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Localized Gleason Grade Group 5 (GG5) prostate cancer has a poor prognosis and is associated with a higher risk of treatment failure, metastases, and death. Treatment intensification with the addition of a brachytherapy (BT) boost to external beam radiation (EBRT) maximizes local control, which may translate into improved survival outcomes.A systematic review and meta-analysis was performed to compare survival outcomes for Gleason GG5 patients treated with androgen deprivation therapy (ADT) and either EBRT or EBRT + BT. The MEDLINE (PubMed), EMBASE and Cochrane databases were searched to identify relevant studies. Survival probabilities for distant metastasis-free survival (DMFS), prostate cancer-specific survival (PCSS), and overall survival (OS) were extracted and pooled to create a summary survival curve for each treatment modality, which were then compared at fixed points in time. An additional analysis was performed among studies directly comparing EBRT and EBRT + BT using a random-effects model.Eight retrospective studies were selected for inclusion, representing a total of 1393 EBRT patients and 877 EBRT + BT patients. EBRT + BT was associated with higher DMFS starting at 6 years (86.8 % vs 78.8 %; p = 0.018) and extending out to 10 years (81.8 % vs 66.1 %; p 0.001), with an overall hazard ratio of 0.53 (p = 0.02). There was no difference in PCSS or OS between treatment modalities. Differences in toxicity were not assessed. There was a wide range of heterogeneity between studies.The addition of BT boost is associated with improved long-term DMFS in Gleason GG5 prostate cancer, but its impact on PCSS and OS remains unclear. These results may be confounded by the heterogeneity across study populations with concern for a risk of bias. Therefore, prospective studies are necessary to further elucidate the survival advantage associated with BT boost, which must ultimately be weighed against the toxicity-related implications of this treatment strategy.

Interstitial brachytherapy (ISBT) is an effective option for delivering conformal high dose radiation to the target volume with better organ-at risk sparing but is thought to be more invasive and painful than other methods. This study investigated pain levels and opioid consumption in patients who received spinal anesthesia (SA) or general anesthesia (GA) for their ISBT.Patients that underwent ISBT from April 2014 to September 2018 were analyzed from a prospective institutional database. The most prevalent malignancies were cervical (45%), recurrent endometrial (27%) and vaginal (20%) cancers. Baseline patient characteristics, radiation treatment details, anesthesia records, and inpatient charts were obtained. Opioid consumption was quantified as oral morphine equivalent per day (OMEq/day) from implantation until removal. Pain score levels were collected by using an 11-point scoring system.Ninety nine patients received GA and 40 patients received SA as their anesthesia for ISBT. During their first admission, 76 patients (55%) required intravenous opioids. Patients receiving SA had significantly lower mean pain scores on the morning of their procedure 6 (Interquartile range [IQR] 2-8) vs. 0 (IQR: 0-1); p0.001]. Pain did not significantly differ between cohorts at any other time. During the first admission, SA patients had a lower median opioid usage of 23 (IQR: 9-47) mg/day compared to GA patients at 38 (IQR: 21-71) mg/day (p = 0.011). No difference in opioid consumption was seen during subsequent admissions.In patients undergoing ISBT, SA provides better immediate pain control post insertion compared to GA. Patients who received SA used lower amounts of opioids during their first ISBT insertion.

Background Isolated local failure (ILF) can occur in patients who initially receive definitive radiation therapy for prostate cancer. Salvage therapy for ILF includes high dose rate (HDR) brachytherapy. Prostate Specific Membrane Antigen (PSMA) Positron Emission Tomography (PET) can accurately detect ILF and can exclude extraprostatic disease. Lutetium-177 PSMA Radioligand Therapy (RLT) is a novel treatment for prostate cancer that can target prostate cancer accurately, while sparing radiation dose to normal tissues. Methods ROADSTER is a phase I/II randomized, single-institution study. Patients with an ILF of prostate cancer after definitive initial radiation therapy are eligible. The ILF will be confirmed with biopsy, magnetic resonance imaging (MRI) and PSMA PET. Patients will be randomized between HDR brachytherapy in two fractions (a standard of care salvage treatment at our institution) (cohort 1) or one treatment of intravenous Lutetium-177 PSMA RLT, followed by one fraction of HDR brachytherapy (cohort 2). The primary endpoints for the phase I portion of the study (n = 12) will be feasibility, defined as 10 or more patients completing the study protocol within 24 months of study activation; and safety, defined as zero or one patients in cohort 2 experiencing grade 3 or higher toxicity in the first 6 months post-treatment. If feasibility and safety are achieved, the study will expand to a phase II study (n = 30 total) where preliminary efficacy data will be evaluated. Secondary endpoints include changes in prostate specific antigen levels, acute toxicity, changes in quality of life, and changes in translational biomarkers. Translational endpoints will include interrogation of blood, urine, and tissue for markers of DNA damage and immune activation with each treatment. Discussion ROADSTER explores a novel salvage therapy for ILF after primary radiotherapy with combined Lutetium-177 PSMA RLT and HDR brachytherapy. The randomized phase I/II design will provide a contemporaneous patient population treated with HDR alone to facilitate assessment of feasibility, tolerability, and biologic effects of this novel therapy. Trial registration NCT05230251 (ClinicalTrials.gov).

To compare toxicities in relation to standard radiation treatments [conventional fractionation RT (CRT) and moderate hypofractionated RT (MRT)] with ultrahypofractionated RT (URT) in the treatment of patients with localized PCa.A searched was performed in Medline, Embase, Cochrane CENTRAL, and LILACS to January 2020 for studies comparing URT to CRT and/or MRT in relation to genitourinary (GU) and gastrointestinal (GI) toxicity in the treatment of patients with localized PCa. URT, MRT and CRT were defined as protocols delivering a daily dose of ≥5 Gy, 2.4-4.9 Gy, and2.4 Gy per fractions regardless total dose, respectively.Eight studies with 2929 patients with localized PCa were included in the analysis. These eight studies did not find any difference between URT and MRT/CRT groups in relation to acute GU toxicity (21.0% × 23.8%, RD -0.04; 95% CI -0.13, 0.06; p = 0.46; IThe present study suggests that acute GU/GI and late GU/GI toxicity are similar between URT and standard protocols. More studies with longer follow-ups directed to oncology outcomes are warranted before any recommendation on this topic.

Background Historically, IBD has been thought to increase the underlying risk of radiation related toxicity in the treatment of prostate cancer. In the modern era, contemporary radiation planning and delivery may mitigate radiation-related toxicity in this theoretically high-risk cohort. This is the first manuscript to report clinical outcomes for men diagnosed with prostate cancer and underlying IBD curatively treated with stereotactic body radiation therapy (SBRT). Methods A large institutional database of patients (n = 4245) treated with SBRT for adenocarcinoma of the prostate was interrogated to identify patients who were diagnosed with underlying IBD prior to treatment. All patients were treated with SBRT over five treatment fractions using a robotic radiosurgical platform and fiducial tracking. Baseline IBD characteristics including IBD subtype, pre-SBRT IBD medications, and EPIC bowel questionnaires were reviewed for the IBD cohort. Acute and late toxicity was evaluated using the CTCAE version 5.0. Results A total of 31 patients were identified who had underlying IBD prior to SBRT for the curative treatment of prostate cancer. The majority (n = 18) were diagnosed with ulcerative colitis and were being treated with local steroid suppositories for IBD. No biochemical relapses were observed in the IBD cohort with early follow up. High-grade acute and late toxicities were rare (n = 1, grade 3 proctitis) with a median time to any GI toxicity of 22 months. Hemorrhoidal flare was the most common low-grade toxicity observed (n = 3). Conclusion To date, this is one of the largest groups of patients with IBD treated safely and effectively with radiation for prostate cancer and the only review of patients treated with SBRT. Caution is warranted when delivering therapeutic radiation to patients with IBD, however modern radiation techniques appear to have mitigated the risk of GI side effects.

Background Nonalcoholic fatty liver disease (NAFLD) is a major nonacquired immune deficiency syndrome-defining condition for persons with human immunodeficiency virus (PWH). We aimed to validate noninvasive tests for the diagnosis of NAFLD in PWH. Methods This is a cross-sectional study of PWH on stable antiretroviral therapy with persistently elevated transaminases and no known liver disease. The area under the receiver operating characteristic curve (AUROC) was calculated to compare the diagnostic accuracy of liver biopsy with abdominal ultrasound, transient elastography (TE) (including controlled attenuation parameter [CAP]), and noninvasive markers of steatosis (triglyceride and glucose index [TyG], hepatic steatosis index [HSI], fatty liver index [FLI]) and fibrosis ([FIB]-4, aminotransferase-to-platelet ratio index [APRI], NAFLD fibrosis score). We developed a diagnostic algorithm with serial combinations of markers. Results Of 146 patients with increased transaminase levels, 69 underwent liver biopsy (90% steatosis, 61% steatohepatitis, and 4% F ≥3). The AUROC for steatosis was as follows: ultrasound, 0.90 (0.75–1); CAP, 0.94 (0.88–1); FLI, 0.81 (0.58–1); HSI, 0.74 (0.62–0.87); and TyG, 0.75 (0.49–1). For liver fibrosis ≥F3, the AUROC for TE, APRI, FIB-4, and NAFLD fibrosis score was 0.92 (0.82–1), 0.96 (0.90–1), 0.97 (0.93–1), and 0.85 (0.68–1). Optimal diagnostic performance for liver steatosis was for 2 noninvasive combined models of tests with TyG and FLI/HSI as the first tests and ultrasound or CAP as the second tests: AUROC = 0.99 (0.97–1, P Conclusions Ultrasound and CAP performed best in diagnosing liver steatosis, and FLI, TyG, and HSI performed well. We propose an easy-to-implement algorithm with TyG or FLI as the first test and ultrasound or CAP as the second test to accurately diagnose or exclude NAFLD.

This exploratory study evaluates immunological changes in high-risk Gleason 9 prostate cancer patients treated with EBRT+BT compared to EBRT alone. Notably, BT demonstrates the potential to elicit a T cell response which may support further investigation using circulating immune cells as predictive and prognostic biomarkers for radiotherapy response.

Purpose/objectives High dose rate (HDR) interstitial brachytherapy (ISBT) boost is integral for definitive radiation treatment of primary vaginal cancer. Technological advances with CT or MRI guidance provide improved precision and ability to treat more extensively invasive tumors over historical techniques, but reported experience is limited. We sought to provide updated outcome and toxicity data for women with primary vaginal cancer undergoing treatment with a modern ISBT technique. Material/methods Databases of primary vaginal carcinoma patients treated at two Canadian academic cancer institutions were combined including patient, tumor and treatment characteristics, and survival outcomes and toxicity data. Descriptive statistics, survival estimates based on the Kaplan-Meier method, and univariable/multivariable Cox proportional hazards regression analyses are reported. Results Between 2002 and 2017, 67 women with primary vaginal cancer were treated with 3D HDR ISBT. FIGO stage distribution was I (22.4%), II (50.8%), III (17.9%), IVa (9.0%). All patients received external beam radiotherapy and HDR ISBT of 500–750 cGy per fraction over 2–4 fractions. Median follow-up was 2.68 years (95% confidence interval: 2.04–6.04). Cumulative rate of grade 3–4 genitourinary/gastrointestinal toxicity was 10.4%. Four patients developed vaginal fistula. Progression-free survival at 2 and 3 years was 73.5% and 66.4% for all patients, 78.3% and 75.0% for stage I-II and 61.6% and 46.2% for stage III-IVa, respectively (log-rank p = 0.252). Conclusions Use of 3D image-guided HDR ISBT boost was safe and resulted in improved survival outcomes compared to historical rates in this series of primary vaginal cancer patients. Prospective study is warranted to better define clinical and dosimetric predictors of local control.

Purpose To investigate the role of androgen deprivation therapy (ADT) in unfavorable intermediate risk (UIR) prostate cancer patients treated with high-dose rate (HDR) brachytherapy (BT) boost. Material and methods Data from 326 consecutive NCCN UIR prostate cancer patients treated in a single institution from 2009 to 2016 with 15 Gy HDR-BT boost plus 37.5 Gy external beam radiotherapy (EBRT) in 15 fractions to prostate and proximal seminal vesicles were retrospectively collected. Baseline information was collected and patients receiving vs. not receiving ADT were matched using a propensity-score model. Primary endpoint was biochemical-failure-free survival (BFFS). Kaplan–Meier estimates and stratified log-rank tests (adjusting for matched design) were used to compare BFFS, castration-resistance (CRFS) and metastasis free survival (MFS) outcomes between both groups. Results A total of 326 patients were included in the analysis of which 52 ADT patients were matched to 104 non-ADT patients in a 1:2 ratio. Median follow-up was 3.4 years and 5.5 years for ADT and non-ADT respectively. No significant baseline differences were observed. ADT was used for a median total time of 6 months (interquartile range [IQR]: 4–6) and delivered a median time of 2.7 months (IQR: 1.7–4.3) prior to HDR-BT. BFFS was significantly improved in the ADT group (stratified log-rank: p = 0.043) with 3-year and 6-year BFFS of 98% and 90% for the ADT group and 92% and 82% for the non-ADT group, respectively. No significant differences were detected for CRFS or MFS. Conclusion Short-term ADT increased BFFS in UIR prostate cancer patients treated with HDR-BT boost plus EBRT.

Purpose Reirradiation (re-RT) using external beam radiation therapy (EBRT) is a novel salvage strategy for local failure in prostate cancer. We performed a systematic review describing oncologic and toxicity outcomes for salvage EBRT/stereotactic radiation therapy (SBRT) re-RT. Methods and Materials A International Prospective Register of Systematic Reviews registered (#141466) systematic review, meta-analysis, and meta-regression was conducted using preferred reporting items for systematic reviews and meta-analyses guidelines. PubMed and EMBASE were searched from inception through September 2019. Outcome measures included local control (LC), biochemical relapse free survival (BRFS), and ≥grade 3 genitourinary (GU)/gastrointestinal (GI) toxicity. EBRT and SBRT data were collected separately. Meta-regression explored disease and toxicity outcomes as a function of equivalent dose in 2 Gy fractions (EQD2), length of follow-up, and partial versus whole prostate reirradiation. Results Nineteen studies representing 13 cohorts were included (428 patients). Weighted mean follow-up was 26.1 months. Median re-RT EQD2 was 77.1 Gy (α/β = 1.5), with 92% of patients receiving SBRT, 52.1% of patients receiving partial prostate re-RT, and 30.1% of patients receiving androgen deprivation therapy with re-RT. LC was 83.2% (95% confidence interval [CI], 75.5%-90.9%) and BRFS was 59.3% (47.9%-70.7%). Reported late toxicity ≥grade 3 was 3.4% (95% CI, 1.0%-5.8%) for GU and 2.0% (95% CI, 0.1%-4.0%) for GI. Meta-regression found higher LC, BRFS, and reported GU/GI toxicity with increasing EQD2, with partial prostate re-RT associated with less reported GU/GI toxicity and no detriment to LC and BRFS. Conclusions Salvage re-RT using EBRT, particularly with SBRT, is an emerging technique to treat isolated local failure of prostate cancer. With short-term follow-up, LC, BRFS, and reported toxicities appear reasonable, although further follow-up is required before definitive statements on late toxicities can be made. Our review is limited by incomplete reporting of androgen deprivation therapy use in the primary literature. Further prospective studies and longer follow-up are needed before considering re-RT as standard practice.

Cervical cancer is a deadly disease and the COVID-19 pandemic has the potential to further impact its lethality. Hypofractionated radiotherapy could mitigate this impact, however robust data in cervical cancer setting still is lacking. Information provided here could help institutions in reducing radiotherapy fractions for cervical cancer patients.

Purpose To compare CTVHR and OAR dimensions and inter-rater agreement between magnetic resonance (MR) and trans-rectal ultrasound (TRUS) images in IB cervical cancer patients. Methods IB cervical cancer patients treated with (chemo)radiotherapy plus MR-guided brachytherapy (BT) were prospectively enrolled in this study. Radiation oncologists contoured CTVHR and OARs in pre-BT MR images (MRI) and intra-operative TRUS images. These contours were subsequently compared in regard to volume and dimension. Contour inter-rater agreement analysis was also investigated using kappa index (KI). Stata 15.0 was used for statistical analysis and a p-value Results TRUS CTVHR volumes were statistically smaller than the respective MRI contoured volumes. TRUS CTVHR thickness was found to be consistently smaller than MRI contours in all patients. No statistical difference was seen in width and height between the two different imaging modalities. MRI contours had a median KI of 0.66 (range: 0.56–0.77) while TRUS-based contours had a median KI of 0.64 (range: 0.47–0.77). Bladder and rectum had very satisfactory KI in both imaging modalities. Vaginal contours had moderate agreement in MR (0.52) and in TRUS images (0.58). Conclusion TRUS images allow good visualization of CTVHR and OARs in IB cervical cancer patients. Inter-rater contour variability was comparable between TRUS and MR images. TRUS is a promising modality on its own for image-guided BT.

PURPOSE We report on our early experience of our prospective multicenter phase 1 dose- escalation study of single-fraction stereotactic partial breast irradiation (S-PBI) for early stage breast cancer after partial mastectomy using a robotic stereotactic radiation system. METHODS AND MATERIALS Thirty women with in situ or invasive breast cancer stage 0, I, or II with tumor size

Background and purpose To identify if, in intermediate risk prostate cancer (IR-PCa), the absolute percentage of biopsied tissue positive for pattern 4 disease (APP4) may be a predictor of outcome. Materials and methods 411 patients with IR-PCa were retrospectively reviewed. APP4 was calculated based on biopsy reports. Multivariable competing risk analysis was then performed on optimized APP4 cutpoints to predict for biochemical failure (BF), androgen deprivation use for BF (ADT-BF) and development of metastases (MD). Results Median follow-up for the cohort was 5.2 (Inter Quartile Range: 2.9–6.6) years. Median baseline PSA was 7.3 (5.3–9.8) ng/mL. 234 (56.9%) patients had T1 and 177 (43.1%) had T2 disease. Median APP4 was 2.00 (0.75–7.50)%. 38 (9.3%) patients experienced BF. The optimal cutpoint of APP4 for BF was >3.3% with an area under the curve (AUC) of 0.66. 17 (4.1%) received ADT-BF. The ADT-BF cutpoint was >6.6% with an AUC of 0.72. Eight (2.0%) developed MD. The MD cutpoint was >17.5% with an AUC of 0.86. Using APP4 >3.3 vs ≤ 3.3, log-transformed baseline PSA ln(PSA) (HR 2.5, 1.1–6.1; p = 0.037) and APP4 (HR 2.3, 1.1–4.7; p = 0.031) predicted for BF. Using APP4 >6.6 vs ≤ 6.6, ln(PSA) (HR 4.2, 1.4–12.4; p = 0.010) and APP4 (HR 3.7, 1.4–10.0; p = 0.009) were predictive of ADT-BF. APP4 >17.5 vs ≤ 17.5 alone was predictive of MD (HR 25.7, 4.9–135.3; p Conclusion APP4 cutpoints of >3.3%, >6.6% and >17.5% were strongly associated with increased risk of BF, ADT-BF and developing MD respectively. These findings may inform future practice when treating IR-PCa but require external validation.

Purpose To describe a technique of penile surface mold high-dose-rate (HDR) brachytherapy and early outcomes. Methods and Materials Five patients diagnosed with a T1aN0 squamous cell carcinoma of the penis were treated using a penile surface mold HDR brachytherapy technique. A negative impression of the penis was obtained using dental alginate. CT images were acquired of the penile impression; subsequently, a virtual model of the patient's penis was generated. The positive model was imported into a computer-assisted design program where catheter paths were planned such that an optimized offset of 5 mm from the penile surface was achieved. The virtual model was converted into a custom applicator. A total dose of 40 Gy was delivered in 10 fractions. Patients were followed at 1, 3, 6, and 12 months after treatment and then every 6 months thereafter. Toxicities were reported using Common Terminology Criteria for Adverse Events v4.0. Results All patients tolerated treatment well. Acute Grade 2 skin reactions were observed within the first month after treatment. Median followup was 35 months. Late Grade 1 skin toxicities were observed. One patient experienced a urethral stricture requiring dilatation. Two patients developed local recurrence. Conclusion This technique allows the delivery of penile HDR brachytherapy as an outpatient procedure with minimal discomfort to the patient during each application and is a repeatable and accurate setup. This technique warrants validation in larger series with longer followup.

Purpose Identifying dominant intraprostatic lesions (DILs) on transrectal ultrasound (TRUS) images during prostate high-dose-rate brachytherapy (HDR-BT) treatment planning is challenging. Multiparametric MRI (mpMRI) is the tool of choice for DIL identification; however, the geometry of the prostate on mpMRI and on the TRUS may differ significantly, requiring image registration. This study evaluates the efficacy of an in-house software for MRI-to-TRUS DIL registration (MR2US) and compares its results to rigid and B-Spline deformable registration. Methods and Materials Ten patients with intermediate-risk prostate cancer, each with mpMRI and TRUS data sets, were included in this study. Five radiation oncologists (ROs) with expertise in TRUS-based HDR-BT were asked to cognitively contour the DIL onto the TRUS image using mpMRI as reference. The contours were analyzed for concordance using simultaneous truth and performance level estimation algorithm. Similarity indices, DIL volumes, and distance between centroid positions were measured to compare the consensus contours against the contours from ROs and the automated algorithms; registration time between all contouring methods was recorded. Results MR2US registration had the highest dice coefficients among all patients with a mean of 0.80 ± 0.13 in comparison to rigid (0.65 ± 0.20) and B-Spline (0.51 ± 0.30). The distance between centroid positions between simultaneous truth and performance level estimation contour and MR2US, rigid, and B-Spline contours were 5 ± 2, 7 ± 5, and 18 ± 11 mm, respectively. The average registration time was significantly shorter for MR2US (11 ± 2 s) and rigid algorithm (7 ± 1 s) compared to ROs (227 ± 27 s) and B-Spline (199 ± 38 s). Conclusions The efficacy of integrating an MRI-delineated DIL into a TRUS-based BT workflow has been validated in this study. The MR2US software is fast and accurate enough to be used for DIL identification in prostate HDR-BT.

Key Points Question What is the hemoglobin transfusion threshold and target recommended for patients with cervical cancer undergoing curative-intent radiotherapy (RT)? Findings In this international Delphi consensus study, 39 experts in gynecologic radiation oncology did not agree on a hemoglobin transfusion threshold, highlighting significant variability in clinical practice. For both external beam RT and brachytherapy, a hemoglobin transfusion target of 9 or more g/dL and less than 12 g/dL, respectively, was agreed on by an 89% consensus. Meaning A liberal packed red blood cell transfusion strategy was recommended by consensus to overcome hypoxia-induced radioresistance in patients with cervical cancer receiving curative RT., Importance Packed red blood cell (PRBC) transfusions are used to treat anemia in patients with cervical cancer undergoing radiotherapy (RT) owing to concerns of hypoxia-induced radioresistance. In the absence of high-quality evidence informing transfusion practices for patients receiving external beam RT (EBRT) and brachytherapy, various arbitrary hemoglobin target levels are used worldwide. Objective To develop consensus statements to guide PRBC transfusion practices in patients with cervical cancer receiving curative-intent RT with EBRT and brachytherapy. Design, Setting, and Participants This international Delphi consensus study was completed between November 1, 2019, and July 31, 2020. A total of 63 international clinical experts in gynecologic radiation oncology were invited; 39 (62%) accepted and consented to participate. Consensus building was achieved using a 3-round anonymous Delphi consensus method. Participants rated their agreement or disagreement with statements using a 5-point Likert scale. An a priori threshold of 75% or more was required for consensus. Main Outcomes and Measures The preplanned primary outcome of this study was to assess hemoglobin transfusion thresholds and targets for both EBRT and brachytherapy by expert consensus. Results Response rates of 100% (39 of 39), 92% (36 of 39), and 97% (35 of 36) were achieved for the first, second, and third rounds of surveys, respectively. Twenty-three experts (59%) practiced in Canada, 11 (28%) in the United States, 3 (8%) in South America, 1 (3%) in Europe, and 1 (3%) in Asia. Consensus was reached for 44 of 103 statements (43%), which were combined to form the final 27-statement consensus guideline. No specific hemoglobin transfusion threshold was agreed on by consensus for EBRT or brachytherapy. By consensus (89% [31 of 35]), a hemoglobin transfusion target for patients who receive a PRBC transfusion should be 9 g/dL or more and less than 12 g/dL. Conclusions and Relevance This study presents the first international expert consensus guideline informing PRBC transfusion practices for patients with cervical cancer undergoing EBRT and brachytherapy. A minimum hemoglobin transfusion target of 9 g/dL was endorsed to balance tumor radiosensitivity with appropriate use of a scarce resource. Randomized clinical trials are required to evaluate the optimal transfusion threshold and target that maximize clinical benefit in this patient population., This international Delphi consensus study developed consensus statements to guide packed red blood cell transfusion practices for patients with cervical cancer receiving curative-intent radiotherapy with external beam radiotherapy and brachytherapy.

PURPOSE/OBJECTIVE(S) To validate the association between body composition and all-cause mortality in men treated with radiation therapy for localized prostate cancer (PCa). Secondarily, to integrate body composition as a factor to help classify patients by risk of all-cause mortality. MATERIALS/METHODS All participants of NRG/RTOG 9406 and NRG/RTOG 0126 with archived computed tomography that extended cranially to include the L4-L5 interface were included. Muscle mass and muscle density were estimated by measuring the cross-sectional area and average attenuation of the paired psoas muscles on a single slice at the level of L4-L5. Bone density was estimated by measuring the average attenuation of the vertebral body cancellous bone on a single slice at mid-L5. Adipose tissue density was estimated by measuring the average attenuation of the subcutaneous adipose tissue on a single slice at L4-L5. Survival analyses, including Cox proportional hazards models, were performed to assess the relationship between body composition variables and all-cause mortality. Recursive partitioning (RPA) was utilized to create a classification tree to classify NRG/RTOG 0126 participants by risk of death, and the discriminant ability of the classification model was validated using the NRG/RTOG 9406 data set. RESULTS Data from 2,066 men was included in this study (864 from NRG/RTOG 9406 and 1,202 from NRG/RTOG 0126). A total of 648 men died in the follow-up period and 51 (7.9%) were due to PCa. Psoas area, psoas density, and vertebral body density were individually associated with overall survival. In the final multivariable model, psoas area, comorbidity score, and age were associated with overall survival (Table). The RPA yielded a classification tree with 4 prognostic groups determined by age, comorbidity, and psoas cross-sectional area. When the RPA classification was applied to the NRG/RTOG 9406 validation set the discriminant ability was preserved (P < 0.001 groupwise log-rank). CONCLUSION The results of this study strongly support that body composition is related to all-cause mortality in men with localized PCa, with most deaths due to causes other than PCa. The inclusion of psoas cross-sectional area in the RPA classification tree suggests that body composition provides additive information to age and comorbidity status for mortality prediction. This study also confirms the feasibility of performing body composition analysis using archived CT scans using NRG Oncology clinical trial data sets. These methods can be applied to other NRG Oncology data sets to further explore how body composition is related to patient outcomes.

PURPOSE/OBJECTIVE(S) Stereotactic Body Radiation Therapy (SBRT) is a standard therapeutic option for men with prostate adenocarcinoma. The median age of prostate cancer in the US is 66 but patients as young as 35 have been reported. Many younger patients will have surgery rather than SBRT for localized prostate cancer but some will be treated with SBRT. There is a paucity of data on the outcomes of this younger subset. This study reports outcomes on patients younger than 50 treated with SBRT at a single institution and compares outcomes to older patients. MATERIALS/METHODS Between April 2006 and December 2020, 3626 patients with prostate cancer were treated with inhomogeneous-dosed SBRT using a robotic linear accelerator and followed at an academic institution. 3173 (87.51%) of patients were treated with a median dose of 3500cGY (3500-3625) delivered over 5 consecutive fractions prescribed to the 83-85% isodose line, and the remaining 453 (12.49%) other patients receiving a median dose of 4500cGY (4500-5400) to the pelvis in conventional fractionation followed by a 3 fraction SBRT boost of 2100 cGY (1950-2100) over 3 consecutive fractions. Androgen deprivation Therapy (ADT) was prescribed in 865 (23.86%) of these cases. The mean age was 67.3 years old. 47 patients were younger than 50 years old (mean age 46.6). 3,579 patients were 50 or older. Patients were divided into prognostic D'Amico risk groups with 44.68%, 48.94%, 6.38% of patients falling in the low, intermediate, and high-risk stratifications in the younger cohort and 24.76%, 56.83%, 18.41% in the older cohort respectively. Pretreatment PSA was 1.72 - 43.2 (median: 5.4) in the younger group and 0.3 - 661 (median: 6.5) in the older group. In the younger group, Gleason scores were 6 in 48.94%, 7 in 46.81%, and 8-10 in 4.25%. 44 younger patients were treated with SBRT alone. 3 patients also received supplemental external beam radiation (median dose 4500cGY) and 5 patients (10.6%) received Androgen Deprivation Therapy (ADT) as part of their treatment regimen. In the older group, Gleason scores were 6 in 30.57%, 7 in 54.06%, and 8-10 in 15.37%. 3129 were treated with SBRT alone. 450 patients also received supplemental external beam radiation (median dose 4500cGY) and 860 patients (24.03%) received Androgen Deprivation Therapy (ADT) as part of their treatment regimen. RESULTS At 64.8 months (range 7 months - 177 months) the 5-year biochemical relapse free survival was 98% in younger patients compared to 99% in older patients using the Phoenix definition of biochemical failure. The 5-year median post treatment PSA was 0.15 in the younger patients and 0.20 in the older patients. There were no significant differences in biochemical relapse free survival between the groups. CONCLUSION This represents the largest series evaluating outcomes in very young patients treated with definitive SBRT for prostate cancer. With 5-year follow up, SBRT is an effective treatment for this younger subset of patients. Continued follow up will be required to see if these results remain durable.

Purpose/Objective(s) Adjuvant radiation plays a significant role in reducing locoregional recurrences in uterine cancers. Standard treatment consists of daily radiation for 5 weeks which can be challenging for patients and the healthcare system, especially during the COVID pandemic. Hypofractionated radiotherapy has been evaluated and established in other pelvic malignancies. This study aims to evaluate the acute urinary and bowel toxicities, and patient reported outcomes following stereotactic hypofractionated adjuvant radiation for endometrial cancer. Materials/Methods This is a prospective phase I/II trial in which patients with endometrial cancer planned for adjuvant radiation received 30 Gy in 5 fractions, every other day or once weekly. Treatment was delivered at two centers with volumetric arc radiation therapy with a body-vacuum immobilization, bowel enema and 3D image-guidance. Toxicity assessment, outcomes and patient reported quality of life (QOL, EORTC core QLQ-C30 and endometrial EN24) were collected at baseline, fractions (F) 3 and 5, and at regular follow-up intervals. Higher scores represent better global QOL/health status or worse symptoms (scale 0 – 100). Changes in QOL over time were investigated with linear mixed-effects models. A P-value threshold of 0.05 was used for statistical significance. A change in QOL score of ≥ 10 points was considered clinically significant. Results The median age of the 41 enrolled patients is 66 (range: 51 – 88). Histologies included 29 endometrioid adenocarcinoma, 8 serous/clear cell, 1 carcinosarcoma, and 3 dedifferentiated. Thirty patients had stage 1 disease while 3 had stage 2 and 8 stage 3. Seven patients received sequential chemotherapy and 3 had additional vault brachytherapy. Median follow-up is 9 months, with worst toxicity (GI or GU) of grade 1 and 2 in 63% and 24% respectively. No patients have experienced a grade 3 or higher toxicity. Patient-reported diarrhea and gastrointestinal domain scores were statistically significantly worse than baseline at F5 (mean paired difference = 27.2; 8.7, P Conclusion Stereotactic hypofractionated radiation for uterine cancers is feasible and well-tolerated with short-term follow-up. Longer follow-up and future randomized studies are needed to further evaluate this treatment.

Background Transoral surgery (TOS), particularly transoral robotic surgery (TORS) has become the preferred modality in the United States for the treatment of early stage oropharyngeal cancer, largely due to assumptions of fewer toxicities and improved quality of life compared to primary radiotherapy (RT). However, these assumptions are based on retrospective analysis, a subset of which utilize primary RT groups not limited to T1-2 stage tumors for which transoral robotic surgery is FDA approved. Thus, there is potential for underestimating survival and overestimating toxicity, including treatment related mortality, in primary RT. Methods Consecutive cases of early T-stage (T1–T2) oropharyngeal cancer presenting to the London Health Sciences Centre between 2014 and 2018 treated with RT or chemoradiation (CRT) were reviewed. Patient demographics, treatment details, survival outcomes and toxicity were collected. Toxicities were retrospectively graded using the Common Terminology Criteria for Adverse Events criteria. Results A total of 198 patients were identified, of which 82% were male and 73% were HPV-positive. Sixty-eight percent of patients experienced a grade 2 toxicity, 48% a grade 3 and 4% a grade 4. The most frequent toxicities were dysphagia, neutropenia and ototoxicity. The rates of gastrostomy tube dependence at 1 and 2 years were 2.5% and 1% respectively. There were no grade 5 (fatal) toxicities. HPV-positive patients experienced improved 5-year overall survival (86% vs 64%, p = 0.0026). Conclusions Primary RT or CRT provides outstanding survival for early T-stage disease, with low rates of severe toxicity and feeding tube dependence. This study provides a reference for comparison for patients treated with primary transoral surgery.

Background Patients with high-risk prostate cancer are at increased risk of lymph node metastasis and are thought to benefit from whole pelvis radiotherapy (WPRT). There has been recent interest in the use of hypofractionated radiotherapy in treating prostate cancer. However, toxicity and cancer outcomes associated with hypofractionated WPRT are unclear at this time. This phase II study aims to investigate the impact in quality of life associated with hypofractionated WPRT compared to conventionally fractionated WPRT. Methods Fifty-eight patients with unfavourable intermediate-, high- or very high-risk prostate cancer will be randomized in a 1:1 ratio between high-dose-rate brachytherapy (HDR-BT) + conventionally fractionated (45 Gy in 25 fractions) WPRT vs. HDR-BT + hypofractionated (25 Gy in 5 fractions) WPRT. Randomization will be performed with a permuted block design without stratification. The primary endpoint is late bowel toxicity and the secondary endpoints include acute and late urinary and sexual toxicity, acute bowel toxicity, biochemical failure-, androgen deprivation therapy-, metastasis- and prostate cancer-free survival of the hypofractionated arm compared to the conventionally fractionated arm. Discussion To our knowledge, this is the first study to compare hypofractionated WPRT to conventionally fractionated WPRT with HDR-BT boost. Hypofractionated WPRT is a more attractive and convenient treatment approach, and may become the new standard of care if demonstrated to be well-tolerated and effective. Trial registration This trial was prospectively registered in ClinicalTrials.gov as NCT04197141 on December 12, 2019.

Background Patients with resected oral cavity squamous cell carcinoma (OCSCC) are often treated with adjuvant radiation (RT) ± concomitant chemotherapy based on pathological findings. Standard RT volumes include all surgically dissected areas, including the tumour bed and dissected neck. RT has significant acute and long-term toxicities including odynophagia, dysphagia, dermatitis and fibrosis. The goal of this study is to assess the rate of regional failure with omission of radiation to the surgically dissected pathologically node negative (pN0) hemi-neck(s) compared to historical control, and to compare oncologic outcomes, toxicity, and quality of life (QoL) profiles between standard RT volumes and omission of RT to the pN0 neck. Methods This is a multicentre phase II study randomizing 90 patients with T1–4 N0–2 OCSCC with at least one pN0 hemi-neck in a 1:2 ratio between standard RT volumes and omission of RT to the pN0 hemi-neck(s). Patients will be stratified based on overall nodal status (nodal involvement vs. no nodal involvement) and use of concurrent chemotherapy. The primary endpoint is regional failure in the pN0 hemi-neck(s); we hypothesize that a 2-year regional recurrence of 20% or less will be achieved. Secondary endpoints include overall and progression-free survival, local recurrence, rate of salvage therapy, toxicity and QoL. Discussion This study will provide an assessment of omission of RT to the dissected pN0 hemi-neck(s) on oncologic outcomes, QoL and toxicity. Results will inform the design of future definitive phase III trials. Trial registration Clinicaltrials.gov identifier: NCT03997643. Date of registration: June 25, 2019, Current version: 2.0 on July 11 2020.

Purpose To determine factors associated with need for post-procedural catheterization in prostate cancer patients treated with 15 Gy high dose-rate brachytherapy boost (HDR-BT). Material and methods Patients treated with 15 Gy HDR-BT followed by EBRT were retrospectively evaluated for development of urinary retention and hematuria requiring catheterization in the first 30 days post procedure. Clinical characteristics and treatment details were obtained and used as independent variables under study. Univariable and multivariable logistic regression analysis were used to determine predictors of post brachytherapy complications and a classification tree for risk of urinary retention was created using recursive partitioning analysis (RPA). Results A total of 425 patients treated with 15 Gy HDR-BT were included in this analysis. 27 patients (6.3%) required catheter placement due to acute urinary retention and thirteen other patients (3%) developed hematuria requiring urinary catheter insertion ± continuous bladder irrigation. Number of needles, prostate volume and prior use of ADT, alpha-blockers or 5α-reductase inhibitors were statistically associated with urinary retention in the univariable logistic regression analysis. In multivariable analysis, prostate volume, previous use of alpha-blocker, and use of ADT remained significant. In the RPA, populations were identified in which the rate of urinary retention ranged from 2% to 50% depending on presence of one or more of these risk factors. Conclusion The overall rate of acute urinary complications post HDR brachytherapy is low, but the individual risk of urinary retention can increase depending on the number of risk factors present. A more patient-directed retention risk estimation can be performed by using the classification risk tree presented here.

We present the case of a woman diagnosed with coronavirus disease 2019 (COVID-19) while undergoing chemoradiation for locally advanced cervix cancer. This diagnosis had implications for the treatment of her cancer, and a number of important decisions had to be made. We present the issues that arose and how her oncologic care was managed.

Background: Coronavirus disease 2019 (COVID-19) is a novel disease associated with a cytokine-mediated, severe, acute respiratory syndrome. Tocilizumab and lenzilumab are recombinant monoclonal antibodies against IL-6 and granulocyte macrophage colony-stimulating factor, respectively, and have been proposed as a potential treatment for acute, hypoxic respiratory failure associated with COVID-19. Results & methodology: We present the case of a 68-year-old man with COVID-19 who was initially treated with hydroxychloroquine and lenzilumab, but continued to develop hypoxemia, requiring an increase in respiratory support with an associated rise in serum inflammatory markers. He was subsequently treated with tocilizumab with marked clinical improvement and a decrease in acute phase reactants within 48 h. Discussion & conclusion: This case demonstrates the effective use of tocilizumab in the treatment of COVID-19 and suggests the superiority of tocilizumab over lenzilumab in the management of this cytokine-mediated syndrome.

Recent phase II clinical trials suggest that stereotactic ablative radiation therapy (SABR) can potentially improve survival for patients with oligometastatic cancer. However, these studies have mostly enrolled primaries other than gynecologic malignancies. While level I evidence is limited, recent publications exploring the use of SABR for oligometastatic gynecologic cancers have indicated a potential role for this treatment in para-aortic lymph node recurrences, and in visceral and brain metastases. The use of SABR for recurrences in the pelvis presents a number of challenges as these patients have often received previous radiation treatment. In these settings, care must be taken to avoid trespassing normal tissue tolerance with SABR leading to toxicity, especially as the potential benefit of SABR in this setting is not based on high-level evidence. Although SABR is feasible and in general safe for oligometastatic gynecologic malignancies, insufficient data are available to indicate whether it is associated with improved survival. Clinical judgment that incorporates patient and tumor factors is needed to determine if SABR is appropriate for selecting patients. Future directions include combining SABR with novel systemic therapies, determining optimal sequencing of treatments, and generating more robust randomized data pertaining to the use of SABR for oligometastatic gynecologic cancers.

Background and purpose: Declining prostate brachytherapy utilization has been reported in several studies, despite strong evidence for efficacy and safety compared to alternatives. We sought to evaluate contemporary trends in brachytherapy, external beam radiotherapy (EBRT) and prostatectomy utilization in a publicly funded healthcare system. Materials and methods: Men with localized prostate cancer diagnosed and treated between 2006 and 2017 in Ontario, Canada were identified using administrative data. Men received EBRT, brachytherapy (monotherapy or boost) or prostatectomy as initial definitive management. Multivariable logistic regression evaluated patient-, tumour-, and provider-factors on treatment utilization. Results: 61,288 men were included. On multivariable regression, the odds of receiving brachytherapy boost increased 24% per year (odds ratio [OR]:1.24, 95% CI 1.22–1.26, p < 0.01), brachytherapy monotherapy increased 3% per year (OR:1.03, 95% CI:1.02–1.04, p < 0.01), and prostatectomy declined by 6% per year (OR:0.94, 95% CI 0.93–0.95, p < 0.01). Treatment year was not significant on multivariable modelling of EBRT. In a separate multivariable model limited to those who received radiotherapy, if the first radiation oncologist seen performed brachytherapy, the OR of receiving brachytherapy monotherapy over EBRT was 5.66 (95% CI: 5.11–6.26, p < 0.01) and 2.88 (95% CI: 2.60–3.19, p < 0.01) for brachytherapy boost over EBRT alone. Substantial geographic, provider and patient variation in treatment receipt was observed. Conclusion: We found increasing brachytherapy utilization, largely driven by increasing utilization of brachytherapy boost. To our knowledge, this is the first report of increasing brachytherapy use in the era of dose escalated EBRT.

Purpose Identifying dominant intraprostatic lesions (DILs) on transrectal ultrasound (TRUS) images during prostate high-dose-rate brachytherapy treatment planning remains a significant challenge. Multiparametric MRI (mpMRI) is the tool of choice for DIL identification; however, the geometry of the prostate on mpMRI and on the TRUS may differ significantly, requiring image registration. This study assesses the dosimetric impact attributed to differences in DIL contours generated using commonly available MRI to TRUS automated registration: rigid, semi-rigid, and deformable image registration, respectively. Methods and Materials Ten patients, each with mpMRI and TRUS data sets, were included in this study. Five radiation oncologists with expertise in TRUS-based high-dose-rate brachytherapy were asked cognitively to transfer the DIL from the mpMRI images of each patient to the TRUS image. The contours were analyzed for concordance using simultaneous truth and performance level estimation (STAPLE) algorithm. The impact of DIL contour differences due to registration variability was evaluated by comparing the STAPLE-DIL dosimetry from the reference (STAPLE) plan with that from the evaluation plans (manual and automated registration) for each patient. The dosimetric impact of the automatic registration approach was also validated using a margin expansion that normalizes the volume of the autoregistered DILs to the volumes of the STAPLE-DILs. Dose metrics including D90, Dmean, V150, and V200 to the prostate and DIL were reported. For urethra and rectum, D10 and V80 were reported. Results Significant differences in DIL coverage between reference and evaluation plans were found regardless of the algorithm methodology. No statistical difference was reported in STAPLE-DIL dosimetry when manual registration was used. A margin of 1.5 ± 0.8 mm, 1.1 ± 0.8 mm, and 2.5 ± 1.6 mm was required to be added for rigid, semi-rigid, and deformable registration, respectively, to mitigate the difference in STAPLE-DIL coverage between the evaluation and reference plans. Conclusion The dosimetric impact of integrating an MRI-delineated DIL into a TRUS-based brachytherapy workflow has been validated in this study. The results show that rigid, semi-rigid, and deformable registration algorithms lead to a significant undercoverage of the DIL D90 and Dmean. A margin of at least 1.5 ± 0.8 mm, 1.1 ± 0.8 mm, and 2.5 ± 1.6 mm is required to be added to the rigid, semi-rigid, and deformable DIL registration to be suitable for DIL-boosting during prostate brachytherapy.

Purpose To determine the dosimetric impact of organ and implant motion/deformation in the context of adaptive planning in image-guided gynecologic brachytherapy using a 3-fraction transperineal approach. Methods and materials Twenty-six patients were analyzed. Each patient was treated with three fractions given over a 24-h period using a single insertion. A planning CT scan (±MRI) was acquired before the first fraction. A verification scan was taken within 1 h following the second fraction. A single plan was delivered for Fractions 1 and 2 with an adaptive plan delivered for Fraction 3. Two evaluation frameworks were established. Framework 1 investigated the effects of motion/deformation from both implant and organs. Framework 2 investigated the impact of implant motion/deformation alone. Differences in high-risk clinical target volume (HRCTV) D90%, V100%, and bladder/rectum D2cc were assessed. Results From implant to verification, the HRCTV D90% and V100% decreased significantly (5.0%, p Conclusions Adaptive planning represents an important aspect of perineal-based interstitial image-guided brachytherapy given in three fractions; its absence would result in plan degradation.

Purpose The purposes of this study were to investigate the pattern of relapse in patients with low- or intermediate-risk prostate cancer treated with 19-Gy high-dose-rate brachytherapy (HDR-BT) and to calculate the dose received by the area of recurrence. Methods and Materials Patients included in this analysis were treated under a Phase II randomized trial that evaluated the role of 19-Gy HDR-BT monotherapy in low- and intermediate-risk prostate cancers. Multiparametric prostate MRI and prostate biopsy were performed in patients with suspicious local recurrence. The site of local relapse was compared with the initial site of disease. The dose received by the site of recurrence was investigated through registration of the posttreatment multiparametric prostate MRI with the HDR-BT treatment plan. Results Eight of 87 treated patients were found to have local recurrence after 19-Gy HDR-BT. Seven of the eight recurrences were at the site of initial bulk disease. Seven patients were found to have a more aggressive histology in the posttreatment biopsy. The mean volume of prostate that had received 100% of prescription dose was 97%. Mean dose to area of recurrence was 29.1 Gy, whereas dose to 98% and dose to 90% of the recurrence were 21.6 Gy and 23.2 Gy, respectively. Conclusions The relapse pattern after a single 19-Gy HDR-BT is predominantly associated with the site of initial disease. This lends some rationale to future strategies of further focused dose escalation to initial site of disease, notwithstanding the fact that the calculated biologically equivalent dose using linear–quadratic assumptions is already very high.

Aims Radiotherapy plays a fundamental role in the treatment of cancer. Currently, the Brazilian public health system cannot match the national radiotherapy demand and many patients requiring radiotherapy are never exposed to this treatment. This study estimated the number of preventable deaths in the public health system if access to radiotherapy was universal. Materials and methods Incidence rates for the year 2016 provided by Instituto Nacional de Cancer were used in this analysis. The number of untreated patients requiring radiotherapy was obtained through the difference between the total number of patients requiring radiotherapy and the total amount of delivered radiotherapy treatments in the public health system. The number of deaths for the three most common cancers in each gender due to radiotherapy shortage was calculated. Initially, the total number of patients per cancer type was divided in stages using Brazilian epidemiological data. Subsequently, previously published tree arm diagrams were used to define the rate of patients requiring radiotherapy in each specific clinical setting. Finally, the clinical benefit of radiotherapy in overall survival was extracted from studies with level 1 evidence. Results Over 596 000 cancer cases were expected in Brazil in 2016. The public health system covers more than 75% of the Brazilian population and an estimated 111 432 patients who required radiotherapy in 2016 did not receive this treatment. Breast, colorectal and cervix cancers are the most frequent malignant tumours in women and prostate, lung and colorectal in men. The number of deaths due to a radiotherapy shortage in the year 2016 for these types of cancer were: (i) breast: 1011 deaths in 10 years; (ii) cervix: 2006 deaths in 2 years; (iii) lung: 1206 deaths in 2 years; (iv) prostate, intermediate risk: 562 deaths in 13 years; high risk: 298 deaths in 10 years; (v) colorectal: 0 deaths, as radiotherapy has no proven benefit in overall survival. Conclusion Thousands of cancer patients requiring radiotherapy do not have access to this treatment in the Brazilian public health system. The shortage of radiotherapy has a significant detrimental effect on cancer survival; over 5000 deaths would probably be prevented in the most common cancer types if radiotherapy access was universal.

Background The majority of human antimicrobial utilization occurs in the outpatient setting. Despite being mainly viral in etiology, upper respiratory tract infections (URIs) were the most common indication for outpatient antimicrobial prescriptions at our institution. Methods Through our electronic health record (EHR), we were able to determine our rate of antibiotic prescriptions for inappropriate URI diagnosis at our primary care practice sites. We selected staff volunteers from each our primary care practice sites to serve as stewardship champions. They were given training in stewardship best practices, and an URI stewardship toolkit which included viral URI prescription pad, EHR order panel, and patient education signage. They were tasked with providing education and feedback to their practice sites. We meet with them on a monthly basis to disseminate prescribing data and education. They also provided feedback from practice sites to the stewardship committee. Results Our decentralized model was put in place in November 2020. In the 6 months prior to the intervention, the average prescribing rate was 29.1%. In the 6 months after the intervention, the average prescribing rate decreased by 15% to 24.8%. During the intervention phase, there was an increase in number of non-COVID URIs diagnosed at our primary care sites. Temporal Trend in Inappropriate Antibiotics Prescribing Rates for Viral URIs Pre- and Post- Intervention Inappropriate antibiotic prescribing rate for viral upper respiratory tract infections from May 2020 until May 2021. Intervention started in December 2021 (arrow). Pre-intervention average was 29.1%. Post-intervention age was 24.8% which is a 15% decline in prescribing rate. Viral Upper Respiratory Infections Visits The total number of visits for presumed viral upper respiratory infections to primary care sites from May 2020 until May 2021. The majority of COVID-19 precautions in the area expired at the end of March 2021. Conclusion We have been able to lower our inappropriate prescriptions for URIs utilizing a decentralized model of stewardship champions. This result was especially notable as the intervention phase corresponded with the end of COVID-19 precautions and an increase in non-COVID URIs diagnosed. The advantage of this approach includes an advocate embedded at each practice site who is familiar with the opportunities and challenges of the site, and a two-way flow of information from practice sites to the stewardship committee. This model provided additional benefit during the COVID-19 pandemic as the ability of centralized staff to travel to off campus clinic sites was curtailed. Disclosures All Authors: No reported disclosures

Purpose/Objective(s) Historically, caution has been warranted when irradiating large target volumes particularly those in close proximity to organs at risk. Prior literature has demonstrated an increased incidence of GI and GU toxicity when men with large prostates were treated with conventionally fractionated radiation therapy. However, there is very limited data regarding the clinical outcomes when SBRT is used as a definitive treatment modality. We explore the long term oncologic, toxicity, and patient reported outcomes of men treated with definitive SBRT with ultra-large prostate glands (≥ 100 cc.) Materials/Methods From 2006 to 2020, a total of 3,393 patients with low and intermediate risk prostate cancer were treated with definitive robotic-SBRT. We performed a retrospective review to identify all patients in this cohort with pre-treatment prostate volumes ≥ 100 cc. Prostate volume was measured at the time of treatment regardless of ADT incorporation. All patients were treated to a total dose of 35-36.25 Gy in 5 fractions. All patients had a minimum of 2 years follow-up and were given pre- and post-treatment EPIC questionnaires at defined intervals. Biochemical control was assessed using the Phoenix definition. Late toxicity was defined using CTCAE version 5.0 and was characterized as occurring ≥ 6 months post treatment. Results A total of 67 patients were identified with ≥ 100 cc prostate glands. Of these, 18 patients received ADT prior to treatment. Overall, the median prostate volume was 139.37 cc (range 100.1 – 227 cc). The D'Amico risk classification was low (n = 19) and intermediate (n = 48). The median age was 70 years (range 54 – 87 years) and the median pretreatment PSA was 8.7 ng/ml. The mean pre-treatment EPIC bowel and urinary scores were 87.8 and 79.7, respectively. One-month following SBRT, mean EPIC bowel and urinary scores worsened to 83.6 and 76.5, respectively. Three months following SBRT, mean epic bowel and urinary scores continued to decline to 83.2 and 77.1, respectively. However, bowel and bladder symptomatology improved by 1 year to 86.16 and 77.19, and by 2 years improved above baseline to 90.00 and 85.78, respectively. There were no high grade (3+) GI toxicities observed, though one grade 3 urinary retention was identified. Excellent oncologic outcomes were observed with a 5-year median PSA nadir of 0.6 ng/mL and a biochemical relapse free survival (bRFS) of 100% at 5 years. Conclusion SBRT has been demonstrated to be oncologically effective with minimal toxicity, and has become a more ubiquitous radiation option in men with localized prostate cancer. Although there is a historical reticence for treatment of men with large glands, we report excellent clinical outcomes. Five-year bRFS was 100% and grade 3+ urinary toxicity was 2%. Although EPIC scores transiently dropped at 1 and 3 months following SBRT, resolution was seen by 1 year following treatment. The use of SBRT for the treatment of localized prostate cancer in men with ultra-large prostate gland is feasible with minimal toxicity.

PURPOSE/OBJECTIVE(S) Decipher is a prognostic 22-gene genomic classifier (GC) prospectively validated post-prostatectomy. Herein, we validate the performance of the GC in pre-treatment biopsy samples within the context of three randomized phase III high-risk definitive radiotherapy trials. MATERIALS/METHODS Following a pre-specified and approved CTEP-CCSC analysis plan (NRG-GU-TS006), we obtained all available formalin-fixed paraffin-embedded tissue from biopsy specimens from the NRG biobank from patients enrolled on NRG/RTOG 9202, 9413, and 9902 phase III randomized trials. After central review, the highest-grade tumors were profiled on clinical-grade whole-transcriptome arrays and GC scores were obtained. The primary objective was to validate the independent prognostic ability of GC for distant metastases (DM), and secondary was prostate cancer-specific mortality (PCSM) and overall survival (OS), with Cox multivariable analyses (MVA). RESULTS GC scores were obtained on 385 samples (n = 90 on 9202, n = 172 on 9413, and n = 123 on 9902), of which 265 passed microarray quality control (69%) and had a median follow-up of 11 years (interquartile range, 9, 13). On MVA, the GC (per 0.1 unit) was independently associated with DM (HR 1.24, 95% CI 1.11-1.39), PCSM (HR 1.27, 95% CI 1.13-1.43), and OS (HR 1.12, 95% CI 1.05-1.20) after adjusting for age, PSA, Gleason score, cT-stage, trial, and randomized treatment arm. For categorical GC, on MVA, GC score ≥ 0.45 (representing the intermediate and high GC categories) had worse DM (HR 2.18, 95% CI 1.25-3.80), PCSM (HR 2.34, 95% CI 1.31-4.16), and OS (HR 1.45, 95% CI 1.03-2.04) outcomes as compared to those with low GC. Cumulative incidence of distant-metastasis at 10-years was 29% (95% CI 20-38%) for intermediate/high GC vs 13% (95% CI 7-18%) for low GC. For the subset with GC > 0.85, the threshold for inclusion in the intensification study of NRG GU009 (PREDICT-RT), at 5-years and 10-years DM was 29% (95% CI 7-52%) and 41% (95% CI 17-66%). GC had similar prognostic ability in patients receiving short-term or long-term androgen-deprivation therapy (ADT). CONCLUSION This is the first validation of any gene expression biomarker on pre-treatment biopsy samples from prospective randomized trials and demonstrates an independent association of GC score with DM, PCSM, and OS. High-risk prostate cancer is a heterogeneous disease state and GC can improve risk stratification to help personalize shared decision-making. NRG-GU009/PREDICT-RT will further determine the optimal therapy based on GC score. NCT04513717.

Background To evaluate the dosimetric performance of multi-channel vaginal cylinder (MCVC) against interstitial brachytherapy (ISBT) for the treatment of vaginal tumors. Methods Vaginal tumors with extension of > 0.5 cm and ≤ 2 cm from the lateral vaginal wall and/or ≤ 1 cm in height above the vaginal vault were retrospectively selected from a ISBT registry trial database. The selected patients were treated with ISBT and targets included the intermediate (IRCTV) or high-risk (HRCTV) clinical target volumes. For technique comparison, a 35 mm MCVC was registered with the interstitial intra-vaginal cylinder. Bladder and rectum contours were transferred from the ISBT to the MCVC-BT plans. Vaginal mucosa was achieved by 3 mm uniform expansion from cylinder surface. Both the ISBT and MCVC-BT plans were optimized using the Inverse Planning Simulated Annealing optimization algorithm. After normalizing target D90 to 700 cGy, dose to organs at risk were measured and compared between ISBT and MCVC plans. Results Six interstitial patient plans met the inclusion criteria for this study. Four patients had vaginal primaries and two recurrent cancers in the vagina. Lower doses to bladder and rectum were seen with ISBT plans. In half of the MCVC plans, the rectal dose met the recommended constraints. For plans in which the rectal constraint was not met, the target volumes were abutting the rectum and had a cranial-caudal length ≥ 5 cm. Dose to vaginal mucosa was lower in ISBT plans directed to the HRCTVs, although no difference was seen in circumferential IRCTVs. Conclusions Overall, ISBT results in decreased dose to OARs as compared to MCVC. However, MCVC BT results in acceptable doses to OARs with possible improvement in vaginal doses for circumferential targets. Careful consideration to tumor geometry and location may help guide optimal techniques in vaginal tumor brachytherapy.

Background Echinococcus multilocularis is a destructive zoonotic cestode with low human incidence. Hydatid disease classically presents with hepatic or lung involvement with infrequent extrahepatic bone destruction. Diagnosis is challenging due to its latency and mimicry. Fig.1: Case 1 - X-ray imaging of the pelvis shows osseous destruction of the iliac crest secondary to known osteomyelitis status post left ilium debridement. Fig.2: Case 1 - Magnetic resonance imaging demonstrates extensive osteomyelitis throughout left ilium. Stable scattered focal fluid collections seen throughout the left lower quadrant. Methods CASE 1: A 57 year-old Albanian male with diabetes, latent TB, and left iliac lytic lesion presented with 4 weeks of left flank pain and was treated with 6 weeks of IV Ceftriaxone and Flagyl. 2 years later he returned with flank pain and purulent lumbar drainage. Hip x-ray suggested chronic osteomyelitis, with left psoas fluid collections on CT. Bartonella, Q fever, Brucella, HIV, AFB and fungal serologies were negative. Hemipelvis debridement revealed structures concerning for hydatid disease. Echinococcus IgG was equivocal. Histopathology was consistent with Echinococcus multilocularis species, and albendazole was started. On follow-up, he presented with left hip tenderness and toe extensor weakness. Labs showed mild leukocytosis. CT revealed progressive destruction of the left iliac with sacroiliac extension concerning for abscess. CASE 2: A 36 year-old female presented with lung and liver cysts, progressive dyspnea, and non-productive cough. She lived in Africa, Asia, and Europe and consumed local street food and unpasteurized milk. Hobbies included spelunking and swimming in freshwater lakes. She had exposure to stray animals, but denied bites or scratches. Over 4 years dyspnea progressed to orthopnea. MR abdomen revealed a 10x6x12cm liver cyst and chest CT showed 2 fluid-attenuating lesions in the LLL and RLL, measuring 4.9 x 6.0 cm and 6.8 x 4.3 cm respectively. Echinococcus, Bartonella, Q fever, Brucella, HIV, AFB and fungal serologies were negative. Schistosomiasis serology was equivocal. Fig. 3: Case 2 - MRI abdomen demonstrating 10x6x12cm liver cyst Fig. 4: Case 2 - Chest CT showed 2 dominant fluid attenuating lesions within the LLL and RLL. The larger lesion in RLL measures 6.8 x 4.3 cm. The left lower lobe lesion measures 4.9 x 6.0 cm. Results Patient 1 underwent type I hemipelvectomy. Patient 2 underwent pulmonary segmentectomy and liver lobectomy. Both were continued on albendazole. Fig. 5: Case 1 - Photo taken during debridement of left ileac and hip. Note presence of white cysts discovered intraoperatively. Fig. 6: Case 1 - Histopathologic slides (H&E stain) demonstrating hooks and scolices consistent with Echinococcus multilocularis. A. Hooklet (100x magnification). B. Hydatid cyst with black-staining structures suggestive of degenerating hooklets. C. Zoomed detail of cyst wall. D. Degenerating hydatid cyst and hooklets. Conclusion Equivocal IgG serology does not exclude infection. History and clinical presentation are key to diagnosis, but histopathology remains the gold standard. Hydatid bone infection progresses insidiously and frequently recurs, depending upon excision and debridement. Finally, echinococcosis demands aggressive long-term therapy and surveillance. Disclosures Claudia R. Libertin, MD, Pfizer, Inc. (Grant/Research Support, Research Grant or Support)

Purpose The purpose of this study was to evaluate the noninferiority of Day 30 dosimetry between a machine learning–based treatment planning system for prostate low-dose-rate (LDR) brachytherapy and the conventional, manual planning technique. As a secondary objective, the impact of planning technique on clinical workflow efficiency was also evaluated. Materials and Methods 41 consecutive patients who underwent I-125 LDR monotherapy for low- and intermediate-risk prostate cancer were accrued into this single-institution study between 2017 and 2018. Patients were 1:1 randomized to receive treatment planning using a machine learning–based prostate implant planning algorithm (PIPA system) or conventional, manual technique. Treatment plan modifications by the radiation oncologist were evaluated by computing the Dice coefficient of the prostate V150% isodose volume between either the PIPA—or conventional—and final approved plans. Additional evaluations between groups evaluated the total planning time and dosimetric outcomes at preimplant and Day 30. Results 21 and 20 patients were treated using the PIPA and conventional techniques, respectively. No significant differences were observed in preimplant or Day 30 prostate D90%, V100%, rectum V100, or rectum D1cc between PIPA and conventional techniques. Although the PIPA group had a larger proportion of patients with plans requiring no modifications (Dice = 1.00), there was no significant difference between the magnitude of modifications between each arm. There was a large significant advantage in mean planning time for the PIPA arm (2.38 ± 0.96 min) compared with the conventional (43.13 ± 58.70 min) technique (p >> 0.05). Conclusions A machine learning–based planning workflow for prostate LDR brachytherapy has the potential to offer significant time savings and operational efficiencies, while producing noninferior postoperative dosimetry to that of expert, conventional treatment planners.

Purpose/objective To report biochemical control associated with single fraction 15 Gy high-dose-rate brachytherapy (HDR-BT) boost followed by external beam radiation (EBRT) in patients with intermediate-risk prostate cancer. Materials and methods A retrospective chart review of all patients with intermediate-risk disease treated with a real-time ultrasound-based 15 Gy HDR-BT boost followed by EBRT between 2009 and 2016 at a single quaternary cancer center was performed. Freedom from biochemical failure (FFBF), cumulative incidence of androgen deprivation therapy use for biochemical or clinical failure post-treatment (CI of ADT) and metastasis-free survival (MFS) outcomes were measured. Results 518 patients met the inclusion criteria for this study. Median age at HDR-BT was 67 years (IQR 61–72). 506 (98%) had complete pathologic information available. Of these, 146 (28%) had favorable (FIR) and 360 (69%) had unfavorable (UIR) intermediate-risk disease. 83 (16%) received short course hormones with EBRT + HDR. Median overall follow-up was 5.2 years. FFBF was 91 (88–94)% at 5 years. Five-year FFBF was 94 (89–99)% and 89 (85–94)% in FIR and UIR patients, respectively (p = 0.045). CI of ADT was 4 (2–6)% at 5 years. Five-year CI of ADT was 1 (0–3)% and 5 (2–8)% in FIR and UIR patients, respectively (p = 0.085). MFS was 97 (95–98)% at 5 years. Five-year MFS was 100 (N/A-100)% and 95 (92–98)% in FIR and UIR patients, respectively (p = 0.020). Conclusion In this large cohort of intermediate-risk prostate cancer patients, 15 Gy HDR-BT boost plus EBRT results in durable biochemical control and low rates of ADT use for biochemical failure.

Glioblastoma is a common aggressive primary malignant brain tumor, and is nearly universal in progression and mortality after initial treatment. Re-irradiation presents a promising treatment option for progressive disease, both palliating symptoms and potentially extending survival. Highly conformal radiation techniques such as stereotactic radiosurgery and hypofractionated radiosurgery are effective short courses of treatment that allow delivery of high doses of therapeutic radiation with steep dose gradients to protect normal tissue. Patients with higher performance status, younger age, and longer interval between primary treatment and progression represent the best candidates for re-irradiation. Multiple studies are also underway involving combinations of radiation and systemic therapy to bend the survival curve and improve the therapeutic index. In the multimodal treatment of recurrent high-grade glioma, the use of surgery, radiation, and systemic therapy should be highly individualized. Here we comprehensively review radiation therapy and techniques, along with discussion of combination treatment and novel strategies.