Citations

Abstract BACKGROUND: Approximately 50% of newly diagnosed breast cancers are stage 1, with the majority being ER/PR-positive, HER2-negative. Genomic assays such as Oncotype DX® have identified pts with reduced distant metastasis and without benefit from chemotherapy, freeing patients from excess toxicity. Also, these genomic assays are prognostic of local-regional recurrence (LRR). The de-escalation of therapy is of interest to pts, providers, and payers. Low risk, as identified by Oncotype and Mammaprint®, is associated with low LRR after BCS and breast radiotherapy (RT). METHODS: We hypothesize that BCS alone is non-inferior to BCS plus RT for ipsilateral breast recurrence (IBR) and breast preservation in women intending appropriate endocrine therapy (ET) for stage 1 (ER and/or PR positive, HER2-negative, with an Oncotype DX Recurrence Score [RS] of ≤18) breast cancer. Stratification is by age (< 60; ≥60), tumor size (≤1 cm; >1-2cm), and RS (< 11; 11-18). Pts are randomized post-BCS to Arm 1 with breast RT using standard methods (hypo- or conventional-fractionated whole breast RT with or without boost, APBI) plus 5 years of ET (tamoxifen or AI) or Arm 2 with 5 years of ET (tamoxifen or AI) alone. The specific regimen of ET in both arms is at the treating physician’s discretion. Eligible pts are stage 1: pT1 (2 cm), pN0, age ≥50 to < 70 years, s/p BCS with negative margins (no ink on tumor), s/p axillary nodal staging (SNB or ALND), ER and/or PR positive (ASCO/CAP), HER2-negative (ASCO/CAP), and have an Oncotype DX RS of ≤18 (diagnostic core biopsy or resected specimen). Primary endpoint is IBR. Secondary endpoints are breast conservation rate, invasive in-breast recurrence, recurrence-free interval, distant disease-free survival, overall survival, patient-reported breast pain, patient-reported worry about recurrence, and adherence to ET. We assume a clinically acceptable difference in IBR of 4% at 10 years to judge omission of RT as non-inferior (10-year event-free survival for RT group is 95.6% versus 91.6% for the omission-of-RT group). The study is designed to be able to detect non-inferiority with 80% power and a one-sided α=0.025, and assuming that there would be a ramp-up in accrual in the first two years of the study (leveling off in Years 3-5), 1,670 (835 per arm) patients are required to be randomized. Conservative loss to follow-up is 1% per year. Some of the T1a pts screened will have Oncotype DX scores >18, making them ineligible for the study. In the accrual process, pts will be required to register (1,714 patients) to ensure that our final randomized cohort is 1,670 pts. Accrual as of 6-30-2022 is 169 screened and 147 randomized. Contact information: Protocol: CTSU member website: https://www.ctsu.org. NRG Oncology Pgh Clinical Coordinating Dpt: 1-800-477-7227 or ccdPGH@NRGOncology.org. Support: U10CA180868, -180822, UG1CA189867. NCT04852887. Citation Format: Julia White, Reena S. Cecchini, Eleanor E. Harris, Eleftherios (Terry) Mamounas, Daniel Stover, Patricia A. Ganz, Reshma Jagsi, Carmen Bergom, Valérie Théberge, Mahmoud B. El-Tamer, Richard Zellars, Dean A. Shumway, Guang-Pei Chen, Stewart J. Anderson, Thomas B. Julian, Norman Wolmark, Wendy Rea. A phase III trial evaluating De-escalation of Breast Radiation (DEBRA) following breast-conserving surgery (BCS) of stage 1, HR+, HER2-, RS ≤18 breast cancer: NRG-BR007 [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr OT1-12-01.

» Lateral epicondylitis (LE) or tennis elbow is a common cause of elbow pain in the general population, especially women in the fourth and fifth decades of life who participate in repetitive forceful movements involving the wrist and forearm. » The pathogenesis of this overuse injury is believed to start from an overload event leading to a microtear in or near the origin of the extensor carpi radialis brevis that is subsequently prone to additional injury and structural weakness over time. » Treatment of LE often begins with a wide variety of nonoperative modalities including rest, nonsteroidal anti-inflammatory drugs, bracing, and physical therapy. For recalcitrant symptoms, additional nonoperative therapies are implemented; however, there remains a lack of comparative efficacy between these adjunct treatments. » In this article, we examine the available literature regarding nonoperative management of LE and provide supplementary insight into the effectiveness of current modalities.

ABSTRACT Introduction Recent military conflicts have resulted in a significant number of lower extremity injuries to U.S. service members that result in amputation or limb preservation (LP) procedures. Service members receiving these procedures report a high prevalence and deleterious consequences of falls. Very little research exists to improve balance and reduce falls, especially among young active populations such as service members with LP or limb loss. To address this research gap, we evaluated the success of a fall prevention training program for service members with lower extremity trauma by (1) measuring fall rates, (2) quantifying improvements in trunk control, and (3) determining skill retention at 3 and 6 months after training. Materials and Methods Forty-five participants (40 males, mean [±SD] age, 34 ± 8 years) with lower extremity trauma (20 with unilateral transtibial amputation, 6 with unilateral transfemoral amputation, 5 with bilateral transtibial amputation, and 14 with unilateral LP procedures) were enrolled. A microprocessor-controlled treadmill was used to produce task-specific postural perturbations which simulated a trip. The training was conducted over a 2-week period and consisted of six 30-minute sessions. The task difficulty was increased as the participant’s ability progressed. The effectiveness of the training program was assessed by collecting data before training (baseline; repeated twice), immediately after training (0 month), and at 3 and 6 months post-training. Training effectiveness was quantified by participant-reported falls in the free-living environment before and after training. Perturbation-induced recovery step trunk flexion angle and velocity was also collected. Results Participants reported reduced falls and improved balance confidence in the free-living environment following the training. Repeated testing before training revealed that there were no pre-training differences in trunk control. The training program improved trunk control following training, and these skills were retained at 3 and 6 months after training. Conclusion This study showed that task-specific fall prevention training reduced falls across a cohort of service members with diverse types of amputations and LP procedures following lower extremity trauma. Importantly, the clinical outcome of this effort (i.e., reduced falls and improved balance confidence) can lead to increased participation in occupational, recreational, and social activities and thus improved quality of life.

Abstract Background STRIDE-II guidelines recommend endoscopic healing as an important treatment goal in Crohn’s disease (CD). This study evaluated the association of achieving endoscopic outcomes at week 12 and clinical outcomes at week 52 of maintenance treatment in patients with CD treated with upadacitinib (UPA). Methods This post-hoc analysis evaluated data from two Phase 3 UPA induction (U-EXCEED and U-EXCEL) trials and the maintenance (U-ENDURE) trial in patients with moderate to severe CD. Patients who responded to 12-week induction therapy with UPA (45 mg per day [QD]) in U-EXCEED or U-EXCEL and received maintenance therapy with UPA (15 or 30 mg QD) up to 52 weeks in U-ENDURE were included. Clinical outcomes (CD activity index [CDAI] remission, CDAI response, steroid-free CDAI remission, high sensitivity C-reactive protein [hs-CRP] level ≤5 mg/L, and fecal calprotectin level [F-cal] ≤250 mcg/g), were evaluated at week 52 and compared between patients who achieved endoscopic response, endoscopic remission and ulcer-free endoscopy (absence of ulceration) at week 12 and those who did not using Chi-square test. Results Of 337 clinical responders included in the analyses, 152 (45.1%), 87 (25.8%), and 75 (22.3%) patients achieved endoscopic response, endoscopic remission, and ulcer-free endoscopy, respectively, at the end of induction. Significantly more patients who achieved an endoscopic response at end of induction (vs those who did not) attained clinical outcomes at week 52 (CDAI remission, 52.0% vs 34.6%; CDAI response, 54.6% vs 39.5%; hsCRP ≤5 mg/L, 52.0% vs 30.8%; and F-cal ≤250 mcg/g, 42.1% vs 21.6%; P≤0.01, Table 1). Patients who achieved an endoscopic response vs those who did not at end of induction were also more likely to attain steroid-free CDAI remission (50.0% vs 30.9%) at week 52, (P≤0.05, Table 1). Similar findings were observed in patients who achieved endoscopic remission vs those who did not at end of induction (P≤0.01, Table 1). Significantly more patients attained CDAI remission (58.7% vs 37.7%), CDAI response (58.7% vs 42.7%), hsCRP ≤5 mg/L (58.7% vs 35.0%) and F-cal ≤250 mcg/g (50.7% vs 25.0%) at week 52, among patients who achieved ulcer-free endoscopy vs those who did not at end of induction (P≤0.05, Table 1). Conclusion Achieving endoscopic outcomes at end of induction is associated with meaningful improvement in symptoms and inflammatory biomarkers at 52 weeks for patients with CD receiving UPA therapy. Endoscopic remission and ulcer-free endoscopy are associated with very similar long-term benefits.

Abstract Background Small bowel fibrostenotic strictures are common in patients with Crohn’s disease (CD). No global consensus recommendations on definitions, diagnosis and clinical management are available. Methods Several systematic reviews followed by a RAND/University of California Los Angeles appropriateness study on the definitions, diagnosis and clinical management of fibrostenosing CD in clinical practice were performed. A panel of 28 global experts and a patient representative were convened. They assessed a total of 152 candidate items. The items were subsequently evaluated for appropriateness. Results No accurate predictive biomarkers are available for naïve or anastomotic fibrostenosing strictures. Accurate diagnosis of fibrostenosing CD requires cross-sectional imaging which should evaluate bowel wall thickness, luminal narrowing and prestenotic dilatation. A potential inflammatory component should be assessed. Abdominal cross-sectional imaging was considered necessary prior to any treatment decision. The panel proposed an approach to medical, endoscopic, and surgical therapies (Figure 1 and Table 1). Technical characteristics for endoscopic balloon dilation and follow up strategies after successful dilation therapy were identified. Appropriateness, types and performance of different surgical approaches in various settings were evaluated. Conclusion This global consensus provides clinical guidance for the diagnostic and therapeutic management of patients with fibrostenotic CD.