Nicola S. Meagher

Comparison of De Novo Cancer Incidence in Australian Liver, Heart and Lung Transplant Recipients

Population‐based evidence on the relative risk of de novo cancer in liver and cardiothoracic transplant recipients is limited. A cohort study was conducted in Australia using population‐based liver (n = 1926) and cardiothoracic (n = 2718) registries (1984–2006). Standardized incidence ratios (SIRs) were computed by cancer type, transplanted organ and recipient age. Cox regression models were used to compare cancer incidence by transplanted organ. During a median 5‐year follow‐up, the risk of any cancer in liver and cardiothoracic recipients was significantly elevated compared to the general population (n = 499; SIR = 2.62, 95%CI 2.40–2.86). An excess risk was observed for 16 cancer types, predominantly cancers with a viral etiology. The pattern of risk by cancer type was broadly similar for heart, lung and liver recipients, except for Merkel cell carcinoma (cardiothoracic only). Seventeen cancers (10 non‐Hodgkin lymphomas), were observed in 415 pediatric recipients (SIR = 23.8, 95%CI 13.8–38.0). The adjusted hazard ratio for any cancer in all recipients was higher in heart compared to liver (1.29, 95%CI 1.03–1.63) and lung compared to liver (1.65, 95%CI 1.26–2.16). Understanding the factors responsible for the higher cancer incidence in cardiothoracic compared to liver recipients has the potential to lead to targeted cancer prevention strategies in this high‐risk population.

Role of radiotherapy in early glottic carcinoma

Early glottic carcinoma has a high local control prospect with radiotherapy. This review evaluates a single centers experience.

De novo Cancer-Related Death in Australian Liver and Cardiothoracic Transplant Recipients

Evidence is sparse on the relative mortality risk posed by de novo cancers in liver and cardiothoracic transplant recipients. A retrospective cohort study was conducted in Australia using population‐based liver (n = 1926) and cardiothoracic (n = 2718) registries (1984–2006). Standardized mortality ratios (SMRs) were computed by cancer type, transplanted organ, recipient age and sex. During a median 5‐year follow‐up, de novo cancer‐related mortality risk in liver and cardiothoracic recipients was significantly elevated compared to the matched general population (n = 171; SMR = 2.83; 95% confidence interval [95%CI], 2.43–3.27). Excess risk was observed regardless of transplanted organ, recipient age group or sex. Non‐Hodgkin lymphoma was the most common cancer‐related death (n = 38; SMR = 16.6; 95%CI, 11.87–22.8). The highest relative risk was for nonmelanocytic skin cancer (n = 23; SMR = 49.6, 95%CI, 31.5–74.5), predominantly in males and in recipients of heart and lung transplants. Risk of death from de novo cancer was high in pediatric recipients (n = 5; SMR = 41.3; 95%CI, 13.4–96.5), four of the five deaths were non‐Hodgkin lymphoma. De novo cancer was a leading cause of late death, particularly in heart and liver transplantation. These findings support tailored cancer prevention strategies, surveillance to promote early detection, and guidelines for managing immunosuppression once cancer occurs.

Latitude gradients for lymphoid neoplasm subtypes in Australia support an association with ultraviolet radiation exposure

Given the uncertainty surrounding solar ultraviolet radiation (UVR) exposure and risk of lymphoid neoplasms, we performed an ecological analysis of national Australian data for incident cases diagnosed between 2002 and 2006. Subtype‐specific incidence was examined by latitude band (<29°S, 29–36°S, ≥37°S), a proxy for ambient UVR exposure, using multiple Poisson regression, adjusted for sex, age‐group and calendar year. Incidence increased with distance from the equator for several mature B‐cell non‐Hodgkin lymphomas, including diffuse large B‐cell [incidence rate ratio (IRR) = 1.37; 95% confidence interval (CI): 1.16–1.61 for latitude ≥37°S relative to <29°S], lymphoplasmacytic (IRR = 1.34; 95% CI: 1.12–1.61), mucosa‐associated lymphoid tissue (IRR = 1.32; 95% CI: 0.97–1.80) and mantle cell lymphoma (IRR = 1.29; 95% CI: 1.05–1.58), as well as plasmacytoma (IRR = 1.52; 95% CI: 1.09–2.11) and plasma cell myeloma (IRR = 1.15; 95% CI: 1.03–1.27). A similar pattern was observed for several mature cutaneous T‐cell neoplasms, including primary cutaneous anaplastic large cell lymphoma (IRR = 4.26; 95% CI: 1.85–9.84), mycosis fungoides/Sézary syndrome (IRR = 1.72; 95% CI: 1.20–2.46), and peripheral T‐cell lymphoma not otherwise specified (NOS) (IRR = 1.53; 95% CI: 1.17–2.00). Incidence of mixed cellularity/lymphocyte‐depleted (IRR = 1.60; 95% CI: 1.16–2.20) and nodular sclerosis Hodgkin lymphoma (IRR = 1.57; 95% CI: 1.33–1.85) also increased with distance from the equator. Many of these subtypes have a known association with infection or immune dysregulation. Our findings support a possible protective effect of UVR exposure on the risk of several lymphoid neoplasms, possibly through vitamin D‐related immune modulation critical in lymphomagenesis.

Survival After Cutaneous Melanoma in Kidney Transplant Recipients: A Population-Based Matched Cohort Study

Transplant recipients are at elevated risk of melanoma and may have poorer outcomes than nontransplant recipients. We conducted a national, population‐based, matched cohort study of Australian kidney transplant recipients and randomly selected members of the general population matched for age, sex, state and year of diagnosis with invasive cutaneous melanoma (1982–2003). Melanoma histopathological characteristics were extracted from cancer registry notifications and death data were obtained from the National Death Index (1982–2011). Histopathology was compared using conditional logistic regression and overall survival analyzed using Cox proportional hazard models. Compared to melanomas in nontransplant recipients (n = 202), melanomas in transplant recipients (n = 75) had a higher Clarks level (p = 0.007) and higher American Joint Committee on Cancer pathologic stage (p = 0.002), but not Breslow thickness (p = 0.11). Posttransplant melanoma conferred higher risk of death (adjusted hazard ratio 4.26, 95% CI 2.71–6.72, p < 0.001) after adjustment for the matching variables, pathologic stage, histological type and anatomic site. This was not explained by transplantation alone. Melanomas in transplant recipients are more invasive than those in nonrecipients. More aggressive tumor behavior is also supported by a markedly poorer outcome. Treatment algorithms developed for the general population with melanoma may not apply to transplant recipients. A review of patient education and skin cancer screening guidelines is warranted.

Retained role of surgery for olfactory neuroblastoma

Olfactory neuroblastoma is a rare paranasal sinus malignancy. The traditional approach was craniofacial resection (CFR) and then postoperative radiotherapy until 1998. This review will chart development of a new protocol.

Lymphoid neoplasm incidence by WHO subtype in Australia 1982-2006

There are limited data characterizing the subtype‐specific incidence of lymphoid neoplasms in the World Health Organization (WHO) Classification era. Data were obtained on all incident lymphoid neoplasms registered in Australia during 1982–2006. Subtypes were grouped using the InterLymph nested hierarchical classification, based on the 2008 WHO Classification. Temporal trends were examined using Joinpoint regression; average annual percentage change in incidence was computed. Multiple Poisson regression was used to compare incidence by sex and age. The incidence of all non‐Hodgkin lymphoma (NHL) increased by 2.5%/year during 1982–1996 and was stable thereafter. During 1997–2006, several mature B‐ and natural killer (NK)‐/T‐cell NHL subtypes increased in incidence, including diffuse large B‐cell (1.3%/year), follicular (2.5%/year), Burkitt (6.8%/year), marginal zone (13.2%/year), mantle cell (4.2%/year), peripheral T‐cell lymphoma (4.7%/year) and plasmacytoma (7.1%/year). While chronic lymphocytic leukemia incidence was stable, small lymphocytic lymphoma incidence declined (8.1%/year). Hodgkin lymphoma (HL) incidence increased during 1997–2006 (2.2%/year), both classical (4.3%/year) and nodular lymphocyte predominant (12.1%/year) HL. Diagnostic artifact, evidenced by a sustained decline in the incidence of NHL not otherwise specified (NOS; 5.8%/year) and lymphoid neoplasms NOS (5.6%/year), limits the interpretation of temporal trends for some subtypes. A marked male predominance was observed for almost all subtypes. Incidence of mature B‐ and NK‐/T‐cell NHL subtypes increased sharply with age, except for Burkitt lymphoma/leukemia. For HL subtypes, a bimodal age distribution was only evident for nodular sclerosis HL. Variation in incidence patterns over time and by sex and age supports etiological differences between lymphoid neoplasm subtypes.

Recurrent Nasopharyngeal Carcinoma: Current Management Approaches

Objectives:Providing the primary recurrence is localized, salvage treatment is possible for nasopharyngeal carcinoma (NPC). This is a review of the experience of retreatment of this malignancy highlighting the roles of surgery and repeat radiotherapy. Methods:The Tumor Registry of the Prince of Wales Cancer Centre was audited for patients with an initial diagnosis of squamous/nonsquamous cell NPC who had primary treatment with radiotherapy, and now presented for retreatment. Features relating to patient, disease and treatment factors were evaluated. The primary end point was subsequent local control, and secondary endpoints were overall and cancer-specific survival. Results:Over a 30-year period 39 patients were eligible, with 25 receiving both primary and retreatment at Prince of Wales Hospital. There were 25 males and 14 females with a median age of 50 years. Thirty-six patients had radiotherapy, 4 had stereotactic radiosurgery, 5 had brachytherapy, and the remainder had external treatment. Surgery was performed in 10 patients, of whom 3 had this as the only retreatment modality. Radiotherapy doses for retreatment ranged from 15 Gy (stereotactic radiosurgery) to 71.28 Gy (mean fractionated dose). Local control was achieved in 16 patients giving an overall rate of 41.0%, and the 5-year overall survival rate was 33.3%. Treatment modality was a significant prognostic factor for local control (P < 0.001) and cancer-specific survival (P < 0.05). Conclusion:The presence of local recurrence after definitive treatment of NPC may still be salvageable. The best outcomes with reirradiation occur in the context of limited volume recurrence and a disease-free interval greater than 18 months.

The importance of blood-borne viruses in elevated cancer risk among opioid-dependent people: a population-based cohort study

Objective To quantify cancer risk in opioid dependence and the association with infection by the oncogenic blood-borne viruses (BBVs) hepatitis C (HCV), hepatitis B (HBV) and HIV. Design Cohort study. Setting New South Wales, Australia. Participants All 45 412 adults aged 16 years or over registered for opioid substitution therapy (OST) between 1985 and 2007. Notifications of cancer, death and infection with HCV, HBV and HIV were ascertained by record linkage with registries. Main outcome measures The ratios of observed to expected number of cancers, standardised incidence ratios (SIRs), and the average annual per cent change (AAPC) in overall age and sex-standardised cancer incidence. Results Overall cancer risk was modestly increased compared to the general population (SIR 1.15, 95% CI 1.07 to 1.23). Excess risk was observed for 11 cancers, particularly lung (4.02, 95% CI 3.32 to 4.82), non-Hodgkins lymphoma (1.51, 95% CI 1.20 to 1.88) and liver (8.04, 95% CI 6.18 to 10.3). Reduced risk was observed for six cancers, including prostate (0.16, 95% CI 0.06 to 0.32) and breast (0.48, 95% CI 0.35 to 0.62). Individuals notified with HCV or HBV had a markedly increased risk of liver cancer; lung cancer risk was also increased in those with HCV. HIV was associated with an elevated risk of liver, anus and kidney cancer, non-Hodgkin lymphoma and Kaposi sarcoma. Cancer risk was not increased in individuals without a BBV notification, apart from pancreatic cancer (3.92, 95% CI 1.07 to 10.0). Cancer incidence increased significantly over time (AAPC 9.4%, 4.2% to 15%, p=0.001). Conclusions BBVs play a major role in the cancer risk profile of opioid-dependent individuals registered for OST. To address the dramatic increasing trend in cancer incidence, the OST setting could be utilised for cancer prevention strategies.

Iatrogenic immunosuppression and risk of non-Hodgkin lymphoma in solid organ transplantation: A population-based cohort study in Australia.

Iatrogenic immunosuppression is a strong risk factor for non‐Hodgkin lymphoma (NHL) but the dose‐related association between individual immunosuppressive agents and NHL risk is unknown. We conducted a population‐based cohort study of 4131 adult Australian liver, heart and lung transplant recipients (1984–2006). We ascertained NHL incidence by probabilistic record linkage between transplant registries and the Australian Cancer Database, and abstracted risk factor data at transplantation and at regular intervals thereafter from medical records. We estimated adjusted hazard ratios (HR) for early (<1 year after transplantation; n = 29) and late (≥1 year; n = 61) NHL using the Fine and Gray proportional subdistribution hazards model that accounted for death as a competing risk. After adjustment for immunosuppression, the risk of both early and late NHL did not significantly differ by organ type. In final models, higher mean daily doses of azathioprine were associated with increased risk of both early [HR 2·20, 95% confidence interval (CI): 1·21–4·01] and late NHL (HR 1·78, 95% CI: 1·12–2·84). There was no association between any other maintenance immunosuppressive agent and NHL risk. This study provides evidence that differences in immunosuppression may explain variation in NHL incidence by organ type, and high doses of azathioprine may independently predict NHL risk.