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Objective/hypothesis: A cone-beam CT (CBCT) imaging system based on a mobile C-arm (Siemens PowerMobil) incorporating a high-performance flat-panel detector (Varian PaxScan) has been developed in our laboratory. We hypothesize that intraoperative C-arm CBCT provides image quality and guidance performance sufficient to assist surgical approach to the frontal recess. Study Design: A preclinical prospective study was conducted using six cadaver heads to assess the performance characteristics and the potential clinical utility of this imaging system. Methods: The mobile C-arm was employed for intraoperative CBCT guidance of the endoscopic approach to twelve frontal recesses. Results: The imaging system is capable of sub-mm 3D spatial resolution with bone and soft-tissue visibility and a field of view sufficient for guidance of head and neck surgery. The system can generate intraoperative, volumetric CT images rapidly with an acceptably low radiation exposure to the patient and with image quality sufficient for most surgical tasks. Moreover, the system is portable and compatible with the surgical setup, providing excellent access to the patient. Finally, the accuracy of the system is not bound to a registration process. Conclusions: The ability to create updated images as surgery progresses introduces the concept of 'near-real-time' CT guidance for head and neck surgery. We found that the use of CBCT increased surgical confidence in accessing the frontal recess, resolved ambiguities with anatomical variations, and provided valuable teaching information to surgeons in training in both preoperative planning and correlation between tri-planar CT scans and intraoperative endoscopic findings. [ABSTRACT FROM AUTHOR]

Abstract Background The purpose of this study was to identify clinical and dosimetric factors associated with radiotherapy induced bone injury (RIBI) following stereotactic lung radiotherapy. Methods Inoperable patients with early stage non-small cell lung cancer, treated with SBRT, who received 54 or 60 Gy in 3 fractions, and had a minimum of 6 months follow up were reviewed. Archived treatment plans were retrieved, ribs delineated individually and treatment plans re-computed using heterogeneity correction. Clinical and dosimetric factors were evaluated for their association with rib fracture using logistic regression analysis; a dose-event curve and nomogram were created. Results 46 consecutive patients treated between Oct 2004 and Dec 2008 with median follow-up 25 months (m) (range 6 – 51 m) were eligible. 41 fractured ribs were detected in 17 patients; median time to fracture was 21 m (range 7 – 40 m). The mean maximum point dose in non-fractured ribs (n = 1054) was 10.5 Gy ± 10.2 Gy, this was higher in fractured ribs (n = 41) 48.5 Gy ± 24.3 Gy (p 0.5), and the volume of the rib receiving at least 25 Gy (V25), were significantly associated with RIBI. As D0.5 and V25 were cross-correlated (Spearman correlation coefficient: 0.57, p 0.5 as a representative dose parameter. On multivariate analysis, age (odds ratio: 1.121, 95% CI: 1.04 – 1.21, p = 0.003), female gender (odds ratio: 4.43, 95% CI: 1.68 – 11.68, p = 0.003), and rib D0.5 (odds ratio: 1.0009, 95% CI: 1.0007 – 1.001, p Using D0.5, a dose-event curve was constructed estimating risk of fracture from dose at the median follow up of 25 months after treatment. In our cohort, a 50% risk of rib fracture was associated with a D0.5 of 60 Gy. Conclusions Dosimetric and clinical factors contribute to risk of RIBI and both should be included when modeling risk of toxicity. A nomogram is presented using D0.5, age, and female gender to estimate risk of RIBI following SBRT. This requires validation.

Aim: To determine the inter-observer variability of defining the prostate gland on cone beam computerised tomography images for the purposes of image-guided radiotherapy. Materials and methods: Five genitourinary oncologists contoured the prostate gland on five cone beam computerised tomography datasets. The variations in prostate boundary delineation and consequent isocentre placement between observers were measured. Variations in volume and centre of mass were calculated. The variation in boundary definition was determined with finite element modelling. Results: The average standard deviation for centre of mass displacements was small, measuring 0.7, 1.8 and 2.8 mm in the left-right, anterior-posterior and superior-inferior directions, respectively. The standard deviation for volume determination was 8.93 cm³ with large variability (3.98-19.00 cm³). The mean difference between the computerised tomography-derived volume and the mean cone beam-derived volume was 16% (range 0-23.7%). The mean standard deviations for left-right, anterior-posterior and superior-inferior boundary displacements were, respectively, 1.8, 2.1 and 3.6 mm. The maximum deviation seen was 9.7 mm in the superior direction. Conclusion: Expert observers had difficulty agreeing upon the location of the prostate peri-prostatic interface on the images provided. The effect on the centre of mass determination was small, and inter-observer variability for prostate detection on cone beam computerised tomography images is not prohibitive to the use of soft tissue guidance protocols. Potential exists for significant systematic matching errors, and points to the need for rigorous therapist image recognition training and development of guidance protocols before clinical implementation of soft tissue cone beam image guidance. [ABSTRACT FROM AUTHOR]

While we recognize the prognostic importance of clinicopathological measures and circulating tumor DNA (ctDNA), the independent contribution of quantitative image markers to prognosis in non-small cell lung cancer (NSCLC) remains underexplored. In our multi-institutional study of 394 NSCLC patients, we utilize pre-treatment computed tomography (CT) and 18 F-fluorodeoxyglucose positron emission tomography (FDG-PET) to establish a habitat imaging framework for assessing regional heterogeneity within individual tumors. This framework identifies three PET/CT subtypes, which maintain prognostic value after adjusting for clinicopathologic risk factors including tumor volume. Additionally, these subtypes complement ctDNA in predicting disease recurrence. Radiogenomics analysis unveil the molecular underpinnings of these imaging subtypes, highlighting downregulation in interferon alpha and gamma pathways in the high-risk subtype. In summary, our study demonstrates that these habitat imaging subtypes effectively stratify NSCLC patients based on their risk levels for disease recurrence after initial curative surgery or radiotherapy, providing valuable insights for personalized treatment approaches., (© 2024. The Author(s).)

Docetaxel +/- ramucirumab remains the standard-of-care therapy for patients with metastatic non-small-cell lung cancer (NSCLC) after progression on platinum doublets and immune checkpoint inhibitors (ICIs). The aim of our study was to investigate whether the cancer gene mutation status was associated with clinical benefits from docetaxel +/- ramucirumab. We also investigated whether platinum/taxane-based regimens offered a better clinical benefit in this patient population. A total of 454 patients were analyzed (docetaxel +/- ramucirumab n=381; platinum/taxane-based regimens n=73). Progression-free survival (PFS) and overall survival (OS) were compared among different subpopulations with different cancer gene mutations and between patients who received docetaxel +/- ramucirumab versus platinum/taxane-based regimens. Among patients who received docetaxel +/- ramucirumab, the top mutated cancer genes included TP53 (n=167), KRAS (n=127), EGFR (n=65), STK11 (n=32), ERBB2 (HER2) (n=26), etc. None of these cancer gene mutations or PD-L1 expression was associated with PFS or OS. Platinum/taxane-based regimens were associated with a significantly longer mQS (13.00 m, 95% Cl: 11.20-14.80 m versus 8.40 m, 95% Cl: 7.12-9.68 m, LogRank P=0.019) than docetaxel +/- ramcirumab. Key prognostic factors including age, histology, and performance status were not different between these two groups. In conclusion, in patients with metastatic NSCLC who have progressed on platinum doublets and ICIs, the clinical benefit from docetaxel +/- ramucirumab is not associated with the cancer gene mutation status. Platinum/taxane-based regimens may offer a superior clinical benefit over docetaxel +/- ramucirumab in this patient population.

Magnetic resonance image guided radiation therapy (MRIgRT) is a relatively new technology that has already shown outcomes benefits but that has not yet reached its clinical potential. The improved soft-tissue contrast provided with MR, coupled with the immediacy of image acquisition with respect to the treatment, enables expansion of on-table adaptive protocols, currently at a cost of increased treatment complexity, use of human resources, and longer treatment slot times, which translate to decreased throughput. Many approaches are being investigated to meet these challenges, including the development of artificial intelligence (AI) algorithms to accelerate and automate much of the workflow and improved technology that parallelizes workflow tasks, as well as improvements in image acquisition speed and quality. This article summarizes limitations of current available integrated MRIgRT systems and gives an outlook about scientific developments to further expand the use of MRIgRT., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Competing Interests: We declare no competing interests.

The pace of technological innovation over the past three decades has transformed the field of radiotherapy into one of the most technologically intense disciplines in medicine. However, the global barriers to access this highly effective treatment are complex and extend beyond technological limitations. Here, we review the technological advancement and current status of radiotherapy and discuss the efforts of the global radiation oncology community to formulate a more integrative 'diagonal approach' in which the agendas of science-driven advances in individual outcomes and the sociotechnological task of global cancer control can be aligned to bring the benefit of this proven therapy to patients with cancer everywhere., (© 2023. Springer Nature America, Inc.)

The development of cone-beam CT guided radiotherapy has transformed radiation oncology in the 20 years since it was first released commercially. The technological pace of change has spurred a massive transformation in our daily clinical practice, forced us to evolve our approach to multi- and inter-disciplinary collaboration, and enabled new treatment paradigms. Further progress in integrating quantitative CT in these robotic platforms promises to do even more by "burying the complexity" of radiotherapy and leveraging the expanding digital fabric that uses machine learning approaches to bring semi-automated expertise to bear on the issues of expertise and quality. This is the only way we will be able to respond to the massive global shortfall in high-quality radiotherapy services across the globe., (© 2023 American Association of Physicists in Medicine.)

Developers and users of artificial-intelligence-based tools for automatic contouring and treatment planning in radiotherapy are expected to assess clinical acceptability of these tools. However, what is 'clinical acceptability'? Quantitative and qualitative approaches have been used to assess this ill-defined concept, all of which have advantages and disadvantages or limitations. The approach chosen may depend on the goal of the study as well as on available resources. In this paper, we discuss various aspects of 'clinical acceptability' and how they can move us toward a standard for defining clinical acceptability of new autocontouring and planning tools.

As frameless stereotactic radiosurgery increase in use, the aim of this study was to evaluate intra-fraction motion through cone-beam CT (CBCT) and high-definition motion management (HDMM) systems. Intra-fraction motion measured between localization, repeat localization and post-treatment CBCTs were correlated to intra-faction motion indicated by the HDMM files using the Pearson coefficient (r). A total of 302 plans were reviewed from 263 patients (114 male, 149 female); 216 pairs of localization-repeat localization, and 260 localization-post-treatment CBCTs were analyzed against HDMM logs. We found the magnitude of intra-fraction motion detected by the HDMM system were larger than the corresponding CBCT results., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: This work was partially supported through a research grant from Elekta and the Canadian Institutes of Health Research (CIHR); the principal investigators of the grants were Dr. David Jaffray and Dr. Caroline Chung., (© 2023 The Authors.)

Tumours exhibit abnormal interstitial structures and vasculature function often leading to impaired and heterogeneous drug delivery. The disproportionate spatial accumulation of a drug in the interstitium is determined by several microenvironmental properties (blood vessel distribution and permeability, gradients in the interstitial fluid pressure). Predictions of tumour perfusion are key determinants of drug delivery and responsiveness to therapy. Pharmacokinetic models allow for the quantification of tracer perfusion based on contrast enhancement measured with non-invasive imaging techniques. An advanced cross-voxel exchange model (CVXM) was recently developed to provide a comprehensive description of tracer extravasation as well as advection and diffusion based on cross-voxel tracer kinetics (Sinno et al 2021). Transport parameters were derived from DCE-MRI of twenty TS-415 human cervical carcinoma xenografts by using CVXM. Tracer velocity flows were measured at the tumour periphery (mean 1.78-5.82 μ m.s -1 ) pushing the contrast outward towards normal tissue. These elevated velocity measures and extravasation rates explain the heterogeneous distribution of tracer across the tumour and its accumulation at the periphery. Significant values for diffusivity were deduced across the tumours (mean 152-499 μ m 2 .s -1 ). CVXM resulted in generally smaller values for the extravasation parameterKext(mean 0.01-0.04 min -1 ) and extravascular extracellular volume fractionve(mean 0.05-0.17) compared to the standard Tofts parameters, suggesting that Toft model underestimates the effects of inter-voxel exchange. The ratio of Tofts' extravasation parameters over CVXM's was significantly positively correlated to the cross-voxel diffusivity ( P < 0.0001) and velocity ( P = 0.0005). Tofts' increasedvemeasurements were explained using Sinno et al (2021)'s theoretical work. Finally, a scan time of 15 min renders informative estimations of the transport parameters. However, a duration as low as 7.5 min is acceptable to recognize the spatial variation of transport parameters. The results demonstrate the potential of utilizing CVXM for determining metrics characterizing the exchange of tracer between the vasculature and the tumour tissue. Like for many earlier models, additional work is strongly recommended, in terms of validation, to develop more confidence in the results, motivating future laboratory work in this regard., (Creative Commons Attribution license.)

Purpose: The role of metastasis-directed therapy (MDT) in molecularly defined oligorecurrent prostate cancer (PCa) remains irresolute. We present extended follow-up and an independent validation cohort of a prospective trial., Methods and Materials: This study consists of 2 sequential single-arm phase-2 trials of patients with biochemical recurrence (prostate specific antigen [PSA] 0.4-3.0 ng/mL) and negative conventional imaging after radical prostatectomy and postoperative radiation therapy. All patients underwent [ 18 F]DCFPyL positron emission tomography/computed tomography. Patients with molecularly defined oligorecurrent prostate cancer underwent MDT with stereotactic body radiation therapy or surgery, without androgen deprivation therapy (ADT). The primary end point was biochemical response (≥50% PSA decline from baseline). Secondary end points included PSA progression-free survival and ADT-free survival. The sample size of 37 MDT patients was determined based on a Simon's 2-stage design with biochemical response rate >20%, and this design was also applied for the subsequent independent validation cohort., Results: Seventy-four patients underwent MDT: 37 each in the initial and validation cohorts. Both cohorts met the prespecified biochemical response rate and completed the planned 2-stages of accrual. For the pooled cohort, the median number of prostate specific membrane antigen positron emission tomography avid lesions was 2 and most (87%) recurrences were nodal. Sixty-four (87%) had stereotactic body radiation therapy and 10 (13%) had surgery. Median follow-up (interquartile range [IQR]) for the initial, validation and combined cohorts were 41 (35-46) months, 14 months (7-21), and 24 months (14-41), respectively. The biochemical response rates for the initial, validation and combined cohorts were 59%, 43%, and 51%, respectively. For the combined cohort, median biochemical progression-free survival was 21 months (95% confidence interval, 13-not reached), and median ADT-free survival was 45 months (95% confidence interval, 31-not reached)., Conclusions: Half of patients treated with MDT for molecularly defined-only oligorecurrent prostate cancer exhibited a biochemical response. This study provides necessary and validated evidence to support randomized trials aiming to determine whether MDT (alone or with systemic therapy) can affect clinically meaningful end points., (Copyright © 2022 Elsevier Inc. All rights reserved.)

While FLASH radiation therapy is inspiring enthusiasm to transform the field, it is neither new nor well understood with respect to the radiobiological mechanisms. As FLASH clinical trials are designed, it will be important to ensure we can deliver dose consistently and safely to every patient. Much like hyperthermia and proton therapy, FLASH is a promising new technology that will be complex to implement in the clinic and similarly will require customized credentialing for multi-institutional clinical trials. There is no doubt that FLASH seems promising, but many technologies that we take for granted in conventional radiation oncology, such as rigorous dosimetry, 3D treatment planning, volumetric image guidance, or motion management, may play a major role in defining how to use, or whether to use, FLASH radiotherapy. Given the extended time frame for patients to experience late effects, we recommend moving deliberately but cautiously forward toward clinical trials. In this paper, we review the state of quality assurance and safety systems in FLASH, identify critical pre-clinical data points that need to be defined, and suggest how lessons learned from previous technological advancements will help us close the gaps and build a successful path to evidence-driven FLASH implementation., (© 2022 The Authors. Medical Physics published by Wiley Periodicals LLC on behalf of American Association of Physicists in Medicine.)

Background: Transfusion carries a risk of transfusion reaction that is often underdiagnosed due to reliance on passive reporting. The study investigated the utility of digital methods to identify potential transfusion reactions, thus allowing real-time intervention for affected patients., Method: The hemovigilance unit monitored 3856 patients receiving 43,515 transfusions under the hemovigilance program. Retrospective comparison data included 298,498 transfusions. Transfusion medicine physicians designed and validated algorithms in the electronic health record that analyze discrete data, such as vital sign changes, to assign a risk score during each transfusion. Dedicated hemovigilance nurses remotely monitor all patients and perform real-time chart reviews prioritized by risk score. When a reaction is suspected, a hemovigilance trained licensed clinician responds to manage the patient and ensure data collection. Board-certified transfusion medicine physicians reviewed data and classified transfusion reactions under various categories according to the Centers for Disease Control hemovigilance definitions., Results: Transfusion medicine physicians diagnosed 564 transfusion reactions (1.3% of transfusions)-a 524% increase compared to the previous passive reporting. The rapid response provider reached the bedside on average at 12.4 min demonstrating logistic feasibility. While febrile reactions were most diagnosed, recognition of transfusion-associated circulatory overload demonstrated the greatest relative increase. Auditing and education programs further enhanced transfusion reaction awareness., Discussion: The model of digitally-enabled expert real-time review of clinical data that prompts rapid response improved recognition of transfusion reactions. This approach could be applied to other patient deterioration events such as early identification of sepsis., (© 2022 AABB.)

For multicenter clinical studies, characterizing the robustness of image-derived radiomics features is essential. Features calculated on PET images have been shown to be very sensitive to image noise. The purpose of this work was to investigate the efficacy of a relatively simple harmonization strategy on feature robustness and agreement. A purpose-built texture pattern phantom was scanned on 10 different PET scanners in 7 institutions with various different image acquisition and reconstruction protocols. An image harmonization technique based on equalizing a contrast-to-noise ratio was employed to generate a "harmonized" alongside a "standard" dataset for a reproducibility study. In addition, a repeatability study was performed with images from a single PET scanner of variable image noise, varying the binning time of the reconstruction. Feature agreement was measured using the intraclass correlation coefficient (ICC). In the repeatability study, 81/93 features had a lower ICC on the images with the highest image noise as compared to the images with the lowest image noise. Using the harmonized dataset significantly improved the feature agreement for five of the six investigated feature classes over the standard dataset. For three feature classes, high feature agreement corresponded with higher sensitivity to the different patterns, suggesting a way to select suitable features for predictive models.

With a widely attended virtual kickoff event on January 29, 2021, the National Cancer Institute (NCI) and the Department of Energy (DOE) launched a series of 4 interactive, interdisciplinary workshops-and a final concluding "World Café" on March 29, 2021-focused on advancing computational approaches for predictive oncology in the clinical and research domains of radiation oncology. These events reflect 3,870 human hours of virtual engagement with representation from 8 DOE national laboratories and the Frederick National Laboratory for Cancer Research (FNL), 4 research institutes, 5 cancer centers, 17 medical schools and teaching hospitals, 5 companies, 5 federal agencies, 3 research centers, and 27 universities. Here we summarize the workshops by first describing the background for the workshops. Participants identified twelve key questions-and collaborative parallel ideas-as the focus of work going forward to advance the field. These were then used to define short-term and longer-term "Blue Sky" goals. In addition, the group determined key success factors for predictive oncology in the context of radiation oncology, if not the future of all of medicine. These are: cross-discipline collaboration, targeted talent development, development of mechanistic mathematical and computational models and tools, and access to high-quality multiscale data that bridges mechanisms to phenotype. The workshop participants reported feeling energized and highly motivated to pursue next steps together to address the unmet needs in radiation oncology specifically and in cancer research generally and that NCI and DOE project goals align at the convergence of radiation therapy and advanced computing., (©2022 by Radiation Research Society. All rights of reproduction in any form reserved.)

Background: Tumor hypoxia is defined as a low oxygen level in tissue and is associated with poor clinical outcome after chemo-/radiotherapy and surgery in many solid tumor types. Positron Emission Tomography (PET) imaging provides a non-invasive means of measuring local variations in the uptake of hypoxia-targeted agents (e.g. FAZA or FMISO). Accurate quantification of uptake is critically dependent on the PET scanner's linear count rate performance. In the context of cervix cancer, high PET agent accumulation in the bladder, low uptake in the tumor, and their relative proximity makes an accurate quantification of the tumor's hypoxic fraction challenging. The purpose of this study was to estimate the impact of PET scanner non-linearity on PET-based estimation of hypoxic fraction., Material and Methods: The impact of PET scanner non-linearity effect was assessed with a NEMA body phantom, using the cylinder as the "bladder-mimicking" compartment and the water filled background as a surrogate region for the tumor. A simple model of the non-linearity effect was then applied to a set of patient-derived FAZA-PET scans (N = 38) to estimate the impact of the non-linearity on the calculated hypoxic fraction (HF) for each patient., Results: The NEMA body phantom measurements revealed a substantial overestimate of activity outside the injected "bladder mimicking" cylinder compartment. This uptake resulted in an overestimate in activity between 1.9 and 0.3 kBq/cc corresponding to distances from 1.0 - 7.0 cm from the cylinder. In the patient-derived PET images, the bladder-to-tumor distance ranged between 1.0 and 3.0 cm. For the 38 patients analyzed, the HF was demonstrated to decrease by 1.1-75.0 % [median 27.2 %] depending on distance and relative uptake levels. Additionally, the magnitude of the effect of the non-linearity was found to depend on the pre-scanning hydration protocol employed (p = 0.0065)., Conclusion: Hypoxia imaging of tumors of the cervix is challenging due to patient specific activity accumulation in the bladder and the non-linear response of PET scanner performance. This can result in a substantial overestimate of the calculated hypoxic fraction in cervical tumors. Additional effort needs to be invested to improve the linearity of PET scanners in anatomical regions proximal to the bladder., (Copyright © 2021 Associazione Italiana di Fisica Medica e Sanitaria. Published by Elsevier Ltd. All rights reserved.)

Profound advances in computational methods, including artificial intelligence (AI), present the opportunity to use the exponentially growing volume and complexity of available cancer measurements toward data-driven personalized care. While exciting, this opportunity has highlighted the disconnect between the promise of compute and the supply of high-quality data. The current paradigm of ad-hoc aggregation and curation of data needs to be replaced with a "metadata supply chain" that provides robust data in context with known provenance, that is, lineage and comprehensive data governance that will allow the promise of AI technology to be realized to its full potential in clinical practice., (©2021 The Authors; Published by the American Association for Cancer Research.)

Predictions of tumour perfusion are key determinants of drug delivery and responsiveness to therapy. Pharmacokinetic models allow for the estimation of perfusion properties of tumour tissues but many assume no dispersion associated with tracer transport away from the capillaries and through the tissue. At the level of a voxel, this translates to assuming no cross-voxel tracer exchange, often leading to the misinterpretation of derived perfusion parameters. Tofts model (TM), a compartmental model widely used in oncology, also makes this assumption. A more realistic description is required to quantify kinetic properties of tracers, such as convection and diffusion. We propose a Cross-Voxel Exchange Model (CVXM) for analysing cross-voxel tracer kinetics. In silico datasets quantifying the roles of convection and diffusion in tracer transport (which TM ignores) were employed to investigate the interpretation of Tofts' perfusion parameters compared to CVXM. TM returned inaccurate values ofKtransandvewhere diffusive and convective mechanisms are pronounced (up to 20% and 300% error respectively). A mathematical equation, developed in this work, predicts and gives the correct physiological interpretation of Tofts've.Finally, transport parameters were derived from dynamic contrast enhanced-magnetic resonance imaging of a TS-415 human cervical carcinoma xenograft by using TM and CVXM. The latter deduced lower values ofKtransandvecompared to TM (lower by up to 63% and 76% respectively). It also allowed the detection of a diffusive flux (mean diffusivity 155 μ m 2 s -1 ) in the tumour tissue, as well as an increased convective flow at the periphery (mean velocity 2.3 μ m s -1 detected). The results serve as a proof of concept establishing the feasibility of using CVXM for accurately determining transport metrics that characterize the exchange of tracer between voxels. CVXM needs to be investigated further as its parameters can be linked to the tumour microenvironment properties (permeability, pressure…), potentially leading to enhanced personalized treatment planning., (© 2021 Institute of Physics and Engineering in Medicine.)

Background: The hypothesis of a curable oligometastatic prostate cancer (PCa) state remains to be clinically-proven. Conventional imaging often fails to localize early recurrences, hampering the potential for radical approaches., Objective: We hypothesize that prostate-specific membrane antigen (PSMA)-targeted PET-MR/CT allows for earlier detection and localization of oligorecurrent-PCa, unveiling a molecularly-defined state amenable to curative-intent metastasis-directed treatment (MDT)., Design/setting/participants: Single-institution single-arm phase-two study. Patients with rising PSA (0.4-3.0 ng/mL) after maximal local therapy (radical prostatectomy and post-operative radiotherapy), negative conventional staging, and no prior salvage hormonal therapy (HT) were eligible., Interventions: All patients underwent [ 18 F]DCFPyL PET-MR/CT. Patients with molecularly-defined oligorecurrent-PCa had MDT (stereotactic ablative body radiotherapy [SABR] or surgery) without HT., Outcome Measurements/statistical Analysis: Primary endpoint was biochemical response (complete, i.e. biochemical 'no evidence of disease' [bNED], or partial response [100% or ≥50% PSA decline from baseline, respectively]) after MDT. Simon's two-stage design was employed (null and alternate hypotheses <5% and >20% response rate, respectively), with α and β of 0.1., Results: Seventy-two patients were enrolled (May/2017-July/2019). Thirty-eight (53%) had PSMA-detected oligorecurrent-PCa amenable for MDT. Thirty-seven (51%) agreed to MDT: 10 and 27 underwent surgery and SABR, respectively. Median follow-up was 15.9 months (IQR 9.8-19.1). Of patients receiving MDT, the overall response rate was 60%, including 22% rendered bNED. One (2.7%) grade 3 toxicity (intra-operative ureteric injury) was observed., Conclusions: PSMA-defined oligorecurrent-PCa can be rendered bNED, a necessary step towards cure, in 1 of 5 patients receiving MDT alone. Randomized trials are justified to determine if MDT +/- systemic agents can expand the curative therapeutic armamentarium for PCa., Patient Summary: We studied men treated for prostate cancer with rising PSA. We found PSMA imaging detected recurrent cancer in three-quarters of patients, and targeted treatment to these areas significantly decreased PSA in half of patients., (Copyright © 2021 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Research into conebeam CT concepts began as soon as the first clinical single-slice CT scanner was conceived. Early implementations of conebeam CT in the 1980s focused on high-contrast applications where concurrent high resolution ( < 200    μ m ), for visualization of small contrast-filled vessels, bones, or teeth, was an imaging requirement that could not be met by the contemporaneous CT scanners. However, the use of nonlinear imagers, e.g., x-ray image intensifiers, limited the clinical utility of the earliest diagnostic conebeam CT systems. The development of consumer-electronics large-area displays provided a technical foundation that was leveraged in the 1990s to first produce large-area digital x-ray detectors for use in radiography and then compact flat panels suitable for high-resolution and high-frame-rate conebeam CT. In this review, we show the concurrent evolution of digital flat panel (DFP) technology and clinical conebeam CT. We give a brief summary of conebeam CT reconstruction, followed by a brief review of the correction approaches for DFP-specific artifacts. The historical development and current status of flat-panel conebeam CT in four clinical areas-breast, fixed C-arm, image-guided radiation therapy, and extremity/head-is presented. Advances in DFP technology over the past two decades have led to improved visualization of high-contrast, high-resolution clinical tasks, and image quality now approaches the soft-tissue contrast resolution that is the standard in clinical CT. Future technical developments in DFPs will enable an even broader range of clinical applications; research in the arena of flat-panel CT shows no signs of slowing down., (© 2021 The Authors.)

Importance  Skull base surgery requires precise preoperative assessment and intraoperative management of the patient. Surgical navigation is routinely used for complex skull base cases; however, the image guidance is commonly based on preoperative scans alone. Objective  The primary objective of this study was to assess the image quality of intraoperative cone-beam computed tomography (CBCT) within anatomical landmarks used in sinus and skull base surgery. The secondary objective was to assess the registration error of a surgical navigation system based on intraoperative CBCT. Design  Present study is a retrospective case series of image quality after intraoperative cone beam CT. Setting  The study was conducted at Toronto General Hospital and Princess Margaret Cancer Centre, University Health Network, Toronto. Participants  A total of 46 intraoperative scans (34 patients, 21 skull base, 13 head and neck) were studied. Main Outcome and Measures  Thirty anatomical landmarks (vascular, soft tissue, and bony) within the sinuses and anterior skull base were evaluated for general image quality characteristics: (1) bony detail visualization; (2) soft-tissue visualization; (3) vascular visualization; and (4) freedom from artifacts (e.g., metal). Levels of intravenous (IV) contrast enhancement were quantified in Hounsfield's units (HU). Standard paired-point registration between imaging and tracker coordinates was performed using 6 to 8 skin fiducial markers and the corresponding fiducial registration error (FRE) was measured. Results  Median score for bony detail on CBCT was 5, remaining at 5 after administration of IV contrast. Median soft-tissue score was 2 for both pre- and postcontrast. Median vascular score was 1 precontrast and 3 postcontrast. Median score for artifacts on CBCT were 2 for both pre-and postcontrast, and metal objects were noted to be the most significant source of artifact. Intraoperative CBCT allowed preresection images and immediate postresection images to be available to the skull base surgeon. There was a significant improvement in mean (standard deviation [SD]) CT intensity in the left carotid artery postcontrast 334 HU (67 HU) ( p  < 10 -10 ). The mean FRE was 1.8 mm (0.45 mm). Conclusion  Intraoperative CBCT in complex skull base procedures provides high-resolution bony detail allowing immediate assessment of complex resections. The use of IV contrast with CBCT improves the visualization of vasculature. Image-guidance based on CBCT yields registration errors consistent with standard techniques., Competing Interests: Conflict of Interest None declared., (Thieme. All rights reserved.)

This study evaluates a long-acting liposomal fluorescence / CT dual-modality contrast agent (CF800) in head and neck cancer to enhance intraoperative tumor demarcation with fluorescence imaging and cone-beam computed tomography (CBCT). CF800 was administered to 12 buccal cancer-bearing rabbits. Imaging was acquired at regular time points to quantify time-dependent contrast enhancement. Surgery was performed 5-7 days after, with intraoperative near-infrared fluorescence endoscopy and CBCT, followed by histological and ex-vivo fluorescence assessment. Tumor enhancement on CT was significant at 24, 96 and 120 hours. Volumetric analysis of tumor segmentation showed high correlation between CBCT and micro-CT. Fluorescence signal was apparent in both ex-vivo and in-vivo imaging. Histological correlation showed [100%] specificity for primary tumor. Sensitivity and specificity of CF800 in detecting nodal involvement require further investigation.CF800 is long acting and has dual function for CT and fluorescence contrast, making it an excellent candidate for image-guided surgery., (Copyright © 2020 Elsevier Inc. All rights reserved.)

One of the largest geometric uncertainties in designing radiotherapy treatment plans for squamous cell cancers of the head and neck is contouring the gross tumor volume. We have previously described a method of projecting mucosal disease contours, visible on endoscopy, to volumetrically reconstructed planning computed tomography (CT) datasets, using electromagnetic (EM) tracking of a flexible endoscope, enabling rigid registration between endoscopic and CT images.However, to achieve better accuracy for radiotherapy planning, we propose refining this initial registration with image-based registration methods. In this paper, several types of cost functions are evaluated based on accuracy and robustness. Three phantoms and eight clinical cases are used to test each cost function, with initial registration of endoscopy to CT provided by the pose of the flexible endoscope recovered from EM tracking. Cost function classes include: cross correlation, mutual information and gradient methods. For each test case, a ground truth virtual camera pose was first defined by manual registration of anatomical features visible in both real and virtual endoscope images. A new set of evenly spaced fiducial points and a sample contour were created and projected onto the CT image to be used in assessing image registration quality. A new set of 5000 displaced poses was generated by random sampling displacements along each translational and rotational dimension. At each pose, fiducial and contour points in the real image were again projected on the CT image. The cost function, fiducial registration error and contouring error values were then calculated.While all cost functions performed well in select cases, only the normalized gradient field function consistently had registration errors less than 2 mm, which is the accuracy needed if this application of registering mucosal disease identified on optical image to CT images is to be used in the clinical practice of radiation treatment planning.(Registration: ClinicalTrials.gov NCT02704169)., (© 2020 Institute of Physics and Engineering in Medicine.)

Integration between a hand-held mass spectrometry desorption probe based on picosecond infrared laser technology (PIRL-MS) and an optical surgical tracking system demonstrates in situ tissue pathology from point-sampled mass spectrometry data. Spatially encoded pathology classifications are displayed at the site of laser sampling as color-coded pixels in an augmented reality video feed of the surgical field of view. This is enabled by two-way communication between surgical navigation and mass spectrometry data analysis platforms through a custom-built interface. Performance of the system was evaluated using murine models of human cancers sampled in situ in the presence of body fluids with a technical pixel error of 1.0 ± 0.2 mm, suggesting a 84% or 92% (excluding one outlier) cancer type classification rate across different molecular models that distinguish cell-lines of each class of breast, brain, head and neck murine models. Further, through end-point immunohistochemical staining for DNA damage, cell death and neuronal viability, spatially encoded PIRL-MS sampling is shown to produce classifiable mass spectral data from living murine brain tissue, with levels of neuronal damage that are comparable to those induced by a surgical scalpel. This highlights the potential of spatially encoded PIRL-MS analysis for in vivo use during neurosurgical applications of cancer type determination or point-sampling in vivo tissue during tumor bed examination to assess cancer removal. The interface developed herein for the analysis and the display of spatially encoded PIRL-MS data can be adapted to other hand-held mass spectrometry analysis probes currently available., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Introduction: The oligometastatic (OM) disease hypothesis of an intermediate metastatic state with limited distant disease deposits amenable for curative therapies remains debatable. Over a third of prostate cancer (PCa) patients treated with radical prostatectomy and postoperative radiotherapy experience disease recurrence; these patients are considered incurable by current standards. Often the recurrence cannot be localised by conventional imaging (CT and bone scan). Combined anatomical imaging with CT and/or MR with positron emission tomography (PET) using a novel second-generation prostate-specific membrane antigen (PSMA) probe, [ 18 F]DCFPyL, is a promising imaging modality to unveil disease deposits in these patients. A new and earlier molecularly defined oligorecurrent (OR) state may be amenable to focal-targeted ablative curative-intent therapies, such as stereotactic ablative radiotherapy (SABR) or surgery, thereby significantly delaying or completely avoiding the need for palliative therapies in men with recurrent PCa after maximal local treatments., Methods and Analysis: This ongoing single-institution phase II study will enrol up to 75 patients total, to include up to 37 patients with response-evaluable disease, who have rising prostate-specific antigen (range 0.4-3.0 ng/mL) following maximal local therapies with no evidence of disease on conventional imaging. These patients will undergo [ 18 F]DCFPyL PET-MR/CT imaging to detect disease deposits, which will then be treated with SABR or surgery. The primary endpoints are performance of [ 18 F]DCFPyL PET-MR/CT, and treatment response rates following SABR or surgery. Demographics and disease characteristics will be summarised and analysed descriptively. Response rates will be described with waterfall plots and proportions., Ethics and Dissemination: Ethics approval was obtained from the institutional Research Ethics Board. All patients will provide written informed consent. [ 18 F]DCFPyL has approval from Health Canada. The results of the study will be disseminated by the principal investigator. Patients will not be identifiable as individuals in any publication or presentation of this study., Trial Registration Numbers: NCT03160794., Competing Interests: Competing interests: UM declares a competing interest with Point Biopharm Inc. as a consultant., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Studies suggest there is utility in computed tomography (CT) radiomics for pancreatic disease; however, the precise biological interpretation of its features is unclear. In this manuscript, we present a novel approach towards this interpretation by investigating sub-micron tissue structure using digital pathology., Methods: A classification-to attenuation (CAT) function was developed and applied to digital pathology images to create sub-micron linear attenuation maps. From these maps, grey level co-occurrence matrix (GLCM) features were extracted and compared to pathology features. To simulate the spatial frequency loss in a CT scanner, the attenuation maps were convolved with a point spread function (PSF) and subsequently down-sampled. GLCM features were extracted from these down-sampled maps to assess feature stability as a function of spatial frequency loss., Results: Two GLCM features were shown to be strongly and positively correlated (r = 0.8) with underlying characteristics of the tumor microenvironment, namely percent pimonidazole staining in the tumor. All features underwent marked change as a function of spatial frequency loss; progressively larger spatial frequency losses resulted in progressively larger inter-tumor standard deviations; two GLCM features exhibited stability up to a 100 µm pixel size., Conclusion: This work represents a necessary step towards understanding the biological significance of radiomics. Our preliminary results suggest that cellular metrics of pimonidazole-detectable hypoxia correlate with sub-micron attenuation coefficient texture; however, the consistency of these textures in face of spatial frequency loss is detrimental for robust radiomics. Further study in larger data sets may elucidate additional, potentially more robust features of biologic and clinical relevance., (Crown Copyright © 2020. Published by Elsevier Ltd. All rights reserved.)

Introduction: Monte Carlo (MC) simulations are a powerful tool for improving image quality in X-ray based imaging modalities. An accurate X-ray source model is essential to MC modeling for CBCT but can be difficult to implement on a GPU while maintaining efficiency and memory limitations. A statistical analysis of the photon distribution from a MC X-ray tube simulation is conducted in hopes of building a compact source model., Materials & Methods: MC simulations of an X-ray tube were carried out using BEAMnrc. The resulting photons were sorted into four categories: primary, scatter, off-focal radiation (OFR), and both (scatter and OFR). A statistical analysis of the photon components (energy, position, direction) was completed. A novel method for a compact (memory efficient) representation of the PHSP data was implemented and tested using different statistical based linear transformations (PCA, ZCA, ICA), as well as a geometrical transformation., Results: The statistical analysis showed all photon groupings had strong correlations between position and direction, with the largest correlation in the primary data. The novel method was successful in compactly representing the primary (error < 2%) and scatter (error < 6%) photon groupings by reducing the component correlations., Discussion & Conclusion: Statistical linear transforms provide a method of reducing the memory required to accurately simulate an X-ray source in a GPU MC system. If all photon types are required, the proposed method reduces the memory requirements by 3.8 times. When only primary and scatter data is needed, the memory requirement is reduced from gigabytes to kilobytes., (Copyright © 2020 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.)

Purpose: To evaluate the electromagnetic (EM) tracking of endoscopes and applicators as a method of positioning a high dose rate (HDR) luminal applicator., Method: An anatomical phantom consisting of a rigid trachea and flexible esophagus was used to compare applicator placement measurements using EM tracking vs the traditional method using two-dimensional (2D) fluoroscopy and surface skin markers. The phantom included a tumor in the esophagus and several pairs of optically visible points inside the lumen that were used to simulate proximal and distal ends of tumors of varying lengths. The esophagus tumor and lung points were visible on a computed tomography (CT) image of the phantom, which was used as ground truth for the measurements. The EM tracking system was registered to the CT image using fiducial markers. A flexible endoscope was tracked using the EM system and the locations of the proximal and distal ends of the tumor identified and this position recorded. An EM-tracked applicator was then inserted and positioned relative to the tumor markings. The applicator path was mapped using the EM tracking. The gross tumor length (GTL) and the distance between the first dwell position and distal edge of tumor (offset) were measured using the EM tracking and 2D fluoroscopy methods and compared to the same measurements on the CT image., Results: The errors in GTL using EM tracking were on average -0.5 ± 1.7 mm and 0.7 ± 3.6 mm for esophagus and lung measurements, similar to errors measured using the 2D fluoroscopy method of -0.9 ± 1.2 mm and 3.4 ± 4.4 mm. Offset measurements were slightly larger while using EM tracking relative to the fluoroscopy method but these were not statistically significant., Conclusions: Electromagnetic tracking for placement of lumen applicators is feasible and accurate. Tracking of the endoscope that is used to identify the proximal and distal ends of the tumor and of the applicator during insertion generates accurate three-dimensional measurements of the applicator path, GTL and offset. Guiding the placement of intraluminal applicators using EM navigation is potentially attractive for cases with complex insertions, such as those with nonlinear paths or multiple applicator insertions., (© 2019 American Association of Physicists in Medicine.)

Quality assurance of data prior to use in automated pipelines and image analysis would assist in safeguarding against biases and incorrect interpretation of results. Automation of quality assurance steps would further improve robustness and efficiency of these methods, motivating widespread adoption of techniques. Previous work by our group demonstrated the ability of convolutional neural networks (CNN) to efficiently classify head and neck (H&N) computed-tomography (CT) images for the presence of dental artifacts (DA) that obscure visualization of structures and the accuracy of Hounsfield units. In this work we demonstrate the generalizability of our previous methodology by validating CNNs on six external datasets, and the potential benefits of transfer learning with fine-tuning on CNN performance. 2112 H&N CT images from seven institutions were scored as DA positive or negative. 1538 images from a single institution were used to train three CNNs with resampling grid sizes of 64 3 , 128 3 and 256 3 . The remaining six external datasets were used in five-fold cross-validation with a data split of 20% training/fine-tuning and 80% validation. The three pre-trained models were each validated using the five-folds of the six external datasets. The pre-trained models also underwent transfer learning with fine-tuning using the 20% training/fine-tuning data, and validated using the corresponding validation datasets. The highest micro-averaged AUC for our pre-trained models across all external datasets occurred with a resampling grid of 256 3 (AUC  =  0.91  ±  0.01). Transfer learning with fine-tuning improved generalizability when utilizing a resampling grid of 256 3 to a micro-averaged AUC of 0.92  ±  0.01. Despite these promising results, transfer learning did not improve AUC when utilizing small resampling grids or small datasets. Our work demonstrates the potential of our previously developed automated quality assurance methods to generalize to external datasets. Additionally, we showed that transfer learning with fine-tuning using small portions of external datasets can be used to fine-tune models for improved performance when large variations in images are present.

Purpose: Precision cancer medicine is dependent on accurate prediction of disease and treatment outcome, requiring integration of clinical, imaging and interventional knowledge. User controlled pipelines are capable of feature integration with varied levels of human interaction. In this work we present two pipelines designed to combine clinical, radiomic (quantified imaging), and RTx-omic (quantified radiation therapy (RT) plan) information for prediction of locoregional failure (LRF) in head and neck cancer (H&N)., Methods: Pipelines were designed to extract information and model patient outcomes based on clinical features, computed tomography (CT) imaging, and planned RT dose volumes. We predict H&N LRF using: 1) a highly user-driven pipeline that leverages modular design and machine learning for feature extraction and model development; and 2) a pipeline with minimal user input that utilizes deep learning convolutional neural networks to extract and combine CT imaging, RT dose and clinical features for model development., Results: Clinical features with logistic regression in our highly user-driven pipeline had the highest precision recall area under the curve (PR-AUC) of 0.66 (0.33-0.93), where a PR-AUC = 0.11 is considered random., Conclusions: Our work demonstrates the potential to aggregate features from multiple specialties for conditional-outcome predictions using pipelines with varied levels of human interaction. Most importantly, our results provide insights into the importance of data curation and quality, as well as user, data and methodology bias awareness as it pertains to result interpretation in user controlled pipelines., (Copyright © 2020 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.)

Hypoxia, the state of low oxygenation that often arises in solid tumours due to their high metabolism and irregular vasculature, is a major contributor to the resistance of tumours to radiation therapy (RT) and other treatments. Conventional RT extends treatment over several weeks or more, and nominally allows time for oxygen levels to increase ("reoxygenation") as cancer cells are killed by RT, mitigating the impact of hypoxia. Recent advances in RT have led to an increase in the use stereotactic body radiotherapy (SBRT), which delivers high doses in five or fewer fractions. For cancers such as pancreatic adenocarcinoma for which hypoxia varies significantly between patients, SBRT might not be optimal, depending on the extent to which reoxygenation occurs during its short duration. We used fluoro-5-deoxy-α-D-arabinofuranosyl)-2-nitroimidazole positron-emission tomography (FAZA-PET) imaging to quantify hypoxia before and after 5-fraction SBRT delivered to patient-derived pancreatic cancer xenografts orthotopically implanted in mice. An imaging technique using only the pre-treatment FAZA-PET scan and repeat dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) scans throughout treatment was able to predict the change in hypoxia. Our results support the further testing of this technique for imaging of reoxygenation in the clinic.

Enabling automated pipelines, image analysis and big data methodology in cancer clinics requires thorough understanding of the data. Automated quality assurance steps could improve the efficiency and robustness of these methods by verifying possible data biases. In particular, in head and neck (H&N) computed-tomography (CT) images, dental artifacts (DA) obscure visualization of structures and the accuracy of Hounsfield units; a challenge for image analysis tasks, including radiomics, where poor image quality can lead to systemic biases. In this work we analyze the performance of three-dimensional convolutional neural networks (CNN) trained to classify DA statuses. 1538 patient images were scored by a single observer as DA positive or negative. Stratified five-fold cross validation was performed to train and test CNNs using various isotropic resampling grids (64 3 , 128 3 and 256 3 ), with CNN depths designed to produce 32 3 , 16 3 , and 8 3 machine generated features. These parameters were selected to determine if more computationally efficient CNNs could be utilized to achieve the same performance. The area under the precision recall curve (PR-AUC) was used to assess CNN performance. The highest PR-AUC (0.92  ±  0.03) was achieved with a CNN depth  =  5, resampling grid  =  256. The CNN performance with 256 3 resampling grid size is not significantly better than 64 3 and 128 3 after 20 epochs, which had PR-AUC  =  0.89  ±  0.03 (p -value  =  0.28) and 0.91  ±  0.02 (p -value  =  0.93) at depths of 3 and 4, respectively. Our experiments demonstrate the potential to automate specific quality assurance tasks required for unbiased and robust automated pipeline and image analysis research. Additionally, we determined that there is an opportunity to simplify CNNs with smaller resampling grids to make the process more amenable to very large datasets that will be available in the future.

A hybrid system for intraoperative cone-beam CT (CBCT) imaging and continuous-wave fluorescence tomography (FT) has been developed using an image-guidance framework. Intraoperative CBCT images with sub-millimeter spatial resolution are acquired with a flat-panel C-Arm. Tetrahedral meshes are generated from CBCT for finite element method implementation of diffuse optical tomography (NIRFAST). Structural data from CBCT is incorporated directly into the optical reconstruction process using Laplacian-type regularization ('soft spatial priors'). Experiments were performed using an in-house optical system designed for indocyanine green (ICG) fluorescence. A dynamic non-contact geometry was achieved using a stereoscopic optical tracker for real-time localization of a laser diode and CCD camera. Source and detector positions were projected onto the boundary elements of the tissue mesh using algorithms for ray-triangle intersection and camera lens calibration. Simulation studies showed the capabilities of a soft-prior approach, even in the presence of segmentation uncertainties. Experiments with ICG targets embedded in liquid phantoms determined the improvements in the quantification of the fluorophore yield, with errors of 85% and  <20% for no priors and spatial priors, respectively. Similar results were observed with the ICG target embedded in ex vivo porcine loin, with errors of 52% and 12%, respectively. A proof-of-principal animal study was performed in a VX2-tumor in vivo rabbit model using liposomal nanoparticles co-encapsulating contrast for CT (iohexol) and fluorescence (ICG) imaging. Fusion of CBCT and FT reconstructions demonstrated concurrent anatomical and functional delineations of contrast enhancement around the periphery of the buccal tumor. These developments motivate future clinical translation of the FT system into an ongoing CBCT-guided head and neck surgery trial.

Radiation therapy (RT) is an essential component of effective cancer care and is used across nearly all cancer types. The delivery of RT is becoming more precise through rapid advances in both computing and imaging. The direct integration of magnetic resonance imaging (MRI) with linear accelerators represents an exciting development with the potential to dramatically impact cancer research and treatment. These impacts extend beyond improved imaging and dose deposition. Real-time MRI-guided RT is actively transforming the work flows and capabilities of virtually every aspect of RT. It has the opportunity to change entirely the delivery methods and response assessments of numerous malignancies. This review intends to approach the topic of MRI-based RT guidance from a vendor neutral and international perspective. It also aims to provide an introduction to this topic targeted towards oncologists without a speciality focus in RT. Speciality implications, areas for physician education and research opportunities are identified as they are associated with MRI-guided RT. The uniquely disruptive implications of MRI-guided RT are discussed and placed in context. We further aim to describe and outline important future changes to the speciality of radiation oncology that will occur with MRI-guided RT. The impacts on RT caused by MRI guidance include target identification, RT planning, quality assurance, treatment delivery, training, clinical workflow, tumour response assessment and treatment scheduling. In addition, entirely novel research areas that may be enabled by MRI guidance are identified for future investigation., (Published by Elsevier Ltd.)

Background: The image-guided operating room (OR) is an emerging standard for dealing with complex cases in many surgical disciplines including neurosurgery, thoracic surgery, maxillofacial trauma, and orthopedic surgery. Its use in head and neck oncological surgery is not well established. The primary aim of this study was to assess the image quality of cone-beam CT (CBCT) under real clinical conditions. The secondary aim was to assess the effect on surgical performance and decision making., Methods: Intraoperative 3D imaging was performed using a CBCT capable C-Arm mounted on a multi-axis robot (Siemens Zeego) in the image-guided OR. All patients had immediate preoperative imaging taken with further intraoperative imaging performed as required. Ten initial patients, comprising 28 intraoperative scans, were used for questionnaire-based image reviews conducted with experienced head and neck clinicians. Scans were assessed for aspects of both image quality and clinical utility, on separate 5-point Likert scales (1-5)., Results: The median rating for bony detail was 4 out of 5. Vascular detail was increased (P < 10 -8 ) from 1 to 3 with the use of IV contrast (region of interest CT# was 284 HU [SD, 47 HU]). Images were rated as 4 for freedom from artifact. Soft tissue definition was 2, with no significant improvement (P = .2) with the addition of IV iodinated contrast. Surgeons rated the greatest clinical utility (4) for the CBCT when assessing postreconstruction imaging of a complex case., Conclusions: The image quality of CBCT in the image-guided OR is good for bony detail and complex oncological reconstructions in the head and neck setting but probably has limited benefit for intraoperative soft tissue delineation. Future studies must also focus on clinical outcomes to help demonstrate the value of the image-guided OR., (© 2019 Wiley Periodicals, Inc.)

A non-contact approach for diffuse optical tomography (DOT) has been developed for on-demand image updates using surgical navigation technology. A stereoscopic optical tracker provides real-time localization of reflective spheres mounted to a laser diode and near-infrared camera. Standard camera calibration is combined with tracking data to determine the intrinsic camera parameters (focal length, principal point and non-linear lens distortion) and the tracker-to-camera transform. Tracker-to-laser calibration is performed using images of laser beam intersection with a tracked calibration surface. Source and detector positions for a finite-element DOT implementation are projected onto the boundary elements of the tissue mesh by finding ray-triangle intersections. A multi-stage model converts camera counts to surface flux by accounting for lens aperture settings, fluorescence filter transmittance, photodetector quantum efficiency, photon energy, exposure time, readout offset and camera gain. The image-guidance framework was applied to an in-house optical tomography system configured for indocyanine green (ICG) fluorescence. Mean target registration errors for camera and laser calibration were less than 1 mm. Surface flux measurements of total reflectance and fluorescence in Intralipid-based fluorescence phantoms (0-2 μg ml -1 ) had mean errors of 3.1% and 4.4%, respectively, relative to diffusion theory predictions. Spatially-resolved reflectance measurements in a calibrated optical phantom agreed with theory for radial distances up to 25 mm from the laser source. Inverse fluorescence reconstructions of a sub-surface fluorescence target confirmed the localization accuracy (average target centroid error of 0.44 mm). This translational research system is under investigation for clinical applications in head and neck surgery, including oral cavity tumor resection, lymph node mapping and free-flap perforator assessment.

Background: Radiotherapy is standard of care for cervical cancer, but major global gaps in access exist, particularly in low-income and middle-income countries. We modelled the health and economic benefits of a 20-year radiotherapy scale-up to estimate the long-term demand for treatment in the context of human papillomavirus (HPV) vaccination., Methods: We applied the Global Task Force on Radiotherapy for Cancer Control investment framework to model the health and economic benefits of scaling up external-beam radiotherapy and brachytherapy for cervical cancer in upper-middle-income, lower-middle-income, and low-income countries between 2015 and 2035. We estimated the unique costs of external-beam radiotherapy and brachytherapy and included a specific valuation of women's caregiving contributions. Model outcomes life-years gained and the human capital and full income net present value of investment. We estimated the effects of stage at diagnosis, radiotherapy delivery system, and simultaneous HPV vaccination (75% coverage) up to a time horizon set at 2072., Findings: For the period from 2015 to 2035, we estimated that 9·4 million women in low-income and middle-income countries required treatment with external-beam radiotherapy, of which 7·0 million also required treatment with brachytherapy. Incremental scale-up of radiotherapy in these countries from 2015 to meet optimal radiotherapy demand by 2035 yielded 11·4 million life-years gained, $59·3 billion in human capital net present value (-$1·5 billion in low-income, $19·9 billion in lower-middle-income, and $40·9 billion in upper-middle-income countries), and $151·5 billion in full income net present value ($1·5 billion in low-income countries, $53·6 billion in lower-middle-income countries, and $96·4 billion in upper-middle-income countries). Benefits increased with advanced stage of cervical cancer and more efficient scale up of radiotherapy. Bivalent HPV vaccination of 12-year-old girls resulted in a 3·9% reduction in incident cases from 2015-2035. By 2072, when the first vaccinated cohort of girls reaches 70 years of age, vaccination yielded a 22·9% reduction in cervical cancer incidence, with 38·4 million requiring external-beam radiotherapy and 28·8 million requiring brachytherapy., Interpretation: Effective cervical cancer control requires a comprehensive strategy. Even with HPV vaccination, radiotherapy treatment scale-up remains essential and produces large health benefits and a strong return on investment to countries at different levels of development., Funding: None., (Copyright © 2019 Elsevier Ltd. All rights reserved.)