PubMed | Head and Neck Unit and Queen Alexandra Hospital
Type: | Journal: The British journal of oral & maxillofacial surgery | Year: 2016
Pentoxifylline has been used to treat complications related to fibrosis for over 20 years. Formerly used to treat those after radiotherapy such as osteoradionecrosis (ORN), it is now being tried for medication-related osteonecrosis of the jaw (MRONJ), which can occur after prolonged use of bisphosphonates. We review theories on the formation of fibrosis in patients with ORN, discuss the pharmacology of pentoxifylline and vitamin E, and report published outcomes. To our knowledge no prospective randomised controlled trial has investigated the benefits of these agents in cases of ORN, but reported outcomes in many published case series are encouraging.
Roe J.W.G.,Head and Neck Unit |
Roe J.W.G.,Institute of Cancer Research |
Ashforth K.M.,Head and Neck Unit
Current Opinion in Otolaryngology and Head and Neck Surgery | Year: 2011
Purpose of review: Oncological treatment outcomes in head and neck cancer suggest both acute and longer-term oropharyngeal dysphagia. Studies have been published exploring the potential to improve swallowing outcomes using more targeted treatment modalities such as intensity-modulated radiotherapy (IMRT) and through the introduction of swallowing exercises prior to treatment. In this article, we will explore the literature relating to prophylactic swallowing exercises for patients undergoing (chemo-)radiotherapy. Recent findings: Recent studies have attempted to evaluate the benefit of prophylactic, pretreatment swallowing exercises for patients undergoing (chemo-)radiotherapy. We identified three peer-reviewed published studies which present data on the potential benefit of exercise. Only one randomized control trial which includes multidimensional swallowing evaluation with instrumental measures has been published. Authors of all the reviewed studies agree that randomized control trials including baseline measures are required with longitudinal follow-up. Summary: More research is required to complement oncological clinical trials evaluating the impact of prophylactic exercise on swallowing outcome. Multidimensional swallowing evaluation including instrumental and patient-reported measures should be conducted pretreatment and longitudinally to develop the evidence base for intervention in patients undergoing organ-preserving treatment protocols. © 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins.
Pacheco-Ojeda L.A.,Head and Neck Unit |
Martinez-Viteri M.A.,Ecuadorian Social Security Hospital
International Surgery | Year: 2010
Carotid body tumors (CBTs) are relatively frequent lesions encountered at high altitudes, such in as the Andean Mountains. A correct preoperative diagnosis is essential for surgical planning and performance. For this reason, we have reviewed the evolution of our experience in the imaging diagnosis of these tumors. Between 1980 and June 2008, 160 CBTs were diagnosed. A total of 138 tumors were operated on, 4 are waiting for surgery, and 18 were not operated on because of age, medical conditions, or patient refusal. We have reviewed retrospectively the modalities of imaging diagnosis in our patients who underwent operation. Among the 138 tumors operated on, a correct preoperative diagnosis was done in 127 cases (92%). The preoperative diagnosis of the remaining 11 patients was unspecified benign tumor for 6 patients and neck lymph node for 5 patients. The imaging methods performed by different radiologists were conventional ultrasound, color Doppler ultrasound, carotid conventional angiography (CA), axial tomography, magnetic resonance and magnetic resonance angiography, and computed tomographic angiography (CTA). Most patients had more than one image study. Review of radiologist reports revealed a correct diagnosis in all carotid CA, magnetic resonance studies, and CTA. Additionally, CTA appeared to be a valuable method to predict the Shamblin group. Clinical suspicion and current image techniques permit a correct diagnosis in practically all cases of CBT.
Ahmed M.,Head and Neck Unit |
Barbachano Y.,Research Data and Statistics Unit |
Riddell A.,Royal Marsden NHS Foundation Trust |
Hickey J.,Head and Neck Unit |
And 6 more authors.
European Journal of Endocrinology | Year: 2011
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. © 2011 European Society of Endocrinology.
Buettner F.,Institute of Cancer Research |
Miah A.B.,Head and Neck Unit |
Gulliford S.L.,Institute of Cancer Research |
Hall E.,Institute of Cancer Research |
And 4 more authors.
Radiotherapy and Oncology | Year: 2012
Purpose: Subjective xerostomia is a common side-effect following radiotherapy for the treatment of head-and-neck cancer. Standard mean dose models previously used to model xerostomia only that partially predict the occurrence of xerostomia. Studies in animal models have suggested that there are regional variations in the radiosensitivity of the parotid glands. In this work we tested the hypothesis that this is also true for the human parotid gland. Methods: We present novel dose-response models explicitly taking the spatial distribution of the radiation dose into account. We considered dose to the submandibular gland and other clinical factors and used a variable-selection algorithm to select the best dose-response model. This methodology was applied to 63 head and neck cancer patients and validated using two independent patient cohorts of 19 and 29 patients, respectively. Results: The predictive accuracy of dose-response models improved significantly when including regional variations of radiosensitivity of the parotid glands compared to standard mean-dose models (p = 0.001, t-test). Beneficial dose-pattern analysis demonstrated the importance of minimising dose to the lateral and cranial component of the human parotid gland in order to avoid xerostomia. Furthermore we found an evidence that surgical removal of the sub-mandibular gland significantly increases the risk of radiation-induced xerostomia. Conclusion: Dose-response models which take the shape of the dose-distribution into account predicted xerostomia significantly better than standard mean-dose models. Our novel model could be used to rank potential treatment plans more reliably according to their therapeutic index and may be useful to generate better treatment plans. © 2012 Elsevier Ireland Ltd. All rights reserved.
Dean J.A.,Institute of Cancer Research |
Welsh L.C.,Head and Neck Unit |
Gulliford S.L.,Institute of Cancer Research |
Harrington K.J.,Head and Neck Unit |
Nutting C.M.,Head and Neck Unit
Radiotherapy and Oncology | Year: 2015
There is currently no standard method for delineating the oral mucosa and most attempts are oversimplified. A new method to obtain anatomically accurate contours of the oral mucosa surfaces was developed and applied to 11 patients. This is expected to represent an opportunity for improved toxicity modelling of oral mucositis. © 2015 The Authors. Published by Elsevier Ireland Ltd.
PubMed | Cancer Research UK Research Institute and Head and Neck Unit
Type: | Journal: Clinical oncology (Royal College of Radiologists (Great Britain)) | Year: 2017
A normal tissue complication probability (NTCP) model of severe acute mucositis would be highly useful to guide clinical decision making and inform radiotherapy planning. We aimed to improve upon our previous model by using a novel oral mucosal surface organ at risk (OAR) in place of an oral cavity OAR.Predictive models of severe acute mucositis were generated using radiotherapy dose to the oral cavity OAR or mucosal surface OAR and clinical data. Penalised logistic regression and random forest classification (RFC) models were generated for both OARs and compared. Internal validation was carried out with 100-iteration stratified shuffle split cross-validation, using multiple metrics to assess different aspects of model performance. Associations between treatment covariates and severe mucositis were explored using RFC feature importance.Penalised logistic regression and RFC models using the oral cavity OAR performed at least as well as the models using mucosal surface OAR. Associations between dose metrics and severe mucositis were similar between the mucosal surface and oral cavity models. The volumes of oral cavity or mucosal surface receiving intermediate and high doses were most strongly associated with severe mucositis.The simpler oral cavity OAR should be preferred over the mucosal surface OAR for NTCP modelling of severe mucositis. We recommend minimising the volume of mucosa receiving intermediate and high doses, where possible.
PubMed | Cancer Research UK Research Institute, Washington University in St. Louis, Head and Neck Unit and Sloan Kettering Cancer Center
Type: Journal Article | Journal: International journal of radiation oncology, biology, physics | Year: 2016
Current normal tissue complication probability modeling using logistic regression suffers from bias and high uncertainty in the presence of highly correlated radiation therapy (RT) dose data. This hinders robust estimates of dose-response associations and, hence, optimal normal tissue-sparing strategies from being elucidated. Using functional data analysis (FDA) to reduce the dimensionality of the dose data could overcome this limitation.FDA was applied to modeling of severe acute mucositis and dysphagia resulting from head and neck RT. Functional partial least squares regression (FPLS) and functional principal component analysis were used for dimensionality reduction of the dose-volume histogram data. The reduced dose data were input into functional logistic regression models (functional partial least squares-logistic regression [FPLS-LR] and functional principal component-logistic regression [FPC-LR]) along with clinical data. This approach was compared with penalized logistic regression (PLR) in terms of predictive performance and the significance of treatment covariate-response associations, assessed using bootstrapping.The area under the receiver operating characteristic curve for the PLR, FPC-LR, and FPLS-LR models was 0.65, 0.69, and 0.67, respectively, for mucositis (internal validation) and 0.81, 0.83, and 0.83, respectively, for dysphagia (external validation). The calibration slopes/intercepts for the PLR, FPC-LR, and FPLS-LR models were 1.6/-0.67, 0.45/0.47, and 0.40/0.49, respectively, for mucositis (internal validation) and 2.5/-0.96, 0.79/-0.04, and 0.79/0.00, respectively, for dysphagia (external validation). The bootstrapped odds ratios indicated significant associations between RT dose and severe toxicity in the mucositis and dysphagia FDA models. Cisplatin was significantly associated with severe dysphagia in the FDA models. None of the covariates was significantly associated with severe toxicity in the PLR models. Dose levels greater than approximately 1.0Gy/fraction were most strongly associated with severe acute mucositis and dysphagia in the FDA models.FPLS and functional principal component analysis marginally improved predictive performance compared with PLR and provided robust dose-response associations. FDA is recommended for use in normal tissue complication probability modeling.
PubMed | Institut Universitaire de France, Head and Neck Unit and The Institute of Cancer Research
Type: Journal Article | Journal: Molecular cancer therapeutics | Year: 2016
Head and neck squamous cell carcinoma (HNSCC) is a leading cause of cancer-related deaths, with increasingly more cases arising due to high-risk human papillomavirus (HPV) infection. Cisplatin-based chemoradiotherapy is a standard-of-care for locally advanced head and neck cancer but is frequently ineffective. Research into enhancing radiation responses as a means of improving treatment outcomes represents a high priority. Here, we evaluated a CHK1 inhibitor (CCT244747) as a radiosensitiser and investigated whether a mechanistically rational triple combination of radiation/paclitaxel/CHK1 inhibitor delivered according to an optimized schedule would provide added benefit. CCT244747 abrogated radiation-induced G2 arrest in the p53-deficient HNSCC cell lines, HN4 and HN5, causing cells to enter mitosis with unrepaired DNA damage. The addition of paclitaxel further increased cell kill and significantly reduced tumor growth in an HN5 xenograft model. Importantly, a lower dose of paclitaxel could be used when CCT244747 was included, therefore potentially limiting toxicity. Triple therapy reduced the expression of several markers of radioresistance. Moreover, the more radioresistant HN5 cell line exhibited greater radiation-mediated CHK1 activation and was more sensitive to triple therapy than HN4 cells. We analyzed CHK1 expression in a panel of head and neck tumors and observed that primary tumors from HPV(+) patients, who went on to recur postradiotherapy, exhibited significantly stronger expression of total, and activated CHK1. CHK1 may serve as a biomarker for identifying tumors likely to recur and, therefore, patients who may benefit from concomitant treatment with a CHK1 inhibitor and paclitaxel during radiotherapy. Clinical translation of this strategy is under development. Mol Cancer Ther; 15(9); 2042-54. 2016 AACR.
PubMed | Cancer Research UK Research Institute and Head and Neck Unit
Type: Journal Article | Journal: Clinical oncology (Royal College of Radiologists (Great Britain)) | Year: 2016
To determine the toxicity and tumour control rates after chemo-intensity-modulated radiotherapy (chemo-IMRT) for locally advanced nasopharyngeal cancers (LA-NPC).Patients with LA-NPC were enrolled in a trial to receive induction chemotherapy followed by parotid-sparing chemo-IMRT. The primary site and involved nodal levels received 65Gy in 30 fractions and at risk nodal levels received 54Gy in 30 fractions. Incidence of grade 2 subjective xerostomia was the primary end point. Secondary end points included incidences of acute and late toxicities and survival outcomes.Forty-two patients with American Joint Committee on Cancer stages II (12%), III (26%) and IV (62%) (World Health Organization subtype: I [5%]; II [40%]; III [55%]) completed treatment between January 2006 and April 2010 with a median follow-up of 32 months. Incidences of grade 2 acute toxicities were: dysphagia 83%; xerostomia 76%; mucositis 97%; pain 76%; fatigue 99% and ototoxicity 12%. At 12 months, grade 2 subjective xerostomia was observed in 31%, ototoxicitiy in 13% and dysphagia in 4%. Two year locoregional control was 86.2% (95% confidence interval: 70.0-94.0) with 2 year progression-free survival at 78.4% (61.4-88.6) and 2 year overall survival at 85.9% (69.3-93.9).Chemo-IMRT for LA-NPC is feasible with good survival outcomes. At 1 year, 31% experiencegrade 2 subjective xerostomia.