Feasibility evaluation of novel AI-based deep-learning contouring algorithm for radiotherapy.

PURPOSE: To evaluate the clinical feasibility of the Siemens Healthineers AI-Rad Companion Organs RT VA30A (Organs-RT) auto-contouring algorithm for organs at risk (OARs) of the pelvis, thorax, and head and neck (H&N). METHODS: Computed tomography (CT) datasets from 30 patients (10 pelvis, 10 thorax, and 10 H&N) were collected. Four sets of OARs were generated on each scan, one set by Organs-RT and the others by three experienced users independently. A physician (expert) then evaluated each contour by assigning a score from the following scale: 1-Must Redo, 2-Major Edits, 3-Minor Edits, 4-Clinically usable. Using the highest-scored OAR from the human users as a reference, the contours generated by Organs-RT were evaluated via Dice Similarity Coefficient (DSC), Hausdorff Distance (HDD), Mean Distance to Agreement (mDTA), Volume comparison, and visual inspection. Additionally, each human user recorded the time to delineate each structure set and time-saving efficiency was measured. RESULTS: The average DSC obtained for the pelvic OARs ranged between (0.81 ± 0.06)Rectum and (0.94 ± 0.03)Bladder . (0.75 ± 0.09)Esophagus to ( 0.96 ± 0.02 ) Rt . Lung ${( {0.96 \pm 0.02} )}_{{\mathrm{Rt}}.{\mathrm{\ Lung}}}$ for the thoracic OARs and (0.66 ± 0.07)Lips to (0.83 ± 0.04)Brainstem for the H&N. The average HDD in cm for the pelvis cohort ranged between (0.95 ± 0.35)Bladder to (3.62 ± 2.50)Rectum , (0.42 ± 0.06)SpinalCord to (2.09 ± 2.00)Esophagus for the thoracic set and ( 0.53 ± 0.22 ) Cerv _ SpinalCord ${( {0.53 \pm 0.22} )}_{{\mathrm{Cerv}}\_{\mathrm{SpinalCord}}}$ to (1.50 ± 0.50)Mandible for the H&N region. The time-saving efficiency was 67% for H&N, 83% for pelvis, and 84% for thorax. 72.5%, 82%, and 50% of the pelvis, thorax, and H&N OARs were scored as clinically usable by the expert, respectively. CONCLUSIONS: The highest agreement registered between OARs generated by Organs-RT and their respective references was for the bladder, heart, lungs, and femoral heads, with an overall DSC≥0.92. The poorest agreement was for the rectum, esophagus, and lips, with an overall DSC⩽0.81. Nonetheless, Organs-RT serves as a reliable auto-contouring tool by minimizing overall contouring time and increasing time-saving efficiency in radiotherapy treatment planning.

Practical guide to the use of radium 223 dichloride.

INTRODUCTION: Bone seeking radiopharmaceuticals have been used for decades in the palliation of pain from bone metastases emerging from prostate cancer. Recent clinical evidence has demonstrated an improved survival in men with metastatic castration resistant prostate cancer (CRPC) with radium 223. MATERIAL AND METHODS: A review of the literature was performed to identify the role of radiopharmaceuticals in the management of prostate cancer. We focused on prospective trials in order to identify the highest level of evidence describing this therapy. Further, we focused on providing a clinical guide for the use of radium 223. RESULTS: The phase III ALSYMPCA trial which compared radium 223 to placebo in men with symptomatic CRPC demonstrated a statistically significant improvement in median overall survival of 3.6 months and an improvement in time to first skeletal related event. There were higher rates of myelosuppression and diarrhea with radium 223, however, no clinically meaningful differences in the frequency of grade 3 or 4 adverse events were observed between the study groups. CONCLUSION: Radium 223 is a safe and effective therapy in men with symptomatic CRPC providing a survival advantage on par with novel antiandrogens, CYP-17 inhibitors, and chemotherapy. Radium 223 has huge potential in combination strategies as well as for use earlier in the natural history of metastatic prostate cancer.

Toxicities after radioembolization with yttrium-90 SIR-spheres: incidence and contributing risk factors at a single center.

PURPOSE: To report the incidence of liver function test (LFT) toxicities after radioembolization with yttrium-90 ((90)Y) SIR-Spheres and review potential risk factors. MATERIALS AND METHODS: Patients receiving (90)Y for radioembolization of primary or metastatic liver tumors had follow-up LFTs 29-571 days after treatment. The incidence and duration of bilirubin, aspartate aminotransferase (AST), and alanine aminotransferase (ALT) toxicities were documented using common terminology criteria. Factors that were assessed included previous intra-arterial (IA) therapy, systemic chemotherapy, low tumor-to-normal liver tissue ratio at mapping angiography, vascular stasis, and higher prescribed (90)Y doses. RESULTS: There were 81 patients who underwent 122 infusions and had follow-up LFTs. Of 122 infusions, 71 (58%) were associated with toxicity. One patient died with radiation-induced liver disease. Grade 3 or greater toxicities occurred in seven (7%) patients after nine procedures. The median durations of laboratory elevations for bilirubin, AST, and ALT were 29 days, 29 days, and 20 days. Toxicity developed after 51 (71%) of 72 infusions with previous IA therapy versus 20 (40%) of 50 infusions in treatment-naïve areas (P = .0006). Absence of previous systemic therapy was associated with greater risk of toxicity versus previous chemotherapy (47% vs 66%, P = .03). Other factors were not associated with increased toxicity. CONCLUSIONS: Mild hepatotoxicity developed frequently after infusion of SIR-Spheres using the body surface area method, with normalization of LFTs in most patients. Grade 3 or greater toxicities were seen in < 10% of infusions. Toxicity was strongly associated with previous IA therapy.

Side-branch embolization before 90Y radioembolization: rate of recanalization and new collateral development.

OBJECTIVE: The purpose of this study was to assess the rate of recanalization and collateral vessel formation after side-branch embolization during mapping angiography for planned (90)Y radioembolization. MATERIALS AND METHODS: Patients who underwent side-branch embolization at mapping angiography before (90)Y administration were included. Embolized vessels included the gastroduodenal artery, right gastric artery, and accessory arteries. Four interventional radiologists reviewed follow-up angiograms to assess recanalization and new collateral formation of embolized vessels. The time to recanalization or new collateral formation was tracked within 60 days and after the final arteriographic study. Differences in outcome among patients who had and those who had not undergone previous arterial directed therapy were reviewed. RESULTS: Fifty-six patients underwent side-branch embolization and follow-up arteriography; 124 treatments were performed after side-branch embolization (median, 2; range, 1-7), and the median follow-up period was 134 days (range, 7-684 days). Recanalization or new collateral vessel formation was found in 6 of 56 patients (10.7%) and in 8 of 56 patients (14.3%) 60 days after treatment or at final angiography, respectively. Embolization of 110 arteries was accomplished (42 gastroduodenal arteries, 46 right gastric arteries, and 22 accessory arteries). Two of 110 arteries (1.8%) recanalized, and four of 110 (3.6%) had new collateral vessels within 60 days. At final evaluation, 2 of 110 arteries (1.8%) had recanalized and 7 of 110 (6.4%) had new collaterals. Previous liver-directed therapy did not affect outcome (p > 0.05). No patient had symptomatic gastrointestinal ulceration. CONCLUSION: In more than 89% of patients, side-branch embolization provides durable occlusion for (90)Y radioembolization without collateral development or recanalization for a bilobar cycle of therapy. Further recanalization and collateral development at longer-term follow-up are minimal.

A phase IB clinical trial of 15 Gy HDR brachytherapy followed by hypofractionated/SBRT in the management of intermediate-risk prostate cancer.

PURPOSE: High dose-rate (HDR) brachytherapy is commonly administered as a boost to external beam radiation therapy (EBRT). Our purpose was to compare toxicity with increasingly hypofractionated EBRT in combination with a single 15 Gy HDR boost for men with intermediate-risk prostate cancer. METHODS AND MATERIALS: Forty-two men were enrolled on this phase IB clinical trial to one of three EBRT dose cohorts: 10 fractions, seven fractions, or five fractions. Patients were followed prospectively for safety, efficacy, and health-related quality of life (Expanded Prostate Index Composite). Efficacy was assessed biochemically using the Phoenix definition. RESULTS: With a median follow up of 36 months, the biochemical disease-free survival was 95.5%. One man developed metastatic disease at 5 years. There was no significant minimally important difference in EPIC PRO for either urinary, bowel, or sexual domains. There was one acute Grade 3 GI and GU toxicity, but no late Grade 3 GU or GI toxicities. CONCLUSION: Fifteen gray HDR brachytherapy followed by a five fraction SBRT approach results in high disease control rates and low toxicity similar to previously reported HDR protocols with significant improvement in patient convenience and resource savings. While mature results with longer follow up are awaited, this treatment approach may be considered a safe and effective option for men with intermediate-risk disease.

Process Mapping and Time Study to Improve Efficiency of New Procedure Implementation for High-Dose Rate Prostate Brachytherapy.

New technologies and procedures have the potential to improve outcomes; however, initial implementation is often associated with a steep learning curve, decreased efficiency, and patient safety implications. Implementation of a real-time, ultrasound-based prostate high-dose rate brachytherapy procedure involved a multidisciplinary team composed of approximately 6-8 team members and numerous complex tasks. To characterize time spent on various aspects of the procedure and improve efficiency, the team developed a detailed process map, time study, and team debriefings. A benchmark was created based on an experienced institution which has performed >100 procedures annually. The process map was analyzed based on clinical tasks and treatment planning tasks. Over the course of 17 cases at a single institution, total procedure time ranged from 222 to 107 minutes. Implementation of the process map resulted in a reduction of total time by 52%. The implementation of a new procedure benefits from the integration and utilization of a process map. We were able to reduce procedure time significantly, which resulted in decreased time under general anesthesia, reduced risk of deep vein thrombosis, improved overall patient safety, patient throughput, and decreases in staffing demands.

Do theoretical potential and advanced technology justify the use of high-dose rate brachytherapy as monotherapy for prostate cancer?

Low-dose rate brachytherapy (LDR-BT), involving implantation of radioactive seeds into the prostate, is an established monotherapy for most low-risk and select intermediate- and high-risk prostate cancer patients. High-dose rate brachytherapy (HDR-BT) is an advanced technology theorized to be more advantageous than LDR-BT from a radiobiological and radiophysics perspective, to the patient himself, and in terms of resource allocation. Studies of HDR-BT monotherapy have encouraging results in terms of biochemical control, patient survival, treatment toxicity and erectile preservation. However, there are still certain limitations that preclude recommending HDR-BT monotherapy for prostate cancer outside the setting of a clinical trial. HDR-BT monotherapy should be considered experimental at present.

High dose rate brachytherapy boost for prostate cancer: a systematic review.

Studies of dose-escalated external beam radiation therapy (EBRT) and low dose rate brachytherapy (LDR-BT) have shown excellent rates of tumor control and cancer specific survival. Moreover, LDR-BT combined with EBRT (i.e. "LDR-BT boost") is hypothesized to improve local control. While phase II trials with LDR-BT boost have produced mature data of outcomes and toxicities, high dose rate (HDR)-BT has been growing in popularity as an alternative boost therapy. Boost from HDR-BT has theoretical advantages over LDR-BT, including improved cancer cell death and better dose distribution from customization of catheter dwell times, locations, and inverse dose optimization. Freedom from biochemical failure rates at five years for low-, intermediate-, high-risk, and locally advanced patients have generally been 85-100%, 80-98%, 59-96%, and 34-85%, respectively. Late Radiation Therapy Oncology Group grade 3-4 toxicities have also been encouraging with <6% of patients experiencing any toxicity. Limitations of current HDR-BT boost studies include reports of only single-institution experiences, and unrefined reports of toxicity or patient quality of life. Comparative effectiveness research will help guide clinicians in selecting the most appropriate treatment option for individual patients based on risk-stratification, expected outcomes, toxicities, quality of life, and cost.

Large prostate gland size is not a contraindication to low-dose-rate brachytherapy for prostate adenocarcinoma.

PURPOSE: Prostate volume greater than 50cc is traditionally a relative contraindication to prostate seed implantation (PSI), but there is little consensus regarding prostate size and clinical outcomes. We report biochemical control and toxicity after low-dose-rate PSI and compare outcomes according to the prostate size. METHODS AND MATERIALS: A total of 429 men who underwent low-dose-rate PSI between 1998 and 2009 were evaluated. Median followup was 38.7 months. Patients were classified by prostate volume into small, medium, and large subgroups. Differences were analyzed using the Mann-Whitney and Pearson's χ(2) tests for continuous and categorical variables, respectively. Cox proportional hazards regression models were used to evaluate effect of prostate size on outcomes. RESULTS: Patient pretreatment factors were balanced between groups except for age (p=0.001). The 10-year actuarial freedom from biochemical failure for all patients treated with PSI was 96.3% with no statistically significant difference between large vs. small/medium prostate size (90% vs. 96.6%, p=0.47). In a multivariate analysis, plan type (hazard ratio [HR]=0.25, p=0.03), dose to 90% of the gland (D90: HR=0.98, p=0.02), volume receiving 200Gy (V200: HR=0.98, p=0.026), and biologic effective dose (HR=0.99, p=0.045), but not prostate size (HR=2.27, p=0.17) were significantly associated with freedom from biochemical failure. Prostate size was not significantly associated with time to maximum American Urologic Association score. CONCLUSION: In men with large prostates, the PSI provides biochemical control and temporal changes in genitourinary toxicity that are comparable with men having smaller glands. Accurate dose optimization and delivery of PSI provides the best clinical outcomes regardless of gland size.

Using qualitative measures to improve quality in radiation oncology.

This article introduces the use of qualitative research techniques in the field of radiation oncology with respect to quality improvement initiatives. The qualitative techniques used in this research include field observations and in-depth, one-on-one interviews with radiation therapy technologists. The observations were conducted in a fast-paced academic institution. This high-pressure, high-throughput environment provided an interesting location for observation of behaviors, workflows, and areas of improvement. Qualitative research is a useful platform for formulating questions and addressing the environment on a larger scale. The information resulting from this research led to immediate changes that improved the efficiency and effectiveness of care provided to patients and identified future initiatives to improve patient safety and the timeliness of care provided. Overall, qualitative research proved to be an exceptional resource for identifying and evaluating a clinical department and demonstrated the usefulness of this method of research for future work.

Optimizing parametrial aperture design utilizing HDR brachytherapy isodose distribution.

Treatment of cervical cancer includes combination of external beam radiation therapy (EBRT) and brachytherapy (BRT). Traditionally, coronal images displaying dose distribution from a ring and tandem (R&T) implant aid in construction of parametrial boost fields. This research aimed to evaluate a method of shaping parametrial fields utilizing contours created from the high-dose-rate (HDR) BRT dose distribution. Eleven patients receiving HDR-BRT via R&T were identified. The BRT and EBRT CT scans were sent to FocalSim (v4.62)(®) and fused based on bony anatomy. The contour of the HDR isodose line was transferred to the EBRT scan. The EBRT scan was sent to CMS-XIO (v4.62)(®) for planning. This process provides an automated, potentially more accurate method of matching the medial parametrial border to the HDR dose distribution. This allows for a 3D-view of dose from HDR-BRT for clinical decision-making, utilizes a paperless process and saves time over the traditional technique.

Combining theoretical potential and advanced technology in high-dose rate brachytherapy boost therapy for prostate cancer.

External beam radiation therapy (EBRT) combined with brachytherapy (BT) is an attractive treatment option for select patients with clinically localized prostate cancer. Either low- or high-dose rate BT may be combined with EBRT ('LDR-BT boost,' 'HDR-BT boost,' respectively). HDR-BT boost has potential theoretical benefits over LDR-BT boost or external beam radiation therapy monotherapy in terms of radiobiology, radiophysics and patient convenience. Based on prospective studies in this review, freedom from biochemical failure (FFBF) rates at 5 years for low-, intermediate- and high-risk patients have generally been 85-100%, 68-97%, 63-85%, respectively; late Radiotherapy and Oncology Group Grades 3 and 4 genitourinary and gastrointestinal toxicities are seen in <8% of patients. HDR-BT boost is now a relatively well-established treatment modality for certain intermediate-risk and high-risk prostate cancer patients, though limitations exist in drawing conclusions from the currently published studies.

Radiotherapy protocol deviations and clinical outcomes: a meta-analysis of cooperative group clinical trials.

BACKGROUND: Noncompliance with radiotherapy (RT) protocol guidelines has been linked to inferior clinical outcomes. We performed a meta-analysis of cooperative group trials to examine the association between RT quality assurance (QA) deviations and disease control and overall survival (OS). METHODS: We searched MEDLINE and the Cochrane Central Register of Controlled Trials for multi-institutional trials that reported clinical outcomes in relation to RT QA results. Hazard ratios (HRs) describing the association between RT protocol noncompliance and patient outcomes were extracted directly from the original studies or calculated from survival curves. Inverse variance meta-analyses were performed to assess the association between RT QA deviations and OS. A second meta-analysis tested the association between RT QA deviations and secondary outcomes, including local or locoregional control, event-free survival, and relapse. Random-effects models were used in cases of statistically significant (P < .10) effect heterogeneity. The Egger test was used to detect publication bias. All statistical tests were two-sided. RESULTS: Eight studies (four pediatric, four adult) met all inclusion criteria and were incorporated into this analysis. The frequency of RT QA deviations ranged from 8% to 71% (median = 32%). In a random-effects model, RT deviations were associated with a statistically significant decrease in OS (HR of death = 1.74, 95% confidence interval [CI] = 1.28 to 2.35; P < .001). A similar effect was seen for secondary outcomes (HR of treatment failure = 1.79, 95% CI = 1.15 to 2.78; P = .009). No evidence of publication bias was detected. CONCLUSION: In clinical trials, RT protocol deviations are associated with increased risks of treatment failure and overall mortality.

Reirradiation of head and neck cancer with high-dose-rate brachytherapy: a customizable intraluminal solution for postoperative treatment of tracheal mucosa recurrence.

PURPOSE: Delivering adequate dose to tracheal mucosa recurrence after multiple prior courses of surgery and radiation presented a challenge for radiation delivery. Tumor bed location and size, combined with previous doses to surrounding areas, complicated the use of external beam therapy with either photons or electrons. High-dose-rate (HDR) brachytherapy was explored to provide sufficient dose coverage. METHODS AND MATERIALS: A 45-year-old gentleman presented with recurrent head and neck cancer. After undergoing additional excision of gross tumor in the tracheal region, radiation was recommended to improve local control. The region of residual tumor was confined to a small superficial lesion at the posterior-superior aspect of the trachea, involving mucosa located along the bend of the trachea, immediately deep to the stoma. External beam treatment was discussed but was not recommended based on recurrence location in the prior radiation field and patient's flexed chin position. HDR technique with a custom applicator was preferred. RESULTS: A three-dimensional HDR plan based on computed tomography used a single catheter optimized to cover gross tumor volume as delineated by physician. Prescribed dose was 5 Gy/fraction for six fractions (two fractions/wk). The applicator position was verified daily with computed tomography and physician setup approval before treatment. The patient was positioned on a wing board to allow access to the stoma. HDR brachytherapy was well tolerated. CONCLUSIONS: Intraluminal HDR brachytherapy is a viable option for providing dose to region inside tracheal stoma. Advantages over photon and electron beam therapy include reduced dose to surrounding tissues previously irradiated, skin dose, and reproducibility of treatment delivery.

High-dose-rate surface brachytherapy to boost elongated, curvilinear incisional scars after extrapleural pneumonectomy for malignant pleural mesothelioma treated with adjuvant intensity-modulated radiation therapy.

PURPOSE: Providing adequate dosimetric coverage of elongated, curvilinear incisions during adjuvant intensity-modulated radiation therapy (IMRT) after extrapleural pneumonectomy (EPP) for malignant pleural mesothelioma (MPM) creates technical challenges. We explored high-dose-rate (HDR) surface brachytherapy to supplement dose to multiple curvilinear incisions. This modality circumvents the technical limitations of relying on multiple en face electron fields while minimizing dose to adjacent normal tissues. METHODS AND MATERIALS: A 59-year-old man presented with a left-sided, Stage III, T3N2M0, epithelioid MPM. After undergoing a left EPP, adjuvant IMRT was recommended to improve local control. An eight-field IMRT plan was designed to encompass the postoperative hemithorax. Incisional scars were lengthy and extended beyond the hemithoracic target volume. Both en face electron and surface HDR plans were prepared and evaluated based on dosimetric coverage of the incisional scars, dose to normal tissues, reliability of setup, and treatment delivery. RESULTS: HDR was preferred. The patient was planned and treated in the right lateral decubitus position. HDR source catheters were placed along the incisions atop 5-mm bolus. A composite plan including IMRT and brachytherapy dose contributions was produced. Boosts of incisional scars were performed in six fractions (three fractions per week) of 3 Gy prescribed to 12 mm from the catheter. HDR brachytherapy was well tolerated. CONCLUSIONS: Surface HDR brachytherapy is a viable option for supplemental dose to incisional scars at risk of local recurrence after EPP for MPM. Advantages over electron beam therapy include avoidance of field abutments and feathering, less tissue-bone interface dose uncertainty and reproducibility of treatment delivery.