Search

Background:Limited data describe patient-reported outcomes (PROs) of localised oesophageal cancer treated with definitive chemoradiotherapy(CRT). The phase 2/3 SCOPE-1 trial assessed the effectiveness of CRT±cetuximab. The trial for the first time provided an opportunity to describe PROs from a multi-centre group of patients treated with CRT that are presented here.Methods:Patients undergoing CRT±cetuximab within the SCOPE-1 trial (258 patients from 36 UK centres) completed generic-, disease- and treatment-specific health-related quality of life (HRQL) questionnaires (EORTC QLQ-C30, QLQ-OES18, Dermatology Life-Quality Index (DLQI)) at baseline and at 7, 13, 24, 52 and 104 weeks. Mean EORTC functional scale scores (>15 point change significant), DLQI scores (>4 point change significant) and proportions of patients (>15% significant) with 'minimal' or 'severe' symptoms are presented.Results:Questionnaire response rates were good. At baseline, EORTC functional scores were high (>75%) and few symptoms were reported except for severe problems with fatigue, insomnia and eating-related symptoms (e.g., appetite loss, dysphagia, dry mouth) in both groups(>15%). Functional aspects of health deteriorated and symptoms increased with treatment and by week 13 global quality of life, physical, role and social function significantly deteriorated and more problems with fatigue, dyspnoea, appetite loss and trouble with taste were reported. Recovery occurred by 6 months (except severe fatigue and insomnia in >15% of patients) and maintained at follow-up with no differences between groups.Conclusions:CRT for localised oesophageal cancer has a significant detrimental impact on many aspects of HRQL; however, recovery is achieved by 6 months and maintained with the exception of persisting problems with severe fatigue and insomnia. The data suggest that the HRQL recovery after definitive CRT is quicker, and there is little lasting deficit compared with treatment including surgery. These data need to be compared with HRQL data from studies evaluating treatments including surgery for oesophageal cancer. [ABSTRACT FROM AUTHOR]

Background:The optimal treatment for localised oesophageal squamous cell carcinoma (SCC) is uncertain. We assessed the feasibility of an RCT comparing neoadjuvant treatment and surgery with definitive chemoradiotherapy.Methods:A feasibility RCT in three centres examined incident patients and reasons for ineligibility using multi-disciplinary team meeting records. Eligible patients were offered participation in the RCT with integrated qualitative research involving audio-recorded recruitment appointments and interviews with patients to inform recruitment training for staff.Results:Of 375 patients with oesophageal SCC, 42 (11.2%) were eligible. Reasons for eligibility varied between centres, with significantly differing proportions of patients excluded because of total tumour length (P=0.002). Analyses of audio-recordings and patient interviews showed that recruiters had challenges articulating the trial design in simple terms, balancing treatment arms and explaining the need for randomisation. Before analyses of the qualitative data and recruiter training no patients were randomised. Following training in one centre 5 of 16 eligible patients were randomised.Conclusions:An RCT of surgical vs non-surgical treatment for SCC of the oesophagus is not feasible in the UK alone because of the low number of incident eligible patients. A trial comparing diverse treatment approaches may be possible with investment to support the recruitment process. [ABSTRACT FROM AUTHOR]

Background:Women treated with supradiaphragmatic radiotherapy (sRT) for Hodgkin lymphoma (HL) at young ages have a substantially increased breast cancer risk. Little is known about how menarcheal and reproductive factors modify this risk.Methods:We examined the effects of menarcheal age, pregnancy, and menopausal age on breast cancer risk following sRT in case-control data from questionnaires completed by 2497 women from a cohort of 5002 treated with sRT for HL at ages <36 during 1956-2003.Results:Two-hundred and sixty women had been diagnosed with breast cancer. Breast cancer risk was significantly increased in patients treated within 6 months of menarche (odds ratio (OR) 5.52, 95% confidence interval (CI) (1.97-15.46)), and increased significantly with proximity of sRT to menarche (Ptrend<0.001). It was greatest when sRT was close to a late menarche, but based on small numbers and needing reexamination elsewhere. Risk was not significantly affected by full-term pregnancies before or after treatment. Risk was significantly reduced by early menopause (OR 0.55, 95% CI (0.35-0.85)), and increased with number of premenopausal years after treatment (Ptrend=0.003).Conclusion:In summary, this paper shows for the first time that sRT close to menarche substantially increases breast cancer risk. Careful consideration should be given to follow-up of these women, and to measures that might reduce their future breast cancer risk. [ABSTRACT FROM AUTHOR]

Three hundred patients with symptomatic, locally advanced or metastatic NSCLC not requiring immediate radiotherapy were enrolled into this randomized multicentre trial comparing gemcitabine + BSC vs BSC alone. Patients allocated gemcitabine received 1000 mg/m[SUP2] on days 1, 8 and 15 of a 28-day cycle, for a maximum of six cycles. The main aim of this trial was to compare patient assessment of a predefined subset of commonly reported symptoms (SS14) from the EORTC QLQ-C30 and LC13 scales. The primary end-points were defined as (1) the percentage change in mean SS14 score between baseline and 2 months and (2) the proportion of patients with a marked (≥ 25%) improvement in SS14 score between baseline and 2 months sustained for ≥4 weeks. The secondary objectives were to compare treatments with respect to overall survival, and multidimensional QL parameters. The treatment groups were balanced with regard to age, gender, Karnofsky performance status (KPS) and disease stage (40% had metastatic disease). The percentage change in mean SS14 score from baseline to 2 months was a 10% decrease (i.e. improvement) for gemcitabine plus BSC and a 1% increase (i.e. deterioration) for BSC alone (P = 0.113, two-samplet-test). A sustained (≥ 4 weeks) improvement (≥25%) on SS14 was recorded in a significantly higher proportion of gemcitabine + BSC patients (22%) than in BSC alone patients (9%) (P = 0.0014, Pearson's chi-squared test). The QLQ-C30 and L13 subscales showed greater improvement in the gemcitabine plus BSC arm (in 11 domains) than in the BSC arm (one symptom item). There was greater deterioration in the BSC alone arm (six domains/items) than in the gemcitabine + BSC arm (three QL domains). Tumour response occurred in 19% (95% CI 13-27) of gemcitabine patients. There was no difference in overall survival: median 5.7 months (95% CI 4.6-7.6) for gemcitabine + BSC patients and 5.9 months (95% CI 5.0-7.9) (log-rank, P = 0.84) for BSC patients, and 1-year... [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article about the trial of minimally invasive versus open oesophagectomy in an issue.

Multidisciplinary cancer teams offer many theoretical benefits, although few have been formally examined. This study evaluated the role of multidisciplinary team (MDT) meetings in recruitment into randomised controlled trials (RCTs). Consecutive MDT patient records were categorised into those with or without a recommendation for a national multicentre RCT. Clinical trial office records identified whether patients were subsequently screened and randomised. In 125 MDT meetings, 350 new patients were discussed, of whom 103 were potentially suitable for a RCT. The MDT recommended 68 patients for the trial, of whom 58 (85%) were screened for trial eligibility. Of the 35 without an MDT trial recommendation, only 23 (66%) were screened (p=0.022). This difference persisted and resulted in a greater proportion of MDT recommended patients being recruited (65% versus 49%; p=0.12). This study demonstrates that trial recommendation by an MDT significantly increases trial screening rates and may improve recruitment.

Thirty-two patients prospectively identified as having poor prognosis high grade glioma, with a MRC prognostic score >25, were treated with a short palliative course of radiotherapy. A total dose of 36 Gy in 12 fractions was given to the tumour, including oedema and a 2 cm margin, using parallel pair fields prescribed to the midplane with MV photons. Twenty-eight patients completed treatment as planned, while four failed to complete treatment because of clinical deterioration or death. The median survival for the whole group was 16 weeks, with seven patients surviving for more than 6 months. Approximately two-thirds of the surviving patients remained at home after the completion of treatment. A matched case-control comparison with data from patients in previous MRC studies who had received a 6-week course of treatment shows that, for this group of patients, survival is similar (hazard ratio 1.0; 95% confidence interval (CI) 0.57-1.74). The 95% CI for the difference in median survival time excludes a reduction of more than 7 weeks with the 36 Gy course. This shortened radiotherapy regimen may therefore be satisfactory for most poor prognosis patients. However, patients with performance status 3 gained little benefit from treatment, and it is suggested that this group should have a trial period of assessment at home prior to a decision on treatment.

The effects of escalating doses of BW12C on normal tissue and tumour blood flow and pO2 in patients were studied. BW12C infusion resulted in a significant reduction in median subcutaneous tissue pO2, and an increase in the proportion of hypoxic values (< or = 2.5 mmHg). In 8 of 9 patients with accessible tumours there was a significant reduction in pO2 during BW12C infusion, but no effect on the proportion of hypoxic values. A rapid decline in normal tissue pO2 in the first 10 min was associated with an increase in skin red cell flux and a reduction of normal subcutaneous tissue, muscle, and tumour red cell flux of 30-50%, that was maintained throughout a subsequent 1-h infusion of BW12C. Tumour perfusion, as measured by dynamic computed tomography, was slightly reduced in five out of six patients studied during BW12C infusion. BW12C reduces both subcutaneous tissue and tumour pO2 in patients. Both haemoglobin modification and reduction in blood flow are probably associated with this effect.

A total of 25 patients with small cell lung cancer (SCLC) were treated with carboplatin and Adriamycin (CA) following symptomatic relapse after initial therapy, or because of static or progressive disease during primary treatment. Nine patients had disease within the thorax, and 16 had extensive metastases at relapse. The overall response rate to CA was 64% (20% complete response: CR; 44% partial response: PR). Survival from presentation in 22 of the patients who have died was 6-36 months (median 13 months), and the median survival from the commencement of CA was 23 weeks (range 1 week-11.5 months). The duration of CR was 4-8 months, and of PR 2-7 months. Hospital admission was required following 12% of cycles for management of the complications of treatment. The increasing use of first line regimens of short duration means that reassessment should be made of the activity of further therapy at relapse.

The effect of combining the oxyhemoglobin-modifying drug BW12C with mitomycin C was investigated in a Phase I study of 18 patients with advanced gastrointestinal cancer. The dose of BW12C was increased from 20 mg/kg to 50 mg/kg to modify the hemoglobin-oxygen saturation curve by up to 48%. The period of maximum modification was then prolonged for up to 3 hr by a maintenance infusion of 4-6 mg/kg/hr. Pharmacokinetics of BW12C and mitomycin C were performed in all patients. Peak levels of BW12C increased from 139 micrograms/ml to 378 micrograms/ml. Plasma half life was independent of dose, with an average of 3.3 hr. BW12C was well tolerated with no severe side effects. Three patients had objective tumour responses.