The ALERT-B questionnaire: A screening tool for the detection of gastroenterological late effects after radiotherapy for prostate cancer.

There is an increasing need to measure treatment-related side effects in normal tissues following cancer therapy. The ALERT-B (Assessment of Late Effects of RadioTherapy - Bowel) questionnaire is a screening tool that is composed of four items related specifically to bowel symptoms. Those patients that respond with a "yes" to any of these items are referred on to gastroenterologist in order to improve the long-term consequences of these side effects of radiological treatment. Here we wish to test the ability of this questionnaire to identify these subsequent gastroenterological complications by tracking prostate cancer patients that were positive with respect to ALERT-B. We also carry out receiver-operator curve (ROC) analysis for baseline data for an overall ALERT-B questionnaire score with respect to subscale data for the Gastrointestinal Symptom Rating Scale (GSRS) and the Expanded Prostate Cancer Index Composite (EPIC-26) questionnaire. 84.4% and 95.7% of patients identified by the ALERT-B questionnaire demonstrated complications diagnosed at 6 and 12 months post-treatment, respectively. ROC curve analysis of baseline data showed that ALERT-B detected clinically relevant levels of side effects established at baseline by the GSRS diarrhoea subscale (AUC = 0.867, 95% CI = 0.795 to 0.926) and at the minimally important level of side effects for the EPIC bowel subscale (AUC = 0.765, 95% CI = 0.617 to 0.913). These results show that ALERT-B provides a simple and effective screening tool for identifying gastroenterological complications after treatment for prostate cancer.

The prognostic value of serum and immunohistochemical tumour markers in advanced gastric cancer.

Using a prospectively acquired database of 290 patients with advanced gastric adenocarcinoma, the prognostic significance of serum levels of carcinoembryonic antigen (CEA) (237 patients), alphafeto protein (AFP) (164 patients), beta-human chorionic gonadotrophin (beta HCG) (165 patients), CA19-9 (64 patients) and CA125 (104 patients) and tissue staining for C-erb B-2 (160 patients) and beta HCG (160 patients) was investigated. Serum was taken prior to 5-fluorouracil (5FU)-based chemotherapy and immunohistochemistry was performed on diagnostic specimens. In the univariate analysis, tumour markers of poor prognosis were CEA > or = 5 micrograms/l (P = 0.01; median survival (MS) 42 versus 35 weeks), serum beta HCG > or = 4 U/l (P = 0.02; MS 42 versus 25 weeks), CA125 > or = 35 U/ml (P = 0.03; MS 43 versus 31 weeks) and CA125 > or = 350 U/ml (P = 0.001; MS 42 versus 17 weeks). Other significant factors were poor performance status, the presence of metastases and poorly differentiated tumour histology. Tumours markers of poor prognosis in the multivariate analysis were serum beta HCG > or = 4 IU/l [hazard ratio (HR) 1.7; 95% confidence interval (CI) 2.8-1.1] and CA125 > or = 350 U/ml (HR 2.2; CI 4.2-1.2). There was a degree of subgroup variability in this model but, in general, other factors correlating with a poor survival were poor performance status, metastases and poorly differentiated tumour histology. This is the largest prognostic study of each tumour marker in advanced disease and demonstrates that serum beta HCG and CA125 in gastric cancer prior to chemotherapy do convey an independent poor prognosis which may reflect not just tumour burden but aggressive biology.

Non surgical interventions for late radiation proctitis in patients who have received radical radiotherapy to the pelvis.

BACKGROUND: Chronic radiation proctitis (inflammation of the rectum) may develop after the completion of pelvic radiotherapy. Presently there is no recommended standard management. OBJECTIVES: To assess the effects of various non-surgical treatment options for the management of late chronic radiation proctitis. SEARCH STRATEGY: We searched the Cochrane Controlled Trials Register, issue 1, 2001, MEDLINE 1966 to 2001, EMBASE 1980 to 2001, CANCERCD 1980 to 2001, Science Citation Index 1991 to 2001, CINAHL 1982 to 2001, as well as sources of grey literature. We also hand searched relevant textbooks and contacted experts in the field. SELECTION CRITERIA: Studies (preferentially randomised controlled trials) of interventions for the non-surgical management of late radiation proctitis in patients who have undergone pelvic radiotherapy as part of their cancer treatment. DATA COLLECTION AND ANALYSIS: The inclusion criteria were independently applied by two of the reviewers (AD and EJM) and where there was disagreement this was resolved by involving a third reviewer to form a consensus. MAIN RESULTS: Six randomised controlled trials were included. None of the trials compared anti-inflammatories with placebo. However rectal sucralfate showed greater clinical improvement for proctitis than anti-inflammatories (odds ratio 14.00, 95% confidence interval 1.46 to 134.26; n=1 study), though no difference was seen for endoscopic improvement (odds ratio 2.74, 95% confidence interval 0.64 to 11.76, n=1 study). The addition of metronidazole to the anti-inflammatory regime also appeared to improve the response rate, as measured by the reduction in rectal bleeding, diarrhoea, erythema and ulceration (n=1 study). Similarly rectal hydrocortisone appeared to be more effective than rectal betamethasone for clinical improvement although no difference was seen in endoscopic improvement (n=1 study). Short chain fatty acid enemas did not appear to be effective compared to placebo (n=2 studies). In the comparison of the heater probe and bipolar electrocautery (n=1 study), there was no discernible difference for severe bleeding after one year, but the heater probe demonstrated a greater increase in the haematocrit and reduced transfusion requirements. REVIEWER'S CONCLUSIONS: Late radiation complications are a relatively rare manifestation, with many potential carers and poor diagnostic criteria. Although certain interventions look promising and may be effective (such as rectal sucralfate, adding metronidazole to the anti-inflammatory regime and heater probes), single small studies (even if well conducted) provide insufficient evidence. The episodic and variable nature of late radiation proctitis also requires placebo controlled studies to establish whether particular treatments are effective. Regional or centralised registers of radiation toxicity should be established so that interventions can be administered in the setting of multi-centre trials with specific entry criteria, formal baseline and therapeutic assessments providing standardised outcome data including quality of life evaluations.

Mitomycin C, carboplatin and protracted venous infusion 5-fluorouracil in advanced oesophago-gastric and pancreatic cancer: results of two phase II studies.

Cisplatin is an active palliative chemotherapy agent in advanced upper gastrointestinal cancer, but it is associated with significant non-haematological toxicity. Substitution of cisplatin by carboplatin in combination chemotherapy regimens may reduce these adverse effects. These two phase II studies evaluated the efficacy and toxicity of the combination of mitomycin C (MMC) 7 mg/m2 q 6 weekly, carboplatin area under the concentration-time curve 5 mg/ml/min q 3 weekly and protracted venous infusion 5-fluorouracil (5FU) 300 mg/m2/day (McarboF) in advanced upper gastrointestinal cancer. Between October 1998 and June 2000, 31 patients were enrolled in the studies, 23 patients in the oesophago-gastric study and eight patients in the pancreatic study. Although non-haematological toxicity was modest, both protocols were closed prematurely because of excessive haematological toxicity and frequent treatment delays. The overall incidence of grade 3/4 neutropenia and thrombocytopenia was 39 and 52%, respectively. The McarboF combination showed significant activity with an overall response rate of 52% in advanced oesophago-gastric cancer. Palliative benefit was also evident with improvement in symptoms of pain and weight loss in over 79 and 50% of patients in the oesophago-gastric study and pancreatic study, respectively. Median overall survival times were 10.6 and 6.6 months for patients with oesophago-gastric and pancreatic cancer, respectively. The McarboF regimen showed promising activity in advanced upper gastrointestinal cancer, with modest non-haematological side-effects. This combination merits further evaluation with modification of the dose and schedule of carboplatin and MMC in order to reduce the severity of haematological toxicity.

Lifestyle factors correlate with the risk of late pelvic symptoms after prostatic radiotherapy.

AIMS: Although technological improvements are reducing the risks of late side-effects of radiotherapy for prostate cancer, the influence of lifestyle has been less well examined. The aim of this study was to correlate the effects of exercise, body mass index and smoking on the incidence and severity of late pelvic symptoms after radical radiotherapy for prostate cancer. MATERIALS AND METHODS: In total, 440 men completed a questionnaire consisting of the Vaizey rectal symptoms score, the National Cancer Institute common symptoms scores for rectal bleeding, erectile function and urinary incontinence, the General Practice Physical Activity Questionnaire and questions regarding smoking, height and weight. The effect of each lifestyle factor on pelvic symptoms was investigated using a non-parametric multivariate ANOVA (Kruskal-Wallis) test and the chi-squared test. RESULTS: At the time of the survey, 63.3% of men were overweight or obese (body mass index > 25 kg/m(2)) and 71% were inactive or moderately inactive. Active men had significantly lower rectal symptoms scores (P < 0.001) and better erectile (P < 0.001) and urinary function (P < 0.01). Men smoking more than five a day had higher rectal symptoms scores (P < 0.001), as did overweight men (P < 0.05). CONCLUSION: The data show lower late pelvic symptoms after radiotherapy among non-smokers and physically active individuals with a body mass index <25. Although these results would ideally require confirmation in a prospective study, we now include advice on lifestyle in our pre-radiotherapy information pack. The high percentage of obesity and inactivity among this cohort of prostate cancer survivors revealed in this study has prompted the development of an exercise/weight reduction programme in our unit.

Gastrointestinal complications of pelvic radiotherapy: are they of any importance?

Radiation induced bowel damage affects 6000 individuals annually in the UK, with a negative impact on quality of life. Our understanding of how to treat these patients is dismally lacking an evidence base. Fibrosis seems to be the unifying underlying cause for most symptoms. Progress in understanding the development and treatment of fibrosis in these patients might have important consequences for patients with other causes of fibrosis in the gastrointestinal tract.

The prognostic value of CEA, beta HCG, AFP, CA125, CA19-9 and C-erb B-2, beta HCG immunohistochemistry in advanced colorectal cancer.

BACKGROUND: Evaluation of the prognostic significance of a group of tumour markers and their ability to predict response to chemotherapy may allow better targeting of palliative treatment in advanced colorectal cancer. PATIENTS AND METHODS: Using a prospectively acquired database of 377 patients (pts) with advanced colorectal adenocarcinoma, the prognostic significance of serum CEA (342 pts), beta HCG (203 pts), AFP (208 pts), CA125 (150 pts), CA-19-9 (76 pts) as well as C-erb B-2 (197 pts). Serum markers were taken prior to 5-FU based chemotherapy and immunohistochemistry was performed on diagnostic samples RESULTS: Tumour markers of poor prognostic significance in the univariate analysis were CEA > or = 5 micrograms/l (p = 0.006; median survival (MS 59 weeks vs 38 weeks) and CA125 > or = 35 U/ml (p = 0.01 MS 51 weeks vs. 30 weeks). Tumour markers elevated at greater than 10 times the normal value which correlated with a poor prognosis were CEA (p = 0.001; MS 47 weeks vs. 35 weeks), Serum beta HCG (p < 0.0001; MS 44 weeks vs. 7 weeks) and CA125 (p < 0.0001; MS 38 weeks vs. 15 weeks). Poor performance status ( > 2) and poorly differentiated tumour histology were also correlated to poor survival. In the multivariate analysis, tumour markers of independent poor prognosis were CEA > or = 5 micrograms/l (Hazard Ratio (HR) 1.8; 95% Confidence Internal (CI) 2.8-1.2), CEA > or = 50 micrograms/l (HR 1.6; CI 2.1-1.2), CA125 > or = 35 U/ml (HR 1.5; CI 2.3-1.0), CA 125 > or = 350 U/ml (HR 5.0; CI 9.6-2.6) and serum BHCG > or = 0 IU/l (HR 11.7; CI 30-4.5). Poor performance status (HR 6.7-5.0) and poorly differentiated histology (HR 2.8-1.0) were the other important factors in the model. No pretreatment tumour marker correlated with response to chemotherapy. CONCLUSIONS: This is the largest prognostic study of each tumour marker in advanced disease and it clarifies previous conflicting reports. Serum AFP, CA19-9 and immunohistochemical stains beta HCG and C-erb B-2 have no prognostic significance. Serum CEA, beta HCG, CA125 in advanced colorectal cancer prior to chemotherapy do convey an independent poor prognosis which may reflect not just tumour burden but aggressive biology.

Intestinal complications after chemotherapy for patients with unresected primary colorectal cancer and synchronous metastases.

BACKGROUND: The role of palliative resection of the primary tumour in patients who present with metastatic colorectal cancer is unclear. AIMS: This study compared the incidence of major intestinal complications in such patients who received chemotherapy treatment with or without prior palliative resection of the primary tumour. PATIENTS: The incidence of intestinal obstruction, perforation, fistula formation, and gastrointestinal haemorrhage, and the requirement for abdominal radiotherapy in patients with metastatic colorectal cancer treated at a single institution over a 10 year period was determined. RESULTS: Eighty two patients received initial treatment with chemotherapy without resection of the primary tumour (unresected group) and 280 patients had undergone prior resection (resected group). In the unresected group, the incidence of peritonitis, fistula formation, and intestinal haemorrhage was 2.4% (95% confidence interval (CI) 0.3-8.5%), 3.7% (95% CI 0.8-10.3%), and 3.7% (95% CI 0.8-10.3%), respectively, and was not significantly different from the resected group. Intestinal obstruction affected 13.4% (95% CI 6.9-22.7%) of patients in the unresected group and 13.2% (95% CI 9.2-17.2%) of patients in the resected group. More patients in the unresected group required >/=3 blood transfusions (14.6% v 7.5%; p=0.048) and abdominal radiotherapy (18.3% v 9.6%; p=0.03) than the resected group. CONCLUSIONS: The incidence of major intestinal complications in patients with unresected colorectal cancer and synchronous metastases who receive initial treatment with chemotherapy is low. Chemotherapy may be successfully used as initial treatment for such patients with no increased risk of most major intestinal complications compared with patients who have undergone initial resection of the primary tumour.