Laura Botta

Prognoses and improvement for head and neck cancers diagnosed in Europe in early 2000s: The EUROCARE-5 population-based study

BACKGROUND Head and neck (H&N) cancers are a heterogeneous group of malignancies, affecting various sites, with different prognoses. The aims of this study are to analyse survival for patients with H&N cancers in relation to tumour location, to assess the change in survival between European countries, and to investigate whether survival improved over time. METHODS We analysed about 250,000 H&N cancer cases from 86 cancer registries (CRs). Relative survival (RS) was estimated by sex, age, country and stage. We described survival time trends over 1999-2007, using the period approach. Model based survival estimates of relative excess risks (RERs) of death were also provided by country, after adjusting for sex, age and sub-site. RESULTS Five-year RS was the poorest for hypopharynx (25%) and the highest for larynx (59%). Outcome was significantly better in female than in male patients. In Europe, age-standardised 5-year survival remained stable from 1999-2001 to 2005-2007 for laryngeal cancer, while it increased for all the other H&N cancers. Five-year age-standardised RS was low in Eastern countries, 47% for larynx and 28% for all the other H&N cancers combined, and high in Ireland and the United Kingdom (UK), and Northern Europe (62% and 46%). Adjustment for sub-site narrowed the difference between countries. Fifty-four percent of patients was diagnosed at advanced stage (regional or metastatic). Five-year RS for localised cases ranged between 42% (hypopharynx) and 74% (larynx). CONCLUSIONS This study shows survival progresses during the study period. However, slightly more than half of patients were diagnosed with regional or metastatic disease at diagnosis. Early diagnosis and timely start of treatment are crucial to reduce the European gap to further improve H&N cancers outcome.

Survival of European adolescents and young adults diagnosed with cancer in 2000–07: population-based data from EUROCARE-5

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, Hodgkins lymphomas, non-Hodgkin lymphomas, astrocytomas, Ewings 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.

Survival of adults with primary malignant brain tumours in Europe; Results of the EUROCARE-5 study

BACKGROUND Primary malignant brain tumours are rare but represent a serious health burden due to their poor survival. This manuscript describes the survival of malignant brain tumours in adults diagnosed 2000-2007 in Europe. METHODS For this study we analysed patients archived in 86 European population-based cancer registries, followed up to 31st December 2008. Only primary malignant neuroepithelial brain tumours (with pathological confirmation) and primary malignant unspecified brain tumours without pathological confirmation were included. We estimated 1-year and 5-year relative survival (RS) weighted by age group and country. We also estimated country-specific and age-specific survival, together with survival differences between time periods (for 1999-2001, 2002-2004 and 2005-2007). RESULTS Glioblastoma represents 49% of all brain tumours, followed by other/unspecified astrocytoma (18%), oligodendroglioma/oligoastrocytoma (9%), ependymoma (1.5%) and embryonal tumours (1%). Five-year RS was 20% for all tumours combined, but ranged from 58% for ependymoma to only 6% for glioblastoma and sharply decreased with increasing age. Differences between countries were relatively small, but generally RS in Ireland/United Kingdom (UK) and Eastern Europe was below the average. An increase in 1-year RS (up to 10-12%) was noted over time, being largest in Central and Northern Europe in patients between 45 and 74years of age. CONCLUSIONS Despite an increase in 1-year RS in most European regions, the survival of primary malignant brain tumours is still poor. Disparities between countries were evident, being even larger at the end of the study period than at the beginning, suggesting differences in availability of the latest treatment modalities.

Available evidence and new biological perspectives on medical treatment of advanced thymic epithelial tumors

Thymic epithelial tumors (TETs) are rare primary mediastinal tumors arising from thymic epithelium. Their rarity and complexity hinder investigations of their causes and therapy development. Here, we summarize the existing knowledge regarding medical treatment of these tumors, and thoroughly review the known genetic aberrations associated with TETs and the present status of potential biological treatments. Epidermal growth factor receptor (EGFR), stem-cell factor receptor, insulin-like growth factor-1 receptor (IGF1R), and vascular endothelial growth factors (VEGF-A, VEGF-B, and VEGF-2) are overexpressed in TETs. EGFR overexpression in TETs is associated with higher stage, and IGF1R overexpression has poor prognostic value. Data indicate that anti-IGF1R monoclonal antibodies, and inhibitors of angiogenesis, somatostatin receptors, histone deacetylase, mammalian target of rapamycin, and cyclin-dependent kinases may be active against TETs. Continued investigations in this field could lead to advancement of targeted and biological therapies for TETs.

Access to clinical trials for adolescents with soft tissue sarcomas: Enrollment in European pediatric Soft tissue sarcoma Study Group (EpSSG) protocols

Adolescents with cancer are enrolled in clinical trials at far lower rates than children. This report compares the number of adolescents (15–19‐year‐olds) and children (0–14‐year‐olds) enrolled in the protocols of the European pediatric Soft tissue sarcoma Study Group (EpSSG) with the number of cases expected to occur.

Prostate cancer changes in clinical presentation and treatments in two decades: an Italian population-based study

INTRODUCTION The incidence of prostate cancer is on the rise in many industrialised countries, including Italy, most likely because of the spread of PSA testing. In Italy, prostate cancer mortality has been dropping since 2000, but it is difficult to understand whether PSA testing is the main reason, considering the role of treatment in prognosis. The objectives of this study were: (1) to describe Italian trends of prostate cancer risk categories and corresponding changes in treatment patterns and (2) to interpret changes in survival over time. METHODS We made a retrospective observational study using population-based cancer registries. We examined two periods, 1996-1999 and 2005-2007, analysing the distribution of patients among risk groups and treatment changes in those intervals. We estimated 7- and 15-year relative survival with the cohort approach, Ederer II method. We analysed 4635 cases. RESULTS There was downward risk migration from the first to the second period. In patients younger than 75 years, there was an increase in radical prostatectomy but not radiotherapy; patients older than 75 years rarely had treatment with radical intent. We noted an improvement of prostate cancer survival in the high-risk group. CONCLUSION These findings raise several questions: the possible overtreatment of low-risk patients undergoing radical treatment; the utility of more aggressive treatment for elderly patients with high-risk disease; and the importance of a multidisciplinary clinical approach to ensure multiple and alternative treatment options. The increase in survival, with the decrease in mortality, suggests an effect of radical treatments on prognosis.

Detection of soluble EpCAM (sEpCAM) in malignant ascites predicts poor overall survival in patients treated with catumaxomab

EpCAM is an attractive target for cancer therapy and the EpCAM-specific antibody catumaxomab has been used for intraperitoneal treatment of EpCAM-positive cancer patients with malignant ascites. New prognostic markers are necessary to select patients that mostly benefit from catumaxomab. Recent data showed that soluble EpCAM (sEpCAM) is capable to block the effect of catumaxomab in vitro. This exploratory retrospective analysis was performed on archived ascites samples to evaluate the predictive role of sEpCAM in catumaxomab-treated patients. Sixty-six catumaxomab-treated patients with an available archived ascites sample were included in this study and tested for sEpCAM by sandwich ELISA. All probes were sampled before treatment start and all patients received at least one catumaxomab infusion. Overall survival, puncture-free survival and time to next puncture were compared between sEpCAM-positive and -negative patients. We detected sEpCAM in ascites samples of 9 patients (13.6%). These patients showed a significantly shorter overall survival. The prognostic significance of sEpCAM in ascites was particularly strong in patients with ovarian cancer. Puncture-free survival and time to next puncture were not significantly different between sEpCAM-positive and -negative patients. We propose sEpCAM in malignant ascites as a potential predictive marker in cancer patients treated with catumaxomab. Prospective studies with larger patients samples are urgently needed to confirm these findings and studies testing dose-intensified catumaxomab in patients with sEpCAM-positive ascites should be envisaged.

Cancer Incidence, Survival, and Mortality Among Adolescents and Young Adults

While the epidemiology of cancer has been studied in children and older adults for more than a half century, little attention had been paid to the cancers in between those that occur in the older adolescents and young adult (AYA) between 15 and 40 years of age. Yet as recently ascertained, more than a million new cases of invasive cancer are diagnosed in AYAs annually worldwide. Not only are the array of cancers that are diagnosed in AYAs unique, accumulating evidence suggests that many are biologically distinct from what appears to be the same neoplasm in younger and older persons. AYA cancers may thereby have different etiologies and require different therapeutic strategies. Many cancers peak in incidence in AYAs, and there is an intermediate peak between the well-known childhood cancer peak and the predominant one that occurs in the elderly. If the cancers that account for the childhood peak are embryonal/fetal cancers and those that account for the peak late in life as the cancers of aging, the AYA peak may be considered as due to cancers of intermediate growth and maturation. For most of the past quarter century, the incidence of the AYA cancers has been increasing for reasons that have not been ascertained. In Europe, the United States, and Japan, the 5-year survival rates of the vast majority of cancers in AYA have been remarkably similar. In the United States, the overall rate of survival improvement had been less in AYAs than in either younger or older patients. The trends and patterns of incidence do offer certain clues as to cancer causation in AYAs and potential methods of prevention. Detailed analyses of incidence patterns by geographic region and demographic factors together with determination of variations in incidence in time and space should provide additional insights into etiology and separate lines of investigation and therapeutic opportunities.

Is the cancer survival improvement in European and American adolescent and young adults still lagging behind that in children

Improvements during 1978 to 2006 in the 5‐year survival rate of adolescents and young adults (AYAs, age 15–39) and children with cancers common to both age groups were evaluated for 1978 to 2006 in Europe and the USA. AYAs had absolute survival increases of 25% and 15% in Europe and the USA, respectively, but in both cases, AYA 5‐year survival was, as of 2006, 4% lower than those in children. Acute lymphoblastic leukemia (ALL) explained most of the survival difference between AYAs and children on both the continents. In the USA, 20‐ to 39‐year‐olds with ALL have had less survival improvement than those in Europe.

A classification prognostic score to predict OS in stage IV well-differentiated neuroendocrine tumors

No validated prognostic tool is available for predicting overall survival (OS) of patients with well-differentiated neuroendocrine tumors (WDNETs). This study, conducted in three independent cohorts of patients from five different European countries, aimed to develop and validate a classification prognostic score for OS in patients with stage IV WDNETs. We retrospectively collected data on 1387 patients: (i) patients treated at the Istituto Nazionale Tumori (Milan, Italy; n = 515); (ii) European cohort of rare NET patients included in the European RARECAREnet database (n = 457); (iii) Italian multicentric cohort of pancreatic NET (pNETs) patients treated at 24 Italian institutions (n = 415). The score was developed using data from patients included in cohort (i) (training set); external validation was performed by applying the score to the data of the two independent cohorts (ii) and (iii) evaluating both calibration and discriminative ability (Harrell C statistic). We used data on age, primary tumor site, metastasis (synchronous vs metachronous), Ki-67, functional status and primary surgery to build the score, which was developed for classifying patients into three groups with differential 10-year OS: (I) favorable risk group: 10-year OS ≥70%; (II) intermediate risk group: 30% ≤ 10-year OS < 70%; (III) poor risk group: 10-year OS <30%. The Harrell C statistic was 0.661 in the training set, and 0.626 and 0.601 in the RARECAREnet and Italian multicentric validation sets, respectively. In conclusion, based on the analysis of three ‘field-practice’ cohorts collected in different settings, we defined and validated a prognostic score to classify patients into three groups with different long-term prognoses.