Mechanisms of Action in FLASH Radiotherapy: A Comprehensive Review of Physicochemical and Biological Processes on Cancerous and Normal Cells.

The advent of FLASH radiotherapy (FLASH-RT) has brought forth a paradigm shift in cancer treatment, showcasing remarkable normal cell sparing effects with ultra-high dose rates (>40 Gy/s). This review delves into the multifaceted mechanisms underpinning the efficacy of FLASH effect, examining both physicochemical and biological hypotheses in cell biophysics. The physicochemical process encompasses oxygen depletion, reactive oxygen species, and free radical recombination. In parallel, the biological process explores the FLASH effect on the immune system and on blood vessels in treatment sites such as the brain, lung, gastrointestinal tract, skin, and subcutaneous tissue. This review investigated the selective targeting of cancer cells and the modulation of the tumor microenvironment through FLASH-RT. Examining these mechanisms, we explore the implications and challenges of integrating FLASH-RT into cancer treatment. The potential to spare normal cells, boost the immune response, and modify the tumor vasculature offers new therapeutic strategies. Despite progress in understanding FLASH-RT, this review highlights knowledge gaps, emphasizing the need for further research to optimize its clinical applications. The synthesis of physicochemical and biological insights serves as a comprehensive resource for cell biology, molecular biology, and biophysics researchers and clinicians navigating the evolution of FLASH-RT in cancer therapy.

Using the genomic adjusted radiation dose (GARD) to personalize the radiation dose in nasopharyngeal cancer.

BACKGROUND: Locally advanced nasopharyngeal cancer (NPC) patients undergoing radiotherapy are at risk of treatment failure, particularly locoregional recurrence. To optimize the individual radiation dose, we hypothesize that the genomic adjusted radiation dose (GARD) can be used to correlate with locoregional control. METHODS: A total of 92 patients with American Joint Committee on Cancer / International Union Against Cancer stage III to stage IVB recruited in a randomized phase III trial were assessed (NPC-0501) (NCT00379262). Patients were treated with concurrent chemo-radiotherapy plus (neo) adjuvant chemotherapy. The primary endpoint is locoregional failure free rate (LRFFR). RESULTS: Despite the homogenous physical radiation dose prescribed (Median: 70 Gy, range 66-76 Gy), there was a wide range of GARD values (median: 50.7, range 31.1-67.8) in this cohort. In multivariable analysis, a GARD threshold (GARDT) of 45 was independently associated with LRFFR (p = 0.008). By evaluating the physical dose required to achieve the GARDT (RxRSI), three distinct clinical subgroups were identified: (1) radiosensitive tumors that RxRSI at dose < 66 Gy (N = 59, 64.1 %) (b) moderately radiosensitive tumors that RxRSI dose within the current standard of care range (66-74 Gy) (N = 20, 21.7 %), (c) radioresistant tumors that need a significant dose escalation above the current standard of care (>74 Gy) (N = 13, 14.1 %). CONCLUSION: GARD is independently associated with locoregional control in radiotherapy-treated NPC patients from a Phase 3 clinical trial. GARD may be a potential framework to personalize radiotherapy dose for NPC patients.

A user-friendly deep learning application for accurate lung cancer diagnosis.

BACKGROUND: Accurate diagnosis and subsequent delineated treatment planning require the experience of clinicians in the handling of their case numbers. However, applying deep learning in image processing is useful in creating tools that promise faster high-quality diagnoses, but the accuracy and precision of 3-D image processing from 2-D data may be limited by factors such as superposition of organs, distortion and magnification, and detection of new pathologies. The purpose of this research is to use radiomics and deep learning to develop a tool for lung cancer diagnosis. METHODS: This study applies radiomics and deep learning in the diagnosis of lung cancer to help clinicians accurately analyze the images and thereby provide the appropriate treatment planning. 86 patients were recruited from Bach Mai Hospital, and 1012 patients were collected from an open-source database. First, deep learning has been applied in the process of segmentation by U-NET and cancer classification via the use of the DenseNet model. Second, the radiomics were applied for measuring and calculating diameter, surface area, and volume. Finally, the hardware also was designed by connecting between Arduino Nano and MFRC522 module for reading data from the tag. In addition, the displayed interface was created on a web platform using Python through Streamlit. RESULTS: The applied segmentation model yielded a validation loss of 0.498, a train loss of 0.27, a cancer classification validation loss of 0.78, and a training accuracy of 0.98. The outcomes of the diagnostic capabilities of lung cancer (recognition and classification of lung cancer from chest CT scans) were quite successful. CONCLUSIONS: The model provided means for storing and updating patients' data directly on the interface which allowed the results to be readily available for the health care providers. The developed system will improve clinical communication and information exchange. Moreover, it can manage efforts by generating correlated and coherent summaries of cancer diagnoses.

Neurological complications of modern radiotherapy for head and neck cancer.

Radiotherapy is one of the mainstay treatment modalities for the management of non-metastatic head and neck cancer (HNC). Notable improvements in treatment outcomes have been observed in the recent decades. Modern radiotherapy techniques, such as intensity-modulated radiotherapy and charged particle therapy, have significantly improved tumor target conformity and enabled better preservation of normal structures. However, because of the intricate anatomy of the head and neck region, multiple critical neurological structures such as the brain, brainstem, spinal cord, cranial nerves, nerve plexuses, autonomic pathways, brain vasculature, and neurosensory organs, are variably irradiated during treatment, particularly when tumor targets are in close proximity. Consequently, a diverse spectrum of late neurological sequelae may manifest in HNC survivors. These neurological complications commonly result in irreversible symptoms, impair patients' quality of life, and contribute to a substantial proportion of non-cancer deaths. Although the relationship between radiation dose and toxicity has not been fully elucidated for all complications, appropriate application of dosimetric constraints during radiotherapy planning may reduce their incidence. Vigilant surveillance during the course of survivorship also enables early detection and intervention. This article endeavors to provide a comprehensive review of the various neurological complications of modern radiotherapy for HNC, summarize the current incidence data, discuss methods to minimize their risks during radiotherapy planning, and highlight potential strategies for managing these debilitating toxicities.

Dosimetric parameters predict radiation-induced temporal lobe necrosis in nasopharyngeal carcinoma patients: A systematic review and meta-analysis.

This systematic review examines the role of dosimetric parameters in predicting temporal lobe necrosis (TLN) risk in nasopharyngeal carcinoma (NPC) patients treated with three-dimensional conformal RT (3D-CRT), intensity-modulated radiation therapy (IMRT) and volumetric modulated arc therapy (VMAT). TLN is a serious late complication that can adversely affect the quality of life of NPC patients. Understanding the relationship between dosimetric parameters and TLN can guide treatment planning and minimize radiation-related complications. A comprehensive search identified relevant studies published up to July 2023. Studies reporting on dosimetric parameters and TLN in NPC patients undergoing 3D-CRT, IMRT, and VMAT were included. TLN incidence, follow-up duration, and correlation with dosimetric parameters of the temporal lobe were analyzed. The review included 30 studies with median follow-up durations ranging from 28 to 110 months. The crude incidence of TLN varied from 2.3 % to 47.3 % and the average crude incidence of TLN is approximately 14 %. Dmax and D1cc emerged as potential predictors of TLN in 3D-CRT and IMRT-treated NPC patients. Threshold values of >72 Gy for Dmax and >62 Gy for D1cc were associated with increased TLN risk. However, other factors should also be considered, including host characteristics, tumor-specific features and therapeutic factors. In conclusion, this systematic review highlights the significance of dosimetric parameters, particularly Dmax and D1cc, in predicting TLN risk in NPC patients undergoing 3D-CRT, IMRT, and VMAT. The findings provide valuable insights that can help in developing optimal treatment planning strategies and contribute to the development of clinical guidelines in this field.

Multi-domain neurocognitive impairment following definitive intensity-modulated radiotherapy for nasopharyngeal cancer: A cross-sectional study.

INTRODUCTION: Neurocognitive impairment from inadvertent brain irradiation is common following intensity-modulated radiotherapy (IMRT) for nasopharyngeal carcinoma (NPC). This study aimed to determine the prevalence, pattern, and radiation dose-toxicity relationship of this late complication. MATERIALS AND METHODS: We undertook a cross-sectional study of 190 post-IMRT NPC survivors. Neurocognitive function was screened using the Montreal Cognitive Assessment-Hong Kong (HK-MoCA). Detailed assessments of eight distinct neurocognitive domains were conducted: intellectual capacity (WAIS-IV), attention span (Digit Span and Visual Spatial Span), visual memory (Visual Reproduction Span), verbal memory (Auditory Verbal Learning Test), processing speed (Color Trail Test), executive function (Stroop Test), motor dexterity (Grooved Pegboard Test) and language ability (Verbal Fluency Test). The mean percentiles and Z-scores were compared with normative population data. Associations between radiation dose and brain substructures were explored using multivariable logistic regression. RESULTS: The median post-IMRT interval was 7.0 years. The prevalence of impaired HK-MoCA was 25.3 % (48/190). Among the participants, 151 (79.4 %) exhibited impairments in at least one neurocognitive domain. The predominantly impaired domains included verbal memory (short-term: mean Z-score, -0.56, p < 0.001; long-term: mean Z-score, -0.70, p < 0.001), processing speed (basic: mean Z-score, -1.04, p < 0.001; advanced: mean Z-score, -0.38, p < 0.001), executive function (mean Z-score, -1.90, p < 0.001), and motor dexterity (dominant hand: mean Z-score, -0.97, p < 0.001). Radiation dose to the whole brain, hippocampus, and temporal lobe was associated with impairments in executive function, verbal memory, processing speed, and motor dexterity. CONCLUSIONS: Neurocognitive impairment is prevalent and profound in post-IMRT NPC survivors. Cognitive assessment and rehabilitation should be considered part of survivorship care.

An Update on Anti-TNF Biosimilar Switching-Real-World Clinical Effectiveness and Safety.

Background: Biological medications for inflammatory bowel disease (IBD) account for a significant burden on provincial budgets. In an effort to curb these rising costs, nationwide switching to biosimilars is expected to be complete in Canada before the end of 2023. Biosimilar products do not require the same rigor for licensing as the originator and therefore there has been appropriate scepticism as to how biosimilars will perform in real-world practice. Methods: We have performed a systematic review including real-world observational studies of adult patients with IBD. The primary outcome was clinical effectiveness and/or safety in patients who had switched from originator to biosimilar anti-TNF. Secondary outcomes included loss of response (LOR), treatment persistence or cessation and immunogenicity. Results: We included 43 studies (7,462 patients [70 percent Crohn's disease: 30 percent ulcerative colitis]; 32 infliximab studies, and 11 adalimumab studies). For infliximab, 75 percent patients were in clinical remission at the time of switch and 75 percent maintained clinical remission beyond 12 months, compared to 78 percent of patients who continued originator. For adalimumab, 86 percent patients were in remission at the time of switch with 82 percent maintaining remission at 6 months follow-up. Injection site pain was higher in patients who switched to a citrate containing adalimumab biosimilar, compared with those who continued originator. All other outcomes (LOR, treatment cessation or persistence and serious adverse events) were similar to patients who continued originator (in comparator cohorts or the available literature). Conclusion: Whilst ongoing vigilance is required, these data are reassuring to both patients and clinicians and will significantly help to reduce health-care costs across Canada.

Computer-assisted and robotic implant surgery: Assessing the outcome measures of accuracy and educational implications.

OBJECTIVE: This scoping review aimed to (1) critically evaluate the outcomes measures used to assess the accuracy of implant placement with Computer Assisted Implant Surgery (CAIS) and (2) review the evidence supporting the efficient implementation of CAIS in training and education of clinicians. METHODS: A scoping literature review was conducted aiming to identify (a) clinical trials assessing accuracy of implant placement with CAIS, and (b) clinical trials or simulation/cadaver studies where CAIS was utilised and assessed for the training/education of clinicians. Studies since 1995 were assessed for suitability and data related to the outcomes measures of accuracy and educational efficacy were extracted and synthesised. RESULTS: Accuracy of CAIS has been mainly assessed through surrogate measures. Individual clinical trials have not shown any difference between static and dynamic CAIS, but recent meta-analyses suggest an advantage of dynamic CAIS in reducing angular deviation. The combination of static and dynamic CAIS might offer higher accuracy than each of the two used alone. Dynamic CAIS is suitable for novice surgeons and might even have added value as an education tool for implant surgery, although mastering the technique requires longer training than static. CONCLUSION: Meta-analyses of large samples, new and diverse outcomes measures, as well as benchmarking of levels of accuracy with specific clinical outcomes will help to better understand the potential and limitations of CAIS. Dynamic CAIS is suitable for novice operators, but educational interventions distributed over longer periods of time will be required for mastery of the process.

Dosimetric and radiobiological comparison between conventional and hypofractionated breast treatment plans using the Halcyon system.

Purpose: The objective of this research is to compare the efficacy of conventional and hypofractionated radiotherapy treatment plans for breast cancer patients, with a specific focus on the unique features of the Halcyon system. Methods and materials: The study collected and analyzed dose volume histogram (DVH) data for two groups of treatment plans implemented using the Halcyon system. The first group consisted of 19 patients who received conventional fractionated (CF) treatment with a total dose of 50 Gy in 25 fractions, while the second group comprised 9 patients who received hypofractionated (HF) treatment with a total dose of 42.56 Gy in 16 fractions. The DVH data was used to calculate various parameters, including tumor control probability (TCP), normal tissue complication probability (NTCP), and equivalent uniform dose (EUD), using radiobiological models. Results: The results indicated that the CF plan resulted in higher TCP but lower NTCP for the lungs compared to the HF plan. The EUD for the HF plan was approximately 49 Gy (114% of its total dose) while that for the CF plan was around 53 Gy (107% of its total dose). Conclusions: The analysis suggests that while the CF plan is better at controlling tumors, it is not as effective as the HF plan in minimizing side effects. Additionally, it is suggested that there may be an optimal configuration for the HF plan that can provide the same or higher EUD than the CF plan.

Circumvention of Gefitinib Resistance by Repurposing Flunarizine via Histone Deacetylase Inhibition.

Gefitinib is an epidermal growth factor receptor tyrosine kinase inhibitor (EGFR TKI) for treating advanced non-small cell lung cancer (NSCLC). However, drug resistance seriously impedes the clinical efficacy of gefitinib. This study investigated the repositioning of the non-oncology drug capable of inhibiting histone deacetylases (HDACs) to overcome gefitinib resistance. A few drug candidates were identified using the in silico repurposing tool "DRUGSURV" and tested for HDAC inhibition. Flunarizine, originally indicated for migraine prophylaxis and vertigo treatment, was selected for detailed investigation in NSCLC cell lines harboring a range of different gefitinib resistance mechanisms (EGFR T790M, KRAS G12S, MET amplification, or PTEN loss). The circumvention of gefitinib resistance by flunarizine was further demonstrated in an EGFR TKI (erlotinib)-refractory patient-derived tumor xenograft (PDX) model in vivo. The acetylation level of cellular histone protein was increased by flunarizine in a concentration- and time-dependent manner. Among the NSCLC cell lines evaluated, the extent of gefitinib resistance circumvention by flunarizine was found to be the most pronounced in EGFR T790M-bearing H1975 cells. The gefitinib-flunarizine combination was shown to induce the apoptotic protein Bim but reduce the antiapoptotic protein Bcl-2, which apparently circumvented gefitinib resistance. The induction of Bim by flunarizine was accompanied by an increase in the histone acetylation and E2F1 interaction with the BIM gene promoter. Flunarizine was also found to upregulate E-cadherin but downregulate the vimentin expression, which subsequently inhibited cancer cell migration and invasion. Importantly, flunarizine was also shown to significantly potentiate the tumor growth suppressive effect of gefitinib in EGFR TKI-refractory PDX in vivo. The findings advocate for the translational application of flunarizine to circumvent gefitinib resistance in the clinic.

Developing an AI-Assisted Educational Chatbot for Radiotherapy Using the IBM Watson Assistant Platform.

Objectives: This study aims to make radiotherapy knowledge regarding healthcare accessible to the general public by developing an AI-powered chatbot. The interactive nature of the chatbot is expected to facilitate better understanding of information on radiotherapy through communication with users. Methods: Using the IBM Watson Assistant platform on IBM Cloud, the chatbot was constructed following a pre-designed flowchart that outlines the conversation flow. This approach ensured the development of the chatbot with a clear mindset and allowed for effective tracking of the conversation. The chatbot is equipped to furnish users with information and quizzes on radiotherapy to assess their understanding of the subject. Results: By adopting a question-and-answer approach, the chatbot can engage in human-like communication with users seeking information about radiotherapy. As some users may feel anxious and struggle to articulate their queries, the chatbot is designed to be user-friendly and reassuring, providing a list of questions for the user to choose from. Feedback on the chatbot's content was mostly positive, despite a few limitations. The chatbot performed well and successfully conveyed knowledge as intended. Conclusions: There is a need to enhance the chatbot's conversation approach to improve user interaction. Including translation capabilities to cater to individuals with different first languages would also be advantageous. Lastly, the newly launched ChatGPT could potentially be developed into a medical chatbot to facilitate knowledge transfer.

ITI consensus report on zygomatic implants: indications, evaluation of surgical techniques and long-term treatment outcomes.

OBJECTIVES: The aim of the ITI Consensus Workshop on zygomatic implants was to provide Consensus Statements and Clinical Recommendations for the use of zygomatic implants. MATERIALS AND METHODS: Three systematic reviews and one narrative review were written to address focused questions on (1) the indications for the use of zygomatic implants; (2) the survival rates and complications associated with surgery in zygomatic implant placement; (3) long-term survival rates of zygomatic implants and (4) the biomechanical principles involved when zygoma implants are placed under functional loads. Based on the reviews, three working groups then developed Consensus Statements and Clinical Recommendations. These were discussed in a plenary and finalized in Delphi rounds. RESULTS: A total of 21 Consensus Statements were developed from the systematic reviews. Additionally, the group developed 17 Clinical Recommendations based on the Consensus Statements and the combined expertise of the participants. CONCLUSIONS: Zygomatic implants are mainly indicated in cases with maxillary bone atrophy or deficiency. Long-term mean zygomatic implant survival was 96.2% [95% CI 93.8; 97.7] over a mean follow-up of 75.4 months (6.3 years) with a follow-up range of 36-141.6 months (3-11.8 years). Immediate loading showed a statistically significant increase in survival over delayed loading. Sinusitis presented with a total prevalence of 14.2% [95% CI 8.8; 22.0] over a mean 65.4 months follow-up, representing the most common complication which may lead to zygomatic implant loss. The international experts suggested clinical recommendations regarding planning, surgery, restoration, outcomes, and the patient's perspective.

Efficacy, safety, and correlative biomarkers of bintrafusp alfa in recurrent or metastatic nasopharyngeal cancer patients: a phase II clinical trial.

Background: The strategy of dual blockade of TGF-ß and PD-L1 pathways has not been previously tested in platinum-refractory recurrent or metastatic nasopharyngeal cancer (R/M NPC) patients. This study aimed to evaluate the safety and efficacy of bintrafusp alfa in refractory R/M NPC patients. Methods: In this single-arm, single-centre phase II clinical trial, 38 histologically confirmed R/M NPC patients were enrolled and administered with bintrafusp alfa every 2 weeks. Primary endpoint was objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1). Secondary endpoints included progression-free survival (PFS), overall survival (OS), duration of response (DOR), and safety. Findings: Thirty-eight patients were accrued (33 men; median age, 54 years). ORR was 23.7% (complete response, n = 2; partial response, n = 7). The median DOR was 19.2 months, median PFS was 2.3 months, median OS was 17.0 months, and 1-year OS rate was 63.2%. Unfortunately, 25 patients (65.7%) progressed within 8 weeks of treatment, 15 patients (39.5%) and 8 patients (21.1%) developed hyper-progressive disease (HPD) per RECIST v1.1 and tumor growth rate (TGR) ratio respectively. Sixteen patients (42.4%) experienced ≥ grade 3 treatment-related adverse events (TRAEs), most commonly anemia (n = 9, 23.7%) and secondary malignancies (n = 4, 10.5%). TRAEs led to permanent treatment discontinuation in 7 patients. Patients with strong suppression of plasma TGFß1 level at week 8 were unexpectedly associated with worse ORR (9.1% vs 44.4%, P = 0.046) and development of HPD. There was no correlation between PD-L1 expression and ORR. Interpretation: Bintrafusp alfa demonstrated modest activity in R/M NPC but high rates of HPD and treatment discontinuation secondary to TRAEs are concerning. Funding: The project was supported by Alice Ho Miu Ling Nethersole Charity Foundation Professorship Endowed Fund and Merck KGaA.

FLASH Radiotherapy and the Use of Radiation Dosimeters.

Radiotherapy (RT) using ultra-high dose rate (UHDR) radiation, known as FLASH RT, has shown promising results in reducing normal tissue toxicity while maintaining tumor control. However, implementing FLASH RT in clinical settings presents technical challenges, including limited depth penetration and complex treatment planning. Monte Carlo (MC) simulation is a valuable tool for dose calculation in RT and has been investigated for optimizing FLASH RT. Various MC codes, such as EGSnrc, DOSXYZnrc, and Geant4, have been used to simulate dose distributions and optimize treatment plans. Accurate dosimetry is essential for FLASH RT, and radiation detectors play a crucial role in measuring dose delivery. Solid-state detectors, including diamond detectors such as microDiamond, have demonstrated linear responses and good agreement with reference detectors in UHDR and ultra-high dose per pulse (UHDPP) ranges. Ionization chambers are commonly used for dose measurement, and advancements have been made to address their response nonlinearities at UHDPP. Studies have proposed new calculation methods and empirical models for ion recombination in ionization chambers to improve their accuracy in FLASH RT. Additionally, strip-segmented ionization chamber arrays have shown potential for the experimental measurement of dose rate distribution in proton pencil beam scanning. Radiochromic films, such as GafchromicTM EBT3, have been used for absolute dose measurement and to validate MC simulation results in high-energy X-rays, triggering the FLASH effect. These films have been utilized to characterize ionization chambers and measure off-axis and depth dose distributions in FLASH RT. In conclusion, MC simulation provides accurate dose calculation and optimization for FLASH RT, while radiation detectors, including diamond detectors, ionization chambers, and radiochromic films, offer valuable tools for dosimetry in UHDR environments. Further research is needed to refine treatment planning techniques and improve detector performance to facilitate the widespread implementation of FLASH RT, potentially revolutionizing cancer treatment.

Effects of Patient-Reported Outcome Tracking and Health Information Provision via Remote Patient Monitoring Software on Patient Outcomes in Oncology Care: A Systematic Review and Meta-Analysis.

OBJECTIVES: The authors sought to 1) review the literature on the remote care model that uses remote patient monitoring software (RPMS) as key mechanisms in oncology care for symptom tracking and health information provision and (2) compare the remote care model to standard care in terms of health-related quality of life, symptom burden, health management self-efficacy, anxiety, and depression. DATA SOURCES: The search was conducted on March 23, 2022, in the Cochrane Library, MEDLINE/PubMed, PsycINFO, and CINAHL databases. RESULTS: The primary strategies for applying digital technology in remote care models are patient-reported outcomes (PRO) tracking and health information delivery. Common PRO measurements applied in the RPMS include quality of life, symptom burden, self-efficacy, anxiety, and depression. Nine randomized controlled trials testing seven RPMS interventions were examined. Compared to standard care, remote patient monitoring via RPMS was related to greater quality of life and lower physical symptom burden during cancer therapy. The RPMS incorporated into routine clinical care with nurses providing remote monitoring performed better on PRO than that not integrated. CONCLUSION: The RPMS-based remote care model improves patient outcomes during cancer treatment, and it is not inferior to standard care until the RPMS function is more integrated with existing clinical care. IMPLICATIONS FOR NURSING PRACTICE: Nurses are well-positioned to engage patients in self-care skills via RPMS and can play a vital role in integrating such a model of remote patient care into routine care practices.

Comparison of Clinical Outcomes, Pathologic Characteristics, and Immune-Related Features of Postradiation vs Sporadic Oral Cavity Squamous Cell Carcinoma.

Importance: Postradiation oral cavity squamous cell carcinoma (OCSCC) is a common secondary malignant neoplasm affecting survivors of head and neck cancer who underwent radiotherapy. The clinical, pathologic, and immune-related features of postradiation OCSCC are poorly characterized, and treatment options are limited because of surgical difficulty and high morbidity associated with reirradiation. Objective: To determine whether postradiation OCSCC has distinctive clinical, pathologic, and immune-related features compared with demographic-matched sporadic OCSCC. Design, Setting, and Participants: This retrospective matched cohort study was conducted at a single tertiary oncology center in Hong Kong. Participants included consecutive patients with OCSCC diagnosed between 2000 and 2020. Patients with postradiation OCSCC were matched with patients with sporadic OCSCC using age, year of diagnosis, sex, and anatomic subsites. Data analysis was performed from July to December 2022. Exposure: Head and neck irradiation involving the oral cavity before the diagnosis of OCSCC. Main Outcomes and Measures: The primary outcomes were relapse pattern, survival, and causes of death. Pathologic features; immunohistochemical staining for programmed death-ligand 1, PD-1, MSH6, PMS2, FOXP3, and Ki67; and mRNA expression of 31 immune-related genes were also analyzed. Results: A total of 173 patients, 60 with postradiation OCSCC (median [IQR] age, 63.8 [53.0-71.7] years; 43 men [71.7%]) and 113 with sporadic OCSCC (median [IQR] age, 64.4 [52.8-70.6] years; 83 men [73.5%]), were included. Patients with postradiation OCSCC had a higher proportion of N0 disease than those with sporadic OCSCC (50 patients [83.3%] vs 56 patients [49.6%]). With a median (IQR) follow-up of 10.2 (1.2-20.5) years, the 10-year relapse-free survival rates were lower in patients with postradiation OCSCC than sporadic OCSCC (29.6% [95% CI, 17.1%-43.2%] vs 52.4% [95% CI, 41.8%-62.0%]; P = .04), and the same was true for overall survival (30.5% [95% CI, 17.6%-44.4%] vs 52.3% [95% CI, 41.4%-62.1%]; P = .03). All relapses in patients with postradiation OCSCC were locoregional, whereas 35.2% of relapses (12 of 34 patients) in patients with sporadic OCSCC were distant. Despite similar 10-year disease-specific survival rates between the 2 groups (68.8% [95% CI, 55.8%-81.0%] vs 67.1% [95% CI, 57.5%-76.5%]; P = .91), patients with postradiation OCSCC had excess mortality due to pneumonia and cerebrovascular events. Postradiation OCSCC exhibited more adverse pathologic features (perineural invasion, worse pattern of invasion, and tumor budding), higher PD-1 expression, and higher gene expression of CD4 and TGF-ß compared with sporadic OCSCC. Conclusions and Relevance: This retrospective matched cohort study found distinctive pathologic characteristics and relapse patterns of postradiation OCSCC compared with sporadic OCSCC, which may be attributable to the lack of adjuvant radiotherapy, aggressive biologic phenotype, and different host immune response. Further exploration of the role of immune checkpoint therapy may be justified.

Exploring the merits of research performance measures that comply with the San Francisco Declaration on Research Assessment and strategies to overcome barriers of adoption: qualitative interviews with administrators and researchers.

BACKGROUND: In prior research, we identified and prioritized ten measures to assess research performance that comply with the San Francisco Declaration on Research Assessment, a principle adopted worldwide that discourages metrics-based assessment. Given the shift away from assessment based on Journal Impact Factor, we explored potential barriers to implementing and adopting the prioritized measures. METHODS: We identified administrators and researchers across six research institutes, conducted telephone interviews with consenting participants, and used qualitative description and inductive content analysis to derive themes. RESULTS: We interviewed 18 participants: 6 administrators (research institute business managers and directors) and 12 researchers (7 on appointment committees) who varied by career stage (2 early, 5 mid, 5 late). Participants appreciated that the measures were similar to those currently in use, comprehensive, relevant across disciplines, and generated using a rigorous process. They also said the reporting template was easy to understand and use. In contrast, a few administrators thought the measures were not relevant across disciplines. A few participants said it would be time-consuming and difficult to prepare narratives when reporting the measures, and several thought that it would be difficult to objectively evaluate researchers from a different discipline without considerable effort to read their work. Strategies viewed as necessary to overcome barriers and support implementation of the measures included high-level endorsement of the measures, an official launch accompanied by a multi-pronged communication strategy, training for both researchers and evaluators, administrative support or automated reporting for researchers, guidance for evaluators, and sharing of approaches across research institutes. CONCLUSIONS: While participants identified many strengths of the measures, they also identified a few limitations and offered corresponding strategies to address the barriers that we will apply at our organization. Ongoing work is needed to develop a framework to help evaluators translate the measures into an overall assessment. Given little prior research that identified research assessment measures and strategies to support adoption of those measures, this research may be of interest to other organizations that assess the quality and impact of research.

Explainable machine learning via intra-tumoral radiomics feature mapping for patient stratification in adjuvant chemotherapy for locoregionally advanced nasopharyngeal carcinoma.

PURPOSE: This study aimed to discover intra-tumor heterogeneity signature and validate its predictive value for adjuvant chemotherapy (ACT) following concurrent chemoradiotherapy (CCRT) in locoregionally advanced nasopharyngeal carcinoma (LA-NPC). MATERIALS AND METHODS: 397 LA-NPC patients were retrospectively enrolled. Pre-treatment contrast-enhanced T1-weighted (CET1-w) MR images, clinical variables, and follow-up were retrospectively collected. We identified single predictive radiomic feature from primary gross tumor volume (GTVnp) and defined predicted subvolume by calculating voxel-wised feature mapping and within GTVnp. We independently validate predictive value of identified feature and associated predicted subvolume. RESULTS: Only one radiomic feature, gldm_DependenceVariance in 3 mm-sigma LoG-filtered image, was discovered as a signature. In the high-risk group determined by the signature, patients received CCRT + ACT achieved 3-year disease free survival (DFS) rate of 90% versus 57% (HR, 0.20; 95%CI, 0.05-0.94; P = 0.007) for CCRT alone. The multivariate analysis showed patients receiving CCRT + ACT had a HR of 0.21 (95%CI: 0.06-0.68, P = 0.009) for DFS compared to those receiving CCRT alone. The predictive value can also be generalized to the subvolume with multivariate HR of 0.27 (P = 0.017) for DFS. CONCLUSION: The signature with its heterogeneity mapping could be a reliable and explainable ACT decision-making tool in clinical practice.

Depth Dose Enhancement in Orthovoltage Nanoparticle-Enhanced Radiotherapy: A Monte Carlo Phantom Study.

BACKGROUND: This study was to examine the depth dose enhancement in orthovoltage nanoparticle-enhanced radiotherapy for skin treatment by investigating the impact of various photon beam energies, nanoparticle materials, and nanoparticle concentrations. METHODS: A water phantom was utilized, and different nanoparticle materials (gold, platinum, iodine, silver, iron oxide) were added to determine the depth doses through Monte Carlo simulation. The clinical 105 kVp and 220 kVp photon beams were used to compute the depth doses of the phantom at different nanoparticle concentrations (ranging from 3 mg/mL to 40 mg/mL). The dose enhancement ratio (DER), which represents the ratio of the dose with nanoparticles to the dose without nanoparticles at the same depth in the phantom, was calculated to determine the dose enhancement. RESULTS: The study found that gold nanoparticles outperformed the other nanoparticle materials, with a maximum DER value of 3.77 at a concentration of 40 mg/mL. Iron oxide nanoparticles exhibited the lowest DER value, equal to 1, when compared to other nanoparticles. Additionally, the DER value increased with higher nanoparticle concentrations and lower photon beam energy. CONCLUSIONS: It is concluded in this study that gold nanoparticles are the most effective in enhancing the depth dose in orthovoltage nanoparticle-enhanced skin therapy. Furthermore, the results suggest that increasing nanoparticle concentration and decreasing photon beam energy lead to increased dose enhancement.

Combining Transoral Nasopharyngeal Brush and Plasma Epstein-Barr Virus DNA in Detecting Locally Recurrent Nasopharyngeal Carcinoma.

OBJECTIVE: To evaluate the sensitivities and specificities of Epstein-Barr virus (EBV) DNA in the detection of locally recurrent or persistent nasopharyngeal carcinoma (NPC) through nasopharyngeal (NP) brush biopsy and plasma, respectively, and whether a combination of both would be superior to the individual tests. STUDY DESIGN: A case-control study was conducted from September 2016 to June 2022. SETTING: A multicentre study at 3 tertiary referral centers in Hong Kong was conducted by the Department of Otorhinolaryngology, Head and Neck Surgery, The Chinese University of Hong Kong. METHODS: Twenty-seven patients with biopsy-confirmed locally recurrent NPC were recruited as study subjects. Magnetic resonance imaging was performed to rule out regional recurrence. The control group consisted of 58 patients with a prior history of NPC who were now disease-free based on endoscopic and imaging findings. Patients underwent both the transoral NP brush (NP Screen®) and blood for plasma Epstein-Barr DNA levels. RESULTS: The sensitivity and specificity of the combined modalities were 84.62% and 85.19%, respectively. The positive predictive value was 73.33% and the negative predictive value was 92.0%. CONCLUSION: The combination of NP brush biopsy and plasma EBV DNA is potentially an additional surveillance modality in detecting the local recurrence of NPC. Further study with a larger sample size would be required to validate the cutoff values.