Adding 6 months of androgen deprivation therapy to postoperative radiotherapy for prostate cancer: a comparison of short-course versus no androgen deprivation therapy in the RADICALS-HD randomised controlled trial.

BACKGROUND: Previous evidence indicates that adjuvant, short-course androgen deprivation therapy (ADT) improves metastasis-free survival when given with primary radiotherapy for intermediate-risk and high-risk localised prostate cancer. However, the value of ADT with postoperative radiotherapy after radical prostatectomy is unclear. METHODS: RADICALS-HD was an international randomised controlled trial to test the efficacy of ADT used in combination with postoperative radiotherapy for prostate cancer. Key eligibility criteria were indication for radiotherapy after radical prostatectomy for prostate cancer, prostate-specific antigen less than 5 ng/mL, absence of metastatic disease, and written consent. Participants were randomly assigned (1:1) to radiotherapy alone (no ADT) or radiotherapy with 6 months of ADT (short-course ADT), using monthly subcutaneous gonadotropin-releasing hormone analogue injections, daily oral bicalutamide monotherapy 150 mg, or monthly subcutaneous degarelix. Randomisation was done centrally through minimisation with a random element, stratified by Gleason score, positive margins, radiotherapy timing, planned radiotherapy schedule, and planned type of ADT, in a computerised system. The allocated treatment was not masked. The primary outcome measure was metastasis-free survival, defined as distant metastasis arising from prostate cancer or death from any cause. Standard survival analysis methods were used, accounting for randomisation stratification factors. The trial had 80% power with two-sided α of 5% to detect an absolute increase in 10-year metastasis-free survival from 80% to 86% (hazard ratio [HR] 0·67). Analyses followed the intention-to-treat principle. The trial is registered with the ISRCTN registry, ISRCTN40814031, and ClinicalTrials.gov, NCT00541047. FINDINGS: Between Nov 22, 2007, and June 29, 2015, 1480 patients (median age 66 years [IQR 61-69]) were randomly assigned to receive no ADT (n=737) or short-course ADT (n=743) in addition to postoperative radiotherapy at 121 centres in Canada, Denmark, Ireland, and the UK. With a median follow-up of 9·0 years (IQR 7·1-10·1), metastasis-free survival events were reported for 268 participants (142 in the no ADT group and 126 in the short-course ADT group; HR 0·886 [95% CI 0·688-1·140], p=0·35). 10-year metastasis-free survival was 79·2% (95% CI 75·4-82·5) in the no ADT group and 80·4% (76·6-83·6) in the short-course ADT group. Toxicity of grade 3 or higher was reported for 121 (17%) of 737 participants in the no ADT group and 100 (14%) of 743 in the short-course ADT group (p=0·15), with no treatment-related deaths. INTERPRETATION: Metastatic disease is uncommon following postoperative bed radiotherapy after radical prostatectomy. Adding 6 months of ADT to this radiotherapy did not improve metastasis-free survival compared with no ADT. These findings do not support the use of short-course ADT with postoperative radiotherapy in this patient population. FUNDING: Cancer Research UK, UK Research and Innovation (formerly Medical Research Council), and Canadian Cancer Society.

Editorial Commentary: High Tibial Osteotomy and Distal Femoral Osteotomy Address Biologics and Biomechanics.

Osteotomies were historically a common treatment for knee osteoarthritis. This has given way to arthroplasty in many patients. However, osteotomies are still an excellent treatment for younger patients with malignment and joint pain. High tibial and distal femoral osteotomy are both mechanical and biological surgeries. Osteotomies about the knee result in both mechanical correction and modulation of the inflammatory environment in the joint resulting from correction of malalignment. This reinforces their importance in the treatment of the knee joint as an organ in which a complex interplay of factors is required for homeostasis. Osteotomy is a critical part of comprehensive treatment of young patients with knee pain, malignment, and cartilage disorders.

Abiraterone acetate plus prednisolone with or without enzalutamide for patients with metastatic prostate cancer starting androgen deprivation therapy: final results from two randomised phase 3 trials of the STAMPEDE platform protocol.

BACKGROUND: Abiraterone acetate plus prednisolone (herein referred to as abiraterone) or enzalutamide added at the start of androgen deprivation therapy improves outcomes for patients with metastatic prostate cancer. Here, we aimed to evaluate long-term outcomes and test whether combining enzalutamide with abiraterone and androgen deprivation therapy improves survival. METHODS: We analysed two open-label, randomised, controlled, phase 3 trials of the STAMPEDE platform protocol, with no overlapping controls, conducted at 117 sites in the UK and Switzerland. Eligible patients (no age restriction) had metastatic, histologically-confirmed prostate adenocarcinoma; a WHO performance status of 0-2; and adequate haematological, renal, and liver function. Patients were randomly assigned (1:1) using a computerised algorithm and a minimisation technique to either standard of care (androgen deprivation therapy; docetaxel 75 mg/m2 intravenously for six cycles with prednisolone 10 mg orally once per day allowed from Dec 17, 2015) or standard of care plus abiraterone acetate 1000 mg and prednisolone 5 mg (in the abiraterone trial) orally or abiraterone acetate and prednisolone plus enzalutamide 160 mg orally once a day (in the abiraterone and enzalutamide trial). Patients were stratified by centre, age, WHO performance status, type of androgen deprivation therapy, use of aspirin or non-steroidal anti-inflammatory drugs, pelvic nodal status, planned radiotherapy, and planned docetaxel use. The primary outcome was overall survival assessed in the intention-to-treat population. Safety was assessed in all patients who started treatment. A fixed-effects meta-analysis of individual patient data was used to compare differences in survival between the two trials. STAMPEDE is registered with ClinicalTrials.gov (NCT00268476) and ISRCTN (ISRCTN78818544). FINDINGS: Between Nov 15, 2011, and Jan 17, 2014, 1003 patients were randomly assigned to standard of care (n=502) or standard of care plus abiraterone (n=501) in the abiraterone trial. Between July 29, 2014, and March 31, 2016, 916 patients were randomly assigned to standard of care (n=454) or standard of care plus abiraterone and enzalutamide (n=462) in the abiraterone and enzalutamide trial. Median follow-up was 96 months (IQR 86-107) in the abiraterone trial and 72 months (61-74) in the abiraterone and enzalutamide trial. In the abiraterone trial, median overall survival was 76·6 months (95% CI 67·8-86·9) in the abiraterone group versus 45·7 months (41·6-52·0) in the standard of care group (hazard ratio [HR] 0·62 [95% CI 0·53-0·73]; p<0·0001). In the abiraterone and enzalutamide trial, median overall survival was 73·1 months (61·9-81·3) in the abiraterone and enzalutamide group versus 51·8 months (45·3-59·0) in the standard of care group (HR 0·65 [0·55-0·77]; p<0·0001). We found no difference in the treatment effect between these two trials (interaction HR 1·05 [0·83-1·32]; pinteraction=0·71) or between-trial heterogeneity (I2 p=0·70). In the first 5 years of treatment, grade 3-5 toxic effects were higher when abiraterone was added to standard of care (271 [54%] of 498 vs 192 [38%] of 502 with standard of care) and the highest toxic effects were seen when abiraterone and enzalutamide were added to standard of care (302 [68%] of 445 vs 204 [45%] of 454 with standard of care). Cardiac causes were the most common cause of death due to adverse events (five [1%] with standard of care plus abiraterone and enzalutamide [two attributed to treatment] and one (<1%) with standard of care in the abiraterone trial). INTERPRETATION: Enzalutamide and abiraterone should not be combined for patients with prostate cancer starting long-term androgen deprivation therapy. Clinically important improvements in survival from addition of abiraterone to androgen deprivation therapy are maintained for longer than 7 years. FUNDING: Cancer Research UK, UK Medical Research Council, Swiss Group for Clinical Cancer Research, Janssen, and Astellas.

Technical development and validation of a clinically applicable microenvironment classifier as a biomarker of tumour hypoxia for soft tissue sarcoma.

BACKGROUND: Soft tissue sarcomas (STS) are rare, heterogeneous tumours and biomarkers are needed to inform management. We previously derived a prognostic tumour microenvironment classifier (24-gene hypoxia signature). Here, we developed/validated an assay for clinical application. METHODS: Technical performance of targeted assays (Taqman low-density array, nanoString) was compared in 28 prospectively collected formalin-fixed, paraffin-embedded (FFPE) biopsies. The nanoString assay was biologically validated by comparing to HIF-1α/CAIX immunohistochemistry (IHC) in clinical samples. The Manchester (n = 165) and VORTEX Phase III trial (n = 203) cohorts were used for clinical validation. The primary outcome was overall survival (OS). RESULTS: Both assays demonstrated excellent reproducibility. The nanoString assay detected upregulation of the 24-gene signature under hypoxia in vitro, and 16/24 hypoxia genes were upregulated in tumours with high CAIX expression in vivo. Patients with hypoxia-high tumours had worse OS in the Manchester (HR 3.05, 95% CI 1.54-5.19, P = 0.0005) and VORTEX (HR 2.13, 95% CI 1.19-3.77, P = 0.009) cohorts. In the combined cohort, it was independently prognostic for OS (HR 2.24, 95% CI 1.42-3.53, P = 0.00096) and associated with worse local recurrence-free survival (HR 2.17, 95% CI 1.01-4.68, P = 0.04). CONCLUSIONS: This study comprehensively validates a microenvironment classifier befitting FFPE STS biopsies. Future uses include: (1) selecting high-risk patients for perioperative chemotherapy; and (2) biomarker-driven trials of hypoxia-targeted therapies.

Abiraterone acetate and prednisolone with or without enzalutamide for high-risk non-metastatic prostate cancer: a meta-analysis of primary results from two randomised controlled phase 3 trials of the STAMPEDE platform protocol.

BACKGROUND: Men with high-risk non-metastatic prostate cancer are treated with androgen-deprivation therapy (ADT) for 3 years, often combined with radiotherapy. We analysed new data from two randomised controlled phase 3 trials done in a multiarm, multistage platform protocol to assess the efficacy of adding abiraterone and prednisolone alone or with enzalutamide to ADT in this patient population. METHODS: These open-label, phase 3 trials were done at 113 sites in the UK and Switzerland. Eligible patients (no age restrictions) had high-risk (defined as node positive or, if node negative, having at least two of the following: tumour stage T3 or T4, Gleason sum score of 8-10, and prostate-specific antigen [PSA] concentration ≥40 ng/mL) or relapsing with high-risk features (≤12 months of total ADT with an interval of ≥12 months without treatment and PSA concentration ≥4 ng/mL with a doubling time of <6 months, or a PSA concentration ≥20 ng/mL, or nodal relapse) non-metastatic prostate cancer, and a WHO performance status of 0-2. Local radiotherapy (as per local guidelines, 74 Gy in 37 fractions to the prostate and seminal vesicles or the equivalent using hypofractionated schedules) was mandated for node negative and encouraged for node positive disease. In both trials, patients were randomly assigned (1:1), by use of a computerised algorithm, to ADT alone (control group), which could include surgery and luteinising-hormone-releasing hormone agonists and antagonists, or with oral abiraterone acetate (1000 mg daily) and oral prednisolone (5 mg daily; combination-therapy group). In the second trial with no overlapping controls, the combination-therapy group also received enzalutamide (160 mg daily orally). ADT was given for 3 years and combination therapy for 2 years, except if local radiotherapy was omitted when treatment could be delivered until progression. In this primary analysis, we used meta-analysis methods to pool events from both trials. The primary endpoint of this meta-analysis was metastasis-free survival. Secondary endpoints were overall survival, prostate cancer-specific survival, biochemical failure-free survival, progression-free survival, and toxicity and adverse events. For 90% power and a one-sided type 1 error rate set to 1·25% to detect a target hazard ratio for improvement in metastasis-free survival of 0·75, approximately 315 metastasis-free survival events in the control groups was required. Efficacy was assessed in the intention-to-treat population and safety according to the treatment started within randomised allocation. STAMPEDE is registered with ClinicalTrials.gov, NCT00268476, and with the ISRCTN registry, ISRCTN78818544. FINDINGS: Between Nov 15, 2011, and March 31, 2016, 1974 patients were randomly assigned to treatment. The first trial allocated 455 to the control group and 459 to combination therapy, and the second trial, which included enzalutamide, allocated 533 to the control group and 527 to combination therapy. Median age across all groups was 68 years (IQR 63-73) and median PSA 34 ng/ml (14·7-47); 774 (39%) of 1974 patients were node positive, and 1684 (85%) were planned to receive radiotherapy. With median follow-up of 72 months (60-84), there were 180 metastasis-free survival events in the combination-therapy groups and 306 in the control groups. Metastasis-free survival was significantly longer in the combination-therapy groups (median not reached, IQR not evaluable [NE]-NE) than in the control groups (not reached, 97-NE; hazard ratio [HR] 0·53, 95% CI 0·44-0·64, p<0·0001). 6-year metastasis-free survival was 82% (95% CI 79-85) in the combination-therapy group and 69% (66-72) in the control group. There was no evidence of a difference in metatasis-free survival when enzalutamide and abiraterone acetate were administered concurrently compared with abiraterone acetate alone (interaction HR 1·02, 0·70-1·50, p=0·91) and no evidence of between-trial heterogeneity (I2 p=0·90). Overall survival (median not reached [IQR NE-NE] in the combination-therapy groups vs not reached [103-NE] in the control groups; HR 0·60, 95% CI 0·48-0·73, p<0·0001), prostate cancer-specific survival (not reached [NE-NE] vs not reached [NE-NE]; 0·49, 0·37-0·65, p<0·0001), biochemical failure-free-survival (not reached [NE-NE] vs 86 months [83-NE]; 0·39, 0·33-0·47, p<0·0001), and progression-free-survival (not reached [NE-NE] vs not reached [103-NE]; 0·44, 0·36-0·54, p<0·0001) were also significantly longer in the combination-therapy groups than in the control groups. Adverse events grade 3 or higher during the first 24 months were, respectively, reported in 169 (37%) of 451 patients and 130 (29%) of 455 patients in the combination-therapy and control groups of the abiraterone trial, respectively, and 298 (58%) of 513 patients and 172 (32%) of 533 patients of the combination-therapy and control groups of the abiraterone and enzalutamide trial, respectively. The two most common events more frequent in the combination-therapy groups were hypertension (abiraterone trial: 23 (5%) in the combination-therapy group and six (1%) in control group; abiraterone and enzalutamide trial: 73 (14%) and eight (2%), respectively) and alanine transaminitis (abiraterone trial: 25 (6%) in the combination-therapy group and one (<1%) in control group; abiraterone and enzalutamide trial: 69 (13%) and four (1%), respectively). Seven grade 5 adverse events were reported: none in the control groups, three in the abiraterone acetate and prednisolone group (one event each of rectal adenocarcinoma, pulmonary haemorrhage, and a respiratory disorder), and four in the abiraterone acetate and prednisolone with enzalutamide group (two events each of septic shock and sudden death). INTERPRETATION: Among men with high-risk non-metastatic prostate cancer, combination therapy is associated with significantly higher rates of metastasis-free survival compared with ADT alone. Abiraterone acetate with prednisolone should be considered a new standard treatment for this population. FUNDING: Cancer Research UK, UK Medical Research Council, Swiss Group for Clinical Cancer Research, Janssen, and Astellas.

Combined Borderline Acetabular Dysplasia and Increased Femoral Anteversion Is Associated With Worse Outcomes in Female Patients Undergoing Hip Arthroscopy for Femoroacetabular Impingement.

PURPOSE: To determine the relationship of increased femoral anteversion and borderline acetabular dysplasia on the outcomes of hip arthroscopy for femoroacetabular impingement in a female cohort of patients. METHODS: This is a retrospective study of female patients undergoing hip arthroscopy for femoroacetabular impingement. All patients had preoperative radiographs and computed tomography scans from which lateral center edge angle (LCEA) and femoral anteversion were measured. Patient outcome was quantified by preoperative and postoperative International Hip Outcome Tool 12-item instrument (iHOT-12). All patients had follow-up at 2 to 4 years postoperatively. Published values for minimum clinically important difference, substantial clinical benefit (SCB), patient acceptable symptomatic state (PASS), and a normal or abnormal hip were used to determine outcome as well as the final score and delta of the iHOT-12. RESULTS: There were 243 female patients included in the cohort (83% follow-up) who had iHOT-12 scores at 2- to 4-year follow-up (mean 36.9 months). Female patients with combined LCEA ≤25° and femoral anteversion >20° had lower final IHOT-12 scores (P = .001) and delta iHOT-12 (P = .010) and were less likely to achieve a normal hip (P = .013), minimum clinically important difference (P = .018), SCB (P < .001), or PASS (P < .001) and more likely to have an abnormal hip (P = .002). In addition, patients with an LCEA ≤25° and normal femoral version were less likely to achieve a normal hip (P = .013), SCB (P < .001), and PASS (P < .001) compared with those with normal acetabular coverage (all P < .05). There was no difference in these outcome measures between the groups with an LCEA >25° with or without increased femoral version. CONCLUSIONS: Female patients with femoral anteversion >20° and borderline acetabular dysplasia did poorly after hip arthroscopy. However, those with increased femoral anteversion and normal acetabular coverage had outcomes similar to control hips. LEVEL OF EVIDENCE: Level IV, case series.

Survival outcomes in endometrial cancer patients according to diabetes: a systematic review and meta-analysis.

BACKGROUND: Diabetes is an established risk factor for endometrial cancer development but its impact on prognosis is unclear and epidemiological studies to date have produced inconsistent results. We aimed to conduct the first systematic review and meta-analysis to compare survival outcomes in endometrial cancer patients with and without pre-existing diabetes. METHODS: We conducted a systematic search of MEDLINE, EMBASE and Web of Science databases up to February 2022 for observational studies that investigated the association between pre-existing diabetes and cancer-specific survival in endometrial cancer patients. Secondary outcomes included overall survival and progression or recurrence-free survival. Quality assessment of included studies was undertaken using the Newcastle-Ottawa Scale and a random-effects model was used to produce pooled hazard ratios (HRs) and 95% confidence intervals (CIs). (PROSPERO 2020 CRD42020196088). RESULTS: In total, 31 studies were identified comprising 55,475 endometrial cancer patients. Pooled results suggested a worse cancer-specific survival in patients with compared to patients without diabetes (n = 17 studies, HR 1.15, 95% CI 1.00-1.32, I2 = 62%). Similar results were observed for progression or recurrence-free survival (n = 6 studies, HR 1.23, 95% CI 1.02-1.47, I2 = 0%) and for overall survival (n = 24 studies, HR 1.42, 95% CI 1.31-1.54, I2 = 46%). CONCLUSION: In this systematic review and meta-analysis, we show that diabetes is associated with a worse cancer-specific and overall survival in endometrial cancer patients.

How Common Is Femoral Retroversion and How Is it Affected by Different Measurement Methods in Unilateral Slipped Capital Femoral Epiphysis?

BACKGROUND: Although femoral retroversion has been linked to the onset of slipped capital femoral epiphysis (SCFE), and may result from a rotation of the femoral epiphysis around the epiphyseal tubercle leading to femoral retroversion, femoral version has rarely been described in patients with SCFE. Furthermore, the prevalence of actual femoral retroversion and the effect of different measurement methods on femoral version angles has yet to be studied in SCFE. QUESTIONS/PURPOSES: (1) Do femoral version and the prevalence of femoral retroversion differ between hips with SCFE and the asymptomatic contralateral side? (2) How do the mean femoral version angles and the prevalence of femoral retroversion change depending on the measurement method used? (3) What is the interobserver reliability and intraobserver reproducibility of these measurement methods? METHODS: For this retrospective, controlled, single-center study, we reviewed our institutional database for patients who were treated for unilateral SCFE and who had undergone a pelvic CT scan. During the period in question, the general indication for obtaining a CT scan was to define the surgical strategy based on the assessment of deformity severity in patients with newly diagnosed SCFE or with previous in situ fixation. After applying prespecified inclusion and exclusion criteria, we included 79 patients. The mean age was 15 ± 4 years, 48% (38 of 79) of the patients were male, and 56% (44 of 79) were obese (defined as a BMI > 95th percentile (mean BMI 34 ± 9 kg/m2). One radiology resident (6 years of experience) measured femoral version of the entire study group using five different methods. Femoral neck version was measured as the orientation of the femoral neck. Further measurement methods included the femoral head's center and differed regarding the level of landmarks for the proximal femoral reference axis. From proximal to distal, this included the most-proximal methods (Lee et al. and Reikerås et al.) and most-distal methods (Tomczak et al. and Murphy et al.). Most proximally (Lee et al. method), we used the most cephalic junction of the greater trochanter as the landmark and, most distally, we used the center base of the femoral neck superior to the lesser trochanter (Murphy et al.). The orientation of the distal femoral condyles served as the distal reference axis for all five measurement methods. All five methods were compared side-by-side (involved versus uninvolved hip), and comparisons among all five methods were performed using paired t-tests. The prevalence of femoral retroversion (< 0°) was compared using a chi-square test. A subset of patients was measured twice by the first observer and by a second orthopaedic resident (2 years of experience) to assess intraobserver reproducibility and interobserver reliability; for this assessment, we used intraclass correlation coefficients. RESULTS: The mean femoral neck version was lower in hips with SCFE than in the contralateral side (-2° ± 13° versus 7° ± 11°; p < 0.001). This yielded a mean side-by side difference of -8° ± 11° (95% CI -11° to -6°; p < 0.001) and a higher prevalence of femoral retroversion in hips with SCFE (58% [95% CI 47% to 69%]; p < 0.001) than on the contralateral side (29% [95% CI 19% to 39%]). These differences between hips with SCFE and the contralateral side were higher and ranged from -17° ± 11° (95% CI -20° to -15°; p < 0.001) based on the method of Tomczak et al. to -22° ± 13° (95% CI -25° to -19°; p < 0.001) according to the method of Murphy et al. The mean overall femoral version angles increased for hips with SCFE using more-distal landmarks compared with more-proximal landmarks. The prevalence of femoral retroversion was higher in hips with SCFE for the proximal methods of Lee et al. and Reikerås et al. (91% [95% CI 85% to 97%] and 84% [95% CI 76% to 92%], respectively) than for the distal measurement methods of Tomczak et al. and Murphy et al. (47% [95% CI 36% to 58%] and 60% [95% CI 49% to 71%], respectively [all p < 0.001]). We detected mean differences ranging from -19° to 4° (all p < 0.005) for 8 of 10 pairwise comparisons in hips with SCFE. Among these, the greatest differences were between the most-proximal methods and the more-distal methods, with a mean difference of -19° ± 7° (95% CI -21° to -18°; p < 0.001), comparing the methods of Lee et al. and Tomczak et al. In hips with SCFE, we found excellent agreement (intraclass correlation coefficient [ICC] > 0.80) for intraobserver reproducibility (reader 1, ICC 0.93 to 0.96) and interobserver reliability (ICC 0.95 to 0.98) for all five measurement methods. Analogously, we found excellent agreement (ICC > 0.80) for intraobserver reproducibility (reader 1, range 0.91 to 0.96) and interobserver reliability (range 0.89 to 0.98) for all five measurement methods in healthy contralateral hips. CONCLUSION: We showed that femoral neck version is asymmetrically decreased in unilateral SCFE, and that differences increase when including the femoral head's center. Thus, to assess the full extent of an SCFE deformity, femoral version measurements should consider the position of the displaced epiphysis. The prevalence of femoral retroversion was high in patients with SCFE and increased when using proximal anatomic landmarks. Since the range of femoral version angles was wide, femoral version cannot be predicted in a given hip and must be assessed individually. Based on these findings, we believe it is worthwhile to add evaluation of femoral version to the diagnostic workup of children with SCFE. Doing so may better inform surgeons as they contemplate when to use isolated offset correction or to perform an additional femoral osteotomy for SCFE correction based on the severity of the slip and the rotational deformity. To facilitate communication among physicians and for the design of future studies, we recommend consistently reporting the applied measurement technique. LEVEL OF EVIDENCE: Level III, prognostic study.

Editorial Commentary: Complete Capsular Closure During Hip Arthroscopy Provides the Most Reliable and Durable Outcome . . . Capsule Closed . . . Case Closed!

The management of the hip capsule has been a recent area of controversy in hip arthroscopy. Over the past 5 years, there has been mounting biomechanical and clinical evidence that complete capsular closure is an important step to achieve the best and most durable outcome from hip arthroscopy. Numerous studies in the laboratory have shown that repairing the capsulotomy during simulated hip arthroscopy establishes normal hip biomechanics. Multiple studies have also reported improved clinical outcomes and less conversion to total hip arthroplasty in patients undergoing capsular repair. We have published that patients improve after revision hip arthroscopy for repair of capsular defects. I think it is safe to say that complete capsular closure after hip arthroscopy is becoming the standard of care in our field.

Acetabular Coverage Decreases at the End of Skeletal Growth: A 3DCT Study of Healthy Hips.

BACKGROUND: Abnormalities in size and position of the acetabulum have been linked to both developmental dysplasia of the hip and femoroacetabular impingement. Owing to its 3-dimensional (3D) complexity, plain radiography and cross-sectional studies [computed tomography (CT) and magnetic resonance imaging] have limitations in their ability to capture the complexity of the acetabular 3D anatomy. The goal of the study was to use 3D computed tomography reconstructions to identify the acetabular lunate cartilage and measure its size at varying ages of development and between sexes. METHODS: Patients aged 10 to 18 years with asymptomatic hips and a CT pelvis for appendicitis were reviewed. Patients were stratified by sex and age: preadolescent (10 to 12), young adolescent (13 to 15), and old adolescent (16 to 18) in equal proportions. Materialise 3-matic was used to generate a 3D pelvic model, and the acetabular lunate cartilage surface area was calculated. The lunate cartilage was divided into anatomic segments: superior (11:00 to 1:00), anterior (1:00 to 4:00), and posterior (8:00 to 11:00). The femoral head surface area was calculated to control for patient size. Mixed effects models were generated predicting segment size where side was treated as a repeated measure. Absolute and relative (lunate cartilage to femoral head) models were generated. RESULTS: Sixty-two patients (124 hips) were included. Females showed a significant decrease in femoral head coverage as age increased overall and in the 3 subsegments. The majority of changes occurred between the preadolescent and young adolescent groups. Males did not show an overall change, but the superior and anterior anatomic subgroups showed a significant decrease in coverage between the young and old adolescent groups. Male lunate cartilages were absolutely, but not relatively, larger than females. No clinically significant side-to-side differences were noted. CONCLUSIONS: The relative femoral head coverage by the acetabular lunate cartilage reduced with increasing age, suggesting the growth of the femoral head outpaces the acetabular lunate cartilage's growth. This was more prominent in females. This study has important implications for expected acetabular coverage changes in the latter aspects of pediatric and adolescent development. LEVEL OF EVIDENCE: Level III-diagnostic study.

Abiraterone for Prostate Cancer Not Previously Treated with Hormone Therapy.

BACKGROUND: Abiraterone acetate plus prednisolone improves survival in men with relapsed prostate cancer. We assessed the effect of this combination in men starting long-term androgen-deprivation therapy (ADT), using a multigroup, multistage trial design. METHODS: We randomly assigned patients in a 1:1 ratio to receive ADT alone or ADT plus abiraterone acetate (1000 mg daily) and prednisolone (5 mg daily) (combination therapy). Local radiotherapy was mandated for patients with node-negative, nonmetastatic disease and encouraged for those with positive nodes. For patients with nonmetastatic disease with no radiotherapy planned and for patients with metastatic disease, treatment continued until radiologic, clinical, or prostate-specific antigen (PSA) progression; otherwise, treatment was to continue for 2 years or until any type of progression, whichever came first. The primary outcome measure was overall survival. The intermediate primary outcome was failure-free survival (treatment failure was defined as radiologic, clinical, or PSA progression or death from prostate cancer). RESULTS: A total of 1917 patients underwent randomization from November 2011 through January 2014. The median age was 67 years, and the median PSA level was 53 ng per milliliter. A total of 52% of the patients had metastatic disease, 20% had node-positive or node-indeterminate nonmetastatic disease, and 28% had node-negative, nonmetastatic disease; 95% had newly diagnosed disease. The median follow-up was 40 months. There were 184 deaths in the combination group as compared with 262 in the ADT-alone group (hazard ratio, 0.63; 95% confidence interval [CI], 0.52 to 0.76; P<0.001); the hazard ratio was 0.75 in patients with nonmetastatic disease and 0.61 in those with metastatic disease. There were 248 treatment-failure events in the combination group as compared with 535 in the ADT-alone group (hazard ratio, 0.29; 95% CI, 0.25 to 0.34; P<0.001); the hazard ratio was 0.21 in patients with nonmetastatic disease and 0.31 in those with metastatic disease. Grade 3 to 5 adverse events occurred in 47% of the patients in the combination group (with nine grade 5 events) and in 33% of the patients in the ADT-alone group (with three grade 5 events). CONCLUSIONS: Among men with locally advanced or metastatic prostate cancer, ADT plus abiraterone and prednisolone was associated with significantly higher rates of overall and failure-free survival than ADT alone. (Funded by Cancer Research U.K. and others; STAMPEDE ClinicalTrials.gov number, NCT00268476 , and Current Controlled Trials number, ISRCTN78818544 .).

Editorial Commentary: The First Hip Arthroscopy Is the Best Hip Arthroscopy, Capsular Defect or Not.

Hip arthroscopy has evolved significantly over the last 5 to 10 years. With this comes the burden of patients with continued pain after their index procedure. Reasons for the need for revision surgery can be many, including incomplete resection of impingement morphology, unrecognized/unaddressed acetabular dysplasia or hip instability, failure to manage the soft tissue appropriately (i.e., labrum or capsule/ligament), or other unrecognized cause of pain, like femoral retroversion or subspine impingement. Like many other orthopaedic procedures, revision hip arthroscopy with or without a defect in the hip capsule has significantly worse outcomes at 2 years compared with primary hip arthroscopy. This emphasizes the importance of proper diagnosis, well-done surgery, and proper rehabilitation the first time to avoid the need for revision hip surgery in the young adult altogether.

Periacetabular Osteotomy Improves Pain and Function in Patients With Lateral Center-edge Angle Between 18° and 25°, but Are These Hips Really Borderline Dysplastic?

BACKGROUND: The treatment of mild or borderline acetabular dysplasia is controversial with surgical options including both arthroscopic labral repair with capsular closure or plication and periacetabular osteotomy (PAO). The degree to which improvements in pain and function might be achieved using these approaches may be a function of acetabular morphology and the severity of the dysplasia, but detailed radiographic assessments of acetabular morphology in patients with a lateral center-edge angle (LCEA) of 18° to 25° who have undergone PAO have not, to our knowledge, been performed. QUESTIONS/PURPOSES: (1) Do patients with an LCEA of 18° to 25° undergoing PAO have other radiographic features of dysplasia suggestive of abnormal femoral head coverage by the acetabulum? (2) What is the survivorship free from revision surgery, THA, or severe pain (modified Harris hip score [mHHS] < 70) and proportion of complications as defined by the modified Dindo-Clavien severity scale at minimum 2-year followup? (3) What are the functional patient-reported outcome measures in this cohort at minimum 2 years after surgery as assessed by the UCLA Activity Score, the mHHS, the Hip disability and Osteoarthritis Outcome Score (HOOS), and the SF-12 mental and physical domain scores? METHODS: Between January 2010 and December 2014, a total of 91 patients with hip pain and LCEA of 18° to 25° underwent a hip preservation surgical procedure at our institution. Thirty-six (40%) of the 91 patients underwent hip arthroscopy, and 56 hips (60%) were treated by PAO. In general, patients were considered for hip arthroscopy when symptoms were predominantly associated with femoroacetabular impingement (that is, pain aggravated by sitting and hip flexion activities) and physical examination showed a positive anterior impingement test with negative signs of instability (negative anterior apprehension test). In general, patients were considered for PAO when symptoms suggested instability (that is, pain with upright activities, abductor fatigue now aggravated by sitting) and clinical examinations demonstrated a positive anterior apprehension test. Bilateral surgery was performed in six patients and only the first hip was included in the study. One patient was excluded because PAO was performed to address dysplasia caused by surgical excision of a proximal femoral tumor associated with multiple epiphyseal dysplasia during childhood yielding a total of 49 patients (49 hips). There were 46 of 49 females (94%), the mean age was 26.5 years (± 8), and the mean body mass index was 24 kg/m (± 4.5). Radiographic analysis of preoperative films included the LCEA, Tönnis acetabular roof angle, the anterior center-edge angle, the anterior and posterior wall indices, and the Femoral Epiphyseal Acetabular Roof index. Thirty-nine of the 49 patients (80%) were followed for a minimum 2-year followup (mean, 2.2 years; range, 2-4 years) and were included in the analysis of survivorship after PAO, complications, and functional outcomes. Kaplan-Meier modeling was used to calculate survivorship defined as free from revision surgery, THA, or severe pain (mHHS < 70) at minimum 2 years after surgery. Complications were graded according to the modified Dindo-Clavien severity. Patient-reported outcomes were collected preoperatively and at minimum 2 years after surgery and included the UCLA Activity Score, the mHHS, the HOOS, and the SF-12 mental and physical domain scores. RESULTS: Forty-six of 49 hips (94%) had at least one other radiographic feature of dysplasia suggestive of abnormal femoral head coverage by the acetabulum. Seventy-three percent of the hips (36 of 49) had two or more radiographic features of hip dysplasia aside from a LCEA of 18° to 25°. The survivorship of PAO at minimum 2 years for the 39 of 49 (80%) patients available was 94% (95% confidence interval, 80%-90%). Three of 39 patients (8%) developed a complication. At a mean of 2.2 years of followup, there was improvement in level of activity (preoperative UCLA score 7 ± 2 versus postoperative UCLA score 6 ± 2; p = 0.02). Hip symptoms and function improved postoperatively, as reflected by a higher mean mHHS (86 ± 13 versus 64 ± 19; p < 0.001) and mean HOOS (386 ± 128 versus 261 ± 117; p < 0.001). Quality of life and overall health assessed by the physical domain of the SF-12 improved (47 ± 11 versus 39 ± 12; p < 0.001). However, with the numbers available, no improvement was observed for the mental domain of the SF-12 (52 ± 8 versus 51 ± 11; p = 0.881). CONCLUSIONS: Hips with LCEA of 18° to 25° frequently have other radiographic features of dysplasia suggestive of abnormal femoral head coverage by the acetabulum. These hips may be inappropriately labeled as "borderline" or "mild" dysplasia on consideration of LCEA alone. A more comprehensive imaging analysis in these hips by the radiographic features of dysplasia included in this study is recommended to identify hips with abnormal coverage of the femoral head by the acetabulum and to plan treatment accordingly. Patients with LCEA of 18° to 25° showed improvement in hip pain and function after PAO with minimal complications and low proportions of persistent pain or reoperations at short-term followup. Future studies are recommended to investigate whether the benefits of symptomatic and functional improvement are sustained long term. LEVEL OF EVIDENCE: Level IV, therapeutic study.

What Is the Reliability and Accuracy of Intraoperative Fluoroscopy in Evaluating Anterior, Lateral, and Posterior Coverage During Periacetabular Osteotomy?

BACKGROUND: Periacetabular osteotomy (PAO) is an established treatment for acetabular dysplasia in the skeletally mature individual. Fluoroscopy is used intraoperatively for osteotomy completion and to judge fragment correction. However, a comprehensive study validating fluoroscopy to judge anterior, lateral, and posterior coverage in PAO has not been reported. QUESTIONS/PURPOSES: (1) Are radiographic and fluoroscopic measures of anterior, lateral, and posterior acetabular coverage reliable? (2) Do fluoroscopic measures of fragment correction accurately measure anterior, lateral, and posterior coverage when compared with postoperative radiographs? METHODS: We performed a retrospective study of patients undergoing PAO with a primary diagnosis of acetabular dysplasia. Between 2012 and 2014 two surgeons performed 287 PAOs with fluoroscopy. To be included in this retrospective study, patients had to be younger than 35 years old, have a primary diagnosis of dysplasia (not retroversion, Perthes, or skeletal dysplasia), have adequate radiographic and fluoroscopic imaging, be a primary PAO (not revision), and in the case of bilateral patients, only the first hip operated on in the study period was included. Based on these criteria, 46% of the PAOs performed were included here (133 of 287). A total of 109 (82%) of the patients were females (109 of 133), and the mean age of the patients represented was 24 years (SD, 7 years). Pre- and postoperative standing radiographs as well as intraoperative fluoroscopic images were reviewed and lateral center-edge angle (LCEA), Tönnis angle (TA), anterior center-edge angle (ACEA), anterior wall index (AWI), and posterior wall index (PWI) were measured. Two fellowship-trained hip preservation surgeons completed all measurements with one reader performing a randomized sample of 49 repeat measurements 4 weeks after the initial reading for purposes of calculating intraobserver reliability. Intra- and interrater reliability was assessed using an intraclass correlation coefficient (ICC) model. Agreement between intraoperative fluoroscopic and postoperative radiographic measures was determined by estimating the ICC with 95% confidence intervals and by Bland-Altman analysis. RESULTS: Intrarater reliability was excellent (ICC > 0.75) for all measures and good for postoperative AWI (ICC = 0.72; 95% confidence interval [CI], 0.48-0.85). Interrater reliability was excellent (ICC > 0.75) for all measures except intraoperative TA (ICC = 0.72; 95% CI, 0.48-0.84). Accuracy of fluoroscopy was good (0.60 < ICC < 0.75) for LCEA (ICC = 0.73; 95% CI, 0.55-0.83), TA (ICC = 0.66; 95% CI, 0.41-0.79), AWI (ICC = 0.63; 95% CI, 0.48-0.74), and PWI (ICC = 0.72; 95% CI, 0.35-0.85) and excellent (ICC > 0.75) for ACEA (ICC = 0.80; 95% CI, 0.71-0.86). Bland-Altman analysis for systematic bias in the comparison between intraoperative fluoroscopy and postoperative radiography found the effect of such bias to be negligible (mean difference: LCEA 2°, TA 2°, ACEA 1°, AWI 0.02, PWI 0.11). CONCLUSIONS: Fluoroscopy is accurate in measuring correction in PAO. However, surgeons should take care not to undercorrect the posterior wall. Based on our study, intraoperative fluoroscopy may be used as an alternative to an intraoperative AP pelvis radiograph to judge final acetabular fragment correction with an experienced surgeon. However, more studies are needed including a properly powered direct comparative study of intraoperative fluoroscopy and intraoperative radiographs. Moreover, the impact of radiographic correction achieved during surgery should be studied to determine the implications for patient-reported outcomes and long-term survival of the hip. LEVEL OF EVIDENCE: Level IV, diagnostic study.

Automatic MRI-based Three-dimensional Models of Hip Cartilage Provide Improved Morphologic and Biochemical Analysis.

BACKGROUND: The time-consuming and user-dependent postprocessing of biochemical cartilage MRI has limited the use of delayed gadolinium-enhanced MRI of cartilage (dGEMRIC). An automated analysis of biochemical three-dimensional (3-D) images could deliver a more time-efficient and objective evaluation of cartilage composition, and provide comprehensive information about cartilage thickness, surface area, and volume compared with manual two-dimensional (2-D) analysis. QUESTIONS/PURPOSES: (1) How does the 3-D analysis of cartilage thickness and dGEMRIC index using both a manual and a new automated method compare with the manual 2-D analysis (gold standard)? (2) How does the manual 3-D analysis of regional patterns of dGEMRIC index, cartilage thickness, surface area and volume compare with a new automatic method? (3) What is the interobserver reliability and intraobserver reproducibility of software-assisted manual 3-D and automated 3-D analysis of dGEMRIC indices, thickness, surface, and volume for two readers on two time points? METHODS: In this IRB-approved, retrospective, diagnostic study, we identified the first 25 symptomatic hips (23 patients) who underwent a contrast-enhanced MRI at 3T including a 3-D dGEMRIC sequence for intraarticular pathology assessment due to structural hip deformities. Of the 23 patients, 10 (43%) were male, 16 (64%) hips had a cam deformity and 16 (64%) hips had either a pincer deformity or acetabular dysplasia. The development of an automated deep-learning-based approach for 3-D segmentation of hip cartilage models was based on two steps: First, one reader (FS) provided a manual 3-D segmentation of hip cartilage, which served as training data for the neural network and was used as input data for the manual 3-D analysis. Next, we developed the deep convolutional neural network to obtain an automated 3-D cartilage segmentation that we used as input data for the automated 3-D analysis. For actual analysis of the manually and automatically generated 3-D cartilage models, a dedicated software was developed. Manual 2-D analysis of dGEMRIC indices and cartilage thickness was performed at each "full-hour" position on radial images and served as the gold standard for comparison with the corresponding measurements of the manual and the automated 3-D analysis. We measured dGEMRIC index, cartilage thickness, surface area, and volume for each of the four joint quadrants and compared the manual and the automated 3-D analyses using mean differences. Agreement between the techniques was assessed using intraclass correlation coefficients (ICC). The overlap between 3-D cartilage volumes was assessed using dice coefficients and means of all distances between surface points of the models were calculated as average surface distance. The interobserver reliability and intraobserver reproducibility of the software-assisted manual 3-D and the automated 3-D analysis of dGEMRIC indices, thickness, surface and volume was assessed for two readers on two different time points using ICCs. RESULTS: Comparable mean overall difference and almost-perfect agreement in dGEMRIC indices was found between the manual 3-D analysis (8 ± 44 ms, p = 0.005; ICC = 0.980), the automated 3-D analysis (7 ± 43 ms, p = 0.015; ICC = 0.982), and the manual 2-D analysis.Agreement for measuring overall cartilage thickness was almost perfect for both 3-D methods (ICC = 0.855 and 0.881) versus the manual 2-D analysis. A mean difference of -0.2 ± 0.5 mm (p < 0.001) was observed for overall cartilage thickness between the automated 3-D analysis and the manual 2-D analysis; no such difference was observed between the manual 3-D and the manual 2-D analysis.Regional patterns were comparable for both 3-D methods. The highest dGEMRIC indices were found posterosuperiorly (manual: 602 ± 158 ms; p = 0.013, automated: 602 ± 158 ms; p = 0.012). The thickest cartilage was found anteroinferiorly (manual: 5.3 ± 0.8 mm, p < 0.001; automated: 4.3 ± 0.6 mm; p < 0.001). The smallest surface area was found anteroinferiorly (manual: 134 ± 60 mm; p < 0.001, automated: 155 ± 60 mm; p < 0.001). The largest volume was found anterosuperiorly (manual: 2343 ± 492 mm; p < 0.001, automated: 2294 ± 467 mm; p < 0.001). Mean average surface distance was 0.26 ± 0.13 mm and mean Dice coefficient was 86% ± 3%. Intraobserver reproducibility and interobserver reliability was near perfect for overall analysis of dGEMRIC indices, thickness, surface area, and volume (ICC range, 0.962-1). CONCLUSIONS: The presented deep learning approach for a fully automatic segmentation of hip cartilage enables an accurate, reliable and reproducible analysis of dGEMRIC indices, thickness, surface area, and volume. This time-efficient and objective analysis of biochemical cartilage composition and morphology yields the potential to improve patient selection in femoroacetabular impingement (FAI) surgery and to aid surgeons with planning of acetabuloplasty and periacetabular osteotomies in pincer FAI and hip dysplasia. In addition, this validation paves way to the large-scale use of this method for prospective trials which longitudinally monitor the effect of reconstructive hip surgery and the natural course of osteoarthritis. LEVEL OF EVIDENCE: Level III, diagnostic study.

Editorial Commentary: Acetabular Paralabral Cysts It's All About Location, Location, Location .

With our increased understanding about the causes of young adult hip pain and femoroacetabular impingement, magnetic resonance imaging has become an important diagnostic tool for identifying labral pathology. However, arthroscopic evaluation is paramount to understanding whether a labral tear truly exists in these patients. Orthopaedic dogma suggests that acetabular paralabral cysts form due to an associated acetabular labral tear. Nevertheless, a cause and effect relationship has not yet been proven in the literature. The location of these paralabral cysts may influence the clinical symptoms that they cause and their diagnostic utility. Further work is needed to fully understand the relevance of acetabular paralabral cysts in patients with femoroacetabular impingement.

Slope-reducing tibial osteotomy decreases ACL-graft forces and anterior tibial translation under axial load.

PURPOSE: Posterior tibial slope (PTS) represents an important risk factor for anterior cruciate ligament (ACL) graft failure, as seen in clinical studies. An anterior closing wedge osteotomy for slope reduction was performed to investigate the effect on ACL-graft forces and femoro-tibial kinematics in an ACL-deficient and ACL-reconstructed knee in a biomechanical setup. METHODS: Ten cadaveric knees with a relatively high native slope (mean ± SD): (slope 10° ± 1.4°, age 48.2 years ± 5.8) were selected based on prior CT measurements. A 10° anterior closing-wedge osteotomy was fixed with an external fixator in the ACL-deficient and ACL-reconstructed knee (quadruple Semi-T/Gracilis-allograft). Each condition was randomly tested with both the native tibial slope and the post-osteotomy reduced slope. Axial loads (200 N, 400 N), anterior tibial draw (134 N), and combined loads were applied to the tibia while mounted on a free moving and rotating X-Y table. Throughout testing, 3D motion tracking captured anterior tibial translation (ATT) and internal tibial rotation (ITR). Change of forces on the reconstructed ACL-graft (via an attached load-cell) were recorded, as well. RESULTS: ATT was significantly decreased after slope reduction in the ACL-deficient knee by 4.3 mm ± 3.6 (p < 0.001) at 200 N and 6.2 mm ± 4.3 (p < 0.001) at 400N of axial load. An increase of ITR of 2.3° ±2.8 (p < 0.001) at 200 N and by 4.0° ±4.1 (p < 0.001) at 400 N was observed after the osteotomy. In the ACL-reconstructed knee, ACL-graft forces decreased after slope reduction osteotomy by a mean of 14.7 N ± 9.8 (p < 0.001) at 200 N and 33.8 N ± 16.3 (p < 0.001) at 400N axial load, which equaled a relative decrease by a mean of 17.0% (SD ± 9.8%), and 33.1% (SD ± 18.1%), respectively. ATT and ITR were not significantly changed in the ACL-reconstructed knee. Testing of a tibial anterior drawing force in the ACL-deficient knee led to a significantly increased ATT by 2.7 mm ± 3.6 (p < 0.001) after the osteotomy. The ACL-reconstructed knee did not show a significant change (n.s.) in ATT after the osteotomy. However, ACL-graft forces detected a significant increase by 13.0 N ± 8.3 (p < 0.001) after the osteotomy with a tibial anterior drawer force, whereas the additional axial loading reduced this difference due to the osteotomy (5.3 N ± 12.6 (n.s.)). CONCLUSIONS: Slope-reducing osteotomy decreased anterior tibial translation in the ACL-deficient and ACL-reconstructed knee under axial load, while internal rotation of the tibia increased in the ACL-deficient status after osteotomy. Especially in ACL revision surgery, the osteotomy protects the reconstructed ACL with significantly lower forces on the graft under axial load.

The Natural History of Femoroacetabular Impingement.

BACKGROUND: Structural hip abnormalities have long been suspected of causing hip osteoarthritis. The concept of deformity of the proximal femur as a cause of osteoarthritis (OA) started with description of the tilt deformity and progressed to the pistol grip, then eventually cam-type femoroacetabular impingement (FAI). Acetabular over-coverage or retroversion as a cause of impingement is commonly referred to as pincer-type FAI. The primary research question we asked was: what is the natural history of hips with FAI? METHODS: We reviewed the literature to identify studies with cross-sectional and longitudinal evidence of the effect of FAI on the development of or association with hip OA. RESULTS: In cross-sectional and longitudinal natural history studies of hip OA, cam-type FAI has consistently shown an association with developing OA. In regard to pincer-type FAI, the data are less convincing with some studies suggesting an increased risk and others showing a protective effect of the acetabular over-coverage. It is clear that not all patients with cam FAI get OA but the altered anatomy does increase the relative risk of developing OA. CONCLUSIONS: Cam-type FAI is associated with the development of hip OA; however, there is no role for prophylactic surgery in the asymptomatic hip with the anatomy predisposing to FAI. Further interventional studies are needed to determine whether surgical correction of cam-type FAI in the symptomatic hip alters the natural history of the condition.

Computed Tomography Scans in Patients With Young Adult Hip Pain Carry a Lifetime Risk of Malignancy.

PURPOSE: To calculate the lifetime risk of malignancy in young adult patients with hip pain using 5 different imaging and radiation dose protocols with or without pre- and postoperative computed tomography (CT). METHODS: Radiographic and CT patient radiation doses were retrospectively reviewed. Imaging protocols for hip pain composed of radiographs with or without pre- and postoperative CT scans were modeled and radiation doses were estimated using the PCXMC computer code. Based on these radiation doses, lifetime attributable risks of cancer and mortality for a 10- through 60-year-old male and female were calculated as published by the committee on the Biological Effects of Ionizing Radiation (BEIR) in the BEIR VII report. Relative risks and number needed to harm (NNH) were calculated for each protocol. RESULTS: Based on a review of our institutional database, 2 CT scan doses were used for this study: a high 5.06 mSv and a low 2.86 mSv. Effective doses of radiation ranged from 0.59 to 0.66 mSv for radiographs alone to 10.71 to 10.78 mSv for radiographs and CT both pre- and postoperatively at the higher dose. Lifetime attributable risk of cancer for radiographs alone was 0.006% and 0.011% for a 20-year-old male and female, respectively. Lifetime attributable risk of cancer for radiographs along with pre- and postoperative CT scans at higher dose was 0.105% and 0.177% for a 20-year-old male and female, respectively. Radiographs alone lead to an NNH of 16,667 for males and 9,090 for females, whereas the protocol with pre- and postoperative CT scans at the higher dose led to an NNH of 952 for males and 564 for females. The relative risk of this protocol compared to radiographs alone was 17.5 for males and 16.1 for females. CONCLUSION: Protocols with CT scans of the hip/pelvis pose a small lifetime attributable risk (0.034%-0.177% for a 20-year-old) but a large relative risk (5-17 times) of cancer compared with radiographs alone in the imaging evaluation for hip pain that decreases with increasing age. CLINICAL RELEVANCE: This study illustrates the need for clinicians to understand the imaging protocols used at their institution to understand the risks and benefits of using those protocols in their practice.