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.

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%.

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.

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.

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.

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.

Surgical workload and outcome after resection for carcinoma of the oesophagus and cardia.

BACKGROUND: Performing cancer surgery in high-volume centres may lead to improved outcomes. This study explored the relationship between annual workload and outcome following resection for carcinoma of the oesophagus and cardia. METHODS: The study was a retrospective case-note review of 1125 patients who had surgery for cardio-oesophageal cancer in the West Midlands region of England. Outcome measures were 30-day mortality and long-term survival. RESULTS: The overall 30-day mortality rate was 10.0 per cent with a median survival of 14 months and a 5-year survival rate of 17.2 per cent. Increasing age, advanced stage of disease and emergency resection independently affected outcome adversely. Forty-one infrequent operators (fewer than four resections per year) performed 146 resections (13.0 per cent), 18 intermediate operators (between four and 11 resections per year) performed 488 resections (43.4 per cent) and five frequent operators (12 or more resections per year) performed 491 resections (43.6 per cent). The 30-day mortality rate was greatest in the infrequent group (15.1 per cent) compared with both the intermediate group (6.6 per cent; adjusted odds 0.40, P = 0.004) and the frequent group (11.8 per cent; odds 0.73, P = 0.28). There were no differences in survival rates between the groups, and no difference in outcome between high- and low-volume hospitals. CONCLUSION: In this unselected population-based series there was little evidence of a trend of improving 30-day mortality rate with increasing workload, or between workload and long-term survival.

Cancer of the colon and rectum in the West Midlands, 1957-1981.

Between 1957 and 1981, 49,904 patients with large bowel cancer were registered at the Birmingham Cancer Registry. The annual incidence was 24.5 per 100,000 population for colonic cancer and 18.4 per 100,000 for that of the rectum. The annual number of patients increased by 41.9 per cent. The age-adjusted 5-year survival rate was 26.4 per cent for colonic carcinoma and 28.2 per cent for rectal cancer. Between 1977 and 1981 these rates increased significantly to 30.3 and 30.0 per cent respectively (P < 0.01). Stage for stage, colonic cancer was associated with longer survival than that of the rectum. Curative and palliative resection rates increased, especially for anterior resection. The operative mortality rate remained constant at 8 per cent. Despite increases in palliative resection rates 50 per cent of these patients required a stoma. Treatment was not undertaken in 37.4 per cent of patients. The end results of treatment are little better than those reported previously from this registry.

The rising trend in oesophageal adenocarcinoma and gastric cardia.

The incidence of cancer of the oesophagus and stomach in the West Midlands region of England have been analysed for the 25 years 1962-86. Overall, cancer of the oesophagus is increasing (from 3.45 per 100,000 in 1962-66 to 4.37 in 1982-86) and stomach cancer is decreasing (19.22 and 16.54 respectively). However, when analysed by histological type and subsite the picture is very different. In oesophagus, squamous cell carcinoma shows only a slight increase whereas for adenocarcinoma the increase is highly significant (from 0.14 to 0.76). In stomach, cardia shows a very similar pattern to adenocarcinoma of oesophagus (increasing from 0.75 to 2.96) but pyloric antrum is decreasing (from 2.63 to 2.32). The rapid changes in investigative procedures over the period have resulted in increasing numbers with histological confirmation and subsite specification but despite these confounding factors, comparative analyses still indicate a real increase in adenocarcinoma of oesophagus and cardia. Although the incidence of both are greater in men than in women, the proportional rates of increase, particularly for cardia, are very similar in both sexes, indicating a common aetiological factor or factors. Analysis by social-economic group reveals that the increases observed are not uniform throughout the population but are relatively higher in professional classes (1 and 2).

Staging carcinoma: its value in cancer of the larynx.

Three thousand four hundred and forty-five cases of cancer of the larynx were examined and 3,235 assigned to their TNM group. While good correlation with prognosis could be seen, the value of the detailed subsite (as opposed to the main laryngeal regions) was limited to defining T1a and T1b and aiding that of T2. T status gives some indication of prognosis, but the N status is of almost overriding importance.

Primary treatment of cancer of the larynx.

Analysis of 3,445 cases of cancer of the larynx with a follow-up of 99.8 per cent shows that over a period in which the survival has improved neither the modality of the treatment nor the severity of the cancer has changed. Improved survival may be due to socioeconomic factors or an improvement in the quality of treatment.

Increasing incidence of adenocarcinoma of the gastric cardia and adjacent sites.

Data in a regional cancer registry covering a population of 5 million and with an efficiency of registration of over 95% have been used to examine incidence trends in oesophageal and gastric carcinoma. In the West Midlands Region of the UK, during the period 1962 to 1981 the age standardised incidence of gastric carcinoma decreased by 20%. However, an analysis by both histological type and detailed site reveals that while the incidence of distal lesions is diminishing, the incidence of adenocarcinoma of the oesophagus and cardia is increasing. The proximal and distal lesions also exhibit marked differences in social class distribution and sex ratio. The results strongly suggest that the aetiological factors involved for cardia and adjoining sites are different from those for pyloric antrum.

Malignant melanoma of the vulva: a clinicopathological study of 50 women.

A clinicopathological review of 50 primary malignant melanomas of the vulva in the West Midlands region of England is presented. The overall 5-year-survival rate was 35%, when adjusted for age. Significant predictors of survival were clinical stage, patient age, tumour ulceration, cell type and mitotic rate. Tumour thickness was of prognostic importance but as a prognostic variable it did not operate independently of stage and as most lesions were deeply invasive at presentation vulval tumours must be separated for prognostic purposes into bands at greater overall thicknesses than those used for skin melanomas generally. There was no significant relation between survival and type of surgery performed as a primary therapeutic procedure.

The Cervex: an ectocervical brush sampler.

The performance of a new ectocervical brush sampler--the Cervex--was compared with the Ayre spatula in 280 paired cervical smears. The Cervex smears were superior in quality of spread, transformation zone sampling in all degrees of cervical patency and in detection of histologically proven epithelial abnormalities, with a false negative rate of 10.9% compared with 20% for the Ayre. Improvement in predictive value was noted in atrophic samples, with increased cellularity and transformation zone representation. Difficulty has been encountered in obtaining adequate samples from the older woman and from those with iatrogenic scarring of the cervix. Although two-sampler techniques may be used, submission of high quality pan-cervical material from a single sampler onto one slide is economically and organizationally attractive. The Cervex seems capable of producing such samples and deserves further evaluation for routine screening.

Gastric cancer: a 25-year review.

Between 1957 and 1981, 31,716 cases of gastric cancer were registered in the West Midlands, UK. The age-standardized incidence has shown a decrease from 17.42 per 100,000 population during the first quinquennium to 15.30 per 100,000 in the last. There was an apparent increase in the proportion of proximal lesions with a decrease in the proportion of distal, antral cancers. The stage of disease at diagnosis remained constant with 79 per cent of patients having stage IV disease. Less than 1 per cent presented with stage I disease. As a result, the curative resection rate was 21 per cent. The operative mortality rates for curative partial gastrectomy and total gastrectomy were 13 and 29 per cent respectively. Surgeons undertaking more than nine total gastrectomies annually had an overall mean operative mortality rate of 22 per cent. Overall age-adjusted survival at 5 years was 5 per cent. Survival at 5 years for stage I, II and III disease was 72, 32 and 10 per cent respectively. There was a significant increase in survival time for those treated by curative resection between 1972 and 1981 compared with the previous decade. The implications for the management of gastric cancer are discussed.

Effect of surgical experience on the results of resection for oesophageal carcinoma.

From 1957 to 1976 oesophageal resection for carcinoma was performed in 1119 patients reported to the West Midlands Cancer Registry. The operations were performed on 581 patients by 127 surgeons who averaged three or less resections per annum (the 'occasional' group). These were compared with 538 patients (the 'frequent' group) whose resections were performed by four surgeons who averaged six or more resections per annum. Operative mortality was 39.4 per cent in the 'occasional' group and 21.6 per cent in the 'frequent' group (P less than 0.001). The age adjusted 5-year survival was 11.1 and 15.2 per cent respectively (P less than 0.05) but when the operative deaths were excluded there was no significant difference. We suggest that oesophageal resection for carcinoma should be performed only where there is an acceptably low operative mortality rate.