Multi-institutional Development and Validation of Contouring Guidelines for Para-aortic Elective Nodal Irradiation in Prostate Cancer Based on Patterns of Involvement on Targeted Molecular Imaging Positron Emission Tomography/Computed Tomography.

PURPOSE: Molecular imaging better identifies anatomic regions of metastatic spread of prostate cancer compared with conventional imaging, resulting in para-aortic (PA) nodal metastases being increasingly identified. Consequently, some radiation oncologists electively treat the PA lymph node region in patients with gross or high risk of PA nodal involvement. The anatomic locations of at-risk PA lymph nodes for prostate cancer are unknown. Our objective was to use molecular imaging to develop guidelines for the optimal delineation of the PA clinical target volume (CTV) in patients with prostate cancer. METHODS AND MATERIALS: We conducted a multi-institutional retrospective cohort study of patients with prostate cancer undergoing 18F-fluciclovine or 18F-DCFPyL prostate-specific membrane antigen positron emission tomography (PET)/computed tomography (CT). Images of patients with PET-positive PA nodes were imported into the treatment planning system, avid nodes were contoured, and measurements were taken in relation to anatomic landmarks. A contouring guideline that encompassed the location of ≥95% of PET-positive PA nodes was created using descriptive statistics and then validated in an independent data set. RESULTS: Five hundred fifty-nine patients had molecular PET/CT imaging in the development data set (78% 18F-fluciclovine, 22% prostate-specific membrane antigen). Seventy-six patients (14%) had evidence of PA nodal metastasis. We determined that expanding the CTV to 1.8 cm left of the aorta, 1.4 cm right of the inferior vena cava (IVC), 7 mm posterior to the aorta/IVC or to the vertebral body, and superiorly to the T11/T12 vertebral interface, with the anterior border 4 mm anterior to the aorta/IVC and inferior border at the bifurcation of the aorta/IVC, resulted in coverage of ≥95% of PET-positive PA nodes. When the guideline was used in the independent validation data set (246 patients with molecular PET/CT imaging, of whom 31 had PA nodal metastasis), 97% of nodes were encompassed, thereby validating our guideline. CONCLUSIONS: We used molecular PET/CT imaging to determine the anatomic locations of PA metastases to develop contouring guidelines for creating a prostate cancer PA CTV. Although the optimal patient selection and clinical benefits of PA radiation therapy remain uncertain, our results will aid in delineating the optimal target when PA radiation therapy is pursued.

ACR Appropriateness Criteria® Cranial Neuropathy: 2022 Update.

Cranial neuropathy can result from pathology affecting the nerve fibers at any point and requires imaging of the entire course of the nerve from its nucleus to the end organ in order to identify a cause. MRI with and without intravenous contrast is often the modality of choice with CT playing a complementary role. The ACR Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision process support the systematic analysis of the medical literature from peer-reviewed journals. Established methodology principles such as Grading of Recommendations Assessment, Development, and Evaluation or GRADE are adapted to evaluate the evidence. The RAND/UCLA Appropriateness Method User Manual provides the methodology to determine the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances in which peer-reviewed literature is lacking or equivocal, experts may be the primary evidentiary source available to formulate a recommendation.

Lymphocyte sparing normal tissue effects in the clinic (LymphoTEC): A systematic review of dose constraint considerations to mitigate radiation-related lymphopenia in the era of immunotherapy.

BACKGROUND: Radiation-related lymphopenia has been associated with suboptimal tumor control rates leading to inferior survival outcomes. To date, no standardized dose constraints are available to limit radiation dose to resident and circulating lymphocyte populations. We undertook this systemic review of the literature to provide a synopsis of the dosimetric predictors of radiation-related lymphopenia in solid malignancies. METHODOLOGY: A systematic literature review of PubMed (National Institutes of Health), Cochrane Central (Cochrane collaboration), and Google Scholar was conducted with the following keywords: "radiation", "lymphopenia", "cancer", "dosimetric predictors" with an inclusion deadline of May 31, 2022. Studies that met prespecified inclusion criteria were designated either Good, Fair, or Poor Quality based on the Newcastle-Ottawa quality assessment. The dosimetric parameters derived from Good Quality studies were tabulated as LymphoTEC dose constraints. Dosimetric parameters derived from Fair and Poor-quality studies were grouped as optional. RESULTS: An initial systematic search of the literature yielded 1,632 articles. After screening, a total of 48 studies met inclusion criteria and were divided into the following categories: central nervous system (CNS, 6), thoracic (11), gastrointestinal (26), gynecologic (2), head and neck, breast, and genitourinary (one each) cancers. Lung mean dose, heart mean dose, brain V25, spleen mean dose, estimated dose to immune cells, and bone marrow V10 were among the strongest predictors for severe lymphopenia related to radiotherapy. CONCLUSION: Optimizing the delivery of radiation therapy to limit dose to lymphocyte-rich structures may curb the negative oncologic impact of lymphocyte depletion. The dose constraints described herein may be considered for prospective validation and future use in clinical trials to limit risk of radiation-related lymphopenia and possibly improve cancer-associated outcomes.

Retrospective Clinical Evaluation of a Decision-Support Software for Adaptive Radiotherapy of Head and Neck Cancer Patients.

Purpose: This study aimed to evaluate the clinical need for an automated decision-support software platform for adaptive radiation therapy (ART) of head and neck cancer (HNC) patients. Methods: We tested RTapp (SegAna), a new ART software platform for deciding when a treatment replan is needed, to investigate a set of 27 HNC patients' data retrospectively. For each fraction, the software estimated key components of ART such as daily dose distribution and cumulative doses received by targets and organs at risk (OARs) from daily 3D imaging in real-time. RTapp also included a prediction algorithm that analyzed dosimetric parameter (DP) trends against user-specified thresholds to proactively trigger adaptive re-planning up to four fractions ahead. The DPs evaluated for ART were based on treatment planning dose constraints. Warning (V95<95%) and adaptation (V95<93%) thresholds were set for PTVs, while OAR adaptation dosimetric endpoints of +10% (DE10) were set for all Dmax and Dmean DPs. Any threshold violation at end of treatment (EOT) triggered a review of the DP trends to determine the threshold-crossing fraction Fx when the violations occurred. The prediction model accuracy was determined as the difference between calculated and predicted DP values with 95% confidence intervals (CI95). Results: RTapp was able to address the needs of treatment adaptation. Specifically, we identified 18/27 studies (67%) for violating PTV coverage or parotid Dmean at EOT. Twelve PTVs had V95<95% (mean coverage decrease of -6.8 ± 2.9%) including six flagged for adaptation at median Fx = 6 (range, 1-16). Seventeen parotids were flagged for exceeding Dmean dose constraints with a median increase of +2.60 Gy (range, 0.99-6.31 Gy) at EOT, including nine with DP>DE10. The differences between predicted and calculated PTV V95 and parotid Dmean was up to 7.6% (mean ± CI95, -2.7 ± 4.1%) and 5 Gy (mean ± CI95, 0.3 ± 1.6 Gy), respectively. The most accurate predictions were obtained closest to the threshold-crossing fraction. For parotids, the results showed that Fx ranged between fractions 1 and 23, with a lack of specific trend demonstrating that the need for treatment adaptation may be verified for every fraction. Conclusion: Integrated in an ART clinical workflow, RTapp aids in predicting whether specific treatment would require adaptation up to four fractions ahead of time.

A comparison of proton stopping power measured with proton CT and x-ray CT in fresh postmortem porcine structures.

PURPOSE: Currently, calculations of proton range in proton therapy patients are based on a conversion of CT Hounsfield units of patient tissues into proton relative stopping power. Uncertainties in this conversion necessitate larger proximal and distal planned target volume margins. Proton CT can potentially reduce these uncertainties by directly measuring proton stopping power. We aim to demonstrate proton CT imaging with complex porcine samples, to analyze in detail three-dimensional regions of interest, and to compare proton stopping powers directly measured by proton CT to those determined from x-ray CT scans. METHODS: We have used a prototype proton imaging system with single proton tracking to acquire proton radiography and proton CT images of a sample of porcine pectoral girdle and ribs, and a pig's head. We also acquired close in time x-ray CT scans of the same samples and compared proton stopping power measurements from the two modalities. In the case of the pig's head, we obtained x-ray CT scans from two different scanners and compared results from high-dose and low-dose settings. RESULTS: Comparing our reconstructed proton CT images with images derived from x-ray CT scans, we find agreement within 1% to 2% for soft tissues and discrepancies of up to 6% for compact bone. We also observed large discrepancies, up to 40%, for cavitated regions with mixed content of air, soft tissue, and bone, such as sinus cavities or tympanic bullae. CONCLUSIONS: Our images and findings from a clinically realistic proton CT scanner demonstrate the potential for proton CT to be used for low-dose treatment planning with reduced margins.

The Impact of Transitioning to Prospective Contouring and Planning Rounds as Peer Review.

PURPOSE: Our peer-review program previously consisted of weekly chart rounds performed before the end of the first week of treatment. In order to perform peer review before the start of treatment when possible, we implemented daily prospective contouring and planning rounds (CPR). METHODS AND MATERIALS: At the time of computed tomography simulation, patients were categorized by the treating physician into 5 treatment groups based on urgency and complexity (ie, standard, urgent, palliative nonemergent, emergent, and special procedures). A scoring system was developed to record the outcome of case presentations, and the results of the CPR case presentations were compared with the time period 2.5 years before CPR implementation, for which peer review was performed retrospectively. RESULTS: CPR was implemented on October 1, 2015, and a total of 4759 patients presented for care through May 31, 2018. The majority were in the standard care path (n = 3154; 66.3%). Among the remainder of the charts, 358 (7.5%), 430 (9.0%), and 179 (3.8%) cases were in the urgent, nonemergent palliative, and emergent care paths, respectively. The remaining patients were in the special procedures group, representing brachytherapy and stereotactic radiosurgery. A total of 125 patients (2.6%) required major changes and were re-presented after the suggested modifications, 102 patients (2.1%) had minor recommendations that did not require a repeat presentation, and 247 cases (5.2%) had minor documentation-related recommendations that did not require editing of the contours. In the 2.5 years before the implementation, records of a total of 1623 patients were reviewed, and only 9 patients (0.6%) had minor recommendation for change. The remainder was noted as complete agreement. CONCLUSIONS: Contouring and planning rounds were successfully implemented at our clinic. Pretreatment and, most often, preplanning review of contours and directives allows for a more detailed review and changes to be made early on in the treatment planning process. When compared with historical case presentations, the CPR method made our peer review more thorough and improved standardization.

The Impact of Academic Facility Type and Case Volume on Survival in Patients Undergoing Curative Radiation Therapy for Muscle-Invasive Bladder Cancer.

PURPOSE: Bladder-preserving curative radiation therapy (RT) has been established as an excellent treatment option for select patients with muscle-invasive bladder cancer (MIBC). However, some clinicians have concerns that good outcomes are only achievable at high-volume facilities (HVFs) and academic centers (ACs), questioning successful reproducibility of curative RT at smaller centers. This study sought to determine whether treatment at ACs or HVFs was associated with better overall survival (OS) than treatment at nonacademic centers or lower-volume facilities. METHODS AND MATERIALS: We performed a retrospective cohort study of National Cancer Database patients (n=2763) with cT2 to cT4 N0 M0 transitional cell MIBC who received curative RT (60-70 Gy) with or without concurrent chemotherapy. Cox proportional hazards models were used to estimate the instantaneous hazard of death as a function of univariate and multivariate patient characteristics and clinical measures. RESULTS: Univariate analysis showed that academic facility type was significantly associated with improved OS (hazard ratio [HR], 0.88; 95% confidence interval [CI] 0.79-0.98; P=.02) whereas higher case volume was not associated with improved survival (HR, 0.97; 95% CI 0.92-1.01; P=.15). Multivariate analysis showed no differences in OS for treatment at ACs versus nonacademic centers (HR, 0.94; 95% CI 0.84-1.06; P=.31) or HVFs versus lower-volume facilities (HR, 0.99; 95% CI 0.94-1.04; P=.60). The 2-year OS rate was 54.5% (95% CI 52.5%-56.4%), and the 5-year OS rate was 28.9% (95% CI 27.0%-30.8%). CONCLUSIONS: Although some providers are cautious about offering curative RT at all centers, this large hospital-based study suggests that facility type and volume are not significantly associated with OS for patients undergoing curative RT after we account for other clinically relevant risk factors. The results of this study demonstrate that curative RT in the treatment of MIBC may be considered for patients regardless of facility type or volume.

Adjuvant therapy in patients with clear cell endometrial carcinoma: An analysis of the National Cancer Database.

OBJECTIVE: To assess the impact of adjuvant treatment, sociodemographic and tumor factors on the survival of patients with non-metastatic clear cell endometrial carcinoma (CCC). METHODS: 4298 patients treated from 1998 to 2011 with Stage I-IVA CCC were identified within the National Cancer Database. FIGO 2009 staging system was used. Adjuvant groups included: hysterectomy (HYS); HYS+vaginal brachytherapy (VBT); HYS+chemotherapy (CT); HYS+external beam radiation therapy (EBRT); HYS+CT+EBRT; and HYS+CT+VBT. Univariable (UVA) and multivariable (MVA) frailty survival analyses were performed. RESULTS: On UVA, higher stage was associated with an increased risk of death. Compared to stage I-IA, the risk of death for stage IB was HR 1.75 (95% CI, 1.50-2.04; p<0.001), stage II was HR 1.77 (95% CI, 1.50-2.10; p<0.001), stage III-IIIB was HR 3.29 (95% CI, 2.86-3.80; p<0.001), stage IIIC-IIIC2 was HR 3.33 (95% CI: 2.94-3.77; p<0.001), and stage IVA was 8.59 (95% CI: 6.60-11.18; p<0.001). Other meaningful predictors of death included black race (p<0.001), public insurance (p<0.001), geographic education attainment (p=0.001), greater comorbidity score (p=0.001), increasing age (p<0.001), and increasing tumor size (p<0.001). After controlling for stage, insurance, race, education attainment, comorbidity score, age, and tumor size adjuvant treatment was not associated with decreased risk of mortality (p=0.26). CONCLUSION: Adjuvant therapy did not have a meaningful effect on survival in this sample from the National Cancer Center Database. Given the aggressive nature of the disease, clinical trials are required to determine the optimal adjuvant therapy in patients with non-metastatic CCC to improve clinical outcomes.

Concurrent chemotherapy is associated with improved survival in elderly patients with bladder cancer undergoing radiotherapy.

BACKGROUND: The current study was conducted to compare the overall survival (OS) of concurrent chemoradiotherapy (CCRT) versus radiotherapy (RT) alone in elderly patients (those aged ≥80 years) with muscle-invasive bladder cancer (MIBC). METHODS: Patients aged ≥80 years with cT2-4, N0-3, M0 transitional cell MIBC who were treated with curative RT (60-70 Gray) or CCRT were identified in the National Cancer Data Base. Univariable and multivariable frailty survival analyses, as well as 1-to-1 propensity score matching, were used to isolate the association between CCRT and OS. RESULTS: A total of 1369 patients who were treated with RT from 2004 through 2013 met eligibility criteria: 739 patients (54%) received RT alone and 630 patients (46%) received CCRT. The median age of the patients was 84 years (range, 80-90 years). The median follow-up was 21 months. The 2-year OS rate was 48%. When comparing CCRT with RT alone, the 2-year OS rate was 56% versus 42% (P<.0001), respectively. Multivariable analysis demonstrated that CCRT (hazard ratio [HR], 0.74; 95% confidence interval [95% CI], 0.65-0.84 [P<.0001]) and a higher RT dose (HR, 0.78; 95% CI, 0.67-0.90 [P<.001]) were associated with improved OS. T4 disease was associated with worse OS (HR, 1.42; 95% CI, 1.15-1.76 [P = .001]). After using 1-to-1 propensity score matching, there remained an OS benefit for the use of CCRT (HR, 0.77; 95% CI, 0.67-0.90 [P<.001]). CONCLUSIONS: CCRT is associated with improved OS compared with the use of RT alone in elderly patients with MIBC, independent of Charlson-Deyo comorbidity score, suggesting that CCRT should be used in this population. Cancer 2017;123:3524-31. © 2017 American Cancer Society.

American Brachytherapy Task Group Report: Adjuvant vaginal brachytherapy for early-stage endometrial cancer: A comprehensive review.

This article aims to review the risk stratification of endometrial cancer, treatment rationale, outcomes, treatment planning, and treatment recommendations of vaginal brachytherapy (VBT) in the postoperative management of endometrial cancer patients. The authors performed a thorough review of the literature and reference pertinent articles pertaining to the aims of this review. Adjuvant VBT for early-stage endometrial cancer patients results in very low rates of vaginal recurrence (0-3.1%) with low rates of late toxicity which are primarily vaginal in nature. Post-Operative Radiation Therapy in Endometrial Cancer 2 (PORTEC-2) supports that VBT results in noninferior rates of vaginal recurrence compared to external beam radiotherapy for the treatment of high-intermediate risk patients. VBT as a boost after external beam radiotherapy, in combination with chemotherapy, and for high-risk histologies have shown excellent results as well though randomized data do not exist supporting VBT boost. There are many different applicators, dose-fractionation schedules, and treatment planning techniques which all result in favorable clinical outcomes and low rates of toxicity. Recommendations have been published by the American Brachytherapy Society and the American Society of Radiation Oncology to help guide practitioners in the use of VBT. Data support that patients and physicians prefer joint decision making regarding the use of VBT, and patients often desire additional treatment for a marginal benefit in risk of recurrence. Discussions regarding adjuvant therapy for endometrial cancer are best performed in a multidisciplinary setting, and patients should be counseled properly regarding the risks and benefits of adjuvant therapy.

Improved overall survival with adjuvant radiotherapy for high-intermediate and high risk Stage I endometrial cancer.

BACKGROUND/PURPOSE: To perform a large analysis of Stage I endometrioid-type endometrial cancer patients to determine the impact of adjuvant radiotherapy (ART) on survival. MATERIAL/METHODS: 132,976 FIGO Stage I endometrioid-type endometrial cancer patients treated surgically were identified within the National Cancer Database (NCDB) comprising Commission on Cancer facilities in the United States. Patients were categorized as observation (OBS) or ART (vaginal brachytherapy, external beam radiotherapy, or both). Univariable generalized linear mixed effects models were used to estimate the odds of receiving ART, and a multivariable frailty survival model was used to estimate the instantaneous hazard of death for those receiving OBS versus ART. Due to the presence of a significant interaction, these estimates were stratified by PORTEC-based low, low-intermediate, high-intermediate, and high risk groups. RESULTS: 104,645 (79%) underwent OBS while 28,331 (21%) received ART. Of those receiving ART, 12,913 (46%) received VBT alone, 12,857 (45%) received EBRT alone, and 2561 (9%) received EBRT+VBT. On univariable analysis, increasing stage/myometrial invasion, higher grade, older age, presence of lymphovascular space invasion, and larger tumor size predicted poorer survival (all p<0.01). On multivariable analysis, patients at high-intermediate risk and high risk experienced improved survival with ART with a hazard ratio of 0.796 (95% CI: 0.731-0.867; p<0.001) and 0.783 (95% CI: 0.693-0.885; p<0.001), respectively. There was no survival benefit for ART among patients at low or low-intermediate risk. CONCLUSIONS: In Stage I high-intermediate and high risk endometrioid-type endometrial cancer patients, ART significantly improves overall survival.

Evaluation of a template-based algorithm for markerless lung tumour localization on single- and dual-energy kilovoltage images.

OBJECTIVE: To evaluate a template-based matching algorithm on single-energy (SE) and dual-energy (DE) radiographs for markerless localization of lung tumours. METHODS: A total of 74 images from 17 patients with Stages IA-IV lung cancer were considered. At the time of radiotherapy treatment, gated end-expiration SE radiographs were obtained at 60 and 120 kVp at different gantry angles (33° anterior and 41° oblique), from which soft-tissue-enhanced DE images were created. A template-based matching algorithm was used to localize individual tumours on both SE and DE radiographs. Tumour centroid co-ordinates obtained from the template-matching software on both SE and DE images were compared with co-ordinates defined by physicians. RESULTS: The template-based matching algorithm was able to successfully localize the gross tumor volume within 5 mm on 70% (52/74) of the SE images vs 91% (66/74) of the DE images (p < 0.01). The mean vector differences between the co-ordinates of the template matched by the algorithm and the co-ordinates of the physician-defined ground truth were 3.2 ± 2.8 mm for SE images vs 2.3 ± 1.7 mm for DE images (p = 0.03). CONCLUSION: Template-based matching on DE images was more accurate and precise than using SE images. Advances in knowledge: This represents, to the authors' knowledge, the largest study evaluating template matching on clinical SE and DE images, considering not only anterior gantry angles but also oblique angles, suggesting a novel lung tumour matching technique using DE subtraction that is reliable, accurate and precise.

Observer Evaluation of a Metal Artifact Reduction Algorithm Applied to Head and Neck Cone Beam Computed Tomographic Images.

PURPOSE AND OBJECTIVES: To quantify, through an observer study, the reduction in metal artifacts on cone beam computed tomographic (CBCT) images using a projection-interpolation algorithm, on images containing metal artifacts from dental fillings and implants in patients treated for head and neck (H&N) cancer. METHODS AND MATERIALS: An interpolation-substitution algorithm was applied to H&N CBCT images containing metal artifacts from dental fillings and implants. Image quality with respect to metal artifacts was evaluated subjectively and objectively. First, 6 independent radiation oncologists were asked to rank randomly sorted blinded images (before and after metal artifact reduction) using a 5-point rating scale (1 = severe artifacts; 5 = no artifacts). Second, the standard deviation of different regions of interest (ROI) within each image was calculated and compared with the mean rating scores. RESULTS: The interpolation-substitution technique successfully reduced metal artifacts in 70% of the cases. From a total of 60 images from 15 H&N cancer patients undergoing image guided radiation therapy, the mean rating score on the uncorrected images was 2.3 ± 1.1, versus 3.3 ± 1.0 for the corrected images. The mean difference in ranking score between uncorrected and corrected images was 1.0 (95% confidence interval: 0.9-1.2, P<.05). The standard deviation of each ROI significantly decreased after artifact reduction (P<.01). Moreover, a negative correlation between the mean rating score for each image and the standard deviation of the oral cavity and bilateral cheeks was observed. CONCLUSION: The interpolation-substitution algorithm is efficient and effective for reducing metal artifacts caused by dental fillings and implants on CBCT images, as demonstrated by the statistically significant increase in observer image quality ranking and by the decrease in ROI standard deviation between uncorrected and corrected images.

Combination Trimodality Therapy Using Vismodegib for Basal Cell Carcinoma of the Face.

Background. For large basal cell carcinomas (BCCs) of the head and neck, definitive surgery often requires extensive resection and reconstruction that may result in prolonged recovery and limited cosmesis. Vismodegib, a small-molecule inhibitor of the hedgehog pathway, is approved for advanced and metastatic BCCs. We present a case of advanced BCC treated with combination of vismodegib, radiotherapy, and local excision resulting in excellent response and cosmesis. Case Presentation. A 64-year-old gentleman presented with a 5-year history of a 7 cm enlarging right cheek mass, with extensive vascularization, central ulceration, and skin, soft tissue, and buccal mucosa involvement. Biopsy revealed BCC, nodular type. Up-front surgical option involved a large resection and reconstruction. After multidisciplinary discussion, we recommended and he opted for combined modality of vismodegib, radiotherapy, and local excision. The patient tolerated vismodegib well and his right cheek lesion decreased significantly in size. He was then treated with radiotherapy followed by local excision that revealed only focal residual BCC. Currently, he is without evidence of disease and has excellent cosmesis. Conclusions. We report a case of locally advanced BCC treated with trimodality therapy with vismodegib, radiotherapy, and local excision, resulting in excellent outcome and facial cosmesis, without requiring extensive resection or reconstructive surgery.

The role of vaginal cuff brachytherapy in endometrial cancer.

OBJECTIVE: The purpose of this article is to review the data, rationale, and recommendations of vaginal brachytherapy (VBT) in the post-operative treatment of endometrial cancer patients. METHODS: The authors performed a thorough review of the medical literature regarding the use of adjuvant VBT in the treatment of endometrial cancer. Relevant data are presented in this review. Additionally, personal and institutional practices from the authors are incorporated where relevant. RESULTS: VBT for the adjuvant treatment of early stage endometrial cancer patients results in a low rate of recurrence (0-3.1%) with very low rates of toxicity. PORTEC-2 supports the use of adjuvant VBT versus external beam radiotherapy specifically for high-intermediate risk endometrial cancer patients. VBT has low rates of acute and chronic gastrointestinal and genitourinary toxicity and very low rates of second primary malignancy. The primary toxicity of VBT is vaginal atrophy and stenosis with controversy regarding the use of vaginal dilators for prevention. Data support that patients prefer to be involved in the decision making process for their adjuvant therapy, and patients have a lower minimal desired benefit of adjuvant VBT than do physicians. Guidelines exist from the American Brachytherapy Society and American Society of Radiation Oncology with support from the Society for Gynecologic Oncologists regarding the use of adjuvant VBT. CONCLUSIONS: VBT decreases the risk of recurrence with minimal toxicity in the adjuvant treatment of endometrial cancer. Adjuvant therapy should be discussed in a multi-disciplinary setting with detailed counseling of the risks and benefits with the patient so that she ultimately makes an informed decision regarding her adjuvant therapy.

Markerless motion tracking of lung tumors using dual-energy fluoroscopy.

PURPOSE: To evaluate the efficacy of dual-energy (DE) vs single-energy (SE) fluoroscopic imaging of lung tumors using a markerless template-based tracking algorithm. METHODS: Ten representative patient breathing patterns were programmed into a Quasar™ motion phantom. The phantom was modified by affixing pork ribs to the surface, and a cedar insert with a small spherical volume was used to simulate lung and tumor, respectively. Sequential 60 kVp (6 mA) and 120 kVp (1.5 mA) fluoroscopic sequences were acquired. Frame-by-frame weighted logarithmic subtraction was performed resulting in a DE fluoroscopic sequence. A template-based algorithm was then used to track tumor motion throughout the DE and SE fluoroscopy sequences. Tracking coordinates were evaluated against ground-truth tumor locations. Fluoroscopic images were also acquired for two lung cancer patients, neither of which had implanted fiducials. RESULTS: For phantom imaging, a total of 1925 frames were analyzed. The algorithm successfully tracked the target on 99.9% (1923/1925) of DE frames vs 90.7% (1745/1925) SE images (p < 0.01). The displacement between tracking coordinates and ground truth for the phantom was 1.4 mm ± 1.1 mm for DE vs 2.0 mm ± 1.3 mm for SE (p < 0.01). Images from two patients, one with a larger tumor and one with a smaller tumor, were also analyzed. For the patient with the larger tumor, the average displacement from physician defined ground truth was 1.2 mm ± 0.6 mm for DE vs 1.4 mm ± 0.7 mm for SE (p = 0.016). For the patient that presented with a smaller tumor, the average displacement from physician defined ground truth was 2.2 mm ± 1.0 mm for DE vs 3.2 mm ± 1.4 mm for SE (p < 0.01). Importantly, for this single patient with the smaller tumor, 15.6% of the SE frames had >5 mm displacements from the ground truth vs 0% for DE fluoroscopy. CONCLUSIONS: This work indicates the potential for markerless tumor tracking utilizing DE fluoroscopy. With DE imaging, the algorithm showed improved detectability vs SE fluoroscopy and was able to accurately track the tumor in nearly all cases.

Planar IGRT dose reduction: A practical approach.

PURPOSE: To retrospectively estimate the cumulative absorbed dose (at the skin) from kilovoltage planar x-rays received by 90 patients treated on a Varian iX and to determine if that dose could be reduced without sacrificing image quality. METHODS AND MATERIALS: To estimate surface dose, measurements were obtained using the "in-air" method by varying the source-to-detector distance from 80 to 100 cm in steps of 5 cm. Energy was varied from 70 to 120 kVp. Using these data, a global equation was developed to estimate the cumulative skin dose by applying the imaging settings (kVp, mAs), patient-specific source-to-skin distance, and total number of images. To reduce the imaging dose, anterior and lateral images of RANDO phantoms were obtained using the same kVp; however, the mAs settings were systematically reduced. Contrast-to-noise ratios (CNRs) were calculated for both the standard phantom images and reduced mAs images. The mAs values were chosen to minimize skin dose while maintaining a similar CNR. Last, daily kV anterior and lateral images were obtained using these reduced mAs settings for 7 patients currently being treated with image guided radiation therapy. CNR was determined and compared with the values obtained on images taken 1 day before this change. RESULTS: Average cumulative kV imaging dose was as large as 162.2 cGy for pelvic cases with standard kVp, mAs. Other doses varied by site and technique. By lowering mAs, this dose could be reduced by 49% with only a 0.9% decrease in CNR. For the 7 patients currently being treated with image guided radiation therapy, CNR values were not statistically different (P = .79), whereas the skin dose was reduced by an average of approximately 50%. CONCLUSIONS: kV planar imaging dose reduction should be considered, given the large cumulative skin dose for certain disease sites. When mAs are reduced, planar dose reduction is clinically feasible without sacrificing image quality.

Prospective evaluation of dual-energy imaging in patients undergoing image guided radiation therapy for lung cancer: initial clinical results.

PURPOSE: A prospective feasibility study was conducted to investigate the utility of dual-energy (DE) imaging compared to conventional x-ray imaging for patients undergoing kV-based image guided radiation therapy (IGRT) for lung cancer. METHODS AND MATERIALS: An institutional review board-approved feasibility study enrolled patients with lung cancer undergoing IGRT and was initiated in September 2011. During daily setup, 2 sequential respiration-gated x-ray images were obtained using an on-board imager. Imaging was composed of 1 standard x-ray image at 120 kVp (1 mAs) and a second image obtained at 60 kVp (4 mAs). Weighted logarithmic subtraction of the 2 images was performed offline to create a soft tissue-selective DE image. Conventional and DE images were evaluated by measuring relative contrast and contrast-to-noise ratios (CNR) and also by comparing spatial localization, using both approaches. Imaging dose was assessed using a calibrated ion chamber. RESULTS: To date, 10 patients with stage IA to IIIA lung cancer were enrolled and 57 DE images were analyzed. DE subtraction resulted in complete suppression of overlying bone in all 57 DE images, with an average improvement in relative contrast of 4.7 ± 3.3 over that of 120 kVp x-ray images (P<.0002). The improvement in relative contrast with DE imaging was seen for both smaller (gross tumor volume [GTV] ≤5 cc) and larger tumors (GTV >5 cc), with average relative contrast improvement ratios of 3.4 ± 4.1 and 5.4 ± 3.6, respectively. Moreover, the GTV was reliably localized in 95% of the DE images versus 74% of the single energy (SE images, (P=.004). Mean skin dose per DE image set was 0.44 ± 0.03 mGy versus 0.43 ± 0.03 mGy, using conventional kV imaging parameters. CONCLUSIONS: Initial results of this feasibility study suggest that DE thoracic imaging may enhance tumor localization in lung cancer patients receiving kV-based IGRT without increasing imaging dose.

Spatial correspondence of 4D CT ventilation and SPECT pulmonary perfusion defects in patients with malignant airway stenosis.

To determine the spatial overlap agreement between four-dimensional computed tomography (4D CT) ventilation and single photon emission computed tomography (SPECT) perfusion hypo-functioning pulmonary defect regions in a patient population with malignant airway stenosis. Treatment planning 4D CT images were obtained retrospectively for ten lung cancer patients with radiographically demonstrated airway obstruction due to gross tumor volume. Each patient also received a SPECT perfusion study within one week of the planning 4D CT, and prior to the initiation of treatment. Deformable image registration was used to map corresponding lung tissue elements between the extreme component phase images, from which quantitative three-dimensional (3D) images representing the local pulmonary specific ventilation were constructed. Semi-automated segmentation of the percentile perfusion distribution was performed to identify regional defects distal to the known obstructing lesion. Semi-automated segmentation was similarly performed by multiple observers to delineate corresponding defect regions depicted on 4D CT ventilation. Normalized Dice similarity coefficient (NDSC) indices were determined for each observer between SPECT perfusion and 4D CT ventilation defect regions to assess spatial overlap agreement. Tidal volumes determined from 4D CT ventilation were evaluated versus measurements obtained from lung parenchyma segmentation. Linear regression resulted in a linear fit with slope = 1.01 (R² = 0.99). Respective values for the average DSC, NDSC(1 mm) and NDSC(2 mm) for all cases and multiple observers were 0.78, 0.88 and 0.99, indicating that, on average, spatial overlap agreement between ventilation and perfusion defect regions was comparable to the threshold for agreement within 1-2 mm uncertainty. Corresponding coefficients of variation for all metrics were similarly in the range: 0.10%-19%. This study is the first to quantitatively assess 3D spatial overlap agreement between clinically acquired SPECT perfusion and specific ventilation from 4D CT. Results suggest high correlation between methods within the sub-population of lung cancer patients with malignant airway stenosis.