Cost-effectiveness analysis of PET-CT-guided management for locally advanced head and neck cancer.

BACKGROUND: A recent large United Kingdom (UK) clinical trial demonstrated that positron-emission tomography-computed tomography (PET-CT)-guided administration of neck dissection (ND) in patients with advanced head and neck cancer after primary chemo-radiotherapy treatment produces similar survival outcomes to planned ND (standard care) and is cost-effective over a short-term horizon. Further assessment of long-term outcomes is required to inform a robust adoption decision. Here we present results of a lifetime cost-effectiveness analysis of PET-CT-guided management from a UK secondary care perspective. METHODS: Initial 6-month cost and health outcomes were derived from trial data; subsequent incidence of recurrence and mortality was simulated using a de novo Markov model. Health benefit was measured in quality-adjusted life years (QALYs) and costs reported in 2015 British pounds. Model parameters were derived from trial data and published literature. Sensitivity analyses were conducted to assess the impact of uncertainty and broader National Health Service (NHS) and personal social services (PSS) costs on the results. RESULTS: PET-CT management produced an average per-person lifetime cost saving of £1485 and an additional 0.13 QALYs. At a £20,000 willingness-to-pay per additional QALY threshold, there was a 75% probability that PET-CT was cost-effective, and the results remained cost-effective over the majority of sensitivity analyses. When adopting a broader NHS and PSS perspective, PET-CT management produced an average saving of £700 and had an 81% probability of being cost-effective. CONCLUSIONS: This analysis indicates that PET-CT-guided management is cost-effective in the long-term and supports the case for wide-scale adoption.

Tetraspanins CD9 and CD151, epidermal growth factor receptor and cyclooxygenase-2 expression predict malignant progression in oral epithelial dysplasia.

BACKGROUND: Prognostic biomarkers aim to improve on the current inadequate method of histological assessment to identify patients with oral epithelial dysplasia at greatest risk of malignant transformation. We aimed to assess the prognostic ability of six protein biomarkers linked to the epidermal growth factor receptor (EGFR) pathway, including three tetraspanins, in a large multicentre oral dysplasia cohort. METHODS: One hundred and forty-eight cases with varying degrees of epithelial dysplasia underwent immunohistochemical assessment for CD9, CD151, CD82, EGFR, Her-2, and COX-2. Scoring was performed independently by two observers. Univariate analyses using both logistic and Cox regression models and a multivariate regression were performed. RESULTS: Malignant progression was significantly greater in those cases with decreased expression of CD9 (P=0.02), and increased expression of CD151 (P=0.02), EGFR (P=0.04), and COX-2 (P=0.003). Histological grade (P=0.0002) and morphology (P=0.03) were also prognostic, whereas smoking and alcohol were not. The optimal combination by backward-variable selection was of histological grade (hazard ratio (HR) 1.64; 95% CI 1.12, 2.40), COX-2 overexpression (HR 1.12; 1.02, 1.24) and CD9 underexpression (HR 0.88; 0.80, 0.97). CD82 and Her-2 demonstrated no prognostic ability. CONCLUSION: This is the first study of the expression and prognostic potential of the tetraspanins in oral dysplasia. A combination of certain biomarkers with clinical factors appeared to improve the accuracy of determining the risk of malignancy in individuals with oral dysplasia. These findings may also offer potential new therapeutic approaches for this condition.

The proportion of tumor-stroma as a strong prognosticator for stage II and III colon cancer patients: validation in the VICTOR trial.

BACKGROUND: The intra-tumor stroma percentage in colon cancer (CC) patients has previously been reported by our group as a strong independent prognostic parameter. Patients with a high stroma percentage within the primary tumor have a poor prognosis. PATIENTS AND METHODS: Tissue samples from the most invasive part of the primary tumor of 710 patients (52% Stage II, 48% Stage III) participating in the VICTOR trial were analyzed for their tumor-stroma percentage. Stroma-high (>50%) and stroma-low (≤50%) groups were evaluated with respect to survival times. RESULTS: Overall and disease-free survival times (OS and DFS) were significantly lower in the stroma-high group (OS P<0.0001, hazard ratio (HR)=1.96; DFS P<0.0001, HR=2.15). The 5-year OS was 69.0% versus 83.4% and DFS 58.6% versus 77.3% for stroma-high versus stroma-low patients. CONCLUSION: This study confirms the intra-tumor stroma ratio as a prognostic factor. This parameter could be a valuable and low cost addition to the TNM status and next to current high-risk parameters such as microsatellite instability status used in routine pathology reporting. When adding the stroma-parameter to the ASCO criteria, the rate of 'undertreated' patients dropped from 5.9% to 4.3%, the 'overtreated' increased with 6.8% but the correctly classified increased with an additional 14%.

Hypofractionated accelerated radiotherapy with concurrent carboplatin for locally advanced squamous cell carcinoma of the head and neck.

AIMS: Hypofractionated accelerated radiotherapy with concurrent carboplatin utilises both advantages of altered fractionation and synchronous chemotherapy to maximise local control in locally advanced head and neck cancer. Such fractionation schedules are increasingly used in the intensity-modulated radiotherapy era and the aim of this study was to determine the outcome of hypofractionated accelerated radiotherapy with carboplatin. MATERIALS AND METHODS: One hundred and fifty consecutive patients with squamous cell carcinoma of the larynx, oropharynx, oral cavity and hypopharynx (International Union Against Cancer [IUAC] stage II-IV) treated with 55Gy in 20 fractions over 25 days with concurrent carboplatin were analysed. Outcome measures were 2 year overall survival, local control and disease-free survival. RESULTS: The median follow-up in surviving patients was 25 months. IUAC stages: II n=15; III n=42; IV n=93. Two year overall survival for all patients was 74.9% (95% confidence interval 66.0-81.7%). Two year local control was 78.3% (95% confidence interval 69.6-84.8%). Two year disease-free survival was 67.2% (95% confidence interval 58.3-74.7%). There were 135 patients with stage III and IV disease. For these patients, the 2 year overall survival, local control and disease-free survival were 74.3% (95% confidence interval 64.7-81.6%), 79.1% (95% confidence interval 69.8-85.9%) and 67.6% (95% confidence interval 58.0-75.4%), respectively. Prolonged grade 3 and 4 mucositis seen at ≥4 weeks were present in 9 and 0.7%, respectively. Late feeding dysfunction (determined by dependence on a feeding tube at 1 year) was seen in 13% of the surviving patients at 1 year. CONCLUSION: Hypofractionated accelerated radiotherapy with concurrent carboplatin achieves a high local control. This regimen should be considered for a radiotherapy dose-escalation study using intensity-modulated radiotherapy.

Correlation of currently used radiobiological parameters with local control and acute and late mucosal toxicity in randomised studies of altered fractionation for locally advanced head and neck cancer.

AIMS: There has been a resurgence in interest in radiobiological modelling in head and neck cancer. The aim of this study was to determine if currently used parameters accurately predict both tumour and toxicity outcomes. MATERIALS AND METHODS: Trials were identified from a recent meta-analysis of altered fractionation. The tumour biologically effective dose (tBED; α/ß=10Gy, t(k) [onset time of accelerated repopulation]=22 days, t(p) [average doubling time during accelerated repopulation]=3 days, α=0.3Gy(-1)), acute mucosal biologically effective dose (amBED; α/ß=10Gy, t(k)=7 days, t(p)=2.5 days, α=0.3Gy(-1)) and late mucosal biologically effective dose (lmBED; α/ß=3Gy) were calculated for each arm of each trial. The correlation between the absolute percentage difference in BED between treatment arms and the observed percentage difference in local control, acute grade 3 mucositis and late grade 3 mucosal reaction was then assessed. RESULTS: A strong correlation was observed between the percentage difference in tBED and the percentage difference in local control (P=0.006). A trend towards a correlation was seen between the percentage difference in amBED and the percentage difference in acute grade 3 mucositis (P=0.06). A significant correlation was observed between the percentage difference in lmBED and the percentage difference in grade 3 late mucosal toxicity (P=0.02). However, a 15% decrease in lmBED between control and experimental arms of the study was necessary for any sparing of late mucosal toxicity to be observed. CONCLUSIONS: Currently used parameters for tumour accurately predict outcomes in randomised trials of altered fractionation. Although the relationship may be more complex for late mucosal reaction, the presence of a correlation is noteworthy given the infrequent reporting or occurrence of this toxicity. In the future, radiobiological modelling with the addition of volumetric parameters will be highly relevant, given attempts to dose escalate with intensity-modulated radiotherapy in poor risk patients and de-escalate in patients with an excellent prognosis.

The risk and interval to malignancy of patients with laryngeal dysplasia; a systematic review of case series and meta-analysis.

BACKGROUND: Laryngeal dysplasia is a pre-malignant condition with wide variability in rates of malignant transformation reported in the literature. The management and follow-up strategies of these lesions vary widely. OBJECTIVES: To assess the risk of and interval to malignant transformation in patients with laryngeal dysplasia, the effect of different treatment modalities on malignant transformation and the effects that risk factors such as smoking, excessive alcohol intake and histological grade may have on this. TYPE OF REVIEW: Systematic of observational studies with attempted meta-analysis. SEARCH STRATEGY: A structured search of Medline (1966 to January 2010), EMBASE (1980 to January 2010), CINAHL (1981 to January 2010) and Cochrane databases (CENTRAL, Cochrane Library, 1995 to January 2010). RESULTS: Nine hundred and forty cases from nine studies were included in the analysis. Overall malignant transformation rate was 14% (confidence interval 8, 22) and mean time to malignant transformation was 5.8 years. The malignant transformation rate is higher with increased severity of dysplasia grade - severe/CIS 30.4%versus mild/moderate 10.6% (P < 0.0002). Treatment modality did not show significant effects. CONCLUSIONS: Laryngeal dysplasia carries a significant risk of malignant transformation. This risk triples with increasing severity of dysplasia. Transformation often occurs late and is not related to the grade of dysplasia. There is little evidence, therefore, to support the early discharge of patients with mild/moderate dysplasia, which is practised by some clinicians.

Radiobiological modelling of the therapeutic ratio for the addition of synchronous chemotherapy to radiotherapy in locally advanced squamous cell carcinoma of the head and neck.

AIMS: To model the therapeutic gain from the addition of synchronous chemotherapy to radiotherapy in locally advanced head and neck cancer. MATERIALS AND METHODS: Refinements to previous methodology, including the derivation of weighted estimates of key parameters from randomised studies and the use of the expected mucosal biologically effective dose concept, have been used to produce an evidence-based assessment of the benefit from the addition of chemotherapy when considering acute grade 3 mucositis and rates of 5-year local control. RESULTS: For a value of alpha=0.3Gy(-1) the additional contribution from chemotherapy to local control was estimated to be 9.3Gy(10) and to grade 3 mucositis 6.4Gy(10). The additional expected mucosal biologically effective dose if radiotherapy dose escalation had been used instead of chemotherapy would have been 11.6Gy(10). Therefore, the mucosal sparing by using synchronous chemotherapy rather than radiotherapy dose escalation was found to be 5.2Gy(10) or the equivalent dose in 2Gy fractions 4.3Gy EQD(2). CONCLUSION: This modelling suggests a small therapeutic gain for the use of synchronous chemotherapy instead of radiotherapy dose escalation. This conclusion is dependent on the linear quadratic model and takes no account of late side-effects. This gain would be greater for agents that enhance the mucosal reaction to a lesser degree. This gain may be less when data for radiotherapy dose escalation to smaller high dose volumes using intensity-modulated radiotherapy are considered.

A systematic review and meta-analysis of the role of positron emission tomography in the follow up of head and neck squamous cell carcinoma following radiotherapy or chemoradiotherapy.

OBJECTIVES: This review examines the effectiveness of positron emission tomography (PET) in the detection of recurrent or persistent head and neck squamous cell carcinoma after radiotherapy or chemoradiotherapy. DESIGN: A systematic review and meta-analysis of trials of PET for detecting residual/recurrent head and neck squamous cell carcinoma treated by radiotherapy or chemoradiotherapy. Trials were quality assessed using the Quality Assessment of Diagnostic Accuracy Studies tool for assessing diagnostic accuracy studies. Quantitative data were extracted and a bivariate random effects model used to calculate pooled sensitivity and specificity. SETTING: Tertiary referral head and neck centre. PARTICIPANTS: Prospective and retrospective studies, excluding reviews, which included patients with head and neck squamous cell carcinoma who had fluorodeoxyglucose PET in the post-treatment phase following primary treatment by radiotherapy or chemoradiotherapy. MAIN OUTCOMES MEASURES: Quality assessment, sensitivity, specificity, false positive rates, false negative rates, positive and negative predictive values. RESULTS: Twenty-seven of 1871 identified studies were eligible for inclusion. The pooled sensitivity and specificity of PET for detecting residual or recurrent head and neck squamous cell carcinoma were 94% [95% confidence interval (CI), 87-97%] and 82% (95% CI, 76-86%) respectively. Positive and negative predictive values were 75% (95% CI, 68-82%), and 95% (95% CI, 92-97%) respectively. Sensitivity was greater for scans performed 10 weeks or more after treatment. CONCLUSIONS: Positron emission tomography is highly accurate in this role. However it is less sensitive early after treatment and has poor anatomical detail. PET may reduce the requirement for check endoscopies and planned neck dissections. A protocol for its use in post-treatment surveillance is proposed.

Chemoradiotherapy for rectal cancer: an updated analysis of factors affecting pathological response.

AIMS: With the aim of improving locoregional control, the use of preoperative chemoradiotherapy (CRT) for rectal cancer has increased. A pathological complete response (pCR) is often used as a surrogate marker for the efficacy of different CRT schedules. By analysing factors affecting pCR, this analysis aims to guide the development of future trials. MATERIALS AND METHODS: Searches of Medline, EMBASE and the electronic American Society of Clinical Oncology abstract databases were carried out to identify prospective phase II and phase III trials using preoperative CRT to treat rectal cancer. Trials were eligible for inclusion if they defined: the CRT drugs, the radiation dose and the pCR rate. Phase I patients were excluded from the analysis. A multivariate analysis examined the effect of the above variables on the pCR rate and in addition the use of neoadjuvant chemotherapy, the type of publication (peer reviewed vs abstract), the year of publication and whether the cancers were stated to be inoperable, fixed or threatening the circumferential resection margin were included. The method of analysis used was weighted linear modelling of the pCR rate. RESULTS: Sixty-four phase II and seven phase III trials were identified including a total of 4732 patients. Statistically significant factors associated with pCR were the use of two drugs, the method of fluoropyrimidine administration (with continuous intravenous 5-fluorouracil being the most effective) and a higher radiotherapy dose. Although the use of two drugs was associated with a higher rate of pCR, no single schedule seemed to be more effective. None of the other factors analysed significantly influenced pCR. CONCLUSIONS: A higher rate of pCR is seen in studies using two drugs, infusional 5-fluorouracil and a radiotherapy dose of 45 Gy and above.

A study of information seeking by cancer patients and their carers.

AIMS: To examine cancer patients' and carers' use of, and attitudes to, the Internet as an information source compared with other media. MATERIALS AND METHODS: The study was carried out in two phases: in phase I, interviews were used to construct a suitable instrument. In phase II, interviews were completed with 800 recently diagnosed patients and 200 carers. RESULTS: Relatively few patients (4.8%), but a high proportion of carers (48%), accessed the Internet directly for cancer information. However, around half of the patients used Internet information provided by someone else, generally a family member. The use of Internet information was uniformly low among ethnic minorities. Those who accessed Internet information reported high levels of satisfaction and generally rated it higher than booklets or leaflets. When asked who they would like to provide Internet information, overwhelmingly patients wanted the hospital doctor to do so. When this was done, there was very high compliance. Carers were much more proactive information seekers than patients. CONCLUSIONS: The Internet is an effective means of information provision in those who use it. Facilitated Internet access and directed use by health professionals would be effective ways of broadening access to this medium.

Attitudes of dentists and dental patients toward advertising.

Twenty years ago, Hite, Bellizzi, and Andrus (1988) examined the attitudes of dentists and consumers toward advertising. This study re-examines those attitudes to see if significant differences still exist. Based on a sample of dentists and consumers, significant differences were found. While attitude of dentists toward advertising is not as negative as it was 20 years ago, their views still tend to lag behind that of consumers. Further, the marketing tools used by dentists today are not consistent with what is seen by consumers and what consumers view as effective. Implications of these findings are discussed.

Improved survival after concurrent weekly cisplatin and radiotherapy for cervical carcinoma with assessment of acute and late side-effects.

AIMS: A recent meta-analysis has shown a survival advantage for the addition of concurrent chemotherapy to radiotherapy in the treatment of cervical carcinoma. Controversy persists about the most appropriate chemotherapy schedule and whether similar results for tumour control and toxicity may be achieved with optimally delivered radiotherapy. A single-centre experience of a concurrent chemotherapy regimen is presented. MATERIALS AND METHODS: All women treated with concurrent chemoradiotherapy at a university hospital from 1 January 1999 to 1 May 2002 were identified. Acute and late complications were scored using the National Cancer Institute Common Toxicity Criteria and RTOG/ EORTC system, respectively. Univariate and multivariate analyses were carried out to examine the relationship between demographics, stage, overall treatment time, radiotherapy dose, selectron insertion, number of chemotherapy cycles and occurrence of acute and late toxicity. RESULTS: Seventy-nine women received concurrent weekly cisplatin (40 mg/m2) with radiotherapy. Thirty-eight per cent had early tumours (FIGO IIA or less) and 62% had locally advanced tumours. Twenty-eight per cent of women had surgery as part of primary treatment. Radiation technique included external-beam pelvic radiotherapy (EBRT) (45-50.4 Gy in 25-28 fractions) and medium-dose rate brachytherapy single insertion (25-27 Gy to point A) or EBRT alone. Median overall treatment time was 49 days (range 23-91 days). Three-year survival rate was 87% (95% confidence interval [CI] 79-95%). Three-year, progression-free survival rate was 75% (95% CI 65-85%). At a median follow-up of 35 months: 27 (34%) women experienced 45 episodes of acute grade 3 or 4, and eight women (10%) experienced 12 late grade 3 or 4 complications. CONCLUSIONS: Weekly cisplatin 40 mg/m2 concurrent with radiotherapy is well tolerated when given to an unselected population of patients. Survival rates seem to be excellent, with both local control and overall survival being at least as good as those in published randomised trials.

Long-term follow-up of a randomised trial designed to determine the need for irradiation following conservative surgery for the treatment of invasive breast cancer.

Four hundred consecutive patients aged under 70 years diagnosed with a clinical T1 or T2 breast cancer were randomised to receive post-operative radiotherapy (n = 208) or not (n = 192), and monitored to record all local recurrences, distant recurrences and deaths for up to 20 years (median 13.7 years). All patients were treated by wide local excision and adjuvant therapy [estrogen receptor (ER) positive: tamoxifen; ER negative: CMF chemotherapy]. Kaplan-Meier and log-rank test methods were used to estimate and compare survival and recurrence. The 20-year Kaplan-Meier rates for local breast recurrence were 28.6% [95% confidence interval (CI) 19.6% to 37.6%] for radiotherapy and 49.8% (95% CI 40.8% to 58.9%). There was no significant difference between the two groups with regard to disease-free or overall survival. The hazard ratio for death among women who received radiation, as compared with those that did not, was 0.91 (95% CI 0.64-1.28; P = 0.59). Therefore, post-operative radiotherapy produced a clear-cut reduction in locoregional recurrence 0.45 (0.31-0.64; P = 0.0001), but did not influence the incidence of distant metastases or time of death. However, of the 119 patients who had a local recurrence, 51 (42.8%) had a distant recurrence, whereas of the 281 without local recurrence only 59 (21%) ever had a distant recurrence. A Cox's regression analysis with local recurrence as a time-dependent variable showed a risk ratio of 5.28 (P < 0.0001). This strong relationship is dependent on the intensity of post-treatment follow-up and investigation.

Pathological complete response following pre-operative chemoradiotherapy in rectal cancer: analysis of phase II/III trials.

Pathological complete response (pCR) has been used as a marker for the efficacy of pre-operative chemoradiotherapy (CRT) schedules in rectal cancer. To date there have been no randomized trials comparing CRT regimens in rectal cancer. Prospective phase II and CRT arms of randomized trials reported up to January 2004 were included, providing they defined the following minimum variables: drugs employed during CRT, radiotherapy dose and pCR rate. Multivariate analysis was used to examine the relationship of these variables on the pCR rate. In addition, the use of neoadjuvant chemotherapy, the type of publication (peer reviewed vs meeting abstract) and whether the tumours were stated to be unresectable/clinically fixed or to have threatened circumferential margins were investigated. The method of analysis was weighted linear modelling of the pCR rate which was normalized by the arcsine transformation. Phase II and phase III trials were identified including a total of 3157 patients. On multivariate analysis only the use of continuous infusion 5FU (p = 0.01), the use of a second drug (p = 0.001) and radiation dose (p = 0.02) were associated with higher rates of pCR. The use of a two drug regimen, the mode of delivery of 5FU and the radiation dose appear to be related to the incidence of pCR following CRT for rectal cancer. These results may generate hypotheses for future randomized trials. Important factors not considered in this analysis include the variability in pathological examination and in the time interval between CRT and surgery. In addition, the toxicity of the CRT regimens requires further investigation.

A regional audit of iatrogenic perforation of tumours of the oesophagus and cardia.

INTRODUCTION: With the rising incidence of oesophageal cancer, palliative treatment has an increasingly important role. With median survival unlikely to exceed 6 months, in advanced disease the palliative therapy chosen must not hasten patient's demise. AIM: To establish the outcome of both modern and historical palliative treatment in oesophageal tumours, with emphasis on the aetiology and outcome of iatrogenic perforation. METHODS: Patients with oesophageal or cardia carcinoma treated within the West Midlands between 1992 and 1996 were identified retrospectively. Information was gathered from hospital case notes and the regional cancer intelligence unit with hospitals visited to capture data. All episodes were entered into a dedicated database. RESULTS: Of the 3660 patients who were treated, 2529 received palliation as primary treatment, with 5259 palliative procedures performed; 164 iatrogenic perforations were recorded; 83 were due to diagnostic endoscopy (endoscopic perforation) with the reminder due to interventional palliative procedures. Median survival from all forms of palliation was 138 days. Following perforation survival was 95 days after interventional palliative procedure and 58 days after endoscopic perforation (P > 0.05). Thirty-day mortality after emergency surgery was 11.8% with mean survival of 7.5 months. CONCLUSION: Perforation at diagnostic endoscopy is associated with substantial mortality despite rapid intervention. Patients with suspected cancer must be investigated with extreme care to reduce iatrogenic complications.

Multicentre prospective audit of surgical outcomes and acute complications following short course pre-operative radiotherapy for resectable rectal cancer.

BACKGROUND: The addition of short course pre-operative radiotherapy to total mesorectal excision reduces local recurrence in resectable adenocarcinoma of the rectum. In a previous retrospective study potential factors associated with early complications following this combination were identified. The aim of this study was to examine these relationships in a prospective multicentre audit. METHODS: One hundred and seven patients who received short course pre-operative radiotherapy in four cancer centres between 1 October 2001 and 30 September 2002 were included. Data including patient age, radiotherapy field length, overall treatment time, operation type, surgical outcomes and complications occurring within 3 months of the 1st day of radiotherapy were collected. These were compared and combined with the previously studied cohort of 176 patients treated at one centre between 1st January 1998 and 31st December 1999. RESULTS: In the prospective cohort only patient age (P=0.001) was significantly associated with acute complications. However, both the overall treatment time (median 9.0 vs 11.0 days P <0.0001) and field length (median 16.6 vs 17.0 cm P=0.03) were significantly shorter in this cohort when compared to the previous retrospective study. In patients from both studies (n=283), increasing age (P=0.002) and field length (independent of operation type) (P=0.02) were independently associated with an increased risk of acute complications. CONCLUSIONS: This study suggests that meticulous selection of patients for short course pre-operative radiotherapy and smaller planning target volumes may be associated with a lower risk of acute complications. The use of MRI scanning to stage pelvic disease may reduce the number of patients with R1 resections receiving short course pre-operative radiotherapy.

A randomised study comparing peripheral blood progenitor mobilisation using intermediate-dose cyclophosphamide plus lenograstim with lenograstim alone.

We conducted a prospective randomised study to compare the efficiency of out-patient progenitor cell mobilisation using either intermediate-dose cyclophosphamide (2 g/m(2)) and lenograstim at 5 micrograms/kg (Cyclo-G-CSF group, n=39) or lenograstim alone at 10 micrograms/kg (G-CSF group, n=40). The end points were to compare the impact of the two regimens on mobilisation efficiency, morbidity, time spent in hospital, the number of apheresis procedures required and engraftment kinetics. Successful mobilisation was achieved in 28/40 (70%) in the G-CSF group vs 22/39 (56.4%) for Cyclo-G-CSF (P=0.21). The median number of CD34+ cells mobilised was 2.3 x 10(6)/kg and 2.2 x 10(6)/kg for G-CSF and cyclo-G-CSF arms following a median of two apheresis procedures. Nausea and vomiting and total time spent in the hospital during mobilisation were significantly greater after Cyclo-G-CSF (P<0.05). Rapid neutrophil and platelet engraftment was achieved in all transplanted patients in both groups. In conclusion, G-CSF at 10 micrograms/kg was as efficient at mobilising progenitor cells as a combination of cyclophosphamide and G-CSF with reduced hospitalisation and side effects and prompt engraftment. When aggressive in-patient cytoreductive regimens are not required to both control disease and generate progenitor cells, the use of G-CSF alone appears preferable to combination with intermediate-dose cyclophosphamide.

External beam radiotherapy in the management of differentiated thyroid cancer.

AIMS: No randomised trials have addressed the use of external beam radiotherapy (EBRT) in the treatment of differentiated thyroid cancer. The indications for EBRT, the technique and recommended dose all remain controversial. MATERIALS AND METHODS: We included patients treated with EBRT with curative intent from two cancer centres between 1988 and 2001. Data were collected from hospital notes, radiotherapy prescriptions and local cancer registry. RESULTS: The indications for treatment in the 41 identified patients were macroscopic residual disease 23 (56%), microscopic residual disease 10 (25%), Hurthle cell variants 3 (7%), multiple lymph-node involvement 3 (7%) and other 2 (5%). Delivered doses ranged from 37.5-66 Gy over 3-6.5 weeks. Rate of local recurrence and overall survival at 5 years were as follows: papillary 26% and 67%; follicular 43% and 48%; well differentiated 21% and 67%; focus of poor differentiation/Hurthle cell variants 69% and 32%; complete excision 25% and 61%; residual disease 37% and 59%; EBRT total dose < 50 Gy 63% and 42%; 50-54 Gy 15% and 72%; > 54 Gy 18%, and 68%. CONCLUSIONS: The results in this study are consistent with previous retrospective studies of EBRT. The wide range of indications and doses used with radical intent highlights the lack of clinical and radiobiological data on the response of differentiated thyroid cancer to EBRT. Despite the small study size, the 5-year local recurrence results indicate a possible dose response within the dose range used.

Late toxicity after short course preoperative radiotherapy and total mesorectal excision for resectable rectal cancer.

AIMS: The late toxicity of short-course preoperative radiotherapy (SCPRT) after total mesorectal excision (TME) in resectable rectal cancer has not been adequately documented. The acute toxicity in a series of 176 consecutive patients has been previously reported. In this study, the late toxicity in the same cohort is presented. MATERIALS AND METHODS: Side-effects occurring more than 3 months after the start of SCPRT were graded using the EORTC/RTOG late radiation toxicity system. We performed multivariate analysis to identify associated factors. RESULTS: Of 176 patients, 15 died within 3 months of SCPRT and five patients were lost to follow-up. One hundred and fifty-six patients were assessable at a median follow-up interval of 41 months: severe (grade 3-4) toxicity was seen in 20 patients (13%), of which 13 were gastrointestinal (8%); three urological (2%); three thromboembolic (2%), and one musculoskeletal (1%). On multivariate analysis, abdomino-perineal (AP) resection (P < 0.02) was associated with a lower risk of grade 3-4 toxicity. CONCLUSIONS: In this retrospective study, the rate of late grade 3-4 toxicity after SCPRT and TME was 13%. Although AP resection seems to be associated with a lower incidence of late toxicity, this could be counterbalanced by the impact of a stoma on quality of life. These factors should be considered when determining the optimal management of resectable rectal cancers.

Toxicity, recurrence and survival after adjuvant radiotherapy treatment for FIGO stage I cancer of the endometrium.

We conducted a retrospective observational study to determine the rate of toxicity, pattern of tumour recurrence and survival associated with radiotherapy treatment for FIGO stage I cancer of the endometrium. All patients had undergone definitive surgery and had been referred to the oncology department of the University Hospital Birmingham, U.K. Two hundred and forty-five women were included in the study; 228 patients were treated with radiotherapy; 160 had external beam radiation alone; 32 had vaginal vault brachytherapy alone; 36 patients had both modalities; and 17 patients were not given radiotherapy. There were nine cases of Grade 3 and 4 radiation reactions, of which four were acute, four were late and one was acute and late toxicity. The severity of both acute and late radiation effects was significantly associated with the delivery of vault brachytherapy (external beam radiotherapy alone compared with brachytherapy alone (1/158 vs 3/32; P = 0.02). Thirty-four patients were diagnosed with tumour recurrence (11 distant, 14 local, 4 patients had both distant and local disease and 5 patients had recurrence diagnosed at the time of death). Patients who received no radiotherapy were at greater risk of local pelvic tumour recurrence (P < 0.0001; hazard ratio [HR] 9.6, 95% confidence interval (CI) 3.5-26.3). Vaginal vault brachytherapy had no discernible effect on the pattern of tumour recurrence. Forty-six patients died during the follow-up period, 28 of these were attributable to carcinoma of the endometrium. There was no difference in survival between the four treatment groups (P = 0.68). The overall 5-year survival rate in our study group was 89.6% (85.4-93.8%). In a proportional hazards model, tumour grade (HR 2.0 per level [1.25, 3.17]; P = 0.004]) and age (HR 1.74 per 10 years [1.12, 2.69]; P = 0.01) were the only factors found to have an independent influence on survival. This study suggests that, although pelvic radiation may not alter overall survival, it does reduce the risk of local disease recurrence. In this study population, vaginal vault brachytherapy using a vaginal stock/dobbie showed no additional benefits compared with external beam radiotherapy; it was, however, associated with a higher rate of both acute and late radiation effects.