Epidemiology, treatment patterns, and clinical outcomes in de novo oligometastatic hormone-sensitive prostate cancer.

BACKGROUND: This study was conducted to better characterize the epidemiology, clinical outcomes, and current treatment patterns of de novo oligometastatic hormone-sensitive prostate cancer (omHSPC) in the United States Veterans Affairs Health Care System. METHODS: In this observational retrospective cohort study, 400 de novo metastatic hormone-sensitive PC (mHSPC) patients diagnosed from January 2015 to December 2020 (follow-up through December 2021) were randomly selected. omHSPC was defined as five or less total metastases (excluding liver) by conventional imaging. Kaplan-Meier methods estimated overall survival (OS) and castration-resistant prostate cancer (CRPC)-free survival from mHSPC diagnosis date and a log-rank test compared these outcomes by oligometastatic status. RESULTS: Twenty percent (79 of 400) of de novo mHSPC patients were oligometastatic. Most baseline characteristics were similar by oligometastatic status; however, men with non-omHSPC had higher median prostate-specific antigen at diagnosis (151.7) than omHSPC (44.1). First-line (1L) novel hormonal therapy was similar between groups (20%); 1L chemotherapy was lower in omHSPC (5%) versus non-omHSPC (14%). More omHSPC patients received metastasis-directed therapy/prostate radiation therapy (14%) versus non-omHSPC (2%). Median OS and CRPC-free survival (in months) were higher in omHSPC versus non-omHSPC (44.4; 95% confidence interval [CI], 33.9-not estimated vs. 26.2; 95% CI, 20.5-32.5, p = .0089 and 27.6; 95% CI, 22.1-37.2 vs. 15.3; 95% CI, 12.8-17.9, p = .0049), respectively. CONCLUSIONS: Approximately 20% of de novo mHSPC were oligometastatic, and OS was significantly longer in omHSPC versus non-omHSPC. Although potentially "curative" therapy use was higher in omHSPC versus non-omHSPC, the percentages were still relatively low. Future studies are warranted given potential for prolonged responses with multimodal therapy inclusive of systemic and local therapies.

Stereotactic Body Proton Therapy Versus Conventionally Fractionated Proton Therapy for Early Prostate Cancer: A Randomized, Controlled, Phase 3 Trial.

PURPOSE: We aimed to determine if ultra-hypofractionated proton therapy delivered via stereotactic body proton therapy (SBPT) is non-inferior to conventionally fractionated proton therapy (CFPT) in patients with early prostate cancer. MATERIALS AND METHODS: This study was a multicenter, randomized, controlled, non-inferiority phase 3 trial that included patients with histologically confirmed low-risk prostate adenocarcinoma defined by Gleason score grouping 1, PSA <10 ng/mL, and clinical stage T1-2a N0 M0 according to AJCC 7th ed. Eligible participants were randomly assigned initially at a 1:1 ratio and later at a 2:1 ratio to SBPT (38 Gy in 5 fractions) or CFPT (79.2 Gy in 44 fractions). The primary endpoint was freedom from failure (FFF) at 2 years from the date of randomization. Non-inferiority for FFF was determined based on one-sided confidence intervals. Toxicities were compared at different time points using Fisher's Exact test. Health-related quality-of-life (HRQoL) was analyzed at different time points using a mixed-effects linear model. This trial is registered with ClinicalTrials.gov, NCT01230866, and is closed to accrual. RESULTS: Between December 10, 2010, and September 29, 2020, 144 patients were enrolled and 135 were randomly assigned (90 to the SBPT group and 45 to the CFPT group). The median follow-up was 5 years (IQR 3.9-5.2). The 2-year FFF was 100% for both groups, with the one-sided 5-year risk difference in FFF between groups reported as 2.63% (90% CI: -1.70%-6.96%), favoring the SBRT arm, thus fulfilling the pre-specified criteria for non-inferiority of SBPT compared to CFPT. Rates of gastrointestinal (GI) and genitourinary (GU) G2 and G3 toxicities did not differ significantly between groups but the the study was not powered to detect significant toxicity differences. Also, HRQoL metrics did not differ significantly between groups over the study median follow up. CONCLUSIONS: SBPT is non-inferior to CFPT regarding FFF, with similar long-term GU and GI toxicity rates and minimal impact in patient reported HRQoL over time.

Diversity and antimicrobial susceptibility patterns of clinical and environmental Salmonella enterica serovars in Western Saudi Arabia.

The diverse environmental distribution of Salmonella makes it a global source of human gastrointestinal infections. This study aimed to detect Salmonella spp. and explore their diversity and antimicrobial susceptibility patterns in clinical and environmental samples. Pre-enrichment, selective enrichment, and selective plating techniques were adopted for the Salmonella detection whereas the API 20E test and Vitek Compact 2 system were used to confirm the identity of isolates. Salmonella serovars were subjected to molecular confirmation by 16S rDNA gene sequencing. Disc diffusion method and Vitek 2 Compact system determined the antibiotic susceptibility of Salmonella serovars. Multiple antibiotic resistance index (MARI) was calculated to explore whether Salmonella serovars originate from areas with heavy antibiotic usage. Results depicted low Salmonella prevalence in clinical and environmental samples (3.5%). The main detected serovars included Salmonella Typhimurium, S. enteritidis, S. Infantis, S. Newlands, S. Heidelberg, S. Indian, S. Reading, and S. paratyphi C. All the detected Salmonella serovars (27) exhibited multidrug resistance to three or more antimicrobial classes. The study concludes that the overall Salmonella serovars prevalence was found to be low in environmental and clinical samples of Western Saudi Arabia (Makkah and Jeddah). However, antimicrobial susceptibility patterns of human and environmental Salmonella serovars revealed that all isolates exhibited multidrug-resistance (MDR) patterns to frequently used antibiotics, which might reflect antibiotic overuse in clinical and veterinary medicine. It would be suitable to apply and enforce rules and regulations from the One Health approach, which aim to prevent antibiotic resistance infections, enhance food safety, and improve human and animal health, given that all Salmonella spp. detected in this investigation were exhibiting MDR patterns.

Should All Patients Receive Extended Oral Antibiotic Prophylaxis? Defining Its Role in Patients Undergoing Primary and Aseptic Revision Total Joint Arthroplasty.

BACKGROUND: Prior studies have demonstrated reduced periprosthetic joint infection (PJI) rates following extended oral antibiotics (EOAs) for high-risk patients undergoing primary total joint arthroplasty (TJA). This study compared 3-month PJI rates in all patients undergoing primary or aseptic revision TJA with or without EOA prophylaxis. METHODS: In total, 2,982 consecutive primary (n = 2,677) and aseptic revision (n = 305) TJAs were performed by a single, fellowship-trained arthroplasty surgeon from 2016 to 2022 were retrospectively reviewed. Beginning January 2020, all patients received 7 days of 300 mg oral cefdinir twice daily immediately postoperatively. Rates of PJI at 3 months were compared between patients who received or did not receive EOA. RESULTS: Rates of PJI at 3 months in patients undergoing primary and aseptic revision TJA were significantly lower in those receiving EOA prophylaxis compared to those who did not (0.41 versus 1.13%, respectively; P = .02). After primary TJA, lower PJI rates were observed with EOA prophylaxis utilization (0.23 versus 0.74%, P = .04; odds ratio [OR] 3.85). Following aseptic revision TJA, PJI rates trended toward a significant decrease with the EOA compared to without (1.88 versus 4.83%, respectively; P = .16; OR 2.71). CONCLUSIONS: All patients undergoing primary or aseptic revision TJA who received EOA prophylaxis were 3.85 and 2.71 times less likely, respectively, to develop PJI at 3 months compared to those without EOA. Future studies are needed to determine if these results are maintained at postoperative time periods beyond 3 months following primary TJA. LEVEL OF EVIDENCE: III, Retrospective review.

Physician- and Patient-Reported Outcomes of the MC1635 Phase 3 Trial of Ultrahypofractionated Versus Moderately Hypofractionated Adjuvant Radiation Therapy After Breast-Conserving Surgery.

PURPOSE: Our aim was to report physician- and patient-reported outcomes of patients with localized breast cancer treated with moderate versus ultrahypofractionated whole breast irradiation (WBI) after breast-conserving surgery (BCS). METHODS AND MATERIALS: Between February 2018 and February 2020, patients with localized breast cancer (pT0-3 pN0-1 M0) were offered participation in a phase 3 randomized clinical trial assessing adjuvant moderate hypofractionation (MHF) to 40 Gy in 15 fractions versus ultrahypofractionation (UHF) to 25 Gy in 5 fractions after BCS, with an optional simultaneously integrated boost. Toxicities, cosmesis, and quality of life were assessed at baseline, end of treatment (EOT), and 3 months, 1 year, 2 years, and 3 years from irradiation using validated metric tools. RESULTS: One hundred seven patients were randomized to MHF (n = 54) or UHF (n = 53) adjuvant WBI. The median follow-up was 42.8 months. Grade 2 radiation dermatitis was experienced by 4 patients (7.4%) in the MHF arm and 2 patients (3.7%) in the UHF arm at EOT (P = .726). No grade 3 or higher toxicities were observed. Deterioration of cosmesis by physician assessment was observed in 2 (6.7%) patients treated in the UHF arm and 1 (1.9%) patient treated in the MHF arm at EOT (P = .534), whereas at 3 months, only 1 (1.8%) patient treated in the MHF arm demonstrated deterioration of cosmesis (P = .315). At EOT, 91% and 94% of patients reported excellent/good cosmesis among those treated with MHF and UHF regimens, respectively (P = .550). At 3 months, more patients within the MHF arm reported excellent/good cosmesis compared with those in the UHF arm (100% vs 91%; P = .030). However, the difference in patient-reported cosmesis disappeared at the 1-, 2-, and 3-year time points. CONCLUSIONS: UHF WBI showed similar treatment-related late toxicities and similar provider-scored cosmesis compared with MHF radiation in patients treated adjuvantly after BCS.

Beam mask and sliding window-facilitated deep learning-based accurate and efficient dose prediction for pencil beam scanning proton therapy.

BACKGROUND: Accurate and efficient dose calculation is essential for on-line adaptive planning in proton therapy. Deep learning (DL) has shown promising dose prediction results in photon therapy. However, there is a scarcity of DL-based dose prediction methods specifically designed for proton therapy. Successful dose prediction method for proton therapy should account for more challenging dose prediction problems in pencil beam scanning proton therapy (PBSPT) due to its sensitivity to heterogeneities. PURPOSE: To develop a DL-based PBSPT dose prediction workflow with high accuracy and balanced complexity to support on-line adaptive proton therapy clinical decision and subsequent replanning. METHODS: PBSPT plans of 103 prostate cancer patients (93 for training and the other 10 for independent testing) and 83 lung cancer patients (73 for training and the other 10 for independent testing) previously treated at our institution were included in the study, each with computed tomography scans (CTs), structure sets, and plan doses calculated by the in-house developed Monte-Carlo dose engine (considered as the ground truth in the model training and testing). For the ablation study, we designed three experiments corresponding to the following three methods: (1) Experiment 1, the conventional region of interest (ROI) (composed of targets and organs-at-risk [OARs]) method. (2) Experiment 2, the beam mask (generated by raytracing of proton beams) method to improve proton dose prediction. (3) Experiment 3, the sliding window method for the model to focus on local details to further improve proton dose prediction. A fully connected 3D-Unet was adopted as the backbone. Dose volume histogram (DVH) indices, 3D Gamma passing rates with a criterion of 3%/3 mm/10%, and dice coefficients for the structures enclosed by the iso-dose lines between the predicted and the ground truth doses were used as the evaluation metrics. The calculation time for each proton dose prediction was recorded to evaluate the method's efficiency. RESULTS: Compared to the conventional ROI method, the beam mask method improved the agreement of DVH indices for both targets and OARs and the sliding window method further improved the agreement of the DVH indices (for lung cancer, CTV D98 absolute deviation: 0.74 ± 0.18 vs. 0.57 ± 0.21 vs. 0.54 ± 0.15 Gy[RBE], ROI vs. beam mask vs. sliding window methods, respectively). For the 3D Gamma passing rates in the target, OARs, and BODY (outside target and OARs), the beam mask method improved the passing rates in these regions and the sliding window method further improved them (for prostate cancer, targets: 96.93% ± 0.53% vs. 98.88% ± 0.49% vs. 99.97% ± 0.07%, BODY: 86.88% ± 0.74% vs. 93.21% ± 0.56% vs. 95.17% ± 0.59%). A similar trend was also observed for the dice coefficients. This trend was especially remarkable for relatively low prescription isodose lines (for lung cancer, 10% isodose line dice: 0.871 ± 0.027 vs. 0.911 ± 0.023 vs. 0.927 ± 0.017). The dose predictions for all the testing cases were completed within 0.25 s. CONCLUSIONS: An accurate and efficient deep learning-augmented proton dose prediction framework has been developed for PBSPT, which can predict accurate dose distributions not only inside but also outside ROI efficiently. The framework can potentially further reduce the initial planning and adaptive replanning workload in PBSPT.

Gold Nanomaterial-Based Microfluidic Paper Analytical Device for Simultaneous Quantification of Gram-Negative Bacteria and Nitrite Ions in Water Samples.

This study presents a rapid microfluidic paper-based analytical device (µPAD) capable of simultaneously monitoring Gram-negative bacteria and nitrite ions (NO2-) for water quality monitoring. We utilize gold nanoparticles (AuNPs) functionalized with polymyxin molecules (AuNPs@polymyxin) to cause color change due to aggregation for the detection of Gram-negative bacteria, and antiaggregation in the presence of o-phenylenediamine (OPD) for NO2- detection. In this study, Escherichia coli (E. coli) serves as the model of a Gram-negative bacterium. Using the developed µPADs, the color changes resulting from aggregation and antiaggregation reactions are measured using a smartphone application. The linear detection ranges from 5.0 × 102 to 5.0 × 105 CFU/mL (R2 = 0.9961) for E. coli and 0.20 to 2.0 µmol/L (R2 = 0.995) for NO2-. The detection limits were determined as 2.0 × 102 CFU/mL for E. coli and 0.18 µmol/L for NO2-. Notably, the newly developed assay exhibited high selectivity with no interference from Gram-positive bacteria. Additionally, we obtained acceptable recovery for monitoring E. coli and NO2- in drinking water samples with no significant difference between our method and a commercial assay by t test validation. The sensor was also employed for assessing the quality of the pond and environmental water source. Notably, this approach can also be applied to human urine samples with satisfactory accuracy. Furthermore, the assay's stability is extended due to its reliance on AuNPs rather than reagents like antibodies and enzymes, reducing costs and ensuring long-term viability. Our cost-effective µPADs therefore provide a real-time analysis of both contaminants, making them suitable for assessing water quality in resource-limited settings.

Proton Therapy in the Adolescent and Young Adult Population.

BACKGROUND: Adolescent and young adult cancer patients are at high risk of developing radiation-associated side effects after treatment. Proton beam radiation therapy might reduce the risk of these side effects for this population without compromising treatment efficacy. METHODS: We review the current literature describing the utility of proton beam radiation therapy in the treatment of central nervous system tumors, sarcomas, breast cancer and Hodgkin lymphoma for the adolescent and young adult cancer population. RESULTS: Proton beam radiation therapy has utility for the treatment of certain cancers in the young adult population. Preliminary data suggest reduced radiation dose to normal tissues, which might reduce radiation-associated toxicities. Research is ongoing to further establish the role of proton therapy in this population. CONCLUSION: This report highlights the potential utility of proton beam radiation for certain adolescent young adult cancers, especially with reducing radiation doses to organs at risk and thereby potentially lowering risks of certain treatment-associated toxicities.

Dose delivery reproducibility for PBS proton treatment of breast cancer patients with and without mask immobilization.

BACKGROUND: Setup reproducibility of the tissue in the proton beam path is critical in maintaining the planned clinical target volume (CTV) dose coverage and sparing the organs at risk (OAR). In this study, we retrospectively evaluated radiation therapy dose reproducibility for proton pencil beam scanning (PBS) treatment of breast cancer patients with and without mask immobilization. METHODS: Ninety-four patients treated between January 2019 and September 2022 with at least one verification CT scan (V-CT) in treatment position were included for this study. All patients were set up with arms up using the Orfit AIO patient positioning system, with (69 patients) or without (25 patients) mask immobilization in chin, neck, shoulder, upper arm, and chest areas. Two to three enface or near enface single field uniform dose PBS beams were optimized using a commercial treatment planning system. Prescription doses were 25 to 60 GyRBE in 5 to 45 fractions. Treatment plan doses re-calculated on V-CTs were compared to the corresponding planned doses. Cumulative doses were also calculated for patients with at least 3 V-CTs by deform and weighted sum doses from V-CTs to corresponding P-CTs. CTV D95%, ipsilateral-lung V40%, esophagus D0.01cc, and heart mean dose were evaluated and reported as percentages of prescription doses. Differences were large dose deteriorations (LDD) if: (1) CTV (V-CT/cumulative D95%) - (Planned D95%) < - 5%; or (2) Ipsilateral-lung (V-CT/cumulative V40%) - (Planned V40%) > 5%; or (3) Esophagus (V-CT/cumulative D0.01cc) - (Planned D0.01cc) > 10%; or (4) Heart (V-CT/cumulative mean) - (Planned mean) > 1.5%. RESULTS: On average, V-CT/cumulative and planned CTV/OAR dose parameter differences were less than 2.2%/1.7% and 3.4%/3.7% for masked and maskless patients, respectively. The percentages of patients with at least one CTV or OAR V-CT/cumulative dose LDD were 20.3%/25.0% and 72.0%/54.0% for masked and maskless patients, respectively. CONCLUSIONS: On average, masked/maskless setups achieved delivered and planned CTV/OAR dose parameters agreed within 2.2%/3.7% for PBS treatment of breast cancer patients in this study. Maskless patients had higher rate of CTV/OAR LDDs compared to masked patients. Dosimetric differences large enough to raise clinical concerns in either group were able to be addressed with replannings.

Beam mask and sliding window-facilitated deep learning-based accurate and efficient dose prediction for pencil beam scanning proton therapy.

PURPOSE: To develop a DL-based PBSPT dose prediction workflow with high accuracy and balanced complexity to support on-line adaptive proton therapy clinical decision and subsequent replanning. METHODS: PBSPT plans of 103 prostate cancer patients and 83 lung cancer patients previously treated at our institution were included in the study, each with CTs, structure sets, and plan doses calculated by the in-house developed Monte-Carlo dose engine. For the ablation study, we designed three experiments corresponding to the following three methods: 1) Experiment 1, the conventional region of interest (ROI) method. 2) Experiment 2, the beam mask (generated by raytracing of proton beams) method to improve proton dose prediction. 3) Experiment 3, the sliding window method for the model to focus on local details to further improve proton dose prediction. A fully connected 3D-Unet was adopted as the backbone. Dose volume histogram (DVH) indices, 3D Gamma passing rates, and dice coefficients for the structures enclosed by the iso-dose lines between the predicted and the ground truth doses were used as the evaluation metrics. The calculation time for each proton dose prediction was recorded to evaluate the method's efficiency. RESULTS: Compared to the conventional ROI method, the beam mask method improved the agreement of DVH indices for both targets and OARs and the sliding window method further improved the agreement of the DVH indices. For the 3D Gamma passing rates in the target, OARs, and BODY (outside target and OARs), the beam mask method can improve the passing rates in these regions and the sliding window method further improved them. A similar trend was also observed for the dice coefficients. In fact, this trend was especially remarkable for relatively low prescription isodose lines. The dose predictions for all the testing cases were completed within 0.25s.

Tunable Radio Frequency Antenna Based on Phase Change Materials.

In conventional communication systems, dedicated tunable circuit elements are used to realize different functions and achieve performance metrics. For example, tuning the center frequency or the input impedance of an antenna in a radio frequency (RF) system is performed by complex impedance-matching circuits. In this paper, the antenna utilizes the temperature-induced irreversible mechanical deformation of a shape memory alloy (SMA) as a natural way to tune the antenna's shape and configuration, thereby providing inherent tunability without bulky circuit elements. This paradigm of material programming for impedance tuning of an SMA-based antenna is validated by both numerical simulation and measurements.

Enantioselective Intramolecular Decarboxylative C-H Bond Func-tionalization of Quinazolinones with Amino Acids by Visible Light Photoredox Catalysis.

The direct visible light-mediated intramolecular decarboxylative C-H functionalization of Csp2 -H bond adjacent to the nitrogen of a heteroarene has been achieved by iridium-catalyzed photodecarboxylative radical cyclization. This method offers rapid entry to the synthesis of quinazolinone scaffolds from easily accessible starting materials. The newly developed protocol is mild, operationally simple, oxidant free and general. The utility of this unique Csp3 -Csp2 bond forming reaction has been demonstrated in the syntheses of Circumdatin, Sclerotigenine and Benzomalvin A class of quinazolinone natural products and their congeners. The present work represents an interesting example of use of memory of chirality in decarboxylative C-C bond forming enantioselective photoredox reaction.

Arthroscopic Pectoralis Minor Release After Reverse Shoulder Arthroplasty: A Novel Consideration for Postarthroplasty Pain.

CASE: A 74-year-old male patient presenting with chronic radiating shoulder pain, paresthesias, and weakness had previously undergone reverse shoulder arthroplasty and anterior cervical discectomy and fusion for an irreparable cuff tear and cervical radiculopathy, respectively. After being diagnosed with neurogenic thoracic outlet syndrome and undergoing physiotherapy, the patient's recalcitrant condition was surgically managed with arthroscopic pectoralis minor tenotomy, suprascapular nerve release, and brachial plexus neurolysis. CONCLUSION: This ultimately led to complete pain relief and improved function. By sharing this case, we aim to shed light on this overlooked pathology and help prevent unnecessary procedures for others suffering from similar conditions.

The Onset and Development of Patella Alta in Children With Patellar Instability.

BACKGROUND: Patella alta is an anatomic risk factor for patellar instability in adolescents that is also linked to the risk factor of trochlear dysplasia. This study aims to determine the age of onset and age-related incidence of patella alta in a pediatric population of patients with patellar instability. We hypothesized that patellar height ratios would not increase with age, suggesting a congenital rather than the developmental origin of patella alta. METHODS: A retrospective cross-sectional cohort of patients was collected with the following inclusion criteria: patients aged 5 to 18 who had a knee magnetic resonance imaging performed from 2000 to 2022 and the International Classification of Diseases code for patellar dislocation. Demographic information and details of the patellar instability episode(s) were collected with a chart review. Sagittal magnetic resonance imaging was used to measure Caton-Deschamps Index (CDI) and the Insall-Salvati Ratio (ISR) by 2 observers. Data were analyzed to assess for associations between patellar height ratios and age of the first dislocation and to assess if the proportion of patients categorized as having patella alta changed with age. RESULTS: The 140 knees included in the cohort had an average age of 13.9 years (SD=2.40; range: 8-18) and were 55% female. Patella alta was present in 78 knees (55.7%) using CDI>=1.2 and in 59 knees (42.1%) using ISR>=1.3. The earliest age patella alta was observed was at age 8 using CDI>=1.2 and age 10 using ISR>=1.3. There were no statistically significant associations between CDI and age without adjustment ( P =0.14) nor after adjustment for sex and body mass index ( P =0.17). The proportion of knees above the CDI threshold for patella alta to the knees below the cutoff did not show a significant change with age ( P =0.09). CONCLUSIONS: Patella alta, as defined by CDI, is seen in patients as young as 8 years old. Patellar height ratios do not change with age in patients with patellar dislocation, suggesting that patella alta is established at a young age rather than developing during the adolescent years. LEVEL OF EVIDENCE: Level III-diagnostic, cross-sectional.

First Report On Physician Assessment and Clinical Acceptability of Custom-Retrained Artificial Intelligence Models for Clinical Target Volume and Organs-at-Risk Auto-Delineation for Postprostatectomy Patients.

PURPOSE: To assess the clinical acceptability of a commercial deep-learning-based auto-segmentation (DLAS) prostate model that was retrained using institutional data for delineation of the clinical target volume (CTV) and organs-at-risk (OARs) for postprostatectomy patients, accounting for clinical and imaging protocol variations. METHODS AND MATERIALS: CTV and OARs of 109 prostate-bed patients were used to evaluate the performance of the vendor-trained model and custom retrained DLAS models using different training quantities. Two new models for OAR structures were retrained (n = 30, 60 data sets), while separate models were trained for a new CTV structure (n = 30, 60, 90 data sets), with the remaining data sets used for testing (n = 49, 19). The dice similarity coefficient (DSC), Hausdorff distance, and mean surface distance were evaluated. Six radiation oncologists performed a qualitative evaluation scoring both preference and clinical utility for blinded structure sets. Physician consensus data sets identified from the qualitative evaluation were used toward a separate CTV model. RESULTS: Both the 30- and 60-case retrained OAR models had median DSC values between 0.91 to 0.97, improving significantly over the vendor-trained model for all OARs except the penile bulb. The brand new 60-case CTV model had a median DSC of 0.70 improving significantly over the 30-case model. DLAS (60-case model) and manual contours were blinded and evaluated by physicians with contours deemed acceptable or precise for 87% and 94% of cases for DLAS and manual delineations, respectively. DLAS-generated CTVs were scored precise or acceptable in 54% of cases, compared with the manual delineation value of 73%. The 30-case physician consensus CTV model did not show a significant difference compared with the randomly selected models. CONCLUSIONS: Custom retraining using institutional data leads to performance improvement in the clinical utility and accuracy of DLAS for postprostatectomy patients. A small number of data sets are sufficient for building an institutional site-specific DLAS OAR model, as well as for training new structures. Data indicates the workload for identifying training data sets could be shared among groups for the male pelvic region, making it accessible to clinics of all sizes.

Pragmatic, Prospective Comparative Effectiveness Trial of Carbon Ion Therapy, Surgery, and Proton Therapy for the Management of Pelvic Sarcomas (Soft Tissue/Bone) Involving the Bone: The PROSPER Study Rationale and Design.

Surgical treatment of pelvic sarcoma involving the bone is the standard of care but is associated with several sequelae and reduced functional quality of life (QOL). Treatment with photon and proton radiotherapy is associated with relapse. Carbon ion radiotherapy (CIRT) may reduce both relapse rates and treatment sequelae. The PROSPER study is a tricontinental, nonrandomized, prospective, three-arm, pragmatic trial evaluating treatments of pelvic sarcoma involving the bone. Patients aged at least 15 years are eligible for inclusion. Participants must have an Eastern Cooperative Oncology Group Performance Status score of two or less, newly diagnosed disease, and histopathologic confirmation of pelvic chordoma, chondrosarcoma, osteosarcoma, Ewing sarcoma with bone involvement, rhabdomyosarcoma (RMS) with bone involvement, or non-RMS soft tissue sarcoma with bone involvement. Treatment arms include (1) CIRT (n = 30) delivered in Europe and Asia, (2) surgical treatment with or without adjuvant radiotherapy (n = 30), and (3) proton therapy (n = 30). Arms two and three will be conducted at Mayo Clinic campuses in Arizona, Florida, and Minnesota. The primary end point is to compare the 1-year change in functional QOL between CIRT and surgical treatment. Additional comparisons among the three arms will be made between treatment sequelae, local control, and other QOL measures.

Initial Quality of Life and Toxicity Analysis of a Randomized Phase 3 Study of Moderately Hypofractionated Radiation Therapy With or Without Androgen Suppression for Intermediate-Risk Adenocarcinoma of the Prostate: PCG GU003.

Purpose: Our objective was to report the quality of life (QoL) analysis and toxicity in patients with intermediate-risk prostate cancer treated with or without androgen deprivation therapy (ADT) in Proton Collaborative Group (PCG) GU003. Methods and Materials: Between 2012 and 2019, patients with intermediate-risk prostate cancer were enrolled. Patients were randomized to receive moderately hypofractionated proton beam therapy (PBT) to 70 Gy relative biologic effectiveness in 28 fractions to the prostate with or without 6 months of ADT. Expanded Prostate Cancer Index Composite, Short-Form 12, and the American Urological Association Symptom Index instruments were given at baseline and 3, 6, 12, 18, and 24 months after PBT. Toxicities were assessed according to Common Terminology Criteria for Adverse Events (version 4). Results: One hundred ten patients were randomized to PBT either with 6 months of ADT (n = 55) or without ADT (n = 55). The median follow-up was 32.4 months (range, 5.5-84.6). On average, 101 out of 110 (92%) patients filled out baseline QoL and patient-reported outcome surveys. The compliance was 84%, 82%, 64%, and 42% at 3, 6, 12, and 24 months, respectively. Baseline median American Urological Association Symptom Index was comparable between arms (6 [11%] ADT vs 5 [9%] no ADT, P = .359). Acute and late grade 2+ genitourinary and gastrointestinal toxicity were similar between arms. The ADT arm experienced a QoL decline of mean scores in the sexual (-16.1, P < .001) and hormonal (-6.3, P < .001) domains, with the largest time-specific hormonal differences at 3 (-13.8, P < .001) and 6 (-11.2, P < .001) months. The hormonal QoL domain returned to baseline 6 months after therapy. There was a trend to baseline in sexual function 6 months after completion of ADT. Conclusions: After 6 months of ADT, sexual and hormonal domains returned to baseline 6 months after completion of treatment for men with intermediate-risk prostate cancer.

Technical note: Comprehensive evaluations of gantry and couch rotation isocentricities for implementing proton stereotactic radiosurgery.

BACKGROUND: Mechanical accuracy should be verified before implementing a proton stereotactic radiosurgery (SRS) program. Linear accelerator (Linac)-based SRS systems often use electronic portal imaging devices (EPIDs) to verify beam isocentricity. Because proton therapy systems do not have EPID, beam isocentricity tests of proton SRS may still rely on films, which are not efficient. PURPOSE: To validate that our proton SRS system meets mechanical precision requirements and to present an efficient method to evaluate the couch and gantry's rotational isocentricity for our proton SRS system. METHODS: A dedicated applicator to hold brass aperture for proton SRS system was designed. The mechanical precision of the system was tested using a metal ball and film for 11 combinations of gantry and couch angles. A more efficient quality assurance (QA) procedure was developed, which used a scintillator device to replace the film. The couch rotational isocentricity tests were performed using orthogonal kV x-rays with the couch rotated isocentrically to five positions (0°, 315°, 270°, 225°, and 180°). At each couch position, the distance between the metal ball in kV images and the imaging isocenter was measured. The gantry isocentricity tests were performed using a cone-shaped scintillator and proton beams at five gantry angles (0°, 45°, 90°, 135°, and 180°), and the isocenter position and the distance of each beam path to the isocenter were obtained. Daily QA procedure was performed for 1 month to test the robustness and reproducibility of the procedure. RESULTS: The gantry and couch rotational isocentricity exhibited sub-mm precision, with most measurements within ±0.5 mm. The 1-month QA results showed that the procedure was robust and highly reproducible to within ±0.2 mm. The gantry isocentricity test using the cone-shaped scintillator was accurate and sensitive to variations of ±0.2 mm. The QA procedure was efficient enough to be completed within 30 min. The 1-month isocentricity position variations were within 0.5 mm, which demonstrating that the overall proton SRS system was stable and precise. CONCLUSION: The proton SRS Winston-Lutz QA procedure using a cone-shaped scintillator was efficient and robust. We were able to verify radiation delivery could be performed with sub-mm mechanical precision.