Depression and anxiety are associated with an increased risk of infection, revision, and reoperation following total hip or knee arthroplasty.

The aim of this study was to determine the prevalence of depressive and anxiety disorders prior to total hip (THA) and total knee arthroplasty (TKA) and to assess their impact on the rates of any infection, revision, or reoperation. Between January 2000 and March 2019, 21,469 primary and revision arthroplasties (10,011 THAs; 11,458 TKAs), which were undertaken in 15,504 patients at a single academic medical centre, were identified from a 27-county linked electronic medical record (EMR) system. Depressive and anxiety disorders were identified by diagnoses in the EMR or by using a natural language processing program with subsequent validation from review of the medical records. Patients with mental health diagnoses other than anxiety or depression were excluded. Depressive and/or anxiety disorders were common before THA and TKA, with a prevalence of 30% in those who underwent primary THA, 33% in those who underwent revision THA, 32% in those who underwent primary TKA, and 35% in those who underwent revision TKA. The presence of depressive or anxiety disorders was associated with a significantly increased risk of any infection (primary THA, hazard ratio (HR) 1.5; revision THA, HR 1.9; primary TKA, HR 1.6; revision TKA, HR 1.8), revision (THA, HR 1.7; TKA, HR 1.6), re-revision (THA, HR 2.0; TKA, HR 1.6), and reoperation (primary THA, HR 1.6; revision THA, HR 2.2; primary TKA, HR 1.4; revision TKA, HR 1.9; p < 0.03 for all). Patients with preoperative depressive and/or anxiety disorders were significantly less likely to report "much better" joint function after primary THA (78% vs 87%) and primary TKA (86% vs 90%) compared with those without these disorders at two years postoperatively (p < 0.001 for all). The presence of depressive or anxiety disorders prior to primary or revision THA and TKA is common, and associated with a significantly higher risk of infection, revision, reoperation, and dissatisfaction. This topic deserves further study, and surgeons may consider mental health optimization to be of similar importance to preoperative variables such as diabetic control, prior to arthroplasty.

Normative Femoral and Tibial Lengths in a Modern Population of Twenty-First-Century U.S. Children.

BACKGROUND: The Green-Anderson (GA) leg-length data remain the gold standard for the age-based assessment of leg lengths in children despite their methodologic weaknesses. We aimed to summarize current growth trends among a cross-sectional cohort of modern U.S. children using quantile regression methods and to compare the median femoral and tibial lengths of the modern U.S. children with those of the GA cohort. METHODS: A retrospective review of scanograms and upright slot-scanning radiographs obtained in otherwise healthy children between 2008 and 2020 was completed. A search of a radiology registry revealed 3,508 unique patients between the ages of 2 and 18 years for whom a standard-of-care scanogram or slot-scanning radiograph had been made. All patients with systemic illness, genetic conditions, or generalized diseases that may affect height were excluded. Measurements from a single leg at a single time point per subject were included, and the latest available time point was used for children who had multiple scanograms made. Quantile regression analysis was used to fit the lengths of the tibia and femur and overall leg length separately for male patients and female patients. RESULTS: Seven hundred patients (328 female and 372 male) met the inclusion criteria. On average, the reported 50th percentile tibial lengths from the GA study at each time point were shorter than the lengths in this study by 2.2 cm (range, 1.4 to 3.3 cm) for boys and 2 cm (range, 1.1 to 3.1 cm) for girls. The reported 50th percentile femoral lengths from the GA study at each time point were shorter than the lengths in this study by 1.8 cm (range, 1.1 to 2.5 cm) for boys and 1.7 cm (range, 0.8 to 2.3 cm) shorter for girls. CONCLUSIONS: This study developed new growth charts for femoral and tibial lengths in a modern U.S. population of children. The new femoral and tibial lengths at nearly all time points are 1 to 3 cm longer than traditional GA data. The use of GA data for epiphysiodesis could result in underestimation of expected childhood growth. LEVEL OF EVIDENCE: Prognostic Level IV . See Instructions for Authors for a complete description of levels of evidence.

The Association Between Preoperative International Normalized Ratio Values and Postoperative Outcomes including Mortality in Geriatric Femoral Neck Fractures Treated With Hemiarthroplasty.

OBJECTIVES: To evaluate the association between preoperative international normalized ratio (INR) and postoperative mortality and other outcomes after hemiarthroplasty for geriatric femoral neck fractures. DESIGN: Retrospective cohort study. SETTING: A single Level-I trauma center. PATIENTS/PARTICIPANTS: Patients ≥55 years of age with OTA/AO 31B proximal femur fractures [1556 patients (1616 hips)]. INTERVENTION: Hip hemiarthroplasty. MAIN OUTCOME MEASUREMENTS: Ninety-day mortality, postoperative transfusion within 72 hours, and 90-day postoperative outcomes. RESULTS: Adjusting for confounders, the association of preoperative INR and 90-day mortality was not statistically significant [hazard ratio (HR): 1.3; 95% confidence interval (CI): 0.97, 1.8; P = 0.08]. Dementia (HR: 1.9; 95% CI: 1.4-2.6; P < 0.001), Charlson Comorbidity Index (HR: 1.1; 95% CI: 1.1-1.2; P < 0.001), and age by decade (HR: 1.4; 95% CI: 1.1-1.8; P = 0.002) were associated with 90-day mortality. Increasing INR was significantly associated with blood transfusion [odds ratio (OR) 1.4; 95% CI 1.03-1.6; P = 0.031]. Preoperative hemoglobin <10 g/dL (OR 13.7; 95% CI 8.4-23.3; P < 0.001) was also associated with a postoperative transfusion, whereas intraoperative tranexamic acid use (OR 0.3; 95% CI 0.2-0.5; P < 0.001) was inversely associated with postoperative transfusion rate. INR was associated with superficial wound infection (HR: 2.0; 95% CI: 1.1-3.7; P = 0.02) and noninfected wound complications (HR: 1.6; 95% CI: 1.1-2.4; P = 0.007). Risk of superficial infection increased when INR was >1.8. CONCLUSION: When controlling for confounders, preoperative INR was not significantly associated with 90-day mortality. Underlying medical conditions contribute to postoperative mortality more than an elevated INR. However, INR is associated with superficial wound complications. This risk becomes statistically significant as INR rises above 1.8. LEVEL OF EVIDENCE: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Epidemiology of Cutaneous Lupus Erythematosus Among Adults Over Four Decades (1976-2018): A Lupus Midwest Network (LUMEN) Study.

OBJECTIVE: To characterize the epidemiological trends and mortality of cutaneous lupus erythematosus (CLE) between 1976 and 2018 in Olmsted County, Minnesota. PATIENTS AND METHODS: In this retrospective population-based cohort study, all incident and prevalent CLE cases among adult residents in Olmsted County, Minnesota, between January 1, 1976, and December 31, 2018, were identified and categorized by subtype through medical record review using the resources of the Rochester Epidemiology Project. RESULTS: The overall incidence rate of CLE between 1976 and 2018 was 3.9 (95% CI, 3.4 to 4.5) per 100,000. The incidence of CLE was relatively stable, with no major trend across sexes or age groups. The age- and sex-adjusted prevalence of CLE was 108.9 per 100,000 on January 1, 2015. Mortality in CLE patients was similar to that of the general population, with a standardized mortality ratio of 1.23 (95% CI, 0.88 to 1.66) with no observed trends in mortality over time. CONCLUSION: In the past 4 decades, the incidence of CLE remained stable. Patients with CLE have mortality comparable to that of the general population.

Rheumatoid Arthritis, Cognitive Impairment, and Neuroimaging Biomarkers: Results from the Mayo Clinic Study of Aging.

BACKGROUND: Observational studies suggested that dementia risk in patients with rheumatoid arthritis (RA) is higher than in the general population. OBJECTIVE: To examine the associations of RA with cognitive decline and dementia, and neuroimaging biomarkers of aging, Alzheimer's disease, and vascular pathology in adult participants in the Mayo Clinic Study of Aging (MCSA). METHODS: Participants with RA were matched 1:3 on age, sex, education, and baseline cognitive diagnosis to participants without RA. RA cases with MRI were also matched with non-cases with available MRI. All available imaging studies (i.e., amyloid and FDG PET, sMRI, and FLAIR) were included. The study included 104 participants with RA and 312 without RA (mean age (standard deviation, SD) 75.0 (10.4) years, 33% male and average follow-up (SD) 4.2 (3.8) years). RESULTS: Groups were similar in cognitive decline and risk of incident dementia. Among participants with neuroimaging, participants with RA (n = 33) and without RA (n = 98) had similar amyloid burden and neurodegeneration measures, including regions sensitive to aging and dementia, but greater mean white matter hyperintensity volume relative to the total intracranial volume (mean (SD)% : 1.12 (0.57)% versus 0.76 (0.69)% of TIV, p = 0.01), and had higher mean (SD) number of cortical infarctions (0.24 (0.44) versus 0.05 (0.33), p = 0.02). CONCLUSION: Although cognitive decline and dementia risk were similar in participants with and without RA, participants with RA had more abnormal cerebrovascular pathology on neuroimaging. Future studies should examine the mechanisms underlying these changes and potential implications for prognostication and prevention of cognitive decline in RA.

Modular Fluted Tapered Stems for Periprosthetic Femoral Fractures: Excellent Results in 171 Cases.

BACKGROUND: Modular fluted tapered (MFT) stems have advanced treatment of Vancouver B2 and B3 periprosthetic femoral fractures, but series to date have been limited with respect to cohort size and follow-up duration. The purpose of this study was to determine implant survivorship, radiographic results, complications, and clinical outcomes of Vancouver B2 and B3 periprosthetic femoral fractures treated with MFT stems in a large series of patients. METHODS: We identified 171 Vancouver B2 (109) and B3 (62) periprosthetic femoral fractures treated with an MFT stem between 2000 and 2018 using our institutional total joint registry. The mean age was 75 years, 50% were female, and the mean body mass index was 29 kg/m2. The median stem diameter was 18 mm and median stem length was 210 mm. The cumulative incidences of revision and reoperation with death as the competing risk were calculated, radiographs were reviewed, and clinical outcomes were evaluated using the Harris hip score (HHS). The mean follow-up was 5 years. RESULTS: The 10-year cumulative incidence of any revision was 10%. There were 17 revisions, of which only 3 were for the distal fluted portion of the MFT stem. Revision indications included periprosthetic joint infection (PJI) (n = 6) and dislocation (n = 11). The 10-year cumulative incidence of any reoperation was 15%. In addition to the above 17 revisions, there were 7 reoperations for superficial wound complications (n = 4), Vancouver B1 periprosthetic femoral fracture (n = 1), vascular occlusion (n = 1), and acetabular cartilage degeneration requiring an acetabular component (n = 1). Radiographically, there was 1 fracture nonunion. All unrevised MFT stems were radiographically well fixed. Subsidence of ≥5 mm occurred in 11%, but all implants were stable at the most recent follow-up. The mean HHS was 75 at 2 years (n = 71). CONCLUSIONS: In this large series of 171 Vancouver B2 and B3 periprosthetic femoral fractures treated with MFT stems, we found that such constructs were associated with a high rate of fracture healing and provided extremely reliable and durable implant fixation, with no revisions for aseptic loosening. Dislocation and PJI were the most common complications. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

COVID-19 Vaccine Uptake Among Patients With Systemic Lupus Erythematosus in the American Midwest: The Lupus Midwest Network (LUMEN).

OBJECTIVE: Patients with systemic lupus erythematosus (SLE) are at higher risk of poor outcomes from coronavirus disease 2019 (COVID-19). The vaccination rate among such patients is unknown. We aimed to assess COVID-19 vaccine uptake among patients with SLE. METHODS: We included 342 patients with SLE from the Lupus Midwest Network (LUMEN) and 350 age-, sex-, race-, and county-matched comparators. Vaccination uptake for influenza, pneumococcal, and zoster vaccines before pandemic restrictions began (up to February 29, 2020) was assessed. First-dose COVID-19 vaccine uptake was electronically retrieved and manually ascertained (December 15, 2020, to July 31, 2021). Time to COVID-19 vaccination, demographics, SLE manifestations, medications, Charlson Comorbidity Index, Area Deprivation Index, and Rural-Urban Commuting Area codes were compared. RESULTS: On July 31, 2021, 83.3% of patients with SLE and 85.5% of comparators were vaccinated against COVID-19. The COVID-19 vaccination rates were similar among SLE and comparators (hazard ratio 0.93, 95% CI 0.79-1.10). Unvaccinated patients with SLE were more likely than vaccinated patients to be men (27.3% vs 14.1%), younger (mean age 54.1 vs 58.8 yrs), have a shorter SLE duration (median 7.3 vs 10.7 yrs), and be less frequently vaccinated with influenza and pneumococcal vaccines. CONCLUSION: Patients with SLE in the Lupus Midwest Network had similar COVID-19 vaccination uptake as matched comparators, most of whom were vaccinated early when the vaccine became available. One in 6 patients with SLE remain unvaccinated.

Clinical predictors of response to methotrexate in patients with rheumatoid arthritis: a machine learning approach using clinical trial data.

BACKGROUND: Methotrexate is the preferred initial disease-modifying antirheumatic drug (DMARD) for rheumatoid arthritis (RA). However, clinically useful tools for individualized prediction of response to methotrexate treatment in patients with RA are lacking. We aimed to identify clinical predictors of response to methotrexate in patients with rheumatoid arthritis (RA) using machine learning methods. METHODS: Randomized clinical trials (RCT) of patients with RA who were DMARD-naïve and randomized to placebo plus methotrexate were identified and accessed through the Clinical Study Data Request Consortium and Vivli Center for Global Clinical Research Data. Studies with available Disease Activity Score with 28-joint count and erythrocyte sedimentation rate (DAS28-ESR) at baseline and 12 and 24 weeks were included. Latent class modeling of methotrexate response was performed. The least absolute shrinkage and selection operator (LASSO) and random forests methods were used to identify predictors of response. RESULTS: A total of 775 patients from 4 RCTs were included (mean age 50 years, 80% female). Two distinct classes of patients were identified based on DAS28-ESR change over 24 weeks: "good responders" and "poor responders." Baseline DAS28-ESR, anti-citrullinated protein antibody (ACPA), and Health Assessment Questionnaire (HAQ) score were the top predictors of good response using LASSO (area under the curve [AUC] 0.79) and random forests (AUC 0.68) in the external validation set. DAS28-ESR ≤ 7.4, ACPA positive, and HAQ ≤ 2 provided the highest likelihood of response. Among patients with 12-week DAS28-ESR > 3.2, ≥ 1 point improvement in DAS28-ESR baseline-to-12-week was predictive of achieving DAS28-ESR ≤ 3.2 at 24 weeks. CONCLUSIONS: We have developed and externally validated a prediction model for response to methotrexate within 24 weeks in DMARD-naïve patients with RA, providing variably weighted clinical features and defined cutoffs for clinical decision-making.

Rising incidence and prevalence of systemic lupus erythematosus: a population-based study over four decades.

OBJECTIVES: To determine the trends in incidence, prevalence and mortality of systemic lupus erythematosus (SLE) in a US population over four decades. METHODS: We identified all the patients with SLE in Olmsted County, Minnesota who fulfilled the European Alliance of Associations for Rheumatology (EULAR)/American College of Rheumatology (ACR) criteria for SLE during 1976-2018. Age-specific and sex-specific incidence and prevalence rates were adjusted to the standard 2000 projected US population. The EULAR/ACR score was used as a proxy for disease severity. Standardised mortality ratio (SMR) was estimated. RESULTS: There were 188 incident SLE cases in 1976-2018 (mean age 46.3±SD 16.9; 83% women). Overall age-adjusted and sex-adjusted annual SLE incidence per 100 000 population was 4.77 (95% CI 4.09 to 5.46). Incidence was higher in women (7.58) than men (1.89). The incidence rate increased from 3.32 during 1976-1988 to 6.44 during 2009-2018. Incidence rates were higher among the racial and ethnic minority populations than non-Hispanic whites. The EULAR/ACR score did not change significantly over time. Overall prevalence increased from 30.6 in 1985 to 97.4 in 2015. During the study period, there was no improvement in SMR over time (p=0.31). CONCLUSIONS: The incidence and prevalence of SLE are increasing in this US population. The increase in incidence may be at least partially explained by the rising ethnic/racial diversity of the population. There was no evidence that the severity of SLE has changed over time. The survival gap between SLE and the general population remains unchanged. As the US population grows more diverse, we might continue to see an increase in the incidence of SLE.

Transgender health and medicine - Are radiological devices prepared?

BACKGROUND & AIMS: To determine if radiological hard- and software offers options beyond the binary female / male classification. METHODS: We surveyed thirteen radiological hardware and six radiological software vendors about the options to enter patient gender. RESULTS: Six of thirteen hardware and five of six software vendors replied to our inquiry. All vendors except one offered a third option in addition to male / female. CONCLUSION: We found that most hard- and software systems provide with a third option for patient gender. These systems allow radiology personnel to accurately document patient gender in the medical record and contribute to an inclusive patient experience in the radiology department. Registering the biological sex in addition to gender may further improve medical care.

Frank Stinchfield Award: Does Bariatric Surgery Prior to Primary Total Hip Arthroplasty Really Improve Outcomes?

BACKGROUND: Optimal management of morbid obesity before total hip arthroplasty (THA) remains debated. Recently, bariatric procedures have become more common with advancements in surgical techniques. We hypothesized that bariatric surgery prior to primary THA would mitigate acute postoperative complications and improve implant survivorship. METHODS: A retrospective review from 1995 to 2020 identified 88 primary THA procedures in 71 unique patients who previously underwent bariatric surgery (73% Roux-en-Y). This cohort was matched 1:1:1 for age, gender, surgical year, American Society of Anesthesiologists score, and Charlson Comorbidity Index to cohorts of patients with body mass index (BMI) <40 kg/m2 and BMI ≥40 kg/m2. Revisions, reoperations, and acute complications were compared. Subgroup analysis then evaluated historical (pre-2012) relative to contemporary (2012 and after) bariatric procedures. RESULTS: Revision rates for bariatric patients were higher relative to controls with low (hazard ratio [HR] 19, P < .01) and high BMI (HR 8, P < .01). Reoperation rates showed a similar increase for bariatric patients when compared to low (HR 9, P < .01) and high BMI (HR 4, P = .01) patients. Moreover, bariatric patients had an increased dislocation risk compared to the low (HR 7, P = .03) and high BMI (HR 17, P < .01) patients. Contemporary bariatric techniques had similar complications, revisions, and reoperations relative to historical procedures. CONCLUSION: Morbidly obese patients undergoing THA have increased risks of certain complications, but it is unclear if bariatric surgery improves this risk. This study found that patients undergoing bariatric surgery have worse implant survivorship and higher dislocation rates compared to patients with naturally low and high BMIs. Further investigation into the post-bariatric metabolic state is warranted. LEVEL OF EVIDENCE: Prognostic Level IV.

Does Bariatric Surgery Prior to Primary Total Knee Arthroplasty Improve Outcomes?

BACKGROUND: Recent advancements in bariatric surgical techniques have increased its utilization for the management of morbid obesity prior to total knee arthroplasty (TKA). We hypothesized that bariatric surgery prior to primary TKA would mitigate postoperative complications and improve implant survivorship. METHODS: A retrospective review from 1992-2020 identified 205 bariatric surgery patients with subsequent primary TKA. This cohort was matched 1:1:1 to patients without bariatric surgery and with BMI <40 kg/m2 and BMI ≥40 kg/m2. Revisions, reoperations, and 90-day complications were evaluated. Subgroup analysis evaluated bariatric patients with BMI >40 kg/m2 at TKA, the time between surgeries, and compared historical to contemporary bariatric techniques. RESULTS: Bariatric patients demonstrated higher revision rates than low (HR 4, P < .01) and high BMI (HR 9, P < .01) controls, and increased reoperations when compared to the low (HR 2, P < .01) and high BMI (HR 6, P < .01) groups. Reoperation for instability was more common in bariatric patients than low (HR 15, P = .01) and high BMI (HR 17, P < .01) groups. Reoperation for infection was higher in bariatric patients relative to the high BMI (HR 6, P = .03), but not the low BMI cohort (HR 3, P = .06). There was no difference in 90-day complications (P = .33). Bariatric patients with high BMI and contemporary bariatric procedures did not significantly impact complications or survivorship, but bariatric surgery >2 years before TKA was associated with higher revision rates (P = .01). CONCLUSION: This study found that bariatric surgery patients who undergo primary TKA have worse implant survivorship, mostly related to infection and instability. Further investigation into perioperative optimization is warranted. LEVEL OF EVIDENCE: Prognostic Level IV.

Incidence, prevalence and mortality of chronic periaortitis: a population-based study.

OBJECTIVES: To evaluate the epidemiology, presentation and outcomes of patients with chronic periaortitis from 1998 through 2018. METHODS: An inception cohort of patients with incident chronic periaortitis from January 1, 1998 through December 31, 2018, in Olmsted County, Minnesota was identified based on comprehensive individual medical record review utilising the Rochester Epidemiology Project medical record linkage system. Inclusion required radiographic and/or histologic confirmation of periarterial soft tissue thickening around at least part of the infra-renal abdominal aorta or the common iliac arteries. Data were collected on demographic characteristics, clinical presentation, renal and radiographic outcomes, and mortality. Incidence rates were age and sex adjusted to the 2010 United States white population. RESULTS: Eleven incident cases of chronic periaortitis were identified during the study period. Average age at diagnosis was 61.8±13.4 years. The cohort included 9 men (82%) and 2 women (18%). Age- and sex-adjusted incidence rates per 100,000 population were 0.26 for females, 1.56 for males and 0.87 overall. Overall prevalence on January 1, 2015 was 8.98 per 100,000 population. Median (IQR) length of follow-up was 10.1 (2.5, 13.8) years. Overall mortality was similar to the expected age, sex, and calendar estimates of the Minnesota population with standardised mortality ratio (95% CI) for the entire cohort 2.07 (0.67, 4.84). CONCLUSIONS: This study reports the first epidemiologic data on chronic periaortitis in the United States. In this cohort of patients with chronic periaortitis, men were 4 times more commonly affected than women. Mortality was not increased compared to the general population.

Outcomes of Frozen Oocyte Donor In Vitro Fertilization (IVF) Cycles Using Fresh Versus Frozen Sperm.

The ability to use frozen sperm for insemination during in vitro fertilization (IVF) is crucial for patients and for reproductive endocrinologists. However, concerns exist regarding the effects of cryopreservation on sperm quality and IVF outcomes. This study compares outcomes of frozen donor oocyte IVF cycles with intracytoplasmic sperm injection (ICSI) of good quality fresh versus frozen ejaculated sperm. Patients who underwent their first frozen donor oocyte IVF cycle between 2013 and 2019 at Mayo Clinic were identified. The primary outcome was live birth rate (LBR). Secondary outcomes included fertilization rate (FR), blastocyst development rate (BR), and clinical pregnancy rate (CPR). Twenty-six patients used fresh sperm and 19 patients utilized frozen sperm; there were no significant demographic differences between the groups. There were no significant differences noted in CPR, FR, and BR. Although the LBR was not statistically different when frozen versus fresh sperm was utilized (52.6% vs. 61.5%, p = 0.55), there was a distinct trend towards improved outcomes with fresh sperm that may be clinically significant. This data suggests that frozen sperm may be an alternative to a fresh sample, however fresh sperm may ultimately be a better option. This finding should be further explored with studies utilizing a larger sample size.

Randomized Study of Maintenance Pemetrexed Versus Observation for Treatment of Malignant Pleural Mesothelioma: CALGB 30901.

BACKGROUND: The role of maintenance therapy for malignant pleural mesothelioma (MPM) is unknown. We performed a randomized phase II trial to determine if continuation of pemetrexed after first-line pemetrexed and platinum would improve progression-free survival (PFS). PATIENTS AND METHODS: Eligible patients with unresectable MPM, without disease progression following 4 to 6 cycles of pemetrexed and platinum were randomized 1:1 to observation or continuation of pemetrexed until progression, stratified by number of cycles (< 6 or 6), cis- or carboplatin containing regimen, and histology. Study size was calculated based on the assumption that observation would produce a median PFS of 3 months and pemetrexed would yield median PFS of 6 months. RESULTS: A total of 72 patients were registered from December 2010 to June 2016. The study closed early after 53 patients were randomized; 49 eligible (22 on the observation arm and 27 on the pemetrexed arm) were included in the analysis. The median PFS was 3 months (95% confidence interval [CI], 2.6-11.9 months) on observation and 3.4 months (95% CI, 2.8-9.8 months) on pemetrexed (hazard ratio [HR], 0.99; 95% CI, 0.51-1.90; P = .9733). The median overall survival (OS) was 11.8 months (95% CI, 9.3-28.7 months) for observation, and 16.3 months (95% CI, 10.5-26.0 months) for pemetrexed (HR, 0.86; 95% CI, 0.44-1.71; P = .6737). Grade 3 or 4 toxicities on the pemetrexed arm included anemia (8%), lymphopenia (8%), neutropenia (4%), and fatigue (4%). A higher baseline level of soluble mesothelin-related peptide was associated with worse PFS (HR, 1.86; 95% CI, 1.00-3.46; P = .049). CONCLUSION: Maintenance pemetrexed following initial pemetrexed and platinum chemotherapy does not improve PFS in patients with MPM.

Phase II Single-Arm Study of Preoperative Letrozole for Estrogen Receptor-Positive Postmenopausal Ductal Carcinoma In Situ: CALGB 40903 (Alliance).

PURPOSE: Primary endocrine therapy for ductal carcinoma in situ (DCIS) as a potential alternative to surgery has been understudied. This trial explored the feasibility of a short-term course of letrozole and sought to determine whether treatment results in measurable radiographic and biologic changes in estrogen receptor (ER)-positive DCIS. PATIENTS AND METHODS: A phase II single-arm multicenter cooperative-group trial was conducted in postmenopausal patients diagnosed with ER-positive DCIS without invasion. Patients were treated with letrozole 2.5 mg per day for 6 months before surgery. Breast magnetic resonance imaging (MRI) was obtained at baseline, 3 months, and 6 months. The primary end point was change in 6-month MRI enhancement volume compared with baseline. RESULTS: Overall, 79 patients were enrolled and 70 completed 6 months of letrozole. Of these, 67 patients had MRI data available for each timepoint. Baseline MRI volumes ranged from 0.004 to 26.3 cm3. Median reductions from baseline MRI volume (1.4 cm3) were 0.6 cm3 (61.0%) at 3 months (P < .001) and 0.8 cm3 (71.7%) at 6 months (P < .001). Consistent reductions were seen in median baseline ER H-score (228; median reduction, 15.0; P = .005), progesterone receptor H-score (15; median reduction, 85.0; P < .001), and Ki67 score (12%; median reduction, 6.3%; P = .007). Of the 59 patients who underwent surgery per study protocol, persistent DCIS remained in 50 patients (85%), invasive cancer was detected in six patients (10%), and no residual DCIS or invasive cancer was seen in nine patients (15%). CONCLUSIONS: In a cohort of postmenopausal women with ER-positive DCIS, preoperative letrozole resulted in significant imaging and biomarker changes. These findings support future trials of extended endocrine therapy as primary nonoperative treatment of some DCIS.