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1.  Adjuvant chemotherapy in elderly patients with pancreatic cancer 
British Journal of Cancer  2013;110(2):313-319.
Adjuvant chemotherapy improves survival for patients with resected pancreatic cancer. Elderly patients are under-represented in Phase III clinical trials, and as a consequence the efficacy of adjuvant therapy in older patients with pancreatic cancer is not clear. We aimed to assess the use and efficacy of adjuvant chemotherapy in older patients with pancreatic cancer.
We assessed a community cohort of 439 patients with a diagnosis of pancreatic ductal adenocarcinoma who underwent operative resection in centres associated with the Australian Pancreatic Cancer Genome Initiative.
The median age of the cohort was 67 years. Overall only 47% of all patients received adjuvant therapy. Patients who received adjuvant chemotherapy were predominantly younger, had later stage disease, more lymph node involvement and more evidence of perineural invasion than the group that did not receive adjuvant treatment. Overall, adjuvant chemotherapy was associated with prolonged survival (median 22.1 vs 15.8 months; P<0.0001). Older patients (aged ⩾70) were less likely to receive adjuvant chemotherapy (51.5% vs 29.8% P<0.0001). Older patients had a particularly poor outcome when adjuvant therapy was not delivered (median survival=13.1 months; HR 1.89, 95% CI: 1.27–2.78, P=0.002).
Patients aged ⩾70 are less likely to receive adjuvant therapy although it is associated with improved outcome. Increased use of adjuvant therapy in older individuals is encouraged as they constitute a large proportion of patients with pancreatic cancer.
PMCID: PMC3899761  PMID: 24263063
pancreatic cancer; adjuvant chemotherapy; elderly
2.  The prognostic and predictive value of serum CA19.9 in pancreatic cancer 
Annals of Oncology  2012;23(7):1713-1722.
Current staging methods for pancreatic cancer (PC) are inadequate, and biomarkers to aid clinical decision making are lacking. Despite the availability of the serum marker carbohydrate antigen 19.9 (CA19.9) for over two decades, its precise role in the management of PC is yet to be defined, and as a consequence, it is not widely used.
We assessed the relationship between perioperative serum CA19.9 levels, survival and adjuvant chemotherapeutic responsiveness in a cohort of 260 patients who underwent operative resection for PC.
By specifically assessing the subgroup of patients with detectable CA19.9, we identified potential utility at key clinical decision points. Low postoperative CA19.9 at 3 months (median survival 25.6 vs 14.8 months, P = 0.0052) and before adjuvant chemotherapy were independent prognostic factors. Patients with postoperative CA 19.9 levels >90 U/ml did not benefit from adjuvant chemotherapy (P = 0.7194) compared with those with a CA19.9 of ≤90 U/ml (median 26.0 vs 16.7 months, P = 0.0108). Normalization of CA19.9 within 6 months of resection was also an independent favorable prognostic factor (median 29.9 vs 14.8 months, P = 0.0004) and normal perioperative CA19.9 levels identified a good prognostic group, which was associated with a 5-year survival of 42%.
Perioperative serum CA19.9 measurements are informative in patients with detectable CA19.9 (defined by serum levels of >5 U/ml) and have potential clinical utility in predicting outcome and response to adjuvant chemotherapy. Future clinical trials should prioritize incorporation of CA19.9 measurement at key decision points to prospectively validate these findings and facilitate implementation.
PMCID: PMC3387824  PMID: 22241899
adjuvant chemotherapy; CA19.9; pancreatic cancer; prognosis
3.  Prefrontal Function at Presentation Directly Related to Clinical Outcome in People at Ultrahigh Risk of Psychosis 
Schizophrenia Bulletin  2009;37(1):189-198.
Background: The prodromal phase of psychosis is characterized by impaired executive function and altered prefrontal activation. The extent to which the severity of these deficits at presentation predicts subsequent clinical outcomes is unclear. Methods: We employed functional magnetic resonance imaging in a cohort of subjects at clinical risk for psychosis and in healthy controls. Images were acquired at clinical presentation and again after 1 year, using a 1.5-T Signa MRI scanner while subjects were performing a verbal fluency task. SPM5 was used for the analysis of imaging data. Psychopathological assessment of the “at-risk” symptoms was performed by using the Comprehensive Assessment for the At-Risk Mental State (CAARMS) and the Positive and Negative Symptom Scale (PANSS). Results: In the at-risk mental state (ARMS) group, between presentation and follow-up, the CAARMS (perceptual disorder and thought disorder subscales) and the PANSS general scores decreased, while the Global Assessment of Functioning (GAF) score increased. Both the ARMS and control groups performed the verbal fluency task with a high degree of accuracy. The ARMS group showed greater activation in the left inferior frontal gyrus but less activation in the anterior cingulate gyrus than controls. Within the ARMS group, the longitudinal normalization of neurofunctional response in the left inferior frontal gyrus was positively correlated with the improvement in severity of hallucination-like experiences. Conclusions: The normalization of the abnormal prefrontal response during executive functioning is associated with 12-month psychopathological improvement of prodromal symptoms.
PMCID: PMC3004199  PMID: 19666832
prodromal psychosis; fMRI; executive functions; ARMS; cognition
4.  The feasibility and results of a population-based approach to evaluating prostate-specific antigen screening for prostate cancer in men with a raised familial risk 
British Journal of Cancer  2006;94(4):499-506.
The feasibility of a population-based evaluation of screening for prostate cancer in men with a raised familial risk was investigated by studying reasons for non-participation and uptake rates according to postal recruitment and clinic contact. The levels of prostate-specific antigen (PSA) and the positive predictive values (PPV) for cancer in men referred with a raised PSA and in those biopsied were analysed. First-degree male relatives (FDRs) were identified through index cases (ICs): patients living in two regions of England and diagnosed with prostate cancer at age ⩽65 years from 1998 to 2004. First-degree relatives were eligible if they were aged 45–69 years, living in the UK and had no prior diagnosis of prostate cancer. Postal recruitment was low (45 of 1687 ICs agreed to their FDR being contacted: 2.7%) but this was partly due to ICs not having eligible FDRs. A third of ICs in clinic had eligible FDRs and 49% (192 out of 389) agreed to their FDR(s) being contacted. Of 220 eligible FDRs who initially consented, 170 (77.3%) had a new PSA test taken and 32 (14.5%) provided a previous PSA result. Among the 170 PSA tests, 10% (17) were ⩾4 ng ml−1 and 13.5% (23) tests above the age-related cutoffs. In 21 men referred, five were diagnosed with prostate cancer (PPV 24%; 95% CI 8, 47). To study further the effects of screening, patients with a raised familial risk should be counselled in clinic about screening of relatives and data routinely recorded so that the effects of screening on high-risk groups can be studied.
PMCID: PMC2361168  PMID: 16434997
prostate-specific antigen; mass screening; family health; prostatic neoplasm
5.  Randomised controlled trial of mammographic screening in women from age 40: results of screening in the first 10 years 
British Journal of Cancer  2005;92(5):949-954.
Debate continues over the effectiveness of screening by mammography in women below age 50. We report here on results of screening in the first 10 years of a randomised trial to study the effect on breast cancer mortality of invitation to annual mammography from age 40 to 41 compared to first invitation to the 3-yearly UK national programme at age 50–52. The trial is taking place in 23 NHS breast screening centres. Between 1991 and 1997, 160 921 women were randomised in the ratio 1 : 2 to intervention and control arms. Screening is by two views at first screen and single view subsequently; data on screening up to and including round five are now complete. Uptake of invitation to screening is between 68 and 70% at all but the latest screening rounds. Rates of referral for assessment are 4.6% at first screen and 3.4% at subsequent screens. Invasive cancer detection rates are 0.09% at first screen, and similar at rescreens until the sixth and later screens. There is little evidence of regular mammography in the trial control arm. The setting of this trial within the NHS breast screening programme should ensure applicability of results to a national programme.
PMCID: PMC2361899  PMID: 15726102
breast; screening; mammography; age; trial
6.  Routine breast screening for women aged 65–69: results from evaluation of the demonstration sites 
British Journal of Cancer  2001;85(9):1289-1294.
Routine programme data and specially designed surveys from 3 demonstration sites were analysed to determine the implications of extending the NHS Breast Screening Programme (NHSBSP), to include routine invitations for women up to 69 years. All women aged 65–69 and registered with GPs in these areas received routine invitations for breast screening along with those aged 50–64. Overall uptake was 71% in women aged 65–69 compared with 78% in younger women, but was ≥ 90% in both groups who had previously attended within 5 years. Recall rates were lower for older women, but with a higher positive predictive value for cancer. The percentages of invasive cancer in different prognostic categories were similar in the 2 age groups. Older women took no longer to screen than younger women. The costs per woman invited or per woman screened were also similar to those for women aged 50–64, whilst the cost per cancer detected was some 34% lower in older women. Breast screening is as cost effective for women aged 65–69 as for those aged 50–64, with a higher cancer detection rate balancing shorter life expectancy. The proposed extension to the national programme will have considerable workforce implications for the NHSBSP and require additional resources. © 2001 Cancer Research Campaign
PMCID: PMC2375256  PMID: 11720462
breast cancer; screening; older women
7.  National Health Service breast screening programme results for 1991-2. 
BMJ : British Medical Journal  1993;307(6900):353-356.
OBJECTIVES--To report the results of the NHS breast screening programme for the year March 1991 to April 1992. DESIGN--A report of statistics was derived from Körner (K62) returns and from the radiology quality assurance programme. MAIN OUTCOME MEASURES--Detection rates for breast cancer and small (< or = 10 mm diameter) invasive cancer, benign biopsy rates, and recall and acceptance rates. RESULTS--The acceptance rate for screening across the United Kingdom was 71.3%. The referral rate for further investigation was 6.2% (regional 4.3-9.0%). The breast cancer detection rate was 6.2 cancers per 1000 women screened (5.1-9.0) and the detection rate of invasive cancers < or = 10 mm was 1.4/1000 (1.0-2.3). 72% of screening programmes reached the target 70% acceptance rate, and 95% of programmes achieved a recall rate of less than 10%. 75% of programmes had a cancer detection rate of more than 5/1000, but only 32% had a detection rate for invasive cancers < or = 10 mm of more than 1.5/1000. CONCLUSIONS--Overall, the results of the screening programme for the year 1991-2 can be regarded as extremely satisfactory, given the size and complexity of the operation.
PMCID: PMC1678248  PMID: 8374416
8.  Anatomical musings 
PMCID: PMC1878615  PMID: 20312762

Results 1-8 (8)