International Rare Cancers Initiative (IRCI).
Ontology highlight
ABSTRACT:
SUBMITTER: Keat N
PROVIDER: S-EPMC4025507 | biostudies-literature | 2013
REPOSITORIES: biostudies-literature
Publications
International Rare Cancers Initiative (IRCI).
Keat Nicola N Law Kate K McConnell Andrea A Seymour Matthew M Welch Jack J Trimble Ted T Lacombe Denis D Negrouk Anastassia A
Ecancermedicalscience 20130521
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Project description:BackgroundThe past three decades have seen rapid improvements in the diagnosis and treatment of most cancers and the most important contributor has been research. Progress in rare cancers has been slower, not least because of the challenges of undertaking research.SettingsThe International Rare Cancers Initiative (IRCI) is a partnership which aims to stimulate and facilitate the development of international clinical trials for patients with rare cancers. It is focused on interventional--usually randomized--clinical trials with the clear goal of improving outcomes for patients. The key challenges are organisational and methodological. A multi-disciplinary workshop to review the methods used in ICRI portfolio trials was held in Amsterdam in September 2013. Other as-yet unrealised methods were also discussed.ResultsThe IRCI trials are each presented to exemplify possible approaches to designing credible trials in rare cancers. Researchers may consider these for use in future trials and understand the choices made for each design.InterpretationTrials can be designed using a wide array of possibilities. There is no 'one size fits all' solution. In order to make progress in the rare diseases, decisions to change practice will have to be based on less direct evidence from clinical trials than in more common diseases.
| S-EPMC4639696 | biostudies-literature
Project description:PurposeTo compare cisplatin plus fluorouracil (FU) versus carboplatin plus paclitaxel in chemotherapy-naïve advanced anal cancer to establish the optimal regimen.Patients and methodsPatients who had not received systemic therapy for advanced anal cancer were randomly assigned 1:1 to intravenous cisplatin 60 mg/m2 (day 1) plus FU 1,000 mg/m2 (days 1-4) every 21 days or carboplatin (area under the curve, 5; day 1) plus paclitaxel 80 mg/m2 (days 1, 8, and 15) every 28 days for 24 weeks, until disease progression, intolerable toxicity, or withdrawal of consent. Primary end point was objective response rate (ORR). Primary and secondary end points were assessed in a hierarchic model to compare the regimens and pick the winner.ResultsWe conducted an international multicenter randomized phase II study in 60 centers between December 2013 and November 2017. Median follow-up was 28.6 months. A total of 91 patients were randomly assigned: 46 to cisplatin plus FU and 45 to carboplatin plus paclitaxel. ORR was 57% (95% CI, 39.4% to 73.7%) for cisplatin plus FU versus 59% (95% CI, 42.1% to 74.4%) for carboplatin plus paclitaxel. More serious adverse events were noted in the cisplatin plus FU arm (62%) compared with the carboplatin plus paclitaxel arm (36%; P = .016). Median progression-free survival was 5.7 months (95% CI, 3.3 to 9.0 months) for cisplatin plus FU compared with 8.1 months (95% CI, 6.6 to 8.8 months) for carboplatin plus paclitaxel. Median overall survival was 12.3 months for cisplatin plus FU (95% CI, 9.2 to 17.7 months) compared with 20 months (95% CI, 12.7 months to not reached) for carboplatin plus paclitaxel (hazard ratio, 2.00; 95% CI, 1.15 to 3.47; P = .014).ConclusionThis is the first international randomized trial to our knowledge conducted in chemotherapy-naïve advanced anal cancer. Although there was no difference in ORR, the association with clinically relevant reduced toxicity and a trend toward longer survival suggest that carboplatin plus paclitaxel should be considered as a new standard of care.
| S-EPMC7406334 | biostudies-literature
Project description:The 2021 WHO classification of the CNS Tumors identifies as "Peripheral nerve sheath tumors" (PNST) some entities with specific clinical and anatomical characteristics, histological and molecular markers, imaging findings, and aggressiveness. The Task Force has reviewed the evidence of diagnostic and therapeutic interventions, which is particularly low due to the rarity, and drawn recommendations accordingly. Tumor diagnosis is primarily based on hematoxylin and eosin-stained sections and immunohistochemistry. Molecular analysis is not essential to establish the histological nature of these tumors, although genetic analyses on DNA extracted from PNST (neurofibromas/schwannomas) is required to diagnose mosaic forms of NF1 and SPS. MRI is the gold-standard to delineate the extension with respect to adjacent structures. Gross-total resection is the first choice, and can be curative in benign lesions; however, the extent of resection must be balanced with preservation of nerve functioning. Radiotherapy can be omitted in benign tumors after complete resection and in NF-related tumors, due to the theoretic risk of secondary malignancies in a tumor-suppressor syndrome. Systemic therapy should be considered in incomplete resected plexiform neurofibromas/MPNSTs. MEK inhibitor selumetinib can be used in NF1 children ≥2 years with inoperable/symptomatic plexiform neurofibromas, while anthracycline-based treatment is the first choice for unresectable/locally advanced/metastatic MPNST. Clinical trials on other MEK1-2 inhibitors alone or in combination with mTOR inhibitors are under investigation in plexiform neurofibromas and MPNST, respectively.
| S-EPMC10093509 | biostudies-literature
Project description:Cancer remains a leading cause of death worldwide, placing a significant burden on healthcare systems as well as the global economy. Rare cancers comprise a group of about 200 cancers that individually occur at extremely low frequencies. In the United States (US), their frequency is approximately 15 cases per 100,000 people, and it is even lower in Europe with approximately 6 cases per 100,000 people. However, combined their frequency of occurrence is much higher than any singular cancer. Cancer treatment and management has tremendously improved in the last decade, particularly with the administration of immune-based therapies. The four most prevalent immune-based therapies are (1) the use of immune-checkpoint inhibitors, (2) macrophage therapy, (3) Chimeric Antigen Receptor (CAR) T cell therapy, and (4) neoantigen-based therapies. In our review, we discuss these various aproaches and their implementation in the treatment of a variety of rare cancers. Furthermore, we discuss their limitations and potential strategies to overcome them to enhance the therapeutic efficacy of these approaches. Finally, our article presents the future directions and other additional immune therapies that may be incorporated into the treatment of rare cancers.
| S-EPMC9890725 | biostudies-literature
Project description:The issue of sustainability is at the top of the political and societal agenda, being considered of extreme importance and urgency. Human individual action impacts the environment both locally (e.g., local air/water quality, noise disturbance) and globally (e.g., climate change, resource use). Urban environments represent a crucial example, with an increasing realization that the most effective way of producing a change is involving the citizens themselves in monitoring campaigns (a citizen science bottom-up approach). This is possible by developing novel technologies and IT infrastructures enabling large citizen participation. Here, in the wider framework of one of the first such projects, we show results from an international competition where citizens were involved in mobile air pollution monitoring using low cost sensing devices, combined with a web-based game to monitor perceived levels of pollution. Measures of shift in perceptions over the course of the campaign are provided, together with insights into participatory patterns emerging from this study. Interesting effects related to inertia and to direct involvement in measurement activities rather than indirect information exposure are also highlighted, indicating that direct involvement can enhance learning and environmental awareness. In the future, this could result in better adoption of policies towards decreasing pollution.
| S-EPMC4551740 | biostudies-literature
Project description: Not available
| S-EPMC3396326 | biostudies-literature
Project description:DICER1 syndrome is a rare genetic disorder that predisposes individuals to multiple cancer types. Through mutations of the gene encoding the endoribonuclease, Dicer, DICER1 syndrome disrupts the biogenesis and processing of miRNAs with subsequent disruption in control of gene expression. Since the first description of DICER1 syndrome, case reports have documented novel germline mutations of the DICER1 gene in patients with cancers as well as second site mutations that alter the function of the Dicer protein expressed. Here, we present a review of mutations in the DICER1 gene, the respective protein sequence changes, and clinical manifestations of DICER1 syndrome. Directions for future research are discussed.
| S-EPMC5977116 | biostudies-literature
Project description:Rare diseases affect millions of people worldwide, and most have a genetic etiology. The incorporation of next-generation sequencing into clinical settings, particularly exome and genome sequencing, has resulted in an unprecedented improvement in diagnosis and discovery in the past decade. Nevertheless, these tools are unavailable in many countries, increasing health care gaps between high- and low-and-middle-income countries and prolonging the "diagnostic odyssey" for patients. To advance genomic diagnoses in a setting of limited genomic resources, we developed DECIPHERD, an undiagnosed diseases program in Chile. DECIPHERD was implemented in two phases: training and local development. The training phase relied on international collaboration with Baylor College of Medicine, and the local development was structured as a hybrid model, where clinical and bioinformatics analysis were performed in-house and sequencing outsourced abroad, due to lack of high-throughput equipment in Chile. We describe the implementation process and findings of the first 103 patients. They had heterogeneous phenotypes, including congenital anomalies, intellectual disabilities and/or immune system dysfunction. Patients underwent clinical exome or research exome sequencing, as solo cases or with parents using a trio design. We identified pathogenic, likely pathogenic or variants of unknown significance in genes related to the patients´ phenotypes in 47 (45.6%) of them. Half were de novo informative variants, and half of the identified variants have not been previously reported in public databases. DECIPHERD ended the diagnostic odyssey for many participants. This hybrid strategy may be useful for settings of similarly limited genomic resources and lead to discoveries in understudied populations.
| S-EPMC11499817 | biostudies-literature
Project description:IntroductionExercise is vital to health and well-being after a cancer diagnosis yet is poorly integrated in cancer care. Knowledge mobilization (KM) is essential to enhance exercise opportunities. We aimed to (1) develop and refine a list of highly important exercise oncology research and KM themes and (2) establish the relative importance of the themes for supporting the implementation of exercise as a standard of care for people living with and beyond cancer.MethodsInformed by the Co-Produced Pathway to Impact KM framework, a modified Delphi study approach was used to develop, rate, and rank exercise oncology research and KM themes through an international stakeholder workshop and a three-round iterative online survey. Open-ended stakeholder feedback from cancer survivors, healthcare practitioners (HCPs), qualified exercise professionals (QEPs), policy makers, and researchers was used to update themes between survey rounds. Themes were ranked from highest to lowest importance and agreement was examined across all stakeholders and within stakeholder groups.ResultsA total of 269 exercise oncology stakeholders from 13 countries participated in the study. Twelve final exercise oncology research and KM themes were produced. The final top ranked research themes were related to: (1) QEP integration into primary cancer care teams, (2) Exercise oncology education for HCPs, and (3) Accessibility of cancer exercise programs & support services. There was statistically significant agreement between stakeholders (p<0.001) and within stakeholder groups (p's≤0.02) on the general rankings of themes (i.e., some themes generally ranked higher and lower compared to others). Low Kendall's W statistics indicated variability related to the specific ranked order of the themes between stakeholders and within stakeholder groups. Moreover, there were key differences in the rankings for specific themes between policy makers and other stakeholder groups that highlight potentially important discordance in the research and KM priorities for policy makers that warrants further study.ConclusionThese findings can be used to guide initiatives and align stakeholders on priorities to support exercise implementation as a standard of cancer care. Additional research is needed to better understand the differences in the proposed research and KM priorities across stakeholders.
| S-EPMC8327176 | biostudies-literature
Project description:Background & aimsPatients with early-onset colorectal cancer (eoCRC) are managed according to guidelines that are not age-specific. A multidisciplinary international group (DIRECt), composed of 69 experts, was convened to develop the first evidence-based consensus recommendations for eoCRC.MethodsAfter reviewing the published literature, a Delphi methodology was used to draft and respond to clinically relevant questions. Each statement underwent 3 rounds of voting and reached a consensus level of agreement of ≥80%.ResultsThe DIRECt group produced 31 statements in 7 areas of interest: diagnosis, risk factors, genetics, pathology-oncology, endoscopy, therapy, and supportive care. There was strong consensus that all individuals younger than 50 should undergo CRC risk stratification and prompt symptom assessment. All newly diagnosed eoCRC patients should receive germline genetic testing, ideally before surgery. On the basis of current evidence, endoscopic, surgical, and oncologic treatment of eoCRC should not differ from later-onset CRC, except for individuals with pathogenic or likely pathogenic germline variants. The evidence on chemotherapy is not sufficient to recommend changes to established therapeutic protocols. Fertility preservation and sexual health are important to address in eoCRC survivors. The DIRECt group highlighted areas with knowledge gaps that should be prioritized in future research efforts, including age at first screening for the general population, use of fecal immunochemical tests, chemotherapy, endoscopic therapy, and post-treatment surveillance for eoCRC patients.ConclusionsThe DIRECt group produced the first consensus recommendations on eoCRC. All statements should be considered together with the accompanying comments and literature reviews. We highlighted areas where research should be prioritized. These guidelines represent a useful tool for clinicians caring for patients with eoCRC.
| S-EPMC11207185 | biostudies-literature