Parametrized rectal dose and associations with late toxicity in prostate cancer radiotherapy.

OBJECTIVE: We investigated possible associations between planned dose-volume parameters and rectal late toxicity in 170 patients having radical prostate cancer radiotherapy. METHODS: For each patient, the rectum was outlined from anorectal junction to sigmoid colon, and rectal dose was parametrized using dose-volume (DVH), dose-surface (DSH) and dose-line (DLH) histograms. Generation of DLHs differed from previous studies in that the rectal dose was parametrized without first unwrapping onto 2-dimensional dose-surface maps. Patient-reported outcomes were collected using a validated Later Effects in Normal Tissues Subjective, Objective, Management and Analytic questionnaire. Associations between dose and toxicity were assessed using a one-sided Mann-Whitney U test. RESULTS: Associations (p < 0.05) were found between equieffective dose (EQD23) and late toxicity as follows: overall toxicity with DVH and DSH at 13-24 Gy; proctitis with DVH and DSH at 25-36 Gy and with DVH, DSH and DLH at 61-67 Gy; bowel urgency with DVH and DSH at 10-20 Gy. None of these associations met statistical significance following the application of a Bonferroni correction. CONCLUSION: Independently confirmed associations between rectal dose and late toxicity remain elusive. Future work to increase the accuracy of the knowledge of the rectal dose, either by accounting for interfraction and intrafraction rectal motion or via stabilization of the rectum during treatment, may be necessary to allow for improved dose-toxicity comparisons. ADVANCES IN KNOWLEDGE: This study is the first to use parametrized DLHs to study associations with patient-reported toxicity for prostate radiotherapy showing that it is feasible to model rectal dose mapping in three dimensions.

Phase II trial of sorafenib in advanced salivary adenoid cystic carcinoma of the head and neck.

BACKGROUND: There is a need to improve the systemic treatment of advanced adenoid cystic carcinoma (ACC). Response rates to chemotherapy are poor and preliminary investigations of molecularly targeted agents have been disappointing. In this study, we evaluate sorafenib, an oral multikinase inhibitor, which has an attractive targeting profile for this disease. METHODS: In a single-arm phase II trial, patients with unresectable locally recurrent and/or metastatic ACC were treated with sorafenib 400 mg bid. RESULTS: Twenty-three patients, median age 51 years, were recruited from 2009 to 2011. Median progression-free survival (PFS) and overall survival (OS) were 11.3 and 19.6 months, respectively. PFS at 6 and 12 months were 69.3% and 46.2%, respectively. Sorafenib was only reasonably well tolerated, and 13 patients (57%) experienced grade 3 toxicity. CONCLUSION: Sorafenib showed modest activity in ACC with a 12-month PFS of 46.2%. Sorafenib 400 mg bid was associated with significant toxicity and, taken together with limited effectiveness, cannot be enthusiastically recommended for further evaluation.

Investigation of a Patient Reported Outcome tool to assess radiotherapy-related toxicity prospectively in patients with lung cancer.

BACKGROUND AND PURPOSE: There is a paucity of data regarding the feasibility and relevance of Patient Reported Outcome (PRO) tools to assess radiotherapy-related toxicity in lung cancer. MATERIAL AND METHODS: From January to June 2013, lung cancer patients undergoing thoracic radiotherapy/chemo-radiotherapy completed nine patient-adapted Common Terminology Criteria for Adverse Events (CTCAE), the European Organisation for Research and Treatment of Cancer Quality of Life (QoL) questionnaire and the Hospital Anxiety and Depression Scale (HADS) at baseline, the end of radiotherapy and at follow-up. Clinicians completed the same CTCAE items and agreement between patients' and clinicians' reporting was assessed using weighted kappa coefficients. QoL and HADS scores were correlated with the patients' and clinicians' reported toxicity. RESULTS: 70/116 patients completed the questionnaires for at least one time point excluding baseline. Agreement between patients' and clinicians' reported toxicity ranged from slight to substantial. Most discrepancies were within one grade and patients reported greater severity than clinicians for most symptoms. QoL and HADS scores were more strongly correlated with the patients' compared to clinicians' matching toxicity reports. The PRO tool was found to be statistically reliable. CONCLUSIONS: The use of a PRO tool in lung cancer radiotherapy is feasible, reliable and acceptable to patients. PROs should be integrated in future clinical trials evaluating new radiotherapy approaches to assess toxicity.

Phase II Trial of Cetuximab and Conformal Radiotherapy Only in Locally Advanced Pancreatic Cancer with Concurrent Tissue Sampling Feasibility Study.

BACKGROUND: Preclinical data have indicated the anti-epidermal growth factor receptor (EGFR) agent cetuximab (Erbitux) as a radiosensitizer in pancreatic cancer, but this has not been specifically addressed in a clinical study. We report the results of an original study initiated in 2007, where cetuximab was tested with radiotherapy (RT) alone in locally advanced pancreatic cancer in a phase II trial (PACER). METHODS: Patients (n = 21) received cetuximab loading dose (400 mg/m(2)) and weekly dose (250 mg/m(2)) during RT (50.4 Gy in 28 fractions). Toxicity and disease response end point data were prospectively assessed. A feasibility study of on-trial patient blood and skin sampling was incorporated. RESULTS: Treatment was well tolerated, and toxicity was low; most patients (71%) experienced acute toxicities of grade 2 or less. Six months posttreatment, stable local disease was achieved in 90% of evaluable patients, but only 33% were free from metastatic progression. Median overall survival was 7.5 months, and actuarial survival was 33% at 1 year and 11% at 3 years, reflecting swift metastatic progression in some patients but good long-term control of localized disease in others. High-grade acneiform rash (P = .0027), posttreatment stable disease (P = .0059), and pretreatment cancer antigen 19.9 (CA19.9) level (P = .0042) associated with extended survival. Patient skin and blood samples yielded sufficient RNA and good quality protein, respectively. CONCLUSIONS: The results indicate that cetuximab inhibits EGFR-mediated radioresistance to achieve excellent local control with minimal toxicity but does not sufficiently control metastatic progression in all patients. Translational studies of patient tissue samples may yield molecular information that may enable individual treatment response prediction.

Five-year outcomes after iodine-125 seed brachytherapy for low-risk prostate cancer at three cancer centres in the UK.

OBJECTIVE: To report the outcomes of >1000 men with low-risk prostate cancer treated with low-dose-rate (LDR) brachytherapy at three large UK cancer centres. PATIENTS AND METHODS: A total of 1038 patients with low-risk prostate cancer (prostate-specific antigen [PSA] ≤10 ng/mL, Gleason score 6, ≤T2b disease) were treated with LDR iodine 125 (I-125) brachytherapy between 2002 and 2007. Patients were treated at three UK centres. PSA and clinical follow-up was performed at each centre. Biochemical recurrence-free survival was reported for the cohort. RESULTS: The median (range) PSA follow-up for the whole group was 5 years (4 months to 9 years). A total of 79 patients had biochemical failure, defined by a rise in PSA level: 16 patients fulfilled the ASTRO definition of biochemical failure, 25 patients fulfilled the Phoenix definition and 38 patients fulfilled both definitions. The 5-year biochemical relapse-free survival (bRFS) rate was 94.1% by the ASTRO definition and 94.2% by the Phoenix definition. The absence of neoadjuvant hormone therapy was predictive of inferior biochemical control as defined by the Phoenix definition (P = 0.033). CONCLUSIONS: Our prospective multicentre series showed excellent bRFS with LDR I-125 brachytherapy for patients with low-risk prostate cancer. Further work is necessary to define the role of neoadjuvant androgen deprivation therapy in combination with brachytherapy.

Evaluation of hypertension and proteinuria as markers of efficacy in antiangiogenic therapy for metastatic colorectal cancer.

BACKGROUND: The vascular endothelial growth factor pathway is strongly implicated in cancer-related angiogenesis. Antiangiogenic agents such as bevacizumab commonly cause hypertension (HTN) and proteinuria (PTN), which may be biomarkers of response and clinical outcome. STUDY: We conducted a retrospective analysis of patients with histologically proven metastatic colorectal cancer (mCRC) treated with either bevacizumab or a tyrosine kinase inhibitor in combination with chemotherapy at The Christie Hospital from January 2006 to September 2009. RESULTS: Of 90 patients evaluated, 50 were eligible. Seventeen (34%), 4 (8%), and 3 (6%) patients developed Common Toxicity Criteria (v 3.0) grades 1, 2, and 3 HTN, respectively. Response rates were 42% for patients with grades 0 to 1 HTN compared with 86% for patients with ≥grade 2 HTN (P=0.043). Median overall survival was 21.6 months for patients with grades 0 to 1 HTN and 25.2 months for patients with ≥grade 2 HTN (P=0.270). Twelve patients (24%) developed grade 1 PTN and 4 patients (8%) developed ≥grade 2 PTN. Median overall survival was 23.9 months for patients with grades 0 to 1 PTN and 4.2 months for those with ≥grade 2 PTN (P=0.028). CONCLUSIONS: To our knowledge, this is the first study to demonstrate the utility of PTN as a surrogate marker of outcome in antiangiogenic therapy for metastatic colorectal cancer. Although HTN is predictive of a significantly higher response rate, the development of PTN during treatment with bevacizumab or tyrosine kinase inhibitor portends poorer survival and should be evaluated prospectively.

Biochemical outcomes for patients with intermediate risk prostate cancer treated with I-125 interstitial brachytherapy monotherapy.

BACKGROUND AND PURPOSE: Routine use of I-125 interstitial brachytherapy (BT) alone in intermediate risk (IR) prostate cancer is controversial. It is often combined with external beam radiotherapy (EBRT). The biochemical outcome of a large cohort of only IR disease treated with BT monotherapy is reported. MATERIALS AND METHODS: Between 2003 and 2007, 615 patients with Memorial Sloan-Kettering Cancer Centre (MSKCC) defined IR disease (one risk factor only-T2b, or Gleason score (GS) 7, or raised initial PSA (iPSA) 10.1-20ng/ml) were treated with BT monotherapy. ASTRO (3 consecutive rises) and Phoenix (nadir plus 2) criteria defined biochemical failure. Potential prognostic factors (pre- and post-implant dosimetric indices, GS 3+4 versus 4+3, androgen deprivation therapy (ADT)) were analysed. RESULTS: Median follow-up was 5.0years. Forty-three patients had stage T2b, 180 had raised iPSA, 392 had GS 7 disease. ADT was received by 108 patients. The 5-year biochemical no evidence of disease (bNED) rates are 87.3% (by ASTRO), 88.6% (by Phoenix). Stratification by risk factor (T2b, GS7, raised iPSA) demonstrated raised iPSA to have poorer outcome only by Phoenix criteria (p=0.0002). Other potential prognostic variables were non-significant. CONCLUSION: Good rates of biochemical control can be achieved in the medium term with BT monotherapy in IR disease. Raised iPSA correlated with a poorer outcome.

The case for including bowel urgency in toxicity reporting after pelvic cancer treatment.

Bowel toxicity is a major complication of cancer treatment, and its accurate reporting is important for assessing outcomes. The NCI's Common Terminology Criteria for Adverse Events (CTCAE) is the preferred method for capturing adverse events after all cancer treatments, particularly within clinical trials. However, the CTCAE version 4 does not include urgency of defecation as an item, despite this being one of the most common and persistent adverse consequences of treatment of pelvic cancers. The importance of bowel urgency to patients is well documented, and this treatment effect has a negative impact on social function and quality of life. Bowel urgency is also important clinically because it may represent significant underlying problems. This article presents the case for including patient reported assessment of bowel urgency as an independent item in cancer treatment adverse event reporting.

Structured gastroenterological intervention and improved outcome for patients with chronic gastrointestinal symptoms following pelvic radiotherapy.

PURPOSE: Fifty percent of patients develop chronic gastrointestinal (GI) symptoms following pelvic radiotherapy that adversely affect quality of life. Fewer than 20 % are referred to a gastroenterologist. We aimed to determine if structured gastroenterological evaluation is of benefit to this patient group. METHODS: Sixty patients with GI symptoms at ≥ 6 months after radical pelvic radiotherapy were identified prospectively from oncology clinics in this service evaluation. Those requiring urgent investigation were excluded. Patients were assessed at baseline using patient-reported questionnaires: inflammatory bowel disease questionnaire (IBDQ), Vaizey incontinence questionnaire, and the Common Terminology Criteria for Adverse Events (CTCAE) pelvis questionnaire. Participants were referred for gastroenterological evaluation using an algorithmic approach. Further assessments were made at 3 and 6 months. RESULTS: Twenty men and 36 women with primary gynecological (31), urological (17), or lower GI (8) tumors were included (mean age, 58.5 years). Median time from radiotherapy to baseline assessment was 3.0 years. Multiple GI symptoms were reported (median, 8; range, 4-16) including frequency, urgency, loose stool, fecal incontinence, flatulence, bloating/distension, and rectal bleeding. Common diagnoses included radiation proctopathy, bile acid malabsorption, diverticulosis, and colonic polyps. Statistically significant improvements in all questionnaire scores between baseline and 6 months were found: IBDQ (p = 0.014), Vaizey (p < 0.0005), and CTCAE rectum-bowel subset (p = 0.001). CONCLUSIONS: Gastroenterological evaluation identifies significant, potentially treatable diagnoses in patients who develop chronic GI symptoms following pelvic radiotherapy. Some findings are incidental and unrelated to previous cancer treatment. Radiation-induced GI symptoms have historically been considered "untreatable." We report the first data to show that structured gastroenterological assessment has the potential to improve outcome by identifying diagnoses and facilitating focused treatment.

Use of Pre-Ablation Radioiodine-131 Scan to Assess the Impact of Surgical Volume and Specialisation following Thyroidectomy for Differentiated Thyroid Carcinoma.

BACKGROUND: We evaluated the relationship between thyroid remnant size following thyroidectomy for differentiated thyroid carcinoma and surgical volume and specialisation by assessing pre-ablation radioiodine-131 ((131)I) thyroid bed uptake (TBU) scanning as a surrogate for residual thyroid tissue. METHODS: We analysed data of 651 patients in our thyroid cancer database. Patients' data were included if the following criteria were met: (1) diagnosis of differentiated thyroid carcinoma, (2) total or near-total thyroidectomy, (3) pre-ablation (131)I scan prior to radioiodine ablation (RAI), (4) no distant metastasis, and (5) >3,000 MBq ablative dose of (131)I. (131)I diagnostic whole-body scans and measurement of thyroglobulin levels were carried out 3-9 months after RAI. 305 patients were included in the final analysis. RESULTS: Four endocrine, 19 otolaryngology and 25 general surgeons performed thyroidectomies with median pre-ablation (131)I TBU values of 1.0, 1.8 and 2.9%, respectively (p = 0.0031). There was a statistically significant relationship between number of thyroidectomies performed and median pre-ablation (131)I TBU values up to the optimal number of 11 operations beyond which there was no further significant difference between surgeons. There were differences in remnant size between endocrine and general surgeons (p = 0.001), otolaryngology and general surgeons (p = 0.023) but not between endocrine and otolaryngology surgeons (p = 0.167). CONCLUSION: Using the pre-ablation (131)I uptake scan as a surrogate for thyroid remnant quantification following thyroidectomy demonstrates the relationship between the surgical volume and size of thyroid remnant. The study also demonstrated beneficial effects of specialisation with specialist surgeons achieving the smallest thyroid remnant.

Dose-escalated hypofractionated intensity-modulated radiotherapy in high-risk carcinoma of the prostate: outcome and late toxicity.

Background. The benefit of dose-escalated hypofractionated radiotherapy using intensity-modulated radiotherapy (IMRT) in prostate cancer is not established. We report 5-year outcome and long-term toxicity data within a phase II clinical trial. Materials and Methods. 60 men with predominantly high-risk prostate cancer were treated. All patients received neoadjuvant hormone therapy, completing up to 6 months in total. Thirty patients were treated with 57 Gy in 19 fractions and 30 patients with 60 Gy in 20 fractions. Acute and 2-year toxicities were reported and patients followed longitudinally to assess 5 year outcomes and long-term toxicity. Toxicity was measured using RTOG criteria and LENT/SOMA questionnaire. Results. Median followup was 84 months. Five-year overall survival (OS) was 83% and biochemical progression-free survival (bPFS) was 50% for 57 Gy. Five-year OS was 75% and bPFS 58% for 60 Gy. At 7 years, toxicity by RTOG criteria was acceptable with no grade 3 or above toxicity. Compared with baseline, there was no significant change in urinary symptoms at 2 or 7 years. Bowel symptoms were stable between 2 and 7 years. All patients continued to have significant sexual dysfunction. Conclusion. In high-risk prostate cancer, dose-escalated hypofractionated radiotherapy using IMRT results in encouraging outcomes and acceptable late toxicity.

Prospective analysis of patient-reported late toxicity following pelvic radiotherapy for gynaecological cancer.

BACKGROUND AND PURPOSE: As late radiotherapy toxicity impacts negatively on the quality-of-life of cancer survivors and is often under reported, a study was set up to prospectively collect patient-reported data in an unselected series of patients with gynaecological malignancy. Aim 1 - To provide 3 year results for the longitudinal study. Aim 2 - To improve the questionnaire used to collect data by identifying redundant items and modifying for use to collect Common Terminology Criteria for Adverse Events (CTCAE) data. MATERIAL AND METHODS: Aim 1 - Patient reported outcome data were collected prospectively by 226 patients before and up to 3 years following radiotherapy for gynaecological cancer using a questionnaire developed to collect LENT subjective data. Aim 2 - A factor analysis was performed to identify which questions gave the most and least information. RESULTS: Aim 1 - Faecal urgency and incontinence (all grades) peaked at 79% and 24%, respectively at 1 year then settled to 69% and 18% at 3 years, respectively. Urinary urgency (all grades) increased with time and was described in 75% at 3 years. Other symptoms reported at 3 years include diarrhoea in 12%, urinary incontinence in 27% and vaginal dryness in 29%. A third of patients did not feel their sex life had changed following treatment, while a quarter felt that it had. Aim 2 - some questions overlapped and others were non-specific. The questionnaire has subsequently been altered. CONCLUSIONS: The extent of late toxicity is substantial. This detailed information is important for both patients and clinicians in terms of treatment decisions and follow-up care. The LENT questionnaire provides a feasible tool for capture of this information in the clinic.

Phase II study of conformal hypofractionated radiotherapy with concurrent gemcitabine in muscle-invasive bladder cancer.

PURPOSE: The aim of this prospective, phase II trial was to determine the response of muscle-invasive bladder cancer (MIBC) to concurrent chemoradiotherapy of weekly gemcitabine with 4 weeks of radiotherapy (RT; GemX). PATIENTS AND METHODS: Fifty patients with transitional cell carcinoma, stage T2-3, N0, M0 after transurethral resection and magnetic resonance imaging, were recruited. Gemcitabine was given intravenously at 100 mg/m(2) on days 1, 8, 15, and 22 of a 28-day RT schedule that delivered 52.5 Gy in 20 fractions. Chemotherapy was stopped for Radiation Therapy Oncology Group (RTOG) grade 3 bladder or bowel toxicity. The primary end points were tumor response, toxicity, and survival. RESULTS: All patients completed RT; 46 tolerated all four cycles of gemcitabine. Two patients stopped after two cycles, and two stopped after three cycles, because of bowel toxicity. Forty-seven patients had a post-treatment cystoscopy; 44 (88%) achieved a complete endoscopic response. At a median follow-up of 36 months (range, 15 to 62 months), 36 patients were alive, and 32 of these had a functional and intact bladder. Fourteen patients died; seven died as a result of metastatic MIBC, five died as a result of intercurrent disease, and two died as a result of treatment-associated deaths. Four patients underwent cystectomy; three because of recurrent disease and one because of toxicity. One patient required a bowel resection for late toxicity. By using Kaplan-Meier analyses, 3-year cancer-specific survival was 82%, and overall survival was 75%. CONCLUSION: Concurrent gemcitabine-based chemoradiotherapy (ie, GemX) produces a high response rate in MIBC and has durable local control and acceptable toxicity, which allows patients to preserve their own bladder. This treatment modality warrants additional investigation in a phase III setting.

Early prostate cancer--which treatment do men prefer and why?

STUDY TYPE: Preference (prospective cohort). LEVEL OF EVIDENCE: 1b. What's known on the subject? and What does the study add? In general the literature suggests that there is a need for improvement in aiding men diagnosed with early prostate cancer in their decision making about treatment options and that our understanding of this process is inadequate. There is limited data analyzing the reasons why these men decide between potentially curative or observational treatments and data evaluating patients' views before and after definitive therapy are scarce. This study begins the process of understanding the reasons underlying a patient's final treatment decision. Being a prospective study, it looks at the thought processes of these men before treatment during the time the decision is made. It also documents how satisfied patients are with their choice after their treatment and whether they would choose the same treatment again. OBJECTIVE: To identify the reasons for patients with localised prostate cancer choosing between treatments and the relationship of procedure type to patient satisfaction post-treatment. PATIENTS AND METHODS: 768 men with prostate cancer (stage T1/2, Gleason≤7, PSA<20 ug/L) chose between four treatments: radical prostatectomy, brachytherapy, conformal radiotherapy and active surveillance. Prior to choosing, patients were counselled by a urological surgeon, clinical (radiation) oncologist and uro-oncology specialist nurse. Pre-treatment reasons for choice were recorded. Post-treatment satisfaction was examined via postal questionnaire. RESULTS: Of the 768 patients, 305 (40%) chose surgery, 237 (31%) conformal beam radiotherapy, 165 (21%) brachytherapy and 61 (8%) active surveillance. Sixty percent of men who opted for radical prostatectomy were motivated by the need for physical removal of the cancer. Conformal radiotherapy was mainly chosen by patients who feared other treatments (n=63, 27%). Most men chose brachytherapy because it was more convenient for their lifestyle (n=64, 39%). Active surveillance was chosen by patients for more varied reasons. Post-treatment satisfaction was assessed in a subgroup who took part in the QOL aspect of this study. Of the respondents to the questionnaire, 212(87.6%) stated that they were satisfied/extremely satisfied with their choice and 171(92.9%) indicated they would choose the same treatment again. CONCLUSION: Men with early prostate cancer have clear reasons for making decisions about treatment. Overall, patients were satisfied with the treatment and indicated that despite different reasons for choosing treatment, they would make the same choice again.

YY1 expression predicts favourable outcome in follicular lymphoma.

AIMS: Follicular lymphoma is the second most common type of non-Hodgkin's lymphoma worldwide. The majority of patients diagnosed as having follicular lymphoma have an indolent form of the disease, but a subset of patients have aggressive disease with a shorter survival interval. Optimal treatment stratification requires a distinction between these two groups, though there are presently few prognostic biomarkers available. The transcription factor YY1 has been shown to play an important role in cancer biology. The authors have previously reported a correlation of Yin Yang 1 (YY1) mRNA levels with survival in FL. This study aimed to validate these findings at the protein level. METHODS: Quantification of YY1 protein was carried out on 26 FL biopsy samples using quantum dot labelled immunohistochemistry. Ki-67 percentage, grade, YY1 protein levels and T cell and macrophage markers were used in a multivariable analysis for survival in 26 cases of FL. RESULTS: Expression levels of YY1 protein were significantly increased in patients alive in comparison with those dead after follow-up (p ≤ 0.025). Kaplan-Meier analysis showed association of higher expression levels of YY1 with longer survival (p ≤ 0.01) (hazard ratio 3.33, 95% CI 1.26 to 8.85). The multivariable analysis identified YY1 protein level as the strongest predictor of outcome (p ≤ 0.018), with none of the other markers being significantly associated with outcome. CONCLUSION: These results support the prognostic utility of YY1 in FL, indicating potential as a clinical biomarker.

Tumour budding and a low host inflammatory response are associated with a poor prognosis in oesophageal and gastro-oesophageal junction cancers.

AIMS: Tumour budding and host inflammatory response are parameters easily assessed histologically that have prognostic significance in many cancers. There have been few studies examining these parameters in oesophageal or gastro-oesophageal cancers. This study aims to address that deficiency. METHODS AND RESULTS: A two-centre, retrospective study was carried out on 356 patients. Tumour budding and host inflammatory response at the invasive front were assessed histologically. Statistical analysis was performed to determine the prognostic significance of these factors. The median number of tumour buds was four (range 0-50) with 172 of 356 cases having five or more buds at the invasive front. The presence of five or more buds was associated with a poor prognosis on univariate analysis (P = 0.0001), as was a sparse or moderate host inflammatory response (P = 0.001). Tumour budding retained prognostic significance when tumours were separated into adenocarcinomas (n = 287) and squamous cell carcinomas (n = 69), but host inflammatory response was a significant prognostic factor only for adenocarcinomas. On multivariate analysis the presence of five or more buds retained significance (P = 0.002). CONCLUSIONS: Tumour budding and host inflammatory response are important prognostic factors in patients with oesophageal/gastro-oesophageal cancer and can be used to identify high-risk patients who would benefit from closer follow-up and adjuvant therapies.

Mucosal melanoma of the head and neck: radiotherapy or surgery?

INTRODUCTION: Head and neck mucosal melanoma (MuM) is rare, comprising < 1% of all melanomas in Western Europe. METHODS: A retrospective analysis of case records of patients treated between 1965 and 2001 was carried out. (Survival outcomes were obtained from the case notes and cancer registry.) The median age of the 68 patients was 63 years (range 29-86 years). Thirty-nine percent were male, and 61% were female. (The minimum follow-up time was 15 months.) The two most common primary sites were the sinonasal complex (65%) and oral cavity (19%). Twenty-one percent of patients presented with metastases (nodal or distant). Fifty-five patients were treated with curative intent: 30 patients with primary radiotherapy and 25 patients with surgery +/- postoperative radiotherapy. RESULTS: The overall survival was 22% at 5 years, and the cancer-specific survival was 32% at 5 years. CONCLUSION: MuM has a poor overall prognosis. Poor prognostic indicators are site at presentation and presentation with metastasis. This series is unique in that a significant proportion of patients were given primary radiotherapy as definitive treatment. Surgery may have advantages, particularly for oral cavity MuM. In contrast to previous reports, definitive radiotherapy is worthy of consideration as curative treatment.

Development of a patient-reported questionnaire for collecting toxicity data following prostate brachytherapy.

PURPOSE: To improve a questionnaire used to collect patient-reported outcomes from patients with early stage prostate cancer treated with brachytherapy. A secondary aim was to adapt the Late Effects of Normal Tissue (LENT) subjective toxicity questionnaire for use to collect Common Terminology Criteria for Adverse Events (CTCAE) data, the current preferred platform for assessing radiation toxicity. MATERIALS AND METHODS: Three hundred and seventy-seven patients were treated with permanent iodine-125 seed implant brachytherapy for early prostate cancer. Toxicity data were collected before and at nine time points post-treatment (0-36 months). Compliance rates for patients completing individual items and item-subsection correlation coefficients were calculated. A factor analysis was carried out to analyse responses to the questionnaire and identify less informative questions, which could be removed. Cronbach's α coefficient was used to measure reliability. RESULTS: Two thousand one hundred and eighty-eight questionnaires were analysed. There was poor compliance for questions specifically relating to operations and bowel medication. We found that the division of the questionnaire into subsections based on anatomical site was reasonable and that certain items could be safely removed. The high mean value for Cronbach's α across all questionnaires (0.752; 95% CI: 0.726-0.779) indicated that the questionnaire was reliable. Fifteen of the 44 questions were removed from the original questionnaires. Questions on urinary incontinence severity, management of urinary and bowel incontinence, effects of reduced flow of urine and the effects of symptoms on activity of daily living and change in sexual function were required to adapt the LENT subjective questionnaire for use to collect CTCAE data. CONCLUSIONS: A questionnaire, validated over 6 years to collect LENT subjective data were adapted and is a reliable approach for collecting CTCAE data after prostate brachytherapy.

Efficacy of data capture for patient-reported toxicity following radiotherapy for prostate or cervical cancer.

We investigated the efficacy of data capture of patient-reported toxicity following radiotherapy by comparing electronic and paper formats. Patient-reported toxicity questionnaires based on items from the NCI Common Terminology Criteria for Adverse Events (CTCAE) were created for patients receiving radiotherapy. Electronic and paper questionnaires had identical questions. Thirty seven gynaecological cancer and 40 prostate cancer patients completed questionnaires. Both questionnaire formats (electronic and paper) were completed by each patient at time points before and after radiotherapy. The average questionnaire and subsection scores for each format were compared directly and by using intra-class correlation (ICC) coefficients. The internal consistency/reliability was assessed by determining Cronbach's alpha coefficient. Patient preference for questionnaire format including clarity and ease-of-use was recorded. 324 questionnaires were collected as part of this study. A similar pattern of average subsection scores was found for the electronic and paper questionnaires. ICC coefficients for the mean overall questionnaire scores and subsection scores were high (>0.8). Cronbach's alpha was generally greater than 0.6, indicating that the reliability was high. Of the patients that responded, 27.3% preferred the electronic format, 25.7% preferred the paper format and 47% had no preference. The average time taken to complete a questionnaire was about 9 minutes for each format. The different questionnaire formats measured toxicity effects consistently and were reliable for both gynaecological cancer and prostate cancer patients. The survey indicated that patients found the questionnaires clear, easy to understand and straightforward to complete. Electronic data capture of patient-reported toxicity for CTCAE is feasible and acceptable.

Effectiveness of a home care nursing program in the symptom management of patients with colorectal and breast cancer receiving oral chemotherapy: a randomized, controlled trial.

PURPOSE: To assess the effectiveness of a symptom-focused home care program in patients with cancer who were receiving oral chemotherapy in relation to toxicity levels, anxiety, depression, quality of life, and service utilization. PATIENTS AND METHODS: A randomized, controlled trial was carried out with 164 patients with a diagnosis of colorectal (n = 110) and breast (n = 54) cancers who were receiving oral capecitabine. Patients were randomly assigned to receive either a home care program by a nurse or standard care for 18 weeks (ie, six cycles of chemotherapy). Toxicity assessments were carried out weekly for the duration of the patients' participation in the trial, and validated self-report tools assessed anxiety, depression, and quality of life. RESULTS: Significant improvements were observed in the home care group in relation to the symptoms of oral mucositis, diarrhea, constipation, nausea, pain, fatigue (first four cycles), and insomnia (all P < .05). This improvement was most significant during the initial two cycles. Unplanned service utilization, particularly the number of inpatient days (57 v 167 days; P = .02), also was lower in the home care group. CONCLUSION: A symptom-focused home care program was able to assist patients to manage their treatment adverse effects more effectively than standard care. It is imperative that patients receiving oral chemotherapy are supported with such programs, particularly during initial treatment cycles, to improve their treatment and symptom experiences.