Metastatic spinal cord compression: review of the evidence for a radiotherapy dose fractionation schedule.

Metastatic spinal cord compression is a frequent medical emergency, and the most common treatment offered is radiotherapy. The routine treatment prescription for spinal cord compression in the UK is 20 Gy in five daily fractions delivered over 1 week. Here, we evaluate the evidence base for the radiotherapy dose for spinal cord compression. Evidence from the four prospective studies conducted so far and retrospective studies does not support a uniform dose of 20 Gy for all patients with spinal cord compression. Available evidence suggests that the radiotherapy dose should be tailored to the individual patient, depending on the subtype of the tumour, the extent of metastatic disease and expected survival. A risk stratification for the optimum dose prescription for patients with spinal cord compression is recommended.

Frequency of screening magnetic resonance imaging to detect occult spinal cord compromise and to prevent neurological deficit in metastatic castration-resistant prostate cancer.

AIMS: Neurological deficit from malignant spinal cord compression (SCC) is a major complication of metastatic castration-resistant prostate cancer (CRPC). The aims of the present study were to determine the incidence of neurological deficit in metastatic prostate cancer patients and to determine the optimal frequency of screening magnetic resonance imaging (MRI) spine required to detect clinically occult radiological SCC (rSCC). MATERIALS AND METHODS: A retrospective analysis of the clinical data of 130 consecutive patients with CRPC, with no functional neurological deficit, who had screening MRI spine from January 2001 to May 2005, was undertaken. Patients found to have rSCC received radiotherapy. All patients were followed-up to document the incidence of neurological deficit. RESULTS: Thirty-seven (28.4%) patients had rSCC on MRI. The proportion of patients free from neurological deficit at 3, 6, 12, 18 and 24 months was 94, 80, 59 and 43%, respectively, in patients who had rSCC on initial MRI and 97.5, 89, 75 and 63%, respectively, in patients who had no rSCC. A high prostate-specific antigen (PSA) level at initial MRI (P = 0.035) and a short PSA doubling time < 3 months (P = 0.009) significantly predicted for neurological deficit on univariate analysis, whereas back pain (P = 0.059), although an important predictive factor, did not attain statistical significance. On multivariate analysis, only rapid PSA doubling time (<3 months) independently predicted for future neurological deficit (P = 0.042). CONCLUSION: MRI spine can be used to detect asymptomatic rSCC in patients with CRPC and serial estimations are required to maintain a low incidence of clinical SCC. If serial screening MRI spine is used to detect rSCC in 90% of patients before the development of neurological signs, the optimum frequency depends on the subset of patients studied. The results of our study suggest that the optimum frequency would be every 4-6 months for patients with previous SCC, rapid or high PSA or back pain and annually for asymptomatic patients.

Whole-body magnetic resonance imaging in the detection of skeletal metastases in patients with prostate cancer.

Whole-body MRI is an effective method for evaluating the entire skeletal system in patients with metastatic disease. This study aimed to compare whole-body MRI and radionuclide bone scintigraph in the detection of skeletal metastases in patients with prostate cancer. Patients with prostate cancer at high risk of skeletal metastasis with (i) prostate-specific antigen of > or =50 ng/mL; (ii) composite Gleason score of > or =8 with prostate-specific antigen of >20 ng/mL; or (iii) node-positive disease were enrolled in this prospective study before systemic treatment was initiated. Whole-body MR images and bone scans of 39 patients were analysed. Seven patients had bone metastases on bone scans, while seven patients had skeletal metastases by whole-body MRI, with concordant findings only in four patients. Compared with the 'gold standard', derived from clinical and radiological follow-up, the sensitivity for both bone scans and MRI was 70%, and the specificity for both was 100%. Magnetic resonance imaging detected 26 individual lesions compared with 18 lesions on bone scans. Only eight lesions were positive on both. Bone scans detected more rib metastases, while MRI identified more metastatic lesions in the spine. Whole-body MRI and radionuclide bone scintigraphy have similar specificity and sensitivity and may be used as complementary investigations to detect skeletal metastases from prostate cancer.

Does magnetic resonance imaging of the spine have a role in the staging of prostate cancer?

AIMS: Magnetic resonance imaging (MRI) is an effective method for evaluating the spine in patients with a high risk of metastatic disease. The aim of this study was to compare MRI spine with radionuclide bone scan in detecting spinal metastases for staging prostate cancer patients. MATERIALS AND METHODS: A cohort of 99 patients with locally advanced prostate cancer at high risk of skeletal metastasis (prostate-specific antigen>10 ng/ml, composite Gleason score>or=8) or equivocal findings on bone scan were included in the retrospective study, and their MRI spine and bone scans were analysed. RESULTS: Ten patients were detected to have definite spinal metastasis by bone scan, whereas 12 patients had definite skeletal metastasis by MRI spine. Compared with the 'gold standard', derived from clinical and radiological follow-up, the sensitivities for radionuclide bone scan and that for MRI spine for detecting skeletal metastasis were 71.4 and 85.7%, respectively (P=0.023), whereas the specificities were 96.5 and 97.7%, respectively (P=0.95). Of the 34 individual metastatic lesions in the spine, 15 were concordantly positive on both scans, whereas five lesions were positive only by bone scan and 11 positive only by MRI. The addition of MRI spine in the staging for prostate cancer resulted in a change of stage and management plan in seven (7%) patients. CONCLUSION: MRI spine has comparable specificity and slightly better sensitivity than bone scan to detect spinal metastasis from prostate cancer.

Quality of life outcome measures following partial glossectomy: assessment using the UW-QOL scale.

BACKGROUND: The consequences of a diagnosis of head and neck cancer and the impact of treatment have a clear and direct influence on well-being and associated quality of life (QOL) in these patients. AIMS: To determine the QOL in head and neck cancer patients following a partial glossectomy operation. DESIGN AND SETTING: Cross-sectional cohort study; Head and Neck Oncology Unit, tertiary referral center. MATERIALS AND METHODS: 38 patients with partial glossectomy were assessed with the University of Washington head and neck quality of life (UW-QOL) scale, version 4. STATISTICAL ANALYSIS: Statistical analysis was performed using the Statistical Package for Social Sciences 10.0 (SPSS Inc, Chicago version III). Information from the scale was correlated using the Mann Whitney test. A P value less than/equal to 0.05 was considered as significant. RESULTS: The mean (sd) composite score of the QOL in our series was 73.6 (16.1). The majority (71.8%) quoted their QOL as good or very good. Swallowing (n = 16, 47.1%), speech (n = 15, 44.1%) and saliva (n = 15, 44.1%) were most commonly cited issues over the last 7 days. On the other hand, the groups with reconstruction, neck dissection, complications and radiotherapy demonstrated a significant reduction of quality of life scores (Mann Whitney test, P < 0.005). CONCLUSION: The composite score and overall QOL as assessed using the UW-QOL scale (version 4) were modestly high in our series of partial glossectomy patients. Swallowing, speech, and saliva are regarded as the most important issues. Stage of the disease, neck dissection, reconstruction, complications, radiotherapy and time since operation were seen to significantly affect domain scores.

Baseline urinary phytoestrogen levels and the natural history of untreated, localised prostate cancer in a British population.

AIM: To determine whether urinary concentrations of phytoestrogens are associated with the rate of disease progression in men with untreated, localised prostate cancer. PATIENTS AND METHODS: Patients with untreated, localised prostatic adenocarcinoma on a prospective clinical study of active surveillance had urine samples collected at baseline. Patients underwent monitoring with serial PSA levels and repeat octant prostate biopsies. Disease progression was defined as either adverse histology on repeat biopsy (primary Gleason grade >or= 4, or >50% positive cores) or radical treatment for PSA velocity >1 ng/mL/year. Time to disease progression was analysed with respect to baseline urinary levels of genistein, enterolactone, daidzein and equol, assayed using liquid chromatography/tandem mass spectrometry. RESULTS: 191 patients were evaluable, with a median follow-up of 2.5 years. 71 patients experienced disease progression. No significant association was seen between time to disease progression and baseline urinary levels of daidzein (p=0.85), genistein (p=0.81), enterolactone (p=0.085) or equol (p=0.33). No significant association was seen between adverse histology on repeat biopsy and urinary levels of either daidzein (p=0.85), genistein (p=0.58), enterolactone (p=0.88) or equol (p=0.71). There was no significant correlation between PSA velocity and urinary levels of daidzein (p=0.90), genistein (p=0.98), enterolactone (p=0.10) or equol (p=0.60). CONCLUSION: These data do not support the hypothesis that phytoestrogens prevent disease progression in men with localised prostate cancer.

Questionnaire analysis of swallowing-related outcomes following glossectomy.

OBJECTIVE: To determine the effects of a partial/total glossectomy on the swallow-related quality of life (QOL). DESIGN: Cross-sectional, single-centre cohort study. PATIENTS AND METHODS: Thirty-one patients who underwent partial/total glossectomy at our centre participated in the study. Main outcome was measured using the MD Andersen Dysphagia Inventory (MDADI) questionnaire. RESULTS: Responses were received from 24 males and 7 females (response rate of 77.5%) with a median age of 50 years (range: 28-72). Median follow-up in patients was 33 months (range 4-210). The mean MDADI total score in our series of patients was 71.7 (SD 18.8). Mean MDADI global score was 64.5 (SD 29.1), mean Emotional score was 71.9 (SD 19.1), mean Functional score was 73.7 (SD 19.1) and mean Physical score was 69.3 (SD 21.7). Statistically significant differences were seen between the global, emotional and physical scores of patients who had received radiotherapy (Mann-Whitney, p < 0.05) and tracheostomy (functional score, Mann-Whitney, p = 0.038). CONCLUSION: The presence of tracheostomy tube and previous radiotherapy affects swallowing outcome in patients who have had surgery for squamous cell carcinoma of the tongue.

Pentoxifylline to treat radiation proctitis: a small and inconclusive randomised trial.

This prospective randomised controlled study of 40 patients could not show a statistically significant advantage with 6 months of pentoxifylline compared with standard measures for late radiation-induced rectal bleeding. However, a modest benefit cannot be excluded and larger randomised placebo-controlled trials with longer durations of pentoxifylline treatment may be justified.

Does flexible videostroboscopy compare with rigid videostroboscopy in the assessment of the neoglottis? A preliminary report.

OBJECTIVE: To evaluate rigid and flexible stroboscopy of the neoglottis. STUDY DESIGN: Prospective pilot study set at a tertiary level Head & Neck Unit. PARTICIPANTS: Twenty-four patients recruited. All had undergone a total laryngectomy and were voicing using a Blom-singer valve. All had stroboscopic evaluation of their neoglottis using flexible and rigid endoscopes. MAIN OUTCOME MEASURES: A rating form was devised based on six parameters with clear definitions. Secondary measures included ability to tolerate the procedure and completeness of the rating form for each parameter using the two systems. RESULTS: There was good reliability between individual raters for the assessment of each system based on Spearman Rho correlation. Importantly, two-thirds of the patients were unable to tolerate the rigid videostroboscopy managed flexible videostroboscopy. Correlation between rigid and flexible videostroboscopy was poor for both raters. Flexible systems picked up more mucosal waves and allowed further analysis of the mucosal wave pattern. CONCLUSIONS: To our knowledge, this is the first study to demonstrate that fibreoptic videstroboscopy is as good as rigid videostroboscopy in the assessment of the neoglottis. In fact, flexible videostroboscopy should be routinely used, as it is better tolerated and allows a more detailed analysis of the neoglottis.

Detection of occult spinal cord compression with magnetic resonance imaging of the spine.

AIMS: Spinal cord compression (SCC) is the most significant complication due to skeletal metastasis from prostate cancer. The early detection of SCC is essential as the neurological status before treatment is the major determinant influencing outcome. The aim of this investigation was to determine the role of magnetic resonance imaging of the spine in detecting SCC or occult SCC in patients with metastatic prostate cancer with no functional neurological deficit (FND). MATERIALS AND METHODS: A retrospective analysis of the clinical data of 150 consecutive patients with metastatic prostate cancer and no FND, who had MRI of the spine from January 2001 to May 2005, was carried out. 'Overt SCC' on MRI was defined as the involvement or compression of either the spinal cord or the cauda equina by an epidural or intramedullary mass lesion and 'occult SCC' as metastatic disease causing impingement, indentation or loss of definition of the thecal sac, which were considered together for statistical purposes as radiological spinal cord compromise (rSCC). RESULTS: Twenty-four (16%) patients had overt SCC, whereas 17 (11.3%) patients had occult SCC. Seven patients had rSCC at multiple non-contiguous sites. The significant clinical determinants of rSCC on univariate analysis were extensive bone metastasis (P=0.005) and back pain (P=0.002). On multivariate analysis, both back pain (P=0.012) and extensive bone metastasis (P=0.047) significantly predicted for rSCC. CONCLUSION: A significant proportion (27.3%) of patients with metastatic prostate cancer may harbour overt or occult SCC in the absence of FND. MRI of the spine for the early diagnosis of SCC may be considered useful in patients with extensive skeletal metastasis and back pain.

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.

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.

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.

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.

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.