Deterministic small-scale undulations of image-based risk predictions from the deep learning of lung tumors in motion.

INTRODUCTION: Deep learning (DL) models that use medical images to predict clinical outcomes are poised for clinical translation. For tumors that reside in organs that move, however, the impact of motion (i.e., degenerated object appearance or blur) on DL model accuracy remains unclear. We examine the impact of tumor motion on an image-based DL framework that predicts local failure risk after lung stereotactic body radiotherapy (SBRT). METHODS: We input pre-therapy free breathing (FB) computed tomography (CT) images from 849 patients treated with lung SBRT into a multitask deep neural network to generate an image fingerprint signature (or DL score) that predicts time-to-event local failure outcomes. The network includes a convolutional neural network encoder for extracting imaging features and building a task-specific fingerprint, a decoder for estimating handcrafted radiomic features, and a task-specific network for generating image signature for radiotherapy outcome prediction. The impact of tumor motion on the DL scores was then examined for a holdout set of 468 images from 39 patients comprising: (1) FB CT, (2) four-dimensional (4D) CT, and (3) maximum-intensity projection (MIP) images. Tumor motion was estimated using a 3D vector of the maximum distance traveled, and its association with DL score variance was assessed by linear regression. FINDINGS: The variance and amplitude in 4D CT image-derived DL scores were associated with tumor motion (R2  = 0.48 and 0.46, respectively). Specifically, DL score variance was deterministic and represented by sinusoidal undulations in phase with the respiratory cycle. DL scores, but not tumor volumes, peaked near end-exhalation. The mean of the scores derived from 4D CT images and the score obtained from FB CT images were highly associated (Pearson r = 0.99). MIP-derived DL scores were significantly higher than 4D- or FB-derived risk scores (p < 0.0001). INTERPRETATION: An image-based DL risk score derived from a series of 4D CT images varies in a deterministic, sinusoidal trajectory in a phase with the respiratory cycle. These results indicate that DL models of tumors in motion can be robust to fluctuations in object appearance due to movement and can guide standardization processes in the clinical translation of DL models for patients with lung cancer.

Tumor-associated alterations in white matter connectivity have prognostic significance in MGMT-unmethylated glioblastoma.

PURPOSE: We investigated the prognostic significance of tumor-associated white matter (TA-WM) tracts in glioblastoma (GBM) using magnetic resonance-diffusion tensor imaging (MR-DTI). We hypothesized that (1) TA-WM tracts harbor microscopic disease not targeted through surgery or radiotherapy (RT), and (2) the greater the extent of TA-WM involvement, the worse the survival outcomes. METHODS: We studied a retrospective cohort of 76 GBM patients. TA-WM tracts were identified by MR-DTI fractional anisotropy (FA) maps. For each patient, 22 TA-WM tracts were analyzed and each tract was graded 1-3 based on FA. A TA-WM score (TA-WMS) was computed based on number of involved tracts and corresponding FA grade of involvement. Kaplan-Meier statistics were utilized to determine survival outcomes, log-rank test was used to compare survival between groups, and Cox regression was utilized to determine prognostic variables. RESULTS: For the MGMT-unmethylated cohort, there was a decrease in OS for increasing TA-WMS (median OS 16.5 months for TA-WMS 0-4; 13.6 months for TA-WMS 5-8; 7.3 months for TA-WMS > 9; p = 0.0002). This trend was not observed in the MGMT-methylated cohort. For MGMT-unmethylated patients with TA-WMS > 6 and involvement of tracts passing through brainstem or contralateral hemisphere, median OS was 8.3 months versus median OS 14.1 months with TA-WMS > 6 but not involving aforementioned critical tracts (p = 0.003 log-rank test). For MGMT-unmethylated patients, TA-WMS was predictive of overall survival in multivariate analysis (HR = 1.14, 95% CI 1.03-1.27, p = 0.012) while age, gender, and largest tumor dimension were non-significant. CONCLUSION: Increased TA-WMS and involvement of critical tracts are associated with decreased overall survival in MGMT-unmethylated GBM.

Long-Term Hearing Outcomes From Gamma Knife Treatment for Vestibulocochlear Nerve Schwannomas in a Large, Tertiary Care, Academic Hospital.

OBJECTIVE: Describe long-term hearing outcomes with audiologic data with modern stereotactic radiosurgery techniques for vestibular schwannoma tumors. BACKGROUND: Since the mid-20th century, stereotactic radiosurgery has been an option for central nervous system tumors. Due to the non-invasive manner of treatment, this was extended to treatment for benign vestibular schwannomas without intracranial surgery. Modern advances have localized radiation and reduced dosage, but data are still lacking in the long-term hearing outcomes of this method of treatment. As one of the national leaders in this procedure, we present our full database of these outcomes over the full time period of our institutions utility of this modality. METHODS: A retrospective review was performed of all patients undergoing stereotactic radiotherapy for vestibular schwannomas within the study period of 1998 to 2019 and their audiograms analyzed along with patient data. Laterality Gardner-Robertson hearing score changes were the primary outcome analyzed for each patient; and controls were placed to accommodate for patient demographic data. RESULTS: Long-term, multi-year audiometric evaluation showed statistically significant loss of serviceable hearing and reduction in hearing ability with the use of stereotactic radiosurgery for treatment of vestibular schwannomas. CONCLUSIONS: Little long-term data exists on the audiometric outcomes related to stereotactic radiosurgery treatment for vestibular schwannomas. Our institution has performed more than 300 stereotactic radiosurgery treatments showing a continued reduction over time in serviceable hearing. Practitioners should advise patients undergoing treatment for vestibular schwannomas with this treatment of long-term results.

Intra- and inter-physician variability in target volume delineation in radiation therapy.

Reduction in setup errors is advocated through daily imaging and adaptive therapy, where the target volume is drawn daily. Previous studies suggest that inter-physician volume variation is significant (1.5 cm standard deviation [SD]); however, there are limited data for intra-physician consistency in daily target volume delineation, which is investigated in this study. Seven patients with lung cancer were chosen based on the perceived difficulty of contouring their disease, varying from simple parenchymal lung nodules to lesions with extensive adjacent atelectasis. Four physicians delineated the gross tumor volume (GTV) for each patient on 10 separate days to see the intra- and inter-physician contouring. Isocenter coordinates (x, y and z), target volume (cm3), and largest dimensions on anterior-posterior (AP) and lateral views were recorded for each GTV. Our results show that the variability among the physicians was reflected by target volumes ranging from +109% to -86% from the mean while isocenter coordinate changes were minimal; 3.8, 1.7 and 1.9 mm for x, y and z coordinates, respectively. The orthogonal image (AP and lateral) change varied 16.3 mm and 15.0 mm respectively among days and physicians. We conclude than when performing daily imaging, random variability in contouring resulted in isocenter changes up to ±3.8 mm in our study. The shape of the target varied within ±16 mm. This study suggests that when using daily imaging to track isocenter, target volume, or treatment parameters, physicians should be aware of personal variability when considering margins added to the target volume in daily decision making especially for difficult cases.

Adaptability and Resilience of Academic Radiation Oncology Personnel and Procedures during COVID-19 Pandemic.

BACKGROUND: A comprehensive response to the unprecedented SARS-CoV-2 (COVID-19) challenges for public health and its impact on radiation oncology patients and personnel for resilience and adaptability is presented. METHODS: The general recommendations included working remotely when feasible, implementation of screening/safety and personal protective equipment (PPE) guidelines, social distancing, regular cleaning of treatment environment, and testing for high-risk patients/procedures. All teaching conferences, tumor boards, and weekly chart rounds were conducted using a virtual platform. Additionally, specific recommendations were given to each section to ensure proper patient treatments. The impact of these measures, especially adaptability and resilience, were evaluated through specific questionnaire surveys. RESULTS: These comprehensive COVID-19-related measures resulted in most staff expressing a consistent level of satisfaction in regard to personal safety, maintaining a safe work environment, continuing quality patient care, and continuing educational activities during the pandemic. There was a significant reduction in patient treatments and on-site patient visits with an appreciable increase in the number of telemedicine e-visits. CONCLUSIONS: Survey results demonstrated substantial adaptability and resilience, including in the rapid recovery of departmental activities during the reactivation phase. In the event of a future public health emergency, the measures implemented may be adopted with good outcomes by radiation oncology departments across the globe.

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.

Transitioning From a Low-Dose-Rate to a High-Dose-Rate Prostate Brachytherapy Program: Comparing Initial Dosimetry and Improving Workflow Efficiency Through Targeted Interventions.

PURPOSE: We transitioned from a low-dose-rate (LDR) to a high-dose-rate (HDR) prostate brachytherapy program. The objective of this study was to describe our experience developing a prostate HDR program, compare the LDR and HDR dosimetry, and identify the impact of several targeted interventions in the HDR workflow to improve efficiency. METHODS AND MATERIALS: We performed a retrospective cohort study of patients treated with LDR or HDR prostate brachytherapy. We used iodine-125 seeds (145 Gy as monotherapy, and 110 Gy as a boost) and preoperative planning for LDR. For HDR, we used iridium-192 (13.5 Gy × 2 as monotherapy and 15 Gy × 1 as a boost) and computed tomography-based planning. Over the first 18 months, we implemented several targeted interventions into our HDR workflow to improve efficiency. To evaluate the progress of the HDR program, we used linear mixed-effects models to compare LDR and HDR dosimetry and identify changes in the implant procedure and treatment planning durations over time. RESULTS: The study cohort consisted of 122 patients (51 who received LDR and 71 HDR). The mean D90 was similar between patients who received LDR and HDR (P = .28). HDR mean V100 and V95 were higher (P < .0001), but mean V200 and V150 were lower (P < .0001). HDR rectum V100 and D1cc were lower (P < .0001). The HDR mean for the implant procedure duration was shorter (54 vs 60 minutes; P = .02). The HDR mean for the treatment planning duration dramatically improved with the implementation of targeted workflow interventions (3.7 hours for the first quartile to 2.0 hours for the final quartile; P < .0001). CONCLUSIONS: We successfully developed a prostate HDR brachytherapy program at our institution with comparable dosimetry to our historic LDR patients. We identified several targeted interventions that improved the efficiency of treatment planning. Our experience and workflow interventions may help other institutions develop similar HDR programs.

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.

A Medicare cost analysis of MRI- versus CT-based high-dose-rate brachytherapy of the cervix: Can MRI-based planning be less costly?

PURPOSE: While some institutions deliver multiple fractions per implant for MRI-based planning, it is common for only one fraction to be delivered per implant with CT-based cervical brachytherapy. The purpose of this study was to compare physician costs, hospital costs, and overall costs for cervical cancer patients treated with either CT-based or MRI-based high-dose-rate (HDR) cervical brachytherapy to determine if MRI-based brachytherapy as described can be financially feasible. METHODS AND MATERIALS: We identified 40 consecutive patients treated with curative intent cervical brachytherapy. Twenty patients underwent CT-based HDR brachytherapy with five fractions delivered in five implants on nonconsecutive days in an outpatient setting with the first implant placed with a Smit sleeve under general anesthesia. Twenty patients received MRI-based HDR brachytherapy with four fractions delivered in two implants, each with MRI-based planning, performed 1-2 weeks apart with an overnight hospital admission for each implant. We used Medicare reimbursements to assess physician costs, hospital costs, and overall cost. RESULTS: The median cost of MRI-based brachytherapy was $14,248.75 (interquartile range [IQR]: $13,421.32-$15,539.74), making it less costly than CT-based brachytherapy with conscious sedation (i.e., $18,278.85; IQR: $17,323.13-$19,863.03, p < 0.0001) and CT-based brachytherapy with deep sedation induced by an anesthesiologist (i.e., $27,673.44; IQR: $26,935.14-$29,511.16, p < 0.0001). CT-based brachytherapy with conscious sedation was more costly than CT-based brachytherapy with deep sedation (p < 0.001). CONCLUSIONS: MRI-based brachytherapy using the described treatment course was less costly than both methods of CT-based brachytherapy. Cost does not need to be a barrier for MRI-based cervical brachytherapy, especially when delivering multiple fractions with the same application.

Advanced small cell carcinoma of the cervix - Successful treatment with concurrent etoposide and cisplatin chemotherapy and extended field radiation: A case report and discussion.

The purpose of this article is to present a case of successful treatment of a patient with stage IVB small cell carcinoma of the cervix (SCCC) who was treated with concurrent chemoradiotherapy (CCRT) consisting of etoposide/cisplatin (EP) chemotherapy, external beam radiation therapy (EBRT), and brachytherapy. The patient has since remained without evidence of disease for nearly six years. This report reviews and summarizes the existing case literature on SCCC.

How one institution overcame the challenges to start an MRI-based brachytherapy program for cervical cancer.

PURPOSE: Adaptive magnetic resonance imaging (MRI)-based brachytherapy results in improved local control and decreased high-grade toxicities compared to historical controls. Incorporating MRI into the workflow of a department can be a major challenge when initiating an MRI-based brachytherapy program. This project aims to describe the goals, challenges, and solutions when initiating an MRI-based cervical cancer brachytherapy program at our institution. MATERIAL AND METHODS: We describe the 6-month multi-disciplinary planning phase to initiate an MRI-based brachytherapy program. We describe the specific challenges that were encountered prior to treating our first patient. RESULTS: We describe the solutions that were realized and executed to solve the challenges that we faced to establish our MRI-based brachytherapy program. We emphasize detailed coordination of care, planning, and communication to make the workflow feasible. We detail the imaging and radiation physics solutions to safely deliver MRI-based brachytherapy. The focus of these efforts is always on the delivery of optimal, state of the art patient care and treatment delivery within the context of our available institutional resources. CONCLUSIONS: Previous publications have supported a transition to MRI-based brachytherapy, and this can be safely and efficiently accomplished as described in this manuscript.

Cervical cancer: A global health crisis.

Cervical cancer is the fourth most common malignancy diagnosed in women worldwide. Nearly all cases of cervical cancer result from infection with the human papillomavirus, and the prevention of cervical cancer includes screening and vaccination. Primary treatment options for patients with cervical cancer may include surgery or a concurrent chemoradiotherapy regimen consisting of cisplatin-based chemotherapy with external beam radiotherapy and brachytherapy. Cervical cancer causes more than one quarter of a million deaths per year as a result of grossly deficient treatments in many developing countries. This warrants a concerted global effort to counter the shocking loss of life and suffering that largely goes unreported. This article provides a review of the biology, prevention, and treatment of cervical cancer, and discusses the global cervical cancer crisis and efforts to improve the prevention and treatment of the disease in underdeveloped countries. Cancer 2017;123:2404-12. © 2017 American Cancer Society.

Improving the Accessibility of Patient Care Through Integration of the Hospital and Radiation Oncology Electronic Health Records.

PURPOSE: Radiation therapy (RT)-specific aspects of a patient's cancer care commonly are documented and scheduled through a radiation oncology electronic health record (rEHR). However, patients who receive RT also receive multidisciplinary care from providers who use the hospital EHR (hEHR). We created an electronic interface to integrate our hEHR and rEHR to improve communication of the RT aspects of care between our department and the rest of the hospital. The objective of this study was to assess the impact of rEHR and hEHR integration on the accessibility of the RT-specific aspects of patient care to providers. METHODS AND MATERIALS: We performed a preintegration and postintegration survey of 175 staff members at our academic cancer center. Respondents rated the importance and accessibility of several RT encounters and documents on a Likert scale. The Wilcoxon-Mann-Whitney, χ2, and Fisher's exact tests were used to compare preintegration and postintegration responses. RESULTS: There were 32 and 19 responses to the pre- and postintegration surveys, respectively. rEHR items most commonly reported to be at least moderately important were the dates of first treatment (n = 29 [91%]), last treatment (n = 29 [91%]), brachytherapy (n = 22 [69%]), radiosurgery (n = 22 [69%]), and computed tomography simulation (n = 21 [66%]). A drastic improvement was found in most items made visible in the hEHR through the interface. CONCLUSION: By integrating our hEHR and rEHR, we improved the communication of patient care between the RT department and the multidisciplinary team. Institutions should pursue and support integration of the EHRs to improve the quality of care provided to patients with cancer.