Summary Background Data from EUROCARE have consistently shown lower survival for adolescents and young adults (AYAs; aged 15–24 years) than for children (0–14 years) for most cancers that affect both ...groups, and modest survival improvements up to 2000–02. AYAs have longer survival than that of adults for most cancers. We used the latest definition of AYAs (aged 15–39 years) and provided estimates of 5-year relative survival for European AYAs with cancer diagnosed in 2000–07, compared with children and adults (40–69 years) with cancer, and assessed survival improvements over time. Methods We analysed data from population-based cancer registries of 27 European countries participating in EUROCARE-5. We used the so-called complete method to estimate 5-year, population-weighted relative survival for 19 cancers affecting AYAs and children, and for 27 cancers affecting AYAs and adults. We assessed relative-survival differences between children versus AYAs, and between AYAs versus adults, using the Z test. We used the period approach to estimate 5-year relative survival over time for children and AYAs, and used a generalised linear model to model survival time trends (1999–2007) and to assess the significance of changes over time. Findings We analysed 56 505 cancer diagnoses in children, 312 483 in AYAs, and 3 567 383 in adults. For all cancers combined, survival improved over time for AYAs (from 79% 95% CI 78·1–80·5 in 1999–2002 to 82% 81·1–83·3 in 2005–07; p<0·0001) and children (from 76% 74·7–77·1 to 79% 77·2–79·4; p<0·0001). Survival improved significantly in children and AYAs for acute lymphoid leukaemia (p<0·0001) and non-Hodgkin lymphoma (p<0·0001 in AYAs and p=0·023 in children). Survival improved significantly in AYAs only for CNS tumours (p=0·0046), astrocytomas (p=0·040), and malignant melanomas (p<0·0001). Survival remained significantly worse in AYAs than in children for eight important cancers: acute lymphoid leukaemias, acute myeloid leukaemias, Hodgkin's lymphomas, non-Hodgkin lymphomas, astrocytomas, Ewing's sarcomas, and rhabdomyosarcomas (p<0·0001 in all cases), and osteosarcomas (p=0·011). Interpretation Notwithstanding the encouraging results for some cancers, and overall, we showed poorer survival in AYAs than in children for the eight important cancers. Recent European initiatives to improve outcomes in AYAs might reduce the survival gap between children and AYAs, but this reduction can only be verified by future population-based studies. Funding Italian Ministry of Health, European Commission.
Summary Background Survival and cure rates for childhood cancers in Europe have greatly improved over the past 40 years and are mostly good, although not in all European countries. The EUROCARE-5 ...survival study estimates survival of children diagnosed with cancer between 2000 and 2007, assesses whether survival differences among European countries have changed, and investigates changes from 1999 to 2007. Methods We analysed survival data for 157 499 children (age 0–14 years) diagnosed between Jan 1, 1978 and Dec 31, 2007. They came from 74 population-based cancer registries in 29 countries. We calculated observed, country-weighted 1-year, 3-year, and 5-year survival for major cancers and all cancers combined. For comparison between countries, we used the corrected group prognosis method to provide survival probabilities adjusted for multiple confounders (sex, age, period of diagnosis, and, for all cancers combined without CNS cancers, casemix). Age-adjusted survival differences by area and calendar period were calculated with period analysis and were given for all cancers combined and the major cancers. Findings We analysed 59 579 cases. For all cancers combined for children diagnosed in 2000–07, 1-year survival was 90·6% (95% CI 90·2–90·9), 3-year survival was 81·0 % (95% CI 80·5–81·4), and 5-year survival was 77·9% (95% CI 77·4–78·3). For all cancers combined, 5-year survival rose from 76·1% (74·4–77·7) for 1999–2001, to 79·1% (77·3–80·7) for 2005–07 (hazard ratio 0·973, 95% CI 0·965–0·982, p<0·0001). The greatest improvements were in eastern Europe, where 5-year survival rose from 65·2% (95% CI 63·1–67·3) in 1999–2001, to 70·2% (67·9–72·3) in 2005–07. Europe-wide average yearly change in mortality (hazard ratio) was 0·939 (95% CI 0·919–0·960) for acute lymphoid leukaemia, 0·959 (0·933–0·986) for acute myeloid leukaemia, and 0·940 (0·897–0·984) for non-Hodgkin lymphoma. Mortality for all of Europe did not change significantly for Hodgkin's lymphoma, Burkitt's lymphoma, CNS tumours, neuroblastoma, Wilms' tumour, Ewing's sarcoma, osteosarcoma, and rhabdomyosarcoma. Disparities for 5-year survival persisted between countries and regions, ranging from 70% to 82% (for 2005–07). Interpretation Several reasons might explain persisting inequalities. The lack of health-care resources is probably most important, especially in some eastern European countries with limited drug supply, lack of specialised centres with multidisciplinary teams, delayed diagnosis and treatment, poor management of treatment, and drug toxicity. In the short term, cross-border care and collaborative programmes could help to narrow the survival gaps in Europe. Funding Italian Ministry of Health, European Commission, Compagnia di San Paolo Foundation.
PURPOSE OF REVIEWChordoma is an exceedingly rare subtype of bone sarcoma. This review aims to provide a comprehensive insight into chordoma epidemiology, and an update on the recent advances in ...disease, biology and medical therapies.
RECENT FINDINGSThe incidence of chordoma is approximately 0.08/100 000 and the 5-year overall age-adjusted relative survival is 72% in the United States and 61% in Europe. Over the last years, significant steps forwards have been done in the comprehension of chordoma complexity, with insights gained into the biology and morphology of this disease. New entities have been described and potentially druggable molecular targets identified. This is becoming all the more relevant today, as new potentially active agents are under development.
SUMMARYChordoma is a complex disease because of its rarity, biological heterogeneity and peculiar clinical behaviour. Despite the progress done, the outcome in this disease remains unsatisfactory and the identification of active systemic treatments remains an urgent, unmet medical need.
In Europe, as in other high-income (HI) countries, quite half of the newly diagnosed patients with head and neck (H and N) cancers are older than 65 years of age and their proportion within the ...prevalent cases is even higher. Moreover, the incidence rate (IR) for all H and N cancers sites increased with age and the survival rate is lower in older patients (≥65), compared with younger patients (<65). The number of older patients affected by H and N cancers will increase because of the increase in life expectancy. The aim of the article is to provide an epidemiological description of H and N cancers in the elderly population.
Incidence and prevalence data by time periods and continents were extracted from the Global Cancer Observatory. The survival information for Europe is obtained from the EUROCARE and RARECAREnet projects. In 2020, according to the results from these data, slightly more than 900,000 cases have been diagnosed with H and N cancers in the world, and approximately 40% were older than 65 years of age. This percentage was higher, reaching approximately 50% in the HI countries. The highest number of cases was in the Asiatic populations, while the highest crude IR was in Europe and Oceania. Among H and N cancers occurring in the elderly, laryngeal and oral cavity cancers were the most common, while nasal cavities and nasopharyngeal cancers were the rarest. This was true for all the countries, excluding some Asiatic populations, in which tumour of the nasopharynx was more common. The five-year survival rate in the European population was low in the elderly, compared with the younger for all H and N cancers, and it ranged from approximately 60% for both salivary-gland type and laryngeal to 22% for hypopharyngeal tumors. For the elderly, the conditional 5-year survival after surviving one year became more than 60% for many H and N epithelial tumors.
The high variability in the H and N cancer incidence around the world is due to the distribution of the major risk factors which for the elderly are mainly alcohol and smoking. The reasons for low survival in the elderly are most likely due to the complexity of treatment, the late arrival of patients at diagnosis, and the difficult access to specialized centers.
Background: Neurovascular coupling (NVC) is the mechanism whereby an increase in neuronal activity (NA) leads to local elevation in cerebral blood flow (CBF) to match the metabolic requirements of ...firing neurons. Following synaptic activity, an increase in neuronal and/or astrocyte Ca2+ concentration leads to the synthesis of multiple vasoactive messengers. Curiously, the role of endothelial Ca2+ signaling in NVC has been rather neglected, although endothelial cells are known to control the vascular tone in a Ca2+-dependent manner throughout peripheral vasculature. Methods: We analyzed the literature in search of the most recent updates on the potential role of endothelial Ca2+ signaling in NVC. Results: We found that several neurotransmitters (i.e., glutamate and acetylcholine) and neuromodulators (e.g., ATP) can induce dilation of cerebral vessels by inducing an increase in endothelial Ca2+ concentration. This, in turn, results in nitric oxide or prostaglandin E2 release or activate intermediate and small-conductance Ca2+-activated K+ channels, which are responsible for endothelial-dependent hyperpolarization (EDH). In addition, brain endothelial cells express multiple transient receptor potential (TRP) channels (i.e., TRPC3, TRPV3, TRPV4, TRPA1), which induce vasodilation by activating EDH. Conclusions: It is possible to conclude that endothelial Ca2+ signaling is an emerging pathway in the control of NVC.
BackgroundSeveral studies have shown significant variation in overall survival rates from childhood cancer between countries, using population-based cancer registry (PBCR) data for all cancers ...combined and for many individual tumour types among children. Without accurate and comparable data on Tumour stage at diagnosis, it is difficult to define the reasons for these survival differences. This is because measurement systems designed for adult cancers do not apply to children's cancers and cancer registries often hold limited information on paediatric tumour stage and the data sources used to define it.AimsThe BENCHISTA project aims to test the application of the international consensus "Toronto Staging Guidelines" (TG) for paediatric tumours by European and non-European PBCRs for six common paediatric solid tumours so that reliable comparisons of stage at diagnosis and survival rates by stage can be made to understand any differences. A secondary aim is to test the data availability and completeness of collection of several 'Toronto' consensus non-stage prognostic factors, treatment types given, occurrence of relapse/progression and cause of death as a descriptive feasibility study.MethodsPBCRs will use their permitted data access channels to apply the Toronto staging guidelines to all incident cases of six solid childhood cancers (medulloblastoma, osteosarcoma, Ewings sarcoma, rhabdomyosarcoma, neuroblastoma and Wilms tumour) diagnosed in a consecutive three-year period within 2014-2017 in their population. Each registry will provide a de-identified patient-level dataset including tumour stage at diagnosis, with only the contributing registry holding the information that would be needed to re-identify the patients. Where available to the registry, patient-level data on 'Toronto' non-stage prognostic factors, treatments given and clinical outcomes (relapse/progression/cause of death) will be included. More than 60 PBCRs have been involved in defining the patient-level dataset items and intend to participate by contributing their population-level data. Tumour-specific on-line training workshops with clinical experts are available to cancer registry staff to assist them in applying the Toronto staging guidelines in a consistent manner. There is also a project-specific help desk for discussion of difficult cases and promotion of the CanStaging online tools, developed through the International Association of Cancer Registries, to further ensure standardisation of data collection. Country-specific stage distribution and observed survival by stage at diagnosis will be calculated for each tumour type to compare survival between countries or large geographical regions.DiscussionThis study will be promote and enhance the collection of standardized staging data for childhood cancer by European and non-European population-based cancer registries. Therefore, this project can be seen as a feasibility project of widespread use of Toronto Staging at a population-level by cancer registries, specifying the data sources used and testing how well standardized the processes can be. Variation in tumour stage distribution could be due to real differences, to different diagnostic practices between countries and/or to variability in how cancer registries assign Toronto stage. This work also aims to strengthen working relationships between cancer registries, clinical services and cancer-specific clinical study groups, which is important for improving patient outcomes and stimulating research.
Several studies have shown significant variation in overall survival rates from childhood cancer between countries, using population-based cancer registry (PBCR) data for all cancers combined and for ...many individual tumour types among children. Without accurate and comparable data on Tumour stage at diagnosis, it is difficult to define the reasons for these survival differences. This is because measurement systems designed for adult cancers do not apply to children's cancers and cancer registries often hold limited information on paediatric tumour stage and the data sources used to define it. The BENCHISTA project aims to test the application of the international consensus "Toronto Staging Guidelines" (TG) for paediatric tumours by European and non-European PBCRs for six common paediatric solid tumours so that reliable comparisons of stage at diagnosis and survival rates by stage can be made to understand any differences. A secondary aim is to test the data availability and completeness of collection of several 'Toronto' consensus non-stage prognostic factors, treatment types given, occurrence of relapse/progression and cause of death as a descriptive feasibility study. PBCRs will use their permitted data access channels to apply the Toronto staging guidelines to all incident cases of six solid childhood cancers (medulloblastoma, osteosarcoma, Ewings sarcoma, rhabdomyosarcoma, neuroblastoma and Wilms tumour) diagnosed in a consecutive three-year period within 2014-2017 in their population. Each registry will provide a de-identified patient-level dataset including tumour stage at diagnosis, with only the contributing registry holding the information that would be needed to re-identify the patients. Where available to the registry, patient-level data on 'Toronto' non-stage prognostic factors, treatments given and clinical outcomes (relapse/progression/cause of death) will be included. More than 60 PBCRs have been involved in defining the patient-level dataset items and intend to participate by contributing their population-level data. Tumour-specific on-line training workshops with clinical experts are available to cancer registry staff to assist them in applying the Toronto staging guidelines in a consistent manner. There is also a project-specific help desk for discussion of difficult cases and promotion of the CanStaging online tools, developed through the International Association of Cancer Registries, to further ensure standardisation of data collection. Country-specific stage distribution and observed survival by stage at diagnosis will be calculated for each tumour type to compare survival between countries or large geographical regions. This study will be promote and enhance the collection of standardized staging data for childhood cancer by European and non-European population-based cancer registries. Therefore, this project can be seen as a feasibility project of widespread use of Toronto Staging at a population-level by cancer registries, specifying the data sources used and testing how well standardized the processes can be. Variation in tumour stage distribution could be due to real differences, to different diagnostic practices between countries and/or to variability in how cancer registries assign Toronto stage. This work also aims to strengthen working relationships between cancer registries, clinical services and cancer-specific clinical study groups, which is important for improving patient outcomes and stimulating research.
Adipose tissue comprises both adipose and non-adipose cells such as mesenchymal stem cells. These cells show a surface antigenic profile similar to that of bone-marrow-derived MSC. The cells derived ...from the dedifferentiation of mature adipocytes (DFAT) are another cell population with characteristics of stemness. The aim of this study is to provide evidence of the stemness, proliferation, and differentiation of human adipose stem cells (hASC) and DFAT obtained from human subcutaneous AT and evaluate their potential use in regenerative medicine. Cell populations were studied by histochemical and molecular biology techniques. Both hASC and DFAT were positive for MSC markers. Their proliferative capacity was similar and both populations were able to differentiate into osteogenic, chondrogenic, and adipogenic lineages. DFAT were able to accumulate lipids and their lipoprotein lipase and
gene expression were high. Alkaline phosphatase and
gene expression were greater in hASC than in DFAT at 14 days but became similar after three weeks. Both cell populations were able to differentiate into chondrocytes, showing positive staining with Alcian Blue and gene expression of
and
. In conclusion, both hASC and DFAT populations derived from AT have a high differentiation capacity and thus may have applications in regenerative medicine.
Non-cancer mortality in cancer patients may be higher than overall mortality in the general population due to a combination of factors, such as long-term adverse effects of treatments, and genetic, ...environmental or lifestyle-related factors. If so, conventional indicators may underestimate net survival and cure fraction. Our aim was to propose and evaluate a mixture cure survival model that takes into account the increased risk of non-cancer death for cancer patients.
We assessed the performance of a corrected mixture cure survival model derived from a conventional mixture cure model to estimate the cure fraction, the survival of uncured patients, and the increased risk of non-cancer death in two settings of net survival estimation, grouped life-table data and individual patients' data. We measured the model's performance in terms of bias, standard deviation of the estimates and coverage rate, using an extensive simulation study. This study included reliability assessments through violation of some of the model's assumptions. We also applied the models to colon cancer data from the FRANCIM network.
When the assumptions were satisfied, the corrected cure model provided unbiased estimates of parameters expressing the increased risk of non-cancer death, the cure fraction, and net survival in uncured patients. No major difference was found when the model was applied to individual or grouped data. The absolute bias was < 1% for all parameters, while coverage ranged from 89 to 97%. When some of the assumptions were violated, parameter estimates appeared more robust when obtained from grouped than from individual data. As expected, the uncorrected cure model performed poorly and underestimated net survival and cure fractions in the simulation study. When applied to colon cancer real-life data, cure fractions estimated using the proposed model were higher than those in the conventional model, e.g. 5% higher in males at age 60 (57% vs. 52%).
The present analysis supports the use of the corrected mixture cure model, with the inclusion of increased risk of non-cancer death for cancer patients to provide better estimates of indicators based on cancer survival. These are important to public health decision-making; they improve patients' awareness and facilitate their return to normal life.
Background
A strong relationship has been observed between comorbidities and the risk of severe/fatal COVID‐19 manifestations, but no score is available to evaluate their association in cancer ...patients. To make up for this lacuna, we aimed to develop a comorbidity score for cancer patients, based on the Lombardy Region healthcare databases.
Methods
We used hospital discharge records to identify patients with a new diagnosis of solid cancer between February and December 2019; 61 comorbidities were retrieved within 2 years before cancer diagnosis. This cohort was split into training and validation sets. In the training set, we used a LASSO‐logistic model to identify comorbidities associated with the risk of developing a severe/fatal form of COVID‐19 during the first pandemic wave (March–May 2020). We used a logistic model to estimate comorbidity score weights and then we divided the score into five classes (<=−1, 0, 1, 2–4, >=5). In the validation set, we assessed score performance by areas under the receiver operating characteristic curve (AUC) and calibration plots. We repeated the process on second pandemic wave (October–December 2020) data.
Results
We identified 55,425 patients with an incident solid cancer. We selected 21 comorbidities as independent predictors. The first four score classes showed similar probability of experiencing the outcome (0.2% to 0.5%), while the last showed a probability equal to 5.8%. The score performed well in both the first and second pandemic waves: AUC 0.85 and 0.82, respectively. Our results were robust for major cancer sites too (i.e., colorectal, lung, female breast, and prostate).
Conclusions
We developed a high performance comorbidity score for cancer patients and COVID‐19. Being based on administrative databases, this score will be useful for adjusting for comorbidity confounding in epidemiological studies on COVID‐19 and cancer impact.
Developement and validation of a COVID‐19 comordity score for cancer patients. The total cancer patient cohort was split into training (70%) and validation (30%) sets. In the training set, comorbidities associated with the risk of developing a severe/fatal form of COVID‐19 were identified and the score weights were estimated. The score performances were then assesed in the validation set, by areas under the receiver operating characteristic curve (AUC) and calibration plots.
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