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Background: Lung neuroendocrine neoplasms (LNENs) are rare solid cancers, with most genomic studies including a limited number of samples. Recently, generating the first multi-omic dataset for atypical pulmonary carcinoids and the first methylation dataset for large-cell neuroendocrine carcinomas led us to the discovery of clinically relevant molecular groups, as well as a new entity of pulmonary carcinoids (supra-carcinoids)., Results: To promote the integration of LNENs molecular data, we provide here detailed information on data generation and quality control for whole-genome/exome sequencing, RNA sequencing, and EPIC 850K methylation arrays for a total of 84 patients with LNENs. We integrate the transcriptomic data with other previously published data and generate the first comprehensive molecular map of LNENs using the Uniform Manifold Approximation and Projection (UMAP) dimension reduction technique. We show that this map captures the main biological findings of previous studies and can be used as reference to integrate datasets for which RNA sequencing is available. The generated map can be interactively explored and interrogated on the UCSC TumorMap portal (https://tumormap.ucsc.edu/?p=RCG_lungNENomics/LNEN). The data, source code, and compute environments used to generate and evaluate the map as well as the raw data are available, respectively, in a Nextjournal interactive notebook (https://nextjournal.com/rarecancersgenomics/a-molecular-map-of-lung-neuroendocrine-neoplasms/) and at the EMBL-EBI European Genome-phenome Archive and Gene Expression Omnibus data repositories., Conclusions: We provide data and all resources needed to integrate them with future LNENs transcriptomic studies, allowing meaningful conclusions to be drawn that will eventually lead to a better understanding of this rare understudied disease., (© World Health Organization, 2020. The World Health Organization has granted the Publisher permission for the reproduction of this article.)

Background: The cumulative burden from rare cancers has not been adequately explored in Canada. This analysis aims to characterize the occurrence of rare cancers among Canadians and estimate the probability of being diagnosed with a rare cancer among cancer patients with different demographic characteristics., Methods: The Canadian Cancer Registry was used for this analysis. Cancer types were classified in three ways: using the SEER site recode scheme; by histology group; and by site/histology group. The age-standardized incidence rate (ASIR) and 95 % confidence intervals (CI) for each cancer type was estimated for diagnoses from 2006 to 2016. Two ASIR thresholds were used to classify cancers as rare:6/100,000/year and 15/100,000/year. Log-binomial regression was used to estimate the adjusted probability of having a rare cancer among those with cancer by age, sex and geographic region., Results: Using the 6/100,000/year threshold, the incidence proportion (IP) of rare cancers ranged from 9.7 %(95 %CI:9.6,9.7 %)-17.0 %(95 %CI:16.9,17.0 %), and ranged from 19.2 %(95 %CI:19.1,19.3 %)-52.5 %(95 %CI:52.0,53.0 %) using the <15/100,000/year threshold. The adjusted probability of being diagnosed with a rare cancer was highest among those aged ≤19 years. There was higher concordance in estimates of the burden of rare cancers across methods to classify cancer types when the lower incidence rate threshold was used to define rare cancers., Interpretation: This analysis yielded evidence that rare cancers comprise a substantial proportion of annual cancer diagnoses among Canadians. Findings from this analysis point to using a lower incidence rate threshold, to generate estimates of the burden of rare cancers that are robust to different cancer classification schemes., (Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Primary neuroendocrine neoplasms (NENs) of the kidney are exceedingly rare malignancies and the available literature is very limited. The natural history and response to treatments is not well characterized. We aimed to describe the presenting features, demographics, tumor characteristics, and treatment outcomes of patients with renal NENs., Patients and Methods: We performed a retrospective analysis of all Mayo Clinic patient records with a tissue diagnosis of a primary renal NEN. Baseline patient and surgical pathologic features and treatment modalities were collected. Time to recurrence after resection and overall survival (OS) were estimated using with survival analysis. Surveillance, Epidemiology, and End Results data were used to estimate the population-wide incidence and OS., Results: A total of 17 patients were included in the present study, with a median follow-up of 62.8 months. Distant metastasis was present in 29% at diagnosis, with 76% experiencing distant metastasis at any point; 24% had a horseshoe kidney. Of the 17 patients, 14 had undergone surgical resection with no evidence of disease postoperatively. Ten of these patients had documented recurrence. The median time to recurrence was 18 months (95% confidence interval, 9-46 months). Only 1 of the 10 patients showed a radiographic response to systemic therapy. Of 9 patients, 4 had stable disease with somatostatin analogs. The median OS was 143 months (95% confidence interval, 50-143 months)., Conclusions: Renal NENs are rare malignancies affecting mostly middle-age patients, with distant metastasis being common. Approximately one half of patients experience stable disease with somatostatin analogs. The OS usually exceeds 5 years., (Copyright © 2019. Published by Elsevier Inc.)

Introduction: Epidemiologic information on rare cancers is scarce outside of the Western countries. The project "surveillance of rare cancers in Asia" (RARECAREnet Asia) provides, for the first time, the burden of rare cancers in some Asian countries based on the latest list., Objectives: 1) to assess whether the European list of rare cancers fits the Asian setting and 2) to compare the incidences of rare cancers between Europe and Asian countries., Material and Methods: Population-based cancer registry data on patients diagnosed from 2011 to 2015 in Japan, Korea, and Taiwan and patients diagnosed from 2000 to 2007 in 94 European registries were analysed. The incidences for all cancers were calculated; they were then grouped into several tiers and families according to the rare cancer list, and whether cancers rare was examined., Results: Rare cancer counts according to the list in the observed population were 196 in Japan, 203 in Korea, 198 in Taiwan, and 198 in the EU. The proportions of rare in overall incidence were 16.3% in Japan, 23.7% in Korea, 24.2% in Taiwan, and 22.2% in the EU. The numbers of newly diagnosed rare cancer cases in 2015 were 140,188 in Japan, 52,071 in Korea, and 24,147 in Taiwan., Conclusion: Most rare cancers in Europe were also rare in the Asian countries considered. The observed differences were due to well-known risk factors. The European definition and list of rare cancers appear to reflect well cancer incidence in East Asia., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Rare cancers, affecting 1 in 5 cancer patients, disproportionally contribute to cancer mortality. This research focuses on liposarcoma, an understudied rare cancer with unknown risk factors and limited treatment options. Liposarcoma incident cases were identified from the U.S. Surveillance, Epidemiology, and End Result (SEER) program and the combined SEER-National Program of Cancer Registries (CNPCR) between 2001-2016. Incidence rates (age-adjusted and age-specific), 5-year survival, and the time trends were determined using SEER*stat software. Three-dimensional visualization of age-time curves was conducted for males and females. SEER liposarcoma cases represented ~30% ( n = 11,162) of the nationwide pool ( N = 37,499). Both sources of data showed males accounting for ~60% of the cases; 82%-86% cases were identified among whites. Age-adjusted incidence was greater among males vs. females and whites vs. blacks, whereas survival did not differ by sex and race. The dedifferentiated (57.2%), pleomorphic (64.1%), and retroperitoneal (63.9%) tumors had the worse survival. Nationwide, liposarcoma rates increased by 19%, with the annual percent increase (APC) of 1.43% (95% confidence interval (CI): 1.12-1.74). The APC was greater for males vs. females (1.67% vs. 0.89%) and retroperitoneal vs. extremity tumors (1.94% vs. 0.58%). Thus, incidence increased faster in the high-risk subgroup (males), and for retroperitoneal tumors, the low-survival subtype. The SEER generally over-estimated the rates and time trends compared to nationwide data but under-estimated time trends for retroperitoneal tumors. The time trends suggest an interaction between genetic and non-genetic modifiable risk factors may play a role in the etiology of this malignancy. Differences between SEER and CNCPR findings emphasize the need for nationwide cancer surveillance.

Background: The Surveillance of Rare Cancers in Europe (RARECARE) project proposed a definition and a list of rare cancers. The Joint Action on Rare Cancers (JARC), launched by the European Union and involving 18 member states and 34 partners, promoted a wide consensus effort to review the list., Patients and Methods: A group of experts was set up, including scientific societies, member state representatives of JARC, representatives of the European Reference Networks dedicated to rare cancers and rare cancer patient advocates. The definition and the list of rare clinical entities, based on the incidence data provided by two European projects (RARECARE and RARECAREnet), were rediscussed through a consensus meeting of the expert panel., Results: By consensus, it was reiterated that the best criterion for a definition of rare cancers is incidence, rather than prevalence. By consensus, the experts slightly modified the composition of the tiers of rare cancers, according to the definition based on an incidence threshold <6/100 000/year, and grouped all rare cancers within 12 families of rare cancers. Even when defined conservatively this way, rare cancers are not rare collectively, since they correspond to 10%-20% of all cancer cases., Conclusions: The list of rare cancers reviewed by JARC should be viewed as a tool in the fight against rare cancers and rare diseases. It may help to appreciate that rare cancers are cancers and rare diseases at the same time, combining issues and difficulties of both. We hope that refinements to the list and a wider understanding of its implications may contribute to increase awareness of problems posed by rare cancers and to improve quality of care in a large group of patients with cancer, who may be discriminated against just because of the low frequency of their diseases., Competing Interests: Competing interests: PGC: honoraria for advisory/speaker’s role from Deciphera Pharmaceuticals, Eisai, Eli Lilly, Nektar Ther, Pfizer, PharmaMar; institutional fundings from Amgen Dompé, AROG, Bayer, Blueprint, Eli Lilly, Daiichi Sankyo Pharma, Epizyme, Glaxo SK, Novartis, Pfizer, PharmaMar., (© Author (s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. Published by BMJ on behalf of the European Society for Medical Oncology.)

The article explores the challenges on treating rare cancer disease for cancer patients in Europe and U.S. Topics discussed include the dilemmas of hospitals and medical centers diagnosis of rare cancer diagnosis, the factors of lack of effective therapies for rare cancer disease and the caring for patients with rare cancer disease.

Background: Five-year relative survival (RS) of adults with bone and soft-tissue cancers in Europe was still <60% by 1995-1999. There was large geographical survival variability, mainly for bone tumours, and survival decreased with increasing age at diagnosis., Methods: Data from 87 population-based cancer registries in 29 countries, extracted from the EUROCARE-5 database, were used to provide updated estimates of survival and describe trends in survival of adults with cancers of these sites across Europe. We calculated 5-year RS for patients diagnosed in 2000-2007. We estimated 5-year RS by the period approach to assess changes in survival between 1999-2001, 2002-2004 and 2005-2007, and provide reliable predictions for recently diagnosed patients., Results: Five-year RS was 60% for adults diagnosed with soft-tissue cancer in 2000-2007 and 53% for those with bone cancer. RS declined with increasing age at diagnosis, especially for bone cancer. Survival from bone cancer varied widely between European regions, from 63 to 62% in Northern and Central Europe to 39% in Eastern Europe. Inter-regional variation was much less for soft-tissue cancer. For both site groupings, there was little evidence of change in five-year RS up to 2002-2004, followed by increases of 3-4% during 2005-2007., Conclusions: Outcomes for adults with bone and soft-tissue cancer in Europe began to improve around 2005; new therapeutic developments are expected to result in further progress. Survival improvements already achieved must be brought more fully to elderly patients and those in Eastern Europe. European Reference Networks on rare cancers will have a vital role in future progress., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Cancer is a complex genetic disease that can arise through the stepwise accumulation of mutations in oncogenes and tumor suppressor genes in a variety of different tissues. While the varied landscapes of mutations driving common cancer types such as lung, breast, and colorectal cancer have been comprehensively charted, the genetic underpinnings of many rare cancers remain poorly defined. Study of rare cancers faces unique methodological challenges, but collaborative enterprises that incorporate next generation sequencing, reach across disciplines (i.e., pathology, genetic epidemiology, genomics, functional biology, and preclinical modeling), engage advocacy groups, tumor registries, and clinical specialists are adding increasing resolution to the genomic landscapes of rare cancers. Here we describe the approaches and methods used to identify SMARCA4 mutations, which drive development of the rare ovarian cancer, small cell carcinoma of the ovary, hypercalcemic type (SCCOHT), and point to the broader relevance of this paradigm for future research in rare cancers.

The search for targeted novel therapies for cancer is ongoing. MicroRNAs (miRNAs) display a number of characteristics making them an attractive and realisable option. In this review, we explore these applications, ranging from diagnostics, prognostics, disease surveillance, to being a primary therapy or a tool to sensitise patients to treatment modalities such as chemotherapy and radiotherapy. We take a particular perspective towards miRNAs and their impact on rare cancers. Advancement in the delivery of miRNAs, from viral vectors and liposomal delivery to nanoparticle based, has led to a number of pre-clinical and clinical applications for microRNA cancer therapeutics. This is promising, especially in the setting of rare cancers.

There are limited published data on the burden of rare cancers in the United States. By using data from the North American Association of Central Cancer Registries and the Surveillance, Epidemiology, and End Results program, the authors provide information on incidence rates, stage at diagnosis, and survival for more than 100 rare cancers (defined as an incidence of fewer than 6 cases per 100,000 individuals per year) in the United States. Overall, approximately 20% of patients with cancer in the United States are diagnosed with a rare cancer. Rare cancers make up a larger proportion of cancers diagnosed in Hispanic (24%) and Asian/Pacific Islander (22%) patients compared with non-Hispanic blacks (20%) and non-Hispanic whites (19%). More than two-thirds (71%) of cancers occurring in children and adolescents are rare cancers compared with less than 20% of cancers diagnosed in patients aged 65 years and older. Among solid tumors, 59% of rare cancers are diagnosed at regional or distant stages compared with 45% of common cancers. In part because of this stage distribution, 5-year relative survival is poorer for patients with a rare cancer compared with those diagnosed with a common cancer among both males (55% vs 75%) and females (60% vs 74%). However, 5-year relative survival is substantially higher for children and adolescents diagnosed with a rare cancer (82%) than for adults (46% for ages 65-79 years). Continued efforts are needed to develop interventions for prevention, early detection, and treatment to reduce the burden of rare cancers. Such discoveries can often advance knowledge for all cancers. CA Cancer J Clin 2017. © 2017 American Cancer Society. CA Cancer J Clin 2017;67:261-272. © 2017 American Cancer Society., (© 2017 American Cancer Society.)

Orphan drugs (ODs) are intended for the diagnosis, prevention, or treatment of rare diseases. Many cancer subtypes, including all childhood cancers, are defined as rare diseases, and over one-third of ODs are now intended to treat oncology indications. However, market access for oncology ODs is becoming increasingly challenging; ODs are prone to significant uncertainty around their cost-effectiveness, while payers must balance the need for these vital innovations with growing sensitivity to rising costs. The objective of this review was to evaluate different mechanisms that have been introduced to facilitate patient access to oncology ODs in five different countries (Australia, Canada, England, France, and Sweden), using eight oncology ODs and non-orphan oncology drugs as examples of their application. A targeted literature review of health technology assessment (HTA) agency websites was undertaken to identify country-specific guidance and HTA documentation for recently evaluated oncology ODs and non-orphan oncology drugs. None of these countries were found to have explicit HTA criteria for the assessment of ODs, and therefore, oncology ODs are assessed through the usual HTA process. However, distinct and additional processes are adopted to facilitate access to oncology ODs. Review of eight case-study drugs showed that these additional assessment processes were rarely used, and decisions were largely driven by proving cost-effectiveness using standard incremental cost-effectiveness ratio (ICER) thresholds. The predominant implication arising from this study is that application of standard HTA criteria to oncology ODs in many countries fails to take into account any uncertainties around their clinical- and cost-effectiveness, resulting in disparities in HTA reimbursement decisions based on differences in addressing or accepting uncertainty. In order to address this issue, HTA agencies should adopt a more flexible approach to cost-effectiveness, as typified by the Tandvårds-och Läkemedelsförmånsverket in Sweden, which takes into account the small patient numbers involved, limited budget impact, and high unmet medical needs.

Soft-tissue sarcomas (STS) are a heterogeneous group of neoplasms which may be subclassified into over 70 specific histologies and may be distributed throughout the body. Approximately one-half arises in the extremities and one-third arises in the abdomen, pelvis, and retroperitoneum. The diversity and rarity of sarcomas combined with the quite large number of affected patients are factors which underline of the importance of networking in diagnosis, therapy, and research dealing with rare cancers. The expertise of the treating center is one of the most significant factors affecting survival in STS. The optimal treatment of locally recurrent disease is to prevent it; aggressive multidisciplinary treatment of the primary disease is thus required, as adjuvant therapies cannot compensate for inadequate surgery. Treatment within specialized multidisciplinary teams (MDTs) is crucial; a body of expertise in all the areas of diagnosis and treatment is required to manage STS appropriately. Conformity to approved treatment guidelines is improved when patients are treated by an MDT in a reference centre. Traditionally, peer-reviewed literature has discussed the surgical management of STS based on the site of origin. While the site of origin remains an important consideration, it has become increasingly clear that surgery must also be tailored to specific sarcoma histology to more accurately reflect tumor biology and pattern of recurrence. All sarcoma operations, included retroperitoneal surgery, should be performed in specialized centres to ensure optimal outcomes.

Rare cancers represent about a quarter of all cancers diagnosed in Europe, and their incidence is increasing. Meanwhile, scientific advances provide techniques, which become more and more sophisticated in the domain of radiotherapy. Treatment options for radiotherapy rare cancers are increasing, but are not yet evaluated. The question of the appropriateness of treatment by modern radiotherapy techniques in rare cancers remains. There are a lot of cases reported in the literature for treating rare cancers by modern technology. These techniques are often used when anatomical and dosimetric constraints do not achieve optimal treatment by surgery or standard radiotherapy. In contrast, standard radiotherapy techniques also provide good results in terms of overall survival and tolerance. They are also less expensive and less complex in terms of dosimetry. The establishment of specialized centers in rare cancers seems essential to evaluate the appropriateness of the use of modern techniques in these cases. Currently, data from the literature does not provide an answer to this question., (Copyright © 2014 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.)

Background: Despite the fact that rare cancer is a new target of cancer control in Japan, the incidence of rare cancers is unknown and there is no generally accepted definition of rare cancers in this country. With the aim of calculating incidences of rare cancers in Japan, we therefore adopted a definition and classification of rare cancers that had been published in the European Union (EU) in 2011., Methods: Using incidence data between 1998 and 2007 submitted by 12 of population based cancer registries in Japan that met our quality criteria and drawing on the EU definition (incidence <6 per 100,000 per year), we estimated the incidences of 845 combinations of tumor sites and histological groups and thus identified the cancers that are rare in Japan., Results: After identifying 193 combinations of tumor sites and histological groups that fit our criteria for rare cancers, we estimated their incidence to be about 75 per 100,000, which corresponds to about 94,800 new diagnoses in 2012 or approximately 15% of all cancer diagnoses. The categorization of rare and common cancers was almost the same in Japan as in EU., Conclusions: The present study provides an indication of the size of the rare cancer burden in Japan and epidemiological information to explore this. We are expecting further discussion based on our results with stakeholders in order to construct a Japanese definition of rare cancers., (Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Rare cancer issues have not been much explored yet because of their low incidence. That is why epidemiological studies have difficulties in identifying indisputable etiological risk factors. An expert opinion, mainly concentrated in some establishments, is required for these cancers' management. However, on account of the potential remoteness of these therapeutic resources, the patients' way of care remains also unstudied. By means of a geographical analysis of a regional exhaustive cohort of sarcoma, diagnosed in 2006 and 2007 and followed during five years at least, we can make progress on these different issues. Gastro-Intestinal and Stromal Tumors (GIST) occur more frequently in privileged territories while liposarcomas arise in more deprived areas. The association between liposarcomas and areas deprivation is significant (P=0.05). Moreover, pre-operative biopsy and some clinical patient characteristics, age, grade or tumor localization, are associated with an increase in the distance covered by patients for the first-line treatment (p ≤ 0,001). In the scope of an interdisciplinary collaboration, the geographical approach develops some hypothesis for rare cancers research, which must be tested by other larger scale studies.