Recurrence of Primary Mucosal Head and Neck Squamous Cell Carcinoma in Solid Organ Transplant Recipients

Background: Patients that undergo a solid organ transplant have been shown to have a higher risk of developing cancer and even subsequent recurrences due to the immunosuppressants required to prevent rejection. Most established literature has been in the setting of cutaneous malignancies. In this study, we examine patients diagnosed with primary mucosal head and neck squamous cell carcinomas (HNSCC) diagnosed post-transplant to analyze their disease characteristics and clinical outcomes. Objectives: To retrospectively characterize patients with primary mucosal HNSCC with history of prior solid organ transplant to define patient and tumor factors as well as analyze their long-term outcomes. Methods: IRB approval was obtained for a retrospective evaluation utilizing our institutional head and neck cancer database. The analysis included patients who had previously undergone a solid organ transplant and subsequently were diagnosed with a primary mucosal HNSCC. These included patients diagnosed from March 2006 to March 2021. The onset of recurrence was analyzed to identify long-term health implications for this patient cohort. Kaplan-Meier analyses were performed to calculate overall and disease-free survival. Results: Out of 1,221 patients in our database, 24 patients met the inclusion criteria. Three patients were excluded due to lack of treatment or follow-up information, creating a sample of 21 patients. Of these, 13 (61.9%) received a liver, 4 (19%) received a kidney, 1 (4.8%) received a lung, and 3 (14.3%) received two transplants. After receiving the transplant, the median time to a HNSCC diagnosis was 6.4 years (range of 0.5 y to 18.5 y). The primary tumors included 8 (36.3%) oropharyngeal, 8 (36.3%) oral cavity, 5 (22.7%) laryngeal, and 1 (4.5%) hypopharyngeal lesion for a total of 22 lesions, with one patient having concurrent primaries of the oral cavity and oropharynx. The cohort included 1 (4.7%) stage 0, 7 (33.3%) stage I, 3 (14.3%) stage II, 3 (14.3%) stage III, and 7 (33.3%) stage IV; no patients had distant metastasis at time of diagnosis. Of the patients, 7 (33.3%) were treated with surgery alone, 6 (28.6%) received post-operative radiation/chemoradiation, 6 (28.6%) were treated with definitive chemoradiation, and 2 (9.5%) received definitive radiation. Median overall survival was 31 months. After treatment, 6 (28.6%) patients experienced a recurrence. Disease-free survival was 72.1% at 12 months. All patients who had a recurrence also died within the follow-up period. The median time of death after recurrence for all six patients was 11.5 months (range of 1 month to 22 mo). Conclusions: Solid organ transplant patients are at a higher risk of developing many different cancers. Treatment of primary mucosal HNSCC is frequently done with curative intent and can be associated with significant morbidity. A better understanding of how solid organ transplant history modifies the disease course can help properly guide treatment decisions. In particular, this series highlights a high rate of mortality among patients who experience a disease recurrence. Further research is needed to better understand the risks associated with recurrence in solid organ transplant patients

Landscape of Oncology-Specific, FDA-Approved, Artificial Intelligence and Machine Learning-Enabled Medical Devices

Purpose/Objective(s): Machine learning (ML), a type of artificial intelligence (AI) technology that uses a data-driven approach for pattern recognition, has been shown by numerous research studies to be beneficial for tasks across healthcare. In this study, we aim to characterize the commercial availability of oncology-specific AI/ML applications in the clinic by performing a detailed analysis of such devices that were approved/cleared by the US Food and Drug Administration (FDA). Materials/Methods: A list of 343 AI/ML-enabled medical devices that were approved or cleared by the FDA up to June 2021 was published by the agency, and this list was used to construct the initial database for our study. The publicly available FDA approval letters for these devices were independently reviewed by two research assistants, and a device was classified as oncology-specific if its primary intended use is related to assisting the diagnosis or treatment of oncologic pathologies. For oncology-specific devices, additional details on device characteristics, FDA regulatory process, and approved indications were obtained. A basic descriptive statistical analysis was performed on the aggregated data. Results: Fifty-two (15.2%) of the 343 AI/ML-enabled medical devices were classified as oncology-specific. The growth of the oncologic-specific devices sharply rose since the mid-2010s, with 49 (94.2%) approved in 2016 or after. Fifty (96.2%) devices were cleared by the 510(k) premarket notification pathway, and, except for one class III device, the remaining 51 devices were considered as class II by the FDA. All but one device was considered Software as a Medical Device (SaMD). Thirty-six (69.2%) devices were intended for diagnostic purposes, of which 24 (66.7%), 9 (14.3%), 1 (6.3%), 1 (6.3%), and 1 (6.3%) was for the detection of breast cancer, lung cancer, prostate cancer, thyroid cancer, and bone cancer, respectively. The 16 devices intended for therapeutic purposes were all related to radiotherapy: 15 are for radiation treatment planning (all included organ auto-segmentation as the main function), and 1 is a linear accelerator equipped with AI/ML algorithms. Conclusion: Our results showed a rapid increase of oncology-specific, FDA-approved, AI/ML-enabled medical devices since 2016. Further study is needed to assess the impact made by these devices on the delivery of oncology care

The Name of the Game: Utilizing Experiential Learning in the Classroom to Engage, Empower and Reflect on Student Learning and Assessment

In the modern post-secondary classroom, there is a push for more experiential and active learning activities for students. A variety of benefits such as engagement, improved learning and self regulated learning have ensued with these different types of learning. Studies regarding these benefits have mostly centered on experiences carefully orchestrated by instructors, rather than experiences that were created by students under the guidance of instructors. Herein is a study of the benefits and efficiency, of the latter type of activity, which requires students to generate chemical puzzles in a large post-secondary classroom. The authors determined that not only is a puzzle generation activity possible, but students’ reflections on instructor examples highlights the potential for learning and for a new form of assessment. Going forward, however, the study also shows more support and examples are required in future iterations of the puzzle framework, to help students create a meaningful experience

Expanding Our Understanding of Adherence: The Role of Health Literacy and Cognitive Function in Adherence and Outcomes in Head and Neck Cancer

Background: Health literacy is the degree to which a person has the capacity to obtain, process, and understand basic information and services needed to make decisions about their health care. Poor health literacy has been associated with difficulties managing medications, assessing and evaluating health information, completing medical and financial forms, and comparing nutritional information of foods. As such, health literacy is closely related to adherence to medical treatment. Cognitive function contributes to one\u27s health literacy, though also independently contributes to adherence. Patients with head and neck cancers require complex, often multimodal care, and both health literacy and cognitive function have been found to be lower than the general population. However no study has examined the interaction between cognitive function and health literacy within treatment for head and neck cancer and outcomes. Objectives: To examine the role of cognitive function and health literacy in adherence to definitive and adjuvant radiotherapy and chemoradiotherapy and disease-free and overall survival in patients with head and neck cancer. Methods: 149 patients who received either definitive or adjuvant radiotherapy or chemoradiotherapy for squamous cell carcinoma of the head and neck and were assessed by psycho-oncology provider before initiating treatment were included. Patients between August 2017 through March 2020 were included. Patients were administered the Montreal Cognitive Assessment (MoCA) and the Rapid Estimate of Adult Literacy in Medicine (REALM-SF) by the psych-oncologist before starting treatment. Cancer and treatment related variables, including adherence, were obtained via chart review. Adherence was defined as having completed the treatment recommended by the Multi-disciplinary Tumor Board. Results: Patients were predominantly male (78%), white (73%), with an average age of 62 years (SD=9.1). The average years of education was 13.6 years (SD=2.6). The mean health literacy score was 6.3 out of 7 (SD=1.3, range 0-7), indicating reading at 7-8th grade level. The mean cognitive function score was 23.8 out of 30 (SD=3.6, range 10-30, scores less than 26 are indicative of cognitive impairment). Sixteen percent of patients were non-adherent to treatment recommendations and this was not associated with either health literacy or cognitive function (P=0.5 & 0.36, respectively). Lower health literacy was associated with later stage at presentation (P\u3c0.05). Health literacy was not associated with disease-free or overall survival (P=0.66 & 0.11, respectively). However, cognitive function was associated with overall survival (P\u3c0.0001) but not disease-free survival (P=0.22). Conclusions: Psychosocial variables such as health literacy and cognitive function are infrequently considered or studied in head and neck cancer. However, there exists significant evidence that patients with head and neck cancer tend to have higher rates of cognitive impairment and lower health literacy than the general population. Further, literacy and cognitive function are known to contribute to health outcomes in other populations. The current study found that cognitive impairment, but not health literacy, is associated with overall survival, while not being associated with treatment adherence. Further research is needed into the pathways that cognitive function interacts with cancer care and survival. This study highlights the need for assessment of cognitive function in patients with head and neck cancer, as identification and intervention with these patients can aid in survival outcomes and quality of life

A framework for the definition and interpretation of the use of surrogate endpoints in interventional trials

Background: Interventional trials that evaluate treatment effects using surrogate endpoints have become increasingly common. This paper describes four linked empirical studies and the development of a framework for defining, interpreting and reporting surrogate endpoints in trials. Methods: As part of developing the CONSORT (Consolidated Standards of Reporting Trials) and SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) extensions for randomised trials reporting surrogate endpoints, we undertook a scoping review, e-Delphi study, consensus meeting, and a web survey to examine current definitions and stakeholder (including clinicians, trial investigators, patients and public partners, journal editors, and health technology experts) interpretations of surrogate endpoints as primary outcome measures in trials. Findings: Current surrogate endpoint definitional frameworks are inconsistent and unclear. Surrogate endpoints are used in trials as a substitute of the treatment effects of an intervention on the target outcome(s) of ultimate interest, events measuring how patients feel, function, or survive. Traditionally the consideration of surrogate endpoints in trials has focused on biomarkers (e.g., HDL cholesterol, blood pressure, tumour response), especially in the medical product regulatory setting. Nevertheless, the concept of surrogacy in trials is potentially broader. Intermediate outcomes that include a measure of function or symptoms (e.g., angina frequency, exercise tolerance) can also be used as substitute for target outcomes (e.g., all-cause mortality)—thereby acting as surrogate endpoints. However, we found a lack of consensus among stakeholders on accepting and interpreting intermediate outcomes in trials as surrogate endpoints or target outcomes. In our assessment, patients and health technology assessment experts appeared more likely to consider intermediate outcomes to be surrogate endpoints than clinicians and regulators. Interpretation: There is an urgent need for better understanding and reporting on the use of surrogate endpoints, especially in the setting of interventional trials. We provide a framework for the definition of surrogate endpoints (biomarkers and intermediate outcomes) and target outcomes in trials to improve future reporting and aid stakeholders' interpretation and use of trial surrogate endpoint evidence

A framework for the definition and interpretation of the use of surrogate endpoints in interventional trials

Background: Interventional trials that evaluate treatment effects using surrogate endpoints have become increasingly common. This paper describes four linked empirical studies and the development of a framework for defining, interpreting and reporting surrogate endpoints in trials. Methods: As part of developing the CONSORT (Consolidated Standards of Reporting Trials) and SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) extensions for randomised trials reporting surrogate endpoints, we undertook a scoping review, e-Delphi study, consensus meeting, and a web survey to examine current definitions and stakeholder (including clinicians, trial investigators, patients and public partners, journal editors, and health technology experts) interpretations of surrogate endpoints as primary outcome measures in trials. Findings: Current surrogate endpoint definitional frameworks are inconsistent and unclear. Surrogate endpoints are used in trials as a substitute of the treatment effects of an intervention on the target outcome(s) of ultimate interest, events measuring how patients feel, function, or survive. Traditionally the consideration of surrogate endpoints in trials has focused on biomarkers (e.g., HDL cholesterol, blood pressure, tumour response), especially in the medical product regulatory setting. Nevertheless, the concept of surrogacy in trials is potentially broader. Intermediate outcomes that include a measure of function or symptoms (e.g., angina frequency, exercise tolerance) can also be used as substitute for target outcomes (e.g., all-cause mortality)-thereby acting as surrogate endpoints. However, we found a lack of consensus among stakeholders on accepting and interpreting intermediate outcomes in trials as surrogate endpoints or target outcomes. In our assessment, patients and health technology assessment experts appeared more likely to consider intermediate outcomes to be surrogate endpoints than clinicians and regulators. Interpretation: There is an urgent need for better understanding and reporting on the use of surrogate endpoints, especially in the setting of interventional trials. We provide a framework for the definition of surrogate endpoints (biomarkers and intermediate outcomes) and target outcomes in trials to improve future reporting and aid stakeholders' interpretation and use of trial surrogate endpoint evidence. Funding: SPIRIT-SURROGATE/CONSORT-SURROGATE project is Medical Research Council Better Research Better Health (MR/V038400/1) funded

Science Communication in a Digital Age: Social Media and the American Fisheries Society

Social media platforms are effective tools used to help communicate and increase involvement in cultural, political, and scientific circles. In 2012, an ad hoc committee was established to explore online fisheries science communication and how social media platforms can be utilized by the American Fisheries Society (AFS). A survey was disseminated to all AFS units (chapters, sections, divisions) and student subunits to better understand the current use of social media within the AFS. A relatively high response rate (82%) provided some confidence in the survey results—namely, that nearly 69% or more of units and subunits used social media. Facebook was the dominant platform used (59%; all others < 15%) and almost exclusively (97%) for the purpose of communication. Education, outreach, and member recruitment were other reasons for social media use. Finally, whether units currently use social media or not at all, it was recommended that AFS-led workshops and assistance would increase the usefulness of social media

Reporting of surrogate endpoints in randomised controlled trial protocols (SPIRIT-Surrogate): extension checklist with explanation and elaboration

Randomised controlled trials often use surrogate endpoints to substitute for a target outcome (an outcome of direct interest and relevance to trial participants, clinicians, and other stakeholders—eg, all cause mortality) to improve efficiency (through shortened duration of follow-up, reduced sample size, and lower research costs), and for ethical or practical reasons. However, their use has a fundamental limitation in terms of uncertainty of the intervention effect on the target outcome and limited information on potential intervention harms. There have been increasing calls for improved reporting of trial protocols that use surrogate endpoints. This report presents the SPIRIT-Surrogate, an extension of the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) checklist, a consensus driven reporting guideline designed for trial protocols using surrogate endpoints as the primary outcome(s). The SPIRIT-Surrogate extension includes nine items modified from the SPIRIT 2013 checklist. The guideline provides examples and explanations for each item. We recommend that all stakeholders (including trial investigators and sponsors, research ethics reviewers, funders, journal editors, and peer reviewers) use this extension in reporting trial protocols that use surrogate endpoints. Its use will allow for improved design of such trials, improved transparency, and interpretation of findings when trials are completed, and ultimately reduced research waste

Reporting of surrogate endpoints in randomised controlled trial reports (CONSORT-Surrogate): extension checklist with explanation and elaboration

Randomised controlled trials commonly use surrogate endpoints to substitute for a target outcome (outcome of direct interest and relevance to trial participants, clinicians, and other stakeholders—eg, all cause mortality) to improve their efficiency (through shorter trial duration, reduced sample size, and thus lower research costs), or for ethical or practical reasons. But reliance on surrogate endpoints can increase the uncertainty of an intervention’s treatment effect and potential failure to provide adequate information on intervention harms, which has led to calls for improved reporting of trials using surrogate endpoints. This report presents a consensus driven reporting guideline for trials using surrogate endpoints as the primary outcomes—the CONSORT (Consolidated Standards of Reporting Trials) extension checklist: CONSORT-Surrogate. The extension includes nine items modified from the CONSORT 2010 checklist and two new items. Examples and explanations for each item are provided. We recommend that all stakeholders (including trial investigators and sponsors, journal editors and peer reviewers, research ethics reviewers, and funders) use this extension in reporting trial reports using surrogate endpoints. Use of this checklist will improve transparency, interpretation, and usefulness of trial findings, and ultimately reduce research waste