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Purpose: Extramural venous invasion (EMVI) is recognized as a poor prognostic factor in rectal cancer. There are well-documented limitations associated with pathology detection of EMVI, including variable reporting and the inability to use it preoperatively to guide neoadjuvant treatment. Magnetic resonance imaging (MRI)-detected EMVI (mrEMVI) has been proposed as an imaging biomarker. This review assesses the prognostic significance of mrEMVI on survival outcomes and whether regression of mrEMVI after neoadjuvant therapy is associated with improvements in survival.Methods and Materials: An electronic search was carried out using MEDLINE and EMBASE databases using the search terms "rectum," "cancer,", "MRI," and "outcomes." A systematic review and meta-analysis were carried out in accordance with Preferred Reporting for Systematic Reviews and Meta-Analyses guidelines using Review Manager software. A qualitative review was performed.Results: A total of 7399 articles were identified, of which 33 were relevant to the review question. After a qualitative assessment, 20 articles were included in the meta-analysis. Baseline mrEMVI positivity is associated with significantly worsened overall survival (hazard ratio [HR] 1.84; 95% confidence interval [CI], 1.33-2.54; P = .0001) and significantly worsened disease-free survival (HR 2.41; 95% CI, 2.02-2.89; P < .00001). After neoadjuvant treatment, a positive mrEMVI status is associated with a significantly worsened overall and disease-free survival. Only 3 papers specifically looked at mrEMVI regression, but the results show that persistent mrEMVI-positive status after treatment is associated with significantly worsened disease-free survival compared with a change in mrEMVI from positive to negative (HR 1.93; 95% CI, 1.39-2.68; P < .0001). A subgroup analysis of MRI-detected lymph node metastases showed no significant association with survival, with a hazard ratio of 1.33 (95% CI, 0.98-1.80; P = .06).Conclusion: mrEMVI is significantly associated with worsened survival outcomes, both at baseline and after neoadjuvant treatment. Additionally, there is evidence that regression of mrEMVI after neoadjuvant treatment is associated with improved survival compared with mrEMVI persistence. The findings of this review emphasize the need for accurate and consistent reporting of mrEMVI status before and after neoadjuvant treatment and support the inclusion of mrEMVI into staging systems preferentially over lymph node metastases. [ABSTRACT FROM AUTHOR]

Purpose: Our purpose was to develop a deep learning-based computed tomography (CT) perfusion mapping (DL-CTPM) method that synthesizes lung perfusion images from CT images.Methods and Materials: This paper presents a retrospective analysis of the pulmonary technetium-99m-labeled macroaggregated albumin single-photon emission CT (SPECT)/CT scans obtained from 73 patients at Queen Mary Hospital in Hong Kong in 2019. The left and right lung scans were separated to double the size of the data set to 146. A 3-dimensional attention residual neural network was constructed to extract textural features from the CT images and reconstruct corresponding functional images. Eighty-four samples were randomly selected for training and cross-validation, and the remaining 62 were used for model testing in terms of voxel-wise agreement and function-wise concordance. To assess the voxel-wise agreement, the Spearman's correlation coefficient (R) and structural similarity index measure between the images predicted by the DL-CTPM and the corresponding SPECT perfusion images were computed to assess the statistical and perceptual image similarities, respectively. To assess the function-wise concordance, the Dice similarity coefficient (DSC) was computed to determine the similarity of the low/high functional lung volumes.Results: The evaluation of the voxel-wise agreement showed a moderate-to-high voxel value correlation (0.6733 ± 0.1728) and high structural similarity (0.7635 ± 0.0697) between the SPECT and DL-CTPM predicted perfusions. The evaluation of the function-wise concordance obtained an average DSC value of 0.8183 ± 0.0752 for high-functional lungs (range, 0.5819-0.9255) and 0.6501 ± 0.1061 for low-functional lungs (range, 0.2405-0.8212). Ninety-four percent of the test cases demonstrated high concordance (DSC >0.7) between the high-functional volumes contoured from the predicted and ground-truth perfusions.Conclusions: We developed a novel DL-CTPM method for estimating perfusion-based lung functional images from the CT domain using a 3-dimensional attention residual neural network, which yielded moderate-to-high voxel-wise approximations of lung perfusion. To further contextualize these results toward future clinical application, a multi-institutional large-cohort study is warranted. [ABSTRACT FROM AUTHOR]

Purpose: Radiation therapy (RT) after breast-conserving surgery reduces locoregional recurrences and improves survival but may cause late side effects. The main purpose of this paper was to investigate long-term side effects after whole breast RT in a randomized clinical trial initiated in 1991 and to report dose-volume data based on individual 3-dimensional treatment plans for organs at risk.Methods and Materials: The trial included 1187 patients with T1-2 N0 breast cancer randomized to postoperative tangential whole breast RT or no further treatment. The prescription dose to the clinical target volume was 48 to 54 Gy. We present 20-year follow-up on survival, cause of death, morbidity, and later malignancies. For a cohort of patients (n = 157) with accessible computed tomography-based 3-dimensional treatment plans in Dicom-RT format, dose-volume descriptors for organs at risk were derived. In addition, these were compared with dose-volume data for a cohort of patients treated with contemporary RT techniques.Results: The cumulative incidence of cardiac mortality was 12.4% in the control group and 13.0% in the RT group (P = .8). There was an increase in stroke mortality: 3.4% in the control group versus 6.7% in the RT group (P = .018). Incidences of contralateral breast cancer and lung cancer were similar between groups. The median Dmean (range) heart dose for left-sided treatments was 3.0 Gy (1.1-8.1), and the corresponding value for patients treated in 2017 was 1.5 Gy (0.4-6.0).Conclusions: In this trial, serious late side effects of whole breast RT were limited and less than previously reported in large meta-analyses. We observed no increase in cardiac mortality in irradiated patients. Doses to the heart were a median Dmean of 3.0 Gy for left-sided RT. The observed increase in stroke mortality may partly be secondary to cardiac side effects, complications to anticoagulant treatment, or to chance, rather than a direct side effect of tangential whole breast irradiation. [ABSTRACT FROM AUTHOR]

Purpose: Preclinical radiation replicating clinical intensity modulated radiation therapy (IMRT) techniques can provide data translatable to clinical practice. For this work, treatment plans were created for oxygen-guided dose-painting in small animals using inverse-planned IMRT. Spatially varying beam intensities were achieved using 3-dimensional (3D)-printed compensators.Methods and Materials: Optimized beam fluence from arbitrary gantry angles was determined using a verified model of the XRAD225Cx treatment beam. Compensators were 3D-printed with varied thickness to provide desired attenuation using copper/polylactic-acid. Spatial resolution capabilities were investigated using printed test-patterns. Following American Association of Physicists in Medicine TG119, a 5-beam IMRT plan was created for a miniaturized (∼1/8th scale) C-shape target. Electron paramagnetic resonance imaging of murine tumor oxygenation guided simultaneous integrated boost (SIB) plans conformally treating tumor to a base dose (Rx1) with boost (Rx2) based on tumor oxygenation. The 3D-printed compensator intensity modulation accuracy and precision was evaluated by individually delivering each field to a phantom containing radiochromic film and subsequent per-field gamma analysis. The methodology was validated end-to-end with composite delivery (incorporating 3D-printed tungsten/polylactic-acid beam trimmers to reduce out-of-field leakage) of the oxygen-guided SIB plan to a phantom containing film and subsequent gamma analysis.Results: Resolution test-patterns demonstrate practical printer resolution of ∼0.7 mm, corresponding to 1.0 mm bixels at the isocenter. The miniaturized C-shape plan provides planning target volume coverage (V95% = 95%) with organ sparing (organs at risk Dmax < 50%). The SIB plan to hypoxic tumor demonstrates the utility of this approach (hypoxic tumor V95%,Rx2 = 91.6%, normoxic tumor V95%,Rx1 = 95.7%, normal tissue V100%,Rx1 = 7.1%). The more challenging SIB plan to boost the normoxic tumor rim achieved normoxic tumor V95%,Rx2 = 90.9%, hypoxic tumor V95%,Rx1 = 62.7%, and normal tissue V100%,Rx2 = 5.3%. Average per-field gamma passing rates using 3%/1.0 mm, 3%/0.7 mm, and 3%/0.5 mm criteria were 98.8% ± 2.8%, 96.6% ± 4.1%, and 90.6% ± 5.9%, respectively. Composite delivery of the hypoxia boost plan and gamma analysis (3%/1 mm) gave passing results of 95.3% and 98.1% for the 2 measured orthogonal dose planes.Conclusions: This simple and cost-effective approach using 3D-printed compensators for small-animal IMRT provides a methodology enabling preclinical studies that can be readily translated into the clinic. The presented oxygen-guided dose-painting demonstrates that this methodology will facilitate studies driving much needed biologic personalization of radiation therapy for improvements in patient outcomes. [ABSTRACT FROM AUTHOR]

Purpose: Kilovoltage intrafraction monitoring (KIM) is a new real-time 3-dimensional image guidance method. Unlike previous real-time image guidance methods, KIM uses a standard linear accelerator without any additional equipment needed. The first prospective clinical trial of KIM is underway for prostate cancer radiation therapy. In this paper we report on the measured motion accuracy and precision using real-time KIM-guided gating.Methods and Materials: Imaging and motion information from the first 200 fractions from 6 patient prostate cancer radiation therapy volumetric modulated arc therapy treatments were analyzed. A 3-mm/5-second action threshold was used to trigger a gating event where the beam is paused and the couch position adjusted to realign the prostate to the treatment isocenter. To quantify the in vivo accuracy and precision, KIM was compared with simultaneously acquired kV/MV triangulation for 187 fractions.Results: KIM was successfully used in 197 of 200 fractions. Gating events occurred in 29 fractions (14.5%). In these 29 fractions, the percentage of beam-on time, the prostate displacement was >3 mm from the isocenter position, reduced from 73% without KIM to 24% with KIM-guided gating. Displacements >5 mm were reduced from 16% without KIM to 0% with KIM. The KIM accuracy was measured at <0.3 mm in all 3 dimensions. The KIM precision was <0.6 mm in all 3 dimensions.Conclusions: Clinical implementation of real-time KIM image guidance combined with gating for prostate cancer eliminates large prostate displacements during treatment delivery. Both in vivo KIM accuracy and precision are well below 1 mm. [ABSTRACT FROM AUTHOR]

Purpose: Chemoradiation therapy (CRT) for patients with locally advanced pancreatic cancer (LAPC) provides survival benefits but may result in considerable toxicity. Health-related quality of life (HRQL) measurements during CRT have not been widely reported. This paper reports HRQL data from the Selective Chemoradiation in Advanced Localised Pancreatic Cancer (SCALOP) trial, including validation of the QLQ-PAN26 tool in CRT.Methods and Materials: Patients with locally advanced, inoperable, nonmetastatic carcinoma of the pancreas were eligible. Following 12 weeks of induction gemcitabine plus capecitabine (GEMCAP) chemotherapy, patients with stable and responding disease were randomized to a further cycle of GEMCAP followed by capecitabine- or gemcitabine-based CRT. HRQL was assessed with the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) and the EORTC Pancreatic Cancer module (PAN26).Results: A total of 114 patients from 28 UK centers were registered and 74 patients randomized. There was improvement in the majority of HRQL scales during induction chemotherapy. Patients with significant deterioration in fatigue, appetite loss, and gastrointestinal symptoms during CRT recovered within 3 weeks following CRT. Differences in changes in HRQL scores between trial arms rarely reached statistical significance; however, where they did, they favored capecitabine therapy. PAN26 scales had good internal consistency and were able to distinguish between subgroups of patients experiencing toxicity.Conclusions: Although there is deterioration in HRQL following CRT, this resolves within 3 weeks. HRQL data support the use of capecitabine- over gemcitabine-based chemoradiation. The QLQ-PAN26 is a reliable and valid tool for use in patients receiving CRT. [ABSTRACT FROM AUTHOR]

Head and neck cancer is the fifth most common cancer in the United States, with an overall survival rate of approximately 40-50%. In an effort to improve patient outcomes, research efforts designed to maximize benefit and reduce toxicities of therapy are in progress. Basic research in cancer biology has accelerated this endeavor and provided preclinical data and technology to support clinically relevant advances in early detection, prognostic and predictive biomarkers. Recent completion of the Human Genome Project has promoted the rapid development of novel "omics" technologies that allow more broad based study from a systems biology perspective. However, clinically relevant application of resultant gene signatures to clinical trials within cooperative groups has advanced slowly. In light of the large numbers of variables intrinsic to biomarker studies, validation of preliminary data for clinical implementation presents a significant challenge and may only be realized with large trials that involve significant patient numbers. The Radiation Therapy Oncology Group (RTOG) Head and Neck Cancer Translational Research Program recognizes this problem and brings together three unique features to facilitate this research: (1) availability of large numbers of clinical specimens from homogeneously treated patients through multi-institutional clinical trials; (2) a team of physicians, scientists, and staff focused on patient-oriented head-and-neck cancer research with the common goal of improving cancer care; and (3) a funding mechanism through the RTOG Seed Grant Program. In this position paper we outline strategic plans to further promote translational research within the framework of the RTOG. [ABSTRACT FROM AUTHOR]

Purpose: Recent imaging studies have demonstrated that there can be significant changes in anatomy from day to day and over the course of radiotherapy as a result of daily positioning uncertainties and physiologic and clinical factors. There are a number of strategies to minimize such changes, reduce their impact, or correct for them. Measures to date have included improved immobilization of external and internal anatomy or adjustment of positions based on portal or ultrasound images. Perhaps the most accurate way is to use CT image–guided radiotherapy, for which the possibilities range from simple correction of setup based on daily CT images to on-line near real-time intensity modulated radiotherapy (IMRT) replanning. In addition, there are numerous intermediate possibilities. In this paper, we report the development of one such intermediate method that takes into account anatomic changes by deforming the intensity distributions of each beam based on deformations of anatomy as seen in the beam''s-eye–view. Methods and materials: The intensity distribution deformations are computed based on anatomy deformations discerned from the changes in the current image relative to a reference image (e.g., the pretreatment CT scan). First, a reference IMRT plan is generated based on the reference CT image. A new CT image is acquired using an in-room CT for every fraction. The anatomic structure contours are obtained for the new image. (For this article, these contours were manually drawn. When image guided IMRT methods are implemented, anatomic structure contours on subsequent images will likely be obtained with automatic or semiautomatic means. This could be achieved by, for example, first deforming the original CT image to match today''s image, and then using the same deformation transformation to map original contours to today''s image.) The reference intensity distributions for each beam are then deformed so that the projected geometric relationship within the beam''s-eye–view between the anatomy (both target and normal tissues) extracted from the reference image and the reference intensity distribution is the same as (or as close as possible to) the corresponding relationship between anatomy derived from today''s image and the newly deformed intensity distributions. To verify whether the dose distributions calculated using the deformed intensity distributions are acceptable for treatment as compared to the original intensity distributions, the deformed intensities are transformed into leaf sequences, which are then used to compute intensity and dose distributions expected to be delivered. The corresponding dose–volume histograms and dose–volume and dose–response indices are also computed. These data are compared with the corresponding data derived (a) from the original treatment plan applied to the original image, (b) from the original treatment plan applied to today''s image, and (c) from a new full-fledged IMRT plan designed based on today''s image. Results: Depending on the degree of anatomic changes, the use of an IMRT plan designed based on the original planning CT for the treatment of the current fraction could lead to significant differences compared to the intended dose distributions. CT-guided setup compared to the setup based on skin marks or bony landmarks may improve dose distributions somewhat. Replanning IMRT based on the current fraction''s image yields the best physically deliverable plan (the “gold standard”). For the prostate and head-and-neck examples studied as proof of principle, the results of deforming intensities within each beam based on the anatomy seen in the beam''s-eye–view are a good approximation of full-fledged replanning compared with other alternatives. Conclusions: Our preliminary results encourage us to believe that deforming intensities taking into account deformation in the anatomy may be a rapid way to produce new treatment plans on-line in near real-time based on daily CT images. The methods we have developed need to be applied to a group of patients for both prostate and head-and-neck cases to confirm the validity of our approach. [Copyright &y& Elsevier]

: PurposeWith the advent of intraoperative optimized planning, the treatment of prostate cancer with permanent implants has reached an unprecedented level of dose conformity. However, because of well-documented (and unavoidable) inaccuracies in seed placement into the gland, carrying out a plan results in a large degree of variability relative to the intended dose distribution. This brings forth the need to periodically readjust the plan to allow for the real positions of seeds already implanted. In this paper, an algorithm for performing this task, hereby described as intraoperative dynamic dose optimization (IDDO), is presented and assessed.: Methods and materialsThe general scheme for performing IDDO consists of three steps: (1) at some point during the implant, coordinates of implanted seeds are identified; (2) seed images are projected onto the reference frame of the ultrasound images for planning; and (3) the plan is reoptimized. Work on the first two steps is reported elsewhere. Here, we focus on the strategy for implementing the reoptimization step. An optimal treatment plan is first obtained based on initial operating room–acquired ultrasound images. We analyze the sensitivity and effect of the IDDO procedure with respect to the total number of reoptimizations performed. Specifically, we consider reoptimizing 2, 3, and 4 times. When two reoptimizations are used, half of the seeds from the initial optimal plan are implanted. The first reoptimization is performed on the remaining possible seed positions, and all the seeds designated in this reoptimized plan are implanted. The second (final) reoptimization is done on the remaining unused seed positions to ensure 100% coverage of the gland and to eliminate possible cold spots in the gland. Similarly, when three reoptimization steps are used, one-third of the seeds from the initial optimized plan, one-half of the seeds from the first reoptimization, and all seeds from the second reoptimization are implanted. The third (final) reoptimization is performed to assist in eliminating possible cold spots. Reoptimizing four times proceeds in a like manner. Fifteen patient cases are used for comparison. Strict dose bounds of 100% and 120% of the prescription dose are imposed on the urethra, and 100% coverage is imposed on the prostate volume. To assist in achieving good conformity, prostate contour points are assigned a target upper dose bound of 150% of the prescription dose.: ResultsA two-way comparison is performed: (a) initial optimized plan, (b) IDDO plan. Postimplant dose analysis, coverage and conformity measures, as well as actual dose received by urethra and rectum are used to gauge the results. The initial optimized plan consistently provides 93% prescription dose coverage to the gland with average conformity index of 1.32. The urethra dose ranges within 100% to 150%, and the maximum dose delivered to the rectum reaches 91% of the prescription dose. On average, about 50% of the urethra receives more than 120% of the prescription dose, and 19% of the rectum volume receives more than the 78% upper dose limit. For the IDDO plan, 100% postimplant coverage with 1.16 conformity is achieved. Urethra and rectum dose is maintained within the prescribed 100% to 120% range and 78% upper bound, respectively.: ConclusionsWith real-time treatment planning, it is possible to dynamically reoptimize treatment plans to account for actual seed positions (as opposed to planned positions) and needle-induced swelling to the gland during implantation. Postimplant analysis shows that the final seed configuration resulting from the IDDO method yields improved dosimetry. The algorithmic design ensures that one can achieve complete coverage while maintaining good conformity, thus sparing excess radiation to external tissue. The study also provides evidence of the possibility of morbidity reduction to urethra and rectum (because of reduced dose delivered to these structures) via the use of IDDO planning. Clinical studies are needed to validate the importance of our approach. [Copyright &y& Elsevier]

Purpose: The precise shape of the three-dimensional dose distributions created by intensity-modulated radiotherapy means that the verification of patient position and setup is crucial to the outcome of the treatment. In this paper, we investigate and compare the use of two different image calibration procedures that allow extraction of patient anatomy from measured electronic portal images of intensity-modulated treatment beams.Methods and Materials: Electronic portal images of the intensity-modulated treatment beam delivered using the dynamic multileaf collimator technique were acquired. The images were formed by measuring a series of frames or segments throughout the delivery of the beams. The frames were then summed to produce an integrated portal image of the delivered beam. Two different methods for calibrating the integrated image were investigated with the aim of removing the intensity modulations of the beam. The first involved a simple point-by-point division of the integrated image by a single calibration image of the intensity-modulated beam delivered to a homogeneous polymethyl methacrylate (PMMA) phantom. The second calibration method is known as the quadratic calibration method and required a series of calibration images of the intensity-modulated beam delivered to different thicknesses of homogeneous PMMA blocks. Measurements were made using two different detector systems: a Varian amorphous silicon flat-panel imager and a Theraview camera-based system. The methods were tested first using a contrast phantom before images were acquired of intensity-modulated radiotherapy treatment delivered to the prostate and pelvic nodes of cancer patients at the Royal Marsden Hospital.Results: The results indicate that the calibration methods can be used to remove the intensity modulations of the beam, making it possible to see the outlines of bony anatomy that could be used for patient position verification. This was shown for both posterior and lateral delivered fields.Conclusions: Very little difference between the two calibration methods was observed, so the simpler division method, requiring only the single extra calibration measurement and much simpler computation, was the favored method. This new method could provide a complementary tool to existing position verification methods, and it has the advantage that it is completely passive, requiring no further dose to the patient and using only the treatment fields. [Copyright &y& Elsevier]