians should be aware that traditional risk prediction models may under-estimate stroke risk in these patients., (© The Author 2015. Published by Oxford University Press on behalf of the Association of Physicians. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Objectives: The aim of this study was to determine the effect of radiotherapy (RT) on intraplaque neovascularization (IPN) in human carotid arteries., Background: Exposure of the carotid arteries to RT during treatment for head and neck cancer is associated with increased risk for stroke. However, the effect of RT on IPN, a precursor to intraplaque hemorrhage and thus associated with plaque vulnerability, is unknown., Methods: In this cross-sectional study, patients who had undergone unilateral RT for head and neck cancer ≥2 years previously underwent B-mode and contrast-enhanced ultrasound of both RT-side and non-RT-side carotid arteries. Presence of IPN during contrast-enhanced ultrasound was judged semiquantitatively as grade 0 (absent), grade 1 (present but limited to plaque base), or grade 2 (extensive and noted within plaque body)., Results: Of 49 patients studied, 38 (78%) had plaques. The number of plaques was significantly greater in the RT than the non-RT arteries. Overall, 48 of 64 RT-side plaques (75%) had IPN compared with 9 of 23 non-RT-side (39%) plaques (p = 0.002). Among patients with plaques, IPN was present in 81% of patients with RT-side plaques and 41% of patients with non-RT-side plaques (p = 0.004). Grade 0 IPN was significantly more common in patients with non-RT-side plaques (25% vs. 61%; p = 0.002), whereas grade 2 plaques were more common on the RT side (31% vs. 9%; p = 0.03). The only clinical variable that predicted the presence or absence of IPN was RT laterality., Conclusions: This is the first study in humans to reveal a significant association between RT and the presence and extent of IPN. This may provide insights into the mechanisms underlying the increased stroke risk among survivors of head and neck cancer treated by RT., (Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Arterial stiffness is thought to be a precursor to atherosclerosis. Conventional arterial stiffness parameters as potential biomarkers of radiation-induced damage were investigated. Patients with head and neck cancer treated with radiotherapy ≥2 years previously to one side of the neck were included. The unirradiated side was the internal control. Beta stiffness index (B) and elastic modulus (Ep) were used to assess arterial stiffness and were measured in proximal, mid, and distal common carotid artery (CCA) and compared with the corresponding unirradiated segments. Fifty patients (68% male; median age 58 years; interquartile range 50-62) were included. Mean ± standard deviation maximum doses to irradiated and unirradiated arteries were 53 ± 13 and 1.9 ± 3.7 Gy, respectively. Differences in B were not significant. Significant differences in Ep were demonstrated-proximal CCA: 1301 ± 1223 versus 801 ± 492 (P < .0001), mid CCA: 1064 ± 818 versus 935.5 ± 793 (P < .0001), and distal CCA: 1267 ± 1084 versus 775.3 ± 551.9 (P < .0001). Surgery had no impact on arterial stiffness. Arterial stiffness is increased in irradiated arteries, in keeping with radiation-induced damage. Prospective data may show an association between arterial stiffness and atherosclerosis in this setting., (© The Author(s) 2015.)

Radiation to the mediastinum is a key component of treatment with curative intent for a range of cancers including Hodgkin's lymphoma and breast cancer. Exposure to radiation is associated with a risk of radiation-induced heart valve damage characterised by valve fibrosis and calcification. There is a latent interval of 10-20 years between radiation exposure and development of clinically significant heart valve disease. Risk is related to radiation dose received, interval from exposure and use of concomitant chemotherapy. Long-term outlook and the risk of valve surgery are related to the effects of radiation on mediastinal structures including pulmonary fibrosis and pericardial constriction. Dose prediction models to predict the risk of heart valve disease in the future and newer radiation techniques to reduce the radiation dose to the heart are being developed. Surveillance strategies for this cohort of cancer survivors at risk of developing significant heart valve complications are required., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

Purpose: Arterial thickening is a precursor to atherosclerosis. Carotid intima-medial thickness (CIMT), a measure of arterial thickening, is a validated surrogate for prediction of cerebrovascular events. This study investigates CIMT as an early marker of radiation-induced carotid artery damage., Materials/methods: Head and neck cancer patients treated with radiotherapy (RT) (minimum dose of 50 Gy) to one side of the neck (unirradiated side as control) at least 2 years previously were included. CIMT was measured in 4 arterial segments: proximal, mid, distal common carotid artery (CCA), and bifurcation and were compared to corresponding unirradiated segments. CIMT measurements >75th percentile of a reference population were considered abnormal and at increased cerebrovascular risk., Results: 50 patients (34 males) with a median age of 58 years (interquartile range (IQR) 50-62) were included. The mean maximum dose to the irradiated and unirradiated artery was 53 Gy (standard deviation (SD) 13 Gy) and 1.9 Gy (SD 3.7 Gy), respectively. Mean CIMT was significantly greater in irradiated versus unirradiated arteries: proximal CCA (0.76 mm ± 0.15 vs 0.68 mm ± 0.14 (p<0.0001), mid CCA (0.74 mm ± 0.2 vs 0.68 mm ± 0.16 (p=0.01), distal CCA (0.77 mm ± 0.2 vs 0.68 mm ± 0.15 (p=0.004), and bifurcation (0.85 mm ± 0.25 vs 0.72 mm ± 0.17 (p=0.001). For all arterial segments, a significantly greater number of CIMT measurements were abnormal on the irradiated side (proximal: p=0.004, mid: p=0.05, distal: p=0.005, bifurcation: p=0.03). There was no effect of time from RT, age, smoking status, surgery and chemotherapy on CIMT difference (irradiated-unirradiated) in all segments., Conclusions: CIMT is increased after RT and may be a useful marker of radiation-induced carotid atherosclerosis. There appears to be no additional effect of other atherosclerotic risk factors on CIMT following RT., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

An automated attenuation correction and normalisation algorithm was developed to improve the quantification of contrast enhancement in ultrasound images of carotid arteries. The algorithm first corrects attenuation artefact and normalises intensity within the contrast agent-filled lumen and then extends the correction and normalisation to regions beyond the lumen. The algorithm was first validated on phantoms consisting of contrast agent-filled vessels embedded in tissue-mimicking materials of known attenuation. It was subsequently applied to in vivo contrast-enhanced ultrasound (CEUS) images of human carotid arteries. Both in vitro and in vivo results indicated significant reduction in the shadowing artefact and improved homogeneity within the carotid lumens after the correction. The error in quantification of microbubble contrast enhancement caused by attenuation on phantoms was reduced from 55% to 5% on average. In conclusion, the proposed method exhibited great potential in reducing attenuation artefact and improving quantification in contrast-enhanced ultrasound of carotid arteries., (Copyright © 2015 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.)

Objectives: We previously described dose-escalated intensity-modulated radiotherapy (IMRT) in squamous cell cancer of the larynx/hypopharynx (SCCL/H) to offer improved locoregional control with a low incidence of toxicity at 2 years. We now present outcome and safety data at 5 years., Materials and Methods: A sequential cohort Phase I/II trial design was used. Patients with SCCL/H received IMRT at two dose levels (DL): DL1, 63 Gy/28 fractions to planning target volume 1 (PTV1) and 51.8 Gy/28 Fx to PTV2; DL2, 67.2 Gy/28 Fx and 56 Gy/28 Fx to PTV1 and PTV2, respectively. Patients received induction cisplatin/5-fluorouracil and concomitant cisplatin., Results: Between 09/2002 and 01/2008, 60 patients (29 DL1, 31 DL2) with stage III (41% DL1, 52% DL2) and stage IV (52% DL1, 48% DL2) disease were recruited. Median (range) follow-up for DL1 was 5.7 (1.0-10.2) years and for DL2 was 6.0 (0.3-8.4) years. Five-year local control rates (95% confidence interval) for DL1 and DL2, respectively, were 68% (50.6-85.4%) and 75% (58.9-91.1%), locoregional progression-free survival rates were 54% (35.6-72.4%) and 62.6% (44.8-80.4%), and overall survival was 61.9% (44.1-79.7) and 67.6 (51.1-84.1%). Five-year laryngeal preservation rates were 66.7% (37.4-87.9%) and 71.4% (44.4-85.8%), respectively. Cumulative toxicities reported were: one patient in DL1 and 2 in DL2 developed benign pharyngeal strictures. No other G3/4 toxicities were reported., Conclusions: Dose-escalated IMRT at DL2 achieves higher 5-year local control, larynx preservation and survival rates with acceptable late toxicity. Recruitment into a Cancer Research UK Phase III study (ART-DECO), with DL2 as the experimental arm, is ongoing., (Copyright © 2014. Published by Elsevier Ltd.)

Objectives: Induction chemotherapy (IC) followed by chemoradiation (CRT) for locally advanced squamous cell head and neck cancer (SCCHN) remains controversial in the absence of clear evidence to define its role. As part of a prospective, randomised, multicentre study of CRT for stage III/IV laryngeal/hypopharyngeal cancers (ART DECO, CRUK/10/018), we have examined the attitudes of oncologists in the United Kingdom (UK) to IC., Materials and Methods: Head and neck oncologists across the UK who expressed an interest in participating in the ART DECO trial were asked to complete a short written questionnaire designed to identify current UK practice of IC for stage III-IVb SCCHN. Completed questionnaires were returned to the clinical trials office prior to patient recruitment., Results: Clinicians from twenty-five/48 centres (52.1%) responded. Twenty centres (80%) elected to use IC in the trial. For stage III disease, 80% of centres did not prescribe IC for T1N1 disease and 60% did not offer IC for T3N0 disease. Patients with bulky primary tumours or extensive nodal disease were more likely to receive IC. Thirteen prescribing centres (65%) use 3 drugs (docetaxel, cisplatin, and 5-fluorouracil) compared to 7 (35%) using 2 drugs (cisplatin and 5-fluorouracil). Fifteen centres (75%) prescribed 2 cycles of IC, and 5 (25%) prescribed 3 cycles. There was variation in the dosage for both the 2- and 3-drug regimens., Conclusion: Results suggest that clinical practice in the UK is currently divided between a 2- versus 3-drug regimen for IC for specific subgroups of patients. A consensus regarding the optimal combinations and dosages is required before further optimization of systemic therapy with other cytotoxics and biological agents is attempted., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Carotid arteries frequently receive significant incidental doses of radiation during the treatment of malignant diseases, including head and neck cancer, breast cancer and lymphoma. Vascular injury after treatment may result in carotid artery stenosis and increased risk of neurological sequelae, such as stroke and transient ischaemic attack. The long latent interval from treatment to the development of clinical complications makes investigation of this process difficult, particularly in regard to the design of interventional clinical studies. Nevertheless, there is compelling clinical evidence that radiation contributes to carotid atherosclerosis. This overview examines the effect of radiotherapy on the carotid arteries, the underlying pathological processes and their clinical manifestations. The use of serum biomarkers in risk-prediction models and the potential value of new imaging techniques as tools for defining earlier surrogate end points will also be discussed., (Copyright © 2013 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.)

Purpose: Carotid arteries frequently receive significant doses of radiation as collateral structures in the treatment of malignant diseases. Vascular injury following treatment may result in carotid artery stenosis (CAS) and increased risk of stroke and transient ischaemic attack (TIA). This systematic review examines the effect of radiotherapy (RT) on the carotid arteries, looking at the incidence of stroke in patients receiving neck radiotherapy. In addition, we consider possible surrogate endpoints such as CAS and carotid intima-medial thickness (CIMT) and summarise the evidence for radiation-induced carotid atherosclerosis., Materials and Methods: From 853 references, 34 articles met the criteria for inclusion in this systematic review. These papers described 9 studies investigating the incidence of stroke/TIA in irradiated patients, 11 looking at CAS, and 14 examining CIMT., Results: The majority of studies utilised suboptimally-matched controls for each endpoint. The relative risk of stroke in irradiated patients ranged from 1.12 in patients with breast cancer to 5.6 in patients treated for head and neck cancer. The prevalence of CAS was increased by 16-55%, with the more modest increase seen in a study using matched controls. CIMT was increased in irradiated carotid arteries by 18-40%. Only two matched-control studies demonstrated a significant increase in CIMT of 36% and 22% (p=0.003 and <0.001, respectively). Early prospective data demonstrated a significant increase in CIMT in irradiated arteries at 1 and 2 years after RT (p<0.001 and <0.01, respectively)., Conclusions: The incidence of stroke was significantly increased in patients receiving RT to the neck. There was a consistent difference in CAS and CIMT between irradiated and unirradiated carotid arteries. Future studies should optimise control groups., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Evaluation of cardiac tumors with cardiovascular imaging aims to establish aetiology, identify complications of tumor and help define management strategy. 2D echocardiography remains the primary diagnostic modality. Additional use of newer echocardiographic techniques such as 3D, strain and contrast echocardiography better characterise tumor morphology, tissue characteristics and vascularity respectively. Cardiac MRI and computed tomography provide complementary information and are able to identify extra-cardiac infiltration and also provide further tissue characterisation. This review explores the non-invasive diagnostic approach to evaluation of cardiac tumors.

Carcinoid tumors are rare, slow-growing tumors found primarily in the GI tract. Carcinoid syndrome develops when vasoactive substances (particularly serotonin) released by carcinoid tumors gain access to the systemic circulation. Carcinoid heart disease develops in patients with carcinoid syndrome and is commonly associated with the development of right-sided valve dysfunction and signs of symptoms of right heart failure. Timely surgical intervention provides relief from symptoms and may improve survival. Management of these patients should be undertaken in a specialized center by a multidisciplinary team with appropriate expertise.

Background and Aim of the Study: Carcinoid heart disease (CaHD) is a rare form of valvular heart disease in patients with carcinoid syndrome (CS). The role of 5-hydroxytryptamine (5-HT) in the pathogenesis of CaHD is unclear. The study aim was to evaluate the association between platelet 5-HT (5-HTplt) and plasma 5-HT (5-HTpls) and valvular dysfunction., Methods: Twelve patients with CaHD, 18 with CS and 10 'normal' subjects were recruited. Patients with CaHD underwent cardiac catheterization and echocardiography. 5-HTplt and 5-HTpls was sampled in blood from the femoral vein, right and left ventricle, and left antecubital fossa vein., Results: Levels of 5-HTpls and 5-HTplt were significantly higher in patients with CaHD (median 5-HTpls 325 nmol/l and 5-HTplt 18.9 nmol/10(9) platelets) and CS (median 5-HTpls 155 nmol/l and 5-HTplt 16.4 nmol/10(9) platelets) when compared to healthy controls (median 5-HTpls 9 nmol/l and 5-HTplt 3.7 nmol/10(9) platelets; p < 0.0001 and p = 0.003, respectively). There was a significant increase in 5-HTplt and 5-HTpls between the femoral vein and right heart (p = 0.007 and p = 0.0002, respectively). There was no significant difference in 5-HTplt or 5-HTpls between the right and left side of the heart, irrespective of the presence of a patent foramen ovale or of left-sided CaHD., Conclusion: Plasma and platelet 5-HT levels are elevated in patients with CaHD. Despite exposure to similar levels of intracardiac plasma and platelet 5-HT, the development of valve dysfunction is heterogeneous. This suggests that individual heart valves have a susceptibility to the development of valvular dysfunction which is not related solely to plasma or platelet 5-HT levels.

Introduction: Over 90% of head and neck cancers overexpress EGFR. This correlates with advanced disease stage and worse prognosis. Strategies to inhibit the EGFR pathway have been developed over the last decade. Zalutumumab is a recent high-affinity completely human IgG1k antibody targeting EGFR., Areas Covered: The mechanism of action and data on efficacy and safety of zalutumumab in head and neck cancer., Expert Opinion: Zalutumumab has demonstrated acceptable toxicity in head and neck cancer patients, with rash being the most common adverse event. The toxicity profile makes zalutumumab an attractive option for patients who are heavily pretreated and/or have poor performance status due to concurrent co-morbidities. As the molecule is fully human, the likelihood of hypersensitivity to the drug is low. Zalutumumab may be effective at low concentrations through antibody-dependent cellular cytotoxicity. Current data from Phase I and II trials identify zalutumumab as a promising drug for the treatment of locally advanced head and neck cancer and recent data from a Phase III randomized trial showed encouraging survival results compared with best supportive care. Results from other ongoing Phase III trials will provide clarification on zalutumumab as a treatment option. The clinical development of this compound has been suspended from June 2011 until a development and commercialization partner is found.

Background: The benefit of induction chemotherapy (IC) before chemoradiotherapy (CRT) for inoperable esophageal adenocarcinoma has not been established. To clarify toxicities and outcomes of combined modality treatment, we performed a retrospective review., Materials and Methods: Sixty-eight consecutive patients were identified. Fifty-one patients had CRT, 17 had radiotherapy (RT). Fifty-eight received IC before RT. IC consisted of 4 cycles of platinum and fluoropyrimidines followed by CRT 54 Gy with concurrent infusional 5-fluorouracil (5-FU) or capecitabine. Response to IC was assessed at 3 months and response to CRT at 3 months. Time to progression (TTP) and overall survival (OS) are reported., Results: Fifty-four patients were men and 14 were women, with median age 72 years (range, 42-87 years). There were 29 stage II, 33 stage III, 4 stage IVa, and 2 stage IVb tumors. The response 3 months after completion of treatment was 39.6%. No grade 4 toxicity was reported, but 10/58 patients had grade 3 toxicity from IC. The median TTP and OS from RT for the entire cohort was 12 months (95% confidence interval [CI], 7-18) and 16 months (95% CI, 5-27), respectively. The 1- and 2-year survival rates from diagnosis were 73% and 47%, respectively. There was no statistically significant difference in TTP or OS in patients who responded to IC compared with those who did not (median TTP 11 vs. 12 months, respectively; P = .8; median OS 15 vs. 14 months, respectively; P = .8)., Conclusion: The outcome in patients with adenocarcinoma of the esophagus after CRT is comparable to unselected surgical series. Response to IC is not always an indicator of eventual outcome., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Purpose: The justification for partial breast radiotherapy after breast conservation surgery assumes that ipsilateral breast tumor relapses (IBTR) outside the index quadrant are mostly new primary (NP) tumors that develop despite radiotherapy. We tested the hypothesis that whole-breast radiotherapy (WBRT) is ineffective in preventing NP by comparing development rates in irradiated and contralateral breasts after tumor excision and WBRT., Methods and Materials: We retrospectively reviewed 1,410 women with breast cancer who were entered into a prospective randomized trial of radiotherapy fractionation and monitored annually for ipsilateral breast tumor relapses (IBTR) and contralateral breast cancer (CLBC). Cases of IBTR were classified into local recurrence (LR) or NP tumors based on location and histology and were subdivided as definite or likely depending on clinical data. Rates of ipsilateral NP and CLBC were compared over a 15-year period of follow-up., Results: At a median follow-up of 10.1 years, there were 150 documented cases of IBTR: 118 (79%) cases were definite or likely LR; 27 (18%) cases were definite or likely NP; and 5 (3%) cases could not be classified. There were 71 cases of CLBC. The crude proportion of definite-plus-likely NP was 1.9% (27/1,410) patients compared with 5% (71/1,410) CLBC patients. Cumulative incidence rates at 5, 10, and 15 years were 0.8%, 2.0%, and 3.5%, respectively, for definite-plus-likely NP and 2.4%, 5.8%, and 7.9%, respectively for CLBC, suggesting a difference in the rates of NP and CLBC., Conclusions: This analysis suggests that WBRT reduces the rate of ipsilateral NP tumors. The late presentation of NP has implications for the reporting of trials that are testing partial breast radiotherapy., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Background: A 48-year-old man presented with diarrhea, flushing, abdominal pain and weight loss of 10 kg over a 6-month period. He subsequently developed dyspnea on exertion., Investigations: Physical examination, laboratory tests, CT of the abdomen, liver biopsy, echocardiography, immunohistochemistry staining of the biopsy specimen for neuroendocrine markers including chromogranin A, synaptophysin and protein gene product 9.5, and (111)In-pentetreotide scintigraphy (Octreoscan)., Diagnosis: Carcinoid tumor of midgut origin with large segment 3 liver metastasis. Carcinoid syndrome and carcinoid heart disease., Management: Symptomatic relief with somatostatin analog therapy and subsequent resection of the segment 3 liver metastasis. Tricuspid and pulmonary valve replacement.

Introduction: Invasive ductal and lobular carcinomas represent 67.9% and 6.3% of breast carcinoma, respectively. Metastatic breast cancer typically involves the lungs, bones, brain, and liver. Studies have shown differing patterns of metastatic spread between ductal and lobular carcinoma. Lobular carcinoma is more likely to metastasise to the gastrointestinal tract., Case Presentation: We report the case of a 49 year old white woman with invasive ductal carcinoma with lobular differentiation who developed submucosal oropharyngeal metastases nearly two years after her original diagnosis after presenting with odynophagia and dysphagia. The patient's symptoms preceded any associated radiological or endoscopic abnormalities by at least 9 months. Repeat computed tomography scan and eventual oropharyngeal biopsy confirmed submucosal metastatic invasive ductal carcinoma, suggesting occult submucosal spread., Conclusion: This case illustrates the importance of maintaining a high index of suspicion for metastatic disease in patients with invasive breast cancer who present with unusual symptoms and a careful search for metastatic sites.

Introduction: Metastatic tumour involvement of the anal canal is rare. Routine pathological evaluation of haemorrhoidectomy specimens has been suggested to be unhelpful and expensive. Selective rather than routine pathological evaluation of haemorrhoidectomy specimens has been recommended., Case Presentation: We report the case of a 69-year-old woman with metastatic colorectal carcinoma who presented with metastatic carcinoma within thrombosed haemorrhoids., Conclusion: We suggest that in patients with colorectal cancer, careful examination of haemorrhoids on colonoscopy as well as histological examination of suspected haemorrhoidal tissue after surgical resection be performed to evaluate for metastasis.

Introduction: Bevacizumab is a monoclonal antibody that inhibits the action of vascular endothelial growth factor (VEGF) thereby acting as an angiogenesis inhibitor. As a result, supply of oxygen and nutrients to tissues is impaired and tumour cell growth is reduced. Reported side effects due to bevacizumab are hypertension and increased risk of bleeding. Bowel perforation has also been reported. Periodontal disease in patients on bevacizumab therapy has not been reported before., Case Presentation: We report a case of a forty-three year old woman who developed periodontitis whilst receiving bevacizumab for lung cancer. The periodontal disease remained stable on discontinuation of the drug., Conclusion: Further investigations are needed to determine the mechanism for bevacizumab-induced periodontal disease.