Project description:Background and objectiveSurveillance is the preferred management strategy for most men with clinical stage I testicular cancer after orchiectomy. However, frequent office visits, imaging tests, and laboratory studies place a significant burden on patients, which may contribute to poor compliance with guideline-recommended surveillance regimens. Identifying strategies to overcome these barriers may help improve quality of life, reduce costs, and improve adherence for patients. We reviewed evidence for three strategies that may help with surveillance redesign: telemedicine, implementing microRNA (miRNA) as a biomarker, and novel imaging protocols.MethodsA web-based literature search for novel imaging strategies, diagnostic utility of miRNA, and telehealth as they relate to early-stage testicular germ cell cancer was completed during the month of August 2022. We focused our search on contemporary PubMed-indexed and Google Scholar-registered manuscripts written in English. Supportive data sourced from current guideline statements were also included. Evidence was compiled for narrative review.Key content and findingsTelemedicine is a safe and acceptable platform for urologic cancer follow-up care, but it requires further study specifically among men with testicular cancer. Access to care may either be improved or reduced depending on system- and patient-level characteristics and should be implemented with this in mind. miRNA may potentially be a helpful biomarker for men with localized disease, but further research on diagnostic accuracy and marker kinetics are needed before implementing it into routine surveillance strategies or using it to deviate from long-standing surveillance regiments. Novel imaging strategies with less frequent imaging and the use of magnetic resonance imaging (MRI) instead of computed tomography (CT) appear to be non-inferior in clinical trials. However, use of MRI requires expert radiologist availability and may be more costly with a lower ability to detect small, early recurrences when used in routine practice.ConclusionsUsing telemedicine, integrating miRNA as a tumor marker, and adopting less intensive imaging strategies may improve guideline-concordant surveillance for men with localized testicular cancer. Future studies are needed to assess the risks and benefits of using these novel approaches separately or together.
Project description:Testicular cancer represents the most curable solid tumor, with a 10-year survival rate of more than 95%. Given the young average age at diagnosis, it is estimated that effective treatment approaches, in particular, platinum-based chemotherapy, have resulted in an average gain of several decades of life. This success, however, is offset by the emergence of considerable long-term morbidity, including second malignant neoplasms, cardiovascular disease, neurotoxicity, nephrotoxicity, pulmonary toxicity, hypogonadism, decreased fertility, and psychosocial problems. Data on underlying genetic or molecular factors that might identify those patients at highest risk for late sequelae are sparse. Genome-wide association studies and other translational molecular approaches now provide opportunities to identify testicular cancer survivors at greatest risk for therapy-related complications to develop evidence-based long-term follow-up guidelines and interventional strategies. We review research priorities identified during an international workshop devoted to testicular cancer survivors. Recommendations include 1) institution of lifelong follow-up of testicular cancer survivors within a large cohort setting to ascertain risks of emerging toxicities and the evolution of known late sequelae, 2) development of comprehensive risk prediction models that include treatment factors and genetic modifiers of late sequelae, 3) elucidation of the effect(s) of decades-long exposure to low serum levels of platinum, 4) assessment of the overall burden of medical and psychosocial morbidity, and 5) the eventual formulation of evidence-based long-term follow-up guidelines and interventions. Just as testicular cancer once served as the paradigm of a curable malignancy, comprehensive follow-up studies of testicular cancer survivors can pioneer new methodologies in survivorship research for all adult-onset cancer.
Project description:BackgroundNumerous transitional care innovations (TCIs) are being developed and implemented to optimize care continuity for older persons when transferring between multiple care settings, help meet their care needs, and ultimately improve their quality of life. Although the implementation of TCIs is influenced by contextual factors, the use of effective implementation strategies is largely lacking. Thus, to improve the implementation of TCIs targeting older persons receiving long-term care services, we systematically developed a set of viable strategies selected to address the influencing factors.MethodsAs part of the TRANS-SENIOR research network, a stepwise approach following Implementation Mapping (steps 1 to 3) was applied to select implementation strategies. Building on the findings of previous studies, existing TCIs and factors influencing their implementation were identified. A combination of four taxonomies and overviews of change methods as well as relevant evidence on their effectiveness were used to select the implementation strategies targeting each of the relevant factors. Subsequently, individual consultations with scientific experts were performed for further validation of the process of mapping strategies to implementation factors and for capturing alternative ideas on relevant implementation strategies.ResultsTwenty TCIs were identified and 12 influencing factors (mapped to the Consolidated Framework for Implementation Research) were designated as priority factors to be addressed with implementation strategies. A total of 40 strategies were selected. The majority of these target factors at the organizational level, e.g., by using structural redesign, public commitment, changing staffing models, conducting local consensus discussions, and organizational diagnosis and feedback. Strategies at the level of individuals included active learning, belief selection, and guided practice. Each strategy was operationalized into practical applications.ConclusionsThis project developed a set of theory and evidence-based implementation strategies to address the influencing factors, along further tailoring for each context, and enhance the implementation of TCIs in daily practice settings. Such work is critical to advance the use of implementation science methods to implement innovations in long-term care successfully.
Project description:Gastric cancer, which has a high incidence and poor prognosis, remains a therapeutic challenge. Recently, neoadjuvant therapy has attracted increasing attention due to high recurrence rate and low survival rate after resection in most patients with advanced stage. Clinical trials show that neoadjuvant approaches confer a significant survival advantage for resectable locally advanced gastric cancer. The specific advantages of chemoradiotherapy compared with chemotherapy have not been clarified; optimal regimens and cycles, particularly in the preoperative setting, should be studied further; and trials aimed at determining the role of targeted and immunological therapies should be conducted.
Project description:RASopathies are a set of clinical syndromes that have molecular and clinical overlap. Genetically, these syndromes are defined by germline pathogenic variants in RAS/MAPK pathway genes resulting in activation of this pathway. Clinically, their common molecular signature leads to comparable phenotypes, including cardiac anomalies, neurologic disorders and notably, elevated cancer risk. Cancer risk in individuals with RASopathies has been estimated from retrospective reviews and cohort studies. For example, in Costello syndrome, cancer incidence is significantly elevated over the general population, largely due to solid tumors. In some forms of Noonan syndrome, cancer risk is also elevated over the general population and is enriched for hematologic malignancies. Thus, cancer surveillance guidelines have been developed to monitor for the occurrence of such cancers in individuals with some RASopathies. These include abdominal ultrasound and urinalyses for individuals with Costello syndrome, while complete blood counts and splenic examination are recommended in Noonan syndrome. Improved cancer risk estimates and refinement of surveillance recommendations will improve the care of individuals with RASopathies.
Project description:BackgroundThe increasing incidence of testicular germ cell tumour (TGCT) combined with its strong heritable basis suggests that stratified screening for the early detection of TGCT may be clinically useful. We modelled the efficiency of such a personalised screening approach, based on genetic risk profiling in combination with other diagnostic tools.MethodsWe compared the number of cases potentially detectable in the population under a number of screening models. The polygenic risk scoring (PRS) model was assumed to have a log-normal relative risk distribution across the 19 currently known TGCT susceptibility variants. The diagnostic performance of testicular biopsy and non-invasive semen analysis was also assessed, within a simulated combined screening programme.ResultsThe area under the curve for the TGCT PRS model was 0.72 with individuals in the top 1% of the PRS having a nine-fold increased TGCT risk compared with the population median. Results from population-screening simulations only achieved a maximal positive predictive value (PPV) of 60%, highlighting broader clinical factors that challenge such strategies, not least the rare nature of TGCT. In terms of future improvements, heritability estimates suggest that a significant number of additional genetic risk factors for TGCT remain to be discovered, identification of which would potentially yield improvement of the PPV to 80-90%.ConclusionsWhile personalised screening models may offer enhanced TGCT risk discrimination, presently the case for population-level testing is not compelling. However, future advances, such as more routine generation of whole genome data is likely to alter the landscape. More targeted screening programs may plausibly then offer clinical benefit, particularly given the significant survivorship issues associated with the successful treatment of TGCT.
Project description:ObjectivesMoving innovations into healthcare organisations to increase positive health outcomes remains a significant challenge. Even when knowledge and tools are adopted, they often fail to become integrated into the long-term routines of organisations. The objective of this study was to identify factors and processes influencing the sustainability of innovations in cancer survivorship care.DesignQualitative study using semistructured, in-depth interviews, informed by grounded theory. Data were collected and analysed concurrently using constant comparative analysis.Setting25 cancer survivorship innovations based in six Canadian provinces.ParticipantsTwenty-seven implementation leaders and relevant staff from across Canada involved in the implementation of innovations in cancer survivorship.ResultsThe findings were categorised according to determinants, processes and implementation outcomes, and whether a factor was necessary to sustainability, or important but not necessary. Seven determinants, six processes and three implementation outcomes were perceived to influence sustainability. The necessary determinants were (1) management support; (2) organisational and system-level priorities; and (3) key people and expertise. Necessary processes were (4) innovation adaptation; (5) stakeholder engagement; and (6) ongoing education and training. The only necessary implementation outcome was (7) widespread staff and organisational buy-in for the innovation.ConclusionsFactors influencing the sustainability of cancer survivorship innovations exist across multiple levels of the health system and are often interdependent. Study findings may be used by implementation teams to plan for sustainability from the beginning of innovation adoption initiatives.
Project description:Incidental detection of urogenital tumors has increased in recent decades owing to the greater use of ultrasonography and cross-sectional imaging. For patients with low-risk prostate cancer or small renal masses, active surveillance represents a valid treatment option. Similarly, for men with small testicular masses <10 mm, active surveillance has been discussed as an alternative to surgery, although little is known regarding the behavior of small testicular germ cell tumors (GCTs). In the Swiss Austrian German Testicular Cancer Cohort Study we identified 849 patients (546 seminoma, 303 nonseminoma) treated with radical inguinal orchiectomy for GCT with a median tumor diameter of 35 mm. A tumor diameter <10 mm was observed in 25 patients (13 seminoma, 12 nonseminoma). Of these, five patients (20%) presented with primary metastatic disease, all of whom had elevated tumor markers and nonseminomatous GCTs. Two patients (8%) with initially localized disease (1 seminoma, 1 nonseminoma) and without elevated tumor markers experienced relapse at 4 mo (nonseminoma) and 14 mo (seminoma) after orchiectomy, despite the fact that the latter had received adjuvant chemotherapy. These findings highlight the metastatic potential of small testicular GCTs and raise the question of whether active surveillance for small testicular masses is safe.Patient summaryThis study on testicular cancer assesses the metastatic potential of small testicular germ cell tumors. Men with small testicular masses should be counseled about the malignant potential of small testicular germ cell tumors.
Project description:Stage-I testicular germ-cell tumor (TGCT) has excellent cure rates. Surveillance is fully included in patient's management, particularly during the first years of follow-up. Surveillance guidelines differ between the academic societies, mainly concerning imaging frequency and long-term follow-up. We evaluated surveillance practice and schedules followed by French specialists and set up a DELPHI method to obtain a consensual surveillance program with an optimal schedule for patients with localized TGCT. First, an online survey on surveillance practice of stage-I TGCT based on clinical-cases was conducted among urologists, radiation-oncologists and medical-oncologists. These results were compared to ESMO/EAU and AFU guidelines. Then a panel of experts assessed surveillance proposals following a Delphi-CM. Statements were drafted after analysis of the previous survey and systematic literature review, with 2 successive rounds to reach a consensus. The study was conducted between July 2018 and May 2019. Concerning the first step: 61 participated to the survey (69% medical-oncologists, 15% urologists, 16% radiation-oncologists). About 65% of practitioners followed clinico-biological guidelines concerning 1 to 5 years of follow-up, but only 25% stopped surveillance after the 5th-year. No physician followed the EAU/ESMO guidelines of de-escalation chest imaging. Concerning the second step: 32 experts (78% medical-oncologists, 16% urologists, 6% radiation-oncologists) participated to the Delphi-CM. Thanks to Delphi-CM, a consensus was reached for 26 of the 38 statements. Experts agreed on clinico-biological surveillance modalities and end of surveillance after the 5th-year of follow-up. For seminoma, abdominal ultrasound was proposed as an option to the abdominopelvic (AP) scan for the 4th-year of follow-up. No consensus was reached regarding de-escalation of chest imaging. To conclude, the survey proved that French TGCT-specialists do not follow current guidelines. With Delphi-CM, a consensus was obtained for frequency of clinico-biological surveillance, discontinuation of surveillance after the 5th-year, stop of AP scan on the 4th-year of follow-up for seminoma. Questions remains concerning type and frequency of chest imaging.
Project description:Although standard therapy for AML has been relatively constant over the past 2 decades, this may be changing with enhanced technologies allowing for the classification of acute myeloid leukemia (AML) into molecularly distinct subsets. Some specific subsets of AML have an excellent prognosis in response to standard therapy, whereas the poor prognosis of AML associated with specific sets of mutations or chromosomal anomalies requires the development of new therapies. Elucidation of the molecular pathogenesis of AML has led to the development of therapies that affect signaling, apoptosis, protein and intermediate metabolism, the surface of the leukemia cell, leukemia cell/stromal interaction, and epigenetic regulation of gene expression.