Gender and immunosuppression impact on Merkel cell carcinoma diagnosis and prognosis. A population based cohort study.

Background: Merkel cell carcinoma (MCC), a rare cutaneous neuroendocrine endocrine tumour is increasing in incidence, and continues to carry a poor prognosis. Objectives: The objectives of this study were to examine all Irish cases of MCC from 1 January 1994 over 2 decades, focusing on gender and organ transplantation recipients (OTRs). Cases were identified from the National Cancer Registry of Ireland. Covariates of interest included age, body site, period of diagnosis, deprivation-status and history of non-melanoma skin cancer (NMSC). Results: In total 314 MCC cases were identified. A female predominance was noted (53.8%). Comparison between age-standardised rates between the earliest period (1994-1996) with the latest period (2012-2014) showed an increase of 105% in total. The trend in age-standardised incidence rates were noted to be increasing significantly (p = 0.0004). Average age at diagnosis was 77.6 years (male 75.1 years, female 79.7 years). Overall, the majority of MCC cases presented on the head and neck (n = 170, 54.1%). Differences in anatomical location of MCCs were noted between genders. Males were found to be more likely to have a history of previous NMSCs (males n = 73 [57.9%], females n = 53 [42.1%]). Thirty-one percentage of patients died from MCC, average survival was 3.5 years in those who died of this malignancy. Ten organ transplant recipients developed MCC. OTR who developed MCC were diagnosed at a younger average age of 65.1 years. Standardized incidence ratio for MCC in OTR was 59.96. A higher proportion of OTR died from MCC (70%), with a shorter median survival of 0.14 years. In competing risks regression, gender was not significantly associated with risk of dying, females having a non-significantly higher hazard of dying. Organ transplant recipients and patients from less deprived areas were at greater risk of dying from MCC. Conclusions: This population based study provides epidemiological, clinical and outcome data for MCC over a 20-year period.

Penile cancer in Ireland - A national review.

OBJECTIVE: Penile cancer is a rare malignancy, with a reported incidence of 1.5/100,000 males in the Republic of Ireland in 2015. The aim of this study was to perform the first national review and to evaluate clinicopathological factors affecting survival. SUBJECTS AND METHODS: All cases of penile cancer in Ireland between 1995 and 2010 were identified through the National Cancer Registry Ireland (NCRI) and analysed to identify factors affecting survival. RESULTS: 360 cases of penile cancer were identified, with a mean age at diagnosis of 65.5 years and 88% (n = 315) of cases occurred in those over 50. 91% (n = 328) of cases were squamous cell carcinomas (SCC). The majority of patients were treated surgically (n = 289), with 57% (n = 206) and 24% (n = 87) undergoing partial penectomy and total penectomy respectively. Only 18% (n = 65) received radiotherapy, and 8% (n = 27) received chemotherapy. Mean overall survival (OS) was 113 months, and five year disease specific survival (DSS) was 70% (95%CI: 59.1-77.8%). Age at diagnosis, nodal status and presence of metastatic disease were independent prognostic markers on multivariate analysis. CONCLUSION: This study represents the first national review of penile cancer in Ireland. The annual incidence and survival rates are comparable to European figures, though superior DSS has previously been reported from our institution, highlighting the role for centralisation of care in Ireland. LEVEL OF EVIDENCE: 2b.

Declining incidence of keratinocyte carcinoma in organ transplant recipients.

BACKGROUND: All organ transplant populations are predisposed to increased rates of keratinocyte carcinoma (KC). Since this increased risk was first appreciated, immunosuppressive regimens have changed and organ transplant recipients (OTRs) have been aggressively screened for KC. There is a perception that these measures have impacted on KC incidence but there is a paucity of population-based studies on post-transplant rates of basal cell carcinoma (BCC). OBJECTIVES: To identify trends in incidence rates for KC following solid organ transplantation over the past two decades. METHODS: This nationwide, population-based study included all solid OTRs transplanted between 1994 and 2014. Patient data were matched to national cancer registry data to determine the standardized incidence ratio (SIR) of KC in solid OTRs compared with the general population. RESULTS: In total 3580 solid OTRs were included. The total follow-up time was 28 407 person-years (median follow-up 7·11 years). The overall SIRs for squamous cell carcinoma (SCC) and BCC were 19·7 and 7·0, respectively. Our study documents a progressive fall in the SIRs for SCC and BCC from peak SIRs (95% confidence intervals) in 1994-1996 of 26·4 (21·5-32·4) and 9·1 (7·4-11·3) to 6·3 (2·3-16·7) and 3·2 (1·4-7·1) in 2012-2014, respectively. The ratio of SCC to BCC has remained at 3 to 1 over the last two decades. CONCLUSIONS: Our study is the first to demonstrate a significant reduction over the past two decades in the incidences of both SCC and BCC following solid organ transplantation. The SCC-to-BCC ratio was maintained, demonstrating that both are reducing equally. This trend coincided with temporal changes in immunosuppressive protocols and the introduction of skin cancer prevention programmes. What's already known about this topic? Prior studies have shown that the risk of cutaneous squamous cell carcinoma (SCC) has declined over recent decades following solid organ transplantation. It is not known whether the risk of basal cell carcinoma (BCC) has reduced in line with this. What does this study add? Our study documents a progressive fall in the risk of SCC and BCC following solid organ transplantation over the last two decades. The SCC-to-BCC ratio was maintained, demonstrating that both are reducing equally. The trends observed in our study coincided with temporal changes in immunosuppressive protocols and the introduction of cancer prevention programmes, suggesting that these factors have positively impacted on the risk of keratinocyte carcinoma in this cohort.

Peritoneal metastases from extra-abdominal cancer - A population-based study.

INTRODUCTION: Peritoneal metastases (PM) are predominantly seen as a manifestation of intra-abdominal malignancy such as colorectal or ovarian cancer. However, extra-abdominal primary cancer can also metastasise to the peritoneum. Population-based data on the incidence of PM from extra-abdominal cancer is lacking. This study aims to assess the patterns and survival of patients in Ireland with PM from extra-abdominal cancers. METHODS: The National Cancer Registry of Ireland database was interrogated to identify patients diagnosed with PM from extra-abdominal malignancy during the period 1994-2012. Patient demographics and tumour characteristics were analysed. RESULTS: 5791 patients were diagnosed with PM during the study period. Of these, 543 (9%) had an extra-abdominal primary malignancy. Breast (40.8%), lung (25.6%) and melanoma (9.3%) were the most common extra-abdominal cancers to develop PM. The majority of patients with peritoneal metastases of breast origin (75%) were diagnosed at a long interval (median interval 59.5 months; range = 1-485) from the diagnosis of the primary. The median survival from diagnosis of PM was 5.8 months compared with 22.6 months from diagnosis of stage IV disease without peritoneal involvement. Survival in patients with lung cancer and melanoma who developed PM was very poor and similar to that in patients with stage IV disease not involving the peritoneum. CONCLUSION: This is the first population-based study to report the incidence of PM secondary to extra-abdominal malignancy. The most common primary cancers were melanoma, breast and lung cancer. Metastatic disease to the peritoneum was uniformly associated with a poor prognosis.

An 18 year population-based study on site of origin and outcome of patients with peritoneal malignancy in Ireland.

Peritoneal malignancy (PM) is predominantly metastatic spread from advanced gastrointestinal or gynaecological cancer. PM is generally considered incurable and therefore has rarely been the focus of novel therapeutic strategies. This study assessed patterns and survival outcomes for patients with PM in Ireland. The National Cancer Registry Ireland database was interrogated to identify patients diagnosed with PM during the period 1994-2012. Patient and tumour characteristics were retrieved and survival outcomes calculated. 5791 patients were diagnosed during the study period. Median age at diagnosis was 68 years; females accounted for 62%. The incidence increased annually from 228 in 1994 to 401 in 2012. Primary PM accounted for 3% of cases. Colorectal (22%), ovarian (16%) and gastric (13%) cancers accounted for the majority of cases of secondary PM. Almost 75% of patients had PM at initial presentation. Almost 40% of patients (n = 2274) underwent surgical intervention, while 44% (n = 2560) had tumour directed chemotherapy. The median survival (MS) in patients with secondary PM was 6.6 months, and did not improve significantly during the study period. Outcomes were best in patients with ovarian cancer (MS 15.9 months) and colorectal cancer (MS 14.3 months) and worst in patients with lung (MS 2.4 months) and pancreas (MS 1.9 months) cancers. This is the first population-based study from Ireland to report the incidence and outcomes for PM. PM is more common than previously reported and survival remains poor. These findings highlight the need for greater clinician awareness and the need to focus on new therapeutic approaches to improve patient outcomes.

Increased non-melanoma skin cancer risk in young patients with inflammatory bowel disease on immunomodulatory therapy: a retrospective single-centre cohort study.

BACKGROUND: Recent studies report an increased risk of non-melanoma skin cancer (NMSC) in immunosuppressed patients with inflammatory bowel disease (IBD). Concurrently, paediatric IBD incidence is rising, with more patients now exposed to immunomodulators from a younger age. OBJECTIVES: To investigate NMSC incidence and to examine the risk associated with immunomodulators in the development of NMSC in patients with IBD. METHODS: This was a retrospective single-centre cohort study. Patients with IBD attending a tertiary adult hospital from 1994 to 2013 were included. Skin cancer incidence was compared with population data from the National Cancer Registry of Ireland (NCRI) to calculate standardized incidence ratio (SIR). Logistic regression was utilized for risk factor analysis. RESULTS: Two thousand and fifty-three patients with IBD were studied. The SIR for NMSC in patients with IBD taking immunomodulators overall was 1.8 (95% CI: 1.0-2.7) with age-specific rates significantly elevated across certain age categories. Exposure to thiopurines (OR: 5.26, 95% CI: 2.15-12.93, P < 0.001) and in particular thiopurines and/or tumour necrosis factor alpha (TNF-α) inhibitors (OR: 6.45, 95% CI: 2.69-15.95, P < 0.001) was significantly associated with NMSC. The majority (82%) of those exposed to a TNF-α inhibitor also had thiopurine exposure. CONCLUSIONS: Compliance with skin cancer preventative measures should be highlighted to all patients with IBD. There should be a low threshold for dermatology referral for immunosuppressed patients, particularly those with a history of exposure to dual immunomodulators from a young age.

Aggressive medullary thyroid cancer, an analysis of the Irish National Cancer Registry.

BACKGROUND AND OBJECTIVES: Medullary thyroid cancer consists of a spectrum of disease that ranges from extremely indolent tumors to aggressive types associated with a high mortality rate. The objective of our study is to evaluate the prognostic factors and outcomes of patients diagnosed with MTC in a homogenous population, and to examine patients diagnosed with MTC for mutations in the RET proto-oncogene from the same period. METHODS: A retrospective analysis of the National Cancer Registry in Ireland was undertaken, between 1998 and 2007. The Kaplan-Meier method was used to determine overall survival and factors predictive of outcome were determined by univariate and multivariate analysis by cox regression using Stata 13 software. MAIN FINDINGS: Forty-three patients were diagnosed with medullary thyroid cancer, 55.8 % were female and 44.2 % were male. A median age of 52 was found. The overall median survival was 6.32 years and the 1- and 5-year overall survival was 88.37 and 62.79 %, respectively, with 10-year survival calculated at 48.63 %. On univariate analysis age, stage and surgical intervention were statistically significant indicators of prognosis. T stage and age remained statistically significant indicators of prognosis on multivariate analysis. Two patients with no history of MEN syndromes or family history of medullary thyroid cancer had RET proto-onocogene mutations. CONCLUSIONS: Our patient cohort was substantially older and presented at an advanced T status than what is commonly seen in the literature. This may account for poor survival outcomes and the very low pick-up of RET mutations in sporadic medullary thyroid cancer.

Increasing skin cancer incidence in young, affluent, urban populations: a challenge for prevention.

BACKGROUND: Nonmelanoma skin cancer (NMSC) is the most common cancer in white people, but is registered inconsistently by population-based registries. OBJECTIVES: To analyse the changing profile of NMSC in a national population, to interpret evolving patterns of sun exposure and to recommend measures to reduce risk. METHODS: We analysed trends in the demographic, clinical and socioeconomic profile of > 50 000 cases of NMSC registered between 1994 and 2011 by the Irish National Cancer Registry, which aims to register all episodes of NMSC in the Irish population to a high degree of completeness. RESULTS: The incidence of cutaneous basal cell (BCC) and squamous cell carcinoma (SCC) was stable from 1994 to 2002, but increased significantly (BCC more than SCC) in the subsequent decade. The largest relative increases in the incidence of BCC were in younger populations and in clothed body sites. The incidence of both cancers was lower in rural areas. Incidence of BCC and, to a lesser extent, of SCC, increased with increasing affluence in urban, but not in rural, areas. CONCLUSIONS: Recent increases in skin cancers on the trunk and limbs in younger people appear to be related to increasing affluence and consequent leisure-related, episodic sun exposure. This population is at high risk of subsequent skin cancers throughout life and will need active surveillance. As preventive programmes are cost-effective in lowering the incidence of NMSC, they should be targeted at leisure exposure in young people. The recording of consistent international data on NMSC should also be a priority.

Increased diagnosis and detection rates of carcinoma in situ of the breast.

The purpose of this study was to identify trends in the diagnosis of carcinoma in situ (CIS) of the breast in the United Kingdom (UK) and the Republic of Ireland (ROI) and to examine the impact of mammography. Data on cases of newly diagnosed CIS of the breast and mode of detection (screen detected or not) were obtained, where available, from regional cancer registries between 1990 and 2007. Age-standardised diagnosis rates for the UK and the ROI, and regional screen detected diagnosis rates were compared by calculating the annual percentage change (APC) over time. The APC of the diagnosis rate amongst women aged 50-64 years (original screening age group) showed a significant 5.9% increase in the UK (1990-2007) and 11.5% increase in the ROI (1994-2007). The rate of diagnosis (50-64 years) stabilized in the UK between 2005 and 2007 and was substantially higher than in other western populations with national screening programmes. The APC of the diagnosis rate amongst those aged 65-69 years showed a significant 12.4% increase in the UK (1990-2007) and 10.3% increase in the ROI (1994-2007). amongst women aged 50-74 years in the UK, approximately 4,300 cases of CIS (≈90% ductal carcinoma in situ) were diagnosed in 2007. Our analyses have shown that screen detected CIS contributed primarily to the increase in diagnosis of CIS of the breast. The high diagnosis rate of screen detected CIS of the breast underlines the need for further research into lesion and patient characteristics that are related to progression of CIS to invasive disease to better target treatment.

Have developments in palliative care services impacted on place of death of colorectal cancer patients in Ireland? A population-based study.

BACKGROUND: Whether developments in palliative care have impacted on where cancer patients die is unknown. We investigated time trends in place of death for colorectal cancer. METHODS: Details were abstracted on 10,175 colorectal cancer deaths during 1994-2004. Time trends were analysed by joinpoint regression. RESULTS: Nearly half (49%) of deaths occurred in acute hospitals, 29% at home, 13% in hospices and 7% in nursing homes. Hospital deaths were unchanged over time. Hospice deaths rose from 6% in 1994 to 17% in 2003. Home deaths decreased significantly, but only in health boards with hospices [estimated annual percentage change (EAPC) = -3.6%, 95%CI -4.19 to -2.97%, p < 0.001]. Nursing home deaths rose significantly in areas without hospices (EAPC = 8.0%, 95%CI 2.27 to -13.94%, p = 0.011). CONCLUSIONS: Most colorectal cancer deaths occur in hospital. Availability of hospice facilities is a key determinant of where the burden of death falls. The results suggest unmet demand for hospice care in Ireland.

Regional variations in testicular cancer rates in Ireland.

BACKGROUND: Traditionally, the incidence of testicular cancer (TCa) has shown a remarkable geographical variation. AIMS: To examine whether the rates of TCa varied within Ireland itself and to find possible explanations for any observations made. METHODS: We observed the incidence of TCa in counties in Ireland between January 1994 and December 2007. The rate of cryptorchidism over the same time was calculated. Incidence of TCa by socio-economic status was reviewed. The role of environmental pollutants was explored. We analysed teenage obesity data as a risk factor for the development of TCa in adulthood. RESULTS: Cork had a significantly higher rate of TCa than any other county in Ireland. Cork also had high rates of cryptorchidism, but interestingly not the highest nationwide. In Cork County specifically, least deprived areas had significantly higher rates of TCa. Organic pollutants previously linked to the development of TCa have been identified in large industries located only in Cork. Teenage obesity rates in Cork were not higher than elsewhere. CONCLUSIONS: There is a higher incidence rate of TCa in Cork than any other county. High rates of cryptorchidism alone cannot explain this. There appears to be a link with higher socio-economic status and possibly industrial pollutants. The association between sedentary lifestyle and the development of TCa is unproven.

Where do people with lung cancer die and how is this changing? A population-based study.

Investigating trends in where cancer patients die may help inform decisions about how healthcare should be organised to support those in need of end-of-life care. We analysed time trends in place of death for lung cancer during 1994-2005, based on 18,078 death certificates. Time trends were analysed by joinpoint regression. 9,485 (53%) deaths occurred in an acute hospital, 5,239 (29%) at home, 2,178 (12%) in hospices and 728 (4%) in nursing homes. Hospice deaths rose from 7% (108/1539) in 1994 to 15% (234/1560) in 2003, falling slightly in 2004-05. Hospital deaths were unchanged over time, but were more common in areas without hospices. Home deaths decreased significantly (annual percentage change (APC)=-2.2%, 95%CI -3.0% to -1.3%). Nursing home deaths rose significantly (APC=5.7%, 95%CI 2.5% to 8.9%). These trends were not explained by temporal changes in the age-sex distribution of deaths. Despite evidence suggesting most cancer patients would prefer to die at home, and developments in palliative care services, home deaths are declining and most lung cancer deaths occur in hospital.

Improved malignant melanoma prognosis at a consultant-delivered multidisciplinary pigmented lesion clinic in Cork.

Early detection and excision is the only effective treatment for malignant melanoma. To assess the effect of a consultant-delivered, rapid-access pigmented lesion clinic (PLC) established at the South Infirmary-Victoria University Hospital (SIVUH), we analyzed melanoma tumour-stage prior to (1998-2002) and after (2003-2007) the advent of the PLC. Patients attending SIVUH had a greater proportion of early-stage tumours (65.3%) compared to the rest of Cork (51.2%), County Cork as a whole (56.7%) and all of Ireland (57.4%). The proportion of SIVUH males with early-stage tumours was statistically significantly higher than the rest of County Cork (chi2 = 11.23, P < 0.05). The proportion of patients > 50y with early-stage tumours was also statistically significantly higher than the rest of County Cork (chi2 = 18.88, P < 0.05), the whole of County Cork (chi2 = 7.84, P < 0.05) and all of Ireland (chi2 = 9.67, P < 0.05). We believe that the early detection and improved prognosis of Cork melanoma patients is at least partly due to the PLC.

Mortality predictions for colon and anorectal cancer for Ireland, 2003-17.

OBJECTIVE: Colorectal cancer mortality predictions for Ireland are presented for all ages and for the age group 0-64 years. METHODS: Log and log-linear Poisson regression modelling was fitted to colorectal cancer mortality data for each year between 1950 and 2002 to predict average European age standardized mortality rates (EASMRs) per 100,000 person years (100,000 PY(-1)) and average numbers of deaths. RESULTS: EASMRs for colon cancer are predicted to fall to 17.3 100,000 PY(-1) (95%PI 14.4, 20.2) in men and to 8.4 100,000 PY(-1) (95%PI 6.9, 10.2) in women by 2013-17. EASMRs for anorectal cancer are also predicted to fall to 8.0 100,000 PY(-1) (95%PI 6.6, 9.5) in men and to 3.0 100,000 PY(-1) (95%PI 2.3, 3.8) in women by this time. Truncated EASMRs for colon cancer for those aged between 0 and 64 years are predicted over the next 15 years to fall from their current levels to 4.4 100,000 PY(-1) (95%PI 3.0, 5.8) in men and to 2.3 100,000 PY(-1) (95%PI 1.5, 3.2) in women. For anorectal cancer, truncated EASMRs for those aged between 0 and 64 years are also predicted over the next 15 years to fall from their current levels to 2.9 100,000 PY(-1) (95%PI 2.0, 3.8) in men and to 0.9 100,000 PY(-1) (95%PI 0.4, 1.3) in women. CONCLUSIONS: Ireland currently has one of the highest colorectal mortality rates in the developed world but recent downward trends, the advent of new screening tests and well targeted public health promotion programmes may lead to further reductions.

Mortality predictions for esophageal, stomach, and pancreatic cancer, Ireland, up to 2015.

BACKGROUND AND AIM OF THE STUDY: An analysis was undertaken to predict numbers of esophageal, stomach, and pancreatic cancer deaths and their World age standardized mortality rates (WASMRs) per 100,000 person years (100,000 PY-1) in Ireland for the years 2005, 2010 and 2015. METHODS: Linear and log-linear Poisson regression models were applied to 1950-2002 Irish cancer mortality data. RESULTS: By 2015, esophageal cancer WASMR for males is expected to rise to 9.1 100,000 PY-1, but for females to fall to 2.3 100,000 PY-1. In women under 65 yr, the WASMR is expected to decline to 0.8 100,000 PY-1 but to increase to 3.6 100,000 PY-1 in men. The stomach cancer WASMR for males is predicted to decrease to 5.3 100,000 PY-1 and for females to 2.9 100,000 PY-1. In males under 65 yr, the WASMR is predicted to fall to 1.7 100,000 PY-1 and to 1.0 100,000 PY-1 in women. The male WASMR for pancreatic cancer is predicted to decrease to 5.9 100,000 PY-1 and to 4.7 100,000 PY-1 in women. In men under 65 yr, the WASMR is predicted to drop to 1.7 100,000 PY-1 and to fall in women to 1.2 100,000 PY-1. CONCLUSIONS: Apart from male esophageal cancer, the findings would indicate that declines in Irish WASMRs for these three cancer types are expected to occur by 2015.

Delays in treatment in the cancer services: impact on cancer stage and survival.

This study describes waiting times for cancer treatment in Ireland, tests for differences between health board areas and investigates if delay affected cancer stage or prognosis. We measured the times between referral, outpatient attendance and treatment for all patients diagnosed with five common cancers in Ireland in 1999. There was a four-fold spread of waiting time between the 25th and 75th centile. The time from referral to treatment was shortest for breast cancer (median 4 weeks), twice this for colorectal cancer, lung cancer and lymphoma, and 15 weeks for prostate cancer. Delays varied significantly, but not consistently, between health boards. Patients with longer waiting times generally had less advanced disease and better survival, suggesting that typical delays are not of clinical significance, but that patients with advanced disease are probably being "fast-tracked" by GPs and hospitals.