Tumors In Europe Research Articles

Gene Expression Profiling of the Peritumoral Immune Cell Infiltrate of Penile Squamous Cell Carcinomas

Penile carcinomas are rare tumors in Europe and need further investigations due to their inferior prognosis in late tumor stages. The presence of disparate immune cell infiltrates was observed in these tumors, which were subsequently demonstrated to give rise to divergent tumor prognoses. The objective was to further characterize this immune cell infiltrate with the use of immunohistochemistry and RNA expression. A total of twelve well-characterized cases of penile squamous cell carcinomas with known infection status by human papillomavirus (HPV) and p16 status were assessed. The cases were classified according to their morphological characteristics, including those exhibiting a pronounced peritumoral immune cell infiltrate and those with less peritumoral immune cell infiltration. The generation of RNA expression data was conducted using the nCounter® PanCancer Immune Profiling Panel. Computational models were employed to calculate the proportions of immune cells. To corroborate the findings, an immunohistochemical analysis was conducted using antibodies against CD20, CD3, CD4, CD8, MUM1, CD68, and CD117. Our cases were clustered according to the immune cell infiltrate detected via histology in a group with less immune cell infiltrate density and in a group with increased immune cell infiltrate density. Generally, all immune cells showed an increased amount in the group with pronounced immune cell infiltrate density. The clusters were found to relate to cell functions, the complement system, cytotoxicity, pathogen defense, regulation, and T-cell functions. In cases exhibiting a pronounced immune cell infiltrate, the top three genes that exhibited the greatest upregulation were GZMA, MICB, and GNLY. No relationship to HPV infection status was demonstrated. Immunohistochemistry validated the data gained via RNA expression and showed a correlation with EPIC and Cibersort. The clustering of cases based on immune cell infiltrate density revealed significant distinctions between groups with lower and higher immune cell infiltrate density. The group with increased immune cel infiltrate density showed a greater abundance of immune cells, aligning with key functions like cytotoxicity, pathogen defense, and T-cell regulation. Among these cases, the genes GZMA, MICB, and GNLY were significantly upregulated, suggesting their involvement in an increased immune response. The role of HPV infection status in our cases with regard to the peritumoral immune cell infiltrate remains inconclusive.

Approved medicines for paediatric solid tumours in Europe: Lessons from the life cycle of a paediatric investigation plan

BackgroundDespite the positive changes brought by the Paediatric Regulation in the European Union (EU) in 2007, drug development in children remains challenging. MethodsTo better understand the issues encountered to reach an authorisation for paediatric patients, we reviewed the pathway of the 11 Paediatric Investigational Plans (PIPs) with indications targeting paediatric solid tumours granted by the Committee for Medicinal Products for Human Use (CHMP) between 2007 and 2022. ResultsOn average 5,5 years were necessary to reach approval after a PIP was agreed. All the PIPs underwent at least one modification (median 3 modifications per PIP). The use of single arm trials, in the context of refractory/relapsed disease in absence of standard of care treatment, was supportive for granting a paediatric indication in the majority of the cases. In 6 out of 11 approved products, extrapolation from adults was used. For 2/11 the approval focused on an older population first compared to the initial age group agreed in the PIP due to the development of a suitable formulation for younger children still ongoing at the time of first approval. Scientific advice sought on paediatric development use of extrapolation from adults, major objections raised by CHMP and post-marketing requirements were examined. ConclusionAnalysing the process necessary to reach an authorisation for paediatric patients, we highlight the major challenges faced in the paediatric approval process and the positive examples of successful drug development that reached final approval. Our analysis is expected to provide useful insights to drug developers, investigators and regulators.

EPID-02. A CLINICALLY RELEVANT SURVIVAL COMPARISON OF PEDIATRIC CENTRAL NERVOUS SYSTEM TUMORS FOR 31 EUROPEAN COUNTRIES – POPULATION-BASED RESULTS FROM THE EUROCARE-6 PROJECT

Abstract BACKGROUND Survival outcomes of pediatric central nervous system (CNS) tumors have been reported to vary largely across countries and regions in Europe. This is the first time the EUROCARE-6 database was used to study survival outcomes for clinically relevant groups of pediatric CNS tumors in Europe. METHOD Survival data of 14,689 children (<15 years) diagnosed with a CNS tumor between 2008 and 2013 from 31 European countries was analyzed. Multivariable cox regression model was used to compare adjusted risks of dying (HR) from major groups of CNS tumors between countries using Germany as reference. RESULTS Five-year observed survival (OS) of low-grade gliomas (LGGs) for most countries was >90%. Three countries with comparable hazard ratios (2.6-2.7) showed to have a significantly higher risk of dying compared to Germany. Large variation in survival was seen for high-grade gliomas (HGGs); 0%-70%. When analyzing HGGs, six countries had a significantly higher risk of dying with hazard ratios ranging from 1.2 to 4.2. When excluding malignant gliomas, NOS (ICD-O-M9380/3) from the HGGs the risk of dying became comparable for two out of the six countries. For HGGs, only one country had a significant lower risk of dying. For Medulloblastomas, 5-year OS within the majority of countries ranged between 40-70% but with some countries having no patients surviving their disease. Seven countries had significantly worse survival outcomes with hazard ratios ranging from 1.7-3.2. No countries were found to have better survival outcomes. CONCLUSIONS This population-based study provides an insightful comparison of survival from CNS tumors in children between European countries corrected for potential incompleteness of non-malignant CNS tumors and misclassification of NOS tumors. Survival disparities were still seen for all tumor groups.

Efficacy and safety of streptozocin-based chemotherapy for gastroenteropancreatic neuroendocrine tumors in Japanese clinical practice.

Streptozocin has been used to treat neuroendocrine tumors in Europe and the USA; however, its actual status in Japan has not been fully clarified owing to the rarity of this disease and the relatively recent approval of streptozocin in Japan. We retrospectively analyzed 53 patients with gastroenteropancreatic neuroendocrine tumors who were treated with streptozocin-based chemotherapy at two Japanese hospitals between January 2004 and June 2023. The overall response and disease control rates were 27.7 and 74.5%, respectively, and the median progression-free survival and overall survival were 7.1 and 20.3months, respectively. Performance status ≥1 showed a significant negative correlation with progression-free survival, and performance status ≥1 and liver tumor burden ≥25% showed a significant negative correlation with overall survival. No significant differences were observed in the treatment response between pancreatic and gastrointestinal neuroendocrine tumors. No treatment-related serious adverse events were observed; however, 87.7% of patients expressed a decrease in the estimated glomerular filtration rate, which negatively correlated with the duration of streptozocin treatment (r=0.43, P=0.0020). In the streptozocin re-administration group (n=5), no differences were found in efficacy between the initial and second streptozocin treatments. Although streptozocin is a safe, streptozocin-induced renal dysfunction is a dilemma in streptozocin responders. Streptozocin may benefit patients with gastroenteropancreatic neuroendocrine tumors, especially those with a good performance status; however, in some cases, planned streptozocin withdrawal or switching to other drugs should be considered.

Diagnosis and treatment of malignant eyelid tumors.

Malignant tumors of the eyelid are much less frequent than benign eyelid alterations. These are frequently incidental findings without symptoms which are often overlooked or misinterpreted by patients. This article gives an overview of clinical aspects, diagnostics and treatment of the five most common malignant eyelid tumors and exemplarily explains the essential principles of evidence-based treatment of malignant eyelid tumors. This narrative review was prepared based on aselective literature search. The depiction of the treatment of eyelid tumors is supported by illustrations of clinical cases. The medical history and inspection provide initial indications of malignancy. Every eyelid change suspected of being malignant should be examined histologically to confirm adiagnosis. By far the most common malignant eyelid tumor in Europe is basal cell carcinoma, which metastasizes only in exceptional cases. Squamous cell carcinomas, sebaceous adenocarcinomas, melanomas and Merkel cell carcinomas occur much less frequently. In these cases, potential metastasis in particular must be considered when making the diagnosis and staging has to be initiated. Surgical excision into healthy tissue with tumor-free margins is the gold standard for malignant eyelid tumors. Non-surgical adjuvant or neoadjuvant forms of evidence-based treatment can be initiated based on the individual case to minimize the risk of recurrence and metastasis. It is essential to recognize eyelid changes at an early stage, to classify them correctly and to initiate the appropriate treatment. The interaction between the general condition and the personal needs of apatient as well as state of the art medicine are the keys to a good personalized treatment.

Locally Advanced Prostate Cancer at High Risk of Progression: A Treatment Strategy, A Review of Clinical Studies

The clinician doctors should be decided the difficult task of determining the exact stage of prostate cancer. This concerns, first of all, stage T3 - or locally progressive, the presence of which indicates that the tumor is spreading beyond the capsule. Prostate cancer is the most common solid tumor in Europe, with an incidence rate of 214 cases per 1,000 men, which is higher than for lung and colorectal cancers [3]. In 2013, prostate cancer ranked 3rd in the structure of oncological diseases in men in Russia, 29,158 new cases of the disease were recorded, 9,535 patients died from prostate cancer. Over the past 5 years, the number of patients with PCa in our country has increased, in particular, in 2015 - 372, in 2016 - 443, in 2019 the number of patients reached 483 (an increase of 23%). There is also an increase in the incidence, which in 2015 amounted to 1.2 patients per 100 thousand of the population, in 2019 this figure was 1.5. (Tillyashaikhov M.N. et al., 2020). The optimal therapy for patients with clinically locally progressive prostate cancer has not been finally determined, and the tactics of treating these patients cause a lively discussion. Many controversial issues regarding the choice of a particular method remain unresolved.

Diagnosis and treatment of malignant eyelid tumors

Malignant tumors of the eyelid are much less frequent than benign eyelid alterations. These are frequently incidental findings without symptoms which are often overlooked or misinterpreted by patients. This article gives an overview of clinical aspects, diagnostics and treatment of the five most common malignant eyelid tumors and exemplarily explains the essential principles of evidence-based treatment of malignant eyelid tumors. This narrative review was prepared based on aselective literature search. The depiction of the treatment of eyelid tumors is supported by illustrations of clinical cases. The medical history and inspection provide initial indications of malignancy. Every eyelid change suspected of being malignant should be examined histologically to confirm adiagnosis. By far the most common malignant eyelid tumor in Europe is basal cell carcinoma, which metastasizes only in exceptional cases. Squamous cell carcinomas, sebaceous adenocarcinomas, melanomas and Merkel cell carcinomas occur much less frequently. In these cases, potential metastasis in particular must be considered when making the diagnosis and staging has to be initiated. Surgical excision into healthy tissue with tumor-free margins is the gold standard for malignant eyelid tumors. Non-surgical adjuvant or neoadjuvant forms of evidence-based treatment can be initiated based on the individual case to minimize the risk of recurrence and metastasis. It is essential to recognize eyelid changes at an early stage, to classify them correctly and to initiate the appropriate treatment. The interaction between the general condition and the personal needs of apatient as well as state of the art medicine are the keys to a good personalized treatment.

Optimizing First-Line Chemotherapy in Metastatic Pancreatic Cancer: Efficacy of FOLFIRINOX versus Nab-Paclitaxel Plus Gemcitabine.

Pancreatic cancer (PC) is one of the most lethal tumors in Europe with an overall 5-year survival rate of 5%. Since 1992, gemcitabine (Gem) has been the treatment of choice for metastatic disease with significant improvement in median overall survival (OS) compared to fluorouracil. A good performance status (PS) at diagnosis appears to be a strong predictive factor for better survival. Overall, 50% of PC are metastatic or locally advanced at diagnosis, and more than 70% of the resected patients will experience a recurrence, with a median OS ranging from 4 to 10 months (mos). FOLFIRINOX (5-fluorouracil, leucovorin, irinotecan, and oxaliplatin) and Nab-paclitaxel (Nab-p) plus Gem have recently increased survival of patients with metastatic PC, over Gem. Treatment with FOLFIRINOX is generally considered more effective with respect to the doublet, with toxicity concerns, FOLFIRINOX achieves an overall response rate (ORR) of 31.6%, while for Nab-p plus Gem ORR is 23%; however, FOLFIRINOX was associated with higher rates of grade 3 and higher adverse events. Although the international guidelines indicate that both regimens can be used as first-line therapy for patients with metastatic PC, FOLFIRINOX is the most widely used; Nab-p plus Gem is more frequently used in patients with lower PS. In this review, we critically analyze these two regimens to give a pragmatic guide to treatment options.

Impact of perioperative chemotherapy in the treatment of patients with gastric cancer.

Perioperative chemotherapy (PeriCh) is the current standard of care for stage II/III gastric cancer tumors in Europe. However, when it concerns patients who endure complications during PeriCh it is unclear if it increases the risk of postoperative complications and other poorer surgical outcomes. We aim to demonstrate if there is an association between having complications during PeriCh and postoperative complications and histopathological response. We conducted a retrospective, transversal, and observational study, including all patients with diagnosed gastric cancer who underwent PeriCh followed by surgical resection during the period of eight years. We included 80 patients with a median age of 64.0years (min 24, max 78). Eighty-eight-point eight percent ended the chemotherapy regime proposed, with a median duration of 42 days, and were also submitted to gastric resection: 58.8% total gastrectomy and 41.2% distal gastrectomy. Twelve-point five percent of the patients had no complications during the PeriCh period and 16.3% had >2 complications. Twenty-five percent of patients had a histological response of <10% of tumor burden, but in 41.3% only regression of <50% could be obtained. No significant association was found between complications during PeriCh and adverse surgical outcomes (P = .497). Patients with complications during PeriCh had slightly higher median time difference from end of PeriCh until surgery, but with no statistical significance (P = .575). In our sample, the existence of association between complications during PeriCh and postoperative complications or histological response was not demonstrated.

917P OPTIMA: Improve care for patients with prostate, breast, and lung cancer through artificial intelligence

OPTIMA (Optimal Treatment for Patients with Solid Tumours in Europe Through Artificial intelligence) is an Innovative Medicines Initiative (IMI) 2 funded public-private research programme that seeks to use artificial intelligence (AI) to improve patients’ care with prostate, breast, and lung cancer. OPTIMA’s goal is to design, develop and deliver the first interoperable, GDPR-compliant real-world data (RWD) and guideline-driven evidence-generation platform in Europe.

Distribution of gastrointestinal neuroendocrine tumors in Europe: results from a retrospective cross-sectional study

BackgroundGastrointestinal (non-pancreatic) neuroendocrine tumors (GI-NETs) represent a rare but increasingly common tumor entity. Prognosis and biological behavior of these tumors is extremely heterogenous and largely dependent on the specific tumor site, stage and differentiation. However, systematic data on the epidemiology of GI-NET, especially in terms of geographic distributions are missing.MethodsWe used the Oncology Dynamics database (IQVIA) to identify a total of 1354 patients with GI-NET from four European countries (Germany, France, Spain, UK) and compared them with regard to major patient and tumor related characteristics including patients’ age, sex, tumor stage, tumor grading and differentiation.ResultsOut of the analyzed 1354 NET patients, 535 were found in the UK (39.5%), 289 in Germany (21.3%), 283 in Spain (20.9%) and 247 in France (18.2%). More patients were male than female (53.8% vs. 46.2%) with no significant differences between the analyzed countries. In contrast, the age distribution varied between the different countries, with the highest number of patients identified in the age groups of 61–70 years (31.0%) and 71–80 years (30.7%). The vast majority of patients showed a tumor origin in the small intestine, in German patients NET of the large intestine were slightly overrepresented and NET of the stomach underrepresented compared to all other countries. More than 80% of patients had stage IV disease at the time of diagnosis. Regarding tumor histology, most tumors showed a G2 tumor; interestingly, a G3 grading was found in 40.9% of patients in Germany (Ki-67 > 20%).ConclusionThe distribution of important patient- and tumor-specific characteristics of neuroendocrine tumors shows regional differences in four major European countries. These data may help to better understand the specific epidemiology of GI-NET in Europe.

Still divergent but on the way to convergence: clinical practice of CNS germ cell tumors in Europe and North America from the perspectives of the East.

Still divergent but on the way to convergence: clinical practice of CNS germ cell tumors in Europe and North America from the perspectives of the East.

Long Noncoding RNA KCNMB2-AS1 Promotes SMAD5 by Targeting miR-3194-3p to Induce Bladder Cancer Progression.

PurposeBladder cancer is a common malignant tumor of the urinary system, with the fourth-highest incidence of male malignant tumors in Europe and the United States. So far, the mechanism of bladder cancer progression and metastasis has not been clarified. The aim of our study was to validate the way of long noncoding RNA (lncRNA) KCNMB2-AS1 on the metabolism and growth of bladder cancer cells by miR-3194-3p/SMAD5.Patients and MethodsThe Gene Expression was analyzed by qRT-PCR in bladder cancer tissues and cell lines, with the highly expressed KCNMB2-AS1 screened out. Cell proliferation was detected by Edu staining and clone formation assay, cell migration, and invasion by wound healing and transwell assays. Cell stemness was determined by assessing sphere-forming ability and stemness marker. Correlation between miRNA and lncRNA/gene was verified by dual‐luciferase assay and RIP, and the effect of KCNMB2-AS1 on bladder cancer growth by nude mice tumor formation experiment.ResultsHere, we revealed the increased level of KCNMB2-AS1 in bladder cancer for the first time. Knockdown of KCNMB2-AS1 in vitro prevented the ability of proliferation, metastasis, and stemness of cancer cells. In vivo, the silencing of KCNMB2-AS1 also prevented tumor growth in vivo. Next, we revealed that KCNMB2-AS1 could interact with miR-3194-3p and uncovered that SAMD5 was a downstream target of miR-3194-3p.ConclusionIn conclusion, KCNMB2-AS1 mediated the bladder cancer cells progress by regulating the miR-3194-3p/SAMD5 signal pathway, which would provide a new target for bladder cancer research.

Adaptation of chemotherapy to the decline tumor markers in patients with poor prognosis nonseminomatous germ cell tumors:Real-world French experience.

385 Background: Personalized chemotherapy based on tumor marker decline is the new standard in poor prognosis germ-cell tumor in Europe since 2014 (GETUG 13, Lancet, Fizazi et al). The purpose of this study was to analyze the reproducibility of the princeps study in patients not selected in clinical routine between 2014 and 2018. Methods: Patients (pts) were eligible if they had at least one criteria of IGCCCG classification for poor prognosis group. They had to be treated according the study terms of GETUG 13 study and did not received prior treatment. They had to received 1 BEP (Bleomycin, Etoposide, Cisplatin). Tumor markers (HCG and AFP) were dosed between day 18 and 21. Then, they received 3 additional BEP if they had favorable tumor marker decline or intensive chemotherapy if they had unfavorable decline. Results: This retrospective study included 104 patients in 14 french centers treated between 2013 and 2018: 22,1 % (n = 23) in the favorable group (Fav), 77,9 % (n = 81) in the unfavorable group (Unfav). Thirty-two pts had PS ≥ 2. In Unfav, there were more pts with HCG &gt; 50 000 UI/L (44,2 % vs 13 %, p = 0,0067), neutrophil-to-lymphocyt ratio was also higher (median 6,4 vs 4,5, p = 0,0199). At cycle 1, all pts received BEP in Fav and 87,5 % (n = 70) in Unfav. After chemotherapy and surgery, 65,2 % in Fav and 41,3 % in Unfav obtained complete response. At 30 months (median follow-up), Fav-OS was 80,5 % (IC95% 55,8 – 92,2) and Unfav-OS was 64,4 % (IC95% 52 – 74,4). At 30 months, rates were 69,6 % (IC95% 46,6 -84,2) and 63.5 % (IC95% 51,9 – 73) respectively. In GETUG 13 study, 3-years OS was 84 % in Fav and 73 % on Unfav; 3-years PFS was 70 % and 59 % respectively. Seven pts died because of toxicity in Unfav (No one in Fav). Neuropathy, anemia and thrombopenia were more frequent in Unfav. Salvage high-dose chemotherapy with stem-cell transplant was required in 4 (66,7 %) pts in Fav and 8 (36,4 %) pts in Unfav. Conclusions: This study showed a reproducibility of the princeps study in terms of PFS and OS. Toxicity seemed more important in real world. For the congress, results will be reported with 50 additional pts.

Current Status of Palliative and Terminal Care for Patients with Primary Malignant Brain Tumors in Japan.

Palliative care and advance care planning (ACP) from the first diagnosis of glioblastoma are important. This questionnaire survey was conducted to understand the current status of palliative care for brain tumors in Japan. Representative characteristics of Japan in comparison with Western countries (P <0.01) are described below: (1) Gender ratio of male in physicians who treat brain tumors in Europe and the United States/Canada are about 70%, but 94% in Japan. (2) The specialty is predominantly neurosurgeon (93%) in Japan. The ratio of neurologists is predominantly 40% in Europe. In the United States/Canada, neurologist (27%) and neurosurgeon (29%) are main parts. (3) Years of medical experience over 15 in physicians is 73% in Japan. Proportions of those with over 15 years are 45% in Europe and 30% in the United States/Canada. (4) In practicing setting, the rate of academic medical centers is about 80% in Europe and the United States/Canada, and ~60% in Japan. Representative differences compared with past domestic data (2007) (P <0.01): (1) In glioblastoma, the rate of explaining about median survival time increases from 39% (2007) to 80% (2018). Explanation about medical conditions to the patient himself with his family increases from 20% (2007) to 39% (2018). (2) Place of death: The rate at hospital is decreasing from 96% (2007) to 79% (2018) and at home is increasing from 3% (2007) to 10% (2018) (3) The rate of ventilator in adult has decreased from 74% (2007) to 54% (2018), but nasal tube feeding has remained unchanged from 62% (2007) to 60% (2018). These results will be shared with physicians to make better care systems for patients with brain tumors.

Oral Cancer: Incidence and Management

Oral cancers are among the 10 most common tumors in Europe and the United States. The major recognized risk factors include smoking and alcohol what is possible explanation for higher incidence among men. The risk of developing a tumor of the oral cavity is 38 times higher in the population that consuming alcohol and cigarettes. Cancer of the oral cavity is a serious disease and only half of the patients survive the next five years.

Changes in the clinicopathological features of surgically treated lung cancer around the millennium

Lung cancer is the most common malignant tumor in Europe and Hungary. In 2010, 10 557 new cases were registered in Hungary; 80-85% of these cases were associated with smoking. In our work we analyzed the data of lung cancer patients of the last 15 years retrospectively. We examined the demographic characteristics, the histological type, the stage of the lung cancer, the type of the surgical procedure used, other supplemental treatment and survival retrospectively. Lung cancer has occurred 50 per cent more often among females in the last decade. This growth is due to the increase of adenocarcinoma cases. Thanks to the improving diagnostic modalities and the routine follow-up of oncological patients, the number of I/A cases has been doubled recently and the preoperative staging and physical condition check-up have become more accurate. Neoadjuvant treatment has been introduced, the proportion of sublobar resections has risen, the ratio of pneumonectomy and sleeve lobectomy has become equal, so many previously unresectable cases turned to be resectable and the tolerance of adjuvant therapy has also improved. Videothoracoscopic lobectomy has become an everyday practice, leading to a decrease in the operative stress on patients. In spite of this development, the five-year survival has not changed significantly, staying around 50%. Orv Hetil. 2018; 159(10): 391-396.

Endoscopic treatment of upper GI tumors in Europe

Endoscopic treatment of upper GI tumors in Europe

Epidemiology of HPV-Positive Tumors in Europe and in the World.

Strong evidence has accumulated in the last 15years showing that infection by certain human papillomaviruses (HPVs) is etiologically involved in a subset of head and neck cancers (HNCs). In this chapter, epidemiologic-related topics on HNCs are reviewed: (i) HPV-attributable fractions and HPV-type distributions by different anatomical HNC sites, using not only HPV DNA but other more specific markers of causality; (ii) an update of the HPV-related HNCs burden worldwide and by regions; and finally, (iii) the determinants for HPV positivity in HNCs, focussing on gender, age, smoking habits, sexual behavior, and other related factors such as tonsillectomy performance. This information is essential in order to understand the burden of the disease and its dynamics and changing patterns, as well as for planning and assessment of the potential impact of HPV-based preventive strategies for HNCs.

Data quality in rare cancers registration: the report of the RARECARE data quality study.

Rare cancers represent 22% of all tumors in Europe; however, the quality of the data of rare cancers may not be as good as the quality of data for common cancer. The project surveillance of rare cancers in Europe (RARECARE) had, among others, the objective of assessing rare cancer data quality in population-based cancer registries (CRs). Eight rare cancers were considered: mesothelioma, liver angiosarcoma, sarcomas, tumors of oral cavity, CNS tumors, germ cell tumors, leukemia, and malignant digestive endocrine tumors. We selected data on 18,000 diagnoses and revised, on the basis of the pathologic and clinical reports (but not on pathologic specimens), unspecified morphology and topography codes originally attributed by CR officers and checked the quality of follow-up of long-term survivors of poor prognosis cancers. A total of 38 CRs contributed from 13 European countries. The majority of unspecified morphology and topography cases were confirmed as unspecified. The few unspecified cases that, after the review, changed to a more specific diagnosis increased the incidence of the common cancer histotypes. For example, 11% of the oral cavity epithelial cancers were reclassified from unspecified to more specific diagnoses: 8% were reclassified as squamous cell carcinoma (commoner) and only 1% as adenocarcinoma (rarer). The revision confirmed the majority of long-term survivors revealing a relative high proportion of mesothelioma long-term survivors. The majority of appendix carcinoids changed behavior from malignant to borderline lesions. Our study suggests that the problem of poorly specified morphology and topography cases is mainly one of difficulty in reaching a precise diagnosis. The awareness of the importance of data quality for rare cancers should increase among registrars, pathologists, and clinicians.