Multi-institutional Collaboration Research Articles

The Pancreatic Cancer Early Detection (PRECEDE) Study is a Global Effort to Drive Early Detection: Baseline Imaging Findings in High-Risk Individuals.

Pancreatic adenocarcinoma (PC) is a highly lethal malignancy with a survival rate of only 12%. Surveillance is recommended for high-risk individuals (HRIs), but it is not widely adopted. To address this unmet clinical need and drive early diagnosis research, we established the Pancreatic Cancer Early Detection (PRECEDE) Consortium. PRECEDE is a multi-institutional international collaboration that has undertaken an observational prospective cohort study. Individuals (aged 18-90 years) are enrolled into 1 of 7 cohorts based on family history and pathogenic germline variant (PGV) status. From April 1, 2020, to November 21, 2022, a total of 3,402 participants were enrolled in 1 of 7 study cohorts, with 1,759 (51.7%) meeting criteria for the highest-risk cohort (Cohort 1). Cohort 1 HRIs underwent germline testing and pancreas imaging by MRI/MR-cholangiopancreatography or endoscopic ultrasound. A total of 1,400 participants in Cohort 1 (79.6%) had completed baseline imaging and were subclassified into 3 groups based on familial PC (FPC; n=670), a PGV and FPC (PGV+/FPC+; n=115), and a PGV with a pedigree that does not meet FPC criteria (PGV+/FPC-; n=615). One HRI was diagnosed with stage IIB PC on study entry, and 35.1% of HRIs harbored pancreatic cysts. Increasing age (odds ratio, 1.05; P<.001) and FPC group assignment (odds ratio, 1.57; P<.001; relative to PGV+/FPC-) were independent predictors of harboring a pancreatic cyst. PRECEDE provides infrastructure support to increase access to clinical surveillance for HRIs worldwide, while aiming to drive early PC detection advancements through longitudinal standardized clinical data, imaging, and biospecimen captures. Increased cyst prevalence in HRIs with FPC suggests that FPC may infer distinct biological processes. To enable the development of PC surveillance approaches better tailored to risk category, we recommend adoption of subclassification of HRIs into FPC, PGV+/FPC+, and PGV+/FPC- risk groups by surveillance protocols.

A Dutch paediatric palliative care guideline: a systematic review and evidence-based recommendations for symptom treatment

BackgroundChildren with life-threatening and life-limiting conditions can experience high levels of suffering due to multiple distressing symptoms that result in poor quality of life and increase risk of long-term distress in their family members. High quality symptom treatment is needed for all these children and their families, even more so at the end-of-life. In this paper, we provide evidence-based recommendations for symptom treatment in paediatric palliative patients to optimize care.MethodsA multidisciplinary panel of 56 experts in paediatric palliative care and nine (bereaved) parents was established to develop recommendations on symptom treatment in paediatric palliative care including anxiety and depression, delirium, dyspnoea, haematological symptoms, coughing, skin complaints, nausea and vomiting, neurological symptoms, pain, death rattle, fatigue, paediatric palliative sedation and forgoing hydration and nutrition. Recommendations were based on evidence from a systematic literature search, additional literature sources (such as guidelines), clinical expertise, and patient and family values. We used the GRADE methodology for appraisal of evidence. Parents were included in the guideline panel to ensure the representation of patient and family values.ResultsWe included a total of 18 studies that reported on the effects of specific (non) pharmacological interventions to treat symptoms in paediatric palliative care. A few of these interventions showed significant improvement in symptom relief. This evidence could only (partly) answer eight out of 27 clinical questions. We included 29 guidelines and two textbooks as additional literature to deal with lack of evidence. In total, we formulated 221 recommendations on symptom treatment in paediatric palliative care based on evidence, additional literature, clinical expertise, and patient and family values.ConclusionEven though available evidence on symptom-related paediatric palliative care interventions has increased, there still is a paucity of evidence in paediatric palliative care. We urge for international multidisciplinary multi-institutional collaboration to perform high-quality research and contribute to the optimization of symptom relief in palliative care for all children worldwide.

Unconventional data, unprecedented insights: leveraging non-traditional data during a pandemic.

The COVID-19 pandemic prompted new interest in non-traditional data sources to inform response efforts and mitigate knowledge gaps. While non-traditional data offers some advantages over traditional data, it also raises concerns related to biases, representativity, informed consent and security vulnerabilities. This study focuses on three specific types of non-traditional data: mobility, social media, and participatory surveillance platform data. Qualitative results are presented on the successes, challenges, and recommendations of key informants who used these non-traditional data sources during the COVID-19 pandemic in Spain and Italy. A qualitative semi-structured methodology was conducted through interviews with experts in artificial intelligence, data science, epidemiology, and/or policy making who utilized non-traditional data in Spain or Italy during the pandemic. Questions focused on barriers and facilitators to data use, as well as opportunities for improving utility and uptake within public health. Interviews were transcribed, coded, and analyzed using the framework analysis method. Non-traditional data proved valuable in providing rapid results and filling data gaps, especially when traditional data faced delays. Increased data access and innovative collaborative efforts across sectors facilitated its use. Challenges included unreliable access and data quality concerns, particularly the lack of comprehensive demographic and geographic information. To further leverage non-traditional data, participants recommended prioritizing data governance, establishing data brokers, and sustaining multi-institutional collaborations. The value of non-traditional data was perceived as underutilized in public health surveillance, program evaluation and policymaking. Participants saw opportunities to integrate them into public health systems with the necessary investments in data pipelines, infrastructure, and technical capacity. While the utility of non-traditional data was demonstrated during the pandemic, opportunities exist to enhance its impact. Challenges reveal a need for data governance frameworks to guide practices and policies of use. Despite the perceived benefit of collaborations and improved data infrastructure, efforts are needed to strengthen and sustain them beyond the pandemic. Lessons from these findings can guide research institutions, multilateral organizations, governments, and public health authorities in optimizing the use of non-traditional data.

Making head and neck cancer clinical data Findable-Accessible-Interoperable-Reusable to support multi-institutional collaboration and federated learning

Abstract Objectives Federated learning (FL) is a group of methodologies where statistical modelling can be performed without exchanging identifiable patient data between cooperating institutions. To realize its potential for AI development on clinical data, a number of bottlenecks need to be addressed. One of these is making data Findable-Accessible-Interoperable-Reusable (FAIR). The primary aim of this work is to show that tools making data FAIR allow consortia to collaborate on privacy-aware data exploration, data visualization, and training of models on each other’s original data. Methods We propose a “Schema-on-Read” FAIR-ification method that adapts for different (re)analyses without needing to change the underlying original data. The procedure involves (1) decoupling the contents of the data from its schema and database structure, (2) annotation with semantic ontologies as a metadata layer, and (3) readout using semantic queries. Open-source tools are given as Docker containers to help local investigators prepare their data on-premises. Results We created a federated privacy-preserving visualization dashboard for case mix exploration of 5 distributed datasets with no common schema at the point of origin. We demonstrated robust and flexible prognostication model development and validation, linking together different data sources—clinical risk factors and radiomics. Conclusions Our procedure leads to successful (re)use of data in FL-based consortia without the need to impose a common schema at every point of origin of data. Advances in knowledge This work supports the adoption of FL within the healthcare AI community by sharing means to make data more FAIR.

One model to unite them all: Personalized federated learning of multi-contrast MRI synthesis

Curation of large, diverse MRI datasets via multi-institutional collaborations can help improve learning of generalizable synthesis models that reliably translate source- onto target-contrast images. To facilitate collaborations, federated learning (FL) adopts decentralized model training while mitigating privacy concerns by avoiding sharing of imaging data. However, conventional FL methods can be impaired by the inherent heterogeneity in the data distribution, with domain shifts evident within and across imaging sites. Here we introduce the first personalized FL method for MRI Synthesis (pFLSynth) that improves reliability against data heterogeneity via model specialization to individual sites and synthesis tasks (i.e., source-target contrasts). To do this, pFLSynth leverages an adversarial model equipped with novel personalization blocks that control the statistics of generated feature maps across the spatial/channel dimensions, given latent variables specific to sites and tasks. To further promote communication efficiency and site specialization, partial network aggregation is employed over later generator stages while earlier generator stages and the discriminator are trained locally. As such, pFLSynth enables multi-task training of multi-site synthesis models with high generalization performance across sites and tasks. Comprehensive experiments demonstrate the superior performance and reliability of pFLSynth in MRI synthesis against prior federated methods.

Clinical implications of AR alterations in advanced prostate cancer: a multi-institutional collaboration.

AR gene alterations can develop in response to pressure of testosterone suppression and androgen receptor targeting agents (ARTA). Despite this, the relevance of these gene alterations in the context of ARTA treatment and clinical outcomes remains unclear. Patients with castration-resistant prostate cancer (CRPC) who had undergone genomic testing and received ARTA treatment were identified in the Prostate Cancer Precision Medicine Multi-Institutional Collaborative Effort (PROMISE) database. Patients were stratified according to the timing of genomic testing relative to the first ARTA treatment (pre-/post-ARTA). Clinical outcomes such as time to progression, PSA response, and overall survival were compared based on alteration types. In total, 540 CRPC patients who received ARTA and had tissue-based (n = 321) and/or blood-based (n = 244) genomic sequencing were identified. Median age was 62 years (range 39-90) at the time of the diagnosis. Majority were White (72.2%) and had metastatic disease (92.6%) at the time of the first ARTA treatment. Pre-ARTA genomic testing was available in 24.8% of the patients, and AR mutations and amplifications were observed in 8.2% and 13.1% of the patients, respectively. Further, time to progression was longer in patients with AR amplifications (25.7 months) compared to those without an AR alteration (9.6 months; p = 0.03). In the post-ARTA group (n = 406), AR mutations and AR amplifications were observed in 18.5% and 35.7% of the patients, respectively. The most common mutation in post-ARTA group was L702H (9.9%). In this real-world clinicogenomics database-driven study we explored the development of AR alterations and their association with ARTA treatment outcomes. Our study showed that AR amplifications are associated with longer time to progression on first ARTA treatment. Further prospective studies are needed to optimize therapeutic strategies for patients with AR alterations.

Pancreatic Adenocarcinoma: Imaging Modalities and the Role of Artificial Intelligence in Analyzing CT and MRI Images.

Pancreatic ductal adenocarcinoma (PDAC) stands out as the predominant malignant neoplasm affecting the pancreas, characterized by a poor prognosis, in most cases patients being diagnosed in a nonresectable stage. Image-based artificial intelligence (AI) models implemented in tumor detection, segmentation, and classification could improve diagnosis with better treatment options and increased survival. This review included papers published in the last five years and describes the current trends in AI algorithms used in PDAC. We analyzed the applications of AI in the detection of PDAC, segmentation of the lesion, and classification algorithms used in differential diagnosis, prognosis, and histopathological and genomic prediction. The results show a lack of multi-institutional collaboration and stresses the need for bigger datasets in order for AI models to be implemented in a clinically relevant manner.

SMERT: Fostering multi-institutional collaboration in medical education research.

SMERT: Fostering multi-institutional collaboration in medical education research.

(233) Perceptions and Use of Penile Regenerative and Aesthetic Therapy Among SMSNA Members

Abstract Introduction Wave therapy (WT) and platelet rich plasma (PRP) have been evaluated in multiple medical contexts, but there is paucity of long-term data to support their applications in erectile dysfunction (ED) and Peyronie’s disease (PD). Despite the American Urological Association and Sexual Medicine Society of North America (SMSNA) recommending against the use of these therapies for ED and PD outside of a clinical trial, many practices offer WT and PRP as penile regenerative therapies. Objective We aim to understand current perceptions and practice patterns of SMSNA members in offering penile regenerative and aesthetic therapies. Methods An anonymous online survey was deemed IRB exempt and administered to current members of SMSNA electronically from 4/2023 to 6/2023 asking practitioner’s demographics, practice information, their familiarity and offering of various types of penile regenerative therapy (focused shockwave therapy [fSWT], radial wave therapy [RWT], PRP, stem cell therapy [SCT], penile botulinum toxin [Botox] injection) and penile aesthetic procedures including girth and length-enhancement. We included current SMSNA members who are physicians in practice or Advance Practice Providers (APPs) that practice in the US. We excluded those who are trainees and practice outside the US. We conducted descriptive statistics using RedCap. Results Of the 500 active SMSNA members, 46 completed the survey (response rate 9%). Participants were predominantly male (N=42, 91%), physician (N=43, 93%), fellowship-trained (N=39, 85%), and in practice for a median of 5 years. Participants mostly practiced in academic settings (N=33, 72%), and saw 10 or more patients with ED weekly (N=35, 76%). Most respondents reported being comfortable describing the differences between types of wave therapy (N=28, 61%). A minority of respondents offered RWT (N=3, 7%) and most indicated that there was no to low evidence to support its use (N=31, 67%). Ten respondents offered fSWT (N=10, 22%) and only a minority reported no to low evidence to support the use of fSWT (N=18, 39%). Five respondents (11%) offered PRP and most reported that there was no or low evidence to support use of PRP (N=31, 67%). None of the respondents offered SCT and most reported that there was no to low evidence to support the use of SCT (N=26, 57%). One respondent (2%) reported offering penile botox treatment while 19 (41%) reported that there was no to low evidence to support its use. A minority of survey respondents offered girth-enhancement procedures with three respondents (7%) offering hyaluronic acid. For length-enhancing procedures, eight respondents (17%) offered cosmetic scrotoplasty and three (7%) offered suprapubic lipectomy. Conclusions Penile regenerative and aesthetic therapies are not common practice among SMSNA members. With the notable exception of fSWT, majority of survey respondents felt that there was little to no evidence supporting penile regenerative and aesthetic therapies. Further understanding the practice patterns of SMSNA members will help identify future opportunities for multi-institutional collaborations to further evaluate the efficacy of these experimental therapies. Disclosure No.

Adherence to American Society of Clinical Oncology (ASCO) language of respect (LoR) guidelines in ASCO Annual Meeting prostate cancer (PCa) abstracts.

94 Background: The ASCO LoR guidelines were adopted by ASCO in advance of the 2020 Annual Meeting to promote use of patient-respectful language in Annual Meeting presentations. The guidelines call on the oncology community to avoid language that dehumanizes people living with cancer or casts blame. We sought to evaluate adherence to these guidelines in PCa abstracts accepted to the 2023 ASCO Annual Meeting. Methods: Six reviewers screened all PCa abstracts presented at the 2023 ASCO Annual Meeting and tabulated all statements that referred to patients related to diagnosis, treatment, or clinical outcome. Sentences were classified according to their compliance with the 3 principal LoR directives: (1) “Do not blame patients,” (2) “Respect the role of the patient,” and (3) “Do not dehumanize patients.” All abstracts were evaluated by two independent reviewers. Each abstract was given a conformity score based on the extent to which the overall abstract adhered to the LoR guidelines. Descriptive statistics were used to characterize compliance across abstracts. Univariate and multivariate analyses were used to identify factors associated with non-compliance with guidelines. Results: We reviewed 195 PCa abstracts. Most abstracts were accepted as poster presentation (52%) followed by publication only (45%) and oral abstract (3%). The majority were clinical (81%) or translational (17%) research. 85% of the abstracts had a first author affiliated with a native-English speaking institution. Most abstracts came from multi-institutional collaborations (84%), and from a single country (67%). In total, 119 (61%) of abstracts contained at least one non-compliant statement. Among the directives not followed, “Do not dehumanize patients” had the lowest compliance score in 49% of statements, followed by “Do not blame the patient” in 17%, and “Respect the role of the patient” in 1%. We explored potential associations between primary author’s institution, country and number of collaborating institutions. Univariate analysis demonstrated greater odds of non-adherence to LoR guidelines in abstracts whose first author was affiliated with an institution in a non-English speaking country (OR 2.80 [95% CI 1.08-7.23, p=.034]. Multivariate analysis was not significant. Conclusions: Despite formal guidelines having been adopted by ASCO in 2020, the majority of PCa abstracts selected for the 2023 ASCO Annual Meeting contained at least one statement that did not adhere to the LoR guidelines. The only factor that identified an increased OR of non-adherent language was submissions from a non-English speaking institution. Translation of the LoR Guidelines into other languages, international educational outreach, and increased attention to language in the abstract review process are recommended.

Male epispadias repair: Outcomes at three sites prior to the establishment of a multi-institutional collaboration

Epispadias, which occurs on the more mild end of the Bladder Exstrophy Epispadias Complex (BEEC) spectrum, presents still with a wide range of severity in boys, from mild glanular epispadias to penopubic epispadias with severe urethral and bladder neck defects. Surgical management ranges from isolated epispadias repair to epispadias repair with bladder neck reconstruction (BNR) with or without pelvic osteotomies. We aimed to evaluate outcomes in epispadias treated at three institutions prior to formation of a formal collaboration. In addition, we sought to delineate outcomes based on anatomic severity at time of diagnosis, and initial procedure performed in cases of penopubic epispadias. IRB approved databases were retrospectively queried at three institutions for patients who underwent repair of epispadias between 1/1993 and 1/2013. Degree of epispadias, age and technique at initial repair, and self-reported continence status at last follow-up were recorded. Continence was categorized as: wet, intermediate (dry 2-3h), or dry, while also distinguishing those who void and those who require clean intermittent catheterization (CIC). Those not seen since 1/1/2015, younger than 10 years at last follow up, or in whom continence data were not recorded were excluded. A total of 48 boys were identified; 36 met inclusion criteria. The epispadias cohort consisted of 8 glanular epispadias (GE) (22%); 8 penile epispadias (PE) (22%), and 20 penopubic epispadias (PPE) (56%) with a median follow-up of 11.3 years (3.2-26.2 years). Overall, 33 of 36 (92%) boys void per urethra. Within the group that voids, 19/33 (58%) are completely dry, while 6/33 (18%) are wet. Among patients who underwent initial epispadias repair without concurrent or subsequent bladder neck reconstruction, continence rates were: GE 63% (5/8); PE 75% (6/8); PPE 71% (5/7). Among the 9 boys with PPE who underwent initial epispadias repair with concurrent BNR, 22% (2/9) were dry with no further surgeries. Overall, 8/20 (40%) of boys with PPE void with complete dryness. This multi-center retrospective review of continence in epispadias demonstrates that even some boys with glanular and penile epispadias can have challenges with continence, and boys with penopubic epispadias may remain wet despite careful preoperative assessment of bladder neck functionality and concurrent BNR. Continence outcomes in boys with all degrees of epispadias can be variable. Even boys with more distal defects may have significant bladder neck deficiency. And those with the most severe form of epispadias may require bladder neck reconstruction to achieve continence.

Finding the right power balance: Better study design and collaboration can reduce dependence on statistical power.

Power analysis currently dominates sample size determination for experiments, particularly in grant and ethics applications. Yet, this focus could paradoxically result in suboptimal study design because publication biases towards studies with the largest effects can lead to the overestimation of effect sizes. In this Essay, we propose a paradigm shift towards better study designs that focus less on statistical power. We also advocate for (pre)registration and obligatory reporting of all results (regardless of statistical significance), better facilitation of team science and multi-institutional collaboration that incorporates heterogenization, and the use of prospective and living meta-analyses to generate generalizable results. Such changes could make science more effective and, potentially, more equitable, helping to cultivate better collaborations.

The Management of Children with Pre-School Medulloblastoma – A Review of Four Decades of Multi-Disciplinary and Multi-Institutional Collaboration.

Background: The management and consequent survival and quality of survival for young children with medulloblastoma have undergone substantial improvement over the last four decades. While many of these changes reflect improvements in pediatric neurosurgical, neuro- imaging and radiation oncologic technology and training, as well as in supportive care experience and expertise, this review will focus particularly upon improvements in chemotherapeutic approaches. Methods: This review focuses only upon prospective clinical trials conducted in young children with newly-diagnosed medulloblastoma since the 1980s. The upper age limits for these trials varied from under three to up to six years of age at diagnosis. Results: Certain but not all trials endeavoring to improve outcomes for young children with now- recognized pathological and molecular low-risk characteristics, specifically the Sonic Hedgehog (SHH) sub-type, representing some 50-60% of young children with medulloblastoma, have reaped substantial gains in event-free and overall survival, irradiation-free survival as well as neuropsychological outcomes. Those successful trials utilized either induction including intravenous high-dose methotrexate and intraventricular (intra-Ommaya) methotrexate without consolidation by marrow-ablative chemotherapy with autologous hematopoietic progenitor cell rescue (AuHPCR), or induction with or without intravenous high-dose methotrexate (but not intra-ventricular methotrexate) followed by consolidation with marrow-ablative chemotherapy with AuHPCR. These two approaches have consistently produced superior outcomes compared with other trials. For children with molecularly-characterized Groups 3 or 4 medulloblastoma, representing those at high-risk of relapse, some modest improvements have been made over the years, but much room for improvement remains, especially for those presenting with the highest- risk molecular characteristics (CMYC-amplified Group 3 medulloblastoma) as well as for children with metastatic disease at initial diagnosis. Conclusions: Substantial gains in improving outcomes for young children with medulloblastoma have been achieved with acceptable short- and long-term morbidities of treatment. However, the inclusion of intra-ventricular therapies (conventional chemotherapeutic, radio-labeled monoclonal antibody or adaptive cellular immunotherapeutic approaches) as well as the identification of targeted systemic therapies (biological and/or immunological) and their incorporation into prospective multi-center clinical trials, must be investigated prospectively if we are to improve outcomes for those children at high-risk for relapse, even with the inclusion of refined irradiation therapeutic approaches.

Heart Sound Abnormality Detection From Multi-Institutional Collaboration: Introducing a Federated Learning Framework.

Early diagnosis of cardiovascular diseases is a crucial task in medical practice. With the application of computer audition in the healthcare field, artificial intelligence (AI) has been applied to clinical non-invasive intelligent auscultation of heart sounds to provide rapid and effective pre-screening. However, AI models generally require large amounts of data which may cause privacy issues. Unfortunately, it is difficult to collect large amounts of healthcare data from a single centre. In this study, we propose federated learning (FL) optimisation strategies for the practical application in multi-centre institutional heart sound databases. The horizontal FL is mainly employed to tackle the privacy problem by aligning the feature spaces of FL participating institutions without information leakage. In addition, techniques based on deep learning have poor interpretability due to their "black-box" property, which limits the feasibility of AI in real medical data. To this end, vertical FL is utilised to address the issues of model interpretability and data scarcity. Experimental results demonstrate that, the proposed FL framework can achieve good performance for heart sound abnormality detection by taking the personal privacy protection into account. Moreover, using the federated feature space is beneficial to balance the interpretability of the vertical FL and the privacy of the data. This work realises the potential of FL from research to clinical practice, and is expected to have extensive application in the federated smart medical system.

A proposed multi-domain, digital model for capturing functional status and health-related quality of life in oncology.

Whereas traditional oncology clinical trial endpoints remain key for assessing novel treatments, capturing patients' functional status is increasingly recognized as an important aspect for supporting clinical decisions and assessing outcomes in clinical trials. Existing functional status assessments suffer from various limitations, some of which may be addressed by adopting digital health technologies (DHTs) as a means of collecting both objective and self-reported outcomes. In this mini-review, we propose a device-agnostic multi-domain model for oncology capturing functional status, which includes physical activity data, vital signs, sleep variables, and measures related to health-related quality of life enabled by connected digital tools. By using DHTs for all aspects of data collection, our proposed model allows for high-resolution measurement of objective data as patients navigate their daily lives outside of the hospital setting. This is complemented by electronic questionnaires administered at intervals appropriate for each instrument. Preliminary testing and practical considerations to address before adoption are also discussed. Finally, we highlight multi-institutional pre-competitive collaborations as a means of successfully transitioning the proposed digitally enabled data collection model from feasibility studies to interventional trials and care management.

Catbirds and crabholes: the 2023 field season at Marco Gonzalez, Belize

After lengthy delays owing to the Covid-19 pandemic, excavations at the Precolumbian Maya site of Marco Gonzalez in Belize resumed in summer 2023. This season represented the in-field commencement of a new multi-institutional collaboration. The implementation of novel approaches and methods included the incorporation of photogrammetry and 3D modelling as a first-line documentation method, a heightened emphasis on the importance of bioarchaeology as a source for constructing narratives about past life at Marco Gonzalez (through the ‘osteobiographical’ approach) and more extensive excavations than had been possible in previous seasons. These approaches and methods proved fruitful, with excavations uncovering seven new burials, as well as a particularly intriguing cache of what resembled grave goods without an associated individual. Moreover, excavations during this field season provided tantalising new evidence as to the scope of the extensive trade and exchange network within which Marco Gonzalez was a vital node, as well as new insights into the mechanics of the industrial-scale salt processing that was both central to life at the site for several centuries during the Late Classic period and seemingly integral to the formation of highly fertile anthropogenic soils (Maya Dark Earths) that are crucially important to a nuanced understanding of the long-term environmental impact of human activity.

Integrative analysis of clinicopathological features defines novel prognostic models for mantle cell lymphoma in the immunochemotherapy era: a report from The North American Mantle Cell Lymphoma Consortium

BackgroundPatients with mantle cell lymphoma (MCL) exhibit a wide variation in clinical presentation and outcome. However, the commonly used prognostic models are outdated and inadequate to address the needs of the current multidisciplinary management of this disease. This study aims to investigate the clinical and pathological features of MCL in the immunochemotherapy era and improve the prognostic models for a more accurate prediction of patient outcomes.MethodsThe North American Mantle Cell Lymphoma Project is a multi-institutional collaboration of 23 institutions across North America to evaluate and refine prognosticators for front-line therapy. A total of 586 MCL cases diagnosed between 2000 and 2012 are included in this study. A comprehensive retrospective analysis was performed on the clinicopathological features, treatment approaches, and outcomes of these cases. The establishment of novel prognostic models was based on in-depth examination of baseline parameters, and subsequent validation in an independent cohort of MCL cases.ResultsIn front-line strategies, the use of hematopoietic stem cell transplantation was the most significant parameter affecting outcomes, for both overall survival (OS, p < 0.0001) and progression-free survival (PFS, p < 0.0001). P53 positive expression was the most significant pathological parameter correlating with inferior outcomes (p < 0.0001 for OS and p = 0.0021 for PFS). Based on the baseline risk factor profile, we developed a set of prognostic models incorporating clinical, laboratory, and pathological parameters that are specifically tailored for various applications. These models, when tested in the validation cohort, exhibited strong predictive power for survival and showed a stratification resembling the training cohort.ConclusionsThe outcome of patients with MCL has markedly improved over the past two decades, and further enhancement is anticipated with the evolution of clinical management. The innovative prognostic models developed in this study would serve as a valuable tool to guide the selection of more suitable treatment strategies for patients with MCL.

State of the art: radiomics and radiomics-related artificial intelligence on the road to clinical translation.

Radiomics and artificial intelligence carry the promise of increased precision in oncologic imaging assessments due to the ability of harnessing thousands of occult digital imaging features embedded in conventional medical imaging data. While powerful, these technologies suffer from a number of sources of variability that currently impede clinical translation. In order to overcome this impediment, there is a need to control for these sources of variability through harmonization of imaging data acquisition across institutions, construction of standardized imaging protocols that maximize the acquisition of these features, harmonization of post-processing techniques, and big data resources to properly power studies for hypothesis testing. For this to be accomplished, it will be critical to have multidisciplinary and multi-institutional collaboration.

Ampullary Adenocarcinoma: A Review of the Mutational Landscape and Implications for Treatment.

Ampullary carcinomas represent less than 1% of all gastrointestinal malignancies with an incidence of approximately 6 cases per 1 million. Histologic examination and immunohistochemistry have been traditionally used to categorize ampullary tumors into intestinal, pancreatobiliary or mixed subtypes. Intestinal-subtype tumors may exhibit improved survival versus the pancreatobiliary subtype, although studies on the prognostic value of immunomorphologic classification have been inconsistent. Genomic classifiers hold the promise of greater reliability, while providing potential targets for precision oncology. Multi-institutional collaboration will be necessary to better understand how molecular classification can guide type and sequencing of multimodality therapy.

Bridging Place-Based Astrobiology Education with Genomics, Including Descriptions of Three Novel Bacterial Species Isolated from Mars Analog Sites of Cultural Relevance.

Democratizing genomic data science, including bioinformatics, can diversify the STEM workforce and may, in turn, bring new perspectives into the space sciences. In this respect, the development of education and research programs that bridge genome science with "place" and world-views specific to a given region are valuable for Indigenous students and educators. Through a multi-institutional collaboration, we developed an ongoing education program and model that includes Illumina and Oxford Nanopore sequencing, free bioinformatic platforms, and teacher training workshops to address our research and education goals through a place-based science education lens. High school students and researchers cultivated, sequenced, assembled, and annotated the genomes of 13 bacteria from Mars analog sites with cultural relevance, 10 of which were novel species. Students, teachers, and community members assisted with the discovery of new, potentially chemolithotrophic bacteria relevant to astrobiology. This joint education-research program also led to the discovery of species from Mars analog sites capable of producing N-acyl homoserine lactones, which are quorum-sensing molecules used in bacterial communication. Whole genome sequencing was completed in high school classrooms, and connected students to funded space research, increased research output, and provided culturally relevant, place-based science education, with participants naming three novel species described here. Students at St. Andrew's School (Honolulu, Hawai'i) proposed the name Bradyrhizobium prioritasuperba for the type strain, BL16AT, of the new species (DSM 112479T = NCTC 14602T). The nonprofit organization Kauluakalana proposed the name Brenneria ulupoensis for the type strain, K61T, of the new species (DSM 116657T = LMG = 33184T), and Hawai'i Baptist Academy students proposed the name Paraflavitalea speifideiaquila for the type strain, BL16ET, of the new species (DSM 112478T = NCTC 14603T).