Transforming mental well-being for people with diabetes: research recommendations from Diabetes UK's 2019 Diabetes and Mental Well-Being Workshop.

AIMS: To identify key gaps in the research evidence base that could help to improve the mental well-being of people with diabetes, and to provide recommendations to researchers and research funders on how best to address them. METHODS: A 2-day international research workshop was conducted, bringing together research experts in diabetes and in mental health, people living with diabetes and healthcare professionals. RESULTS: The following key areas needing increased financial investment in research were identified: understanding the mechanisms underlying depression; understanding the multifactorial impact of social stigma; improving the language used by healthcare professionals; supporting people who find it difficult to engage with their diabetes; supporting significant others; supporting people with diabetes and eating disorders; improving models of care by learning from best practice; the potential benefits of screening and managing diabetes distress in routine diabetes care pathways; primary prevention of mental health issues at the time of diagnosis of diabetes; establishing the effectiveness of diabetes therapies on mood and other mental health issues; and understanding the impact of current diabetes technologies on mental health. Research recommendations as to how to address each of these priority areas were also developed. CONCLUSIONS: This inaugural position statement outlines recommendations to address the urgent unmet need related to the mental well-being of people living with diabetes, and calls on the research community and funders to develop research programmes and strategies to reduce this need.

Expression of hypoxia-inducible factor-1α predicts benefit from hypoxia modification in invasive bladder cancer.

BACKGROUND: The addition of carbogen and nicotinamide (CON) to radiotherapy (RT) improves overall survival in invasive bladder cancer. We explored whether expression of the hypoxia marker hypoxia-inducible factor-1α (HIF-1α) alone or in combination with other markers predicted benefit from CON. METHODS: A retrospective study was carried out using material from patients with high-grade invasive bladder carcinoma enrolled in the BCON phase III trial of RT alone or with CON (RT+CON). HIF-1α expression was studied in 137 tumours using tissue microarrays and immunohistochemistry. Data were available from other studies for carbonic anhydrase IX and glucose transporter 1 protein and gene expression and tumour necrosis. RESULTS: Patients with high HIF-1α expression had improved 5-year local relapse-free survival with RT+CON (47%) compared with RT alone (21%; hazard ratio (HR) 0.48, 95% CI 0.26-0.8, P=0.02), no benefit was seen with low HIF-1α expression (HR 0.81, 95% CI 0.43-1.50, P=0.5). Combinations of markers including necrosis also predicted benefit but did not improve on prediction using necrosis alone. CONCLUSIONS: HIF-1α may be used to predict benefit from CON in patients with bladder cancer but does not improve on use of necrosis.

CT scan does not predict optimal debulking in stage III-IV epithelial ovarian cancer: a multicentre validation study.

Our aim was to design and validate a model of CT findings that predict suboptimal cytoreduction in primary surgery (PS) for Stage III-IV epithelial ovarian cancer (EOC). We performed a retrospective review of preoperative CT scans of patients undergoing PS for EOC in a cancer centre in London, UK, between November 1995 and October 2003 (n = 91). Radiological features predictive of suboptimal cytoreduction were identified and the model tested in a second cohort undergoing PS in Manchester, June 2005 - March 2007 (n = 35). In the London cohort, liver surface disease and infrarenal para-aortic lymph node involvement predicted suboptimal cytoreduction with 80% accuracy. Accuracy of these predictors dropped to 63% when applied to the Manchester cohort. We concluded that CT prediction of suboptimal cytoreduction is unreliable and may not be reproducible. In the absence of favourable data from larger, prospective trials, it should not be used to guide management.

Thrombosis in ovarian cancer: a case control study.

BACKGROUND: Thrombotic events are common in cancer patients and have been associated with an adverse prognosis in large registry-based studies. METHODS: A retrospective cohort of 417 patients with ovarian cancer treated at a tertiary cancer centre between 2006 and 2009 was studied to identify the incidence and risk factors for thrombotic events and the prognostic impact of thrombosis. Patient outcomes were evaluated against a matched control group without thrombosis. RESULTS: Ninety-nine thrombotic events occurred in 90 patients (21.6%) from 8 months before diagnosis to 56 months following diagnosis, peaking in the 4 months following diagnosis. Patients with thrombosis were older (mean 65 vs 61 years, P=0.007), had a worse performance status (PS ≥2: 29.9% vs 9.5%, P<0.0001) and had a more advanced FIGO stage (FIGO III/IV 75.6% vs 56.9%, P<0.0001) than patients without thrombosis. Shorter overall survival was seen in patients with pulmonary embolism and pelvic/lower limb deep vein thrombosis than without thrombosis (P=0.001). When the control group was matched for stage and PS, no survival difference was seen (P=0.91). CONCLUSION: Ovarian cancer patients with thrombotic events had a shorter survival. However, when matched for prognostic factors (PS and FIGO stage), thrombosis did not impact upon prognosis.

Insufficiency fractures in patients treated with pelvic radiotherapy and chemotherapy for uterine and cervical cancer.

Insufficiency fractures are recognised consequences of radiotherapy in gynaecological malignancy with reported incidences between 2.7% and 89%. We aimed to determine the incidence and risk factors for insufficiency fractures in patients receiving radical pelvic radiotherapy for uterine and cervical cancer. A case-note review was undertaken of patients treated between January 2007 and December 2008. Insufficiency fractures were identified from radiographs, computed tomography and magnetic resonance images. Chi-squared and Mann-Whitney tests were performed to determine associations between insufficiency fractures and chemotherapy, steroids and age. A total of 285 patients received pelvic radiotherapy, 137 with uterine and 148 with cervical cancer. Mean age was 59 years. A total of 144 patients received chemotherapy, 101 concurrently and 35 adjuvantly. Bone abnormalities affected 67 patients, 33 had pelvic insufficiency fractures, 12 had multiple fractures and 3 patients developed femoral head avascular necrosis. Use of chemotherapy was not associated with development of fractures (P = 0.949). However, cervical cancer patients had a significantly higher incidence of insufficiency fractures (P = 0.018) and bone pain (P = 0.03) compared with uterine cancer patients. This suggests concurrent chemotherapy may be a significant factor in increasing insufficiency fractures and bone morbidity in these patients and highlights a need for further research to identify, prevent and reduce these long-term complications.

Cisplatin plus capecitabine as first-line chemotherapy for recurrent or metastatic head and neck squamous cell cancer: experience outside of a trial setting.

PURPOSE: Cisplatin/5-fluorouracil (5-FU) is an accepted palliative chemotherapy treatment for head and neck squamous cell carcinoma, improving quality of life but not overall survival. Capecitabine in place of 5-FU removes the morbidity of an infusional regime with potential benefit in patient well-being. This study looks at outcomes for cisplatin plus capecitabine (PX) outside of a trial setting. METHODS: Consecutive patients receiving this treatment in a single centre were retrospectively analysed. Cisplatin (mean dose 75 mg/m²) was given on day 1 of a 3-week cycle and capecitabine (mean dose 808 mg/m² twice daily) on days 1-14, for up to 6 cycles. RESULTS: Sixty-five patients (median age 58.6 years) received a median of 4 cycles of chemotherapy. The overall response rate was 30.7%, with a median overall survival of 7.3 months. Treatment was well tolerated with a 10.7% grade 3 and a 1.5% grade 4 neutropenia rate, with no other grade 4 toxicities. One patient died of neutropenic sepsis whilst on treatment. Twenty-seven percent of patients stopped treatment early due to chemotherapy-related side effects. CONCLUSION: PX is well tolerated outside the trial setting with outcomes similar to historical published literature. Ease of administration and benefit to patient convenience make it an attractive alternative to standard palliative treatment.

Value of the Hospital Anxiety and Depression Scale in the follow up of head and neck cancer patients.

BACKGROUND: Few studies have prospectively investigated psychological morbidity in UK head and neck cancer patients. This study aimed to explore changes in psychological symptoms over time, and associations with patients' tumour and treatment characteristics, including toxicity. METHODS: Two hundred and twenty patients were recruited to complete the Hospital Anxiety and Depression Scale and the Late Effects on Normal Tissue (Subjective, Objective, Management and Analytic) ('LENT-SOMA') questionnaires, both pre- and post-treatment. RESULTS: Anxiety was highest pre-treatment (38 per cent) and depressive symptoms peaked at the end of treatment (44 per cent). Anxiety significantly decreased and depression significantly increased, comparing pre- versus post-treatment responses (p < 0.001). Hospital Anxiety and Depression Scale scores were significantly correlated with toxicity, age and chemotherapy (p < 0.01 for all). CONCLUSION: This is the first study to analyse the relationship between Hospital Anxiety and Depression Scale scores and toxicity scores in head and neck cancer patients. It lends support for the use of the Hospital Anxiety and Depression Scale and the Late Effects on Normal Tissue (Subjective, Objective, Management and Analytic) questionnaire in routine clinical practice; furthermore, continued surveillance is required at multiple measurement points.

Nasopharyngeal carcinoma: a retrospective review of demographics, treatment and patient outcome in a single centre.

AIMS: Nasopharyngeal cancer (NPC) is relatively uncommon, especially in the Western world. We report our single institution experience of 20 years of data in 128 patients with NPC, including responses to different treatment modalities and outcomes by histological subtype. MATERIALS AND METHODS: NPC patients presenting from 1992 to 2005 were located on the cancer registry database. Demographic data included age, gender, length of presenting symptoms and stage. World Health Organization classification (2005) was used for histological subtyping. The date of recurrence and survival outcomes were analysed using Kaplan-Meier curves. RESULTS: Presentation data were analysed from 128 patients; the survival analysis included 123 patients. The median age at presentation was 57.7 years. Stage III and IV presentation rates were 34 and 38%, respectively. The most common presenting symptom was a palpable neck lump (55%) and the median duration of symptoms was 16 weeks. Forty-eight patients received radiotherapy alone and 75 received chemoradiotherapy. The median overall survival in chemoradiotherapy patients was 80.3 months versus 28.5 months with radiotherapy alone (P = 0.003). A significant difference was also seen with recurrence-free survival (RFS) (P = 0.017). Type 1 keratinising carcinoma had a significantly worse overall survival (P = 0.04) and a similar but non-statistically significant trend was seen for RFS (P = 0.051). The multivariate analysis for overall survival showed that histological subtype (hazard ratio 2.7, 95% confidence interval 1.3-5.5, P = 0.034), age (hazard ratio 2.3, 95% confidence interval 1.1-4.9, P = 0.018) and N stage (hazard ratio 3.7, 95% confidence interval 1.4-9.4, P = 0.024) were prognostic factors. CONCLUSIONS: We present the first large-scale, single-centre retrospective review of NPC in a UK-based population. Demographic data were similar to that in other Western populations, with a significantly worse survival outcome in the keratinising group. Further prospective study of outcome in Western populations accounting for newer radiotherapy techniques such as intensity-modulated radiotherapy and dose escalation, particularly in the keratinising population who were more likely to present with an isolated local recurrence, is recommended.

Lack of prognostic effect of carbonic anhydrase-9, hypoxia inducible factor-1α and bcl-2 in 286 patients with early squamous cell carcinoma of the glottic larynx treated with radiotherapy.

AIMS: To evaluate the prognostic significance of potential tumour markers of hypoxia and apoptosis in early squamous cell carcinoma of the glottic larynx managed with radiotherapy. MATERIALS AND METHODS: In total, 382 patients with T1 and T2 squamous cell carcinoma of the glottic larynx (vocal cords) received radical radiotherapy (50-55 Gy, in 16 fractions in 98% of cases). Pre-treatment haemoglobin was available for 328 patients; biopsy samples were available for 286. Immunohistochemistry was carried out for carbonic anhydrase-9 (CA-9), hypoxia inducible factor-1α (HIF-1α) and Bcl-2. RESULTS: At 5 years, locoregional control was achieved in 88.2%, cancer-specific survival in 95.0% and overall survival in 78.7%. Adverse prognostic factors for locoregional tumour recurrence were pre-treatment haemoglobin <13.0 g/dl (P = 0.035, Log rank test; sensitivity 0.28, specificity 0.84) and stage T2 rather than T1 (P = 0.002). The effect of haemoglobin level on locoregional control was not significant when stratified by the median of 14.2 g/dl (P = 0.43) or as a continuous variable (P = 0.59). High CA-9 (P = 0.11), HIF-1α (P = 0.67) and Bcl-2 (P = 0.77) expression had no prognostic significance. CONCLUSIONS: High CA-9, HIF-1α and Bcl-2 do not add to the prognostic significance of tumour stage and lower haemoglobin in predicting failure of local control in early glottic larynx squamous cell carcinoma managed with radiotherapy. The effect of haemoglobin was not strong enough to be useful as a prognostic biomarker.

Prediction of post-treatment trismus in head and neck cancer patients.

Our aim was to establish the incidence of trismus over time, together with risk factors (including quality of life (QoL)) for the prediction of trismus after treatment in patients with cancer of the head and neck. It was a longitudinal study of 152 patients accepted for primary operation who attended the head and neck cancer clinic of a tertiary referral cancer centre in the United Kingdom. A total of 87 patients was studied prospectively. Our results showed that 41/87 (47%) of patients presented with trismus, 57/80 (71%) had postoperative trismus, and 41/52 (79%) had trismus 6 months after operation or radiotherapy (trismus defined as a maximum mouth opening of ≤ 35 mm). Men and those who drank a lot of alcohol were less likely to have trismus after treatment. QoL variables showed that pain, eating, chewing, taste, saliva, social functioning, social contact, and dry mouth were significantly more impaired in the trismus group than among those without trismus. Postoperative differences in QoL between the two groups highlighted problems with social function and role-playing, fatigue, activity, recreation, and overall reduction in QoL. Women, and those who do not drink alcohol, are at particularly high risk of developing trismus, and, to prevent it and treat it, patients may benefit from multidisciplinary management at an early stage during treatment.

Gastrointestinal symptoms after pelvic radiotherapy: a national survey of gastroenterologists.

PURPOSE: Seventeen thousand patients receive treatment with radical pelvic radiotherapy annually in the UK. Up to 50% develop significant gastrointestinal symptoms. The National Cancer Survivorship Initiative has identified access to specialist medical care for those with complications after cancer as one of their four key needs. We aimed to determine the current practice of British gastroenterologists with regards to chronic gastrointestinal symptoms after pelvic radiotherapy. METHODS: A questionnaire was developed and sent up to a maximum of five times to all UK consultant gastroenterologists. RESULTS: Eight hundred sixty-six gastroenterologists were approached and 165 (20%) responded. Sixty-one percent saw one to four patients annually with bowel symptoms after radiotherapy. Eighteen percent rate the current treatments as effective "often" or "most of the time". Forty-seven percent of gastroenterologists consider themselves "confident with basic cases", with 11% "confident in all cases". Fifty-nine percent thinks a gastroenterologist with a specialist interest should manage these patients. Although only 29% thinks a specific service is required for these patients, 34% rates the current service as inadequate. The ideal service was considered to be gastroenterology-led, multidisciplinary and regional. Low referral rates, poor evidence-base and poor funding are cited as reasons for the current patchy services. CONCLUSIONS: The low response rate contrasts with that from a parallel survey of clinical oncologists. This may reflect the opinion that radiation-induced bowel toxicity is not a significant issue, which may be because only a small proportion of patients are referred to gastroenterologists. The development of new, evidence-based gastroenterology-led services is considered the optimal way to meet the needs of these patients.

Long-term safety of growth hormone replacement after CNS irradiation.

CONTEXT: Radiotherapy is a central component in the treatment of many brain tumors, but long-term sequelae include GH deficiency and increased risk of secondary neoplasms. It is unclear whether replacement therapy with GH (GHRT) further increases this risk. OBJECTIVE: The objective of the study was to assess the effect of GHRT on the incidence of secondary tumors and tumor recurrence after cranial irradiation. DESIGN AND SETTING: We conducted a retrospective matched-pairs analysis of previously irradiated patients, with and without GHRT, attending a tertiary center between 1994 and 2009. PATIENTS: We reviewed the records for all patients undergoing GHRT at our institution over the study period. PATIENTS were included if they had received cranial irradiation, GHRT for at least 12 months, and records of serial magnetic resonance imaging data and data for dose and fractionation of irradiation were available. GH-naïve control patients were selected from a radiotherapy database of patients attending the same hospital. PATIENTS were matched for date of radiotherapy, age, site of primary diagnosis, radiation dose, and fractionation. MAIN OUTCOME MEASURE: The primary outcome measure was risk of tumor recurrence or secondary tumor. RESULTS: Matched controls were identified for 110 GH-treated patients. Median follow-up was 14.5 yr. No significant differences were apparent in the number of tumor recurrences (six vs. eight, GHRT vs. control group) or secondary tumors (five vs. three, respectively) between groups. CONCLUSIONS: Our study demonstrates no increased risk for recurrent or secondary neoplasms in patients receiving GHRT, thus supporting a high safety profile of GHRT after central nervous system irradiation.

Late-onset bowel dysfunction after pelvic radiotherapy: a national survey of current practice and opinions of clinical oncologists.

AIMS: Seventeen thousand patients receive treatment with radical pelvic radiotherapy annually in the UK. It is common for patients to develop gastrointestinal symptoms after treatment. The aim of this study was to determine the current practice of clinical oncologists in the UK with respect to late-onset bowel dysfunction after pelvic radiotherapy, and to discuss the wider issues surrounding current and future service provision for this patient group. MATERIALS AND METHODS: A questionnaire was developed to establish current practice. This was sent to the 314 clinical oncologists in the UK who treat pelvic malignancies up to a maximum of three times. RESULTS: One hundred and ninety (61%) responses were received. Most oncologists (76%) screen for gastrointestinal dysfunction after pelvic radiotherapy, usually through history taking rather than formal tools. Clinical oncologists view toxicity as a significant problem, with most estimating that up to 24% of patients at 1 year have bowel symptoms. Most oncologists refer less than 50% of their symptomatic patients, with most referring less than 10%. These referrals are 31% to a gastroenterologist, 23% to a gastrointestinal surgeon and 33% to both. Most (58%) do not have access to a gastroenterologist or a gastrointestinal surgeon with a specialist interest in their area. Sixty-five per cent of oncologists think a service is required specifically for patients with bowel dysfunction after pelvic radiotherapy, but half (52%) think that the current service in their area is inadequate. CONCLUSIONS: Clinical oncologists recognise late-onset bowel dysfunction after pelvic radiotherapy as a significant problem, but one that is linked to poor recognition of symptoms and an inadequate patchy service.

Phase II study of short-course capecitabine plus oxaliplatin (XELOX) followed by maintenance capecitabine in advanced colorectal cancer: XelQuali study.

PURPOSE: To evaluate the efficacy, safety and quality of life of a short course of oxaliplatin plus capecitabine (XELOX) followed by single-agent capecitabine in patients with previously untreated, inoperable, metastatic colorectal cancer. METHODS: Patients received intravenous oxaliplatin 130 mg/m(2) on d1 plus oral capecitabine 1,000 mg/m(2) twice daily (bid) on d1-14 every 21 days for four cycles. Patients achieving stable disease (SD) or better than received capecitabine 1,250 mg/m(2) bid on d1-14 every 21 days until disease progression. The primary endpoint was progression-free survival (PFS). RESULTS: Overall, 21/45 (47%) of patients responded to the initial XELOX chemotherapy whilst SD or better was documented in 76%. Median PFS was 6.7 (95% CI 5.7-9.6) months, and median overall survival (OS) was 20.5 (95% CI 13.1-28.1) months. In the 34 patients who then received capecitabine maintenance therapy, the median PFS was 8.1 (95% CI 6.2-11.8) months and median OS was 23.1 (95% CI 17.8-28.5) months. A marked reduction in the vast majority of all grades of adverse event occurred on switching from initial XELOX to maintenance capecitabine chemotherapy including grades 1-2 (77 vs. 47%) and grade 3 (7 vs. 3%) neuropathy, diarrhoea and lethargy. CONCLUSIONS: Short-course XELOX followed by capecitabine maintenance therapy provides an active and well-tolerated treatment option for patients with previously untreated metastatic colorectal cancer. A median OS of more than 20 months is promising and by limiting the number of oxaliplatin infusions, this approach minimises the risk of unwanted cumulative neurotoxicity, is cheaper and more convenient for both patients and healthcare providers.

Symptoms experienced by cancer patients during the first year from diagnosis: patient and informal caregiver ratings and agreement.

OBJECTIVE: The aim of this study was to explore the symptom experience of patients with cancer, identify changes in symptoms over time, and explore the congruence of symptom reports between patients and their informal caregivers. METHOD: This was a prospective longitudinal evaluation of symptoms over 1 year from start of treatments (T1) using the Memorial Symptom Assessment Scale. Assessments and follow up took place at 3 months (T2), 6 months (T3) and 12 months (T4). A heterogeneous sample of 100 patients with cancer participated, providing 325 assessments over time. Furthermore, 82 caregivers also participated, providing 238 dyadic patient-caregiver assessments over the same time. RESULTS: The most commonly occurring, and by far most distressing, symptom was "lack of energy." Common symptoms reported were lack of concentration, difficulties sleeping, shortness of breath, cough, pain, dry mouth, and feeling drowsy. Symptom occurrence and distress improved over time, particularly from T2 to T3 (p < 0.05), but the "chronicity" of some generic symptoms was notable. Caregivers tended to overestimate occurrence and distress compared to patients, particularly in symptoms of psychological nature; κ statistics had a highest coefficient of 0.45, suggesting moderate agreement between patients and caregivers at best. SIGNIFICANCE OF RESULTS: More attention needs to be paid to the commonly reported symptoms by patients, as they have the potential of impacting on quality of life (QOL). As patient-caregiver reports had moderate agreement, effort should be directed to improving this agreement, as caregivers are often communicating patient symptoms to clinicians.

Electroglottogram approximate entropy: a novel single parameter for objective voice assessment.

BACKGROUND: The electroglottogram approximate entropy value is a numerical variable which gives an overall measure of voice quality. It is derived by analysing the complexity of the electroglottogram waveform using regulatory statistics. AIMS: (1) To use electroglottogram approximate entropy to measure voice quality in patients with glottic pathology and in normal subjects, to ascertain whether this parameter can distinguish between pathological and normal voices. (2) To ascertain whether electroglottogram approximate entropy can measure voice change over time within individual subjects. (3) To determine any correlation between electroglottogram approximate entropy and the grade-roughness-breathiness-asthenia-strain scale. METHODS: One hundred and forty-one normal volunteers were recruited to characterise electroglottogram approximate entropy in the normal voice. One hundred and eighty-six patients with glottic squamous cell carcinoma underwent electroglottogram approximate entropy measurement prior to radiotherapy and then three to six months and one year after treatment. Subjects' voices were categorised by a speech therapist using the grade-roughness-breathiness-asthenia-strain scale. RESULTS: The mean electroglottogram approximate entropy of the normal volunteers was 0.302 (range 0.05-0.42). The mean electroglottogram approximate entropy of the glottic squamous cell carcinoma patients was significantly lower prior to treatment, at 0.227 (range 0.001-0.397; p < 0.0005), but improved after radiotherapy to 0.277 at three to six months and 0.282 at one year. Electroglottogram approximate entropy results correlated significantly with grade-roughness-breathiness-asthenia-strain scale results. CONCLUSION: Electroglottogram approximate entropy can be used to assess change in voice quality resulting from glottic morphological abnormality. Electroglottogram approximate entropy values improve as voice quality improves after treatment. Electroglottogram approximate entropy values correlate significantly with grade-roughness-breathiness-asthenia-strain scale results.

Can synchronous chemotherapy be added to accelerated hypofractionated radiotherapy in patients with base of tongue cancer?

AIM: To evaluate the tolerability of synchronous chemotherapy and accelerated hypofractionated radiotherapy in patients with locally advanced squamous cell carcinoma of the base of the tongue. MATERIALS AND METHODS: Between 1999 and 2004, 43 patients with stage II-IV squamous cell carcinoma of the base of the tongue were treated with a combined modality of radiotherapy (prescribed 55 Gy in 20 fractions), synchronous chemotherapy and in some cases surgical neck dissection. End points were acute and late toxicity, 3 year locoregional control, overall survival, cancer-specific survival and compliance. RESULTS: The median follow-up for surviving patients was 3.9 years. All patients completed radiotherapy and 30% received neoadjuvant chemotherapy. The median time for the completion of treatment was 27 days (range 25-36). Overall, only 42% completed the prescribed synchronous chemotherapy. However, compliance increased to 60% in patients who did not receive neoadjuvant chemotherapy. Grade 3 mucositis developed in 90% of patients. Prolonged grade 3 mucositis (>4 weeks) was seen in 24/43 (56%) and none developed grade 4 mucositis. There were no toxic deaths. Feeding tube dependency at 1 year was 14%. The 3 year locoregional control, overall survival and cancer-specific survival were 70, 60 and 60%, respectively. Clinical T staging was most significantly associated with poor overall survival, cancer-specific survival and local control. Distant metastases occurred in 6/43 patients (14%), 5/6 without locoregional recurrence. CONCLUSION: The addition of synchronous chemotherapy to accelerated hypofractionated radiotherapy consistently led to grade 3 mucositis. Tumour control rates compare well with published outcomes. Higher mucosal toxicity and lower synchronous chemotherapy compliance compared with other series may suggest that this approach is at the limit of patient tolerability. However, the tumour site investigated and the choice of synchronous chemotherapy agent may also be important. Compliance may be improved using intensity-modulated radiotherapy and agents that do not enhance mucosal toxicity. Longer fractionation will probably increase compliance with chemotherapy, particularly when induction is used before synchronous treatment.

Primary radiotherapy for carcinoma of the retromolar trigone: a useful alternative to surgery.

AIMS: Squamous cell carcinoma of the retromolar trigone is uncommon. The standard initial treatment is primary surgery, which usually involves microvascular reconstruction with a composite flap. Some patients are considered unsuitable for this procedure. This retrospective study examined the outcome and toxicity for patients with squamous cell carcinoma of the retromolar trigone treated with definitive radiotherapy in a single centre. MATERIALS AND METHODS: Between 1991 and 2000, 43 patients were treated with definitive radiotherapy with a median dose of 50Gy in 16 fractions over 21 days. Hospital case notes and radiotherapy records were analysed. RESULTS: The median age was 66 years (range 39-84 years). Nodal disease was evident in 13 (30.2%) patients. Twenty-one patients (51.2%) had stage I/II disease and 20 patients (48.8%) had stage III/IV disease. After a median follow-up of 59 months, 13 (30.2%) patients were alive and well, nine (20.9%) patients had died of an intercurrent illness and 21 (48.8%) had died of their disease. Five-year locoregional control was 46.5% (95% confidence interval 29.7-61.7), cause-specific survival was 45.7% (95% confidence interval 29.1-60.8) and overall survival was 30.9% (95% confidence interval 17.5-46.3). Osteoradionecrosis was documented in two patients. DISCUSSION: This hypofractionated regimen is convenient for this patient population and produced comparable outcomes to longer fractionation schedules without an increase in late toxicity.

Clinical features of oral chemotherapy: results of a longitudinal prospective study of breast and colorectal cancer patients receiving capecitabine in the UK.

The aim was to describe the clinical sequelae of patients treated with capecitabine in terms of adverse events, treatment modifications and therapy cessation throughout the treatment trajectory. A total of 1232 toxicity assessments were undertaken on colorectal and breast cancer patients receiving palliative and adjuvant treatment prior to treatment and at days 7, 14 and 21 for six cycles of chemotherapy. Most common adverse events were diarrhoea, nausea, palmar-plantar erythrodysesthesia (PPE), fatigue and pain which were experienced by over 80% of subjects. Grades 2 and 3 adverse events were common (n= 916 and n= 113) but their development into grade 4 was uncommon (n= 2). There was a downward trend in the percentage incidence of toxicity; however, PPE increased. Almost 60% of subjects completed six cycles, or planned treatment. Some 40% of subjects commenced treatment on a dose reduction (<1250 mg/m(2)), and this increased to 70% at cycle 6. In total, 2.8-11.6% of subjects experienced toxicity-related treatment deferrals. While adverse events are common with capecitabine the lack of grade 4 adverse events support the efficacy of current clinical management strategies. The deferral and dose reduction data indicate that cycles 1 and 2 are important and require careful management and clinical interventions in order to prevent high-grade adverse events.