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Background ASCO/CCO guidelines recommend brachytherapy boost for intermediate-risk (IR) or high-risk (HR) prostate cancer (PCa) patients. Stereotactic ablative body radiotherapy (SABR) is an emerging technique for PCa but its use in HR disease is limited. We compare efficacy, toxicity, and quality-of-life (QoL) in patients treated on 2 prospective protocols that used SABR boost or MR-guided HDR brachytherapy boost (MR-HDR) with 6-18 months of androgen deprivation therapy (ADT). Methods In XXXXXX study (study 1), patients received 40Gy to prostate and 25Gy to pelvis in 5 weekly fractions. In XXXXXX (study 2), patients received HDR-BT 15Gy x 1 to the prostate and ≤22.5Gy to the MRI nodule, followed by 25Gy in 5 weekly fractions to pelvis. All patients received between 6 and 18 months of androgen deprivation therapy. Results Thirty patients (NCCN 7% unfavorable IR, and 93% HR) completed study 1 while 31 patients (NCCN 3% favorable IR, 47% Unfavorable IR and 50% HR) completed treatment as per study 2. Median follow-up was 72 and 62 months, respectively. In study 2, 6 patients had BF and all 6 developed metastatic disease. Actuarial 5-year BF was 0% for study 1 and 18.2% for study 2 (p=0.005). There was no significant difference in worst acute or late GI or GU toxicity. Grade 3 late GU toxicity was noted in 3% of the patients in study 2 (HDR-BT boost). There was no significant difference in QoL or minimally clinical important change. Conclusions In the context of 5-fraction pelvic radiotherapy and ADT, there does not appear to be a significant difference in toxicity or QoL between SABR vs. HDR BT boost. While efficacy favored the SABR boost cohort, this should be viewed in the context of limitations and biases associated with comparing two sequential phase II studies.

The ASCO/CCO guidelines recommend brachytherapy (BT) boost for eligible intermediate- (IR) or high-risk (HR) prostate cancer (PCa) patients. We present efficacy, toxicity and quality-of-life (QoL) outcomes in patients treated on a prospective protocol of MRI dose-painted high-dose-rate BT boost (HDR-BT) followed by 5-fraction pelvic radiotherapy (RT) and 6-18 months of androgen deprivation therapy (ADT).In this phase I/II study, IR or HR PCa patients received HDR-BT 15 Gy × 1 to prostate and up to 22.5 Gy to MRI nodule, followed by 25 Gy in 5, weekly fractions to pelvis. Toxicity was assessed using CTCAEv3.0, and QoL was captured using EPIC questionnaire. Biochemical failure (BF; nadir + 2.0), and proportion of patients with PSA 0.4 ng/ml at 4-years (4yPSARR) were evaluated. A minimally clinically important change (MCIC) was recorded if QoL score decreased0.5 standard deviation of baseline scores.Thirty-one patients (NCCN 3.2% favorable IR, 48.4% unfavorable IR and 48.4% HR) completed treatment with a median follow-up of 61 months. Median D90 to MR nodule was 19.0 Gy and median prostate V100% was 96.5%. The actuarial 5-year BF rate was 18.2%, and the 4yPSARR was 71%. One patient died of PCa. Acute grade 2 and 3 toxicities: GU: 50%, 7%, and GI: 3%, none, respectively. Late grade 2 and 3 toxicities were: GU: 23%, 3%, and GI: 7%, none, respectively. Proportion of patients with MCIC was 7.7% for urinary domain and 32.0% for bowel domain.This novel treatment protocol incorporating MRI dose-painted HDR-BT boost and 5-fraction pelvic RT with ADT is well tolerated.

Background Class II obesity (body mass index BMI ≥35 kg/m2) is a contraindication to heart transplantation (HT). Although few single-center studies (case reports/series and small cohorts) have reported promising outcomes of bariatric surgery (BS) in patients with obesity and ventricular assist devices, low sample sizes have made their analysis and interpretation challenging. Methods and Results We conducted a systematic search in ClinicalTrials.gov, Cochrane, Embase, PubMed, Google Scholar, and most relevant bariatric and heart failure journals. We extracted baseline and outcome individual participant data for every ventricular assist device patient undergoing BS with reported postoperative BMI and their respective timepoints when BMI data were measured. Fourteen references with 29 patients were included. The mean age was 41.9 ± 12.2 years, 82.8% underwent laparoscopic sleeve gastrectomy, and 39.3% had reported perioperative adverse events. The mean pre-BS BMI was 45.5 ± 6.6 kg/m2 and decreased significantly during follow-up (rho –0.671; P Conclusions BS may help patients with obesity and ventricular assist devices to lose a significant amount of weight and improve their candidacy for HT or even achieve myocardial recovery.

We analyzed in detail the outcomes of eight patients with ventricular assist devices (VADs) and obesity who underwent laparoscopic sleeve gastrectomy (LSG) at a single heart transplant (HT) center. This comprehensive analysis included body mass index (BMI) trends from VAD implantation to the time of LSG; BMI and percentage of excess BMI lost during follow-up; adverse outcomes; and changes in echocardiographic parameters, fasting lipids, unplanned hospitalizations, and functional status. We also identified the patients who achieved the following outcomes: listing for HT, HT, 50% excess BMI loss, and BMI

Background Prostate stereotactic ablative radiotherapy (SABR) regimens differ in time, dose, and fractionation. We report an update of a multicentre, Canadian randomized phase II study to investigate the impact of overall treatment time on quality of life (QOL), efficacy, and toxicity. Methods Men with intermediate risk prostate cancer were randomized to 40 Gy in 5 fractions delivered every other day (EOD) versus once per week (QW). Primary outcome was proportion of patients experiencing a minimally clinically important change (MCIC) in acute bowel QOL using EPIC. Secondary outcomes were toxicity, biochemical failure (BF), other QOL domains, and the rate of salvage therapy. Findings 152 men from 3 centers were randomized; the median follow-up was 62 months. Results are described for EOD versus QW. Acute bowel and urinary QOL was reported previously. Late changes in QOL were not significantly different between the two arms. There were 1 (1.3%) vs 3 (2.7%) late grade 3 + GI toxicities (p = 0.36) and 5 (6.7%) vs 2 (2.7%) late grade 3 GU toxicities (p = 0.44). Two and 5 patients had BF (5-year failure rate 3.0 vs 7.2%, p = 0.22); 0 and 4 patients received salvage therapy (p = 0.04). 5-Year OS and CSS was 95.8% and 98.6% with no difference between arms (p = 0.49, p = 0.15). 3 patients in the QW arm developed metastases. Interpretation Although we previously reported that weekly prostate SABR had better bowel and urinary QOL compared to EOD, the updated results show no difference in late toxicity, QOL, BF, or PSA kinetics. Patients should be counseled that QW SABR reduces short-term toxicity compared to QW SABR.

Purpose Dose-escalated stereotactic ablative radiotherapy (SABR) to the whole prostate may be associated with better outcomes but has a risk of increased toxicity. An alternative approach is to focally boost the dominant intraprostatic lesion (DIL) seen on magnetic resonance imaging. We report the toxicity and quality-of-life (QOL) outcomes of 2 phase 2 trials of prostate and pelvic SABR, with or without a simultaneous DIL boost. Methods and Materials The first trial treated patients with high-risk prostate cancer to a dose of 40 Gy to the prostate and 25 Gy to the pelvis in 5 fractions. The second trial treated patients with intermediate-risk and high-risk prostate cancer to a dose of 35 Gy to the prostate, 25 Gy to the pelvis, and a DIL boost up to 50 Gy in 5 fractions. Acute toxicities, late toxicities, and QOL were assessed. Results Thirty patients were enrolled in each trial. In the focal boost cohort, the median DIL D90% was 48.3 Gy. There was no significant difference in acute grade ≥2 gastrointestinal or genitourinary toxicity between the 2 trials or in cumulative worst late gastrointestinal or genitourinary toxicity up to 24 months. There was no significant difference in QOL domain scores or minimally clinical important change between the 2 trials. Conclusions Prostate and pelvic SABR with a simultaneous DIL boost was feasible. Acute grade ≥2 toxicity, late toxicity, and QOL seemed to be comparable to a cohort that did not receive a focal boost. Further follow-up will be required to assess long-term outcomes, and randomized data are required to confirm these findings.

Purpose SABR offers an effective treatment option for clinically localized prostate cancer. Here we report the dosimetric predictors of late toxicity and quality of life (QOL) in a pooled cohort of patients from four phase II trials. Methods The combined cohort included all three prostate cancer risk groups. The prescription dose was 35–40 Gy in 5 fractions. Toxicity (CTCAE) and QOL (EPIC) were collected. Multiple dosimetric parameters for the bladder, rectum and penile bulb were collected. Univariate (UVA) followed by multivariate (MVA) logistic regression analysis was conducted to search for significant dosimetric predictors of late GI/GU toxicity, or minimal clinically important change in the relevant QOL domain. Results 258 patients were included with median follow up of 6.1 years. For QOL, bladder Dmax, V38, D1cc, D2cc, D5cc and rectal V35 were predictors of urinary and bowel MCIC on UVA. On MVA, only bladder V38 remained significant. For late toxicity, various parameters were significant on UVA but only rectal Dmax, V38 and bladder D2cc were significant predictors on MVA. Conclusions This report confirms that the high-dose regions in the bladder and rectum are more significant predictors of late toxicity and QOL after prostate SABR compared to low-dose regions. Caution must be taken to avoid high doses and hotspots in those organs.

In heart failure with reduced ejection fraction (HFrEF), there is an 'obesity paradox', where survival is better in patients with a higher body mass index (BMI) and weight loss is associated with worse outcomes. We examined the effect of a sodium-glucose co-transporter 2 inhibitor according to baseline BMI in the Dapagliflozin And Prevention of Adverse-outcomes in Heart Failure trial (DAPA-HF).Body mass index was examined using standard categories, i.e. underweight (18.5 kg/mWe confirmed an 'obesity survival paradox' in HFrEF. We showed that dapagliflozin was beneficial across the wide range of BMI studied.ClinicalTrials.gov NCT03036124.

A 60-year-old female with underlying emphysema and left ventricular assist device (LVAD) HeartMate 3 presented with progressive hemoptysis, dyspnea, and right chest pain. Baseline hemoglobin was 11.1 g/dL and INR 2.9.

Purpose Stereotactic ablative radiotherapy (SABR) is appealing for prostate cancer (PCa) due to low α/β, and increasing the dose per fraction could improve the therapeutic index and lead to a better quality of life (QOL). Here we report the outcomes of a QOL comparison between two phase II clinical trials: two vs. five fraction prostate SABR. Methods Patients had low or intermediate risk PCa. The doses prescribed were 26 Gy/2 and 40 Gy/5. Expanded prostate cancer index composite was collected. Urinary, bowel and sexual domains were analyzed. Minimal clinically important change (MCIC) was defined as >0.5 standard deviation. Results 30 and 152 patients were treated with 2-fraction and 5-fraction SABR. Median follow-up was 55 and 62 months. Five-year biochemical failure rate was 3.3% and 4.6%. The 2-fraction cohort had a significantly better mean QOL over time in the bowel domain ( p = 0.0004), without a significant difference in the urinary or sexual domains. The 2-fraction cohort had a significantly lower rate of bowel MCIC (17.8% vs 42.3%, p = 0.01), but there was no difference in urinary (24.1% vs 35.7%) or sexual (15.3% vs 29.2%) MCIC. For MCIC x2 (moderate QOL change), the 2-fraction trial had significantly lower MCIC rates in both the bowel (7.1% vs 24%, p = 0.04) and sexual (0 vs 17.6%, p = 0.01) domains. Conclusions 2-Fraction SABR is feasible to deliver and well tolerated, with significant signals of improved bowel and sexual QOL. A randomized trial of two vs. five fractions for prostate SABR is needed to confirm the promising findings of this study.

To report the 5-year outcomes from a single institution, prospective, phase 1/2 study on hypofractionated, accelerated radiation therapy to the prostate bed after radical prostatectomy.Patients enrolled in this study were all eligible for postoperative radiation therapy and received a prescribed dose of 51 Gy in 17 fractions to the prostate bed. On follow-up, gastrointestinal (GI) and genitourinary (GU) toxicity was assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events version 3.0; prostate-specific antigen (PSA) was evaluated and quality of life was assessed using the Expanded Prostate Cancer Index Composite (EPIC) questionnaire.A total of 30 patients were enrolled between 2008 and 2011. Median age was 65 (52-75) years. Median pretreatment PSA was 0.12 ng/mL (0.01-1.42). Twenty-six (93%) patients had Gleason ≤7 disease, 13 (43%) had pT3 disease, and 20 (67%) had positive margins. Twenty-six patients (87%) underwent radiation therapy as salvage treatment. After a median follow-up of 6.4 (2.1-8.1) years, no patient experienced Common Terminology Criteria for Adverse Events grade 3/4 toxicity. Eleven patients (37%) had grade 2 genitourinary and 2 (7%) had grade 2 gastrointestinal toxicity. At baseline and 5 years after radiation therapy, mean EPIC urinary domain score was 80% (standard deviation, 18%) and 82% (17%). Mean EPIC bowel domain score was 93% (13%) and 93% (15%). One patient (4%) had a minimally clinically important change in urinary domain score and 1 patient (4%) had a minimally clinically important change in bowel domain score. Nelson-Aalen estimated cumulative incidence of biochemical failure was 31% (nadir +0.2) and 18% (nadir +2.0) at 5 years. Four-year PSA ≥0.4 was predictive of subsequent androgen deprivation therapy use (Nelson-Aalen cumulative incidence: 1.45; P .0001). Five patients (17%) received hormonal therapy for biochemical failure. Nelson-Aalen estimated cumulative incidence of hormone therapy use was 14% at 5 years. All patients who received hormone therapy had PSA0.4 at 4 years.In this phase 1/2 study, hypofractionated postoperative radiation therapy seems to have good clinical efficacy without significant late toxicity. Phase 3 studies are warranted.

Coronary angiography remains the gold standard post-transplant screening test for cardiac allograft vasculopathy. This procedure has traditionally been performed via femoral approach. Data on safety and efficacy of radial approach in cardiac transplant patients remains scarce. Single center retrospective study including all cardiac transplant patients who underwent coronary angiography via transradial approach (TRA) or transfemoral approach (TFA). Safety and efficacy outcomes were compared between the 2 groups. Primary end points included major bleeding, vascular complications, crossover to femoral approach, contrast use and radiation exposure. A total of 201 patients were included. 96 patients (47.8%) underwent angiography via TRA. At baseline, no significant differences with regards to age, gender, or traditional risk factors such as HTN, DM, hyperlipidemia were noted between the 2 groups. Most patients underwent intravascular ultrasound (n = 179, 89%) with no statistically significant differences between the 2 groups (TRA: 90.6% vs TFA: 87.6%, P = 0.5). Additionally, there were no statistically significant differences in radiation exposure, amount of contrast use and fluoroscopy time between the 2 groups. Although there were trends toward increased bleeding among TFA group, these were not statistically significant and were mostly driven by access site hematomas. Use of TRA increased over time and Conversion from TRA to TFA was low (n = 4, 4.2%). Coronary angiography via the radial approach in cardiac transplant recipients is feasible, safe and is associated with low a risk of bleeding with no significant increase in radiation exposure when compared to the traditional femoral approach.

To report on long-term results of elective pelvic nodal irradiation (EPNI) and a simultaneous hypofractionated prostate boost for high-risk prostate cancer.This was a prospective single-arm study. Patients with high-risk disease (cT3, PSA20 ng/mL, or Gleason score 8-10) were eligible. Patients received 45 Gy in 25 fractions to the prostate and pelvic lymph nodes with a simultaneous intensity-modulated radiotherapy boost of 22.5 Gy to the prostate (total dose 67.5 Gy in 25 fractions), with androgen deprivation therapy (ADT) for 2-3 years. The primary endpoint was biochemical failure. Secondary endpoints included distant metastases and overall survival. Multivariable analysis was performed to look for predictive factors. Late toxicity was assessed using CTCAE v3.0.230 patients enrolled. Median follow-up was 11.2 years (IQR 8.1-12.9). At 10 years, cumulative incidence of biochemical failure was 33.4%, distant metastasis was 16.5%, and overall survival was 76.3%. On multivariable analysis, PSA nadir ≥0.05 ng/mL was associated with biochemical failure (HR 6.8, 95% CI 4-11.8, p 0.001) and distant metastases (HR 7.5, 95% CI 3.9-14.5, p 0.0001). PSA nadir ≥0.1 ng/mL (HR 5.2, 95% 2.2-12, p = 0.0001) and ADT use ≤12 months (versus24 months) (HR 2.3, 95% CI 1.3-3.9, p = 0.004) were associated with worse survival. The 5-year cumulative incidence of any late grade ≥3 gastrointestinal and genitourinary toxicity was 2.3% and 7.5%, respectively.EPNI and a simultaneous hypofractionated prostate boost combined with long-term ADT for high-risk prostate cancer resulted in acceptable 10-year biochemical control and survival with low grade ≥3 toxicity.

The role of elective nodal irradiation (ENI) in localized prostate cancer (PCa) is controversial. With increasing use of SBRT to the prostate, data is needed regarding the safety and efficacy of ENI using ultra-hypofractionated radiation (UHRT).Between 2013-2020, 4 prospective clinical trials of intermediate or high-risk PCa receiving dose-escalated RT to the prostate (via HDR brachytherapy or SBRT boost) and ENI using UHRT (25 Gy in 5 weekly fractions) were conducted. Primary endpoints included acute genitourinary and gastrointestinal toxicities (CTCAE v3.0/4.0), and secondary endpoints included late genitourinary and gastrointestinal toxicities, patient-reported quality of life (EPIC) and biochemical failure (Phoenix definition).One-hundred sixty-five patients were enrolled, of whom 98 (59%) had high-risk disease. ADT was used in 141 (85%). Median follow-up was 38 months (IQR 10-63). The worst acute genitourinary and gastrointestinal toxicities respectively were 48% and 7.5% for grade 2, and 2.7% and 0% for grade 3. Cumulative incidence of late grade 2+ genitourinary and gastrointestinal toxicities at 36 months were 58% and 11.3% and for late grade 3+ toxicities were 1% and 0%, respectively. No grade 4+ acute or late toxicities were observed. Bowel and sexual toxicity significantly worsened up to 1-year compared to baseline. Over time, urinary (p 0.0001), bowel (p = 0.0018) and sexual (p 0.0001) scores significantly improved. The 3-year biochemical recurrence-free survival was 98%.ENI using UHRT is associated with low incidence of grade 3+ toxicity, while grade 1-2 acute genitourinary and gastrointestinal toxicity is common. Randomized phase 3 trials are needed.

Purpose of review Hypertension (HTN) and obesity are major risk factors for cardiac remodeling and dysfunction, leading to left ventricular hypertrophy (LVH) and heart failure (HF). In this review, we discuss the complex mechanisms and effects of HTN and obesity, and their treatments in LVH, ventricular function, and HF. Recent findings Obesity and HTN impact the heart through overlapping neurohormonal pathways. However, the relationship between obesity and cardiomyopathy is more complex, and additional metabolic and hemodynamic pathways seem to contribute to cardiac dysfunction in these patients. Weight loss and blood pressure (BP) control help to prevent and reverse at least some of the damage caused by obesity and HTN even beyond what would be expected from solely the hemodynamic changes. Summary Obesity and HTN cause maladaptive changes in the heart that can lead to LVH and HF. Weight loss and BP control help to, at least partially, reverse some of these changes and improve clinical outcomes in patients with HF.

We present 2 relevant cases of eosinophilic myocarditis (EM) in patients that presented with cardiogenic shock, one of whom received a durable ventricular assist device followed by heart transplantation, with the diagnosis of EM being made based on analysis of the excisional biopsy obtained during implantation of the ventricular assist device. The second patient was initially misdiagnosed with peripartum cardiomyopathy and underwent abortion, to later being diagnosed with EM through endomyocardial biopsy. These two cases highlight the importance of high clinical suspicion for EM based on eosinophilia, comorbidities, and presentation, as well as the value of early diagnosis and therapeutic interventions, including corticosteroids, and advanced heart failure therapies, such as mechanical circulatory support and heart transplantation.

Objectives Patients with end-stage heart failure (ESHF) treated with ventricular assist devices (VADs) tend to gain weight after implantation, which is associated with higher complication rates and is a contraindication for heart transplantation (HT). The objective was to analyze the outcomes of obese patients with ESHF and VADs who underwent laparoscopic sleeve gastrectomy (LSG) at Ochsner Medical Center in New Orleans, which is the only program performing VADs and HT in the State of Louisiana, and also one of the largest VAD centers in the USA. Data description This dataset contains detailed baseline, perioperative, and long-term data of patients with VADs undergoing LSG. These variables were collected retrospectively from electronic medical records. Patients who achieved ≥ 50% excess BMI loss, BMI ≤ 35 kg/m2, listing for HT, HT, or myocardial recovery were identified and the timing to each of these milestones was documented. These data can be used alone or in combination with other datasets to achieve a larger sample size with more power for further analysis of these variables, which include the most important, standard, and objective bariatric and ESHF outcomes of patients with VADs undergoing LSG. Elaboration of composite outcomes is feasible.

Objectives Patients with end-stage heart failure (ESHF) treated with ventricular assist devices (VADs) tend to gain weight, which may prevent them from receiving heart transplantation (HT) if their body mass index (BMI) reaches ≥ 35 kg/m2. The objective was to synthesize all cases available in the literature and describe the most important outcomes of bariatric surgery (BS) in VAD patients, including BMI trends, reaching a BMI 2, listing for HT, achieving HT, myocardial recovery, and mortality. These data were obtained for an individual participant data (IPD) meta-analysis and include available IPD for every case in the scientific literature describing VAD patients undergoing BS during VAD support with documented postoperative BMI (and time of measurement) during follow-up. Data description These data include baseline, periprocedural, and long-term outcomes for the 29 patients meeting selection criteria. The composite outcome includes reaching a BMI 2, listing for HT, receiving HT, and myocardial recovery, indicating significant BMI loss associated with major ESHF outcomes. As multiple centers are becoming more experienced in this field, the present data can be merged with their databases to form larger samples that will allow to perform further statistical analysis to identify outcome predictors and improve clinical protocols and outcomes.

Prostate stereotactic body radiotherapy (SBRT) regimens differ in time, dose, and fractionation. We completed a multicentre, randomized phase II study to investigate the impact of overall treatment time on quality of life (QOL).Men with low and intermediate-risk prostate cancer were randomly assigned to 40 Gy in 5 fractions delivered once per week (QW) vs. every other day (EOD). QOL was assessed using the Expanded Prostate Cancer Index Composite. The primary endpoint was the proportion with a minimum clinically important change (MCIC) in bowel QOL during the acute (≤12 week) period, and analysis was by intention-to-treat. ClinicalTrials.gov NCT01423474.152 men from 3 centres were randomized with median follow-up of 47 months. Patients treated QW had superior acute bowel QOL with 47/69 (68%) reporting a MCIC compared to 63/70 (90%) treated EOD (p = 0.002). Fewer patients treated QW reported moderate-severe problems with bowel QOL during the acute period compared with EOD (14/70 [20%] vs. 40/70 [57%], p 0.001). Acute urinary QOL was also better in the QW arm, with 52/67 (78%) vs 65/69 (94%) experiencing a MCIC (p = 0.006). There were no significant differences in late urinary or bowel QOL at 2 years or last follow-up.Prostate SBRT delivered QW improved acute bowel and urinary QOL compared to EOD. Patients should be counselled regarding the potential for reduced short-term toxicity and improved QOL with QW prostate SBRT.

Optimal prostate SABR dose-fractionation is unknown. This study compares long-term outcomes from two prospective trials.Study1 patients had low-risk PCa and received 35 Gy/5. Study2 patients had low/intermediate-risk PCa and received 40 Gy/5. Biochemical failure (BF) was defined as nadir + 2.114 patients were included (study1, n = 84; study2, n = 30). Median follow-up was 9.6 years and 6.9 years. Median nPSA was 0.4 and 0.1 ng/ml. Nine patients had BF (8 in study1, 1 in study2); two were managed with ADT and four had local salvage. The BF rate was 2.5% and 12.8% at 5 and 10 years for study1 and 3.3% at 5 years for study 2. BF probability was 0% if PSA0.4 at 4 years, and 20.5% at 10 years if PSA ≥0.4 (p = 0.02). Nine patients died, none of PCa. No patient has metastases or castrate-resistance. At 10 years, OS and CSS were 90.4% (p = 0.25) and 100%.Dose-escalated prostate SABR was associated with lower nPSAs but no difference in BF, OS, CSS or MFS. PSA0.4 at 4 years was a predictor of biochemical control. Half of patients with BF were successfully salvaged. Given that this is a favorable-risk cohort, longer follow-up will be needed to see if the lower nPSA translates into lower BF rates.

PURPOSE/OBJECTIVE(S) To report on the long-term results of patients with localized high risk prostate cancer treated with elective pelvic nodal irradiation (EPNI) and a simultaneous hypofractionated prostate boost along with adjuvant androgen deprivation therapy (ADT). MATERIALS/METHODS This was a prospective single-institution single-arm phase II study. Patients with high-risk prostate cancer (any of cT3 disease, PSA > 20 ng/mL, or Gleason score 8-10) were eligible. Patients underwent radiotherapy to a dose of 45 Gy in 25 fractions to the prostate and pelvic lymph nodes with a simultaneous image-guided (matched to prostatic fiducial markers) IMRT boost of 22.5 Gy to the prostate for a total of 67.5 Gy in 25 fractions (2.7 Gy per fraction) over 5 weeks. Patients were to receive ADT for 2-3 years. Endpoints included biochemical failure (Phoenix definition), distant radiographic failure, and overall survival. Univariate and multivariable analyses were performed to look for predictive factors. Late toxicity was assessed using CTCAE v3.0 for 5 years. RESULTS Two hundred thirty patients (median age 71 years) were enrolled from 2004-2010. Median follow-up was 11.2 years (IQR 8.1-12.9). 67% of patients had Gleason score ≥ 8, 44% had PSA > 20 ng/mL, and 27% had cT3 disease. Median ADT duration was 30 months (IQR 21-33). Median PSA nadir was 0.02 ng/mL (IQR 0.02-0.02). Cumulative incidence of testosterone recovery (> 1.7 nmol/L) was 47.6% and 77.5% at 5 and 10 years, respectively. Cumulative incidence of biochemical failure was 15% and 33.4% at 5 and 10 years, respectively. At 10 years, the cumulative incidence of distant metastasis was 16.5%, and overall survival was 76.3%. On multivariable analysis, PSA nadir > 0.05 ng/mL was predictive of biochemical failure (HR 6.8, 95% CI 4-11.8, P 0.1 ng/mL (HR 5.2, 95% 2.2-12, P = 0.0001) and ADT use 24 months) (HR 2.3, 95% CI 1.3-3.9, P = 0.004) were predictive of worse survival. The 5-year cumulative incidence of any late grade ≥ 3 gastrointestinal and genitourinary toxicity was 2.3% and 7.5%, respectively. CONCLUSION This was a large prospective study evaluating EPNI and a simultaneous hypofractionated prostate boost over 5 weeks combined with 2-3 years of ADT for localized high risk prostate cancer with very mature follow-up. Ten-year biochemical control and overall survival rates were favorable. Lower PSA nadir predicted for higher biochemical control, less distant failure, and longer overall survival. ADT duration of ≤ 12 months was associated with decreased overall survival.

PURPOSE/OBJECTIVE(S) The role of elective nodal irradiation (ENI) in localized prostate cancer (PCa) is controversial. With the increasing use of SBRT to the prostate, data is needed regarding the safety and efficacy of ENI using ultra-hypofractionated radiation (UHRT). MATERIALS/METHODS Between 2013 and 2020, 4 prospective clinical trials of intermediate or high-risk PCa receiving dose-escalated RT to the prostate (via either HDR brachytherapy or SBRT boost) and ENI using UHRT (25Gy in 5 weekly fractions) were conducted. Primary endpoints included acute genitourinary and gastrointestinal toxicities (CTCAE v3.0/4.0), and secondary endpoints included late genitourinary and gastrointestinal toxicities and biochemical failure (Phoenix definition). RESULTS One hundred sixty-five patients were enrolled, of whom 98 (59%) had high risk disease. ADT was used in 141 (85%). Median follow-up was 38 months (IQR 10-63). The worst acute genitourinary and gastrointestinal toxicities respectively were 48% and 7.5% for grade 2, and 2.7% and 0% for grade 3. Cumulative incidence of late grade 2+ genitourinary and gastrointestinal toxicities at 36 months were 58% and 11.3% and for late grade 3+ toxicities were 1% and 0%, respectively. No grade 4+ acute or late toxicities were observed. The 3-year biochemical recurrence-free survival was 98%. CONCLUSION ENI using UHRT is associated with low incidence of grade 3+ toxicity, while grade 1-2 acute genitourinary and gastrointestinal toxicity is common. Randomized phase 3 trials are needed.

Aims To report health-related quality of life (HRQOL) and toxicity in prostate cancer patients treated with single-fraction high dose rate (HDR) brachytherapy boost and external beam radiotherapy (EBRT). Materials and methods Patients with intermediate-risk prostate cancer were accrued to a phase II clinical trial of 15 Gy HDR boost and EBRT to a dose of 37.5 Gy in 15 fractions. HRQOL (Expanded Prostate Cancer Index Composite [EPIC]), urinary symptoms (International Prostate Symptom Score [IPSS]), erectile function (International Index of Erectile Function [IIEF]) and toxicity (Common Terminology Criteria for Adverse Events [CTCAE], version 3.0) were monitored prospectively. Univariate and multivariate logistic regression analysis was used to investigate associations between HRQOL/toxicity and baseline covariates. Results The median follow-up time was 5.2 years. The change in the median EPIC scores from baseline to year 5 in the urinary domain was from 91 to 85 ( P = 0.0028), in the bowel domain was from 98 to 96 ( P = 0.03), in the sexual domain was from 63 to 35 ( P P = 0.93). Fifty-nine per cent and 46% of the patients with normal erectile function at baseline remained potent at year 1 and year 5, respectively. Late genitourinary toxicity grade 1, 2 and ≥3 occurred in 29, 59 and 4% of patients, respectively. The rates of late gastrointestinal toxicity grade 1, 2 and ≥3 were documented as 45, 19 and 0%, respectively. On multivariate logistic regression analysis, patients with larger prostates were more likely to develop a urinary late toxicity grade ≥2 ( P = 0.01). The dose to 10% of the urethra was the only factor associated with a decline in the EPIC urinary domain score ( P = 0.012). Prostate volume >43 ml was associated with higher late genitourinary toxicity grade ≥2. Conclusions Single 15 Gy HDR brachytherapy with EBRT has a low rate of late genitourinary and gastrointestinal toxicities. Late urinary morbidity may be minimised by limiting the dose to the urethra, particularly for patients with larger prostates.

Purpose To investigate if stereotactic ablative radiotherapy (SABR) dose is associated with PSA at 3years (PSA 3y ) in the treatment of localized prostate cancer and to explore predictors of late genitourinary (GU) toxicity. Materials and methods Three prospective trials of SABR were undertaken at our institution: 1) 35Gy/5 fractions/29days; 2) 40Gy/5 fractions/29days; 3) 40Gy/5 fractions/11 or 29days. PSA 3y was analyzed as a continuous variable. Toxicity was defined as the worst new toxicity and assessed using the radiation therapy oncology group (RTOG) late morbidity scheme. Univariate and multivariable regression analyses were conducted to assess the association between dose and PSA 3y , and to explore predictors of late grade 2+ GU toxicity. Results Median PSA3y was 0.64 (intraquartile range (IQR): 0.41–1.12) and 0.27 (IQR: 0.12–0.55) ng/mL for patients treated with 35 and 40Gy respectively. A dose of 40Gy was an independent predictor of lower PSA 3y on multivariable analysis ( p p p =0.001) predicted for late grade 2+ GU toxicity on multivariable logistic regression. Conclusions This analysis suggests that higher SABR dose is associated with lower PSA 3y . Strategies to allow safe SABR dose escalation should be further investigated.

Background There is paucity of knowledge about the efficacy of bariatric surgery (BS) to achieve sustained weight loss in ventricular assist device (VAD) patients. Furthermore, the wide range of body mass index (BMI) and length of follow-up have made it impossible for small cohort studies to predict BMI trends after BS in VAD patients, in whom evidence from the general bariatric population may not be accurate. Methods We conducted a systematic search in ClinicalTrials.gov, Cochrane, Embase and PubMed. We also screened for references in Google Scholar, meeting proceedings, journal sites, and among citations in included studies. We extracted individual participant data of obese patients with VADs who underwent BS. We used Spearman's correlation test to analyze trends in BMI data. P Results For the 29 patients included, the mean age was 41.9 (± 12.2) years. All patients underwent either laparoscopic sleeve gastrectomy or laparoscopic Roux-en-Y gastric bypass. The baseline BMI at the time of BS was 45.2 (± 6.7) kg/m2. Every patient had lower BMI during follow-up than at the time of BS (Figure 1). Seven patients experienced some degree of weight gain ≥ 12 months after BS. There were statistically significant correlations (all P Conclusions Obese patients with VADs experience significant decreases in BMI, especially in excess BMI, over time after undergoing BS, although some patients re-gained some weight after one year. These results are promising, but further research, ideally with large registries combining bariatric, VAD, and transplantation outcomes, could provide more valuable insight to help identify predictive factors and guide patient selection for BS with VADs.

Immune thrombocytopenic purpura (ITP) is an acquired thrombocytopenia where autoantibodies are generated against platelet antigens. Primary ITP is often idiopathic, whereas secondary ITP has many potential causes, including drug induced, infection related (human immunodeficiency virus, hepatitis C), leukemias, or autoimmune such as systemic lupus erythematosus. ITP is a common cause of thrombocytopenia in asymptomatic individuals, where evidence of bleeding may be minor or absent. Chronic silent bleeding leading to extreme anemia in patients with ITP is rare, and evidence of multiorgan damage is even rarer; hence the relevance of this case report. Here we describe a case of primary ITP with severe chronic blood loss leading to profound anemia causing renal failure and a type II non–ST elevation myocardial infarction. Our patient underwent extensive workup for the etiology of both thrombocytopenia and anemia and was eventually treated with packed red blood cell and platelet transfusions, along with intravenous steroids and immunoglobulin therapy.

Pulmonary hypertension (PH) is a life-threatening disease with complex pathophysiology. The World Health Organization has classified PH in 5 groups according to etiology, the fifth of which corresponds to PH due to unknown or multiple mechanisms; including sarcoidosis-associated PH (SAPH). Although this system has been used to guide treatment recommendations according to each group, it does not provide much insight into the heterogeneous group 5. Furthermore, pulmonary vasodilators have been contraindicated for patients in this cluster which represents a challenge for the management of SAPH which can sometimes improve with these PH-directed drugs. In this review, we discuss the classification of SAPH; as well as the evidence behind the use of pulmonary vasodilator, invasive procedures, and lung transplantation for treating SAPH; and the little that is known about his disease in the setting of cardiac sarcoidosis.

Acute kidney injury (AKI) is a common complication of percutaneous coronary interventions (PCI), and it is associated with increased morbidity, mortality, and healthcare costs. Post-PCI AKI is a major quality outcome measured by the National Cardiovascular Data Registry for hospitals that perform PCI. We report the experience of a large, tertiary center with high standardized, post-PCI AKI rates in which we implemented multilevel interventions that included: (1) a multidisciplinary education module for all personnel involved in care of patients undergoing cardiac angiography, (2) a standardized electronic medical record based preprocedure hydration protocol order set for patients undergoing cardiac angiography, and (3) a hydration task list to be completed by the care team the evening before the procedure or prior to admission. All this resulted in a constant decrease of the post-PCI AKI rates in remarkable magnitude, significantly stronger than the national tendency, demonstrating a center-specific behavior.

High-dose-rate brachytherapy boost plus external beam radiation therapy is an established option for intermediate-risk prostate cancer (PCa). Stereotactic body radiation therapy (SBRT) boost can potentially mimic high-dose-rate boost and could be a viable alternative. Here we report the long-term outcomes of a phase 1 dose-escalation trial of single-fraction SBRT boost.Patients had intermediate-risk PCa and were accrued to 3 different SBRT single-fraction dose-level cohorts (10 Gy, 12.5 Gy, and 15 Gy). All received supplemental radiation therapy afterwards (37.5 Gy in 15 fractions). Three gold fiducials were implanted for image guidance. Patients were simulated and treated with a foley catheter and intrarectal balloon. A T2 magnetic resonance imaging scan was used for contouring, and a cine magnetic resonance imaging scan was used to calculate patient-specific internal target volume margins. Toxicity and quality-of-life data were collected using Common Terminology Criteria for Adverse Events v3.0 and the Expanded Prostate Cancer Index Composite.30 patients were accrued, 10 in each cohort. Median follow-up was 72 months. 60% had unfavorable intermediate-risk PCa. Two patients in the 15 Gy cohort developed late grade ≥3 gastrointestinal and genitourinary toxicity, with 1 patient suffering from a grade-4 rectal fistula after a rectal ulcer was biopsied repeatedly. Two patients had biochemical failure. Median PSA nadir was 0.4 ng/mL with 10 Gy, 0.09 ng/mL with 12.5 Gy and 0.07 ng/mL with 15 Gy. Median PSA at 4 years as well as proportion achieving a nadir0.2 ng/mL improved significantly with higher doses. There was no significant change in quality of life from baseline in any of the domains, and the minimal clinically important change was not statistically different between the 3 cohorts.Other than a grade 4 toxicity, which may in part be due to repeated biopsies of a rectal ulcer, single-fraction SBRT boost was feasible and well tolerated. Larger studies are warranted to better document the outcomes of such an approach.

Objective. To assess 1-year mortality after transcatheter aortic valve replacement (TAVR) in patients with bicuspid aortic stenosis (AS). Background. Clinical trials have proven the beneficial effect of TAVR on mortality in patients with tricuspid AS. Individuals with bicuspid AS were excluded from these trials. Methods. A meta-analysis using literature search from the Cochrane, PubMed, ClinicalTrials, SCOPUS, and EMBASE databases was conducted to determine the effect of TAVR on 1-year mortality in patients with bicuspid AS. Short-term outcomes that could potentially impact one-year mortality were analyzed. Results. After evaluating 380 potential articles, 5 observational studies were selected. A total of 3890 patients treated with TAVR were included: 721 had bicuspid and 3,169 had tricuspid AS. No statistically significant difference between the baseline characteristics of the two groups of patients was seen outside of mean aortic gradient. Our primary endpoint of one-year all-cause mortality revealed 85 deaths in 719 patients (11.82%) with bicuspid AS compared to 467 deaths in 3100 patients (15.06%) with tricuspid AS, with no difference between both groups [relative risk (RR) 1.03; 95% CI 0.70-1.51]. Patients with bicuspid AS were associated with a decrease in device success (RR 0.62; 95% CI 0.45-0.84) and an increase in moderate-to-severe prosthetic valve regurgitation (RR 1.55; 95% CI 1.07-2.22) after TAVR compared to patients with tricuspid AS. The effect of meta-regression coefficients on one-year all-cause mortality was not statistically significant for any patient baseline characteristics. Conclusion. When comparing TAVR procedure in tricuspid AS versus bicuspid AS, there was no difference noted in one-year all-cause mortality.

Purpose Although the outcomes of bariatric surgery (BS) in patients with ventricular assist devices (VADs) are promising, the evidence is limited to case reports or very small retrospective cohorts. Hence, no study has tried or been able to identify potential predictors of successful outcomes in this high-risk population, which could aid patient selection. Methods This study combined the individual participant data (IPD) of patients with VADs who underwent BS at Ochsner Medical Center (OMC) and patients of references identified through a systematic search in ClinicalTrials.gov, Cochrane, Embase, and PubMed. Patients who underwent BS during VAD support, as staged interventions, were included if their IPD for post-BS BMI were available. Datasets from the literature search and OMC were merged in an IPD meta-analysis to identify predictors of the composite outcome: body mass index (BMI) Results Among the 38 patients, 18 (58%) were male, the mean age was 42 (±12.5) years, and 33 (86.9%) underwent sleeve gastrectomy, while 5 (13.2%) had Roux-en-Y gastric bypass. During a follow-up of 20 (12-30) months, 30 patients achieved the composite outcome, among whom 22 were listed for HT, 17 underwent HT, and 3 experienced recovery and VAD explantation. Time to composite outcome was 10 (3-17) months. Among all baseline variables, preoperative BMI was the only statistically significant predictor for achieving the composite outcome (p Conclusion Preoperative BMI was the only statistically significant predictor for the composite clinical outcome due to its impact in postoperative BMI during follow-up. Most patients received HT. This reflects the important role of a BMI ≥35 kg/m2 as a contraindication for HT. It is likely that more patients, especially those with shorter follow-up, would have reached the composite outcome after primary references were published or conclusion of this study. Future larger studies may be able to identify additional predictors of clinical outcomes.

Background: Pulmonary angioplasty has been performed in patients with sarcoidosis-associated pulmonary hypertension (SAPH) but most evidence comes from case reports and small case series. Overall outcomes remain unclear. We conducted an individual participant data (IPD) meta-analysis of baseline, procedural, and outcome data of pulmonary angioplasty in patients with SAPH. Methods: We performed searches and systematically reviewed references from PubMed, Embase, Cochrane, ClinicalTrials.gov, and grey literature. We included IPD of patients who underwent pulmonary angioplasty for SAPH. Those without definitive diagnosis of sarcoidosis or with other causes of pulmonary vascular stenosis or compression were excluded. Results: Of 1293 screened references, 7 were included. IPD was obtained for 17 patients (median age 60 (55-65) years; 82.4% female); most of whom were Scadding stages III or IV and had NYHA FC III or IV. All patients with documented changes in 6-minute-walk distance (6MWD) had a significant improvement that ranged from 12.6 to 102.4% (P < 0.01). There were no deaths during a median follow-up of 6 (3-18) months. Conclusions: Pulmonary angioplasty with or without stenting of focal stenosis or compressions of pulmonary vessels may lead to significant improvement in 6MWD in patients with SAPH. However, this study had a small sample and some methodological limitations, such as analysis mostly of case reports and series. Randomized controlled clinical trials and/or large multicenter registry studies are needed to provide higher evidence in this topic.

Background Sleeve gastrectomy (SG) may be a useful intervention to help obese patients with ventricular assist devices (VADs) to improve their candidacy for heart transplantation (HT). However, much remains unknown about perioperative adverse events, weight changes and long-term outcomes. Methods Medical histories of all patients who underwent any bariatric surgery during VAD support in our large VAD/HT center were reviewed. Continuous variables were expressed in means (± standard deviations) or medians (p25-p75) and categorical variables were represented in percentages. The differences between body mass indices (BMIs) at different timepoints were analyzed with paired t-test and Spearman's correlations. P-values ≤ 0.05 were considered statistically significant. Results Between July 2016 and January 2020, eight patients with VADs underwent SG (age 43.8 [± 13.9] years old, 50% males). Mean time between VAD implantation and SG was 29.4 (± 16) months. There was a significant increase in BMI from VAD implantation (37.8 [± 6.7] kg/m2) to the time of SG (42.7 [± 4.5] kg/m2), p = 0.02). Other baseline, perioperative, and postoperative data can be found in Table 1. As early as 3-month after SG, BMIs had significantly decreased to 36.8 (± 4.2) kg/m2, (p Conclusions In this cohort, SG was an effective and safe means to help VAD patients to lose significant amount of weight in a short period of time, reversing the previous trend of weight gain after VAD implantation. Most of the patients did not require ICU admission or blood transfusion. Sleeve gastrectomy should be considered in morbidly obese VAD patients to improve their candidacy for HT.

Introduction Bleeding is a potentially deadly complication of anticoagulation in patients with ventricular assist devices. Management of anticoagulation in this population requires a multidisciplinary approach, especially in the setting of life-threatening bleeding. Case Report A 60-year-old female with emphysema and a HeartMate 3 presented with progressive hemoptysis, dyspnea, and right chest pain. Her hemoglobin was 11.1 g/dL (baseline) and her INR was 2.9. Chest CT showed enlargement of a right lung bullae with intra-bullae hemorrhage (Figure 1). Anticoagulation was held. She had symptomatic hypotension that the thoracic surgeons attributed to recent diuretics. On hospital day two, her hemoglobin decreased to 6.1 g/dL, she had low-flow and no-flow alarms, and hypoxic respiratory failure. She required intubation, blood transfusion, and four inotropes/vasopressors. A chest tube drained 2.7 L of blood with hemodynamic improvement. Angiography showed no active contrast extravasation. Her hemothorax persisted and angiography was repeated the third day; failing again to yield a culprit. However, the interventional radiologists empirically plugged the right inferior pulmonary artery and the bloody chest tube output decreased to 200 mL the following day. She underwent surgical washout with removal of 1 L of clot. Anticoagulation was restarted. She had an ischemic stroke without residual neurologic deficit and a ventilator-associated pneumonia and was discharged on the 32nd day. Discussion This patient had a strong indication for anticoagulation but developed a life-threatening bleed. Her initial hemoglobin was at baseline and she had received diuretics prior to arrival which confounded the severity of her condition. Although angiography was nondiagnostic, holding anticoagulation and empiric plugging of the suspected vessel were lifesaving, at the expense of developing a stroke; fortunately, without permanent neurologic deficit. Conclusion/Teaching point This case highlights the importance of coordinated and intensive multidisciplinary management to achieve early bleeding-source control in patients with mechanical circulatory support; especially when that entails challenging hemorrhagic and thromboembolic complications.

Background Body mass index (BMI) ≥ 35 kg/m2 is a major contraindication for heart transplantation (HT). Consequently, many patients who would otherwise be good HT candidates require ventricular assist devices (VADs) as destination therapy. Furthermore, some HT candidates who initially had a BMI Methods A systematic search was performed in ClinicalTrials.gov, Cochrane, Embase and PubMed. Other sources screened included Google Scholar, meeting proceedings, journal sites, and references cited in included studies. Selected subjects were obese, adult patients with VADs who underwent BS and had follow-up BMI data. Results Twelve references with 29 patients (age 41.9 [± 12.2] years, 63.6% male) were included. The baseline BMI was 45.2 (± 6.7) kg/m2. Most patients (82.8%) underwent sleeve gastrectomy while 17.2% received Roux-en-Y gastric bypass. Median follow-up was 24 (12-30) months. Eleven (39.3%) patients had postoperative adverse events after BS. Among the 23 patients with documented listing status (listed vs. not listed for HT) after BS, 78.3% lost enough weight and were listed for HT. Thirteen patients underwent HT 14.4 (± 7) months after BS, and three patients had myocardial recovery with VAD explantation after weight loss. Twenty-two of 28 (78.6%) patients achieved the composite outcome of BMI Conclusions In VAD patients who are not HT candidates due to obesity, BS may allow for enough weight loss to improve their candidacy for HT or even achieve myocardial recovery. Although there were no deaths reported during HT-free 1-year follow-up, there was a high rate of adverse events during the postoperative period. However, the rate of these events may decrease as programs become more experienced with BS in VAD patients.

Background Mechanical heart valves may pose hemodynamic challenges leading to significant heart failure during pregnancy, especially if thrombosis or stenosis occurs. On the other hand, warfarin can have teratogenic effects, and expectant mothers may try to avoid it during pregnancy. Case A 38-year-old woman with 30-week pregnancy complained of progressive dyspnea on minimal exertion. She had a history of congenital mitral valve abnormality for which had undergone mechanical valve replacement 21 years prior, with subsequent mechanical valve thrombosis after she held her warfarin for several days during a previous pregnancy which was treated successfully with tissue plasminogen activator (tPA). The patient's anticoagulation had been changed to enoxaparin from weeks 7 to 12 to decrease the risk of teratogenesis. Her international normalized ratio (INR) remained therapeutic afterwards, so her mildly elevated mean mitral gradient (MMG) was initially attributed to increased cardiac output of pregnancy. However, as her dyspnea worsened, concerns for thrombosis increased. She underwent transthoracic echocardiography (TTE) which evidenced that her MMG had increased from 12 to 20-22 mmHg over the last 3 months prior to presentation, with no decrease in her right or left ventricular systolic functions. Fluoroscopy and transesophageal echocardiography (TEE) showed no anterior leaflet mobility. She was admitted to the cardiovascular critical care unit where she received tPA infusion for 24 hours with subsequent TTE evaluation. Although the MMG normalized, there was still residual leaflet restriction. Fibrinolytics were continued for a total of 48 hours, and she was bridged to warfarin with heparin (goal partial thromboplastin time [PTT] 2-2.5 of control range). Her INR goal range was increased to 3-4. She underwent cesarean section and tubal ligation at 34 weeks of pregnancy. Neither she nor her baby had complications. Conclusion This case supports the cautious use of fibrinolysis in pregnant patients presenting with progressive heart failure secondary to mechanical valve thrombosis under intensive, multi-disciplinary monitoring by cardiologist and maternofetal medicine specialists.

Acute necrotizing eosinophilic myocarditis (ANEM) is a rapidly progressing, life-threatening condition that may be associated with other immunologic and respiratory diseases. A 30-year-old woman with a 13-week pregnancy presented with NYHA class III symptoms and moderate biventricular dysfunction.

HeartMate 3 (HM3) is a leading ventricular assist device. However one of its distinguishing design features; free rotation of the outflow graft, is associated with a risk of graft torsion and compression. A 56-year-old woman with a HM3 as destination therapy presented with progressive dyspnea and

Eosinophilic myocarditis (EM) is rapidly progressing and warrants high suspicion index, early steroid therapy, and thorough evaluation. A 44-year-old man with recently diagnosed heart failure with biventricular dysfunction presented with cardiogenic shock. He had a history of asthma and pulmonary

328 Background: The ASCO/CCO guidelines recommend brachytherapy boost for all eligible intermediate- or high-risk localized prostate cancer patients. We present efficacy, survival and late toxicity outcomes in patients treated on a prospective, single institutional protocol of MRI dose painted HDR brachytherapy boost (HDR-BT) followed by pelvic stereotactic body radiotherapy (SBRT) and androgen deprivation therapy (ADT). Methods: A phase I/II study was performed where intermediate (IR) or high-risk (HR) prostate cancer patients received HDR-BT 15Gy x 1 to the prostate and up to 22.5Gy to the MRI nodule and followed by gantry-based SBRT 25Gy in 5 weekly fractions delivered to pelvis, seminal vesicles and prostate. ADT was used for 6-18 months. CTCAEv3 was used to assess toxicities and was captured q6months x 5 years. Biochemical failure (BF; nadir + 2 definition), nadir PSA, proportion of patients with PSA < 0.4 ng/ml at 4 years (4yPSARR), incidence of salvage therapy, cause specific survival and overall survival were calculated. Day 0 was HDR-BT date for all time-to-event analyses. Results: Thirty-two patients (NCCN 3% favorable IR, 47% unfavorable IR and 50% HR) completed the planned treatment with a median follow-up of 50 months; 31 of these had an MRI nodule. Four patients had BF with actuarial 4-year BF rate of 11.5%; 3 of these received salvage ADT. Median nPSA was 0.02 ng/ml; 4yPSARR was 68.8%. One patient died (of prostate cancer) at 45 months. For late toxicities, grade 1, 2 and 3+ GU and GI toxicities were: 40.6%, 37.5%, 3% and 28.1%, 0%, 0%, respectively. Conclusions: This novel treatment protocol incorporating MRI-dose painted HDR brachytherapy boost and SBRT pelvic radiation for intermediate- and high-risk prostate cancer in combination with ADT is feasible, effective and well tolerated. Clinical trial information: 12345678. [Table: see text]

372 Background: The ASCO/CCO guidelines recommend brachytherapy boost for all eligible intermediate- or high-risk localized prostate cancer patients. Stereotactic body radiotherapy (SBRT) is an emerging treatment for prostate cancer but its use in high risk disease is limited. We compare efficacy, survival and late toxicity outcomes in patients treated on 2 prospective, phase 2 protocols that both use pelvic SBRT and androgen deprivation therapy (ADT). One used MR-guided HDR brachytherapy boost (SPARE) and the other uses a SBRT boost (SATURN). Methods: SPARE was a phase I/II study where intermediate (IR) or high-risk (HR) prostate cancer patients received HDR-BT 15Gy x 1 to the prostate and up to 22.5Gy to the MRI nodule and followed by gantry-based SBRT 25Gy in 5 weekly fractions delivered to pelvis. ADT was used for 6-18 months. SATURN was a phase II study where high risk patients received 40Gy to prostate and 25Gy to pelvis along in 5 weekly fractions with 12-18 months ADT. CTCAEv3 was used to assess toxicities and was captured q6months x 5 years. Biochemical failure (BF; nadir + 2 definition), nadir PSA, proportion of patients with PSA < 0.4 ng/ml at 4 years (4yPSARR), incidence of salvage therapy, cause specific survival were calculated. Day 0 was first day of RT for all time-to-event analyses. Results: Thirty-two patients (NCCN 3% favorable IR, 47% unfavorable IR (UIR), 50% HR) completed SPARE while 30 patients (7% UIR, 93% HR) completed SATURN. Median follow-up of 50 and 48 months, respectively. Actuarial 4-year BF was 11.5% and 0%. Median nPSA was 0.02 ng/ml for both studies. 4yPSARR was 69% and 93%. 4-year cause-specific survival was 96% and 100%. Toxicities are listed in Table. Conclusions: In the context of SBRT pelvis and ADT, SBRT boost provides similar efficacy for unfavorable risk prostate cancer with acceptable but worse toxicities compared to HDR boost. A randomized study is recommended to answer this question. Clinical trial information: 01953055. [Table: see text]

319 Background: Dose-escalated SABR to the whole prostate may be associated with better outcomes, but at a risk of increased toxicity. An alternative approach is to focally boost the dominant intraprostatic lesion (DIL) seen on MRI. We report the toxicity and quality of life (QOL) outcomes of two phase II trials of prostate and pelvic SABR, with or without a simultaneous DIL boost. Methods: The first trial treated patients with high-risk prostate cancer (PCa) to a dose of 40 Gy to the prostate and 25 Gy to the pelvis in 5 fractions. The second trial treated patients with intermediate-risk and high-risk PCa to a dose of 35 Gy to the prostate, 25 Gy to the pelvis, and a DIL boost up to 50 Gy in 5 fractions. Acute toxicities, late toxicities and QOL were assessed. Results: 30 patients were enrolled in each trial. In the focal boost cohort, the median DIL D90% was 48.3 Gy. There was no significant difference in acute grade ≥2 GI or GU toxicity between the two trials, or cumulative worst late GI or GU toxicity up to 24 months. There was no significant difference in QOL domain scores or minimally clinical important change between the two trials. Conclusions: Prostate and pelvic SABR with a simultaneous DIL boost was feasible and did not lead to a significant change in toxicity or QOL when compared to a cohort that did not receive a focal boost. Further follow-up will be required to assess long-term outcomes. Clinical trial information: NCT02911636.

We conducted a pooled analysis of four prospective stereotactic body radiotherapy (SBRT) trials of low- and intermediate-risk prostate cancer to evaluate the incidence of prostate-specific antigen (PSA) bounce and its correlation with the time-dose-fraction schedule. The correlation between bounce with PSA response at 4 years (nadir PSA 0.4 ng/ml) and biochemical failure-free survival (BFFS) was also explored.The study included four treatment groups: 35 Gy/five fractions once per week (QW) (TG-1; n = 84); 40 Gy/five fractions QW (TG-2; n = 100); 40 Gy/five fractions every other day (TG-3; n = 73); and 26 Gy/two fractions QW (TG-4; n = 30). PSA bounce was defined as a rise in PSA by 0.2 ng/ml (nadir + 0.2) or 2 ng/ml (nadir + 2.0) above nadir followed by a decrease back to nadir. Patients with fewer than three follow-up PSA tests were excluded from the pooled analysis.In total, 287 patients were included, with a median follow-up of 5.0 years. The pooled 5-year cumulative incidence of bounce by nadir + 2.0 was 8%. The 2-year cumulative incidences of PSA bounce by nadir + 0.2 were 28.9, 21, 19.6 and 16.7% (P = 0.12) and by nadir + 2.0 were 7.2, 8, 2.7 and 6.7% (P = 0.32) for TG-1 to TG-4, respectively. Multivariable analysis revealed that for nadir + 2.0, pre-treatment PSA (odds ratio 0.49; 95% confidence interval 0.26-0.97) correlated with PSA bounce. Although PSA bounce by nadir + 0.2 (odds ratio 0.10; 95% confidence interval 0.04-0.24) and nadir + 2.0 (odds ratio 0.29; 95% confidence interval 0.09-0.93) was associated with a lower probability of PSA response at 4 years, there was no association between bounce by nadir + 0.2 (hazard ratio 0.36; 95% confidence interval 0.08-1.74) or nadir + 2 (hazard ratio 1.77; 95% confidence interval 0.28-11.07) with BFFS.The incidence of PSA bounce was independent of time-dose-fraction schedule for prostate SBRT. One in 13 patients experienced a bounce high enough to be misinterpreted as biochemical failure, and clinicians should avoid early salvage interventions in these patients. There was no association between PSA bounce and BFFS.

Background The retention rates (RR) of biological therapies (BT) have been extensively studied in European countries and the United States, but there is a lack of information about them in emerging populations. Objectives To analyse BT retention rates and variables associated to them at the BIOBADAGUAY registry Methods Patients with a chronic inflammatory arthritis enrolled in the Paraguayan-Uruguayan biological register (BIOBADAGUAY) between2015 and 2017 where included in the study. Phase I of the study was focused in the global RR analysis and association with clinical and epidemiological variables. In phase II we analysed BT retention rate according to different discontinuation motives and association with clinical and epidemiological variables. Survival analysis was performed using Kaplan-Meier estimators and proportional hazard regression models Results A total of 778 BTs where included in the study (etanercept n=184, adalimumab n=440, rituximab n=44, infliximab n=27, tocilizumab n=75, and others n=8). The underlying diagnosis associated to these BTs were rheumatoid arthritis (RA;58.2%), juvenile arthritis (JIA; 14.2%), ankylosing spondylitis (SA; 12.5%) and psoriatic arthritis (PA; 8,0%). In phase I we found that mean survival times were 322 (±17.9), 315 (±22.32), 289(±8.52) and 233 (±16.69) weeks for AS, PA, RA and JIA respectively. The survival association analysis has shown that JIA diagnosis (p=2.26 × 10–4, HR=1.80 [95%CI, 1.32–2.46]), corticosteroids (p=1.54 × 10–2, HR=1.38 [95% CI, 1.06–1.79]), and previous BT (p=3.32 × 10–2, HR=1.43 [95% CI, 1.03–1.98]) were variables significantly associated with a lower BT retention. In phase II, we stratified the survival analysis by cause of discontinuation. We found that corticoids (p=9.48 × 10–4 HR=2.02 [95% CI, 1.33–3.06]), female gender (p=4.36 × 10–2, HR=1.66 [95% CI, 1.01–2.72]) and previous BT (p=2.56 × 10–2, HR=1.72 [95% CI, 1.07–2.78]) were associated with lower BT retention due to inefficacy. When we analysed withdrawn according to adverse events, we found that RA (p=02,80 × 10–2, HR=1,83[IC 95% 1,07–3,15]), previous BT (p=4,83 × 10–2, HR=1,76[IC 95% 1,00–3,09]) and age (p=7,14 × 10–5, HR=1,05 [IC 95% 1,02–1,05]) were significantly associated with therapy discontinuation. In the group of treatments with discontinuation due to remission, we found that JIA diagnosis (p=7,93 × 10–8, HR=30,58 [IC 95% 8,77–106,71]), age (p=7,83 × 10–6, HR 0,83[IC 95% 0,76–0,90]) and gender (p=4,36 × 10–2, HR 1,66[IC 95% 1,01–2,72]) were associated to discontinuation due to remission. Conclusions Our results show that different sets of clinical and demographical variables are significantly associated to biological therapy survival depending on the discontinuation cause. Disclosure of Interest None declared