Two New Faces of Amifostine: Protector from DNA Damage in Normal Cells and Inhibitor of DNA Repair in Cancer Cells

Amifostine protects normal cells from DNA damage induction by ionizing radiation or chemotherapeutics, whereas cancer cells typically remain uninfluenced. While confirming this phenomenon, we have revealed by comet assay and currently the most sensitive method of DNA double strand break (DSB) quantification (based on γH2AX/53BP1 high-resolution immunofluorescence microscopy) that amifostine treatment supports DSB repair in γ-irradiated normal NHDF fibroblasts but alters it in MCF7 carcinoma cells. These effects follow from the significantly lower activity of alkaline phosphatase measured in MCF7 cells and their supernatants as compared with NHDF fibroblasts. Liquid chromatography–mass spectrometry confirmed that the amifostine conversion to WR-1065 was significantly more intensive in normal NHDF cells than in tumor MCF cells. In conclusion, due to common differences between normal and cancer cells in their abilities to convert amifostine to its active metabolite WR-1065, amifostine may not only protect in multiple ways normal cells from radiation-induced DNA damage but also make cancer cells suffer from DSB repair alteration

Rare ovarian tumours: Epidemiology, treatment challenges in and outside a network setting

Purpose of the review: More than 50% of all gynaecological cancers can be classified as rare tumours (defined as an annual incidence of <6 per 100,000) and such tumours represent an important challenge for clinicians. Recent findings: Rare cancers account for more than one fifth of all new cancer diagnoses, more than any of the single common cancers alone. Reviewing the RARECAREnet database, some of the tumours occur infrequently, whilst others because of their natural history have a high prevalence, and therefore appear to be more common, although their incidence is also rare. Harmonization of medical practice, guidelines and novel trials are needed to identify rare tumours and facilitate the development of new treatments. Ovarian tumours are the focus of this review, but we comment on other rare gynaecological tumours, as the diagnosis and treatment challenges faced are similar. Future: This requires European collaboration, international partnerships, harmonization of treatment and collaboration to overcome the regulatory barriers to conduct international trials. Whilst randomized trials can be done in many tumour types, there are some for which conducting even single arm studies may be challenging. For these tumours alternative study designs, robust collection of data through national registries and audits could lead to improvements in the treatment of rare tumours. In addition, concentring the care of patients with rare tumours into a limited number of centres will help to build expertise, facilitate trials and improve outcomes

Long-term survival for lymphoid neoplasms and national health expenditure (EUROCARE-6): a retrospective, population-based study

Background: Management of lymphoid malignancies requires substantial health system resources. Total national health expenditure might influence population-based lymphoid malignancy survival. We studied the long-term survival of patients with 12 lymphoid malignancy types and examined whether different levels of national health expenditure might explain differences in lymphoid malignancy prognosis between European countries and regions. Methods: For this observational, retrospective, population-based study, we analysed the EUROCARE-6 dataset of patients aged 15 or older diagnosed between 2001 and 2013 with one of 12 lymphoid malignancies defined according to International Classification of Disease for Oncology (third edition) and WHO classification, and followed up to 2014 (Jan 1, 2001-Dec 31, 2014). Countries were classified according to their mean total national health expenditure quartile in 2001-13. For each lymphoid malignancy, 5-year and 10-year age-standardised relative survival (ASRS) was calculated using the period approach. Generalised linear models indicated the effects of age at diagnosis, gender, and total national health expenditure on the relative excess risk of death (RER). Findings: 82 cancer registries (61 regional and 21 national) from 27 European countries provided data eligible for 10-year survival estimates comprising 890 730 lymphoid malignancy cases diagnosed in 2001-13. Median follow-up time was 13 years (IQR 13-14). Of the 12 lymphoid malignancies, the 10-year ASRS in Europe was highest for hairy cell leukaemia (82·6% [95% CI 78·9-86·5) and Hodgkin lymphoma (79·3% [78·6-79·9]) and lowest for plasma cell neoplasms (29·5% [28·9-30·0]). RER increased with age at diagnosis, particularly from 55-64 years to 75 years or older, for all lymphoid malignancies. Women had higher ASRS than men for all lymphoid malignancies, except for precursor B, T, or natural killer cell, or not-otherwise specified lymphoblastic lymphoma or leukaemia. 10-year ASRS for each lymphoid malignancy was higher (and the RER lower) in countries in the highest national health expenditure quartile than in countries in the lowest quartile, with a decreasing pattern through quartiles for many lymphoid malignancies. 10-year ASRS for non-Hodgkin lymphoma, the most representative class for lymphoid malignancies based on the number of incident cases, was 59·3% (95% CI 58·7-60·0) in the first quartile, 57·6% (55·2-58·7) in the second quartile, 55·4% (54·3-56·5) in the third quartile, and 44·7% (43·6-45·8) in the fourth quartile; with reference to the European mean, the RER was 0·80 (95% CI 0·79-0·82) in the first, 0·91 (0·90-0·93) in the second, 0·94 (0·92-0·96) in the third, and 1·45 (1·42-1·48) in the fourth quartiles. Interpretation: Total national health expenditure is associated with geographical inequalities in lymphoid malignancy prognosis. Policy decisions on allocating economic resources and implementing evidence-based models of care are needed to reduce these differences. Funding: Italian Ministry of Health, European Commission, Estonian Research Council

Complete cancer prevalence in Europe in 2020 by disease duration and country (EUROCARE-6): a population-based study

Background Cancer survivors-people living with and beyond cancer-are a growing population with different health needs depending on prognosis and time since diagnosis. Despite being increasingly necessary, complete information on cancer prevalence is not systematically available in all European countries. We aimed to fill this gap by analysing population-based cancer registry data from the EUROCARE-6 study. Methods In this population-based study, using incidence and follow-up data up to Jan 1, 2013, from 61 cancer registries, complete and limited-duration prevalence by cancer type, sex, and age were estimated for 29 European countries and the 27 countries in the EU (EU27; represented by 22 member states that contributed registry data) using the completeness index method. We focused on 32 malignant cancers defined according to the third edition of the International Classification of Diseases for Oncology, and only the first primary tumour was considered when estimating the prevalence. Prevalence measures are expressed in terms of absolute number of prevalent cases, crude prevalence proportion (reported as percentage or cases per 100 000 resident people), and age-standardised prevalence proportion based on the European Standard Population 2013. We made projections of cancer prevalence proportions up to Jan 1, 2020, using linear regression. Findings In 2020, 23 711 thousand (95% CI 23 565-23 857) people (5 center dot 0% of the population) were estimated to be alive after a cancer diagnosis in Europe, and 22 347 thousand (95% CI 22 210-22 483) in EU27. Cancer survivors were more frequently female (12 818 thousand [95% CI 12 720-12 917]) than male (10 892 thousand [10 785-11 000]). The five leading tumours in female survivors were breast cancer, colorectal cancer, corpus uterine cancer, skin melanoma, and thyroid cancer (crude prevalence proportion from 2270 [95%CI 2248-2292] per 100 000 to 301 [297-305] per 100 000). Prostate cancer, colorectal cancer, urinary bladder cancer, skin melanoma, and kidney cancer were the most common tumours in male survivors (from 1714 [95% CI 1686-1741] per 100 000 to 255 [249-260] per 100 000). The differences in prevalence between countries were large (from 2 to 10 times depending on cancer type), in line with the demographic structure, incidence, and survival patterns. Between 2010 and 2020, the number of prevalent cases increased by 3 center dot 5% per year (41% overall), partly due to an ageing population. In 2020, 14 850 thousand (95% CI 14 681-15 018) people were estimated to be alive more than 5 years after diagnosis and 9099 thousand (8909-9288) people were estimated to be alive more than 10 years after diagnosis, representing an increasing proportion of the cancer survivor population. Interpretation Our findings are useful at the country level in Europe to support evidence-based policies to improve the quality of life, care, and rehabilitation of patients with cancer throughout the disease pathway. Future work includes estimating time to cure by stage at diagnosis in prevalent cases. Copyright (c) 2024 Elsevier Ltd. All rights reserved