National Cancer Registry Ireland Research Articles

The Irish experience of changes in treatment outcomes in patients diagnosed with glioblastoma multiforme over a 10 year period.

e12512 Background: Glioblastoma Multiforme (GBM) is the most common primary brain tumour in adults. The most recent figures from the National Cancer Registry of Ireland revealed 180 new cases of GBM diagnosed in Ireland in 2008. In 2005 a phase III clinical trial demonstrated a significant improvement in survival over two and subsequently five years with the addition of concurrent and adjuvant temozolomide (TMZ) to radical radiotherapy (RT) (Stupp R, Hegi M, van den Bent M et al. Effects of radiotherapy with concomitant and adjuvant temozolomide versus radiotherapy alone on survival in glioblastoma in a randomised phase III study: 5-year analysis of the EORTC-NCIC trial. Lancet Oncol 2009:10:459-66.) The aim of this study was to investigate if the demonstrated improved survival in the literature translated to clinical practice. Methods: This is a retrospective study looking at 273 patients diagnosed with GBM and treated with adjuvant RT over a ten year period from 1998 to 2008 in Dublin, Ireland. The statistical analysis was carried out using SPSS v16. Results: The median survival for the overall group (n=273) was 7.6 months. In total 146 patients received radical RT. 103 received radical RT with concurrent and adjuvant TMZ. 43 patients received RT alone. The median survival for radical RT with TMZ was 13.4 months (95% CI 10.9-15.8) vs. 8.6 months for RT alone (95% CI 6.9-10.7, P=0.011). Two year survival figures were 21.2 vs. 4.7% respectively. A multivariate analysis identified independent predictors of survival. Palliative RT had a HR of 2.62 of death at any time (95% CI 1.66-4.12, p<0.0001) as compared to radical RT. Patients who did not receive TMZ were at a significant higher risk of death than those patients who did (HR 1.86, 95% CI 1.31 – 2.63, p<0.0001). With regards to surgical procedure biopsy only was inferior to any debulking (HR 1.54 95% CI 1.14-2.00, p< 0.004). Conclusions: This paper demonstrates improved treatment outcomes evidenced in a large phase III clinical trial translate to routine clinical practice. As shown on multivariate analysis radical debulking, radical RT, concurrent and adjuvant TMZ are independent predictors of survival.

Drinking water fluoridation and osteosarcoma incidence on the island of Ireland

The incidence of osteosarcoma in Northern Ireland was compared with that in the Republic of Ireland to establish if differences in incidence between the two regions could be related to their different drinking water fluoridation policies. Data from the Northern Ireland Cancer Registry (NICR) and the National Cancer Registry of Ireland (NCRI) on osteosarcoma incidence in the respective populations were used to estimate the age-standardised and age-specific incidence rates in areas with and without drinking water fluoridation. One hundred and eighty-three osteosarcoma cases were recorded on the island of Ireland between 1994 and 2006. No significant differences were observed between fluoridated and non-fluoridated areas in either age-specific or age-standardised incidence rates of osteosarcoma. The results of this study do not support the hypothesis that osteosarcoma incidence in the island of Ireland is significantly related to public water fluoridation. However, this conclusion must be qualified, in view of the relative rarity of the cancer and the correspondingly wide confidence intervals of the relative risk estimates.

Regional variations in testicular cancer rates in Ireland: clusters and communities

We welcome Alsinnawi et al.’s [1] paper on rates of testicular cancer. However, the authors imply an association with persistent organic pollutants (POPs), particularly polychlorinated biphenyls (PCBs) and higher socio-economic groups that does not stand up to scrutiny. No new evidence of a link between testicular cancer and POPs is presented in this paper. The authors state that PCBs and testicular cancer are ‘directly linked’. The authors cite two small studies which show a weak positive association between testicular cancer and PCBs. A recent, large and well-designed case–control study shows an inverse association between testicular cancer and several individual and grouped PCBs [2]. A more comprehensive synthesis of the total body of evidence is needed. They state ‘there does certainly seem to be a link with higher socio-economic status’. An aggregate of electoral districts in Cork with higher socio-economic status (SES) may have a greater incidence of testicular cancer, but this does not mean that testicular cancer is occurring at a greater frequency in men in higher socio-economic groups. SES was not recorded for individual men who had testicular cancer in this study. This is potential ecological bias [3]. The socio-economic status of cases is not collected by the National Cancer Registry of Ireland (NCRI). This is important when cancer rates for a small area are published. The socio-economic composition of a small area may be different from that of the comparison areas. Many specific cancers are linked to both socio-economic group and other known causes of cancer (smoking for instance). The confounding effect of social class on cancer, particularly in small areas, should always be considered before hypothesising a novel carcinogen. Worldwide, there is a strong public perception that environmental exposures are directly responsible for cancer. This is seldom the case. The epidemiological criteria for successful investigation of cancer clusters are a high relative risk (between 10 and 20); a rare cancer; the purported causative agent can be reliably measured in the environment; bio-monitoring is possible; there is heterogeneity of exposure in an area and a plausible route of exposure can be assessed [4]. These conditions are often not met, and most of them are not present in this study. However, the epidemiology may not matter as much as we think [5]. The strategic learning from the vast literature on cancer clusters is that regardless of the quality and validity of epidemiological and environmental investigation, if there has not been early and effective communication with the public, the scientific approach will not satisfy [6]. Publishing cancer rates without a comprehensive communication and investigation plan is not advised. This paper may cause anxiety, while it offers no plan of action and ignores the necessity of dealing with the community’s risk perception. Ireland needs a dedicated multi-disciplinary environment and health unit, with epidemiological, environmental and Public Health expertise. This unit could then respond to possible cancer clusters and other community environment and health concerns in a timely, coordinated, U. B. Fallon (&) Department of Public Health Medicine, HSE Dublin Mid-Leinster, Tullamore, Co. Offaly, Ireland e-mail: unab.fallon@hse.ie

Abstract P3-11-05: Association between Propanolol Use and Both Breast Cancer Incidence and Mortality

Abstract Background: The neurotransmitter epinephrine has been shown to promote breast cancer tumor cell migration, mediated through the ≥2 adrenergic pathway. In-vitro and in-vivo studies have demonstrated that the non-selective ≥1/≥2 adrenergic receptor antagonist propranolol inhibits the effects of epinephrine on breast cancer cell motility. Based on these studies we hypothesize that propranolol use prior to breast cancer diagnosis may result in a lower risk of locally advanced or metastatic disease at diagnosis and decrease the risk of breast cancer recurrence and mortality. Methods: To test these hypotheses we conducted a series of matched observational studies in a largely unscreened population, using pharmacy claims data linked to cancer registry data from the National Cancer Registry Ireland (NCRI, 2000-2007, n=5,949). Conditional logistic regression was used to estimate the odds ratio (OR) and 95% confidence intervals (CI) for stage at diagnosis. A Cox proportional hazard model was used to estimate the hazard ratio (HR) for breast cancer mortality. All analyses were repeated with atenolol, a selective ≥1 adrenergic receptor antagonist. Results: 71 patients taking propranolol in the year prior to breast cancer diagnosis were identified from the NCRI database (mean age 65; Stage-1 19.7%; Stage-2 57.8%; Stage-3 8.5%; Stage-4 8.5%; Unknown 5.6%). Patients taking propranolol in the year prior to breast cancer diagnosis were matched (1:2) using propensity scores to patients not taking a β-blocker by age, tumor grade, comorbidities, co-medications, demographics and socio-economic status. The odds of developing a T4 tumour for patients taking propranolol was OR 0.22, 95%CI 0.02, 0.98. (Atenolol: OR 1.29, 95%CI 0.83, 2.00). There was a twofold increase in the odds of developing a N0/M0 tumour (OR 2.02, 95%CI 1.03, 3.99) for patients taking propranolol in the year prior to breast cancer diagnosis compared to patients not taking a β-blocker after matching (1:2) for age, tumor size, tumor grade, and co-medications. (Atenolol OR 0.94, 95%CI 0.73, 1.19). Patients taking propranolol at the time of breast cancer diagnosis were matched to patients not taking a β-blocker (1:2) by age, tumor stage, tumor grade and comorbidities. At five years the cumulative probability of breast cancer death was 12.3% in patients taking propranolol and 33.3% in matched controls, HR 0.22, 95%CI 0.08, 0.61. (Atenolol HR 1.02, 95%CI 0.79, 1.31). Discussion: The use of propranolol, a non-selective ≥1/≥2 adrenergic receptor antagonist, results in a statistically significant reduction in the risk of locally advanced or metastatic breast cancer. The use of propranolol was also associated with a significant reduction in breast cancer mortality. No effect was observed with the use of a selective ≥1 adrenergic receptor antagonist. This suggests that the effects of propranolol in breast cancer are mediated through the ≥2 adrenergic pathway, supporting preclinical observations. To our knowledge, this is the first epidemiological study to examine the effects of propranolol on breast cancer stage at presentation and survival. Our results provide rationale for further investigation of this agent in breast cancer patients. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P3-11-05.

Geographical analysis of cancer incidence in Ireland: A comparison of two Bayesian spatial models

Aims: Our objective was to describe the geographical variation in cancer incidence using gastro-intestinal and non-melanoma skin cancer incidence data in Ireland using two different Bayesian spatial models and to compare the performance of these models. Methods: Cases diagnosed between 1994 and 2003 were extracted from the National Cancer Registry of Ireland. Population data were estimated from census data. For each of 3401 electoral divisions (EDs), relative risk (RR) estimates were calculated and smoothed using a conditional autoregressive model (CAR) and a spatial partition model introduced by Hegarty and Barry using a product partition model (PPM). The results were compared by mapping the ratio of the two RR estimates and other mainly descriptive statistics. Results: The two methods gave broadly similar results. For gastro-intestinal cancers the RRs were lower in a northwest/southeast band across the country with greater RRs around Dublin, Cork and in Donegal. Greater RR of non-melanoma skin cancer was observed in coastal areas. Median differences between the RR estimates were small (=0.01). The range of RRs was wider when estimated by the CAR model illustrating that the PPM smoothed the data to a greater extent than the CAR model. Conclusions: The two approaches gave similar results providing stronger evidence for the resulting geographical patterns. PPMs give a more global picture of the risk distribution whereas CAR models provide more local estimates. The observed patterns may reflect socio-demographic or geographic variations in risk factors or access to cancer services. By helping to identify those risks, these maps may help in the optimal allocation of scarce health resources.

Is there under-treatment of pancreatic cancer? Evidence from a population-based study in Ireland

Although clinical trials suggest that chemotherapy can improve survival for both resected and unresected pancreatic cancer patients, the extent to which it is used in routine clinical practice is unclear. We conducted a population-based investigation of treatment patterns and factors influencing treatment receipt and mortality for pancreatic cancer. We included 3173 patients with primary invasive pancreatic cancer, diagnosed in 1994–2003, from the National Cancer Registry (Ireland). Analysis was done by joinpoint regression, logistic regression and Cox proportional hazards. Propensity score methods were used to compare mortality in those who received chemotherapy and in ‘matched’ patients who did not. Seven percent of patients had a resection and 12% received chemotherapy. The resection rate did not change significantly over time and less than a quarter of patients with localised disease underwent resection. Chemotherapy use increased by 20% per annum, reaching 20% among unresected and 39% among resected patients in 2002–2003. Forty two percent of patients were untreated, and this percentage was unchanged over time. After adjusting for clinical factors, patient characteristics were significantly associated with treatment receipt; older and unmarried patients were less likely to be treated. Among resected patients, risk of death fell by 10% per annum. Chemotherapy receipt was associated with significantly reduced mortality among both surgical (hazard ratio (HR) = 0.50, 95% confidence intervals (CIs) 0.27–0.91) and non-surgical patients (HR = 0.48, 95% CI 0.38–0.61). Our findings suggest that there may be potential for extended dissemination of chemotherapy, and possibly also for greater utilisation of curative resection, in routine practice which, in turn, has potential to improve survival at the population level.

Inequity in colorectal cancer treatment and outcomes: a population-based study

Several uncertainties surround optimal management of colorectal cancer. We investigated treatment patterns and factors influencing treatment receipt and mortality in routine clinical practice. We included 15 249 individuals, recorded by the National Cancer Registry (Ireland), with primary invasive colon or rectal tumours, diagnosed during 1994–2002. Logistic regression and Cox proportional hazards were used to determine factors associated with treatment receipt within 1 year of diagnosis and with mortality, respectively. A total of 78% had colorectal resection, 31% chemotherapy, and 13% radiotherapy (4% colon; 28% rectum). Half of stage IV patients underwent resection. Chemotherapy and radiotherapy use increased by at least 10% per annum. There was a notable increase in pre-operative radiotherapy from 2000 onwards. Patient-related factors were significantly associated with treatment receipt. Patients who were male, older, not married, or smokers had significantly higher risks of death. Chemotherapy was significantly associated with lower mortality for stage III, but not stage II, colon cancer. For rectal cancer, pre-operative radiotherapy was associated with reduced mortality. Surgery and chemotherapy were associated with longer survival for stage IV patients. The observed inequities in treatment and outcomes suggest that there is potential for further dissemination of therapies in routine practice. Improving treatment availability overall, and equity, has the potential to reduce mortality.

Rising incidence of renal cell carcinoma in Ireland

To determine the trend in the incidence of renal cell carcinoma in Ireland, and evaluate changes in the modes of presentation and outcomes. Data on all histologically diagnosed renal cancers in Ireland over a 12-year period (1994-2005) were retrieved from the database of the National Cancer Registry of Ireland. Data on all renal cancer deaths in Ireland in the period 1994-2004 were obtained from the Central Statistics Office. There were 2,485 cases of renal cell carcinoma from 1994 to 2005, of which 64% were in males and 36% in females. The average age of females at diagnosis fell from 63 years in 1994 to 58 years in 2005, with little change in the average age in males. The age-adjusted incidence of renal cell carcinoma per 100,000 person-year increased from 5.2 in 1994 to 6.8 in 2005, an annual percentage change of +3.4%. The percentage of incidental renal cell carcinoma increased from 5% in 1999 to 21% in 2003. The age-adjusted mortality rate for males increased from 4.8 per 100,000 person-year in 1994 to 7.3 in 2004, while that for females decreased from 2.6 to 2.3 in the same period. There was no overall increase in survival over the study period. While the incidence of renal cell carcinoma is increasing in Ireland, largely, but not entirely, due to an increase in incidentally diagnosed cancers, mortality is increasing in males only.

Patterns of care and effects on mortality for cancers of the oesophagus and gastric cardia: A population-based study

Background We investigated temporal trends in treatment, and factors influencing treatment receipt and survival, for upper gastrointestinal cancers in routine community-based clinical practice. Patients and methods Oesophageal and gastric-cardia cancers, diagnosed during the period 1994–2001, were sourced from the National Cancer Registry (Ireland). Analysis was by Joinpoint regression and multivariate logistic and Cox models. Results Thirty-five percent of patients received surgery, 35% radiotherapy and 24% chemotherapy. Over time chemo- and radiotherapy receipt increased significantly, whilst surgery decreased. Treatment patterns varied by tumour site, histology and stage. Older and/or unmarried patients were significantly less likely to receive treatment. Among surgically treated patients, those aged 70+ had higher mortality. Among both surgical and non-surgical patients, those receiving chemotherapy or radiotherapy had a modest, short-term, survival benefit. Conclusions The use of adjuvant therapies is increasing in routine practice. After adjusting for clinical factors, patient-related factors predicted treatment and mortality. Improving equity in gastrointestinal cancer treatment may help improve survival.

Treatment and survival for non-Hodgkin’s lymphoma: Influence of histological subtype, age, and other factors in a population-based study (1999–2001)

Aims This population-based study investigates the use of chemotherapy and radiotherapy for non-Hodgkin’s lymphoma (NHL) treatment in clinical practise generally, and for specific histologies, and identifies factors associated with treatment and survival. Methods Data for NHL patients, diagnosed during 1999–2001, were obtained from the National Cancer Registry (Ireland). Multivariate models were analysed on survival and treatment. Results 45–77% of patients received chemotherapy, 22–34% of patients received the radiotherapy, depending on the histology. Patients aged <65, married, with early stage B-cell aggressive disease were more likely to receive chemotherapy( P < 0.05). Patients >65 or with advanced stage were less likely to receive radiation ( P < 0.05). Survival was poorer in older( P < 0.001) and unmarried patients ( P < 0.05), and those with B-cell aggressive lymphoma( P < 0.001). Patients who received chemotherapy and radiation had lower hazard ratios. Conclusions Overall, the use of chemotherapy and radiation in this European population was similar to the findings in the US where older patients received treatment less often. However, the age disparity here was greater than that in the US.

Looking on from the sidelines: the use of Geographical Information Systems in Health Boards in Ireland 2003

Smith et al. (2003) present a heartening review of the development of Geographical Information Systems in Health Authorities in England and Wales over the period 1991-2001. Although Smith et al. (2003) note that 'there is still considerable scope for the wider uptake and use of GIS within the NHS', they clearly outline growth both in the extent of GIS use in Health Authorities, and in the increasing level of sophistication associated with its use. In neighbouring Ireland, however, the situation in regards to GIS in the Health Boards remains in its fragile infancy. Despite the promised reward and benefits of GIS described in some publications (e.g. De Lepper et al. 1995; Lang 2000), GIS develop ments in the health field in Ireland remain stunted, uneven and uncoordinated (Houghton 2001a). In early 2003, a survey was conducted examining GIS use, resources and training in Health Boards and allied health organizations in the Republic of Ireland. At the time of conducting this survey the Republic of Ireland was effectively composed of eight Health Boards.' Results show that five out of the eight Irish Health Boards had a GIS. These systems were generally based within Departments of Public Health, although in one case a comparatively advanced system was solely located within an ambulance service. The most common GIS package within the Boards was ArcView (used by three Boards). Given its global market share, it was perhaps surprising that only one of the Boards was using Maplnfo. The survey revealed that four out of five of the Health Boards that had a GIS were using their systems for purely display purposes (creating 'pretty pictures'). This is reflected in the fact that none of the Health Boards contacted had purchased any add-on software modules such as (ArcView's) Spatial Analyst. Some indication of the relative lack of use of GIS is reflected in the fact that just two Boards had GPS units, while only one Health Board had a digitizing tablet (this Board was also the only one possessing a plotter). Although the cost of purchasing digital maps from the Ordnance Survey of Ireland (OSI) is by no means cheap, it appears to have proven by no means prohibitive. All of the Boards with a GIS had purchased a variety of raster and boundary maps of their respective areas. However, only two boards had purchased vector maps detailing information other than administrative boundaries. In light of the proliferation of topic-specific state funded health agencies in Ireland in recent years, this survey was also conducted with two of these leading agencies. Those surveyed were the National Cancer Registry of Ireland (www.ncri.ie), and the National Disease Surveillance Centre (www.ndsc.ie). Both of these organizations have a GIS (ArcView in both cases). However, once again it was noted that neither system was being utilized as a GIS, rather than as a more basic mapping package, with both packages primarily being used for display purposes. These results obviously focus attention on the barriers to both uptake of GIS in Health Boards in

Patterns of initial management of lung cancer in the Republic of Ireland: a population-based observational study

Objectives: To examine geographic and temporal trends in the patterns of initial management of lung cancer in Ireland, and to describe differences in case management according to health board of residence. Design: Population-based observational study using the database of the National Cancer Registry of Ireland. Patients: 7286 patients with primary malignant lung tumours who were diagnosed in Ireland during the 5-year period from 1994 to 1998. Methods: We compared health boards in terms of treatment patterns of small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC) cases adjusting for differences in age, gender, and deprivation status. Result: Only half of the patients received any cancer-specific treatment. Radiotherapy was the most commonly employed single-treatment modality (21.7%) followed by surgery (12.3%) and chemotherapy (8.8%). Relative to the Eastern Health Board, the risk of being untreated was significantly higher for NSCLC patients living in the Western, Mid-Western, North, and South-Eastern Health Boards. For SCLC, only the Mid-Western and South-Eastern Heath Boards had significantly higher relative risks. For both groups, older patients were less likely to receive treatment, but we could not adjust for stage and comorbidity. Conclusion: We found wide regional variations in treatment rates of lung cancer in Ireland.