Oncology Literature Research Articles

Compassion fatigue in surgical oncologists: A scoping review.

343 Background: The practice of clinical oncology includes diverse and complex clinical, interpersonal and ethical challenges that can lead to physical and/or emotional distress, including burnout (BO), compassion fatigue (CF), secondary traumatic stress (STS) or moral distress (MDS), which potentially impacts patient care and provider well-being. Surgical oncology presents additional stressors and challenges, yet little is known about CF, STS, and MDS in this population, and the greater body of literature in oncology is heterogenous.The aim of this paper is to review current literature regarding CF, MDS, and STS in clinical oncologists, with a focus on surgical oncologists. Methods: Searches of OVID Medline and Embase databases were performed, as well as relevant bibliographies to identify articles related to CF, STS and MDS in clinical and surgical oncologists. Descriptive analysis was completed on relevant articles to address common definitions, themes, and potential aggravating/protective factors. Results: 619 articles were retrieved, of which 196 underwent data extraction. Of these, 48 articles were related to CF, MDS, or STS in oncologists and 5 included surgical oncologists. There was no data specific to surgical oncologists. Definitions of the terms were inconsistent across the literature. Potential contributing factors for CF/STS/MDS are related to the work environment, time pressures, and poor communication skills. In contrast, self-care, supportive colleagues/supervisors, and experience appear to be protective. Conclusions: This study highlights a need for standardized definitions to accurately capture and explore each of these phenomena. Further research is needed to provide insight into the challenges faced by surgical oncologists and how to support them.

Assessing the Reporting Quality of Machine Learning Algorithms in Head and Neck Oncology.

This study aimed to assess reporting quality of machine learning (ML) algorithms in the head and neck oncology literature using the TRIPOD-AI criteria. A comprehensive search was conducted using PubMed, Scopus, Embase, and Cochrane Database of Systematic Reviews, incorporating search terms related to "artificial intelligence," "machine learning," "deep learning," "neural network," and various head and neck neoplasms. Two independent reviewers analyzed each published study for adherence to the 65-point TRIPOD-AI criteria. Items were classified as "Yes," "No," or "NA" for each publication. The proportion of studies satisfying each TRIPOD-AI criterion was calculated. Additionally, the evidence level for each study was evaluated independently by two reviewers using the Oxford Centre for Evidence-Based Medicine (OCEBM) Levels of Evidence. Discrepancies were reconciled through discussion until consensus was reached. The study highlights the need for improvements in ML algorithm reporting in head and neck oncology. This includes more comprehensive descriptions of datasets, standardization of model performance reporting, and increased sharing of ML models, data, and code with the research community. Adoption of TRIPOD-AI is necessary for achieving standardized ML research reporting in head and neck oncology. Current reporting of ML algorithms hinders clinical application, reproducibility, and understanding of the data used for model training. To overcome these limitations and improve patient and clinician trust, ML developers should provide open access to models, code, and source data, fostering iterative progress through community critique, thus enhancing model accuracy and mitigating biases. NA Laryngoscope, 2024.

763. TEXTBOOK ONCOLOGIC OUTCOME FOLLOWING TRIMODALITY THERAPY FOR ESOPHAGEAL ADENOCARCINOMA

Abstract Background Although the concept of textbook oncologic outcome (TOO) as an emerging quality benchmark has been validated in the general surgical oncology literature, data regarding the frequency of achieving TOO and its impact on subsequent survival outcomes in patients with esophageal adenocarcinoma (EAC) who undergo trimodality therapy remain undefined. Methods Patients with adenocarcinoma of the esophagus/gastroesophageal junction (GEJ, Siewert I/II) who underwent neoadjuvant chemoradiation and esophagectomy at a single institution (2000-2022) were retrospectively identified. Patients undergoing salvage resection were excluded. TOO was defined according to a published consensus definition: length of stay (LOS) ≤14 days, R0, ≥20 resected lymph nodes, no anastomotic leak (any grade), no Clavien-Dindo (CD) grade ≥3 complications, no hospital or intensive care unit (ICU) readmission, and no reoperation. Multivariable logistic regression was used to identify clinicopathologic features associated with TOO. Multivariable Cox regression and landmark analyses were used to quantify the association between TOO and OS. Results Of 1138 patients, TOO was observed in 38.2% (435): 90.9% (1034) R0, 60.9% (693) ≥20 lymph nodes, 89.9% (1023) no anastomotic leak, and 98.4% (1120) no in-hospital mortality. Features independently associated with reduced odds of TOO included: cervical anastomosis (OR 0.50, P=0.001), preoperative delay ≥90 days after neoadjuvant therapy (OR 0.62, P=0.004), induction chemotherapy (OR 0.74, P=0.039), coronary artery disease (OR 0.67, P=0.043). Among patients who underwent esophagectomy <90 days after neoadjuvant therapy and survived ≥30 days, TOO was independently associated with improved OS (HR 0.80, P=0.018). TOO remained associated with improved OS using 90-day (P=0.014) and 120-day (P=0.037) landmarks. Conclusions Although TOO is difficult to achieve following trimodality therapy for EAC, it is strongly associated with improved long-term overall survival. As such, further efforts are warranted to explore the utility of TOO as a quality benchmark in EAC patients and to validate its impact across varying practice settings.

Subgrading of G2 Pancreatic Neuroendocrine Tumors as 2A (Ki67 3% to < 10%) Versus 2B (10% to ≤ 20%) Identifies Behaviorally Distinct Subsets in Keeping with the Evolving Management Protocols

BackgroundGrade 1/2 PanNETs are mostly managed similarly, typically without any adjunct treatment with the belief that their overall metastasis rate is low. In oncology literature, Ki67-index of 10% is increasingly being used as the cutoff in stratifying patients to different protocols, although there are no systematic pathology-based studies supporting this approach.MethodsKi67-index was correlated with clinicopathologic parameters in 190 resected PanNETs. A validation cohort (n = 145) was separately analyzed.ResultsIn initial cohort, maximally selected rank statistics method revealed 12% to be the discriminatory cutoff (close to 10% rule of thumb). G2b cases had liver/distant metastasis rate of almost threefold higher than that of G2a and showed significantly higher frequency of all histopathologic signs of aggressiveness (tumor size, perineural/vascular invasion, infiltrative growth pattern, lymph node metastasis). In validation cohort, these figures were as striking. When all cases were analyzed together, compared with G1, the G2b category had nine times higher liver/distant metastasis rate (6.1 vs. 58.5%; p < 0.001) and three times higher lymph node metastasis rate (20.5 vs. 65.1%; p < 0.001).ConclusionsG2b PanNETs act very similar to G3, supporting management protocols that regard them as potential therapy candidates. Concerning local management, metastatic behavior in G2b cases indicate they may not be as amenable for conservative approaches, such as watchful waiting or enucleation. This substaging should be considered into diagnostic guidelines, and clinical trials need to be devised to determine the more appropriate management protocols for G2b (10% to ≤ 20%) group, which shows liver/distant metastasis in more than half of the cases, which at minimum warrants closer follow-up.

Dose Rate Effects from the 1950s through to the Era of FLASH.

Numerous dose rate effects have been described over the past 6-7 decades in the radiation biology and radiation oncology literature depending on the dose rate range being discussed. This review focuses on the impact and understanding of altering dose rates in the context of radiation therapy, but does not discuss dose rate effects as relevant to radiation protection. The review starts with a short historic review of early studies on dose rate effects, considers mechanisms thought to underlie dose rate dependencies, then discusses some current issues in clinical findings with altered dose rates, the importance of dose rate in brachytherapy, and the current timely topic of the use of very high dose rates, so-called FLASH radiotherapy. The discussion includes dose rate effects in vitro in cultured cells, in invivo experimental systems and in the clinic, including both tumors and normal tissues. Gaps in understanding dose rate effects are identified, as are opportunities for improving clinical use of dose rate modulation.

Same-day Discharge Following Vaginal Hysterectomy and Native-tissue Apical Repair for Uterovaginal Prolapse: A Prospective Cohort Study.

The safety and feasibility of same-day discharge (SDD) has been consistently reported across the benign and gynecologic oncology literature. However, outcomes of SDD in the urogynecology population are sparse. The objectives of this study were to describe the success of SDD following vaginal hysterectomy and native-tissue colpopexy, and to compare the incidence of postoperative adverse events in patients discharged same-day versus postoperative day 1 (POD1). Further objectives were to compare pain, quality of recovery (QoR), and satisfaction between the groups. This was a single-center, prospective cohort study of patients with planned SDD. A standardized ERAS protocol was utilized. The QoR-40 questionnaire was administered at baseline, POD2, and the 6-week postoperative visit. Pain scores were captured similarly, and a satisfaction survey was administered at 6 weeks. The primary outcome was composite adverse events defined as any postoperative adverse event and/or health care utilization, excluding telephone calls, and urinary tract infection. A total of 101 patients were enrolled in the study; the primary outcome was available for 99. SDD was achieved for 76 patients (77.0%); 23 patients stayed overnight (23.2%). The overall incidence of composite adverse events was 20.2% (95% CI, 13.5-29.2), and was not different between the groups (26.1% vs 18.4%, p = 0.42). Additionally, there were no differences in the QoR-40 or pain scores on POD2 and at 6 weeks. Patient satisfaction was high and similar between the groups. Successful SDD was achieved in 77.0% of the patients. SDD following vaginal hysterectomy and native-tissue colpopexy appears to be safe, feasible, and associated with good QoR and a high degree of patient satisfaction.

Meaningful consumer involvement in cancer care: a systematic review on co-design methods and processes.

Although the benefits of consumer involvement in research and health care initiatives are known, there is a need to optimize this for all people with cancer. This systematic review aimed to synthesize and evaluate the application of co-design in the oncology literature and develop recommendations to guide the application of optimal co-design processes and reporting in oncology research, practice, and policy. A systematic review of co-design studies in adults with cancer was conducted, searching MEDLINE, CINAHL, Embase, and PsycINFO databases and included studies focused on 2 concepts, co-design and oncology. A total of 5652 titles and abstracts were screened, resulting in 66 eligible publications reporting on 51 unique studies. Four frameworks were applied to describe the co-design initiatives. Most co-design initiatives were designed for use in an outpatient setting (n = 38; 74%) and were predominantly digital resources (n = 14; 27%) or apps (n = 12; 23%). Most studies (n = 25; 49%) used a co-production approach to consumer engagement. Although some studies presented strong co-design methodology, most (n = 36; 70%) did not report the co-design approach, and 14% used no framework. Reporting was poor for the participant level of involvement, the frequency, and time commitment of co-design sessions. Consumer participation level was predominantly collaborate (n = 25; 49%). There are opportunities to improve the application of co-design in oncology research. This review has generated recommendations to guide 1) methodology and frameworks, 2) recruitment and engagement of co-design participants, and 3) evaluation of the co-design process. These recommendations can help drive appropriate, meaningful, and equitable co-design, leading to better cancer research and care.

Examining global and gender disparities in high-impact evidence synthesis on lung cancer: A 2000-2024 analysis of Cochrane Library.

e23021 Background: Most cancer-related deaths occur in low-middle-income countries (LMICs), yet LMICs are underrepresented in global oncology research. Women have also historically been underrepresented in clinical literature. High-impact evidence synthesis influences guidelines and practice worldwide, so equitable authorship can ensure that issues presented are applicable globally. The Cochrane Library is a repository of high-impact systematic reviews that can be authored from all over the world. So, we aimed to analyze the representation of LMICs and women in the authorship of lung-cancer-related Cochrane Reviews. Methods: From the topic 'Lung and Airways' in the Cochrane Library, we included all studies related to lung cancer, published till February 2, 2024. We extracted the authors’ national affiliations, categorizing them into LMICs and non-LMICs based on the 2023 World Bank income classifications. Collaboratives/ groups were considered as a single entity. Following this, we manually captured at least one webpage for each author showing their gender or gender pronouns. For authors whose gender could not be determined via manual search, we used Gender-API, an artificial intelligence-based software, to determine their gender based on their name and country. Authors with &lt; 90% certainty of gender on Gender-API were categorized as unknown. Results: We included 42 reviews that had 233 authors, including three group authors. United Kingdom (22.32%; n = 52/233), followed by Australia (16.31%; n = 38/233), Spain (13.3%; n = 31/233), China (9.01%; n = 21/233) and France (6.87%; n = 16/233) were the most represented countries. There were no authors from LMICs. Manually, we ascertained gender for 85.04% (n = 194/228) of authors, and overall, for 94.74% (n = 216/228). Women constituted 42.6% (n = 92/216) of all authors. They were, however, better represented as first authors (50%; n = 19/38) and corresponding authors (54.05%; n = 20/37). Conclusions: Despite suffering the brunt of cancer, LMICs had no representation in lung-cancer-related Cochrane reviews. While authorship had a male preponderance overall, women were well represented as first and corresponding authors. Addressing authorship disparities in global oncology literature, via mentorship and capacity building, can improve its applicability and utilization.

Utilizing large language models (LLMs) to pre-label candidate concepts from in conceptual development landscape reviews in oncology.

e23198 Background: Labeling and identifying concepts from qualitative studies and patient interviews in oncology can be challenging and time consuming, often requiring several iterations. Large language models (LLMs) may be tailored to serve as a ‘co-pilot’, thus reducing errors and time to completion. We therefore aimed to examine whether utilizing LLMs to pre-label concepts (i.e., how patient’s feel or function) from medical oncology literature text can be done at comparable accuracy as human. To examine whether such LLM pre-labelling can dramatically reduce the time required for manual labor in conceptual development landscape reviews in oncology. Methods: We developed GPT-4 (OpenAI) prompts to pre-label concepts reported in abstracts of qualitative study references. We further developed GPT-4 prompts to categorize each pre-labeled concept into one of the following relevant high-level category: clinician reported symptoms, cognitive impacts, symptoms due to treatment, symptoms due to diagnosis, emotional impacts, impact on caregiver, other impacts, physical appearance, physical function, and social impacts. The prompts were extended to also capture diagnosis, treatments, patient reported outcomes, as well as generic terms or irrelevant terms that would otherwise erroneously be captured under the concept category in the early iterations of the prompt-engineering. The prompts were tested on 48, 37, and 38 (total of 123) eligible references from three conceptual development reviews covering colorectal cancer (CRC), non-small cell lung cancer (NSCLC), and acute myeloid leukemia (AML), respectively. Results: The LLM pre-labelled a total of 153, 131, and 159 candidate concepts across the CRC, NSCLC, and AML reviews, respectively. In all three reviews, clinical reported symptoms, emotional impacts, and social impacts all accounted for 18-25% each of the pre-labelled concepts, whereas physical function and social impact accounted for 5-9% each. A total of 2 (1.3%), 3 (2.3%) and 4 (2.5%) pre-labels were predicted to belong to the wrong high-level category. Incorrectly categorized labels were dispersed across most categories and should have been categorized as ‘other impacts’. In the NSCLC review, one pre-label categorized as impact on caregiver and two as other impacts were erroneously extracted concepts. Conclusions: LLMs are effective at capturing and pre-labelling concepts for further review, evident by the high number of concept labels extracted. Further high-level categorization with LLMs to guide manual reviewers also appears highly accurate.

Unlocking the potential: the neutrophil-to-lymphocyte ratio (NLR) and the platelet-to-lymphocyte ratio (PLR) as biomarkers informing immunotherapy outcomes in lung cancer patients — single oncology center experience and literature review

Unlocking the potential: the neutrophil-to-lymphocyte ratio (NLR) and the platelet-to-lymphocyte ratio (PLR) as biomarkers informing immunotherapy outcomes in lung cancer patients — single oncology center experience and literature review

Hypoxia-induced miR-181a-5p up-regulation reduces epirubicin sensitivity in breast cancer cells through inhibiting EPDR1/TRPC1 to activate PI3K/AKT signaling pathway

Breast carcinoma (BC) ranks as a predominant malignancy and constitutes the second principal cause of mortality among women globally. Epirubicin stands as the drug of choice for BC therapeutics. Nevertheless, the emergence of chemoresistance has significantly curtailed its therapeutic efficacy. The resistance mechanisms to Epirubicin remain not entirely elucidated, yet they are conjectured to stem from diminished tumor vascular perfusion and resultant hypoxia consequent to Epirubicin administration. In our investigation, we meticulously scrutinized the Gene Expression Omnibus database for EPDR1, a gene implicated in hypoxia and Epirubicin resistance in BC. Subsequently, we delineated the impact of EPDR1 on cellular proliferation, motility, invasive capabilities, and interstitial-related proteins in BC cells, employing methodologies such as the CCK-8 assay, Transwell assay, and western blot analysis. Our research further unveiled that hypoxia-induced miR-181a-5p orchestrates the regulation of BC cell duplication, migration, invasion, and interstitial-related protein expression via modulation of EPDR1. In addition, we identified TRPC1, a gene associated with EPDR1 expression in BC, and substantiated that EPDR1 influences BC cellular dynamics through TRPC1-mediated modulation of the PI3K/AKT signaling cascade. Our findings underscore the pivotal role of EPDR1 in the development of BC. EPDR1 was found to be expressed at subdued levels in BC tissues, Epirubicin-resistant BC cells, and hypoxic BC cells. The overexpression of EPDR1 curtailed BC cell proliferation, motility, invasiveness, and the expression of interstitial-related proteins. At a mechanistic level, the overexpression of hypoxia-induced miR-181a-5p was observed to inhibit the EPDR1/TRPC1 axis, thereby activating the PI3K/AKT signaling pathway and diminishing the sensitivity to Epirubicin in BC cells. In summation, our study demonstrates that the augmentation of hypoxia-induced miR-181a-5p diminishes Epirubicin sensitivity in BC cells by attenuating EPDR1/TRPC1 expression, thereby invigorating the PI3K/AKT signaling pathway. This exposition offers a theoretical foundation for the application of Epirubicin in BC therapy, marking a significant contribution to the existing body of oncological literature.

Angiosarcoma in children: the experience of the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology and literature review

Angiosarcoma is a rare and highly malignant endothelial tumor, which occurs mainly in adults and is extremely rare in children and adolescents. The German guidelines for the treatment of soft tissue sarcomas provided by the Cooperative Weichteilsarkom Studiengruppe in 2012 included a separate therapeutic regimen for pediatric angiosarcoma consisting of a combination of vincristine/doxorubicin/cyclophosphamide (VDC) and paclitaxel. The aim of this article was to describe the epidemiological, clinical, and morphological characteristics of angiosarcoma, to review treatment approaches, and to present the experience of the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology of Ministry of Healthcare of the Russian Federation in the treatment of children with angiosarcoma. Our study was approved by the Independent Ethics Committee and the Scientific Council of the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology of Ministry of Healthcare of the Russian Federation. The study included 5 patients diagnosed with angiosarcoma who had received treatment between 2012 and 2022. The patients’ parents gave consent to the use of their child's data, including photographs, for research purposes and in publications. Data on the patients’ age, gender, tumor location and extension, performed treatment and outcomes of the disease were analyzed. The male:female ratio was 0.66:1 and the median age was 5.2 years. Tumors were located in the soft tissues (n = 3) and in the bones (n = 2). In all the cases, invasion of the surrounding tissues was observed. There were no distant metastases at the time of diagnosis. Two (40%) patients underwent primary resection (R1) and 3 (60%) patients had tumor biopsy. Four patients received therapy according to the German guidelines for the treatment of angiosarcoma (VDC/paclitaxel courses), and 1 patient received treatment according to the guidelines for the management of non-rhabdomyosarcoma soft-tissue sarcomas (courses with vincristine, ifosfamide, doxorubicin/ vincristine, ifosfamide, actinomycin D). Objective response to treatment was achieved in 3 (60%) cases. Local control treatment of these 3 patients consisted of radiation therapy with a total dose of 50.4 Gy after R1 resection in 2 cases and biopsy in 1 case. After a median follow-up of 32 months, 2 patients who had received VDC/paclitaxel were alive without events (with complete and partial response), 3 patients died of progressive disease. Our data confirm the aggressive behavior of angiosarcoma in children. Protocol therapy that includes multiagent chemotherapy based on paclitaxel and doxorubicin along with local control treatment makes it possible to achieve a long-term control of the disease in some patients. However, further research on molecular and genetic characteristics of angiosarcoma is required to find potential novel targets for molecular targeted therapy. Further studies investigating the effectiveness of checkpoint inhibitors in angiosarcoma are also needed.

Anti(angiogenic) food components: can be a major source of bias in the investigation of angiogenesis inhibitors.

Natural and diet-derived angiogenesis inhibitors/promotors are widely found in diets. These compounds can in several ways impact the results of oncological research of angiogenesis inhibitors. We very briefly overview some of the most important examples to show how these compounds can create a bias in current research of cancer. Implications of this expert opinion cover similar angiogenesis-related diseases. Significant intra-individual differences in terms of dietary intake and differential effect of food processing techniques result in differential bioactivity and bioavailability of these compounds. There are only a handful of validated dietary questionnaire to quantify natural angiogenesis inhibitors/promotors. A corollary consequence is that participants in non-randomized clinical trials will have different baseline levels of serum/plasma/tissue/organ diet-derived angiogenesis inhibitors/promotors. This will lead to creation of clinical uncertainty and a hidden bias and consequently creation of translational efficiency bias, sampling efficiency, and waste of resources. We call for developing and validating a semi-quantitative food frequency questionnaire (FFQ) to gather data on these agents, specifically designed for oncological research because there is a clear gap in the literature of oncology. This might facilitate the discovery of better prognostic, diagnostic, preventive measures, and therapeutic agents for the management of different cancers. Implications of this paper cover similar settings like ophthalmologic research.

Ethics-Guided Radiation Therapy (EGRT): A necessity in radiation oncology practice

Medical ethics principles have been the basis of medical practice since early human civilization. The well-accepted principles are autonomy, beneficence, non-maleficence, and justice. With the advancement of academia, industry, medicine, and technology, there is a need to empower ethics-guided radiation therapy (EGRT). A PubMed search was done on Oct. 22, 2023, using the words: (“Radiotherapy”[Mesh]) AND “Ethics, Clinical”[Mesh]) and the results were a total of 58. Among these, 17 titles seem to be in relation, but only a handful were of intimate relation to ethics and radiotherapy. An additional handful of non-PubMed references were found. EGRT, in my opinion, is a new acronym for an old concept that needs further elaboration and experts’ consensus in the modern radiation oncology literature. In parallel with the technological advances in radiotherapy, like intensity-modulated radiation therapy “IMRT” and image-guided radiation therapy “IGRT,” we are aiming to create an initiative to establish EGRT to be like a model that every radiation oncologist can follow in the daily radiotherapy practice. The coming work will be composed of an extensive literature review, international survey, and expert consensus, and it is intended to be a base for further efforts in this aspect.

Survival analysis from the INCREASE study in PH-ILD: evaluating the impact of treatment crossover on overall mortality

ObjectiveA post-hoc analysis of the INCREASE trial and its open-label extension (OLE) was performed to evaluate whether inhaled treprostinil has a long-term survival benefit in patients with pulmonary hypertension associated...

The Concerning Disaggregation of Gender and Racial/Ethnicity Disparity Investigation at Recent ASCO Annual Meetings.

There has been a recent emphasis in the peer-reviewed oncology literature on examining disparities by gender. Such emphasis provides an excellent opportunity to simultaneously examine race/ethnicity disparities in the same cohort. The degree to which gender disparities research has been performed concomitantly with racial disparities research at prominent oncologic societies has yet to be investigated. ABSTRACTs presented at the American Society of Clinical Oncology (ASCO) annual meeting were reviewed. Abstracts selected for the oral abstract or clinical science symposium sessions at the 2020, 2021, and 2022 annual meetings were evaluated to determine the amount of gender disparities research presented. Such research was further assessed to determine whether racial/ethnicity disparities were examined simultaneously. From 2020 to 2022, 1219 abstracts were presented at the ASCO annual meetings, oral abstract or clinical science symposium sessions. Of these, 7 involved gender disparities examination, of which only 2 (29%) concomitantly examined race/ethnicity. No study since 2020 concomitantly examined gender and racial disparities. More than 70% of gender disparities work presented at ASCO has been disaggregated from concomitant racial disparities examination, with complete disaggregation since 2021. Gender disparities work remains a miniscule aspect of the overall research landscape. Future work in examining gender disparities may be best aggregated with racial/ethnicity disparities to optimize timely solutions in both areas; such work could potentially be incentivized from the inclusion criteria of future funding mechanisms.

ChatGPT is an Unreliable Tool for Reviewing Radiation Oncology Literature

To assess whether ChatGPT, a popular deep learning text generation tool, can serve as a resource for in-training and practicing clinicians by accurately identifying and summarizing studies related to radiation oncology. Three question templates (Q1-Q3, shown in Table 1) were applied to eight cancer types to compile 24 questions posed to ChatGPT. Cancer types were designated as either common (breast, non-small cell lung, prostate, p16 positive oropharyngeal, and rectal) or uncommon (hypopharyngeal, medulloblastoma, and vulvar). ChatGPT's responses to each question were then reviewed to quantify the number of studies referenced in the response, the percentage of studies listed that were real studies, and the percentage of studies listed that were correctly summarized. Outcomes were compared between cancer types (common vs uncommon) and question types using Wilcoxon rank sum tests. As a secondary analysis, we assessed internal consistency of ChatGPT's responses by querying ChatGPT with three identical iterations of Q1-Q3 for breast cancer and comparing its responses between iterations. Across all 24 of ChatGPT's responses, there were 78 studies referenced, of which 37 (47.4%) were real studies and 7 (9.0%) were correctly summarized. On average, each response included 3.25 (standard deviation (SD): 0.74) studies, of which 44.0% (SD: 44.2%) were real studies and 7.8% (SD: 14.6%) were correctly summarized. The proportion of correctly summarized studies was not significantly different between common vs uncommon cancers [p = 0.29], between questions that specified randomized-control trials (Q3) vs not (Q1 or Q2) [p = 0.94], or between questions that specified intensity modulated radiotherapy (Q2) vs not (Q1 or Q3) [p = 0.31]. Across the three iterations of ChatGPT queries for breast cancer, the number of studies listed for Q1, Q2, and Q3 ranged from 3 to 5, 2 to 3, and 3 to 5, respectively; the number of correctly summarized studies listed for each question ranged from 0 to 2, 0 to 1, and 0 to 1, respectively. ChatGPT's responses consistently included a large proportion of non-existent and incorrectly summarized studies. Furthermore, our secondary analysis suggests variability in the content and accuracy of ChatGPT responses to identical questions, raising further concerns regarding reliability. Overall, our findings argue against the use of ChatGPT as a tool for reviewing literature related to radiation oncology.

Benefits beyond cardiometabolic health: the potential of frequent high intensity 'exercise snacks' to improve outcomes for those living with and beyond cancer.

High intensity interval training (HIIT) has been shown to consistently elicit rapid and significant adaptations in a number of physiological systems, across many different healthy and clinical populations. In addition, there is increasing interest in how some acute, yet transient responses to high intensity exercise potentially reduce the risks of particular diseases. Recent work has shown that discrete, brief bouts of high intensity exercise (termed 'exercise snacks') can improve glucose control and vascular health and thus counter the negative cardiometabolic consequences of prolonged, uninterrupted periods of inactivity. In this brief review, we advance the case, using evidence available from pre-clinical studies in the exercise oncology literature, that brief, frequently completed bouts of high intensity exercise embedded within an individual's overall daily and weekly physical activity schedule, may transiently impact the tumour microenvironment and improve the health outcomes for those who have been diagnosed and treated for cancer.

Declarations of Independence: How Embedded Multicollinearity Errors Affect Dosimetric and Other Complex Analyses in Radiation Oncology

The statistical technique of multiple regression, commonly referred to as “multivariable regression,” is often used in clinical research to quantify the relationships between multiple predictor variables and a single outcome variable of interest. The foundational theory underpinning multivariable regression assumes that all predictor variables are independent of one another. In other words, the effect of each independent variable is measured by its contribution to the regression equation while all other variables remain unchanged. In the presence of correlations between two or more variables, however, it is impossible to change one variable without a consequent change in the variable(s) it is linked to. This condition, known as “multicollinearity,” can introduce errors into multivariable regression models by affecting estimates of the regression coefficients that quantify the relationship between individual predictor variables and the outcome variable. Errors that arise due to violations of the multicollinearity assumption are of special interest to radiation oncology researchers. Because of high levels of correlation among variables derived from points along individual organ dose-volume histogram (DVH) curves, as well as strong intercorrelations among dose-volume parameters in neighboring organs, dosimetric analyses are particularly subject to multicollinearity errors. For example, dose-volume parameters for the heart are strongly correlated not only with other points along the heart DVH curve but are likely also correlated with dose-volume parameters in neighboring organs such as the lung. In this paper, we describe the problem of multicollinearity in accessible terms and discuss examples of violations of the multicollinearity assumption within the radiation oncology literature. Finally, we provide recommendations regarding best practices for identifying and managing multicollinearity in complex data sets.

Prevalence of primary malignant tumours, rates of pathological fracture, and mortality in the setting of metastatic bone disease.

The modern prevalence of primary tumours causing metastatic bone disease is ill-defined in the oncological literature. Therefore, the purpose of this study is to identify the prevalence of primary tumours in the setting of metastatic bone disease, as well as reported rates of pathological fracture, postoperative complications, 90-day mortality, and 360-day mortality for each primary tumour subtype. The Premier Healthcare Database was queried to identify all patients who were diagnosed with metastatic bone disease from January 2015 to December 2020. The prevalence of all primary tumour subtypes was tabulated. Rates of long bone pathological fracture, 90-day mortality, and 360-day mortality following surgical treatment of pathological fracture were assessed for each primary tumour subtype. Patient characteristics and postoperative outcomes were analyzed based upon whether patients had impending fractures treated prophylactically versus treated completed fractures. In total, 407,893 unique patients with metastatic bone disease were identified. Of the 14 primary tumours assessed, metastatic bone disease most frequently originated from lung (24.8%), prostatic (19.4%), breast (19.3%), gastrointestinal (9.4%), and urological (6.5%) malignancies. The top five malignant tumours resulting in long bone pathological fracture were renal (5.8%), myeloma (3.4%), female reproductive (3.2%), lung (2.8%), and breast (2.7%). Following treatment of pathological fractures of long bones, 90-day mortality rates were greatest for lung (12.1%), central nervous system (10.5%), lymphoma (10.4%), gastrointestinal (10.1%), and non-renal urinary (10.0%) malignancies. Finally, our study demonstrates improved 90-day and 360-day survival in patients treated for impending pathological fracture compared to completed fracture, as well as significantly lower rates of deep vein thrombosis, pulmonary embolism, urinary tract infection, and blood transfusion. This study defines the contemporary characteristics of primary malignancies resulting in metastatic bone disease. These data should be considered by surgeons when prognosticating patient outcomes during treatment of their metastatic bone disease.