External Validation of a Digital Pathology-based Multimodal Artificial Intelligence Architecture in the NRG/RTOG 9902 Phase 3 Trial.

BACKGROUND: Accurate risk stratification is critical to guide management decisions in localized prostate cancer (PCa). Previously, we had developed and validated a multimodal artificial intelligence (MMAI) model generated from digital histopathology and clinical features. Here, we externally validate this model on men with high-risk or locally advanced PCa treated and followed as part of a phase 3 randomized control trial. OBJECTIVE: To externally validate the MMAI model on men with high-risk or locally advanced PCa treated and followed as part of a phase 3 randomized control trial. DESIGN, SETTING, AND PARTICIPANTS: Our validation cohort included 318 localized high-risk PCa patients from NRG/RTOG 9902 with available histopathology (337 [85%] of the 397 patients enrolled into the trial had available slides, of which 19 [5.6%] failed due to poor image quality). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Two previously locked prognostic MMAI models were validated for their intended endpoint: distant metastasis (DM) and PCa-specific mortality (PCSM). Individual clinical factors and the number of National Comprehensive Cancer Network (NCCN) high-risk features served as comparators. Subdistribution hazard ratio (sHR) was reported per standard deviation increase of the score with corresponding 95% confidence interval (CI) using Fine-Gray or Cox proportional hazards models. RESULTS AND LIMITATIONS: The DM and PCSM MMAI algorithms were significantly and independently associated with the risk of DM (sHR [95% CI] = 2.33 [1.60-3.38], p < 0.001) and PCSM, respectively (sHR [95% CI] = 3.54 [2.38-5.28], p < 0.001) when compared against other prognostic clinical factors and NCCN high-risk features. The lower 75% of patients by DM MMAI had estimated 5- and 10-yr DM rates of 4% and 7%, and the highest quartile had average 5- and 10-yr DM rates of 19% and 32%, respectively (p < 0.001). Similar results were observed for the PCSM MMAI algorithm. CONCLUSIONS: We externally validated the prognostic ability of MMAI models previously developed among men with localized high-risk disease. MMAI prognostic models further risk stratify beyond the clinical and pathological variables for DM and PCSM in a population of men already at a high risk for disease progression. This study provides evidence for consistent validation of our deep learning MMAI models to improve prognostication and enable more informed decision-making for patient care. PATIENT SUMMARY: This paper presents a novel approach using images from pathology slides along with clinical variables to validate artificial intelligence (computer-generated) prognostic models. When implemented, clinicians can offer a more personalized and tailored prognostic discussion for men with localized prostate cancer.

Cardiovascular Mortality and Duration of Androgen Deprivation in Locally Advanced Prostate Cancer: Long-term Update of NRG/RTOG 9202.

BACKGROUND: Androgen deprivation therapy (ADT) has been associated with coronary heart disease and myocardial infarction (MI) in prostate cancer patients, but controversy persists regarding its effects on cardiovascular mortality (CVM). OBJECTIVE: We assessed the long-term relationship between ADT and CVM in a prostate cancer randomized trial (NRG Oncology/Radiation Therapy Oncology Group 9202). DESIGN, SETTING, AND PARTICIPANTS: From 1992 to 1995, 1554 men with locally advanced prostate cancer (T2c-T4, prostate-specific antigen <150 ng/ml) received radiotherapy with 4 mo (short-term [STADT]) versus 28 mo (longer-term [LTADT]) of ADT. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Using the Fine-Gray and Cox regression models, the relationship between ADT and mortality was evaluated. RESULTS AND LIMITATIONS: With a median follow-up of 19.6 yr, LTADT was associated with improved overall survival (OS) versus STADT (adjusted hazard ratio [HR] 0.88; p = 0.03) and prostate cancer survival (subdistribution HR [sHR] 0.70, p = 0.003). Comparing LTADT with STADT, prostate cancer mortality improved by 6.0% (15.6% [95% confidence interval 13.0-18.3%] vs 21.6% [18.6-24.7%]) at 15 yr, while CVM increased by 2.2% (14.9% [12.4-17.6%] vs 12.7% [10.4-15.3%]). In multivariable analyses, LTADT was not associated with increased CVM versus STADT (sHR 1.22 [0.93-1.59]; p = 0.15). An association between LTADT and MI death was detected (sHR 1.58 [1.00-2.50]; p = 0.05), particularly in patients with prevalent cardiovascular disease (CVD; sHR 2.54 [1.16-5.58]; p = 0.02). CONCLUSIONS: With 19.6 yr of follow-up, LTADT was not significantly associated with increased CVM in men with locally advanced prostate cancer. Patients may have increased MI mortality with LTADT, particularly those with baseline CVD. Overall, there remained a prostate cancer mortality benefit and no OS detriment with LTADT. PATIENT SUMMARY: In a long-term analysis of a large randomized prostate cancer trial, radiation with 28 mo of hormone therapy did not increase the risk of cardiovascular death significantly versus 4 mo of hormone therapy. Future studies are needed for patients with pre-existing heart disease, who may have an increased risk of myocardial infarction death with longer hormone use.

Effects of Androgen Deprivation Therapy on Prostate Cancer Outcomes According to Competing Event Risk: Secondary Analysis of a Phase 3 Randomised Trial.

BACKGROUND: Previous studies indicate that the benefit of short-term androgen deprivation therapy (ADT) with radiotherapy (RT) for prostate cancer depends on competing risks. OBJECTIVE: To determine whether a quantitative method to stratify patients by risk for competing events (omega score) could identify subgroups that selectively benefit from ADT. DESIGN, SETTING, AND PARTICIPANTS: An ancillary analysis of NRG/RTOG 9408 phase 3 trial (NCT00002597) involving 1945 prostate cancer patients was conducted. INTERVENTION: Short-term ADT. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: We applied generalised competing event regression models incorporating age, performance status, comorbidity, T category, Gleason score (GS), and prostate-specific antigen (PSA), to stratify patients according to relative hazards for primary cancer-related events (distant metastasis or prostate cancer death) versus competing noncancer mortality. We tested interactions between ADT and subgroups defined by standard risk criteria versus relative risk (RR) using the omega score. RESULTS AND LIMITATIONS: T2b, higher GS, and higher PSA were associated with an increased RR for cancer-related versus competing mortality events (a higher omega score); increased age and comorbidity were associated with a decreased omega score. Of 996 patients with low-risk/favourable intermediate-risk (FIR) disease, 286 (28.7%) had a high omega score (≥0.314). Of 768 patients with unfavourable intermediate-risk disease, 175 (22.8%) had a low omega score. The overall discordance in risk classification was 26.1%. Both standard criteria and omega score identified significant interactions for the effect of ADT on cancer-related events and late mortality in low- versus high-risk subgroups. Within the low-risk/FIR subgroup, a higher omega score identified patients in whom ADT significantly reduced cancer events and improved event-free survival. Limitations are the need for external/prospective validation and lower RT doses than contemporary standards. CONCLUSIONS: Stratification based on competing event risk is useful for identifying prostate cancer patients who selectively benefit from ADT. PATIENT SUMMARY: We analysed the effectiveness of androgen deprivation therapy (ADT) for localised prostate cancer among patients, defined by the relative risk (RR) for cancer versus noncancer events. Among patients with traditional low-risk/favourable intermediate-risk disease, those with a higher RR benefitted from short-term ADT.

Analysis of a Biopsy-Based Genomic Classifier in High-Risk Prostate Cancer: Meta-Analysis of the NRG Oncology/Radiation Therapy Oncology Group 9202, 9413, and 9902 Phase 3 Randomized Trials.

PURPOSE: Decipher is a genomic classifier (GC) prospectively validated postprostatectomy. We validated the performance of the GC in pretreatment biopsy samples within the context of 3 randomized phase 3 high-risk definitive radiation therapy trials. METHODS AND MATERIALS: A prespecified analysis plan (NRG-GU-TS006) was approved to obtain formalin-fixed paraffin-embedded tissue from biopsy specimens from the NRG biobank from patients enrolled in the NRG/Radiation Therapy Oncology Group (RTOG) 9202, 9413, and 9902 phase 3 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 for the GC for distant metastases (DM), and secondary for prostate cancer-specific mortality (PCSM) and overall survival (OS) with Cox univariable and multivariable analyses. RESULTS: GC scores were obtained on 385 samples, of which 265 passed microarray quality control (69%) and had a median follow-up of 11 years (interquartile range, 9-13). In the pooled cohort, on univariable analysis, the GC was shown to be a prognostic factor for DM (per 0.1 unit; subdistribution hazard ratio [sHR], 1.29; 95% confidence interval [CI], 1.18-1.41; P < .001), PCSM (sHR, 1.28; 95% CI, 1.16-1.41; P < .001), and OS (hazard ratio [HR], 1.16; 95% CI, 1.08-1.22; P < .001). On multivariable analyses, the GC (per 0.1 unit) was independently associated with DM (sHR, 1.22; 95% CI, 1.09-1.36), PCSM (sHR, 1.23; 95% CI, 1.09-1.39), and OS (HR, 1.12; 95% CI, 1.05-1.20) after adjusting for age, Prostate Specific Antigen, Gleason score, cT stage, trial, and randomized treatment arm. GC had similar prognostic ability in patients receiving short-term or long-term androgen-deprivation therapy, but the absolute improvement in outcome varied by GC risk. CONCLUSIONS: This is the first validation of a gene expression biomarker on pretreatment prostate cancer 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.

Analysis of MRE11 and Mortality Among Adults With Muscle-Invasive Bladder Cancer Managed With Trimodality Therapy.

Importance: Bladder-preserving trimodality therapy can be an effective alternative to radical cystectomy for treatment of muscle-invasive bladder cancer (MIBC), but biomarkers are needed to guide optimal patient selection. The DNA repair protein MRE11 is a candidate response biomarker that has not been validated in prospective cohorts using standardized measurement approaches. Objective: To evaluate MRE11 expression as a prognostic biomarker in MIBC patients receiving trimodality therapy using automated quantitative image analysis. Design, Setting, and Participants: This prognostic study analyzed patients with MIBC pooled from 6 prospective phase I/II, II, or III trials of trimodality therapy (Radiation Therapy Oncology Group [RTOG] 8802, 8903, 9506, 9706, 9906, and 0233) across 37 participating institutions in North America from 1988 to 2007. Eligible patients had nonmetastatic MIBC and were enrolled in 1 of the 6 trimodality therapy clinical trials. Analyses were completed August 2020. Exposures: Trimodality therapy with transurethral bladder tumor resection and cisplatin-based chemoradiation therapy. Main Outcomes and Measures: MRE11 expression and association with disease-specific (bladder cancer) mortality (DSM), defined as death from bladder cancer. Pretreatment tumor tissues were processed for immunofluorescence with anti-MRE11 antibody and analyzed using automated quantitative image analysis to calculate a normalized score for MRE11 based on nuclear-to-cytoplasmic (NC) signal ratio. Results: Of 465 patients from 6 trials, 168 patients had available tissue, of which 135 were analyzable for MRE11 expression (median age of 65 years [minimum-maximum, 34-90 years]; 111 [82.2%] men). Median (minimum-maximum) follow-up for alive patients was 5.0 (0.6-11.7) years. Median (Q1-Q3) MRE11 NC signal ratio was 2.41 (1.49-3.34). Patients with an MRE11 NC ratio above 1.49 (ie, above first quartile) had a significantly lower DSM (HR, 0.50; 95% CI, 0.26-0.93; P = .03). The 4-year DSM was 41.0% (95% CI, 23.2%-58.0%) for patients with an MRE11 NC signal ratio of 1.49 or lower vs 21.0% (95% CI, 13.4%-29.8%) for a ratio above 1.49. MRE11 NC signal ratio was not significantly associated with overall survival (HR, 0.84; 95% CI, 0.49-1.44). Conclusions and Relevance: Higher MRE11 NC signal ratios were associated with better DSM after trimodality therapy. Lower MRE11 NC signal ratios identified a poor prognosis subgroup that may benefit from intensification of therapy.

Sensitizing brain metastases to stereotactic radiosurgery using hyperbaric oxygen: A proof-of-principle study.

PURPOSE: Increased oxygen levels may enhance the radiosensitivity of brain metastases treated with stereotactic radiosurgery (SRS). This project administered hyperbaric oxygen (HBO) prior to SRS to assess feasibility, safety, and response. METHODS: 38 patients were studied, 19 with 25 brain metastases treated with HBO prior to SRS, and 19 historical controls with 27 metastases, matched for histology, GPA, resection status, and lesion size. Outcomes included time from HBO to SRS, quality-of-life (QOL) measures, local control, distant (brain) metastases, radionecrosis, and overall survival. RESULTS: The average time from HBO chamber to SRS beam-on was 8.3 ± 1.7 minutes. Solicited adverse events (AEs) were comparable between HBO and control patients; no grade III or IV serious AEs were observed. Radionecrosis-free survival (RNFS), radionecrosis-free survival before whole-brain radiation therapy (WBRT) (RNBWFS), local recurrence-free survival before WBRT (LRBWFS), distant recurrence-free survival before WBRT (DRBWFS), and overall survival (OS) were not significantly different for HBO patients and controls on Kaplan-Meier analysis, though at 1-year estimated survival rates trended in favor of SRS + HBO: RNFS - 83% vs 60%; RNBWFS - 78% vs 60%; LRBWFS - 95% vs 78%; DRBWFS - 61% vs 57%; and OS - 73% vs 56%. Multivariate Cox models indicated no significant association between HBO treatment and hazards of RN, local or distant recurrence, or mortality; however, these did show statistically significant associations (p < 0.05) for: local recurrence with higher volume, radionecrosis with tumor resection, overall survival with resection, and overall survival with higher GPA. CONCLUSION: Addition of HBO to SRS for brain metastases is feasible without evident decrement in radiation necrosis and other clinical outcomes.

Adding Short-Term Androgen Deprivation Therapy to Radiation Therapy in Men With Localized Prostate Cancer: Long-Term Update of the NRG/RTOG 9408 Randomized Clinical Trial.

PURPOSE: For men with localized prostate cancer, NRG Oncology/Radiation Therapy Oncology Group (RTOG) 9408 demonstrated that adding short-term androgen deprivation therapy (ADT) to radiation therapy (RT) improved the primary endpoint of overall survival (OS) and improved disease-specific mortality (DSM), biochemical failure (BF), local progression, and freedom from distant metastases (DM). This study was performed to determine whether the short-term ADT continued to improve OS, DSM, BF, and freedom from DM with longer follow-up. METHODS AND MATERIALS: From 1994 to 2001, NRG/RTOG 9408 randomized 2028 men from 212 North American institutions with T1b-T2b, N0 prostate adenocarcinoma and prostate-specific antigen (PSA) ≤20ng/mL to RT alone or RT plus short-term ADT. Patients were stratified by PSA, tumor grade, and surgical versus clinical nodal staging. ADT was flutamide with either goserelin or leuprolide for 4 months. Prostate RT (66.6 Gy) was started after 2 months. OS was calculated at the date of death from any cause or at last follow-up. Secondary endpoints were DSM, BF, local progression, and DM. Acute and late toxic effects were assessed using RTOG toxicity scales. RESULTS: Median follow-up in surviving patients was 14.8 years (range, 0.16-21.98). The 10-year and 18-year OS was 56% and 23%, respectively, with RT alone versus 63% and 23% with combined therapy (HR 0.94; 95% confidence interval [CI], 0.85-1.05; P = .94). The hazards were not proportional (P = .003). Estimated restricted mean survival time at 18 years was 11.8 years (95% CI, 11.4-12.1) with combined therapy versus 11.3 years with RT alone (95% CI, 10.9-11.6; P = .05). The 10-year and 18-year DSM was 7% and 14%, respectively, with RT alone versus 3% and 8% with combined therapy (HR 0.56; 95% CI, 0.41-0.75; P < .01). DM and BF favored combined therapy at 18 years. Rates of late grade ≥3 hepatic, gastrointestinal, and genitourinary toxicity were ≤1%, 3%, and 8%, respectively, with combined therapy versus ≤1%, 2%, and 5% with RT alone. CONCLUSIONS: Further follow-up demonstrates that OS converges at approximately 15 years, by which point the administration of 4 months of ADT had conferred an estimated additional 6 months of life.

Randomized Phase III Trial Evaluating Radiation Following Surgical Excision for Good-Risk Ductal Carcinoma In Situ: Long-Term Report From NRG Oncology/RTOG 9804.

PURPOSE: To our knowledge, NRG/RTOG 9804 is the only randomized trial to assess the impact of whole breast irradiation (radiation therapy [RT]) versus observation (OBS) in women with good-risk ductal carcinoma in situ (DCIS), following lumpectomy. Long-term results focusing on ipsilateral breast recurrence (IBR), the primary outcome, are presented here. PATIENTS AND METHODS: Eligible patients underwent lumpectomy for DCIS that was mammogram detected, size ≤ 2.5 cm, final margins ≥ 3 mm, and low or intermediate nuclear grade. Consented patients were randomly assigned to RT or OBS. Tamoxifen use was optional. Cumulative incidence was used to estimate IBR, log-rank test and Gray's test to compare treatments, and Fine-Gray regression for hazard ratios (HRs). RESULTS: A total of six hundred thirty-six women were randomly assigned from 1999 to 2006. Median age was 58 years and mean pathologic DCIS size was 0.60 cm. Intention to use tamoxifen was balanced between arms (69%); however, actual receipt of tamoxifen varied, 58% RT versus 66% OBS (P = .05). At 13.9 years' median follow-up, the 15-year cumulative incidence of IBR was 7.1% (95% CI, 4.0 to 11.5) with RT versus 15.1% (95% CI, 10.8 to 20.2) OBS (P = .0007; HR = 0.36; 95% CI, 0.20 to 0.66); and for invasive LR was 5.4% (95% CI, 2.7 to 9.5) RT versus 9.5% (95% CI, 6.0 to 13.9) OBS (P = .027; HR = 0.44; 95% CI, 0.21 to 0.91). On multivariable analysis, only RT (HR = 0.34; 95% CI, 0.19 to 0.64; P = .0007) and tamoxifen use (HR = 0.45; 95% CI, 0.25 to 0.78; P = .0047) were associated with reduced IBR. CONCLUSION: RT significantly reduced all and invasive IBR for good-risk DCIS with durable results at 15 years. These results are not an absolute indication for RT but rather should inform shared patient-physician treatment decisions about ipsilateral breast risk reduction in the long term following lumpectomy.

ACR-ABS-ACNM-ASTRO-SIR-SNMMI practice parameter for selective internal radiation therapy or radioembolization for treatment of liver malignancies.

PURPOSE: The American College of Radiology (ACR), American Brachytherapy Society (ABS), American College of Nuclear Medicine (ACNM), American Society for Radiation Oncology (ASTRO), Society of Interventional Radiology (SIR), and Society of Nuclear Medicine and Molecular Imaging (SNMMI) have jointly developed a practice parameter on selective internal radiation therapy (SIRT) or radioembolization for treatment of liver malignancies. Radioembolization is the embolization of the hepatic arterial supply of hepatic primary tumors or metastases with a microsphere yttrium-90 brachytherapy device. MATERIALS AND METHODS: The ACR -ABS -ACNM -ASTRO -SIR -SNMMI practice parameter for SIRT or radioembolization for treatment of liver malignancies was revised in accordance with the process described on the ACR website (https://www.acr.org/ClinicalResources/Practice-Parameters-and-Technical-Standards) by the Committee on Practice Parameters-Interventional and Cardiovascular Radiology of the ACR Commission on Interventional and Cardiovascular, Committee on Practice Parameters and Technical Standards-Nuclear Medicine and Molecular Imaging of the ACR Commission on Nuclear Medicine and Molecular Imaging and the Committee on Practice Parameters-Radiation Oncology of the ACR Commission on Radiation Oncology in collaboration with ABS, ACNM, ASTRO, SIR, and SNMMI. RESULTS: This practice parameter is developed to serve as a tool in the appropriate application of radioembolization in the care of patients with conditions where indicated. It addresses clinical implementation of radioembolization including personnel qualifications, quality assurance standards, indications, and suggested documentation. CONCLUSIONS: This practice parameter is a tool to guide clinical use of radioembolization. It focuses on the best practices and principles to consider when using radioemboliozation effectively. The clinical benefit and medical necessity of the treatment should be tailored to each individual patient.

ACR-ASTRO Practice Parameter for Communication: Radiation Oncology.

AIM/OBJECTIVES/BACKGROUND: Timely, accurate, and effective communications are critical to quality in contemporary medical practices. Radiation oncology incorporates the science and technology of complex integrated radiation treatment delivery and the art of managing individual patients. Through written physical and/or electronic reports and direct communication, radiation oncologists convey critical information regarding patient care, services provided, and quality of care. Applicable practice parameters need to be revised periodically regarding medical record documentation for professional and technical components of services delivered. METHODS: The ACR-ASTRO Practice Parameter for Communication: Radiation Oncology was revised according to the process described on the American College of Radiology (ACR) Web site ("The Process for Developing ACR Practice Parameters and Technical Standards," www.acr.org/ClinicalResources/Practice-Parametersand-Technical-Standards) by the Committee on Practice Parameters of the ACR Commission on Radiation Oncology in collaboration with the American Society for Radiation Oncology (ASTRO). Both societies then reviewed and approved the document. RESULTS: This practice parameter addresses radiation oncology communications in general, including (a) medical record, (b) electronic, and (c) doctor-patient communications, as well as specific documentation for radiation oncology reports such as (a) consultation, (b) clinical treatment management notes (including inpatient communication), (c) treatment (completion) summary, and (d) follow-up visits. CONCLUSIONS: The radiation oncologist's participation in the multidisciplinary management of patients is reflected in timely, medically appropriate, and informative communication with the referring physician and other members of the health care team. The ACR-ASTRO Practice Parameter for Communication: Radiation Oncology is an educational tool designed to assist practitioners in providing appropriate communication regarding radiation oncology care for patients.

ACR-ASTRO Practice Parameter for Image-guided Radiation Therapy (IGRT).

AIM/OBJECTIVES/BACKGROUND: The American College of Radiology (ACR) and the American Society for Radiation Oncology (ASTRO) have jointly developed the following practice parameter for image-guided radiation therapy (IGRT). IGRT is radiation therapy that employs imaging to maximize accuracy and precision throughout the entire process of treatment delivery with the goal of optimizing accuracy and reliability of radiation therapy to the target, while minimizing dose to normal tissues. METHODS: The ACR-ASTRO Practice Parameter for IGRT was revised according to the process described on the ACR website ("The Process for Developing ACR Practice Parameters and Technical Standards," www.acr.org/ClinicalResources/Practice-Parametersand-Technical-Standards) by the Committee on Practice Parameters of the ACR Commission on Radiation Oncology in collaboration with the ASTRO. Both societies then reviewed and approved the document. RESULTS: This practice parameter is developed to serve as a tool in the appropriate application of IGRT in the care of patients with conditions where radiation therapy is indicated. It addresses clinical implementation of IGRT including personnel qualifications, quality assurance standards, indications, and suggested documentation. CONCLUSIONS: This practice parameter is a tool to guide clinical use of IGRT and does not make recommendations on site-specific IGRT directives. It focuses on the best practices and principles to consider when using IGRT effectively, especially with the significant increase in imaging data that is now available with IGRT. The clinical benefit and medical necessity of the imaging modality and frequency of IGRT should be assessed for each patient.

ACR-ASTRO Practice Parameter for the Performance of Stereotactic Body Radiation Therapy.

AIM/OBJECTIVES/BACKGROUND: To standardize the practice of stereotactic body radiation therapy (SBRT), the American College of Radiology (ACR) and the American Society for Radiation Oncology (ASTRO) cooperatively developed the practice parameter for SBRT. SBRT is a treatment technique that delivers radiation dose to a well-defined extracranial target in 5 fractions or less and usually employs a higher dose per fraction than used in conventional radiation. METHODS: The ACR-ASTRO Practice Parameter for the Performance of Stereotactic Body Radiation Therapy was revised according to the process described on the ACR website ("The Process for Developing ACR Practice Parameters and Technical Standards," www.acr.org/ClinicalResources/Practice-Parameters-and-Technical-Standards) by the Committee on Practice Parameters of the ACR Commission on Radiation Oncology in collaboration with the ASTRO. Both societies then reviewed and approved the document. RESULTS: Given the complexities of SBRT, a separate document was created to develop a technical standard for the medical physics of SBRT (ACR-AAPM Technical Standard for Medical Physics Performance Monitoring of Stereotactic Body Radiation Therapy). Workflow, qualifications and responsibilities of personnel, specifications, documentation, quality control/safety/improvement, simulation/treatment, and follow-up were addressed in this practice parameter. CONCLUSIONS: This practice parameter assists practitioners in providing safe and appropriate SBRT treatment and care for patients when clinically indicated. As technologies and techniques continue to evolve, this document will be reviewed, revised and renewed accordingly to a 5 year or sooner timeline specified by the ACR.

Modified Goldilocks Design with strict type I error control in confirmatory clinical trials.

Goldilocks Design (GD) utilizes predictive probability to adaptively select a trial's sample size based on accumulating data. In order to control type I error at a desired level for a subset of the null space, extensive simulations at the study design stage are required to choose critical values, which is a challenge for this type of Bayesian adaptive design to be used for confirmatory trials. In this article, we propose a Modified Goldilocks Design (MGD) where type I error is analytically controlled over the entire null space. We do so by applying the conditional invariance principle and a combination test approach on [Formula: see text]-values that are obtained from independent cohorts of subjects. Simulation studies show that despite analytic control of type I error rate, the proposed MGD has similar power when compared with the original GD. We further apply it to an example trial with time-to-event endpoint in oncology.

ACR-ASTRO Practice Parameter for the Performance of Proton Beam Radiation Therapy.

AIM/OBJECTIVES/BACKGROUND: The American College of Radiology (ACR) and the American Society for Radiation Oncology (ASTRO) have jointly developed the following practice parameter for proton beam radiation therapy. Proton radiotherapy is the application of a high-energy proton beam to a patient in a clinical setting with therapeutic intent. Proton radiotherapy may permit improved therapeutic ratios with lower doses to sensitive normal structures and greater dose to target tumor tissues. METHODS: A literature search was performed to identify published articles regarding clinical outcomes, reviews, quality assurance methodologies, and guidelines and standards for proton radiation therapy. Selected articles are referenced in the text. The following recommendations are based on firsthand experiences of multiple clinical authorities who employ proton therapy and have been peer reviewed by experts at different practicing institutions. RESULTS: This practice parameter is developed to serve as a tool in the appropriate application of this evolving technology in the care of cancer patients or other patients with conditions where radiation therapy is indicated. It addresses clinical implementation of proton radiation therapy, including personnel qualifications, quality assurance standards, indications, and suggested documentation. CONCLUSIONS: This practice parameter is a tool to guide technical use of proton therapy and does not assess the relative clinical indication of proton radiotherapy when compared with other forms of radiotherapy, but to focus on the best practices required to deliver proton therapy safely and effectively, when clinically indicated. Costs of proton treatments are high, and the economic costs of proton radiotherapy may also need to be considered.