Assessment and topographic characterization of locoregional recurrences in head and neck tumours

Purpose: To evaluate the differences between three methods of classification of recurrences in patients with head and neck tumours treated with Radiation Therapy (RT). Materials and methods: 367 patients with head and neck tumours were included in the study. Tumour recurrences were delineated in the CT images taken during patient follow-up and deformable registration was used to transfer this volume into the planning CT. The methods used to classify recurrences were: methodCTV quantified the intersection volume between the recurrence and the Clinical Target Volume (CTV); methodTV quantified the intersection between the Treated Volume and the recurrence (for method CTV and TV, recurrences were classified in-field if more than 95% of their volume were inside the volume of interest, marginal if the intersection was between 20-95% and outfield otherwise); and methodCOM was based on the position of the Centre Of Mass of the recurrence. A dose assessment in the recurrence volume was also made. Results: The 2-year Kaplan-Meier locoregional recurrence incidence was 10%. Tumour recurrences occurred in 22 patients in a mean time of 16.5 ± 9.4 months resulting in 28 recurrence volumes. The percentage of in-field recurrences for methods CTV, TV and COM was 7%, 43% and 50%, respectively. Agreement between the three methods in characterizing individually in-field and marginal recurrences was found only in six cases. Methods CTV and COM agreed in 14. The percentage of outfield recurrences was 29% using all methods. For local recurrences (in-field or marginal to gross disease) the average difference between the prescribed dose and D 98% in the recurrence volume was -5.2 ± 3.5% (range: -10.1%-0.9%). Conclusions: The classification of in-field and marginal recurrences is very dependent on the method used to characterize recurrences. Using methods TV and COM the largest percentage of tumour recurrences occurred in-field in tissues irradiated with high doses. Keywords: Head and neck tumours, Radiation therapy, Characterization of tumour recurrences, Geometric methods, Dosimetric assessmen

Standardisation of Target Volume Delineation for Carotid-sparing Intensity-modulated Radiotherapy in Early Glottis Cancer.

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

Plaque Neovascularization Is Increased in Human Carotid Atherosclerosis Related to Prior Neck Radiotherapy A Contrast-Enhanced Ultrasound Study

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. (C) 2016 by the American College of Cardiology Foundation

The emerging potential of magnetic resonance imaging in personalizing radiotherapy for head and neck cancer: an oncologist's perspective.

Head and neck cancer (HNC) is a challenging tumour site for radiotherapy delivery owing to its complex anatomy and proximity to organs at risk (OARs) such as the spinal cord and optic apparatus. Despite significant advances in radiotherapy planning techniques, radiation-induced morbidities remain substantial. Further improvement would require high-quality imaging and tailored radiotherapy based on intratreatment response. For these reasons, the use of MRI in radiotherapy planning for HNC is rapidly gaining popularity. MRI provides superior soft-tissue contrast in comparison with CT, allowing better definition of the tumour and OARs. The lack of additional radiation exposure is another attractive feature for intratreatment monitoring. In addition, advanced MRI techniques such as diffusion-weighted, dynamic contrast-enhanced and intrinsic susceptibility-weighted MRI techniques are capable of characterizing tumour biology further by providing quantitative functional parameters such as tissue cellularity, vascular permeability/perfusion and hypoxia. These functional parameters are known to have radiobiological relevance, which potentially could guide treatment adaptation based on their changes prior to or during radiotherapy. In this article, we first present an overview of the applications of anatomical MRI sequences in head and neck radiotherapy, followed by the potentials and limitations of functional MRI sequences in personalizing therapy

Attenuation correction and normalisation for quantification of contrast enhancement in ultrasound Images of carotid arteries

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 invivo contrast-enhanced ultrasound (CEUS) images of human carotid arteries. Both invitro and invivo 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

Feasibility of intensity-modulated and image-guided radiotherapy for locally advanced esophageal cancer

BACKGROUND:In this study the feasibility of intensity-modulated radiotherapy (IMRT) and tomotherapy-based image-guided radiotherapy (IGRT) for locally advanced esophageal cancer was assessed.METHODS:A retrospective study of ten patients with locally advanced esophageal cancer who underwent concurrent chemotherapy with IMRT (1) and IGRT (9) was conducted. The gross tumor volume was treated to a median dose of 70Gy (62.4-75Gy).RESULTS:At a median follow-up of 14months (1-39 months), three patients developed local failures, six patients developed distant metastases, and complications occurred in two patients (1 tracheoesophageal fistula, 1 esophageal stricture requiring repeated dilatations). No patients developed grade 3-4 pneumonitis or cardiac complications.CONCLUSIONS:IMRT and IGRT may be effective for the treatment of locally advanced esophageal cancer with acceptable complications.This item is part of the UA Faculty Publications collection. For more information this item or other items in the UA Campus Repository, contact the University of Arizona Libraries at [email protected]

Do traditional risk stratification models for cerebrovascular events apply in irradiated head and neck cancer patients?

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

Evaluation of radiotherapy techniques for radical treatment of lateralised oropharyngeal cancers : Dosimetry and NTCP.

Aim The aim of this study was to investigate potential advantages and disadvantages of three-dimensional conformal radiotherapy (3DCRT), multiple fixed-field intensity-modulated radiotherapy (IMRT) and volumetric-modulated arc therapy (VMAT) in terms of dose to the planning target volume (PTV), organs at risk (OARs) and normal tissue complication probability (NTCP) for delivering ipsilateral radiotherapy.Materials and methods 3DCRT, IMRT and VMAT were compared in patients with well-lateralised primary tonsillar cancers who underwent primary radical ipsilateral radiotherapy. The following parameters were compared: conformity index (CI); homogeneity index (HI); dose-volume histograms (DVHs) of PTVs and OARs; NTCP, risk of radiation-induced cancer and dose accumulation during treatment.Results IMRT and VMAT were superior to 3DCRT in terms of CI, HI and dose to the target volumes, as well as mandible and dose accumulation robustness. The techniques were equivalent in terms of dose and NTCP for the contralateral oral cavity, contralateral submandibular gland and mandible, when specific dose constraint objectives were used on the oral cavity volume. Although the volume of normal tissue exposed to low-dose radiation was significantly higher with IMRT and VMAT, the risk of radiation-induced secondary malignancy was dependant on the mathematical model used.Conclusion This study demonstrates the superiority of IMRT/VMAT techniques over 3DCRT in terms of dose homogeneity, conformity and consistent dose delivery to the PTV throughout the course of treatment in patients with lateralised oropharyngeal cancers. Dosimetry and NTCP calculations show that these techniques are equivalent to 3DCRT with regard to the risk of acute mucositis when specific dose constraint objectives were used on the contralateral oral cavity OAR

Delayed DNA double-strand break repair following platin-based chemotherapy predicts treatment response in head and neck squamous cell carcinoma.

Introduction The aim of this study was to investigate if defective repair of DNA double-strand break (DSB) in head and neck squamous cell carcinoma (HNSCC) could be used as an early predictor of treatment response.Methods Tumour biopsy 24-36 h following induction chemotherapy (IC) and pre-treatment biopsies were stained for RAD51 and geminin (S-phase marker) for immunofluorescence in patients with HNSCC. The difference between RAD51 score (percentage of geminin-positive cells that were also positive for RAD51) was calculated for the two specimens. Tumours with a percentage difference of⩽10% were deemed to have repaired IC-induced DSBs, and were classified as 'RAD51 negative'. Response at 3 months post treatment and human papilloma virus (HPV) status were assessed.Results Thirteen pairs of samples were available for analyses. Three samples were classified as RAD51 negative and 10 as RAD51 positive at 24 h post IC. All of the three patients with tumours classified as RAD51 negative had partial response or progressive disease and the 10 patients with tumours deemed RAD51 positive had a complete response. 100% of the HPV-positive tumours were RAD51 positive and had a complete response.Conclusions We have demonstrated that impaired DSB DNA repair may underlie enhanced treatment sensitivity of HPV-positive HNSCC and repair capacity following platinum-induced DNA damage predicts response in HNSCC. This has potential as a biomarker for patient selection in trials of DNA damage response pathway modulation

Cost-effectiveness of collaborative care for chronically ill patients with comorbid depressive disorder in the general hospital setting, a randomised controlled trial

Background. Depressive disorder is one of the most common disorders, and is highly prevalent in chronically ill patients. The presence of comorbid depression has a negative influence on quality of life, health care costs, self-care, morbidity, and mortality. Early diagnosis and well-organized treatment of depression has a positive influence on these aspects. Earlier research in the USA has reported good results with regard to the treatment of depression with a collaborative care approach and an antidepressant algorithm. In the UK 'Problem Solving Treatment' has proved to be feasible. However, in the general hospital setting this approach has not yet been evaluated. Methods/Design. CC: DIM (Collaborative Care: Depression Initiative in the Medical setting) is a two-armed randomised controlled trial with randomisation at patient level. The aim of the trial is to evaluate the treatment of depressive disorder in general hospitals in the Netherlands based on a collaborative care framework, including contracting, 'Problem Solving Treatment', antidepressant algorithm, and manual-guided self-help. 126 outpatients with diabetes mellitus, chronic obstructive pulmonary disease, or cardiovascular diseases will be randomised to either the intervention group or the control group. Patients will be included if they have been diagnosed with moderate to severe depression, based on the DSM-IV criteria in a two-step screening method. The intervention group will receive treatment based on the collaborative care approach; the control group will receive 'care as usual'. Baseline and follow-up measurements (after 3, 6, 9, and 12 months) will be performed by means of questionnaires. The primary outcome measure is severity of depressive symptoms, as measured with the PHQ-9. The secondary outcome measure is the cost-effectiveness of these treatments according to the TiC-P, the EuroQol and the SF-36. Discussion. Earlier research has indicated that depressive disorder is a chronic, mostly recurrent illness, which tends to cluster with physical comorbidity. Even though the treatment of depressive disorder based on the guidelines for depression is proven effective, these guidelines are often insufficiently adhered to. Collaborative care and 'Problem Solving Treatment' will be specifically tailored to patients with depressive disorders and evaluated in a general hospital setting in the Netherlands