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K J Harrington

Publications and source records attributed to K J Harrington.

At least 19 recordsLinked to original sources
PubMed2006

Quality of life following total laryngectomy: assessment using the UW-QOL scale.

OBJECTIVES: To determine the quality of life (QOL) in patients using valved speech following total laryngectomy with a validated patient self-report scale. STUDY DESIGN: Cross-sectional cohort study. PATIENTS: 63 patients following total laryngectomy using valved speech. INTERVENTION: University of Washington Quality of Life (UW-QOL) questionnaire. MAIN OUTCOME MEASURES: Patient perception of the QOL over the last 7 days following total laryngectomy in response to specific questions and correlated with sociodemographic and treatment factors. RESULTS: Responses were received from 44 males and 11 females (response rate: 87.3%) with a median age of 66 years (range: 40-84). The mean (SD) composite score of the QOL in our series of patients with total laryngectomy was 81.3 (10.9). As regards the overall QOL, 80% of our patients cited it as very good (45.5%) to good (34.5%). Patients identified speech, appearance, and activity as the most important issues following total laryngectomy. Only age and pharyngo-oesophageal segment closure were significant predictors of QOL scores (Student t test, p < 0.05) and not other demographic and treatment variables. CONCLUSIONS: The composite score and overall QOL were high in our series of total laryngectomy patients and this possibly reflects adequate multidisciplinary management. We strongly urge the use of prospective longitudinal studies that will adequately identify any QOL changes over time. Although the UW-QOL questionnaire is a simple and brief scale, it has limitations that can curtail its effective use in laryngectomy patients and we advise supplementing it with the use of domain-specific questionnaires.

Adult↗
PubMed2006

Voice-related Quality of Life in laryngectomees: assessment using the VHI and V-RQOL symptom scales.

The primary purpose of this study was to investigate the effect of the voice impairment across the physical, emotional, and functional domains in patients using valved speech following total laryngectomy with the help of two symptom specific scales. The study design used was a cross-sectional cohort. The setting was the Head and Neck Oncology Unit of a tertiary referral centre. Subjects were 54 patients who had undergone total laryngectomy. Two voice-specific questionnaires, the Voice-Related Quality of Life (V-RQOL-short form) Measure, and the Voice Handicap Index (VHI-long form) were used. The main outcome measure was patient perception of the voice following total laryngectomy in response to specific questions correlated with sociodemographic/treatment factors. Responses were received from 40 males and 14 females (response rate of 85.7%) with a median age of 63.4 years (range: 37-84). The V-RQOL overall analysis showed that 3 patients (5.6%) scored "excellent," 29 patients (53.7%) "fair to good," 14 patients (25.9%) "poor to fair," and 8 patients (14.8%) "poor." Analysis of the VHI revealed that 20 patients (37.0%) had a minimal handicap, 20 patients (37.0%) a moderate handicap, and 14 patients (25.9%) had a serious voice handicap. The individual domain or subscale scores for the VHI revealed a mean (SD) functional score of 15.8 (7.7), a physical score of 13.6 (7.2), and finally an emotional score of 11.6 (8.9). Functional aspects of the voice were significantly affected by age, radiotherapy, and chemotherapy (Spearman rho, P=0.01; Mann-Whitney, P=0.04 and P=0.01). The physical aspects of the voice were significantly affected by age and chemotherapy (Spearman rho, P=0.004; Mann-Whitney, P=0.04). Only age significantly affected the emotional aspects of the voice (Spearman rho, P=0.002). We found a strong correlation (Spearman rho, P<0.001) between the V-RQOL and VHI questionnaires. Our study revealed that the V-RQOL and VHI scores in our series of patients following voice restoration in laryngectomees were consistent with that reported in the literature. Only age, radiation, and chemotherapy were seen to influence the voice handicap scores. In addition, both symptom scales had good correlation between them and either one could be used with reliability in laryngectomees with a few modifications.

Adult↗
PubMed2006

Gefitinib (ZD1839, Iressa) as palliative treatment in recurrent or metastatic head and neck cancer.

To assess the level of activity and toxicity of gefitinib (ZD1839, Iressatrade mark) in a population of patients with locally recurrent and/or metastatic head and neck cancer. Patients were recruited into an expanded access programme through the multidisciplinary head and neck clinics at the Royal Marsden and St George's Hospitals. Patients were required to have received at least one course of standard systemic chemotherapy or radiation therapy, or be medically unfit for chemotherapy. Patients were commenced on single-agent gefitinib at a dose of 500 mg day(-1). Clinical, symptomatic and radiological response, time to progression (TTP), survival and toxicity were recorded. A total of 47 patients were enrolled (35 male and 12 female) with a median age of 62 years (range 18-93 years). The observed clinical response rate was 8% with a disease control rate (complete response, partial response, stable disease) of 36%. In all, 34% of patients experienced an improvement in their symptoms. The median TTP and survival were 2.6 and 4.3 months, respectively. Acneiform folliculitis was the most frequent toxicity observed (76%) but the majority of cases were grade 1 or 2. Only four patients experienced grade 3 toxicity of any type (all cases of folliculitis). Gefitinib was well tolerated and yielded symptomatic improvement in one-third of patients. However, this agent appeared to possess limited antitumour activity in this group of patients with head and neck cancer in whom the objective response rate, median TTP and survival were all lower than has been reported in a previous study.

Administration, Oral↗
PubMed2006

Multidimensional assessment of female tracheoesophageal prosthetic speech.

OBJECTIVE: The objective of this study was to undertake a multidimensional assessment of female tracheoesophageal prosthetic speech. STUDY DESIGN: A cross-sectional cohort study. SETTING: Head and Neck Unit in a tertiary oncology referral centre. PATIENTS: Ten female and 10 male total laryngectomy patients with no signs of recurrence and using voice prosthesis were compared to 10 normal female speakers. INTERVENTION(S): Electroglottographic and acoustic analysis of voice parameters for both sustained vowel /i/ and connected speech, perceptual evaluation using GRBAS (with 2 experienced raters) and questionnaire assessment using the University of Washington Quality of Life and the Voice Handicap Index. Statistical analysis was done using the Statistical Package for Social Sciences, (v. 14, SPSS Inc., Chicago III). RESULTS: Median age of the female larygectomy patients was 65 years (range: 41-81), that of male laryngectomees was 66.5 years (range: 40-79) and that of the normal female subjects was 47.5 years (range: 35-72). All electroglottographic, acoustic parameters and GRBAS ratings of the female laryngectomy patients were significantly worse as compared with the normal female subjects. The median fundamental frequency (111.8 Hz) was comparable to male tracheoesophageal speakers (115.8 Hz). Mean composite University of Washington Quality of Life score and overall Voice Handicap Index score was 79.3(12.5) and 47.5(27.6) for the female laryngectomy patients and for the males was 81.2 (9.6) and 39.4(18.7). CONCLUSIONS: Gender frequency differences as seen in normal subjects are lost following a laryngectomy operation as evidenced by electroglottographic and perceptual data. Although the quality of life scores are comparable to the male tracheoesophageal speakers, they exhibit a greater voice handicap as compared to their male counterparts.

Adult↗
PubMed2006

Can objective parameters derived from videofluoroscopic assessment of post-laryngectomy valved speech replace current subjective measures? An e-tool-based analysis.

OBJECTIVES: The primary purpose of this study was to assess the pharyngoesophageal segment in total laryngectomy patients using a videofluoroscopy e-tool. STUDY DESIGN: Cross-sectional study. SETTING: Head and Neck Oncology Unit, Tertiary Referral Centre. PATIENTS: Forty-two patients following total laryngectomy. INTERVENTION: Videofluoroscopy using an e-tool (JRuler). MAIN OUTCOME MEASURES: Subjective and objective videofluoroscopy parameters correlated with the GRBAS scale and treatment variables. RESULTS: Of 32 men and 10 women, mean age 63.5 years (10.8) the majority (64.3%) had a reasonable voice (good = 11 and poor = 4 patients). Comparing subjective and objective parameters, significant correlations were only seen with a smaller minimal neoglottic distance at phonation with no regurgitation of barium at phonation (P = 0.05) and a type 1 shape of neoglottis at phonation (P = 0.02). There were also significant correlations between smaller maximum sub-neoglottic distance at phonation and type 1 shape of neoglottis (P = 0.02), smaller maximum sub-neoglottic distance at rest and absence of stasis of barium at phonation (P = 0.05) and the length of neoglottis at phonation and type 1 shape of neoglottis (P = 0.01). For perceptual evaluation, significant correlation was seen only between G1 voice and a smaller minimal neoglottic distance at phonation (P = 0.03) amongst the subjective and objective parameters. There were no correlations between visual parameters and the clinical parameters. CONCLUSIONS: Our observations suggest that this interesting concept has limitations. While objective and quantifiable data can be obtained using videofluoroscopy in laryngectomees, only a few correlate with each other and with voice quality.

Cross-Sectional Studies↗
PubMed2006

Questionnaire analysis of the swallowing-related outcomes following total laryngectomy.

OBJECTIVE: To determine the effects of a total laryngectomy on the swallow and subsequent quality of life in head and neck cancer patients. DESIGN: Cross-sectional single centre cohort study. SETTING: Head and Neck Oncology Unit, Tertiary Referral Unit. PATIENTS: Sixty-two patients who underwent total laryngectomy at our centre participated in the study. METHODS: Subjects were stratified by age, sex, tumour stage, other procedures such as myotomy and nerve re-implantation. Pharyngectomy, glossectomy, flap reconstruction, neck dissection and previous radio- and chemotherapy were also assessed to see if they affected swallow and subsequent quality of life. Main outcome was measured using the MD Anderson Dysphagia Inventory questionnaire. RESULTS: Responses were received from 46 males and 16 females (response rate of 80.5%) with a mean age of 64.7 years (SD 9.4). Median follow-up in patients was 90 months (range 1-276). The mean MD Anderson Dysphagia Inventory total score in our series of patients was 77.7 (SD 16.6). MD Anderson Dysphagia Inventory global score was 79.4 (SD 22.6), Emotional score was 77.7 (SD 17.8), Functional score 81.3 (SD 15.9) and Physical score was 74.1(SD 18). Statistically significant differences were seen between the emotional scores of glossectomised and non-glossectomised patients (Mann Whitney, P = 0.04). No significant correlation was seen between the subscale scores and the remaining treatment variables such as age, gender, site, tumour stage, myotomy, nerve implantation, radiotherapy, reconstruction and major complications. CONCLUSION: This questionnaire study is the largest of its type to assess the swallow of patients who have undergone laryngectomy at a single centre. The overall result confirmed that most patients had a subjectively good swallow. Only glossectomy and the method of PE segment closure were shown to significantly affect swallowing outcomes following surgery. We recommend further work especially prospective studies pre and post surgery using this or similarly validated instruments to fully assess swallow in the laryngectomy population.

Adult↗
PubMed2005

A modified Inflammatory Bowel Disease questionnaire and the Vaizey Incontinence questionnaire are simple ways to identify patients with significant gastrointestinal symptoms after pelvic radiotherapy.

After radiotherapy for pelvic cancer, chronic gastrointestinal problems may affect quality of life (QOL) in 6-78% of patients. This variation may be due to true differences in outcome in different diseases, and may also represent the inadequacy of the scales used to measure radiotherapy-induced gastrointestinal side effects. The aim of this study was to assess whether outcome measures used for nonmalignant gastrointestinal disease are useful to detect gastrointestinal morbidity after radiotherapy. Results obtained from a Vaizey Incontinence questionnaire and a modified Inflammatory Bowel Disease questionnaire (IBDQ)--both patient completed--were compared to those from a staff administered Late Effects on Normal Tissue (LENT)--Subjective, Objective, Management and Analytic (SOMA) questionnaire in patients who had completed radiotherapy for a pelvic tumour at least 3 months previously. In all, 142 consecutive patients were recruited, 72 male and 70 female, median age 66 years (range 26-90 years), a median of 27 (range 3-258) months after radiotherapy. In total, 62 had been treated for a gynaecological, 58, a urological and 22, a gastrointestinal tract tumour. Of these, 21 had undergone previous gastrointestinal surgery and seven suffered chronic gastrointestinal disorders preceding their diagnosis of cancer. The Vaizey questionnaire suggested that 27% patients were incontinent for solid stools, 35% for liquid stools and 37% could not defer defaecation for 15 min. The IBDQ suggested that 89% had developed a chronic change in bowel habit and this change significantly affected 49% patients: 44% had more frequent or looser bowel movements, 30% were troubled by abdominal pain, 30% were troubled by bloating, 28% complained of tenesmus, 27% were troubled by their accidental soiling and 20% had rectal bleeding. At least 34% suffered emotional distress and 22% impairment of social function because of their bowels. The small intestine/colon SOMA median score was 0.1538 (range 0-1) and the rectal SOMA median score was 0.1428 (range 0-1). Pearson's correlations for the IBDQ score and small intestine/colon SOMA score was -0.630 (P<0.001), IBDQ and rectum SOMA -0.616 (P<0.001), IBDQ and Vaizey scores -0.599 (P<0.001), Vaizey and small intestine/colon SOMA 0.452 (P<0.001) and Vaizey and rectum SOMA 0.760 (P<0.001). After radiotherapy for a tumour in the pelvis, half of all patients develop gastrointestinal morbidity, which affects their QOL. A modified IBDQ and Vaizey questionnaire are reliable in assessing new gastrointestinal symptoms as well as overall QOL and are much easier to use than LENT SOMA.

Adult↗
PubMed2005

Radioiodine therapy of colon cancer following tissue-specific sodium iodide symporter gene transfer.

We investigated the feasibility of using radioiodine therapy in colon carcinoma cells (HCT 116) following tumor-specific expression of the human sodium iodide symporter (hNIS) using the carcinoembryonic antigen (CEA) promoter. HCT 116 cells were stably transfected with an expression vector, in which hNIS cDNA has been coupled to a CEA promoter fragment. This promoter is responsible for tissue-specific expression of CEA in gastrointestinal tract epithelium, and has been shown to target therapeutic genes to colorectal cancer cells. Functional NIS expression was confirmed by iodide uptake assay, Western blot analysis, immunostaining and in vitro clonogenic assay. The stably transfected HCT 116 cells concentrated (125)I about 10-fold in vitro without evidence of iodide organification. In contrast, transfection of control cancer cells without CEA expression did not result in iodide accumulation. Western blot analysis using a hNIS-specific antibody revealed a band of approximately 90 kDa. In addition, immunostaining of stably transfected HCT 116 cells revealed hNIS-specific membrane-associated immunoreactivity. In an in vitro clonogenic assay approximately 95% of stably transfected HCT 116 cells were killed by exposure to (131)I, while only about 5% of NIS-negative control cells were killed. Further, using an adenovirus carrying the NIS gene linked to the CEA promoter, high levels of tumor-specific radioiodide accumulation were induced in HCT 116 cells. In conclusion, a therapeutic effect of (131)I has been demonstrated in colon carcinoma cells following induction of tumor-specific iodide uptake activity by CEA promoter-directed NIS expression in vitro. This study demonstrates the potential of NIS as a therapeutic gene allowing radioiodine therapy of colon cancer following tumor-specific NIS gene transfer.

Blotting, Western↗
PubMed2005

Management of non-Hodgkin's lymphoma of the thyroid: the Royal Marsden Hospital experience.

A retrospective review was conducted of patients treated for thyroid non-Hodgkin's lymphoma (TNHL) at the Royal Marsden Hospital between 1936 and 1996 to determine the effect of radiotherapy (RT) on outcome. 91 patients were identified from the Thyroid Unit Database. There were 77 females and 14 males with a median age of 65 years (range 22-87 years). RT was delivered according to two separate policies: (1) involved field radiotherapy (IFRT) to the thyroid bed and cervical lymph nodes; (2) extended field radiotherapy (EFRT) covering the thyroid bed, cervical and mediastinal lymph nodes. 89 patients received RT as part of definitive treatment following surgery, to a dose of approximately 40 Gy. 25 patients received IFRT and 64 patients EFRT. 27 patients received cytotoxic chemotherapy. 18 patients (72%) treated with IFRT died of TNHL with a median relapse free survival (RFS) of 10 months and a median overall survival (OS) of 21 months. In contrast, only 29 patients (46%) treated with EFRT died of TNHL with a median RFS of 76 months (p = 0.01 for RFS with respect to IFRT and p = 0.04 for OS). Significantly more patients treated with IFRT relapsed locally (52% vs 27%). There was no difference in the rates of systemic relapse (20% vs 22%). EFRT alone for Stage I, but not for Stage II disease, yielded acceptable rates of local control and disease free survival with doses of at least 40 Gy. These historical data strongly support the addition of combination chemotherapy to the treatment regimen in all patients with Stage II disease. Indeed, in recent years this has become the standard of care for all cases of thyroid lymphoma unless the histology is of marginal zone type (mucosa associated lymphoma tissue (MALT) lymphoma).

Adult↗
PubMed2004

A prognostic index that predicts outcome following palliative whole brain radiotherapy for patients with metastatic malignant melanoma.

To determine the outcome of patients with metastatic malignant melanoma (MMM) treated with palliative whole brain radiotherapy (WBRT) and to identify factors that predict treatment outcome to assist future trial design, a retrospective study was performed on patients with MMM who received WBRT at the Royal Marsden Hospital between 1998 and 2003. Data regarding patient factors, tumour factors and survival were collected. A total of 112 patients were identified and full data were available for 102 patients. The median age was 53 years (range 25-81 years), 66.7% were male and 33.3% female. The median dose prescribed was 20 Gy in five fractions as a mid-plane dose. The median survival after WBRT for the whole group was 51 days (range 3-1386). In an attempt to define prognostic groups, we used the validated RTOG recursive partitioning analysis (RPA) classification for brain metastasis (class 1: Karnofsky Performance Score (KPS) >/=70%, age <65 years with no extracranial metastasis; class 3: KPS <70%; class 2: all others). The median survivals were 151, 71 and 21 days for RPA class 1, 2 and 3, respectively (P<0.001). Multivariate analysis showed that RPA class, leptomeningeal involvement, presence and number of extracranial metastatic sites and progressive disease in the brain on imaging before WBRT are important independent predictive factors. A prognostic index was derived from these factors that allowed identification of patients unlikely to benefit from WBRT. In conclusion, the RTOG RPA classification is valid when applied to patients with MMM. Patients in RPA class 1 and good prognosis class 2 are likely to benefit from palliative WBRT and should be considered for entry into trials that aim to improve duration of response. We identified that patients with RPA class 3, leptomeningeal involvement or RPA class 2 with poor prognostic index are unlikely to benefit from palliative WBRT.

Adult↗
PubMed2004

Targeted radiosensitisation by pegylated liposome-encapsulated 3', 5'-O-dipalmitoyl 5-iodo-2'-deoxyuridine in a head and neck cancer xenograft model.

5-Iodo-2'-deoxyuridine (IUdR) is an effective radiosensitiser but its clinical development has been limited by toxicity. Prolonged intravenous infusions of IUdR are necessary for optimal tumour uptake but cause dose-limiting myelosuppression. The lack of selective tumour uptake can lead to radiosensitisation of adjacent normal tissues and enhanced local radiation toxicity. Liposomal IUdR delivery offers selective targeting of tumour tissues and avoidance of local and systemic toxicity. In these studies, we report the development of a pegylated liposome containing a lipophilic IUdR derivative (3', 5'-O-dipalmitoyl-5-iodo-2'-deoxyuridine) for use in a head and neck cancer xenograft model. Initial studies confirmed the ability of IUdR to sensitise two head and neck cancer cell lines to single fractions of radiotherapy (SFRT) and this effect was seen to correlate with the thymidine replacement index in KB cells. In vivo delivery of single doses of either unencapsulated IUdR or pegylated liposomal IUdR (PLIUdR) to nude mice bearing KB xenograft tumours did not enhance the effect of SFRT delivered 16 h later. When PLIUdR was delivered by a protracted administration schedule to a dose of 48 mg kg(-1) over 7 days, it enhanced the effect of both 4.5 Gy SFRT and fractionated radiotherapy. PLIUdR was at least as effective as unencapsulated IUdR delivered by multiple intravenous injections or continuous subcutaneous infusion. Immunohistochemistry with a specific anti-IUdR monoclonal antibody confirmed greater levels of tumour staining in tumours from animals treated with PLIUdR compared with those treated with unencapsulated IUdR.

Animals↗
PubMed2004

Residual or recurrent head and neck cancer presenting with nerve root compression affecting the upper limbs.

Nerve root and spinal cord compression are oncological emergencies that require early detection and prompt management. These phenomena are most frequently diagnosed in patients with haematogenous metastases from lung, breast and prostate cancers and are rarely seen in patients with squamous cell cancer of the head and neck (SCCHN). SCCHN tends to spread by direct extension and lymphatic metastasis, with haematogenous dissemination occurring late in the natural history of the disease. In this paper, we report three patients with residual or relapsed SCCHN who presented with symptoms and signs of nerve root compression affecting the upper limbs caused by locoregional lymphatic spread of disease.

Aged↗
PubMed2003

Raynaud's phenomenon after radical radiotherapy for tumours of the head and neck.

Endothelial cell injury is implicated in the development of radiation induced tissue damage and may also be involved in the pathophysiology of secondary Raynaud's phenomenon. Two patients are presented in whom the typical symptoms and signs of Raynaud's phenomenon developed as a late complication of radical radiotherapy. One had Raynaud's of the tongue and one of the lip. Both patients had a prior history of primary Raynaud's phenomenon and in each case the symptoms were repeatedly precipitated by sudden cold exposure. The possible pathogenesis of radiation induced Raynaud's phenomenon in the head and neck region is discussed.

Aged↗
PubMed2003

Definitive radiotherapy for extramedullary plasmacytomas of the head and neck.

Extramedullary plasmacytoma of the head and neck region (EMPHN) is an uncommon malignant plasma cell neoplasm. In this study we conducted a retrospective analysis of our experience of EMPHN with particular emphasis on the role of definitive radiotherapy. From 1982 to 2001, 10 patients (6 males, 4 females) with EMPHN were treated in our institution. Of nine patients treated at initial diagnosis, all received definitive radiotherapy. One patient treated at relapse underwent surgical resection followed by post-operative radiotherapy. The median age at diagnosis was 55 years (range 35-84 years). The disease was most frequently localized in the paranasal sinuses (50%). All nine patients who received definitive radiotherapy at a dose of 40-50 Gy achieved a complete response. The median follow up period was 29 months (range 7-67 months). Four patients (40%) relapsed, three have died of their disease. Two patients (20%) with paranasal sinus disease subsequently relapsed with multiple myeloma at 10 months and 24 months, respectively. Our results indicate that treatment of EMPHN with radiotherapy achieves excellent rates of local control. The relapse rate in neck nodes of 10% does not justify elective irradiation of the uninvolved neck.

Adult↗
PubMed2002

Managing side effects of radiotherapy in head and neck cancer.

Curative radiotherapy for head and neck cancer causes very significant side effects. In addition to their considerable impact on the patient's quality of life, these effects can prejudice treatment outcome. This review looks at the management of the adverse effects of radiotherapy for head and neck cancer.

Dose-Response Relationship, Radiation↗