A Couch Mounted Smartphone-based Motion Monitoring System for Radiation Therapy.

PURPOSE: Surface-guided radiation-therapy (SGRT) systems are being adopted into clinical practice for patient setup and motion monitoring. However, commercial systems remain cost prohibitive to resource-limited clinics around the world. Our aim is to develop and validate a smartphone-based application using LiDAR cameras (such as on recent Apple iOS devices) for facilitating SGRT in low-resource centers. The proposed SGRT application was tested at multiple institutions and validated using phantoms and volunteers against various commercial systems to demonstrate feasibility. METHODS AND MATERIALS: An iOS application was developed in Xcode and written in Swift using the Augmented-Reality (AR) Kit and implemented on an Apple iPhone 13 Pro with a built-in LiDAR camera. The application contains multiple features: 1) visualization of both the camera and depth video feeds (at a ∼60Hz sample-frequency), 2) region-of-interest (ROI) selection over the patient's anatomy where motion is measured, 3) chart displaying the average motion over time in the ROI, and 4) saving/exporting the motion traces and surface map over the ROI for further analysis. The iOS application was tested to evaluate depth measurement accuracy for: 1) different angled surfaces, 2) different field-of-views over different distances, and 3) similarity to a commercially available SGRT systems (Vision RT AlignRT and Varian IDENTIFY) with motion phantoms and healthy volunteers across 3 institutions. Measurements were analyzed using linear-regressions and Bland-Altman analysis. RESULTS: Compared with the clinical system measurements (reference), the iOS application showed excellent agreement for depth (r = 1.000, P < .0001; bias = -0.07±0.24 cm) and angle (r = 1.000, P < .0001; bias = 0.02±0.69°) measurements. For free-breathing traces, the iOS application was significantly correlated to phantom motion (institute 1: r = 0.99, P < .0001; bias =-0.003±0.03 cm; institute 2: r = 0.98, P < .0001; bias = -0.001±0.10 cm; institute 3: r = 0.97, P < .0001; bias = 0.04±0.06 cm) and healthy volunteer motion (institute 1: r = 0.98, P < .0001; bias = -0.008±0.06 cm; institute 2: r = 0.99, P < .0001; bias = -0.007±0.12 cm; institute 3: r = 0.99, P < .0001; bias = -0.001±0.04 cm). CONCLUSIONS: The proposed approach using a smartphone-based application provides a low-cost platform that could improve access to surface-guided radiation therapy accounting for motion.

Modifiable Post-Mastectomy Radiation Therapy Factors and Impact on Implant-Based Breast Reconstruction Outcomes.

INTRODUCTION: Intensity modulated radiation therapy (IMRT) and other modifiable radiation factors have been associated with decreased radiation toxicity. These factors could allow for improved reconstructive outcomes in patients requiring post-mastectomy radiation therapy (PMRT). However, they have not yet been well-studied in implant-based breast reconstruction (IBBR). METHODS: We performed a retrospective chart review of patients who underwent mastectomy with immediate tissue expander placement followed by PMRT. Radiation characteristics were collected, including radiation technique, bolus regimen, X-ray energy, fractionation, maximum radiation hot spot (DMax), and tissue volume receiving >105% (V105%) or >107% (V107%) of the prescription dose. Reconstructive complications occurring after initiation of PMRT were analyzed with respect to these radiation characteristics. RESULTS: 68 patients (70 breasts) were included in this study. The overall complication rate was 28.6%, with infection being the most common complication (24.3%), requiring removal of the tissue expander or implant in greater than half of infections (15.7%). DMax was greater in patients who required explant after PMRT, and this approached statistical significance (114.5+/-7.2% v. 111.4+/-4.4%, p=0.059). V105% and V107% were also greater in patients who required explant after PMRT (42.1+/-17.1% v. 33.0+/-20.9% and 16.4+/-14.5% v. 11.3+/-14.6%, respectively), however this was not statistically significant (p=0.176 and p=0.313, respectively). There were no significant differences in complication rates between patients with respect to radiation technique or other radiation characteristics studied. CONCLUSIONS: Minimizing the radiation hot spots and volumes of tissue receiving greater than the prescription dose of radiation may improve reconstructive outcomes in patients undergoing IBBR followed by PMRT.

Early-stage Breast Cancer: Tailored External Beam Fractionation Approaches for Treatment of the Whole or Partial Breast.

Historically, radiotherapy fractionation for early-stage breast cancer primarily consisted of 1.8-2 Gy per fraction given once daily to a total dose of 45-66 Gy over 5-7 weeks for whole breast treatment. Partial breast treatment employed larger dose per fraction (3.4-3.85 Gy) in 10 fractions given twice daily over 1 week. Radiobiologically, breast cancer is increasingly appreciated as a low alpha-beta ratio malignancy that is best treated with larger dose per fraction. Over the past 10 years, there have been increasing data from multiple large randomized clinical trials that support the use of shorter treatment courses: first hypofractionated regimens consisting of 15-20 treatments, and more recently, ultra-hypofractionated regimens as short as 5 treatments. Simultaneously, data from modern partial breast irradiation (PBI) trials support once daily treatment regimens ranging from 1-5 treatments. Shorter treatment courses represent less treatment burden on patients, reduced financial impact, and potentially improved access to care for patients with transportation and/or socioeconomic barriers. Here we review the evolution of whole and partial breast treatment regimens for early-stage breast cancer.

Positive margins after mastectomy in patients with invasive lobular carcinoma of the breast: Incidence and management strategies.

BACKGROUND: Surgical treatment of invasive lobular carcinoma (ILC) is challenging due to its diffuse growth pattern, and the positive margin rate after mastectomy is poorly described. METHODS: We retrospectively determined the positive margin rate in those with stage I-III ILC undergoing mastectomy. We evaluated the relationship between management strategy and recurrence free survival (RFS). RESULTS: In 357 patients, the positive margin rate was 10.6% overall and 18.7% in those with T3 tumors. Having a positive margin was associated with significantly shorter RFS on multivariate analysis (p = 0.01). Undergoing additional local treatment (radiation or re-excision) for a positive margin was significantly associated with improved RFS (p = 0.004). Older women with positive margins were significantly less likely to undergo additional local therapy. CONCLUSIONS: Even mastectomy fails to clear margins in a high proportion of patients with large ILC tumors, a finding which may warrant testing neoadjuvant strategies even prior to planned mastectomy.

Experimentally determined spectral optimization for dedicated breast computed tomography.

PURPOSE: The current study aimed to experimentally identify the optimal technique factors (x-ray tube potential and added filtration material/thickness) to maximize soft-tissue contrast, microcalcification contrast, and iodine contrast enhancement using cadaveric breast specimens imaged with dedicated breast computed tomography (bCT). Secondarily, the study aimed to evaluate the accuracy of phantom materials as tissue surrogates and to characterize the change in accuracy with varying bCT technique factors. METHODS: A cadaveric breast specimen was acquired under appropriate approval and scanned using a prototype bCT scanner. Inserted into the specimen were cylindrical inserts of polyethylene, water, iodine contrast medium (iodixanol, 2.5 mg/ml), and calcium hydroxyapatite (100 mg/ml). Six x-ray tube potentials (50, 60, 70, 80, 90, and 100 kVp) and three different filters (0.2 mm Cu, 1.5 mm Al, and 0.2 mm Sn) were tested. For each set of technique factors, the intensity (linear attenuation coefficient) and noise were measured within six regions of interest (ROIs): Glandular tissue, adipose tissue, polyethylene, water, iodine contrast medium, and calcium hydroxyapatite. Dose-normalized contrast to noise ratio (CNRD) was measured for pairwise comparisons among the six ROIs. Regression models were used to estimate the effect of tube potential and added filtration on intensity, noise, and CNRD. RESULTS: Iodine contrast enhancement was maximized using 60 kVp and 0.2 mm Cu. Microcalcification contrast and soft-tissue contrast were maximized at 60 kVp. The 0.2 mm Cu filter achieved significantly higher CNRD for iodine contrast enhancement than the other two filters (p = 0.01), but microcalcification contrast and soft-tissue contrast were similar using the copper and aluminum filters. The average percent difference in linear attenuation coefficient, across all tube potentials, for polyethylene versus adipose tissue was 1.8%, 1.7%, and 1.3% for 0.2 mm Cu, 1.5 mm Al, and 0.2 mm Sn, respectively. For water versus glandular tissue, the average percent difference was 2.7%, 3.9%, and 4.2% for the three filter types. CONCLUSIONS: Contrast-enhanced bCT, using injected iodine contrast medium, may be optimized for maximum contrast of enhancing lesions at 60 kVp with 0.2 mm Cu filtration. Soft-tissue contrast and microcalcification contrast may also benefit from lower tube potentials (60 kVp). The linear attenuation coefficients of water and polyethylene slightly overestimate the values of their corresponding tissues, but the reported differences may serve as guidance for dosimetry and quality assurance using tissue equivalent phantoms.

The characterization of breast anatomical metrics using dedicated breast CT.

PURPOSE: Accurate anatomical characterization of the breast is useful in breast phantom development and computer modeling of breast imaging technologies. Capitalizing on the three-dimensional capabilities of dedicated breast CT (bCT), a number of parameters which describe breast shape and fibroglandular distribution are defined. METHODS: Among 219 bCT data sets, the effective diameter and length of the pendant breast as well as the breast volume were measured and characterized for each bra cup size. The volume glandular fraction (VGF) was determined as a function of patient age, BIRADS density, bra cup size, and breast diameter. The glandular fraction was examined in coronal and sagittal planes of the breast, and the radial distribution of breast glandular fraction within a coronal bCT image was examined for three breast regions. The areal glandular fraction (AGF) was estimated from two-dimensional projections of the breast (simulated by projecting bCT data sets) and was compared to the corresponding VGF. RESULTS: The effective breast diameter and length increase with increasing bra cup size. The mean breast diameters (+/- standard error) of bra cup sizes A/AA, B, C, and D/DD were 11.1 +/- 0.5, 11.4 +/- 0.3, 13.0 +/- 0.2, and 13.7 +/- 0.2 cm, respectively. VGF was lower among older women and those with larger breast diameter and larger bra cup size. VGF increased as a function of the reported BIRADS density. AGF increased with VGF. Fibroglandular tissue was distributed primarily in the central portion of the breast. CONCLUSIONS: Breast metrics were examined and a number of parameters were defined which may be useful for breast modeling. The reported data may provide researchers with useful information for characterizing the breast for various imaging or dosimetry tasks.

A pilot, randomized controlled trial of telementorship: A useful tool during social distancing.

BACKGROUND: During social distancing, resident mentorship may be an unmet need. Telementorship, mentorship through video conferencing software, presents a unique approach to overcome these challenges. AIMS: This study evaluated whether telementorship through video conference increased access to mentorship encounters and decreased perceived barriers to access, factors that determine likelihood to maintain mentor relationships, and quality of mentorship. METHODS: A year-long randomized, prospective cohort study was conducted in 2016-2017 with pairs of resident mentors from seven different training programs and medical student mentees, randomized to telementorship or in-person mentorship. The number of quarterly encounters was monitored and demographic predictors of meeting were determined. Likert scale survey responses were analyzed with linear regression. RESULTS: Forty-three of 46 (93.5%) volunteer mentor-mentee pairs participated. Telementorship did not alter likelihood of meeting or attitudes toward mentorship barriers (time and distance). Mentee satisfaction increased from 42.5% to 65.4% (P<0.05) throughout the year. Operating room-based practice (P<0.05) and higher postgraduate level (P=0.02) decreased the likelihood of meeting. CONCLUSION: Telementorship provided an equal number of encounters compared to the pairs who were asked to meet in-person. Telementorship may serve as an adjunct modality for flexible communication. RELEVANCE FOR PATIENTS: Medical mentorship is a key component to medical education. Effective mentorship increases academic research productivity, job satisfaction, and advancement of clinical skills, which translate to improved patient care.

Contrast-enhanced dedicated breast CT: initial clinical experience.

PURPOSE: To quantify contrast material enhancement of breast lesions scanned with dedicated breast computed tomography (CT) and to compare their conspicuity with that at unenhanced breast CT and mammography. MATERIALS AND METHODS: Approval of the institutional review board and the Radiation Use Committee and written informed consent were obtained for this HIPAA-compliant study. Between September 2006 and April 2009, 46 women (mean age, 53.2 years; age range, 35-72 years) with Breast Imaging Reporting and Data System category 4 or 5 lesions underwent unenhanced breast CT and contrast material-enhanced breast CT before biopsy. Two radiologists independently scored lesion conspicuity for contrast-enhanced breast CT versus mammography and for contrast-enhanced breast CT versus unenhanced breast CT. Mean lesion voxel intensity was measured in Hounsfield units and normalized to adipose tissue intensity on manually segmented images obtained before and after administration of contrast material. Regression models focused on conspicuity and quantified enhancement were used to estimate the effect of pathologic diagnosis (benign vs malignant), lesion type (mass vs calcifications), breast density, and interradiologist variability. RESULTS: Fifty-four lesions (25 benign, 29 malignant) in 46 subjects were analyzed. Malignant lesions were seen significantly better at contrast-enhanced breast CT than at unenhanced breast CT (P < .001) or mammography (P < .001). Malignant calcifications (malignant lesions manifested mammographically as microcalcifications only, n = 7) were seen better at contrast-enhanced breast CT than at unenhanced breast CT (P < .001) and were seen similarly at contrast-enhanced breast CT and mammography. Malignant lesions enhanced 55.9 HU +/- 4.0 (standard error), whereas benign lesions enhanced 17.6 HU +/- 6.1 (P < .001). Ductal carcinoma in situ (n = 5) enhanced a mean of 59.6 HU +/- 2.8. Receiver operating characteristic curve analysis of lesion enhancement yielded an area under the receiver operating characteristic curve of 0.876. CONCLUSION: Conspicuity of malignant breast lesions, including ductal carcinoma in situ, is significantly improved at contrast-enhanced breast CT. Quantifying lesion enhancement may aid in the detection and diagnosis of breast cancer.

Volume assessment accuracy in computed tomography: a phantom study.

There is a broad push in the cancer imaging community to eventually replace linear tumor measurements with three-dimensional evaluation of tumor volume. To evaluate the potential accuracy of volume measurement in tumors by CT, a gelatin phantom consisting of 55 polymethylmethacrylate (PMMA) spheres spanning diameters from 1.6 mm to 25.4 mm was fabricated and scanned using thin slice (0.625 mm) CT (GE LightSpeed 16). Nine different reconstruction combinations of field of view dimension (FOV = 20, 30, 40 cm) and CT kernel (standard, lung, bone) were analyzed. Contiguous thin-slice images were averaged to produce CT images with greater thicknesses (1.25, 2.50, 5.0 mm). Simple grayscale thresholding techniques were used to segment the PMMA spheres from the gelatin background, where a total of 1800 spherical volumes were evaluated across the permutations studied. The geometric simplicity of the phantom established upper limits on measurement accuracy. In general, smaller slice thickness and larger sphere diameters produced more accurate volume assessment than larger slice thickness and smaller sphere diameter. The measured volumes were smaller than the actual volumes by a common factor depending on slice thickness; overall, 0.625 mm slices produced on average 18%, 1.25 mm slices produced 22%, 2.5 mm CT slices produced 29%, and 5.0 mm slices produced 39% underestimates of volume (mm3). Field of view did not have a significant effect on volume accuracy. Reconstruction algorithm significantly affected volume accuracy (p < 0.0001), with the lung kernel having the smallest error, followed by the bone and standard kernels. The results of this investigation provide guidance for CT protocol development and may guide the development of more advanced techniques to promote quantitatively accurate CT volumetric analysis of tumors.

Intensity modulated Ir-192 brachytherapy using high-Z 3D printed applicators.

Gynecologic cancers are often asymmetric, yet current Ir-192 brachytherapy techniques provide only limited radial modulation of the dose. The shielded solutions investigated here solve this by providing the ability to modulate between highly asymmetric and radially symmetric dose distributions at a given location. To find applicator designs that can modulate between full dose and less than 50% dose, at the dimensions of the urethra, a 2D calculation algorithm was developed to narrow down the search space. Two shielding design types were then further investigated using Monte Carlo and Boltzmann-solver dose calculation algorithms. 3D printing techniques using ISO 10993 certified biocompatible plastics and 3D printable tungsten-loaded plastics were tested. It was also found that shadowing effects set by the shape of the shielding cannot be easily modulated out, hence careful design is required. The shielded applicator designs investigated here, allow for reduction of the dose by over 50% at 5 mm from the applicator surface in desired regions, while also allowing radially symmetric dose with isodose line deviations less than 0.5 mm from circular. The shielding designs were also chosen with treatment delivery time in mind. Treatment times for these shielded designs were found to be less than 1.4 times longer than a 6-channel unshielded cylinder for the equivalent fully symmetric dose distribution. The 2D calculation methods developed here provide a simple way to rapidly evaluate shielding designs, while the 3D printing techniques also allow for devices with novel shapes to be rapidly prototyped. Both TOPAS Monte Carlo and Acuros BV calculations show that significant dose shaping and organ at risk sparing can be achieved without significantly compromising the plan in regions that require the full dose.

Telemedicine in Radiation Oncology: Is It Here to Stay? Impacts on Patient Care and Resident Education.

PURPOSE: Telemedicine was rapidly and ubiquitously adopted during the COVID-19 pandemic. However, there are growing discussions as to its role postpandemic. METHODS AND MATERIALS: We surveyed patients, radiation oncology (RO) attendings, and RO residents to assess their experience with telemedicine. Surveys addressed quality of patient care and utility of telemedicine for teaching and learning core competencies. Satisfaction was rated on a 6-point Likert-type scale. The quality of teaching and learning was graded on a 5-point Likert-type scale, with overall scores calculated by the average rating of each core competency required by the Accreditation Council for Graduate Medical Education (range, 1-5). RESULTS: Responses were collected from 56 patients, 12 RO attendings, and 13 RO residents. Patient feedback was collected at 17 new-patient, 22 on-treatment, and 17 follow-up video visits. Overall, 88% of patients were satisfied with virtual visits. A lower proportion of on-treatment patients rated their virtual visit as "very satisfactory" (68.2% vs 76.5% for new patients and 82.4% for follow-ups). Only 5.9% of the new patients and none of the follow-up patients were dissatisfied, and 27% of on-treatment patients were dissatisfied. The large majority of patients (88%) indicated that they would continue to use virtual visits as long as a physical examination was not needed. Overall scores for medical training were 4.1 out of 5 (range, 2.8-5.0) by RO residents and 3.2 (range, 2.0-4.0) by RO attendings. All residents and 92% of attendings indicated they would use telemedicine again; however, most indicated that telemedicine is best for follow-up visits. CONCLUSIONS: Telemedicine is a convenient means of delivering care to patients, with some limitations demonstrated for on-treatment patients. The majority of both patients and providers are interested in using telemedicine again, and it will likely continue to supplement patient care.

Predicting Survival for Patients With Metastatic Disease.

PURPOSE: This prospective study aimed to determine the accuracy of radiation oncologists in predicting the survival of patients with metastatic disease receiving radiation therapy and to understand factors associated with their accuracy. METHODS AND MATERIALS: This single-institution study surveyed 22 attending radiation oncologists to estimate patient survival. Survival predictions were defined as accurate if the observed survival (OS) was within the correct survival prediction category (0-6 months, >6-12 months, >12-24 months, and >24 months). The physicians made survival estimates for each course of radiation, yielding 877 analyzable predictions for 689 unique patients. Data analysis included Stuart's Tau C, logistic regression models, ordinal logistic regression models, and stepwise selection to examine variable interactions. RESULTS: Of the 877 radiation oncologists' predictions, 39.7% were accurate, 26.5% were underestimations, and 33.9% were overestimations. Stuart's Tau C showed low correlation between OS and survival estimates (0.3499), consistent with the inaccuracy reported in the literature. However, results showed less systematic overprediction than reported in the literature. Karnofsky performance status was the most significant predictor of accuracy, with greater accuracy for patients with shorter OS. Estimates were also more accurate for patients with lower Karnofsky performance status. Accuracy by patient age varied by primary site and race. Physician years of experience did not correlate with accuracy. CONCLUSIONS: The sampled radiation oncologists have a 40% accuracy in predicting patient survival. Future investigation should explore how survival estimates influence treatment decisions and how to improve survival prediction accuracy.

Increases in Serial Pretreatment 18F-FDG PET-CT Metrics Predict Survival in Early Stage Non-Small Cell Lung Cancer Treated With Stereotactic Ablative Radiation Therapy.

PURPOSE: Quantitative changes in positron emission tomography with computed tomography imaging metrics over serial scans may be predictive biomarkers. We evaluated the relationship of pretreatment metabolic tumor growth rate (MTGR) and standardized uptake value velocity (SUVV) with disease recurrence or death in patients with early-stage non-small cell lung cancer treated with stereotactic ablative radiation therapy (SABR). METHODS AND MATERIALS: Under institutional review board approval, we retrospectively identified patients who underwent positron emission tomography with computed tomography at diagnosis and staging and simulation for SABR. Two cohorts underwent SABR between November 2005 to October 2012 (discovery) and January 2012 to April 2016 (validation). MTGR and SUVV were calculated as the daily change in metabolic tumor volume and maximum standardized uptake value, respectively. Cox proportional hazard models identified predictors of local, regional, and distant recurrence and death for the combined cohort. MTGR and SUVV thresholds dichotomizing risk of death in the discovery cohort were applied to the validation cohort. RESULTS: A total of 152 lesions were identified in 143 patients (92 lesions in 83 discovery cohort patients). In multivariable models, increasing MTGR trended toward increased hazard of distant recurrence (hazard ratio, 6.98; 95% confidence interval, 0.67-72.61; P = .10). In univariable models, SUVV trended toward risk of death (hazard ratio, 11.8, 95% confidence interval, 0.85-165.1, P = .07). MTGR greater than 0.04 mL/d was prognostic of decreased survival in discovery (P = .048) and validation cohorts (P < .01). CONCLUSIONS: MTGR greater than 0.04 mL/d is prognostic of death in patients with non-small cell lung cancer treated with SABR. Increasing SUVV trends, nonsignificantly, toward increased risk of recurrence and death. MTGR and SUVV may be candidate imaging biomarkers to study in trials evaluating systemic therapy with SABR for patients at high risk of out-of-field recurrence.

Multi-Institutional Analysis of Prostate-Specific Antigen Kinetics After Stereotactic Body Radiation Therapy.

PURPOSE: Understanding prostate-specific antigen (PSA) kinetics after radiation therapy plays a large role in the management of patients with prostate cancer (PCa). This is particularly true in establishing expectations regarding PSA nadir (nPSA) and PSA bounces, which can be disconcerting. As increasingly more patients are being treated with stereotactic body radiation therapy (SBRT) for low- and intermediate-risk PCa, it is imperative to understand the PSA response to SBRT. METHODS AND MATERIALS: PSA data from 5 institutions were retrospectively analyzed for patients with localized PCa treated definitively with SBRT alone from 2004 to 2016. Patients received 35 to 40 Gy in 5 fractions, per institutional standards. Patients who had less than 12 months of PSA data or received androgen deprivation therapy were excluded from this study. Linear and logistic multivariable analysis were performed to identify predictors of nPSA, bounce, and biochemical recurrence, and joint latent class models were developed to identify significant predictors of time to biochemical failure. RESULTS: A total of 1062 patients were included in this study. Median follow-up was 66 months (interquartile range [IQR], 36.4-89.9 months). Biochemical failure per the Phoenix criteria occurred in 4% of patients. Median nPSA was 0.2 ng/mL, median time to nPSA was 40 months, 84% of patients had an nPSA ≤0.5 ng/mL, and 54% of patients had an nPSA ≤0.2 ng/mL. On multivariable analysis, nPSA was a significant predictor of biochemical failure. Benign PSA bounce was noted in 26% of patients. The median magnitude of PSA bounce was 0.52 ng/mL (IQR, 0.3-1.0 ng/mL). Median time to PSA bounce was 18.1 months (IQR, 12.0-31.1 months). On multivariable analysis, age and radiation dose were significantly associated with a lower incidence of bounce. Joint latent class models modeling found that nPSA and radiation dose were significantly associated with longer time to biochemical failure. CONCLUSIONS: In this multi-institutional cohort of patients with long-term follow-up, we found that SBRT led to low nPSAs. In turn, lower nPSAs are associated with reduced incidence of, and longer time to, biochemical failure. Benign PSA bounces occurred in a quarter of patients, as late as several years after treatment. Further studies are needed to directly compare the PSA response of patients who receive SBRT versus other treatment modalities.

Long-term Outcomes of Stereotactic Body Radiotherapy for Low-Risk and Intermediate-Risk Prostate Cancer.

Importance: Stereotactic body radiotherapy harnesses improvements in technology to allow the completion of a course of external beam radiotherapy treatment for prostate cancer in the span of 4 to 5 treatment sessions. Although mounting short-term data support this approach, long-term outcomes have been sparsely reported. Objective: To assess long-term outcomes after stereotactic body radiotherapy for low-risk and intermediate-risk prostate cancer. Design, Setting, and Participants: This cohort study analyzed individual patient data from 2142 men enrolled in 10 single-institution phase 2 trials and 2 multi-institutional phase 2 trials of stereotactic body radiotherapy for low-risk and intermediate-risk prostate cancer between January 1, 2000, and December 31, 2012. Statistical analysis was performed based on follow-up from January 1, 2013, to May 1, 2018. Main Outcomes and Measures: The cumulative incidence of biochemical recurrence was estimated using a competing risk framework. Physician-scored genitourinary and gastrointestinal toxic event outcomes were defined per each individual study, generally by Radiation Therapy Oncology Group or Common Terminology Criteria for Adverse Events scoring systems. After central review, cumulative incidences of late grade 3 or higher toxic events were estimated using a Kaplan-Meier method. Results: A total of 2142 men (mean [SD] age, 67.9 [9.5] years) were eligible for analysis, of whom 1185 (55.3%) had low-risk disease, 692 (32.3%) had favorable intermediate-risk disease, and 265 (12.4%) had unfavorable intermediate-risk disease. The median follow-up period was 6.9 years (interquartile range, 4.9-8.1 years). Seven-year cumulative rates of biochemical recurrence were 4.5% (95% CI, 3.2%-5.8%) for low-risk disease, 8.6% (95% CI, 6.2%-11.0%) for favorable intermediate-risk disease, 14.9% (95% CI, 9.5%-20.2%) for unfavorable intermediate-risk disease, and 10.2% (95% CI, 8.0%-12.5%) for all intermediate-risk disease. The crude incidence of acute grade 3 or higher genitourinary toxic events was 0.60% (n = 13) and of gastrointestinal toxic events was 0.09% (n = 2), and the 7-year cumulative incidence of late grade 3 or higher genitourinary toxic events was 2.4% (95% CI, 1.8%-3.2%) and of late grade 3 or higher gastrointestinal toxic events was 0.4% (95% CI, 0.2%-0.8%). Conclusions and Relevance: In this study, stereotactic body radiotherapy for low-risk and intermediate-risk disease was associated with low rates of severe toxic events and high rates of biochemical control. These data suggest that stereotactic body radiotherapy is an appropriate definitive treatment modality for low-risk and intermediate-risk prostate cancer.

18F-EF5 PET-based Imageable Hypoxia Predicts Local Recurrence in Tumors Treated With Highly Conformal Radiation Therapy.

PURPOSE: Tumor hypoxia contributes to radiation resistance. A noninvasive assessment of tumor hypoxia would be valuable for prognostication and possibly selection for hypoxia-targeted therapies. 18F-pentafluorinated etanidazole (18F-EF5) is a nitroimidazole derivative that has demonstrated promise as a positron emission tomography (PET) hypoxia imaging agent in preclinical and clinical studies. However, correlation of imageable hypoxia by 18F-EF5 PET with clinical outcomes after radiation therapy remains limited. METHODS AND MATERIALS: Our study prospectively enrolled 28 patients undergoing radiation therapy for localized lung or other tumors to receive pretreatment 18F-EF5 PET imaging. Depending on the level of 18F-EF5 tumor uptake, patients underwent functional manipulation of tumor oxygenation with either carbogen breathing or oral dichloroacetate followed by repeated 18F-EF5 PET. The hypoxic subvolume of tumor was defined as the proportion of tumor voxels exhibiting higher 18F-EF5 uptake than the 95th percentile of 18F-EF5 uptake in the blood pool. Tumors with a hypoxic subvolume ≥ 10% on baseline 18F-EF5 PET imaging were classified as hypoxic by imaging. A Cox model was used to assess the correlation between imageable hypoxia and clinical outcomes after treatment. RESULTS: At baseline, imageable hypoxia was demonstrated in 43% of all patients (12 of 28), including 6 of 16 patients with early-stage non-small cell lung cancer treated with stereotactic ablative radiation therapy and 6 of 12 patients with other cancers. Carbogen breathing was significantly associated with decreased imageable hypoxia, while dichloroacetate did not result in a significant change under our protocol conditions. Tumors with imageable hypoxia had a higher incidence of local recurrence at 12 months (30%) than those without (0%) (P < .01). CONCLUSIONS: Noninvasive hypoxia imaging by 18F-EF5 PET identified imageable hypoxia in about 40% of tumors in our study population. Local tumor recurrence after highly conformal radiation therapy was higher in tumors with imageable hypoxia.

Differentiation of ductal carcinoma in-situ from benign micro-calcifications by dedicated breast computed tomography.

PURPOSE: Compare conspicuity of ductal carcinoma in-situ (DCIS) to benign calcifications on unenhanced (bCT), contrast-enhanced dedicated breast CT (CEbCT) and mammography (DM). METHODS AND MATERIALS: The institutional review board approved this HIPAA-compliant study. 42 women with Breast Imaging Reporting and Data System 4 or 5 category micro-calcifications had breast CT before biopsy. Three subjects with invasive disease at surgery were excluded. Two breast radiologists independently compared lesion conspicuity scores (CS) for CEbCT, to bCT and DM. Enhancement was measured in Hounsfield units (HU). Mean CS ± standard deviations are shown. Receiver operating characteristic analysis (ROC) measured radiologists' discrimination performance by comparing CS to enhancement alone. Statistical measurements were made using ANOVA F-test, Wilcoxon rank-sum test and robust linear regression analyses. RESULTS: 39 lesions (17 DCIS, 22 benign) were analyzed. DCIS (8.5 ± 0.9, n=17) was more conspicuous than benign micro-calcifications (3.6 ± 2.9, n=22; p<0.0001) on CEbCT. DCIS was equally conspicuous on CEbCT and DM (8.5 ± 0.9, 8.7 ± 0.8, n=17; p=0.85) and more conspicuous when compared to bCT (5.3 ± 2.6, n=17; p<0.001). All DCIS enhanced; mean enhancement (90HU ± 53HU, n=17) was higher compared to benign lesions (33 ± 30HU, n=22) (p<0.0001). ROC analysis of the radiologists' CS showed high discrimination performance (AUC=0.94) compared to enhancement alone (AUC=0.85) (p<0.026). CONCLUSION: DCIS is more conspicuous than benign micro-calcifications on CEbCT. DCIS visualization on CEbCT is equal to mammography but improved compared to bCT. Radiologists' discrimination performance using CEBCT is significantly higher than enhancement values alone. CEbCT may have an advantage over mammography by reducing false positive examinations when calcifications are analyzed.

SBRT and HDR brachytherapy produce lower PSA nadirs and different PSA decay patterns than conventionally fractionated IMRT in patients with low- or intermediate-risk prostate cancer.

PURPOSE: To compare patterns of prostate-specific antigen (PSA) response following stereotactic body radiation therapy (SBRT), high-dose-rate (HDR) brachytherapy, and conventionally fractionated intensity modulated radiation therapy (IMRT) in patients with low- or intermediate-risk prostate cancer (CaP). METHODS AND MATERIALS: Eligible study patients included 439 patients with low- or intermediate-risk prostate cancer who were treated with radiation therapy (RT) alone between 2003 and 2013, remained free of biochemical recurrence, and had at least 2 PSA values within the first year following RT. Of these, 130 were treated with SBRT, 220 with HDR brachytherapy, and 89 with IMRT. Multivariate regression analysis was used to compare PSA nadirs (nPSA), time to nPSA, and PSA bounce parameters among the 3 modalities. Indicator variable analysis was used to develop empirical models of PSA decay using the treatment modalities as indicator variables. RESULTS: Significantly more patients treated with SBRT or HDR brachytherapy achieved raw nPSAs of <0.5 ng/mL compared with patients treated with IMRT (76.2% and 75.9% vs 44.9%, respectively; P < .0001 for SBRT or HDR brachytherapy vs IMRT). On multivariate analysis, nPSA was significantly lower with SBRT and HDR compared with IMRT (P < .0001). Time to nPSA and bounce parameters was not significantly different among IMRT, SBRT, and HDR. Overall, SBRT and HDR brachytherapy caused significantly larger PSA decay rates (P < .001). When truncating follow-up at 1000 days, the corresponding decay rates were larger for all 3 modalities, with no significant differences between them. CONCLUSIONS: Stereotactic body radiation therapy and HDR brachytherapy produce lower nPSAs than IMRT. Within 1000 days of follow-up, the modalities produce similar rates of PSA decay; subsequently, decay continues (albeit at a slower pace) after SBRT and HDR brachytherapy but plateaus with IMRT. Because nPSA is a validated predictor of long-term outcome, these data not only suggest a distinct radiobiological effect with SBRT and HDR brachytherapy, but also predict for clinical outcomes that might equal or surpass those of IMRT.