Surgical management and outcomes of colorectal cancer liver metastases.

BACKGROUND: This population-based study investigated the frequency of hepatic resections for colorectal cancer metastases across England and their outcome. METHODS: Individuals who underwent surgery for colorectal cancer between January 1998 and June 2004 within the English National Health Service were identified via the National Cancer Data Repository. All episodes of care in the 3 years after the initial operation were examined to determine the frequency of liver resection. Variations in the use of liver resection and survival were assessed. RESULTS: Some 114 155 individuals underwent surgery for colorectal cancer over the study period, of whom 3116 (2.7 per cent) subsequently had one or more hepatic resections. The hepatectomy rate increased from 1.7 per cent in 1998 to 3.8 per cent in 2004. There was significant variation in the rate of liver resection across cancer networks (range 1.1-4.3 per cent) and hospitals (range 0.7-6.8 per cent). The crude 5-year survival rate after liver resection was 44.2 (95 per cent confidence interval (c.i.) 42.4 to 46.1) per cent from the time of hepatectomy and 45.9 (95 per cent c.i. 44.1 to 47.7) per cent from the time of colectomy. This was comparable to the 5-year survival rate of patients with stage III disease (42.2 (95 per cent c.i. 41.7 to 42.7) per cent). CONCLUSION: The rate of resection of liver metastases increased over the study period but varied significantly across the country. Patients who underwent liver resection had 5-year survival comparable to that of patients with stage III colorectal cancer.

Unacceptable variation in abdominoperineal excision rates for rectal cancer: time to intervene?

OBJECTIVE: To determine the variation in the rates of use of abdominoperineal excision (APE) by cancer network, hospital trust and surgeon across England between 1998 and 2004 and determine if any variation could be explained by differences in patient characteristics such as stage of disease, age, gender or socioeconomic deprivation. DESIGN: Retrospective study of a population-based dataset comprised of cancer registry and hospital episode statistics data. SETTING: All NHS providers of rectal cancer surgery within England. PATIENTS: 31,223 patients diagnosed with rectal cancer and receiving a major abdominal procedure within the NHS in England between 1998 and 2004. MAIN OUTCOME MEASURE: Rates and odds of use of APE were determined in relation to patient case-mix and each patient's managing surgeon, trust and cancer network. RESULTS: The rate of use of APE decreased from 30.5% in 1998 to 23.0% in 2004. Males, the economically deprived and those managed by surgeons operating on fewer than seven rectal cancer cases per year were all significantly more likely to receive an APE. There were also significant variations in the odds of receiving an APE over time and between individual surgeons and hospital trusts independently of patient case-mix. CONCLUSIONS: Over the study period the use of APE decreased but statistically significant variation was observed in its application independently of case mix. Reducing this variation will remove inequalities, reduce colostomy rates, and improve outcomes in rectal cancer. Rates of APE use could be a national performance measure.

The management of interruptions to radiotherapy in head and neck cancer: an audit of the effectiveness of national guidelines.

AIMS: To re-audit national radiotherapy practice in head and neck cancer to assess the effect of new guidelines. MATERIALS AND METHODS: A two-part electronic audit assessing departmental policies and the management of interruptions was carried out from April to June 2005. All patients commencing treatment within this audit period were eligible for assessment. The outcome measures were: frequency and causes of interruptions to therapy; policy and compliance with policy for managing interruptions; prolongation; time between first visit to clinic and start of treatment. RESULTS: Forty-eight out of 57 centres returned data on 631 patients. Overall, 397/631 (63%) patients had one or more treatment interruptions. The causes of interruptions were generally the same as the 2002 audit. Of interrupted cases, 88% completed treatment within 1 day of the target. This is a major improvement on 62% within 1 day in the 2002 audit. Overall, 92% of all cases completed treatment within 1 day of the target and 95% within 2 days in the 2005 audit. There was also an improvement in waiting times; 52% of patients started treatment within the target of 4 weeks compared with 41% from the 2002 data. CONCLUSIONS: There has been an improvement in the radiotherapy service for head and neck cancer patients with better management of gaps in treatment. Waiting times for radical radiotherapy have shortened, but remain unacceptable.

Patterns of care for brachytherapy in Europe. Results in Spain.

INTRODUCTION: In 2003 ESTRO began a project whose primary objective, was to make a map in the European area of infrastructures in technology and personnel for brachytherapy. MATERIAL AND METHOD: A survey and a web site were elaborated. The survey was sent to the 76 Spanish Radiation Oncology departments in May 2003. RESULTS: By the end of 2003, 66 (86.8%) services had responded, 40 (71.4%) of which had brachytherapy. The services with brachytherapy treated 73.5% of the total patients, an average of 1,199 patients. The mean number of patients treated with brachytherapy by department was 135.5 and the number of applications was 265 annually. The average number of specialists was 7, 4 of them trained in brachytherapy. The average weekly work load of the radiation oncologists, physicists, and technicians was 22.6 h, 13.8 h and 21.0 h, respectively. The mean time dedicated to each patient by radiation oncologists, physicists and technicians was 9.2 h; 6.19 h; 7.2 h, respectively. The total number of afterloaders was 43 (22 HDR, 18 LDR, 3 PDR). The tumours most frequently treated with brachytherapy were gynaecological (56.24%), breast (14.2%) and prostate (11.7%). High dose rate was used in 47.46% of the patients and low dose rate in 47.24%. Between 1997 and 2002 there was an increase of 50.53% in patients treated with brachytherapy. CONCLUSIONS: The survey shows the brachytherapy resources and activity in Spain up to 2003. Increased use of brachytherapy in prostate tumours, prevalence of gynaecology brachytherapy and similar number of treatments with HDR and LDR are demonstrated in the Patterns of Care of Brachytherapy in Europe (PCBE) study in Spain.

Preliminary analysis of the resources in brachytherapy in Europe and its variability of use.

PURPOSE: The main objective of the program <> is to establish a group with detailed information on brachytherapy throughout Europe. METHODS: The data was compiled by the general coordinator, the ESTRO, and the <> through a website. RESULTS: A total of 32 countries reported data from at least 50% of their centres (criteria of inclusion). Countries were grouped in three categories based on the time of incorporation to the European Union. The majority of treatments belonged to gynaecological tumours. A large spread was found regarding workload of specialists depending on centre and group. CONCLUSION: Collection of information by a website is a feasible methodology. An increase in brachytherapy treatment was observed in all 3 groups by a rate of more than 20% (year 2002 versus year 1997). These results advocate for the continuation of the PCBE study to demonstrate the development in the field, such as an increase or decrease of patient numbers per tumour category.

Activity of gemcitabine in patients with non-small cell lung cancer: a multicentre, extended phase II study.

Gemcitabine is a novel nucleoside analogue with activity in solid tumours. This study assessed the objective response rate to gemcitabine given weekly intravenously at a dose of 1250 mg/m2 for 3 weeks followed by 1 week of rest (one cycle) in chemonaive patients with inoperable non-small cell lung cancer (NSCLC). 161 patients with NSCLC were recruited from 10 sites in nine countries. Most patients had stage IIIb (31.3%) or IV (64.6%) disease, and 93.8% had a performance status of 0 or 1 according to the WHO scale. Of 151 evaluable patients, there were 3 complete responses and 30 partial responses lasting at least 4 weeks for an objective response rate of 21.8% (95% CI 15.5-29.3%). All responses were validated by an extramural Oncology Review Board. The mean duration of response was 8.8 months. The mean survival for all patients (16.1% of patients still alive 26 months after last patient started treatment) was 11.5 months. Improvements were also observed in secondary efficacy parameters such as performance status, weight, analgesic requirement, pain, and other disease-related symptoms including cough, dyspnoea, haemoptysis, anorexia, somnolence and hoarseness. Haematological and non-haematological toxicity was mild given the biological activity of gemcitabine. This study confirms gemcitabine as one of the most active agents in NSCLC with the added benefit of a modest toxicity profile and ease of administration on an out-patient basis. Gemcitabine is a suitable candidate for combination chemotherapy in patients with NSCLC.

The activity of 10-, 14-, and 21-day schedules of single-agent etoposide in previously untreated patients with extensive small cell lung cancer.

Pharmacologic studies in patients with small cell lung cancer treated with differing schedules of intravenous etoposide over 1 to 8 days have suggested that etoposide's antitumor cytotoxicity is related to duration of exposure to low plasma levels of drug. Three phase II studies have been performed in 78 patients with extensive small cell lung cancer examining the efficacy and toxicity of 50-mg doses of oral etoposide given twice daily for 14 days every 3 weeks, once daily for 21 days every 4 weeks, and twice daily for 10 days every 3 weeks. Partial response rates were observed in 76%, 52%, and 70% of patients, respectively. Median response duration appeared similar in all three schedules, but the time to achieve a response appeared longer in the 21-day, once-daily schedule. Bone marrow toxicity was generally mild, but occasionally severe nadir blood counts were observed. These studies demonstrate that prolonged administration of low-dose oral etoposide is very active in small cell lung cancer, and that a twice-daily regimen is preferable in view of the greater rapidity of response and possibly higher response rate. The optimal duration of a twice-daily, 50-mg dosage schedule remains to be determined.

The achievement of isoeffective bronchial mucosal dose during endobronchial brachytherapy.

PURPOSE: The use of endobronchial brachytherapy in the treatment of lung cancer is increasing due to the more widespread availability of high dose rate afterloading equipment. The complications include small airway (segmental and small lobar bronchi) fibrosis, stenosis, and obstructive complications in addition to hemorrhage. A progressive reduction in the diameter of the bronchial lumen occurs at each division of the bronchial tree. If uniform dwell times along a bronchial catheter treatment length are used, this will result in higher doses being given to the bronchial mucosa in the distal part of the treatment volume where the brachytherapy source mucosa distances are smaller, and underdosage proximally, where the source mucosa distances are larger. METHODS AND MATERIALS: The known mathematical relationships of the sequential reductions in the diameter of the bronchial lumen have been incorporated into two methods of optimization, which have been compared to uniform dwell times along a treatment length from trachea to segmental bronchus. RESULTS: The resulting isodose plots are presented, and demonstrate the extent of the overdosage distally, and the underdosage proximally when using uniform dwell times, and the achievement of isoeffective mucosal doses when using differential dwell times. CONCLUSION: This refinement in brachytherapy technique offers the potential for reduced normal tissue complications and possibly improved tumor control by reducing overdosage and underdosage, respectively.

Indicators of free radical activity in patients developing radiation pneumonitis.

PURPOSE: Radiation pneumonitis is thought to occur as the result of excess free radical generation following radiotherapy. Various in vitro studies have shown that large doses of irradiation can cause membrane lipid peroxidation and the oxidation of protein sulphuryl groups. We, therefore, studied two circulating markers of lipid peroxidation and an indicator of "catalytic iron" (potentially available iron to catalyze the generation of free radicals) in patients undergoing radiotherapy. METHODS AND MATERIALS: The 9,11 diene conjugate of 9,12 linoleic acid, expressed as their molar ratio (percentage molar ratio (MR)) and thiobarbituric acid reactive acid-substances (TBARS), as well as levels of circulating desferrioxamine-chelatable iron assay, were assayed. Serial blood samples were taken over a 3-month period in 25 patients with inoperable nonsmall cell lung cancer. RESULTS: Ten patients developed radiation pneumonitis. The patients who developed pneumonitis showed a tendency for the serum percentage molar ratio to increase after a week. The change in the percentage molar ratio between Time 0 and 1 week of radiotherapy was significantly higher in the group that subsequently developed pneumonitis compared to the group that did not (p = 0.002). The initial serum TBARS levels in patients were not significantly elevated compared to controls and there was no difference in the serum TBARS levels in the pneumonitis and nonpneumonitis groups throughout the study period. After 1 week of radiotherapy the group that subsequently developed pneumonitis had a significantly higher level of desferrioxamine-chelatable iron (DFx-iron) compared with the nonpneumonitis group (p = 0.05). CONCLUSION: These data suggest that both the percentage MR and DFx-iron appear to reflect an increased susceptibility to develop radiation pneumonitis and after 1 week of radiotherapy they indicate patients who are likely to subsequently develop pneumonitis. Hence, these indicators could indicate the group of patients that could benefit from intervention therapies with antioxidants.

A national audit of radiotherapy in head and neck cancer.

AIMS: To undertake a national audit of radiotherapy practice in head and neck cancer to estimate compliance with published guidelines and national standards. METHODS: A two-part electronic data entry form was distributed to all U.K. radiotherapy centres in September 2000. The first part examined the centres' policies for managing interruptions, the second collected summaries of the management of 50 consecutive patients treated in each centre for head and neck cancer. The outcome measures were: frequency and causes of interruptions to therapy: policy and compliance with policy for managing interruptions; prolongation; and time between first visit to clinic and start of treatment. RESULTS: Fifty-five out of 56 centres returned data on a total of 2553 patients. Overall, 1467 (55%) patients had one or more treatment interruptions. Of patients whose treatment was interrupted, 56% still completed on time due to compensatory steps, but in 32% no attempted compensation was undertaken. Seven centres had no policy for dealing with treatment interruptions. Centres whose policies included treatment on bank (public) holidays achieved higher compliance and fewer prolonged cases than those whose policies did not. Average time from first visit to head and neck oncology clinic to starting radiotherapy was 40 days; six centres had an average wait of less than 28 days. CONCLUSIONS: This audit demonstrates wide variations in the quality of care between centres, failure to comply with guidelines for compensation for gaps and failure to meet national targets (for waiting times) that have serious implications both for patient outcomes and for the success of the National Cancer Plan.

[A phase II multicenter study of gemcitabine in non small cell lung cancers]. / Etude multicentrique de phase II de la gemcitabine dans les cancers bronchiques non à petites cellules (CBNPC).

Gemcitabine is a novel pyrimidine nucleoside whose activity has been demonstrated on solid tumors. We report here the results of a multicentre phase II trial of gemcitabine in chemonaive patients with inoperable non small cell lung cancer (NSCLC). Gemcitabine was given weekly at a dose of 1,250 mg/m2 administered as a 30 min intravenous infusion, for 3 weeks followed by 1 week of rest (1 cycle). All the 161 patients included were evaluable for toxicity and 151 of them were evaluable for efficacy. The majority of patients had a stage IIIb (31.1%) or stage IV (64.6%) disease; 10.6%, 83.2% and 6.2% of patients had a WHO performance status (PS) 0, 1, and 2, respectively. Adenocarcinoma accounted for 52.2% of cases and squamous cell carcinoma for 43.5% of cases. Three complete responses and 30 partial responses gave an objective response (OR) rate of 21.8% (95% confidence interval; 15.5-29.3%). All responses were validated by an independent Oncology Review Board. Median duration of response was 7.6 months. Median time to progression was 4.6 months (3.3 months in non responders and 7.6 months in responders). Median survival was 7.3 months in non responders and 13.4 months in responders (p < 0.001), which gave an overall median survival of 8.9 months (95% CI: 0.1-21.9 months) in the entire study population. An improvement of symptoms and personal state was also observed. Treatment was well tolerated. Neutropenia was the only dose limiting toxicity. WHO grade 3 or 4 neutropenia occurred in 19.6% and 5.7% of patients, respectively. With a 21.8% OR rate, this multicentre study confirms the activity of gemcitabine as a single agent in patients with inoperable NSCLC. Its good tolerance and original mode of action make gemcitabine a drug of choice in the therapeutic strategy of these tumors.

Gemcitabine plus best supportive care (BSC) vs BSC in inoperable non-small cell lung cancer--a randomized trial with quality of life as the primary outcome. UK NSCLC Gemcitabine Group. Non-Small Cell Lung Cancer.

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/m2 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 (> or = 25%) improvement in SS14 score between baseline and 2 months sustained for > or =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-sample t-test). A sustained (> or = 4 weeks) improvement (> or =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 survival was 25% for gemcitabine + BSC and 22% for BSC. Overall, 74 (49%) gemcitabine + BSC patients and 119 (79%) BSC patients received palliative radiotherapy. The median time to radiotherapy was 29 weeks for gemcitabine + BSC patients and 3.8 weeks for BSC. Patients treated with gemcitabine + BSC reported better QL and reduced disease-related symptoms compared with those receiving BSC alone. These improvements in patient-assessed QL were significant in magnitude and were sustained.