Trends in cardiac CT utilization for patients with pediatric and congenital heart disease: A multicenter survey study.

BACKGROUND: The use of cardiac CT (CCT) has increased dramatically in recent years among patients with pediatric and congenital heart disease (CHD), but little is known about trends and practice pattern variation in CCT utilization for this population among centers. METHODS: A 21-item survey was created to assess CCT utilization in the pediatric/CHD population in calendar years 2011 and 2021. The survey was sent to all non-invasive cardiac imaging directors of pediatric cardiology centers in North America in September 2022. RESULTS: Forty-one centers completed the survey. In 2021, 98% of centers performed CCT in pediatric and CHD patients (vs. 73% in 2011), and 61% of centers performed >100 CCTs annually (vs. 5% in 2011). While 62% of centers in 2021 utilized dual-source technology for high-pitch helical acquisition, 15% of centers reported primarily performing CCT on a 64-slice scanner. Anesthesia utilization, use of medications for heart rate control, and type of subspecialty training for physicians interpreting CCT varied widely among centers. 50% of centers reported barriers to CCT performance, with the most commonly cited concerns being radiation exposure, the need for anesthesia, and limited CT scan staffing or machine access. 37% (11/30) of centers with a pediatric cardiology fellowship program offer no clinical or didactic CCT training for categorical fellows. CONCLUSION: While CCT usage in the CHD/pediatric population has risen significantly in the past decade, there is broad center variability in CCT acquisition techniques, staffing, workflow, and utilization. Potential areas for improvement include expanding CT scanner access and staffing, formal CCT education for pediatric cardiology fellows, and increasing utilization of existing technological advances.

Long-Term Follow-Up of Second-Degree Heart Block in Children.

Little is known about the outcomes of children with second-degree heart block. We aimed to determine whether children with structurally normal hearts and Mobitz 1, 2:1 block or Mobitz 2 are at increased risk for progressing to complete heart block (CHB) or requiring a pacemaker (PM) at long-term follow-up. We searched our institutional electrophysiology database for children with potentially concerning second-degree block on ambulatory rhythm monitoring between 2009 and 2021, defined as frequent episodes of Mobitz 1 or 2:1 block, episodes of Mobitz 1 or 2:1 block with additional evidence of conduction disease (i.e. first-degree heart block, bundle branch block), or episodes of Mobitz 2. Ambulatory rhythm monitor, ECG, and demographic data were reviewed. The primary composite outcome was CHB on follow-up rhythm monitor or PM placement. 20 patients were in the final analysis. Six (30%) patients either developed CHB but do not have a PM (4 = 20%) or have a PM (2 = 10%). Median follow-up was 5.8 years (IQR 4.4-7.0). Patients with CHB or PM were more likely to have second-degree block at maximum sinus rate (67% vs. 0%, p = 0.003), a below normal average heart rate (67% vs. 14%, p = 0.04), and 2:1 block on initial ECG (50% vs. 0%, p = 0.02). In this study of children with potentially concerning second-degree block, 30% of patients progressed to CHB or required a PM. Second-degree block at maximum sinus rate, a low average heart, and 2:1 block on initial ECG were associated with increased risk of disease progression.

Trends in Time to Extubation for Pediatric Postoperative Cardiac Patients and Its Correlation With Changes in Clinical Outcomes: A Virtual PICU Database Study.

OBJECTIVES: Mechanical ventilation is often used in children after cardiac surgery but can impair hemodynamics and cause lung injury. Early extubation may improve ICU length of stay and survival. We aimed to describe trends in early extubation rates and evaluate if centers that more commonly practice early extubation have better severity-adjusted outcomes. DESIGN: Retrospective analysis was performed of admissions in the Virtual Pediatric Systems (VPS, LLC) database from 2009 to 2018. Early extubation was defined as patients extubated in the operating room or within 6 hours of PICU admission. SETTING: PICUs participating in the VPS database. PATIENTS: Children in the VPS database who underwent cardiac surgery. INTERVENTIONS: None. MEASUREMENT AND MAIN RESULTS: Among 69,739 subjects, 20% were neonates, 47% underwent early extubation, 5.3% failed extubation, and 2.5% died. Overall, early extubation rates did not change over the study period. Centers were placed in one of four groups based on their early extubation rate in lower complexity surgeries. Centers that most commonly used early extubation had more ICU-free time among all patients in univariable analysis (lowest early extubation group, 23.8 d [interquartile range, 18.2-25.9 d]; highest early extubation group, 24.7 d [20.0-26.2 d]; p < 0.001). After adjusting for center volume, sex, age, surgical complexity, and preoperative ICU admission, increasing center-level early extubation rates were not associated with more ICU-free days. Higher center-level early extubation rate was not associated with mortality in univariable or multivariable analysis but was associated with decreased extubation failure rate (lowest early extubation group, 6.4%; highest early extubation group, 3.6%; p < 0.001). CONCLUSIONS: In this large, multicenter database study, early extubation rates in postoperative cardiac patients did not significantly change between 2009 and 2018. Centers that performed early extubation more frequently did not have shorter ICU stays or difference in mortality rates but did have lower reintubation rates.

Management of Pulmonary Hypertension in the Pediatric Patient.

Pediatric pulmonary hypertension (PH) is a rare disease with historically very high morbidity and mortality. In the past 20 years, there has been a growing recognition that pediatric PH, although having similarities to adult PH, is a unique entity with its own particular pathogeneses, presentation, and management. With better understanding and earlier diagnosis of pediatric PH, and as more medications have become available, survival of children with PH has also significantly improved. This article reviews the various forms of PH in childhood, with a focus on both established and investigational therapies that are available for children with PH.

Performance of a Prostate-Specific Membrane Antigen Positron Emission Tomography/Computed Tomography-Derived Risk-Stratification Tool for High-risk and Very High-risk Prostate Cancer.

Importance: Prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) can detect low-volume, nonlocalized (ie, regional or metastatic) prostate cancer that was occult on conventional imaging. However, the long-term clinical implications of PSMA PET/CT upstaging remain unclear. Objectives: To evaluate the prognostic significance of a nomogram that models an individual's risk of nonlocalized upstaging on PSMA PET/CT and to compare its performance with existing risk-stratification tools. Design, Setting, and Participants: This cohort study included patients diagnosed with high-risk or very high-risk prostate cancer (ie, prostate-specific antigen [PSA] level >20 ng/mL, Gleason score 8-10, and/or clinical stage T3-T4, without evidence of nodal or metastatic disease by conventional workup) from April 1995 to August 2018. This multinational study was conducted at 15 centers. Data were analyzed from December 2020 to March 2021. Exposures: Curative-intent radical prostatectomy (RP), external beam radiotherapy (EBRT), or EBRT plus brachytherapy (BT), with or without androgen deprivation therapy. Main Outcomes and Measures: PSMA upstage probability was calculated from a nomogram using the biopsy Gleason score, percentage positive systematic biopsy cores, clinical T category, and PSA level. Biochemical recurrence (BCR), distant metastasis (DM), prostate cancer-specific mortality (PCSM), and overall survival (OS) were analyzed using Fine-Gray and Cox regressions. Model performance was quantified with the concordance (C) index. Results: Of 5275 patients, the median (IQR) age was 66 (60-72) years; 2883 (55%) were treated with RP, 1669 (32%) with EBRT, and 723 (14%) with EBRT plus BT; median (IQR) PSA level was 10.5 (5.9-23.2) ng/mL; 3987 (76%) had Gleason grade 8 to 10 disease; and 750 (14%) had stage T3 to T4 disease. Median (IQR) follow-up was 5.1 (3.1-7.9) years; 1221 (23%) were followed up for at least 8 years. Overall, 1895 (36%) had BCR, 851 (16%) developed DM, and 242 (5%) died of prostate cancer. PSMA upstage probability was significantly prognostic of all clinical end points, with 8-year C indices of 0.63 (95% CI, 0.61-0.65) for BCR, 0.69 (95% CI, 0.66-0.71) for DM, 0.71 (95% CI, 0.67-0.75) for PCSM, and 0.60 (95% CI, 0.57-0.62) for PCSM (P < .001). The PSMA nomogram outperformed existing risk-stratification tools, except for similar performance to Staging Collaboration for Cancer of the Prostate (STAR-CAP) for PCSM (eg, DM: PSMA, 0.69 [95% CI, 0.66-0.71] vs STAR-CAP, 0.65 [95% CI, 0.62-0.68]; P < .001; Memorial Sloan Kettering Cancer Center nomogram, 0.57 [95% CI, 0.54-0.60]; P < .001; Cancer of the Prostate Risk Assessment groups, 0.53 [95% CI, 0.51-0.56]; P < .001). Results were validated in secondary cohorts from the Surveillance, Epidemiology, and End Results database and the National Cancer Database. Conclusions and Relevance: These findings suggest that PSMA upstage probability is associated with long-term, clinically meaningful end points. Furthermore, PSMA upstaging had superior risk discrimination compared with existing tools. Formerly occult, PSMA PET/CT-detectable nonlocalized disease may be the main driver of outcomes in high-risk patients.

Prior COVID-19 Infection, Mental Health, Food and Financial Insecurity, and Association With COVID-19 Vaccination Coverage and Intent Among College-Aged Young Adults, US, 2021.

INTRODUCTION: More than 700,000 COVID-19 cases have been linked to American colleges and universities since the beginning of the pandemic. However, studies are limited on the effects of the pandemic on college-aged young adults and its association with their COVID-19 vaccination status and intent. METHODS: Using the Census Bureau's Household Pulse Survey (HPS), a large, nationally representative survey fielded from April 14 through May 24, 2021, we assessed the effects of the pandemic (COVID-19 infection, mental health, food and financial security) on COVID-19 vaccination coverage (≥1 dose) and intentions toward vaccination among college-aged young adults in the United States (N = 6,758). We examined factors associated with vaccination coverage and intent, and reasons for not getting vaccinated. RESULTS: Approximately one-fifth (19.6%) of college-aged young adults had a previous diagnosis of COVID-19, 43.5% and 39.1% reported having anxiety or depression, respectively, 10.9% reported that they sometimes or often did not have enough food to eat, and 22.6% and 12.3% found it somewhat or very difficult, respectively, to pay for household expenses. Of college-aged young adults, 63.1% had received at least 1 dose of the COVID-19 vaccine, 15.4% probably would be vaccinated or were unsure about getting the vaccine, and 14.0% probably will not or definitely will not get vaccinated. Adults who were non-Hispanic Black (vs non-Hispanic White) or had food or financial insecurities (vs did not) were less likely to be vaccinated or intend to be vaccinated. Among adults who probably will not or definitely will not be vaccinated, more than one-third said that they did not believe a vaccine was needed. CONCLUSION: Ensuring high and equitable vaccination coverage among college-aged young adults is critical for safely reopening in-person learning and resuming prepandemic activities.

Toxicity After Stereotactic Body Radiation Therapy for Prostate Cancer in Patients With Inflammatory Bowel Disease: A Multi-institutional Matched Case-Control Series.

PURPOSE: To evaluate the safety of stereotactic body radiation therapy (SBRT) for prostate cancer in men with inflammatory bowel disease (IBD). METHODS AND MATERIALS: We queried a consortium database for patients with IBD receiving SBRT for prostate cancer between 2006 and 2012. Identified patients were matched with patients without a history of IBD in a 3:1 fashion based on dose, fractionation, use of androgen deprivation therapy, and age distribution. Logistic regression was used to evaluate the association between having IBD and experiencing acute and late gastrointestinal (GI) and genitourinary (GU) toxicities as scored on the Common Terminology Criteria for Adverse Events scale. Time to late toxicity was evaluated using proportional hazard Cox models. Our study was limited by absence of data on prostate size, baseline International Prostate Symptom Score, and rectal dose-volume histogram parameters. RESULTS: Thirty-nine patients with flare-free IBD at time of treatment (median follow-up 83.9 months) and 117 matched controls (median follow-up 88.7 months) were identified. A diagnosis of IBD was associated with increased odds of developing any late grade GI toxicity (odds ratio [OR] 6.11, P <.001) and GU toxicity (odds ratio 6.14, P < .001), but not odds of developing late grade ≥2 GI (P = .08) or GU toxicity (P = .069). Acute GI and GU toxicity, both overall and for grade ≥2 toxicities, were more frequent in men with IBD (P < .05). Time to late GI and GU toxicity of any grade was significantly shorter in patients with IBD (P < .001). Time to late grade ≥2 GU, but not grade ≥2 GI toxicity, was also shorter in patients with IBD (P = .044 for GU and P = .144 for GI). CONCLUSIONS: Patients with IBD who received SBRT for PCa had a higher likelihood of developing acute GI and GU toxicity, in addition to experiencing lower grade late toxicities that occurred earlier. However, patients with IBD did not have a higher likelihood for late grade ≥2 GI or GU toxicity after SBRT compared with the control cohort. Interpretation of this data are limited by the small sample size. Thus, men with IBD in remission should be properly counseled about these risks when considering SBRT.

Comparison of Multimodal Therapies and Outcomes Among Patients With High-Risk Prostate Cancer With Adverse Clinicopathologic Features.

Importance: The optimal management strategy for high-risk prostate cancer and additional adverse clinicopathologic features remains unknown. Objective: To compare clinical outcomes among patients with high-risk prostate cancer after definitive treatment. Design, Setting, and Participants: This retrospective cohort study included patients with high-risk prostate cancer (as defined by the National Comprehensive Cancer Network [NCCN]) and at least 1 adverse clinicopathologic feature (defined as any primary Gleason pattern 5 on biopsy, clinical T3b-4 disease, ≥50% cores with biopsy results positive for prostate cancer, or NCCN ≥2 high-risk features) treated between 2000 and 2014 at 16 tertiary centers. Data were analyzed in November 2020. Exposures: Radical prostatectomy (RP), external beam radiotherapy (EBRT) with androgen deprivation therapy (ADT), or EBRT plus brachytherapy boost (BT) with ADT. Guideline-concordant multimodal treatment was defined as RP with appropriate use of multimodal therapy (optimal RP), EBRT with at least 2 years of ADT (optimal EBRT), or EBRT with BT with at least 1 year ADT (optimal EBRT with BT). Main Outcomes and Measures: The primary outcome was prostate cancer-specific mortality; distant metastasis was a secondary outcome. Differences were evaluated using inverse probability of treatment weight-adjusted Fine-Gray competing risk regression models. Results: A total of 6004 men (median [interquartile range] age, 66.4 [60.9-71.8] years) with high-risk prostate cancer were analyzed, including 3175 patients (52.9%) who underwent RP, 1830 patients (30.5%) who underwent EBRT alone, and 999 patients (16.6%) who underwent EBRT with BT. Compared with RP, treatment with EBRT with BT (subdistribution hazard ratio [sHR] 0.78, [95% CI, 0.63-0.97]; P = .03) or with EBRT alone (sHR, 0.70 [95% CI, 0.53-0.92]; P = .01) was associated with significantly improved prostate cancer-specific mortality; there was no difference in prostate cancer-specific mortality between EBRT with BT and EBRT alone (sHR, 0.89 [95% CI, 0.67-1.18]; P = .43). No significant differences in prostate cancer-specific mortality were found across treatment cohorts among 2940 patients who received guideline-concordant multimodality treatment (eg, optimal EBRT alone vs optimal RP: sHR, 0.76 [95% CI, 0.52-1.09]; P = .14). However, treatment with EBRT alone or EBRT with BT was consistently associated with lower rates of distant metastasis compared with treatment with RP (eg, EBRT vs RP: sHR, 0.50 [95% CI, 0.44-0.58]; P < .001). Conclusions and Relevance: These findings suggest that among patients with high-risk prostate cancer and additional unfavorable clinicopathologic features receiving guideline-concordant multimodal therapy, prostate cancer-specific mortality outcomes were equivalent among those treated with RP, EBRT, and EBRT with BT, although distant metastasis outcomes were more favorable among patients treated with EBRT and EBRT with BT. Optimal multimodality treatment is critical for improving outcomes in patients with high-risk prostate cancer.

Dose-response with stereotactic body radiotherapy for prostate cancer: A multi-institutional analysis of prostate-specific antigen kinetics and biochemical control.

BACKGROUND AND PURPOSE: The optimal dose for prostate stereotactic body radiotherapy (SBRT) is still unknown. This study evaluated the dose-response relationships for prostate-specific antigen (PSA) decay and biochemical recurrence (BCR) among 4 SBRT dose regimens. MATERIALS AND METHODS: In 1908 men with low-risk (50.0%), favorable intermediate-risk (30.9%), and unfavorable intermediate-risk (19.1%) prostate cancer treated with prostate SBRT across 8 institutions from 2003 to 2018, we examined 4 regimens (35 Gy/5 fractions [35/5, n = 265, 13.4%], 36.25 Gy/5 fractions [36.25/5, n = 711, 37.3%], 40 Gy/5 fractions [40/5, n = 684, 35.8%], and 38 Gy/4 fractions [38/4, n = 257, 13.5%]). Between dose groups, we compared PSA decay slope, nadir PSA (nPSA), achievement of nPSA ≤0.2 and ≤0.5 ng/mL, and BCR-free survival (BCRFS). RESULTS: Median follow-up was 72.3 months. Median nPSA was 0.01 ng/mL for 38/4, and 0.17-0.20 ng/mL for 5-fraction regimens (p < 0.0001). The 38/4 cohort demonstrated the steepest PSA decay slope and greater odds of nPSA ≤0.2 ng/mL (both p < 0.0001 vs. all other regimens). BCR occurred in 6.25%, 6.75%, 3.95%, and 8.95% of men treated with 35/5, 36.25/5, 40/5, and 38/4, respectively (p = 0.12), with the highest BCRFS after 40/5 (vs. 35/5 hazard ratio [HR] 0.49, p = 0.026; vs. 36.25/5 HR 0.42, p = 0.0005; vs. 38/4 HR 0.55, p = 0.037) including the entirety of follow-up, but not for 5-year BCRFS (≥93% for all regimens, p ≥ 0.21). CONCLUSION: Dose-escalation was associated with greater prostate ablation and PSA decay. Dose-escalation to 40/5, but not beyond, was associated with improved BCRFS. Biochemical control remains excellent, and prospective studies will provide clarity on the benefit of dose-escalation.

A Systematic Review and Meta-analysis of Local Salvage Therapies After Radiotherapy for Prostate Cancer (MASTER).

CONTEXT: Management of locally recurrent prostate cancer after definitive radiotherapy remains controversial due to the perceived high rates of severe genitourinary (GU) and gastrointestinal (GI) toxicity associated with any local salvage modality. OBJECTIVE: To quantitatively compare the efficacy and toxicity of salvage radical prostatectomy (RP), high-intensity focused ultrasound (HIFU), cryotherapy, stereotactic body radiotherapy (SBRT), low-dose-rate (LDR) brachytherapy, and high-dose-rate (HDR) brachytherapy. EVIDENCE ACQUISITION: We performed a systematic review of PubMed, EMBASE, and MEDLINE. Two- and 5-yr recurrence-free survival (RFS) rates and crude incidences of severe GU and GI toxicity were extracted as endpoints of interest. Random-effect meta-analyses were conducted to characterize summary effect sizes and quantify heterogeneity. Estimates for each modality were then compared with RP after adjusting for individual study-level covariates using mixed-effect regression models, while allowing for differences in between-study variance across treatment modalities. EVIDENCE SYNTHESIS: A total of 150 studies were included for analysis. There was significant heterogeneity between studies within each modality, and covariates differed between modalities, necessitating adjustment. Adjusted 5-yr RFS ranged from 50% after cryotherapy to 60% after HDR brachytherapy and SBRT, with no significant differences between any modality and RP. Severe GU toxicity was significantly lower with all three forms of radiotherapeutic salvage than with RP (adjusted rates of 20% after RP vs 5.6%, 9.6%, and 9.1% after SBRT, HDR brachytherapy, and LDR brachytherapy, respectively; p ≤ 0.001 for all). Severe GI toxicity was significantly lower with HDR salvage than with RP (adjusted rates 1.8% vs 0.0%, p < 0.01), with no other differences identified. CONCLUSIONS: Large differences in 5-yr outcomes were not uncovered when comparing all salvage treatment modalities against RP. Reirradiation with SBRT, HDR brachytherapy, or LDR brachytherapy appears to result in less severe GU toxicity than RP, and reirradiation with HDR brachytherapy yields less severe GI toxicity than RP. Prospective studies of local salvage for radiorecurrent disease are warranted. PATIENT SUMMARY: In a large study-level meta-analysis, we looked at treatment outcomes and toxicity for men treated with a number of salvage treatments for radiorecurrent prostate cancer. We conclude that relapse-free survival at 5 years is equivalent among salvage modalities, but reirradiation may lead to lower toxicity.

Time-Driven Activity-Based Costing Comparison of Stereotactic Radiosurgery to Multiple Brain Lesions Using Single-Isocenter Versus Multiple-Isocenter Technique.

PURPOSE: Stereotactic radiosurgery (SRS) historically has been used to treat multiple brain lesions using a multiple-isocenter technique-frequently associated with significant complexity in treatment planning and long treatment times. Recently, given innovations in planning algorithms, patients with multiple brain lesions may now be treated with a single-isocenter technique using fewer total arcs and less time spent during image guidance (though with stricter image guided radiation therapy tolerances). This study used time-driven activity-based costing to determine the difference in cost to a provider for delivering SRS to multiple brain lesions using single-isocenter versus multiple-isocenter techniques. METHODS AND MATERIALS: Process maps, consisting of discrete steps, were created for each phase of the SRS care cycle and were based on interviews with department personnel. Actual treatment times (including image guidance) were extracted from treatment record and verify software. Additional sources of data to determine costs included salary/benefit data of personnel and average list price/maintenance costs for equipment. RESULTS: Data were collected for 22 patients who underwent single-isocenter SRS (mean lesions treated, 5.2; mean treatment time, 30.2 minutes) and 51 patients who underwent multiple-isocenter SRS (mean lesions treated, 4.4; mean treatment time, 75.2 minutes). Treatment time for multiple-isocenter SRS varied substantially with increasing number of lesions (11.8 minutes/lesion; P < .001), but to a much lesser degree in single-isocenter SRS (1.8 minutes/lesion; P = .029). The resulting cost savings from single-isocenter SRS based on number of lesions treated ranged from $296 to $3878 for 2 to 10 lesions treated. The 2-mm planning treatment volume margin used with single-isocenter SRS resulted in a mean 43% increase of total volume treated compared with a 1-mm planning treatment volume expansion. CONCLUSIONS: In a comparison of time-driven activity-based costing assessment of single-isocenter versus multiple-isocenter SRS for multiple brain lesions, single-isocenter SRS appears to save time and resources for as few as 2 lesions, with incremental benefits for additional lesions treated.

Prostate-specific antigen kinetics and biochemical control following stereotactic body radiation therapy, high dose rate brachytherapy, and low dose rate brachytherapy: A multi-institutional analysis of 3502 patients.

BACKGROUND AND PURPOSE: Stereotactic body radiation therapy (SBRT), low dose rate brachytherapy (LDR-BT) and high dose rate brachytherapy (HDR-BT) are ablative-intent radiotherapy options for prostate cancer (PCa). These vary considerably in dose delivery, which may impact post-treatment prostate-specific antigen (PSA) patterns and biochemical control. We compared PSA kinetics between SBRT, HDR-BT, and LDR-BT, and assessed their relationships to biochemical recurrence-free survival (BCRFS). METHODS AND MATERIALS: Retrospective PSA data were analyzed for 3502 men with low-risk (n = 2223; 63.5%), favorable intermediate-risk (n = 869; 24.8%), and unfavorable intermediate-risk (n = 410; 11.7%) PCa treated with SBRT (n = 1716; 49.0%), HDR-BT (n = 512; 14.6%), or LDR-BT (n = 1274; 36.4%) without upfront androgen deprivation therapy at 10 institutions from 1990 to 2017. We compared nadir PSA (nPSA), time to nPSA, achievement of nPSA <0.2 ng/mL and <0.5 ng/mL, rates of nPSA <0.4 ng/mL at 4 years, and BCRFS. RESULTS: Median follow-up was 72 months. Median nPSA and nPSA <0.2 ng/mL were stratified by risk group (interaction p ≤ 0.001). Median nPSA and time to nPSA were 0.2 ng/mL at 44 months after SBRT, 0.1-0.2 ng/mL at 37 months after HDR-BT, and 0.01-0.2 ng/mL at 51 months after LDR-BT (mean log nPSA p ≤ 0.009 for LDR-BT vs. SBRT or HDR-BT for low/favorable intermediate-risk). There were no differences in nPSA <0.4 ng/mL at 4 years (p ≥ 0.51). BCRFS was similar for all three modalities (p ≥ 0.27). Continued PSA decay beyond 4 years was predictive of durable biochemical control. CONCLUSION: LDR-BT led to lower nPSAs with longer continued decay compared to SBRT and HDR-BT, but no differences in BCRFS.

Kahook Dual Blade goniotomy in post penetrating keratoplasty steroid-induced ocular hypertension.

PURPOSE: Steroid-induced ocular hypertension (OHTN) after penetrating keratoplasty (PKP) may cause irreversible damage to the optic nerve and graft failure. The purpose of this study is to report the first case of a post PKP patient with poorly controlled IOP, successfully treated with Kahook Dual Blade (KDB) goniotomy in both eyes. OBSERVATIONS: The patient was a 62-year old male with prior PKP in both eyes for lattice corneal degeneration. After an uncomplicated phacoemulsification in the left eye, his IOP increased to 32 mmHg on maximum tolerated IOP lowering therapy, including oral acetazolamide. This patient was dependent on scleral contact lenses for his irregular astigmatism post PKP to achieve his best-corrected visual acuity. Thus, we needed to consider a conjunctival sparing procedure and decided to proceed with performing a KDB goniotomy in the left eye. At 29 months follow up the visual acuity (VA) remained at 20/20 and IOP 13 mmHg on dorzolamide/timolol combination drop. A year following, his right eye also required KDB goniotomy combined with cataract surgery to treat his cataract and elevated IOP of 28 mm Hg. At 18 months post KDB goniotomy, the right eye VA was 20/50 and IOP 13 mmHg on dorzolamide/timolol combination drop. CONCLUSIONS: This case demonstrates KDB goniotomy may be a good surgical alternative for post PKP steroid-induced OHTN or glaucoma, especially in patients requiring scleral contact lens for their visual rehabilitation.

Development and Validation of a Comprehensive Multivariate Dosimetric Model for Predicting Late Genitourinary Toxicity Following Prostate Cancer Stereotactic Body Radiotherapy.

Purpose: Dosimetric predictors of toxicity after Stereotactic Body Radiation Therapy (SBRT) are not well-established. We sought to develop a multivariate model that predicts Common Terminology Criteria for Adverse Events (CTCAE) late grade 2 or greater genitourinary (GU) toxicity by interrogating the entire dose-volume histogram (DVH) from a large cohort of prostate cancer patients treated with SBRT on prospective trials. Methods: Three hundred and thirty-nine patients with late CTCAE toxicity data treated with prostate SBRT were identified and analyzed. All patients received 40 Gy in five fractions, every other day, using volumetric modulated arc therapy. For each patient, we examined 910 candidate dosimetric features including maximum dose, volumes of each organ [CTV, organs at risk (OARs)], V100%, and other granular volumetric/dosimetric indices at varying volumetric/dosimetric values from the entire DVH as well as ADT use to model and predict toxicity from SBRT. Training and validation subsets were generated with 90 and 10% of the patients in our cohort, respectively. Predictive accuracy was assessed by calculating the area under the receiver operating curve (AROC). Univariate analysis with student t-test was first performed on each candidate DVH feature. We subsequently performed advanced machine-learning multivariate analyses including classification and regression tree (CART), random forest, boosted tree, and multilayer neural network. Results: Median follow-up time was 32.3 months (range 3-98.9 months). Late grade ≥2 GU toxicity occurred in 20.1% of patients in our series. No single dosimetric parameter had an AROC for predicting late grade ≥2 GU toxicity on univariate analysis that exceeded 0.599. Optimized CART modestly improved prediction accuracy, with an AROC of 0.601, whereas other machine learning approaches did not improve upon univariate analyses. Conclusions: CART-based machine learning multivariate analyses drawing from 910 dosimetric features and ADT use modestly improves upon clinical prediction of late GU toxicity alone, yielding an AROC of 0.601. Biologic predictors may enhance predictive models for identifying patients at risk for late toxicity after SBRT.

Gantry-Mounted Linear Accelerator-Based Stereotactic Body Radiation Therapy for Low- and Intermediate-Risk Prostate Cancer.

PURPOSE: To establish the safety and efficacy of gantry-mounted linear accelerator-based stereotactic body radiation therapy (SBRT) for low- and intermediate-risk prostate cancer. METHODS: We pooled 921 patients enrolled on 7 single-institution prospective phase II trials of gantry-based SBRT from 2006 to 2017. The cumulative incidences of biochemical recurrence (defined by the Phoenix definition) and physician-scored genitourinary (GU) and gastrointestinal (GI) toxicities (defined per the original trials using Common Terminology Criteria for Adverse Events) were estimated using a competing risk framework. Multivariable logistic regression was used to evaluate the relationship between late toxicity and prespecified covariates: biologically effective dose, every other day versus weekly fractionation, intrafractional motion monitoring, and acute toxicity. RESULTS: Median follow-up was 3.1 years (range, 0.5-10.8 years). In addition, 505 (54.8%) patients had low-risk disease, 236 (25.6%) had favorable intermediate-risk disease, and 180 (19.5%) had unfavorable intermediate-risk disease. Intrafractional motion monitoring was performed in 78.0% of patients. The 3-year cumulative incidence of biochemical recurrence was 0.8% (95% confidence interval [CI], 0-1.7%), 2.2% (95% CI, 0-4.3%), and 5.1% (95% CI, 1.0-9.2%) for low-, favorable intermediate-, and unfavorable intermediate-risk disease. Acute grade ≥2 GU and GI toxicity occurred in 14.5% and 4.6% of patients, respectively. Three-year cumulative incidence estimates of late grade 2 GU and GI toxicity were 4.1% (95% CI, 2.6-5.5%) and 1.3% (95% CI, 0.5-2.1%), respectively, with late grade ≥3 GU and GI toxicity estimates of 0.7% (95% CI, 0.1-1.3%) and 0.4% (95% CI, 0-0.8%), respectively. The only identified significant predictors of late grade ≥2 toxicity were acute grade ≥2 toxicity (P < .001) and weekly fractionation (P < .01), although only 12.4% of patients were treated weekly. CONCLUSIONS: Gantry-based SBRT for prostate cancer is associated with a favorable safety and efficacy profile, despite variable intrafractional motion management techniques. These findings suggest that multiple treatment platforms can be used to safely deliver prostate SBRT.

Dosimetric predictors of patient-reported toxicity after prostate stereotactic body radiotherapy: Analysis of full range of the dose-volume histogram using ensemble machine learning.

BACKGROUND AND PURPOSE: This study aims to evaluate the associations between dosimetric parameters and patient-reported outcomes, and to identify latent dosimetric parameters that most correlate with acute and subacute patient-reported urinary and rectal toxicity after prostate stereotactic body radiotherapy (SBRT) using machine learning methods. MATERIALS AND METHODS: Eighty-six patients who underwent prostate SBRT (40 Gy in 5 fractions) were included. Patient-reported health-related quality of life (HRQOL) outcomes were derived from bowel and bladder symptom scores on the Expanded Prostate Cancer Index Composite (EPIC-26) at 3 and 12 months post-SBRT. We utilized ensemble machine learning (ML) to interrogate the entire dose-volume histogram (DVH) to evaluate relationships between dose-volume parameters and HRQOL changes. The latent predictive dosimetric parameters that were most associated with HRQOL changes in urinary and rectal function were thus identified. An external cohort of 26 prostate SBRT patients was acquired to further test the predictive models. RESULTS: Bladder dose-volume metrics strongly predicted patient-reported urinary irritative and incontinence symptoms (area under the curves [AUCs] of 0.79 and 0.87, respectively) at 12 months. Maximum bladder dose, bladder V102.5%, bladder volume, and conformity indices (V50/VPTV and V100/VPTV) were most predictive of HRQOL changes in both urinary domains. No strong rectal toxicity dosimetric association was identified (AUC = 0.64). CONCLUSION: We demonstrated the application of advanced ML methods to identify a set of dosimetric variables that most highly correlated with patient-reported urinary HRQOL. DVH quantities identified with these methods may be used to achieve outcome-driven planning objectives to further reduce patient-reported toxicity with prostate SBRT.

Clinical Assessment of Prostate Displacement and Planning Target Volume Margins for Stereotactic Body Radiotherapy of Prostate Cancer.

Purpose: To assess the optimal planning target volume (PTV) margins for stereotactic body radiotherapy (SBRT) of prostate cancer based on inter- and intra-fractional prostate motion determined from daily image guidance. Methods and Materials: Two hundred and five patients who were enrolled on two prospective studies of SBRT (8 Gy × 5 fractions) for localized prostate cancer treated at a single institution between 2012 and 2017 had complete inter- and intra-fractional shift data available. All patients had scheduled kilovoltage planar imaging during SBRT with rigid registration to intraprostatic fiducials prior to each of four half-arcs delivered per fraction, as well as cone beam CT verification of anatomy prior to each fraction. Inter- and intra- fractional shift data were obtained to estimate the required PTV margins based on the classic van Herk formula. Inter- and intra-fractional motion were compared between patients with and without severe toxicities using the independent two-sample Wilcoxon test. Results: The margins required to account for inter-fractional motion were estimated to be 0.99, 1.52, and 1.45 cm in lateral (LR), longitudinal (SI), and vertical (AP) directions, respectively. The margins required to account for intra-fractional motion were estimated to be 0.19, 0.27, and 0.31 cm in LR, SI and AP directions, respectively. Large intra-fractional shifts were mostly observed in the SI and AP directions, with 2.0 and 5.4% of patients experiencing average intra-fractional motion >3 mm in the SI and AP directions, respectively, compared with none experiencing mean shifts >3 mm in the LR direction. Six patients experienced grade 3 gastrointestinal or genitourinary toxicity. There were no significant differences in mean inter- or intra-fractional motion in any of the cardinal directions compared to patients without severe toxicity (inter-fractional p = 0.46-0.99, intra-fractional p = 0.10-0.84). Conclusion: The inter- and intra-fractional margins estimated from this study are in line with prior reported values. Intra-fractional prostate motion was generally small with larger margins required for the SI and AP directions, notably just slightly exceeding the commonly used 3 mm posterior PTV margin even with realignment between half-arcs. Development of severe toxicity was not significantly associated with the degree of inter- or intra-fractional motion.

Refractive outcomes among glaucoma patients undergoing phacoemulsification cataract extraction with and without Kahook Dual Blade goniotomy.

BACKGROUND: Glaucoma patients undergoing phacoemulsification alone have a higher rate of refractive surprise compared to patients without glaucoma. This risk is further increased with combined filtering procedures. Indeed, there are few and conflicting reports on the effect of combined phacoemulsification and micro-invasive glaucoma surgery (MIGS). Here, we look at refractive outcomes of glaucoma patients undergoing phacoemulsification with and without Kahook Dual Blade (KDB) goniotomy. METHODS: Retrospective chart review of 385 glaucomatous eyes of 281 patients, which underwent either phacoemulsification alone (n = 309) or phacoemulsification with KDB goniotomy (n = 76, phaco-KDB) at the University of Colorado. The main outcome was refractive surprise defined as the difference in target and postoperative refraction spherical equivalent greater than ±0.5 Diopter (D). RESULTS: Refractive surprise greater than ±0.5 D occurred in 26.3% of eyes in the phaco-KDB group and 36.2% in the phacoemulsification group (p = 0.11). Refractive surprise greater than ±1.0 D occurred in 6.6% for the phaco-KDB group and 9.7% for the phacoemulsification group (p = 0.08). There was no significant difference in risk of refractive surprise when pre-operative IOP, axial length, keratometry or performance of KDB goniotomy were assessed in univariate analyses. CONCLUSION: There was no difference between refractive outcomes of glaucomatous patients undergoing phacoemulsification with or without KDB goniotomy.

Optimum time for angle visualization during ab interno glaucoma surgery: Before or after phacoemulsification.

PURPOSE: To determine whether it is more advantageous to perform ab interno glaucoma surgeries involving the angle before or after phacoemulsification. SETTING: University of Colorado Health Eye Center, Aurora, USA. DESIGN: Retrospective case series. METHODS: Video recordings were taken of eyes having phacoemulsification with or without angle surgery. From the videos, still images of the angle before and after cataract surgery were obtained. Four glaucoma physicians independently reviewed the images and were masked to whether the images presented side-by-side were captured before or after cataract surgery. The reviewers used a 5-point rating scale to assess which of the 2 presented images showed the best visualization of the angle. Patient and ocular characteristics were analyzed to determine predictive factors for better view before or after phacoemulsification. RESULTS: Twenty side-by-side comparisons (20 eyes of 20 patients) were reviewed and rated. The mean rating of all surgeons was 2.93, nearing the "3-no difference" response. The most common response was "3-no difference" between each photograph (32.5%), followed by "4-post phacoemulsification image somewhat better" (30%), and "2-pre-phacoemulsification image somewhat better" (27.5%). No ocular characteristic, including anterior chamber depth, angle pigmentation, or cumulative dissipation energy, was found to be predictive of surgeon preference. CONCLUSION: In combination phacoemulsification and angle-based glaucoma procedures, there appears to be no significant angle visualization difference whether the surgeon chooses to complete angle surgery before or after phacoemulsification; therefore, the decision of surgical order should rely on surgeon preference.