Influence of a regional centralised upper gastrointestinal cancer service model on patient safety, quality of care and survival.

AIMS: The aim of this study was to determine outcomes of a reconfigured centralised upper gastrointestinal (UGI) cancer service model, allied to an enhanced recovery programme, when compared with historical controls in a UK cancer network. MATERIALS AND METHODS: Details of 606 consecutive patients diagnosed with UGI cancer were collected prospectively and outcomes before (n = 251) and after (n = 355) centralisation compared. Primary outcome measures were rates of curative treatment intent, operative morbidity, length of hospital stay and survival. RESULTS: The rate of curative treatment intent increased from 21 to 36% after centralisation (P < 0.0001). Operative morbidity (mortality) and length of hospital stay before and after centralisation were 40% (2.5%) and 16 days, compared with 45% (2.4%) and 13 days, respectively (P = 0.024). The median and 1 year survival (all patients) improved from 8.7 months and 39.0% to 10.8 months and 46.8%, respectively, after centralisation (P = 0.032). On multivariate analysis, age (hazard ratio 1.894, 95% confidence interval 0.743-4.781, P < 0.0001), centralisation (hazard ratio 0.809, 95% confidence interval 0.668-0.979, P = 0.03) and overall radiological TNM stage (hazard ratio 3.905, 95% confidence interval 1.413-11.270, P < 0.0001) were independently associated with survival. CONCLUSION: These outcomes confirm the patient safety, quality of care and survival improvements achievable by compliance with National Health Service Improving Outcomes Guidance.

Prognostic significance of circumferential resection margin involvement following oesophagectomy for cancer and the predictive role of endoluminal ultrasonography.

BACKGROUND: The optimum multimodal treatment for oesophageal cancer, and the prognostic significance of histopathological tumour involvement of the circumferential resection margin (CRM+) are uncertain. The aims of this study were to determine the prognostic significance of CRM+ after oesophagectomy and to identify endosonographic (endoluminal ultrasonography (EUS)) features that predict a threatened CRM+. METHODS: Two hundred and sixty-nine consecutive patients underwent potentially curative oesophagectomy (103 surgery alone, 124 neoadjuvant chemotherapy (CS) and 42 chemoradiotherapy (CRTS)). Primary outcome measures were disease-free survival (DFS) and overall survival (OS). RESULTS: CRM+ was reported in 98 (38.0%) of all, and in 90 (62.5%) of pT3 patients. Multivariate analysis of pathological factors revealed: lymphovascular invasion (HR 2.087, 95% CI 1.396-3.122, P<0.0001), CRM+ (HR 1.762, 95% CI 1.201-2.586, P=0.004) and lymph node metastasis count (HR 1.563, 95% CI 1.018-2.400, P=0.041) to be independently and significantly associated with DFS. Lymphovascular invasion (HR 2.160, 95% CI 1.432-3.259, P<0.001) and CRM+ (HR 1.514, 95% CI 1.000-2.292, P=0.050) were also independently and significantly associated with OS. Multivariate analysis revealed EUS T stage (T3 or T4, OR 24.313, 95% CI 7.438-79.476, P<0.0001) and use or not of CRTS (OR 0.116, 95% CI 0.035-0.382, P<0.0001) were independently and significantly associated with CRM+. CONCLUSION: A positive CRM was a better predictor of DFS and OS than standard pTNM stage.

Stage for stage comparison of recurrence patterns after definitive chemoradiotherapy or surgery for oesophageal carcinoma.

AIMS: Definitive chemoradiotherapy (dCRT) has been advocated as an alternative treatment for oesophageal carcinoma, but received criticism for perceived poorer locoregional disease control when compared with surgery. The aim of this study was to determine the relative incidence and pattern of oesophageal carcinoma recurrence after dCRT and surgery in patients receiving stage-directed therapy with curative intent. MATERIALS AND METHODS: In total, 623 consecutive patients with oesophageal carcinoma (207 squamous cell carcinoma, 416 adenocarcinoma) were studied. The primary outcome measure was disease-free survival, adjusted for baseline differences in gender, age and histological cell type. RESULTS: Three hundred and eleven patients deemed unsuitable for surgery on the grounds of performance status (n = 137), bulky local disease (n = 121) or personal choice (n = 53) received dCRT and 312 surgery (200 received neoadjuvant chemotherapy). Oesophageal carcinoma recurrence was diagnosed in 44.1% of patients after dCRT compared with 40.7% after surgery (P = 0.222). Locoregional recurrence was more common after dCRT than after surgery (24.1% versus 9.3%, P < 0.0001). In contrast, distant metastases were more common after surgery than after dCRT (22.8% versus 12.9%, P = 0.001). The median time to recurrence in patients receiving dCRT and surgery were 15 and 17 months, respectively (P = 0.052). Stage-related disease-free 2 year survival for dCRT versus surgery was: stage I (68.6 versus 85.6%, P = 0.069), stage II (36.9 versus 47.4%, P = 0.011), stage III (31.0 versus 28.6, P = 0.878), stage IVa (21.4 versus 26.3%, P = 0.710). CONCLUSIONS: These findings provide further support for a randomised trial of dCRT versus surgery in both oesophageal squamous cell carcinoma and adenocarcinoma.

Comparison of patients' needs and doctors' perceptions of information requirements related to a diagnosis of oesophageal or gastric cancer.

The aim of this study was to assess the information needs of patients diagnosed with oesophageal and gastric cancer and to compare these with their perceived information needs in the opinion of junior doctors. One hundred patients and 100 doctors responded to a questionnaire regarding the information needs of cancer patients. Seventy-nine per cent of patients wanted as much information as possible about their diagnosis, but only 35% of doctors were willing to give all the available information (P < 0.0001). Seventy-seven per cent of patients wanted to receive their diagnosis from a consultant whereas only 5% of doctors believed that patients should receive their diagnoses from a consultant (P < 0.0001). Eighty-four per cent of doctors were willing to communicate a serious illness with a good prognosis, yet only 43% would communicate a diagnosis with a poor prognosis (P < 0.0001). All 100 doctors had received formal training in breaking bad news, but 20 considered this inadequate. Socio-economic deprivation was associated with poor access to supplementary Internet derived information (P < 0.001). The majority of patients with a diagnosis of oesophagogastric cancer want a great deal of information regarding their illness, which contrasts with doctors' perceptions. Adequate training in information disclosure may help address this issue.

Induction chemotherapy followed by chemoradiation in locally advanced pancreatic cancer: an effective and well-tolerated treatment.

AIMS: The treatment of locally advanced pancreatic cancer varies enormously both within the UK and internationally. Although chemoradiation is the treatment of choice in the USA, in the UK this modality is used infrequently because of concerns regarding both its efficacy and its toxicity. We reviewed our experience with induction chemotherapy and selective chemoradiation in an attempt to show that it is a well-tolerated treatment that may be superior to chemotherapy alone. MATERIALS AND METHODS: Case notes of patients with locally advanced pancreatic cancer referred to the Velindre Cancer Centre between 1 March 2005 and 31 October 2007 were reviewed. Data on patient demographics, tumour characteristics, treatment and overall survival were collected retrospectively. Toxicity data during chemoradiation were collected prospectively. Patients who had non-progressive disease after 3 months of chemotherapy were planned for chemoradiation using three-dimensional conformal radiotherapy to a total dose of 4500-5040cGy in 25-28 daily fractions with gemcitabine as a radiosensitiser. RESULTS: Of the 91 referrals, 69 (76%) were fit for active oncological treatment; 43/69 (62%) patients were considered for induction chemotherapy followed by chemoradiation and 16/43 (37%) patients received chemoradiation. The median overall survival for patients receiving primary chemotherapy (n=26) was 9.2 (6.8-11.9) months and was 15.3 (11.6-upper limit not reached) months for patients who received chemoradiation (n=16). During the induction chemotherapy 8/16 (50%) patients experienced grade 3/4 toxicity and there were five hospital admissions. During chemoradiation there were 6/16 (37.5%) cases of grade 3/4 toxicity and two hospital admissions. There were no treatment-related deaths. Overall, 94.5% of the intended radiotherapy dose and 84% of the concurrent chemotherapy dose was delivered. CONCLUSIONS: In this UK network, about half of patients were considered for chemoradiation, but only 18% received it. Survival and treatment-related toxicity are consistent with data from other chemoradiation trials and in our series chemoradiation was tolerated better than chemotherapy alone. This supports the view that 'consolidation' chemoradiation is a viable treatment option that should be considered in selected patients with locally advanced non-metastatic pancreatic cancer.

Stage-for-stage comparison of definitive chemoradiotherapy, surgery alone and neoadjuvant chemotherapy for oesophageal carcinoma.

BACKGROUND: Definitive chemoradiotherapy (dCRT) has been proposed as an alternative therapy for selected patients with oesophageal cancer. The aim of this study was to determine the outcomes of dCRT, surgery alone, and neoadjuvant chemotherapy followed by surgery (CS) in patients with oesophageal cancer. METHODS: Consecutive patients diagnosed with oesophageal cancer and managed by a multidisciplinary team were staged by computed tomography and endoluminal ultrasonography. Those deemed unsuitable for surgery on the grounds of performance status, bulky local disease or personal choice received dCRT. The primary outcome measure was overall survival measured from date of diagnosis. RESULTS: Of 417 patients, 173 received dCRT, 126 underwent surgery alone and 118 received CS. The incidence of grade III/IV toxicity after dCRT and CS was 39.3 and 60.2 per cent respectively. Operative morbidity rates were 42.9 and 44.4 per cent after surgery alone and CS respectively. Thirty-day mortality rates were zero, 7.9 and 0.8 per cent after dCRT, surgery alone and CS respectively. Overall 2-year survival rates were 44.3, 56.2 and 42.4 per cent (P = 0.422). CONCLUSION: These findings support the need for a randomized trial of dCRT versus CS for resectable oesophageal cancer.

Prognostic significance of failure to cross esophageal tumors by endoluminal ultrasound.

SUMMARY: Failure to intubate and cross esophageal tumors by endosonography is reported in as many as 30% of cases and is thought to be associated with an especially poor prognosis. The aim of this study was to audit the above in a large consecutive case series of Endoscopic Ultrasound (EUS) examinations for esophageal cancer performed in a regional specialist cancer network with particular reference to outcome. A consecutive series of 411 patients underwent EUS examination by a specialist radiologist over a period of 9 years. Forty (10%) of patients required dilation, and there was total failure to cross the tumor in 12 patients (2.9%). Failure to traverse the primary tumor was associated with a diagnosis of squamous cell cancer (8 of 12 patients, 66%, rho = -0.182, P = 0.011). Limited staging information was obtained in 7 of these patients, which altered the computed tomography stage in 5 patients (71%, 3 upstaged, 2 downstaged). Six patients received definitive chemoradiotherapy, two patients surgery and four patients palliative chemotherapy. The median and 5-year survival in patients whose tumors were not crossed was 10 months and 28%, respectively, compared with 24 months and 24%, respectively in patients whose tumors were fully assessed. Failure to cross esophageal tumors in practice was far less common than the literature suggests, and esophageal tumor luminal stenosis should no longer be considered a limitation of endosonography.

Prospective cohort comparison of neoadjuvant chemoradiotherapy versus chemotherapy in patients with oesophageal cancer.

BACKGROUND: Chemotherapy and chemoradiotherapy are common neoadjuvant treatments for resectable T3 N0-1 M0 oesophageal carcinoma. The aim of this study was to compare the outcomes of these therapies in consecutive cohorts of patients. METHODS: Between January 1998 and December 2001, 88 patients received neoadjuvant chemoradiotherapy (two cycles of cisplatin and 5-fluorouracil (5-FU), prior to 45 Gy in 25 F concurrent radiotherapy with cisplatin and 5-FU). From 2002, 117 patients received neoadjuvant chemotherapy (76 patients had two cycles of cisplatin and 41 had four cycles of epirubicin, cisplatin and 5-FU). The primary outcome measure was survival, and analysis was by intention to treat. RESULTS: Postoperative morbidity and mortality rates were 56 per cent (40 patients) and 10 per cent (seven patients) respectively in the chemoradiotherapy group, compared with 47 per cent (46 patients) and 1 per cent (one patient) in the chemotherapy group (P = 0.008). The cumulative 5-year survival rate by intention to treat was 35 per cent after chemoradiotherapy versus 21 per cent after chemotherapy (P = 0.188). The cumulative corrected 5-year survival rate after completed treatment was 44 per cent for chemoradiotherapy compared with 25 per cent for chemotherapy (P = 0.032). CONCLUSION: Neoadjuvant chemoradiotherapy should remain an option for patients with satisfactory performance status.

Prospective comparison of transthoracic versus transhiatal esophagectomy following neoadjuvant therapy for esophageal cancer.

Transthoracic esophagectomy (TT) has been championed as a better cancer operation than transhiatal esophagectomy (TH) because the approach facilitates meticulous wide tumor excision and lymphadenectomy. However, neoadjuvant chemoradiotherapy (CRTS) and chemotherapy (CS) have been reported to improve outcomes, and we aimed to compare outcomes after multimodal therapy related to the operative approach. One hundred and fifty-one consecutive patients were studied prospectively. All patients were staged with computed tomography and endoluminal ultrasound, and treatment decisions were related to stage and performance status. One hundred and nineteen TT (median age 58 years, 92 male, 54 CRTS, 65 CS) were performed compared to 32 TH (median age 57 year, 27 male, 14 CRTS, 18 CS). Primary outcome measure was survival. Post-operative morbidity and mortality were 54% and 4%, respectively, after TT compared with 59% and 6% after TH (chi2 0.239 df 1, P=0.625). Recurrent cancer was no less frequent after TT (52%) than after TH (37.5%, chi2 2.151 df=1, P=0.142). Cumulative uncorrected 5-year survival was 34% after TT compared with 53% after TH (log rank 1.44, df=1, P=0.2298). Median survival was also similar in lymph node positive patients (TT vs. TH, 23 months vs. 22 months, respectively, log rank 0.25, df=1, P=0.6199). Despite the fact that patients receiving multimodal therapy and a TH esophagectomy were less fit, operative morbidity, mortality and recurrence were similar, and survival did not differ significantly when compared with multimodal TT esophagectomy.

Small cell oesophageal carcinoma: an institutional experience and review of the literature.

Primary small cell oesophageal carcinoma (SCOC) is rare, prognosis is poor and there is no established optimum treatment strategy. It shares many clinicopathologic features with small cell carcinoma of the lung; therefore, a similar staging and treatment strategy was adopted. Sixteen cases referred to Velindre hospital between 1998 and 2005 were identified. Patients received platinum-based combination chemotherapy if appropriate. Those with limited disease (LD) received radical radiotherapy (RT) to all sites of disease on completion of chemotherapy. Median survival of all patients was 13.2 months. Median survival of patients with LD was significantly longer than those with extensive disease (24.4 vs 9.1 months, P=0.034). This is one of the largest single institution series in the world literature. Combined modality therapy using platinum-based combination chemotherapy and radical RT may allow a nonsurgical approach to management, avoiding the morbidity of oesophagectomy. Prophylactic cranial irradiation is controversial, and should be discussed on an individual basis.

A clinical review of the investigation and management of carcinoma of unknown primary in a single cancer network.

AIMS: Carcinoma of unknown primary (CUP) is a common encounter in oncological practice and represents 2.0-6.0% of all invasive malignancies. Evidence to support particular therapeutic strategies in this patient population is scarce, and empirical therapies are frequently derived from research on patients where the primary tumour site is known. MATERIALS AND METHODS: This retrospective study reviewed the management of all patients recorded to have a diagnosis of CUP in a single cancer centre over a period of 12 months. Health records were reviewed documenting the CUP subtype, the investigations carried out both in the referring cancer unit and subsequently at the cancer centre and the recommended treatment (type and regimen), together with survival. The outcomes were examined in respect to a number of prognostic factors. Statistical tests were considered significant at P < 0.05. RESULTS: One hundred and sixty-six patients were recorded to have a diagnosis of CUP, representing 3.7% of all referrals to the cancer centre. The median age of patients was 68 years (range 32-94 years), and 52.0% were women. The three most common CUP subgroups were CUP-liver/multiple sites (25.0%), CUP-bone (21.0%) and CUP-brain (16.0%). The remaining subgroups occurred at frequencies of less than 10% each. Histological confirmation was only obtained in 55.0% of cases. Even within a single subtype, 41 patients with CUP-liver/multiple sites underwent a total of 19 different investigations before any treatment being given. Forty-seven (28.0%) patients received radiotherapy, 30 (18.0%) received chemotherapy and 58 (35.0%) received supportive care alone. Nine different 5-fluorouracil-containing regimens were used in 11 patients treated with chemotherapy for CUP-liver. The overall median survival for all patients was 4.0 months. Survival was better in patients with a good performance status (0-1) and absent liver metastases (median survival 15.0 months; 95% confidence interval 8.0-22.1) and those who received chemotherapy (median survival 13.0 months; 95% confidence interval 7.4-18.6). Multivariate analysis confirmed female gender (P = 0.006), a good performance status (0/1) (P < 0.0001) and absent liver metastases (P = 0.002) as favourable prognostic indicators. CONCLUSIONS: The appropriate management of patients with CUP is unclear and this study revealed a high degree of variation in clinical practice. This area is in urgent need of clinical research to ensure that the treatment of CUP is evidence based. Until such time, clinical recommendations are suggested for the investigation and treatment of such patients. Therapeutic progress will be facilitated by designating a clinical lead for CUP in each clinical network.

Prognostic significance of body mass indices for patients undergoing esophagectomy for cancer.

The aim of this study was to determine the role of body mass index (BMI) in a Western population on outcomes after esophagectomy for cancer. Two hundred and fifteen consecutive patients undergoing esophagectomy for esophageal cancer of any cell type were studied prospectively. Patients with BMIs > 25 kg/m were classified as overweight and compared with control patients with BMIs below these reference values. Ninety-seven patients (45%) had low or normal BMIs, 86 patients (40%) were overweight, and a further 32 (15%) were obese. High BMIs were associated with a higher incidence of adenocarcinoma versus squamous cell carcinoma (83%vs. 14%, P = 0.041). Operative morbidity and mortality were 53% and 3% in overweight patients compared with 49% (P = 0.489) and 8% (P = 0.123) in control patients. Cumulative survival at 5 years was 27% for overweight patients compared with 38% for control patients (P = 0.6896). In a multivariate analysis, age (hazard ratio [HR] 1.492, 95% CI 1.143-1.948, P = 0.003), T-stage (HR 1.459, 95% CI 1.028-2.071, P = 0.034), N-stage (HR 1.815, 95% CI 1.039-3.172, P = 0.036) and the number of lymph node metastases (HR 1.008, 95% CI 1.023-1.158, P = 0.008), were significantly and independently associated with durations of survival. High BMIs were not associated with increased operative risk, and long-term outcomes were similar after R0 esophagectomy.

Multidisciplinary team management is associated with improved outcomes after surgery for esophageal cancer.

We aim to compare the outcomes of patients undergoing R0 esophagectomy by a multidisciplinary team (MDT) with outcomes after surgery alone performed by surgeons working independently in a UK cancer unit. An historical control group of 77 consecutive patients diagnosed with esophageal cancer and undergoing surgery with curative intent by six general surgeons between 1991 and 1997 (54 R0 esophagectomies) were compared with a group of 67 consecutive patients managed by the MDT between 1998 and 2003 (53 R0 esophagectomies, 26 patients received multimodal therapy). The proportion of patients undergoing open and closed laparotomy and thoracotomy decreased from 21% and 5%, respectively, in control patients, to 13% and 0% in MDT patients (chi2 = 11.90, DF = 1, P = 0.001; chi2 = 5.45, DF = 1, P = 0.02 respectively). MDT patients had lower operative mortality (5.7%vs. 26%; chi2 = 8.22, DF = 1, P = 0.004) than control patients, and were more likely to survive 5 years (52%vs. 10%, chi2 = 15.05, P = 0.0001). In a multivariate analysis, MDT management (HR = 0.337, 95% CI = 0.201-0.564, P < 0.001), lymph node metastases (HR = 1.728, 95% CI = 1.070-2.792, P = 0.025), and American Society of Anesthesiologists grade (HR = 2.207, 95% CI = 1.412-3.450, P = 0.001) were independently associated with duration of survival. Multidisciplinary team management and surgical subspecialization improved outcomes after surgery significantly for patients diagnosed with esophageal cancer.

Definitive chemoradiation in patients with inoperable oesophageal carcinoma.

We performed a retrospective study of 90 consecutive cases with inoperable carcinoma of the oesophagus treated with definitive chemoradiation at a single cancer centre between 1995 and 2002. For the last 4 years, 73 patients have received therapy according to an agreed protocol. This outpatient-based regimen involves four cycles of chemotherapy, cycles 3 and 4 given concurrently with 50 Gy external beam radiotherapy (XRT) delivered in 25 fractions over 5 weeks. Cisplatin 60 mg m(-2) day(-1) is given every 3 weeks together with continuous infusional 5-fluorouracil 300 mg m(-2) day(-1), reduced to 225 mg m(-2) day(-1) during the XRT. In all, 45 (50%) patients suffered one or more WHO grade 3/4 toxicity, grade 3 in 93% cases. Patients received more than 90% of the planned chemoradiation schedule. The median overall survival was 26 (15, >96) months, 51% (41, 64) and 26% (13, 52) surviving 2 and 5 years, respectively. Advanced stage, particularly T4 disease, was associated with a worse prognosis. Patients considered not suitable for surgery for reasons other than their disease, mainly co-morbidity, had a significantly better outcome, median survival 40 (26, >96) months, 2- and 5-year survivals 67% (54, 84) and 32% (13, 79), respectively (P<0.001). This schedule is a feasible, tolerable and effective treatment for patients with oesophageal cancer considered unsuitable for surgery.

The significance of cardiac doses received during chemoradiation of oesophageal and gastro-oesophageal junctional cancers.

AIM: Although radiation-induced cardiotoxicity has been described in patients with breast cancer and Hodgkin's disease, the effect of oesophageal radiotherapy on the heart has not been evaluated. This study was designed to evaluate the dose received by the heart during chemoradiotherapy (CT-RT) for oesophageal cancer, to assess its impact on cardiac function, and explore methods of reducing this dose. METHODS: Cardiac doses were calculated from dose-volume histograms in 15 patients with carcinoma of mid and lower oesophagus undergoing combined technique treatment, in whom pre- and post-treatment multigated acquisition scans were available. Chemotherapy consisted of cisplatin and 5-fluorouracil with or without paclitaxel. The radiotherapy was delivered in two phases to a total dose of 45-50 Gy in 25 fractions. RESULTS: There was a significant reduction in median ejection fraction after CT-RT (63% to 58%, P = 0.003). The median dose received by the heart using three-dimensional conformal technique was 27.4 Gy (interquartile range 25.8-34.2 Gy). If shielding blocks were not used, as would be the case with conventional planning, the median dose would have been 35 Gy (interquartile range 28.2-37.7 Gy), which is significantly higher (P = 0.002). The use of a three-field technique throughout treatment also reduced the median cardiac dose from 27.4 Gy to 22.7 Gy (P = 0.001) and the volume of heart receiving 70% of total dose from 63.8% to 25% (P = 0.001). CONCLUSION: This study highlights the significant dose of radiation received by the heart during oesophageal CT-RT, with consequent reduction in cardiac ejection fraction. Conformal radiotherapy reduces cardiac doses received. The cardiac, as well as the pulmonary, side effects of CT-RT needs to be borne in mind, especially when using this treatment before radical surgery.