Can an in-person hands-on applicator-based teaching session improve trainee knowledge and comfort with complex gynecologic brachytherapy?

INTRODUCTION: With the emergence of imaged-based planning and hybrid applicators the complexity of gynecologic brachytherapy has dramatically increased. Despite the known advantages of brachytherapy, notable national declines in utilization of brachytherapy have been documented. Clearly improved education in the sphere of gynecologic brachytherapy is needed. We hypothesize that a hands-on applicator-based training session would improve trainee comfort with gynecologic brachytherapy. METHODS AND MATERIALS: An in-person, applicator-based, hands-on training session was held with trainees from both radiation and gynecologic oncology programs. Trainees practiced assembling and handling applicators while receiving instruction on clinical scenarios in which various applicators are used in gynecologic cancer brachytherapy. Pre- and post-session, participants were administered an objective test of 10 pictorial-based case vignettes to quantify ability to select the correct applicator based on the interpretation of T2-weighted MR images. Participants additionally received a subjective survey to quantify comfort and experience with gynecologic brachytherapy using Likert-type question formatting. RESULTS: A total of 14 trainees participated. Most common case volume experience was 0-10 intracavitary (57%), 0-10 hybrid (71%), and 0-10 interstitial (71%). Pre-session, the most common answer to comfort level was "not comfortable still learning" for all brachytherapy types, and most common answer to largest gap in knowledge was all facets of brachytherapy. Average case-based test score was 3.5/10 pre-session versus 5.3/10 post-session (p = 0.028). Post-session, all respondents reported improved comfort level with brachytherapy. Post-session, most common answer to largest gap in knowledge was applicator/patient selection, and applicator/patient selection was also the largest area of identified improvement. 100% of participants felt repeating the session in the future would be helpful. CONCLUSIONS: Hands-on training with applicators improves both subjective and objective comfort with gynecologic brachytherapy. With 100% of participants requesting to implement this session into resident training, we suggest national opportunities might exist to expand educational processes and improve utilization of complex gynecologic brachytherapy in practice.

Clinical and Imaging Outcomes After Trigeminal Schwannoma Radiosurgery: Results From a Multicenter, International Cohort Study.

BACKGROUND AND OBJECTIVES: An international, multicenter, retrospective study was conducted to evaluate the long-term clinical outcomes and tumor control rates after stereotactic radiosurgery (SRS) for trigeminal schwannoma. METHODS: Patient data (N = 309) were collected from 14 international radiosurgery centers. The median patient age was 50 years (range 11-87 years). Sixty patients (19%) had prior resections. Abnormal facial sensation was the commonest complaint (49%). The anatomic locations were root (N = 40), ganglion (N = 141), or dumbbell type (N = 128). The median tumor volume was 4 cc (range, 0.2-30.1 cc), and median margin dose was 13 Gy (range, 10-20 Gy). Factors associated with tumor control, symptom improvement, and adverse radiation events were assessed. RESULTS: The median and mean time to last follow-up was 49 and 65 months (range 6-242 months). Greater than 5-year follow-up was available for 139 patients (45%), and 50 patients (16%) had longer than 10-year follow-up. The overall tumor control rate was 94.5%. Tumors regressed in 146 patients (47.2%), remained unchanged in 128 patients (41.4%), and stabilized after initial expansion in 20 patients (6.5%). Progression-free survival rates at 3 years, 5 years, and 10 years were 91%, 86%, and 80 %. Smaller tumor volume (less than 8 cc) was associated with significantly better progression-free survival ( P = .02). Seventeen patients with sustained growth underwent further intervention at a median of 27 months (3-144 months). Symptom improvement was noted in 140 patients (45%) at a median of 7 months. In multivariate analysis primary, SRS ( P = .003) and smaller tumor volume ( P = .01) were associated with better symptom improvement. Adverse radiation events were documented in 29 patients (9%). CONCLUSION: SRS was associated with long-term freedom (10 year) from additional management in 80% of patients. SRS proved to be a valuable salvage option after resection. When used as a primary management for smaller volume tumors, both clinical improvement and prevention of new deficits were optimized.

Treatment of Internal Mammary Nodes is Associated With Improved Overall Survival in Breast Cancer: A Meta-Analysis.

INTRODUCTION: The role of internal mammary nodal irradiation (IMNI) as a component of regional nodal radiotherapy is a controversial issue in breast radiation oncology with conflicting results presented in recent landmark trials. We thus created a meta-analysis of available data to better ascertain the potential benefit of IMNI. We hypothesize that with the increased power available within a meta-analysis, IMNI will prove to improve overall survival (OS) in breast cancer. METHODS: Literature search was conducted for prospective studies comparing IMNI to no IMNI. Primary endpoint was OS and secondary endpoints included local recurrence, regional recurrence, disease-free survival (DFS), breast cancer mortality (BCM), distant metastasis-free survival (DMFS), grade 2+ skin toxicity, cardiac events, and pneumonitis events. Subgroup analyses were performed for tumor location (medial/central vs. lateral), and nodal status (pN+ vs. pN0). Fixed-effect model was used if there was no heterogeneity, random-effects model otherwise. RESULTS: Four studies with a total of 5258 patients (IMNI: n=2592; control: n=2666) were included in the study. Pooled results showed IMNI significantly improved OS for all-comers (hazard ratio [HR]=0.89; 95% CI 0.81-0.97; P =0.008), as well as subgroups of pN+ with medial/central tumor location (HR=0.84; 95% CI 0.73-0.96; P =0.01) and pN+ with lateral tumor location (HR=0.87; 95% CI 0.77-0.99; P =0.04). There was no significant difference in OS for subgroups of pN0 and medial/central tumor location. There was no difference in local recurrence, but regional recurrence was significantly improved ( P =0.04). Endpoints of DFS (HR 0.91, 95% CI 0.84-0.99 P =0.03), BCM (HR 0.87, 95% CI 0.77-0.98, P =0.03), and DMFS (HR=0.87; 95% CI, 0.78-0.98; P =0.02) were all improved with IMNI. Grade 2+ skin toxicity, cardiac events and pneumonitis events were not significantly different between patient in the IMNI and no IMNI groups. CONCLUSION: Inclusion of IMN irradiation improves OS, DFS, BCM, and DMFS in breast cancer. Largest effect on OS was noted in the subgroup of patients with pN+ and medial/central tumor location.

The role of obesity in treatment planning for early-stage cervical cancer.

OBJECTIVES: Optimal management of obese patients with early-stage cervical cancer is debated despite evidence of non-inferior survival in obese patients undergoing radical hysterectomy with pelvic lymphadenectomy (RH) compared to primary radiation with or without radiosensitizing chemotherapy (RT). Objectives included describing patient factors affecting disposition to RH versus RT; comparing RH outcomes for obese (BMI >30 mg/m2) and non-obese patients; and comparing differences in recurrence free survival (RFS) and overall survival (OS). METHODS: This was a single institution cohort study of all cervical cancer patients who underwent RH or were candidates for RH based on clinical stage. Demographic, clinicopathologic and treatment outcomes were collected and analyzed. RESULTS: RT patients (n = 39, 15%) had a higher BMI (p = 0.004), older age (p < 0.001), more life-limiting comorbidities (LLC) (p < 0.001), larger tumor size (p = 0.001), and higher clinical stage (p = 0.013) compared to RH patients (n = 221, 85%). On multivariable survival analysis there was no difference in OS based on treatment modality; significant predictors of worse OS were larger tumor size, higher number of LLC and recurrence. Among the RH group, obese patients had a longer operative time (p = 0.01) and more LLC (p = 0.02); there were no differences in demographic or clinicopathologic characteristics, operative outcomes, RFS or OS compared to non-obese patients. CONCLUSION: In this cohort of RH-eligible cervical cancer patients, BMI was independently associated with disposition to RT. Studies demonstrate that RH is feasible and safe in obese patients with no difference in RFS or OS when compared to non-obese patients. Thus, the decision for disposition to RT should not be based on obesity alone.

Intracranial intraoperative radiotherapy (IORT): evaluation of electrocorticography and peri-operative seizure risk.

BACKGROUND: Intra-operative radiotherapy (IORT) for brain metastases (BMs) and primary brain tumors has emerged as an adjuvant radiation modality that allows for consolidation of care into a single anesthetic episode with surgical resection. Yet, there is a paucity of data regarding the impact that IORT may have on peri-operative and long-term seizure risk. METHODS: A retrospective analysis of patients receiving IORT during tumor resection was performed via registry including data regarding peri-operative anti-seizure medications and anesthetic agents. Intra-operative neuromonitoring was performed using electrocorticography (ECoG) captured before-, during-, and after-IORT then analyzed for evidence of seizure or significant baseline changes. Kaplan-Meir estimations were used for overall survival analysis relative to documented clinical seizure incidence post-IORT. RESULTS: Of the 24 consecutive patients treated with IORT during tumor resection included, 18 (75%) patients were diagnosed with BMs while 6 (25%) had newly-diagnosed glioblastoma. Mean and median survival times were 487 and 372 days, respectively. Clinical seizures occurred in 3 patients post-IORT, 2 BMs patients within 9 months and 1 glioblastoma patient at 14 months. IORT time represented 9.5% of anesthetic time. ECoG recordings were available for 5 patients (4 BMs; 1 glioblastoma), with mean recording durations of 13% of the total anesthetic time and no evidence of high-frequency oscillations or seizure activity. CONCLUSIONS: IORT is an option for delivery of definitive radiation in surgically resected brain tumors without increasing the peri-operative or long-term risk of seizure. ECoG data during the delivery of radiation fail to demonstrate any electrophysiological changes in response to ionizing radiation.

Outcomes of 3D MRI based HDR brachytherapy with hybrid multichannel vaginal cylinder applicator and freehand needles for treatment of vaginal disease.

Freehand needles can be used with multichannel vaginal cylinders (MCVC) to cover vaginal cancer >7 mm thick or with supra-vaginal extension. We report our institutional outcomes using this novel hybrid technique. Patients with vaginal malignancies treated with HDR BT using MCVC plus freehand needles from 2014-2021 at our institution were identified. Clinical characteristics, details of brachytherapy, initial response, and overall local control (LC) outcomes were recorded. LC was analyzed via Kaplan-Meier method. 34 patients were identified with median follow-up 1.9 years. 19 patients had primary endometrial cancer with vaginal recurrence/disease, and remaining had primary vaginal cancer or other primaries. 7 patients had recurrence after previous RT course. 25 patients received EBRT with median dose 45 Gy in 25 fractions, and rest received BT alone. Median HR-CTV D90 for patients treated with EBRT plus BT was 77.4 Gy. 30 patients had complete local response to BT on initial examination and/or follow-up imaging. 1 and 2-year LC rates in patients without prior RT treated with EBRT + BT were 94.1% and 94.1%, respectively. 1 and 2-year LC rates for those without prior RT were 88.1% and 76.4%, respectively. 1 and 2-year LC rates for those with prior RT were 68.6% and 34.3%, respectively. 1 patient had vaginal laceration requiring surgical repair, and 1 patient developed small bowel obstruction 1 month after BT, with no additional acute grade 3+ toxicities identified. Our approach with MCVC plus freehand needles with MRI-based planning was feasible and safe, with excellent initial local response and low rate of serious toxicities.

Factors associated with ductal carcinoma in situ (DCIS) treatment patterns and patient-reported outcomes across a large integrated health network.

PURPOSE: To examine associations between ductal carcinoma in situ (DCIS) patients' characteristics, treating locations and DCIS treatments received and to pilot assessing quality-of-life (QoL) values among DCIS patients with diverse backgrounds. METHODS: We performed a retrospective tumor registry review of all patients diagnosed and treated with DCIS from 2018 to 2019 in the UPMC-integrated network throughout central and western Pennsylvania. Demographics, clinical information, and administered treatments were compiled from tumor registry records. We categorized contextual factors such as different hospital setting (academic vs. community), socioeconomic status based on the neighborhood deprivation index (NDI) as well as age and race. QoL survey was administered to DCIS patients with diverse backgrounds via QoL questionnaire breast cancer module 23 and qualitative assessment questions. RESULTS: A total of 912 patients were reviewed. There were no treatment differences noted for age, race, or NDI. Mastectomy rate was higher in academic sites than community sites (29 vs. 20.4%; p = 0.0045), while hormone therapy (HT) utilization rate was higher in community sites (74 vs. 62%; p = 0.0012). QoL survey response rate was 32%. Only HT side effects negatively affected in QoL scores and there was no significant difference in QoL domains and decision-making process between races, age, NDI, treatment groups, and treatment locations. CONCLUSION: Our integrated health network did not show chronically noted disparities arising from social determinates of health for DCIS treatments by implementing clinical pathways and system-wide peer review. Also, we demonstrated feasibility in collecting QoL for DCIS women with diverse backgrounds and different socioeconomic statuses.

Dosimetry and Toxicity Outcomes in Patients Treated with Hypofractionated Regional Nodal Irradiation for Breast Cancer: What is the Best Dose-Volume Limit to Minimize Risks of Radiation Pneumonitis?

PURPOSE: Although published data have supported the use of hypofractionated regional nodal irradiation (HF-RNI) for breast cancer, limited dosimetric data exist to evaluate predictors of lung toxicity. The ongoing RT CHARM trial limits the percentage of ipsilateral lung volume that receives ≥18 Gy to 35 to 40%. We assessed dosimetry, toxicity, and disease outcomes in patients with breast cancer treated with HF-RNI with a particular focus on pneumonitis. METHODS AND MATERIALS: We retrospectively reviewed all patients with breast cancer treated with HF-RNI (40-43 Gy in 15-16 fractions) after either lumpectomy or mastectomy at The University of Pittsburgh Medical Center from September 2018 to December 2021 to collect dosimetric and outcomes data. All post-radiation therapy chest computed tomography (CT) scans were manually reviewed for evidence of acute (≤6 months postradiation) or chronic (>6 months postradiation) pneumonitis. RESULTS: One-hundred-ninety-one patients qualified with a median follow-up of 20.3 months (range, 5.1-42.2). Acute grade 1 (G1) pneumonitis was observed in 6.8% of the overall cohort (13 of 191 patients) and 39.4% of the patients (13 of 33) who received a chest CT ≤6 months postradiation therapy. Only 1 patient developed acute G2 pneumonitis. Chronic G1 pneumonitis was observed in 29.8% of the overall cohort (57 of 191 patients) and 77% of patients (57 of 74 patients) who received a chest CT >6 months postradiation therapy. No patients developed acute G3+ or chronic G2+ pneumonitis. CONCLUSIONS: Rates of symptomatic pneumonitis were low in this cohort of patients treated with HF-RNI, even with integration of HER2/neu-directed therapy, chemotherapy, hormone therapy, and internal mammary nodal irradiation. Lung V20Gy <26% appeared safe in this cohort to limit symptomatic pneumonitis, though this is not meant to represent the safe upper limit. Given the low event rate of symptomatic pneumonitis, data from larger cohorts will be needed to assess dosimetric predictors and the safe upper limit of lung dose.

Stereotactic Body Radiation Therapy (SBRT) for Spinal Metastases: Real-world Outcomes From an International Multi-institutional SBRT Registry.

OBJECTIVE: The objective of this study was to compare clinical outcomes following single fraction versus fractionated stereotactic body radiotherapy (SBRT) for spinal metastases. MATERIALS AND METHODS: A multi-institutional registry was queried for patients with spinal metastases treated with single-fraction or fractionated SBRT. Potential predictive factors of local control (LC) and overall survival were evaluated. Pretreatment and posttreatment Visual Analog Scale scores were analyzed to examine initial and durable pain responses and complete response (CR) rates. Logistic regression was utilized to assess potential correlations between pain response, biologically effective dose (BED), and fractionation. RESULTS: Four hundred sixty-six patients with 514 lesions treated with SBRT were identified; 209 and 104 lesions had information on LC and pain, respectively. The median pain score of patients with symptoms was 6 (range: 3 to 10). The median follow-up was 8.9 months (range: 0.4 to 125.5 mo). Utilizing Karnofsky Performance Score, age, and primary site (lung and/or nonbreast), 1-year overall survival rates were 76.1%, 59.1%, 54.9%, 37.2%, and 23.5% for patients with 0 to 4 of these factors, respectively (P<0.0001). One- and 2-year LC rates were 79.9% and 73.6%, respectively. Eighty-six patients (82.7%) had an initial pain response with a median decline of 3.5 and a CR rate of 47.1%. Sixty-five patients (62.5%) had a durable pain response with a median decline of 2 and a CR rate of 20.2%. Higher initial CR rates were observed with BED10 ≥51 Gy10 (58.7% vs. 37.9%; P=0.04). CONCLUSIONS: Following SBRT, encouraging palliative responses with >80% and 60% of patients having initial and durable pain responses, respectively. Dose escalation may result in improved initial CR rates. Performance status, age, and primary histology are factors to consider in the absence of pain.

Is Radiation Therapy Cost-Effective in the Positron Emission Tomography/Computed Tomography Era for Early-Stage Favorable Hodgkin Lymphoma With Alternative Payment Models?

PURPOSE: Despite multiple randomized trials, variation in practice remains regarding the most effective treatment for early-stage, favorable-risk Hodgkin lymphoma. With increasing emphasis on alternative payment models, we investigate the cost-effectiveness of chemotherapy alone versus combined modality therapy (CMT). METHODS AND MATERIALS: A Markov model was formed to compared 2 cycles of adriamycin, bleomycin, vinblastine, and dacarbazine (ABVD) to 2 cycles of ABVD followed by 20 Gy in 10 fractions involved-site radiation therapy. Modalities were compared using the incremental cost-effectiveness ratio, with effectiveness measured in quality-adjusted life years (QALYs) and evaluated with a willingness to pay a threshold of $100,000 per QALY gained. RESULTS: The base case analysis showed that CMT is cost-effective compared with ABVD alone, with an incremental cost-effectiveness ratio of $8028 per QALY gained and an incremental cost of $236 gaining 0.029 QALYs. On sensitivity analyses, the results were the most sensitive to changes in recurrence rates. If the recurrence rate differences were ≥6%, CMT was cost-effective. CONCLUSIONS: CMT is a cost-effective strategy for early-stage, favorable-risk Hodgkin lymphoma based on currently available evidence. However, small variations in recurrence-rate estimates dramatically affect strategy cost-effectiveness.

Radiation Toxicity in Patients With Collagen Vascular Disease: A Meta-Analysis of Case-Control Studies.

PURPOSE: Several retrospective series have reported that patients with collagen vascular disease (CVD) are at increased risk of radiation (RT) toxicity. However, the evidence is mixed, and many series lack control groups. We performed a meta-analysis including only case-cohort or randomized studies that examined the risk of RT toxicity for patients with CVD compared with controls. METHODS AND MATERIALS: Meta-analysis of Observational Studies in Epidemiology guidelines were used to perform a comprehensive search identifying case-control or randomized studies reporting RT toxicity outcomes for patients with CVD versus controls. Data were synthesized from studies reporting grade 2 to 3 or more (G2/3 +) acute and late RT toxicities. Results were analyzed with fixed effects meta-analysis on the random-effects model for between-study heterogeneity; otherwise, the fixed-effects model was used. Hazard ratio or odds ratio (OR) were the effect-size estimators, as appropriate. RESULTS: Ten studies were included, with 4028 patients (CVD: 406, control: 3622). Patients with CVD had higher rates of acute G2/3 + toxicity (26.2% vs 16.5%, OR [odds ratio] 2.01; P < .001) and late G2/3 + toxicity (18.4% vs 10.1%, OR 2.37; P < .001). Higher rates of late G2/3 + toxicity were observed for CVD patients with systemic lupus erythematous (21% vs 9.7%; OR 2.55, P = .03), systemic scleroderma (31.8% vs 9.7%, OR 3.85; P = .03), rheumatoid arthritis (11.7% vs 8.4%, OR = 2.56; P = .008), and those irradiated to the pelvis/abdomen (32.2% vs 11.9%, OR 3.29; P = .001), breast (14.7% vs 4.4%, OR 3.51; P = .003), thorax (12.5% vs 8.7%, OR 3.46; P < .001), and skin (14.6% vs 5.2%, OR 2.59; P = .02). Late grade 5 toxicities were significantly higher for patients with CVD, although absolute rates were low (3.9% vs 0.6%, OR = 7.81; P = .01). CONCLUSIONS: Moderate and severe toxicities are more likely in patients with CVD, with variable risk depending on toxicity grade, CVD subtype, treatment site, and dose. Severe toxicities are uncommon. These factors should be considered when informing patients of treatment-related risks and monitoring for morbid treatment sequelae.

Cost-Effectiveness of Prophylactic Cranial Irradiation Versus MRI Surveillance for Extensive-Stage Small Cell Lung Cancer.

PURPOSE: Owing to conflicting prospective data, controversy exists regarding prophylactic cranial irradiation (PCI) in extensive-stage small cell lung cancer (ES-SCLC). We evaluated the cost-effectiveness of PCI versus magnetic resonance imaging (MRI) surveillance for patients with ES-SCLC based on currently available evidence and in the context of the proposed Centers for Medicare & Medicaid Services alternative payment model. METHODS AND MATERIALS: A Markov state transition model was constructed to perform a cost-effectiveness analysis comparing MRI surveillance alone with PCI for ES-SCLC. Clinical parameters were obtained from clinical trial data, and cost data were based on 2019 Medicare reimbursement. Strategies were compared using the incremental cost-effectiveness ratio (ICER) with effectiveness in quality-adjusted life years (QALYs) and evaluated with a willingness-to-pay threshold of $100,000 per QALY gained. One-way and probabilistic sensitivity analyses were performed to consider model uncertainty. RESULTS: In the base-case scenario, PCI was not cost-effective in this model, with an ICER of $168,456 per QALY gained compared with MRI surveillance alone, assuming that overall survival was 10 months for MRI surveillance alone and 12.5 months for PCI. One-way sensitivity analysis showed that results were most sensitive to the variation of overall survival and cognitive decline rates between the 2 groups. In a scenario analysis in which all patients received hippocampal-avoidance PCI, the model results became nearly cost-effective with PCI. CONCLUSIONS: PCI was not found to be cost-effective within this model compared with MRI surveillance alone, owing to the neurocognition decline effect of PCI based on available evidence. Hippocampal-avoidance PCI may be a potential cost-effective strategy for ES-SCLC, with confirmation expected after an ongoing prospective clinical trial (The Southwest Oncolology Group MRI Brain Surveillance Alone Versus MRI Surveillance And Prophylactic Cranial Irradiation [MAVERICK]), which includes assessments of cognitive function.

Primary Hypothyroidism in Childhood Cancer Survivors Treated With Radiation Therapy: A PENTEC Comprehensive Review.

PURPOSE: From the Pediatric Normal Tissue Effects in the Clinic (PENTEC) initiative, a systematic review and meta-analysis of publications reporting on radiation dose-volume effects for risk of primary hypothyroidism after radiation therapy for pediatric malignancies was performed. METHODS AND MATERIALS: All studies included childhood cancer survivors, diagnosed at age <21 years, whose radiation therapy fields exposed the thyroid gland and who were followed for primary hypothyroidism. Children who received pituitary-hypothalamic or total-body irradiation were excluded. PubMed and the Cochrane Library were searched for studies published from 1970 to 2017. Data on age at treatment, patient sex, radiation dose to neck or thyroid gland, specific endpoints for hypothyroidism that were used in the studies, and reported risks of hypothyroidism were collected. Radiation dose-volume effects were modeled using logistic dose response. Relative excess risk of hypothyroidism as a function of age at treatment and sex was assessed by meta-analysis of reported relative risks (RR) and odds ratios. RESULTS: Fifteen publications (of 1709 identified) were included for systematic review. Eight studies reported data amenable for dose-response analysis. At mean thyroid doses of 10, 20, and 30 Gy, predicted rates of uncompensated (clinical) hypothyroidism were 4%, 7%, and 13%, respectively. Predicted rates of compensated (subclinical) hypothyroidism were 12%, 25%, and 44% after thyroid doses of 10, 20, and 30 Gy, respectively. Female sex (RR = 1.7, P < .0001) and age >15 years at radiation therapy (RR = 1.3, P = .005) were associated with higher risks of hypothyroidism. After a mean thyroid dose of 20 Gy, predicted risks of hypothyroidism were 13% for males <14 years of age, increasing to 29% for females >15 years of age. CONCLUSION: A radiation dose response for risk of hypothyroidism is evident; a threshold radiation dose associated with no risk is not observed. Thyroid dose exposure should be minimized when feasible. Data on hypothyroidism after radiation therapy should be better reported to facilitate pooled analyses.

Initial Data Pooling for Radiation Dose-Volume Tolerance for Carotid Artery Blowout and Other Bleeding Events in Hypofractionated Head and Neck Retreatments.

PURPOSE: Dose-volume data for injury to carotid artery and other major vessels in stereotactic body radiation therapy (SBRT)/SABR head and neck reirradiation were reviewed, modeled, and summarized. METHODS AND MATERIALS: A PubMed search of the English-language literature (stereotactic and carotid and radiation) in April 2018 found 238 major vessel maximum point doses in 6 articles that were pooled for logistic modeling. Two subsequent studies with dose-volume major vessel data were modeled separately for comparison. Attempts were made to separate carotid blowout syndrome from other bleeding events (BE) in the analysis, but we acknowledge that all except 1 data set has some element of BE interspersed. RESULTS: Prior radiation therapy (RT) dose was not uniformly reported per patient in the studies included, but a course on the order of conventionally fractionated 70 Gy was considered for the purposes of the analysis (with an approximately ≥6-month estimated interval between prior and subsequent treatment in most cases). Factors likely associated with reduced risk of BE include nonconsecutive daily treatment, lower extent of circumferential tumor involvement around the vessel, and no surgical manipulation before or after SBRT. CONCLUSIONS: Initial data pooling for reirradiation involving the carotid artery resulted in 3 preliminary models compared in this Hypofractionated Treatment Effects in the Clinic (HyTEC) report. More recent experiences with alternating fractionation schedules and additional risk-reduction strategies are also presented. Complications data for the most critical structures such as spinal cord and carotid artery are so limited that they cannot be viewed as strong conclusions of probability of risk, but rather, as a general guideline for consideration. There is a great need for better reporting standards as noted in the High Dose per Fraction, Hypofractionated Treatment Effects in the Clinic introductory paper.

Do air gaps with image-guided vaginal cuff brachytherapy impact failure rates in patients with high-intermediate risk FIGO Stage I endometrial cancer?

PURPOSE: The aim of this study was to assess the impact of air gaps at the cylinder surface on the rate of vaginal cuff failure (VCF) after image-guided adjuvant vaginal cuff brachytherapy (VCBT) in the treatment of high-intermediate risk (HIR) FIGO (Fédération Internationale de Gynécologie et d'Obstétrique (International Federation of Gynecology and Obstetrics)) Stage I endometrial cancer. METHODS AND MATERIALS: A retrospective review of patients treated with image-guided VCBT from 2009 to 2016 for HIR FIGO Stage I endometrial cancer was performed. Air gaps present at the applicator surface on the first postinsertion CT were contoured. Vaginal cuff failure-free survival (VCFFS) was measured from the first fraction of VCBT to VCF. RESULTS: A total of 234 patients were identified. Air gaps were present on the first postinsertion CT scan in 82% of patients. The median number of air gaps was 2 (interquartile range [IQR] 1-3), median depth of the largest air gap was 2.7 mm (IQR 2.1-3.4 mm), and the median cumulative volume of air gaps was less than 0.1 cm3 (range < 0.1-0.7 cm3). At a median followup of 56 months (IQR 41-69), 12 patients (5%) experienced VCF, of which 4 had isolated VCF and 8 had synchronous pelvic or distant failure. Five-year VCFFS and isolated VCFFS were 96% (95% confidence interval 93-98%) and 98% (95% confidence interval 96-100%), respectively. On univariate analysis, no factors, including the presence, number, maximum depth, or cumulative volume of air gaps, were predictive for VCFFS. CONCLUSIONS: In this population, VCFFS remained high despite most patients having air gaps present on postinsertion CT scan.

Dose homogeneity analysis of adjuvant radiation treatment in surgically resected brain metastases: Comparison of IORT, SRS, and IMRT indices.

PURPOSE: Although surgery remains a treatment option for symptomatic brain metastases, the need for adjuvant radiation after surgery is widely accepted as standard. Despite a multitude of randomized trials aimed at identifying the ideal radiation treatment plan for surgically resected metastases, the development of new delivery regiments necessitates a periodic re-evaluation of dosimetric performance/outcome. Here, we compare the homogeneity index (HI) across three platforms: single-session stereotactic radiosurgery (SRS), multisession stereotactic radiotherapy, and intraoperative radiotherapy (IORT). METHODS AND MATERIALS: Patients treated with IORT after surgical resection of brain metastases were identified and dosimetric parameters collected from the dose-volume histograms based on the development of conformal plans for adjuvant radiation using Gamma Knife-SRS (GK-SRS), linear accelerator based intensity-modulated radiation therapy, and IORT. HIs were calculated using four established methods and compared across platforms within the patient cohort. Statistical analyses were performed using analysis of variance. RESULTS: The mean maximal doses for the GK-SRS and IMRT plans were 30 Gy and 29 Gy with margin prescription doses of 16 Gy and 24 Gy, respectively. The IORT dose was 30 Gy to the applicator surface. HIs varied based on calculation methods, but maintained consistency when comparing across platforms with IORT having the lower mean HI value (0.56; 95% confidence interval (CI) 0.55-0.60) in single-fraction treatment, compared with GK-SRS (0.77; 95% CI 0.76-0.80). The mean multisession IMRT HI was lower than both single-fraction treatment modalities at 0.41 (95% CI 0.40-0.42). CONCLUSIONS: When using the HI as the primary dosimetric parameter for adjuvant radiation plans after surgical resection of brain metastases IORT offers improved dose homogeneity compared with GK-SRS in single-fraction treatment, whereas fractionated LINAC-based IMRT was superior with respect to the HI in comparison among all three methods.

Cost-Effectiveness Analysis of Biological Signature DCISionRT Use for DCIS Treatment.

BACKGROUND: Currently it remains difficult to identify patients most likely to benefit from radiotherapy (RT) for ductal carcinoma-in-situ (DCIS), thus leading to wide variation in practice patterns. The genomic risk assessment tool DCISionRT (PreludeDX) has been validated to prognosticate recurrence risk and predict RT benefit. We aimed to study the cost-effectiveness analysis comparing DCIS treatments based on DCISionRT testing to traditional clinicopathologic risk factors. PATIENTS AND METHODS: A Markov state transition model was constructed to perform a cost-effectiveness analysis comparing breast-conserving surgery with or without RT using DCISionRT testing vs. traditional clinicopathologic risk factors. Clinical parameters were obtained from clinical trial data and cross-validation studies. Cost data were based on 2019 Medicare reimbursement. Incremental cost-effectiveness ratio (ICER) was calculated as incremental cost per quality-adjusted life-year (QALY) gained comparing DCIS treatments using DCISionRT testing to traditional clinicopathologic risk factors and evaluated with a willingness-to-pay threshold of US$100,000 per QALY gained. To account for uncertainty, 1-way and probabilistic sensitivity analyses were performed. RESULTS: Base case analysis showed that DCIS management using DCISionRT testing was a cost-effective strategy, resulting in an ICER of $74,331 per QALY gained compared to clinicopathology-based treatment. Model results were sensitive to a variation of the proportion of genomic-high, low-risk patients receiving RT in DCISionRT testing strategy, and changes in DCISionRT testing cost. CONCLUSION: DCISionRT testing could potentially be a cost-effective strategy compared to traditional decision making for DCIS treatments, optimizing RT benefit based on an accurate recurrence risk assessment.

Head and Neck Tumor Control Probability: Radiation Dose-Volume Effects in Stereotactic Body Radiation Therapy for Locally Recurrent Previously-Irradiated Head and Neck Cancer: Report of the AAPM Working Group.

PURPOSE: Stereotactic body radiation therapy (SBRT) has emerged as a viable reirradiation strategy for locally recurrent previously-irradiated head and neck cancer. Doses in the literature have varied, which challenges clinical application of SBRT as well as clinical trial design. MATERIAL & METHODS: A working group was formed through the American Association of Physicists in Medicine to study tumor control probabilities for SBRT in head and neck cancer. We herein present a systematic review of the available literature addressing the dose/volume data for tumor control probability with SBRT in patients with locally recurrent previously-irradiated head and neck cancer. Dose-response models are generated that present tumor control probability as a function of dose. RESULTS: Data from more than 300 cases in 8 publications suggest that there is a dose-response relationship, with superior local control and possibly improved overall survival for doses of 35 to 45 Gy (in 5 fractions) compared with <30 Gy. CONCLUSION: Stereotactic body radiation therapy doses equivalent to 5-fraction doses of 40 to 50 Gy are suggested for retreatment.