Research-intensive cancer care in the NHS in the UK.

In the late 1990 s, in response to poor national cancer survival figures, government monies were invested to enhance recruitment to clinical cancer research. Commencing with England in 2001 and then rolling out across all four countries, a network of clinical cancer research infrastructure was created, the new staff being linked to existing clinical care structures including multi-disciplinary teams. In parallel, a UK-wide co-ordination of cancer research funders driven by the 'virtual' National Cancer Research Institute, combined to create a 'whole-system approach' linking research funders, researchers and NHS clinicians all working to the same ends. Over the next 10 years, recruitment to clinical trials and other well-designed studies, increased 4-fold, reaching 17% of the incident cancer population, the highest national rate world-wide. The additional resources led to more studies opened, and more patients recruited across the country, for all types of cancers and irrespective of additional clinical research staff in some hospitals. In 2006, a co-ordinated decision was made to increasingly focus on randomized trials, leading to increased recruitment, without any fall-off in accrual to non-randomized and observational studies. The National Cancer Research Network has supported large successful trials which are changing clinical practice in many cancers.

Strengthening clinical cancer research in the United Kingdom.

BACKGROUND: In 1999, 270,000 cases of cancer were registered in the United Kingdom, placing a large burden on the NHS. Cancer outcome data in 1999 suggested that UK survival rates were poorer than most other European countries. In the same year, a Department of Health review noted that clinical trials accrual was poor (<3.5% of incident cases) and hypothesised that increasing research activity might improve outcomes and reduce the variability of outcomes across England. Thus, the National Cancer Research Network (NCRN) was established to increase participation in cancer clinical research. METHODS: The NCRN was established in 2001 to provide a robust infrastructure for cancer clinical research and improvements in patient care. Remit of NCRN is to coordinate, support and deliver cancer clinical research through the provision of research support staff across England. The NCRN works closely with similar networks in Scotland, Wales and the Northern Ireland. A key aim of NCRN is to improve the speed of research and this was also assessed by comparing the speed of study delivery of a subset of cancer studies opening before and after NCRN was established. RESULTS: Patient recruitment increased through NCRN, with almost 32,000 (12% of annual incident cases) cancer patients being recruited each year. Study delivery has improved, with more studies meeting the recruitment target - 74% compared with 39% before NCRN was established. CONCLUSION: The coordinated approach to cancer clinical research has demonstrated increased accrual, wide participation and successful trial delivery, which should lead to improved outcomes and care.

The impact of the Calman-Hine report on the processes and outcomes of care for Yorkshire's breast cancer patients.

BACKGROUND: The 1995 Calman-Hine plan outlined radical reform of the UK's cancer services with the aim of improving outcomes and reducing inequalities in National Health Service cancer care. Its main recommendation was to concentrate care into the hands of site-specialist multidisciplinary teams. This study aimed to determine whether these teams improved processes and outcomes of care for breast cancer patients. PATIENTS AND METHODS: All patients diagnosed and treated with breast cancer in the Yorkshire region of the UK from 1995 to 2000 were identified within the Northern and Yorkshire Cancer Registry and Information Service database. Changes in the use of breast-conserving surgery, adjuvant radiotherapy following breast-conserving surgery and 5-year survival were assessed among these patients in relation to their managing breast cancer team's degree of adherence to the manual of cancer service standards (which outlines the specification of the 'ideal' breast cancer team) and the extent of site specialisation of each team's surgeons. RESULTS: Variation was observed in the extent to which the breast cancer teams in Yorkshire had conformed to the Calman-Hine recommendations. Increases in adherence to the recommendations in the manual of cancer service standards were associated with a reduction in the use of breast-conserving surgery [odds ratio (OR) = 0.83, 95% confidence interval (CI) = 0.70-0.98, P < 0.01]. Increases in both surgical specialisation (OR = 1.23, 95% CI = 1.00-1.55, P = 0.06) and adherence to the manual of cancer service standards (OR = 1.22, 95% CI = 0.97-1.52, P = 0.05) were associated with the increased use of radiotherapy following breast-conserving surgery. There was a trend towards improved 5-year survival (hazard ratio = 0.93, 95% CI = 0.86-1.01, P = 0.10) in relation to increasing surgical site specialisation. All these effects were present after adjustment for the casemix factors of age, stage of disease, socio-economic background and year of diagnosis. CONCLUSIONS: The extent of implementation of the Calman-Hine report has been variable and, on the basis of limited clinical and organisational information available, its recommendations appear to be associated with improvements in processes and outcomes of care for breast cancer patients.

Psychological distress and concerns of elderly patients treated with palliative radiotherapy for lung cancer.

We conducted a prospective observational cohort study of 83 elderly patients (aged 75 and above) being treated with palliative radiotherapy for lung cancer, with a comparison group of 49 younger patients (aged 65 and under). Psychological distress and concerns were measured before and after treatment using the Hospital Anxiety and Depression Scale (HADS) and a Concerns Checklist. Psychosocial morbidity was common, however, prevalence was similar in both age groups. There was a trend towards worsening of both anxiety and depression scores after treatment, but this did not reach statistical significance. Younger patients reported more concerns than the older group (median 12 vs 10) but this too was not statistically significant. Concerns about the illness and symptoms were more likely to have been addressed by the care team than were concerns about psychosocial issues such as the family and the future. People of all ages have similar concerns and levels of anxiety and depression whilst receiving palliative radiotherapy for lung cancer. Further research is needed to explore the use of screening tools, like those used in this study, to identify patients' difficulties and target interventions to improve their quality of life.

The impact of the Calman-Hine report on the processes and outcomes of care for Yorkshire's colorectal cancer patients.

The 1995 Calman-Hine plan outlined radical reform of the UK's cancer services with the aim of improving outcomes and reducing inequalities in NHS cancer care. Its main recommendation was to concentrate care into the hands of site-specialist, multi-disciplinary teams. This study aimed to determine if the implementation of Calman-Hine cancer teams was associated with improved processes and outcomes of care for colorectal cancer patients. The design included longitudinal survey of 13 colorectal cancer teams in Yorkshire and retrospective study of population-based data collected by the Northern and Yorkshire Cancer Registry and Information Service. The population was all colorectal cancer patients diagnosed and treated in Yorkshire between 1995 and 2000. The main outcome measures were: variations in the use of anterior resection and preoperative radiotherapy in rectal cancer, chemotherapy in Dukes stage C and D patients, and five-year survival. Using multilevel models, these outcomes were assessed in relation to measures of the extent of Calman-Hine implementation throughout the study period, namely: (i) each team's degree of adherence to the Manual of Cancer Service Standards (which outlines the specification of the 'ideal' colorectal cancer team) and (ii) the extent of site specialisation of each team's surgeons. Variation was observed in the extent to which the colorectal cancer teams in Yorkshire had conformed to the Calman-Hine recommendations. An increase in surgical site specialisation was associated with increased use of preoperative radiotherapy (OR=1.43, 95% CI=1.04-1.98, P<0.04) and anterior resection (OR=1.43, 95% CI=1.16-1.76, P<0.01) in rectal cancer patients. Increases in adherence to the Manual of Cancer Service Standards was associated with improved five-year survival after adjustment for the casemix factors of age, stage of disease, socioeconomic status and year of diagnosis, especially for colon cancer (HR=0.97, 95% CI=0.94-0.99 P<0.01). There was a similar trend of improved survival in relation to increased surgical site specialisation for rectal cancer, although the effect was not statistically significant (HR=0.93, 95% CI=0.84-1.03, P=0.15). In conclusion, the extent of implementation of the Calman-Hine report has been variable and its recommendations are associated with improvements in processes and outcomes of care for colorectal cancer patients.

Do elderly people with lung cancer benefit from palliative radiotherapy?

The median age at diagnosis of patients with lung cancer is currently around 70 and is rising, yet the trials on which treatment is based included few elderly people. We conducted a prospective observational cohort study of 83 elderly patients (aged 75 and above) being treated with palliative radiotherapy for lung cancer, with a comparison group of 49 younger patients (aged 65 and under). Response to treatment was evaluated by patient-assessed symptom and quality of life scores using the EORTC QLQ-C30 and its companion lung module LC17. This is to date the largest prospective study of elderly lung cancer patients in routine practice. We found no significant differences in response or toxicity between the two groups. Elderly people with lung cancer should be offered palliative radiotherapy the same as younger patients, with the same expectation of benefit.

The long term survival of rectal cancer patients following abdominoperineal and anterior resection: results of a population-based observational study.

AIMS: The surgical management of rectal cancer is not uniform. Both abdominoperineal (APR) and anterior resection (AR) are used in potentially curative surgery but there is no definitive evidence regarding comparative survival outcomes and no randomised controlled trials. We sought to determine if any differences in survival existed between patients who received AR or APR. In addition, we sought to determine how variations in surgical management relate to the degree of specialisation and caseload of the managing consultant. PATIENTS AND METHODS: A retrospective study of population-based data collected by the Northern and Yorkshire Cancer Registry and Information Service was undertaken. All patients (3521) diagnosed with rectal cancer in the former Yorkshire Regional Health Authority (population 3.6 million) between 1986 and 1994 who received either an APR or AR were included. Survival was assessed in relation to the surgical methods adopted. In addition, we determined whether the extent of specialisation of the managing consultant influenced the type of operation adopted. RESULTS: A Log Rank test, stratified for sex and age, showed a statistically significant 6.7% 5-year survival advantage for patients receiving AR (p=0.0064). AR was more likely to be performed by more specialist colorectal cancer surgeons (p<0.001). CONCLUSIONS: This evidence suggests that the outcomes of the two main surgical procedures used in curative surgery for rectal cancer are different and that, when possible, AR should be the operation of choice. Our results show no indication of excess risk associated with this procedure compared with APR.

Trends in postoperative radiotherapy delay and the effect on survival in breast cancer patients treated with conservation surgery.

The adequate timing of adjuvant radiotherapy (RT) in breast cancer has become a subject of increasing interest in recent years. A population-based study was undertaken to determine the influence of demographic and clinical factors on the postoperative RT delay in patients treated with breast-conserving surgery (BCS) and to assess the impact of delay on survival. In total, 7800 breast cancer patients treated with BCS and adjuvant RT between 1986 and 1998 in Yorkshire were included in the study. The median interval between surgery and the start of RT (S-RT interval) was 8 weeks (7 weeks for chemotherapy negative and 11 for chemotherapy positive patients). This interval increased substantially over time from 5 weeks during 1986-1988, irrespective of patients' chemotherapy status, to 10 and 17 weeks among chemotherapy negative and chemotherapy positive patients, respectively, in 1997-1998. The S-RT interval was also significantly influenced by travel time to RT centre, year and at which RT centre patient had the treatment (P<0.001). Overall, 5-year survival was 82%. Patients with S-RT intervals longer than 9 weeks had a trend towards an increased relative risk of death. This reached a statistical significance at 20-26 weeks (RR 1.49, 95% CI (1.16-1.92)). The findings of our study suggest that delaying the initiation of RT for 20-26 weeks after surgery is associated with decreased survival in patients treated with conservation surgery.

Breast cancer teams: the impact of constitution, new cancer workload, and methods of operation on their effectiveness.

National guidance and clinical guidelines recommended multidisciplinary teams (MDTs) for cancer services in order to bring specialists in relevant disciplines together, ensure clinical decisions are fully informed, and to coordinate care effectively. However, the effectiveness of cancer teams was not previously evaluated systematically. A random sample of 72 breast cancer teams in England was studied (548 members in six core disciplines), stratified by region and caseload. Information about team constitution, processes, effectiveness, clinical performance, and members' mental well-being was gathered using appropriate instruments. Two input variables, team workload (P=0.009) and the proportion of breast care nurses (P=0.003), positively predicted overall clinical performance in multivariate analysis using a two-stage regression model. There were significant correlations between individual team inputs, team composition variables, and clinical performance. Some disciplines consistently perceived their team's effectiveness differently from the mean. Teams with shared leadership of their clinical decision-making were most effective. The mental well-being of team members appeared significantly better than in previous studies of cancer clinicians, the NHS, and the general population. This study established that team composition, working methods, and workloads are related to measures of effectiveness, including the quality of clinical care.

Surgeon workload and survival from breast cancer.

The formation of multidisciplinary breast teams across the UK is intended to concentrate the assessment and treatment of breast cancer into the hands of high volume specialists. We undertook a retrospective population-based study in order to determine the trends in surgeon breast cancer workload in Yorkshire, UK, and to investigate whether patients treated by low-workload surgeons had poorer survival. Of 11 329 female breast cancer patients diagnosed in 1989-1994 in Yorkshire, 6% were managed by surgeons with a mean annual workload of less than 10 new patients, while surgeons with workloads of 10-29, 30-49 and >50 treated 21, 21 and 52%, respectively. Over the study period, increasing number of patients were managed by surgeons with higher workloads. Patients treated by low-workload surgeons had poorer survival. Five-year survival was 60% in the lowest workload category compared to 68% in the highest category. The relative risk of death was increased by 15% (RR=1.15, 95% CI 1.03-1.28) and by 10% (RR=1.10, 95% CI 1.02-1.18) for patients managed by surgeons with workloads <10 and 10-29 cases per annum in comparison to patients managed by surgeons with workloads of >50. The results of this study suggest increasing site specialisation in breast cancer among general surgeons. It also provides further evidence that the management of patients by surgeons with low workloads decreases overall survival.

Increased incidence of renal parenchymal carcinoma in the Northern and Yorkshire region of England, 1978-1997.

Kidney cancer remains relatively rare, but incidence and mortality rates are reported to be rising steadily across the world. To determine if such increases were occurring in the UK, we examined the rates of incidence and mortality in different histological subtypes of kidney cancer in the Northern and Yorkshire region of England. Details of all 8741 cases diagnosed between 1978 and 1997 were extracted from the population-based Northern and Yorkshire Cancer Registry. For all types of tumour, both incidence and mortality rates increased over the study period. Overall age-standardised incidence rates increased by 86% for renal parenchymal carcinoma (RPC) (80% for males, 90% for females) from 2.8 to 5.2 cases per 100000 (3.8-6.8 male, 2.0-3.8 female). There were incidence increases in all age groups, all Carstairs index groups and in both urban and rural populations. Although increased incidental detection of kidney tumours by improved investigational techniques may account for some of this rise, we believe it unlikely that it accounts for all of the increase observed. Potential aetiological causes for the increased rates include hypertension, smoking, a diet lacking fruit and vegetables, analgesic use and, particularly, obesity.

Lung cancer: district active treatment rates affect survival.

STUDY OBJECTIVE: This study investigates variation in management and treatment of lung cancer patients and determines the impact of any variation in treatment on survival. DESIGN: A retrospective study of population based data held by the Northern & Yorkshire Cancer Registry and Information Service (NYCRIS), comparing active treatment rates for lung cancer with survival by districts. SETTING The then 17 districts in Yorkshire and South Humber, England. PATIENTS: 22 654 patients registered with lung cancer between 1986 and 1994 and followed up until end of 1996. RESULTS: The overall rates of active treatment (surgery, radiotherapy, and chemotherapy) varied between districts from 37% to 56%. One year survival (with 95% CI) was significantly better in the districts with highest rates of active treatment 23% (22% to 24%) compared with 19% (17% to 20%) for those with lowest treatment rates. Non-small cell lung cancer patients (55%) in the districts with highest active treatment rates had an age adjusted relative risk of death during the follow up period, relative to risk of death in the districts with the lower treatment rates of 0.88 (0.83 to 0.92). Clinically diagnosed patients (34%) had an age adjusted RR of 0.92 (0.86 to 0.96). RR in small cell cancer (11%) was not significant. CONCLUSION: This study has shown wide variations in the rates of active treatment for lung cancer patients within districts across one large region of England. Active treatment was strongly associated with improved survival, especially in non-small cell lung cancer.

Lung cancer referral patterns in the former Yorkshire region of the UK.

The purpose of this study was to find out what proportion of patients are referred as lung cancer guidelines assume, whether different referral pathways result in different management and what proportion of patients are seen within recommended time intervals between referral and treatment. A randomly selected sample of 400 lung cancer cases registered with the former Yorkshire Cancer Registry database in 1993 was selected for casenote analysis. Mode of presentation, speciality of initial referral, treatment by specialist, time intervals for key points in the referral pathways were analyzed. A total of 362 (90.5%) of case-notes were available. Less than half of lung cancer patients (173, 47.8%) presented to hospital with a chest X-ray diagnosis of lung cancer. Forty-one (11.3%) presented as self-referrals to Accident and Emergency and the remainder were referred without a diagnosis of lung cancer by other routes, mainly via GPs. Patients who did not present initially with a lung cancer diagnosis were less likely to receive specialist care (62%:96%), or have their diagnosis histologically confirmed (57.1%:80.3%) or receive surgery or radical radiotherapy (6.9%:13.9%). Nine per cent of all 362 patients did not receive a specialist opinion. Eighty per cent of patients referred by a GP with CXR suspected lung cancer were seen at hospital within 2 weeks. Only 32.4% of those receiving active treatment were treated within 8 weeks of clinical diagnosis or first hospital visit. Lung cancer patients presenting to hospital without a suspicious CXR are less likely to have specialist care, histological confirmation of their cancer and have lower rates of active treatment (surgery, any radiotherapy or chemotherapy).

Progress in establishing non-surgical oncology within English cancer units.

In 1995 the Department of Health recommended a minimum standard of five non-surgical oncology sessions per week at Cancer Units. Postal surveys of cancer units in England were conducted in 1996 and 1999 to establish the level of provision. Substantial progress has been made from 20-60% of responding units meeting the minimum standard.

Genetic and biochemical approach for characterization of resistance to Bacillus thuringiensis toxin Cry1Ac in a field population of the diamondback moth, Plutella xylostella.

Four subpopulations of a Plutella xylostella (L.) strain from Malaysia (F(4) to F(8)) were selected with Bacillus thuringiensis subsp. kurstaki HD-1, Bacillus thuringiensis subsp. aizawai, Cry1Ab, and Cry1Ac, respectively, while a fifth subpopulation was left as unselected (UNSEL-MEL). Bioassays at F(9) found that selection with Cry1Ac, Cry1Ab, B. thuringiensis subsp. kurstaki, and B. thuringiensis subsp. aizawai gave resistance ratios of >95, 10, 7, and 3, respectively, compared with UNSEL-MEL (>10,500, 500, >100, and 26, respectively, compared with a susceptible population, ROTH). Resistance to Cry1Ac, Cry1Ab, B. thuringiensis subsp. kurstaki, and B. thuringiensis subsp. aizawai in UNSEL-MEL declined significantly by F(9). The Cry1Ac-selected population showed very little cross-resistance to Cry1Ab, B. thuringiensis subsp. kurstaki, and B. thuringiensis subsp. aizawai (5-, 1-, and 4-fold compared with UNSEL-MEL), whereas the Cry1Ab-, B. thuringiensis subsp. kurstaki-, and B. thuringiensis subsp. aizawai-selected populations showed high cross-resistance to Cry1Ac (60-, 100-, and 70-fold). The Cry1Ac-selected population was reselected (F(9) to F(13)) to give a resistance ratio of >2,400 compared with UNSEL-MEL. Binding studies with (125)I-labeled Cry1Ab and Cry1Ac revealed complete lack of binding to brush border membrane vesicles prepared from Cry1Ac-selected larvae (F(15)). Binding was also reduced, although less drastically, in the revertant population, which indicates that a modification in the common binding site of these two toxins was involved in the resistance mechanism in the original population. Reciprocal genetic crosses between Cry1Ac-reselected and ROTH insects indicated that resistance was autosomal and showed incomplete dominance. At the highest dose of Cry1Ac tested, resistance was recessive while at the lowest dose it was almost completely dominant. The F(2) progeny from a backcross of F(1) progeny with ROTH was tested with a concentration of Cry1Ac which would kill 100% of ROTH moths. Eight of the 12 families tested had 60 to 90% mortality, which indicated that more than one allele on separate loci was responsible for resistance to Cry1Ac.