Concepts In Oncology Research Articles

Current status and perspectives in environmental oncology.

Cancer stands as a leading global cause of death, with its etiology characterized by complexity and multifaceted factors. Growing research indicates a strong correlation between environmental factors and cancer incidence, underscoring the critical importance of intervening in environmental risk factors to mitigate cancer occurrence. Despite this, specialized research institutions focusing on the intersection of environment and cancer remain scarce, with global investment in cancer prevention significantly trailing behind efforts in diagnosis and treatment. Against the backdrop of rapid global climate change, industrialization, urbanization, aging populations, and the globalization of lifestyles, we proposed the concept of Environmental Oncology (EO) to address these challenges. We discussed the rationale and necessity of developing EO and presented a comprehensive research framework focusing on cancer prevention and treatment. Future EO research will aim to identify cancer causes and implement early prevention strategies using advanced scientific technologies and methods. By emphasizing multidisciplinary collaboration and integrating molecular biology at the micro level, EO will explore the relationship between external and internal environments and cancer. EO will identify potential therapeutic targets by studying the pathways through which environmental exposures lead to carcinogenesis. EO will develop early warning systems and disseminate research findings by collecting big data, employing robust statistical models, and establishing research centers.

Use Cases Requiring Privacy-Preserving Record Linkage in Paediatric Oncology.

Large datasets in paediatric oncology are inherently rare. Therefore, it is paramount to fully exploit all available data, which are distributed over several resources, including biomaterials, images, clinical trials, and registries. With privacy-preserving record linkage (PPRL), personalised or pseudonymised datasets can be merged, without disclosing the patients' identities. Although PPRL is implemented in various settings, use case descriptions are currently fragmented and incomplete. The present paper provides a comprehensive overview of current and future use cases for PPRL in paediatric oncology. We analysed the literature, projects, and trial protocols, identified use cases along a hypothetical patient journey, and discussed use cases with paediatric oncology experts. To structure PPRL use cases, we defined six key dimensions: distributed personalised records, pseudonymisation, distributed pseudonymised records, record linkage, linked data, and data analysis. Selected use cases were described (a) per dimension and (b) on a multi-dimensional level. While focusing on paediatric oncology, most aspects are also applicable to other (particularly rare) diseases. We conclude that PPRL is a key concept in paediatric oncology. Therefore, PPRL strategies should already be considered when starting research projects, to avoid distributed data silos, to maximise the knowledge derived from collected data, and, ultimately, to improve outcomes for children with cancer.

Decoding Metastasis: From Cell Death to Fusion in Cancer Progression.

Metastasis is one of the key concepts in modern oncology, which connects the movement of cancer cells in the body with changes in their characteristics and functions. The review examines the main aspects of metastasis, including theories, facts and discoveries that help to better understand this phenomenon and develop new approaches to its treatment. In this article, we also proposed the theory of cell fusion with the formation of hybrid cells as one of the factors of metastasis. We believe that the fusion of tumor cells with other types of motile cells (leukocytes and bone marrow progenitor cells) may represent an additional mechanism of tumor spread. Cells of bone marrow origin, including cells of the myeloid and macrophage lineages, are the best candidates for heterotypic fusion in regenerative conditions. Events such as cell fusion may play a role in tumor dedifferentiation and progression. We presented a number of arguments and data from our own research that speak in favor of the proposed theory. It should be noted that if the fusion of a normal cell with a tumor cell is one of the possible triggers of tumorigenesis and cancer spread, the mechanisms underlying this process may provide possible new targets for treatment. Therefore, their analysis will expand our arsenal of therapeutic tools by adding completely new targets - cell signaling molecules - and will provide the impetus for reconsidering the tumor microenvironment from a different angle.

Current status of precision oncology in adult glioblastoma.

The concept of precision oncology, the application of targeted drugs based on comprehensive molecular profiling, has revolutionized treatment strategies in oncology. This review summarizes the current status of precision oncology in glioblastoma (GBM), the most common and aggressive primary brain tumor inadults with a median survival below 2 years. Targeted treatments without prior target verification have consistently failed. Patients with BRAF V600E-mutated GBM benefit from BRAF/MEK-inhibition, whereas targeting EGFR alterations was unsuccessful due to poor tumor penetration, tumor cell heterogeneity, and pathway redundancies. Systematic screening for actionable molecular alterations resulted in low rates (< 10%) of targeted treatments. Efficacy was observed in one-third and currently appears to be limited to BRAF-, VEGFR-, and mTOR-directed treatments. Advancing precision oncology for GBM requires consideration of pathways instead of single alterations, new trial concepts enabling rapid and adaptive drug evaluation, a focus on drugs with sufficient bioavailability in the CNS, and the extension of target discovery and validation to the tumor microenvironment, tumor cell networks, and their interaction with immune cells and neurons.

How do patients interpret and respond to a novel patient-reported eastern cooperative oncology group performance status (ECOG)?

Performance status is an important concept in oncology, but is typically clinician-reported. Efforts are underway to include patient-reported measures in cancer care, which may improve patient symptoms, quality of life and overall survival. The purpose of this study was to gain a preliminary understanding of how patients determined their physical performance status based on a novel patient-reported version of the Eastern Cooperative Oncology Group Performance Status (ECOG) scale. We conducted qualitative interviews, including concept elicitation and cognitive interviewing as part of the Patient Reports of Physical Functioning Study (PROPS) to investigate how participants selected their answers to a novel patient-reported ECOG. Participants were administered the patient-reported ECOG and asked to describe devices and modifications used to keep up with daily activities. Participants generally understood the ECOG as intended. Participants with recent changes in status had some difficulty selecting an answer. Most participants used modifications and assistive devices in their daily lives but did not incorporate these into their rational for the ECOG. The potential benefits of a patient-reported ECOG are numerous and this study demonstrates that participants were able to understand and answer the patient-reported ECOG as intended. We recommend future evaluation for the most-appropriate recall period, whether to include modifications in the ECOG instructions, and if increasing the number of response options to the patient-reported ECOG may improve confidence when providing an answer.

Ultrasound-guided percutaneous biopsy for focal liver lesions: Adverse events and diagnostic yield in a single-centre analysis.

Ultrasound-guided biopsy of focal liver lesions (FLL) is a well-established procedure with crucial impact on therapeutic decisions. The safety and accuracy depend on needle type, tumour location and comorbidities. Modern oncological concepts often require large tumour specimens which may increase the procedural risk. We retrospectively collected data from consecutively scheduled ultrasound-guided FLL biopsies performed in an interdisciplinary ultrasound unit at a university hospital from 2015-2020. We analysed complication rates, diagnostic accuracy, and patient outcome in a one-year period. Of 426 scheduled interventions, 339 were included: 322 primary biopsies (40% female, median age 65 years, median BMI 25.4 kg/m2) and 17 rebiopsies in cases with undetermined diagnosis. Indications comprised 309 (96%) cases with suspected malignant lesions. Important comorbidities were type 2 diabetes (n = 107, 33%) and cirrhosis (n = 64, 20%). A conclusive histopathological diagnosis was achieved in 270 (84%) cases with a weak association with lesion size (OR 1.12 per cm, 95%CI 0.99-1.27). Greater BMI (OR 0.60 per 10 BMI points, 95%CI 0.34-1.05) showed a trend towards an insufficient diagnosis. Relevant complications occurred in 8 (2.5%) cases (2 major; 1 life-threatening). Multiple passes showed a trend towards adverse events (OR 2.32 for > 1 pass, 95%CI 0.99-5.42). 93 (29%) patients died during a median follow-up of 171 days. Ultrasound-guided FLL biopsy is an efficient and safe diagnostic measure. The limitations of the procedure and its associated risks should be considered in patients with advanced malignancies.

Abstract PO1-19-05: COGNITION/-GUIDE – Implementation of Precision Oncology in Early High-Risk Breast Cancer

Abstract Background: The concept of precision oncology is nowadays increasingly implemented into clinical practice but is predominantly restricted to the metastatic setting limiting the benefits to prolongation of progression-free-survival (PFS). Implementation of precision oncology at an earlier disease stage with less tumor burden, heterogeneity and a higher capacity of tumor lesions to inform on the molecular tumor landscape holds the promise to impact cure rates. Methods: The prospective COGNITION/-GUIDE precision oncology platform encompasses the COGNITION diagnostic multi-omics biomarker screening platform (NCT05906407) linked to the multi-arm phase II COGNITION-GUIDE umbrella trial (NCT05332561). Based on a two-step consenting procedure, patients with early breast cancer (eBC) and poor response towards standard-of-care (SOC) neoadjuvant chemotherapy (NACT) are first enrolled into the COGNITION diagnostic platform. Residual bulk tumors are subjected to whole-genome- (WGS)/whole exome- (WES) and RNA-sequencing to enable streamlined detection of a rigorous biomarker-framework for subsequent genomics-guided arm allocation. Pilot analyses revealed that 78% (81/104) of high-risk tumors (TNBC or HER2+ BC with non-pCR or HR+/HER2- BC with non-pCR and CPS-EG score ≥ 3, or ypN+ and CPS-EG score ≥ 2) can be successfully sequenced and discussed within an interdisciplinary molecular tumor board. In 67% (70/104) eligible biomarker-profiles could be identified for potential biomarker-guided therapeutic intervention. In a second step, having completed all standard-of-care neoadjuvant and post-neoadjuvant treatments (except endocrine therapy, which can be administered simultaneously to the experimental therapy), patients can be enrolled into one of 6 biomarker-based arms in the COGNITION-GUIDE phase II trial (atezolizumab, inavolisib, ipatasertib, olaparib, sacituzumab govitecan or trastuzumab/pertuzumab). Primary end point is invasive disease-free survival (IDFS) at 4 years after surgery in the whole study population. Secondary endpoints are overall survival (OS), IDFS in each treatment arm, distant disease-free survival (DDFS) and patient-reported outcomes (PROs). Enrollment in COGNITION-GUIDE started in Q2/2023 and 240 patients will be enrolled in 5 German sites until Q2/2027. A comprehensive biomarker discovery program is integrated on longitudinal tumor tissue and liquid biopsies for exploratory analyses. Further clinical work and accrual will be reported at the meeting. Conclusion: The theranostic COGNITION/-GUIDE platform moves the concept of precision oncology to a potentially curative but still high-risk stage of eBC following SOC NACT. Hence, this novel application in the field of precision oncology harbours the prospect to increase cure rates. Citation Format: Verena Thewes, Luise Strassl, Marc Zapatka, Mario Hlevnjak, Constantin Pixberg, Christian Maurer, Katharina Smetanay, Carlo Fremd, Laura Michel, Sabine Heublein, Celina V. Wagner, Jan-Philip Suppelna, Lars Buschhorn, Albrecht Stenzinger, Renate Haidinger, Eva Schumacher-Wulf, Sibylle Loibl, Pauline Wimberger, Jens-Uwe Blohmer, Peter A. Fasching, Wolfgang Janni, Richard F. Schlenk, Peter Lichter, Andreas Schneeweiss. COGNITION/-GUIDE – Implementation of Precision Oncology in Early High-Risk Breast Cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-19-05.

Management of surgical diseases of Primary Hyperparathyroidism: indications of the United Italian Society of Endocrine Surgery (SIUEC).

A task force of the United Italian society of Endocrine Surgery (SIUEC) was commissioned to review the position statement on diagnostic, therapeutic and health‑care management protocol in parathyroid surgery published in 2014, at the light of new technologies, recent oncological concepts, and tailored approaches. The objective of this publication was to support surgeons with modern rational protocols of treatment that can be shared by health-care professionals, taking into account important clinical, healthcare and therapeutic aspects, as well as potential sequelae and complications. The task force consists of 12 members of the SIUEC highly trained and experienced in thyroid and parathyroid surgery. The main topics concern diagnostic test and localization studies, mode of admission and waiting time, therapeutic pathway (patient preparation for surgery, surgical treatment, postoperative management, management of major complications), hospital discharge and patient information, outpatient care and follow-up, outpatient initial management of patients with pHPT.

Advances and residual knowledge gaps in the neck management of head and neck squamous cell carcinoma patients with advanced nodal disease undergoing definitive (chemo)radiotherapy for their primary.

Substantial changes have been made in the neck management of patients with head and neck squamous cell carcinomas (HNSCC) in the past century. These have been fostered by changes in cancer epidemiology and technological progress in imaging, surgery, or radiotherapy, as well as disruptive concepts in oncology. We aimed to review changes in nodal management, with afocus on HNSCC patients with nodal involvement (cN+) undergoing (chemo)radiotherapy. Anarrative review was conducted to review current advances and address knowledge gaps in the multidisciplinary management of the cN+ neck in the context of (chemo)radiotherapy. Metastatic neck nodes are associated with poorer prognosis and poorer response to radiotherapy, and have therefore been systematically treated by surgery. Radical neck dissection (ND) has gradually evolved toward more personalized and less morbid approaches, i.e., from functional to selective ND. Omission of ND has been made feasible by use of positron-emission tomography/computed tomography to monitor the radiation response in cN+ patients. Human papillomavirus-driven oropharyngeal cancers and their cystic nodes have shown dramatically better prognosis than tobacco-related cancers, justifying aspecific prognostic classification (AJCC) creation. Finally, considering the role of lymph nodes in anti-tumor immunity, de-escalation of ND and prophylactic nodal irradiation in combination are intense areas of investigation. However, the management of bulky cN3 disease remains an issue, as aggressive multidisciplinary strategies or innovative combined treatments have not yet significantly improved their prognosis. Personalized neck management is an increasingly important aspect of the overall therapeutic strategies in cN+ HNSCC.

Targeted DNA sequencing of high-grade serous ovarian carcinoma reveals association of TP53 mutations with platinum resistance when combined with gene expression.

High-grade serous ovarian carcinoma (HGSC) is the most common subtype of ovarian cancer and is among the most fatal gynecological malignancies worldwide, due to late diagnosis at advanced stages and frequent therapy resistance. In 47 HGSC patients, we assessed somatic and germline genetic variability of a custom panel of 144 known or suspected HGSC-related genes by high-coverage targeted DNA sequencing to identify the genetic determinants associated with resistance to platinum-based therapy. In the germline, the most mutated genes were DNAH14 (17%), RAD51B (17%), CFTR (13%), BRCA1 (11%), and RAD51 (11%). Somatically, the most mutated gene was TP53 (98%), followed by CSMD1/2/3 (19/19/36%), and CFTR (23%). Results were compared with those from whole exome sequencing of a similar set of 35 HGSC patients. Somatic variants in TP53 were also validated using GENIE data of 1287 HGSC samples. Our approach showed increased prevalence of high impact somatic and germline mutations, especially those affecting splice sites of TP53, compared to validation datasets. Furthermore, nonsense TP53 somatic mutations were negatively associated with patient survival. Elevated TP53 transcript levels were associated with platinum resistance and presence of TP53 missense mutations, while decreased TP53 levels were found in tumors carrying mutations with predicted high impact, which was confirmed in The Cancer Genome Atlas data (n = 260). Targeted DNA sequencing of TP53 combined with transcript quantification may contribute to the concept of precision oncology of HGSC. Future studies should explore targeting the p53 pathway based on specific mutation types and co-analyze the expression and mutational profiles of other key cancer genes.

"Cancer Perspectives And Recent Advances In Anti-Cancer Drug Research: A Review In The Lens Of Siddha Medicine"

Introduction: Cancer is a global health challenge, demanding innovative approaches for prevention, diagnosis, and treatment. Despite ongoing research efforts, finding a definitive cure for cancer remains a formidable challenge. In response to these challenges, the concept of integrative oncology has gained prominence, aiming to combine conventional treatments with evidence-based complementary therapies. Objective: This review explores the integration of Siddha medicine, an ancient South Indian system, with modern oncology to offer holistic cancer care. Siddha perspectives on cancer, its classifications, etiopathogenesis, diagnostic methodologies, and treatment modalities are thoroughly analysed in comparison with modern approach. Recent research on Siddha medicines demonstrating anti-cancer potential is also being reviewed through a systematic literature analysis. Methodology: Analyses of various Siddha texts is done to know the terminologies and categories of cancer. Siddha's etiopathogenesis, diagnostic methodologies and Siddha treatment modalities are discussed, emphasizing the balance of humours. Recent research on Siddha medicines for cancer treatment is compiled through a systematic literature review. Discussion: The manuscript decodes Siddha's conceptual framework underlying cancer hallmarks, aligning Vatham, Pitham, and Kabam with the eight hallmark capabilities. Siddha diagnostic methodologies, including pulse reading and urine examination, are compared with modern techniques. Siddha treatment modalities, rooted in herbal formulations, are presented. A comprehensive compilation of Siddha drugs with anti-cancer potential is provided, supported by in-vitro, in-vivo, and clinical studies. Conclusion: The multifaceted nature of cancer necessitates a comprehensive approach, and Siddha medicine provides unique insights. While Siddha may not directly align with modern diagnostics, its holistic principles contribute valuably to cancer discussions. Integrating Siddha into mainstream oncology requires scientific rigor, with further research and clinical trials to validate safety and efficacy. The fusion of Siddha wisdom with modern oncology holds promise for a more holistic and patient-centric cancer care approach.

Interpreting and integrating genomic tests results in clinical cancer care: Overview and practical guidance.

The last decade has seen rapid progress in the use of genomic tests, including gene panels, whole-exome sequencing, and whole-genome sequencing, in research and clinical cancer care. These advances have created expansive opportunities to characterize the molecular attributes of cancer, revealing a subset of cancer-associated aberrations called driver mutations. The identification of these driver mutations can unearth vulnerabilities of cancer cells to targeted therapeutics, which has led to the development and approval of novel diagnostics and personalized interventions in various malignancies. The applications of this modern approach, often referred to as precision oncology or precision cancer medicine, are already becoming a staple in cancer care and will expand exponentially over the coming years. Although genomic tests can lead to better outcomes by informing cancer risk, prognosis, and therapeutic selection, they remain underutilized in routine cancer care. A contributing factor is a lack of understanding of their clinical utility and the difficulty of results interpretation by the broad oncology community. Practical guidelines on how to interpret and integrate genomic information in the clinical setting, addressed to clinicians without expertise in cancer genomics, are currently limited. Building upon the genomic foundations of cancer and the concept of precision oncology, the authors have developed practical guidance to aid the interpretation of genomic test results that help inform clinical decision making for patients with cancer. They also discuss the challenges that prevent the wider implementation of precision oncology.

Transplant Oncology: An Emerging Discipline of Cancer Treatment.

Transplant oncology is an emerging concept of cancer treatment with a promising prospective outcome. The applications of oncology, transplant medicine, and surgery are the core of transplant oncology to improve patients' survival and quality of life. The main concept of transplant oncology is to radically cure cancer by removing the diseased organ and replacing it with a healthy one, aiming to improve the survival outcomes and quality of life of cancer patients. Subsequently, it seeks to expand the treatment options and research for hepatobiliary malignancies, which have seen significantly improved survival outcomes after the implementation of liver transplantation (LT). In the case of colorectal cancer (CRC) in the transplant setting, where the liver is the most common site of metastasis of patients who are considered to have unresectable disease, initial studies have shown improved survival for LT treatment compared to palliative therapy interventions. The indications of LT for hepatobiliary malignancies have been slowly expanded over the years beyond Milan criteria in a stepwise manner. However, the outcome improvements and overall patient survival are limited to the specifics of the setting and systematic intervention options. This review aims to illustrate the representative concepts and history of transplant oncology as an emerging discipline for the management of hepatobiliary malignancies, in addition to other emerging concepts, such as the uses of immunotherapy in a peri-transplant setting as well as the use of circulating tumor DNA (ctDNA) for surveillance post-transplantation.

The Use of Problem-Based Learning Curriculum to Increase Medical Student Exposure to Radiation Oncology

In recent years, there has been a decline in the number of radiation oncology residency applicants. New techniques to recruit students to the field are necessary. Early exposure to oncology care in pre-clinical years may translate to increased student interest in oncology-related fields and improved understanding of oncologic treatment modalities. We propose that a cancer-specific problem-based learning (PBL) case will increase exposure to oncology during pre-clinical years. A PBL case regarding pancreatic cancer was created by a radiation oncology resident/faculty member and the gastrointestinal course director for first-year medical students (n = 140) at a single institution. The one-hour small group case focused on oncologic work up, multi-disciplinary care and radiotherapy concepts. Students were provided with a case prompt and resources to review prior to the PBL session. Volunteer radiation oncology facilitators then guided students through the case to achieve desired learning objectives. Following the PBL, students completed an optional nine-question survey regarding their experience. A total of 76 (54%) medical students completed the post-PBL survey. The majority (89%) of students reported that the case motivated them to learn more about oncology, and almost all (99%) noted improved understanding of the multidisciplinary nature of cancer care. 75 (99%) students reported increased understanding of how radiotherapy is delivered. 62 (82%) students reported increased motivation to learn about radiation oncology. 38 (50%) students reported that they plan to participate in an elective in oncology. 36 (47%) reported that they are considering pursuing an oncologic field. There was an increase in the number of subscribers to the Oncology Interest Group (43% increase from previous year) and positive feedback was noted from free-text responses from participants. Integrating a cancer-specific PBL case facilitated by radiation oncology educators into the pre-clinical curriculum is an effective avenue to introduce oncology concepts and stimulate interest in oncology amongst first-year medical students.

Evaluation of OMOP CDM, i2b2 and ICGC ARGO for supporting data harmonization in a breast cancer use case of a multicentric European AI project

ObjectiveObservational research in cancer poses great challenges regarding adequate data sharing and consolidation based on a homogeneous data semantic base. Common Data Models (CDMs) can help consolidate health data repositories from different institutions minimizing loss of meaning by organizing data into a standard structure. This study aims to evaluate the performance of the Observational Medical Outcomes Partnership (OMOP) CDM, Informatics for Integrating Biology & the Bedside (i2b2) and International Cancer Genome Consortium, Accelerating Research in Genomic Oncology (ICGC ARGO) for representing non-imaging data in a breast cancer use case of EuCanImage. MethodsWe used ontologies to represent metamodels of OMOP, i2b2, and ICGC ARGO and variables used in a cancer use case of a European AI project. We selected four evaluation criteria for the CDMs adapted from previous research: content coverage, simplicity, integration, implementability. Resultsi2b2 and OMOP exhibited higher element completeness (100% each) than ICGC ARGO (58.1%), while the three achieved 100% domain completeness. ICGC ARGO normalizes only one of our variables with a standard terminology, while i2b2 and OMOP use standardized vocabularies for all of them. In terms of simplicity, ICGC ARGO and i2b2 proved to be simpler both in terms of ontological model (276 and 175 elements, respectively) and in the queries (7 and 20 lines of code, respectively), while OMOP required a much more complex ontological model (615 elements) and queries similar to those of i2b2 (20 lines). Regarding implementability, OMOP had the highest number of mentions in articles in PubMed (130) and Google Scholar (1,810), ICGC ARGO had the highest number of updates to the CDM since 2020 (4), and i2b2 is the model with more tools specifically developed for the CDM (26). ConclusionICGC ARGO proved to be rigid and very limited in the representation of oncologic concepts, while i2b2 and OMOP showed a very good performance. i2b2′s lack of a common dictionary hinders its scalability, requiring sites that will share data to explicitly define a conceptual framework, and suggesting that OMOP and its Oncology extension could be the more suitable choice. Future research employing these CDMs with actual datasets is needed.

Liquid Biopsy - A new diagnostic concept in oncology

The analysis of tumor cells circulating in the blood or of products of tumor cells circulating in other body fluids has gained increasing attention in recent years and is summarized under the term liquid biopsy (LB). LB includes the analysis of circulating tumor cells, cell-free circulating tumor-associated nucleic acids, extracellular vesicles, proteins, or other products that are released into the peripheral bloodstream by the primary or metastatic tumor. For a huge number of solid tumor entities, LB has already been successfully applied in preclinical and clinical studies for the detection, risk stratification, treatment monitoring and relapse detection. LB provides valuable real-time information on tumor cell development, therapeutic targets, and mechanisms of therapy resistance using a non-invasive peripheral blood test. In this article, the most important LB analytes and the current state of research are presented. In addition, the remaining obstacles and the diverse efforts to implement LB in clinical routine are critically discussed.

Precision oncology medicines and the need for real world evidence acceptance in health technology assessment: Importance of patient involvement in sustainable healthcare

Precision oncology has made remarkable strides in improving clinical outcomes, offering hope to patients with historically difficult-to-treat, as well as rare or neglected cancers. However, despite rapid advancement, precision oncology has reached a critical juncture, where patient access to these life-saving medicines may be hampered by strict requirements by Health Technology Assessment (HTA) bodies for randomised controlled trials (RCTs) for assessing new medicines against appropriate comparator. The very nature of precision oncology—matching a tumour’s unique molecular alterations to targeted therapies predicted to elicit response—can make the use of RCTs very difficult, as only a very small number of patients might qualify for a given therapy within a traditional clinical trial setting. Real-world evidence (RWE) has been accepted for regulatory decision-making but has yet to reach widespread acceptance by HTA bodies. As the oncology treatment landscape has evolved towards favouring the concept of precision oncology, there is a growing need for flexibility in the way HTA bodies evaluate new medicines. We must acknowledge that current assessment methodologies can limit access to life-changing medicines for many patients who have no alternative options and that a growing number of precision oncology medicines with proven clinical benefits in rare tumours cannot be reasonably evaluated using traditional methodologies. The objectives of this paper are to advocate a change in mindset regarding best practices in drug assessment models and to propose alternative approaches when considering indications for which RWE is the most compelling data source available.

Utilizing graphic organizers to actively learn pediatric dental and oncology concepts.

Journal of Dental EducationAccepted Articles ADVANCING THROUGH INNOVATIONOpen Access Utilizing graphic organizers to actively learn pediatric dental and oncology concepts Michael Suh DDS, Corresponding Author Michael Suh DDS [email protected] Department of Pediatric Dentistry, University of Pacific, Arthur A. Dugoni School of Dentistry, San Francisco, USA Correspondence Michael Suh, DDS, University of Pacific, Arthur A. Dugoni School of Dentistry, 155 5th St., San Francisco, CA 94103, USA. Email: [email protected]Search for more papers by this author Michael Suh DDS, Corresponding Author Michael Suh DDS [email protected] Department of Pediatric Dentistry, University of Pacific, Arthur A. Dugoni School of Dentistry, San Francisco, USA Correspondence Michael Suh, DDS, University of Pacific, Arthur A. Dugoni School of Dentistry, 155 5th St., San Francisco, CA 94103, USA. Email: [email protected]Search for more papers by this author First published: 06 June 2023 https://doi.org/10.1002/jdd.13292 This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as https://doi.org/10.1002/jdd.13292 AboutPDF ToolsExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Accepted ArticlesAccepted, unedited articles published online and citable. The final edited and typeset version of record will appear in the future. RelatedInformation

Importance of interdisciplinarity in modern oncology: results of a national intergroup survey of the Young Oncologists United (YOU).

Modern, personalized treatment concepts in oncology require an interdisciplinary and multiprofessional collaboration. In addition to its relevance in patient care, interdisciplinary collaboration is also becoming increasingly important in clinical research as well as medical education and resident training in oncology. Between November 2021 and March 2022, an online survey was conducted among German early career research groups, represented by Young Oncologists United (YOU). The aim was to identify the status and need for interdisciplinarity at clinic, educational, and research levels. A total of 294 participants completed the questionnaire in full. 90.7% of the respondents fully or predominantly agreed with the statement that interdisciplinary work plays a major role in their daily clinical work. 78.9% wished for more interdisciplinary collaboration. Of the 49.7% of participants who have never participated in an interdisciplinary research project, 80.1% said they would like to participate in such a study project in the future. Lack of time resources, too much organizational effort, and possible political conflicts between institutions were identified as factors that make practical implementation difficult. 74.1% declared their willingness to become active in an oncology early career research group. Interdisciplinary collaboration has become increasingly important in oncology. Networks that span different disciplines could help to promote interdisciplinary research projects among young scientists and improve exchange in professional practice and education with the implication of improved patient care.

Genomic therapy matching in rare and refractory cancers: Updated results from a retrospective cohort study in the Molecular Screening and Therapeutic (MoST) program.

1540 Background: Biomarker actionability and therapy matching are two central concepts in precision oncology. However, the best strategy to align therapy with genomic alterations remains unclear. Here we report the updated results from a cohort study conducted in an Australian precision oncology program (MoST, ACTRN12616000908437), examining a therapy matching strategy based on comprehensive genomic profiling (CGP) results. Methods: All patients (pts) with rare or advanced solid tumours undergoing CGP from 2016 to 2021 after exhausting standard treatments were included. The primary outcome was overall survival (OS) from the date of CGP result, estimated using the Kaplan-Meier method. Pts were grouped according to tiers of actionability determined by matching against the TOPOGRAPH knowledge base ( https://topograph.info ) and stratified into clinically active (Tier 1-3, therapies with evidence from prospective trials), investigational (Tier 3B and 4, therapies with evidence from another cancer type, preclinical, or retrospective studies), or unmatched tier groups. To assess between-group differences in OS, hazard ratios (HR) were estimated in a time-varying Cox regression model adjusting for time to initiation of subsequent therapy. Results: This updated analysis included 3,383 pts (79% rare and less common). The median follow-up was 22.6 months (mo). For 2,065 pts who did not receive treatment after CGP, the median OS (mOS) was 8.2 mo (95% CI 7.4 to 9.0). For 1,318 pts who received ≥1 line of therapy after CGP, the mOS was 14.1 mo (13.4 to 15.2). 1,270 pts (38%) carried a genomic alteration linked to clinically active therapies (Tier 1-3). Of these, 116 (3.4%) received matched treatment after CGP, experiencing longer survival compared with 410 (32.2%) that received only unmatched therapy (mOS 21.2 v 12.8 mo, HR 0.58, 0.45 to 0.76, P&lt;0.001). Whilst receiving a matched therapy in the investigational tier group (n=133, T3B/4) did not show significant differences in outcomes (mOS 14.5 v unmatched 12.8 mo, n=536, HR 0.88, 0.72 to 1.08, p=0.24), exploratory analyses identified differences in survival for a subset of 41 pts with Switch/Sucrose Non-Fermentable complex mutations receiving matched Tier 4 therapies (mOS 30.1 v 9.6 mo, HR 0.29, 0.17 to 0.51, P&lt;0.0001). Pts receiving repurposed drugs that matched solely on biomarkers in non-cognate cancer types (Tier 3B) showed no survival difference over unmatched therapy (n=35 v 469, mOS 13.6 v 12.5 mo, HR 0.96, 0.65 to 1.41, p=0.83). Conclusions: This study provides insight into how biomarker-linked therapies can be rationally prioritised in rare and advanced cancer populations. Addressing the barriers of access to Tier 1-3 therapies may broaden the utility of genomic biomarker testing. Off-label drug repurposing without direct supporting evidence should only be undertaken in a clinical trial setting.