Citations

Abstract Purpose: To evaluate prediction of response and event-free survival (EFS) following neoadjuvant endocrine therapy by SET2,3 index of nonproliferation gene expression related to estrogen and progesterone receptors adjusted for baseline prognosis. Experimental Design: A correlative study was conducted of SET2,3 measured from gene expression profiles of diagnostic tumor (Agilent microarrays) in 379 women with cStage II–III breast cancer from the American College of Surgeons Oncology Group Z1031 neoadjuvant aromatase inhibitor trial SET2,3 was dichotomized using the previously published cutoff. Fisher exact test was used to assess the association between SET2,3 and low proliferation at week 2–4 [Ki67 ≤ 10% or complete cell-cycle arrest (CCCA; Ki67 ≤ 2.7%)] and PEPI-0 rate in cohort B, and the association between SET2,3 and ypStage 0/I in all patients. Cox models were used to assess EFS with respect to SET2,3 excluding cohort B patients who switched to chemotherapy. Results: Patients with high SET2,3 had higher rate of pharmacodynamic response than patients with low SET2,3 (Ki67 ≤ 10% in 88.2% vs. 56.9%, P < 0.0001; CCCA in 50.0% vs. 26.2%, P = 0.0054), but rate of ypStage 0/I (24.0% vs. 20.4%, P = 0.4580) or PEPI = 0 (28.4% vs. 20.6%, P = 0.3419) was not different. Patients with high SET2,3 had longer EFS than patients with low SET2,3 (HR, 0.52, 95% confidence interval: 0.34–0.80; P = 0.0026). Conclusions: This exploratory analysis of Z1031 data demonstrated a higher rate of pharmacodynamic suppression of proliferation and longer EFS in high SET2,3 disease relative to low SET2,3 disease. The ypStage 0/I rate and PEPI = 0 rate were similar with respect to SET2,3.

OBJECTIVE Conventional spinal cord stimulators (SCSs) have demonstrated efficacy in individuals with failed back surgery syndrome (FBSS). However, a subgroup of patients may become refractory to the effects of conventional waveforms over time. The objective of this study was to systematically review and evaluate the current literature on the use of novel waveform spinal cord stimulation for the management of FBSS refractory to conventional SCSs. METHODS A comprehensive electronic search of the literature published in electronic databases, including Ovid MEDLINE and Epub Ahead of Print, Ovid Cochrane Central Register of Controlled Trials, Ovid Cochrane Database of Systematic Reviews, and Scopus, was conducted using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The outcomes of interest were reduction in back pain and/or leg pain after conversion from conventional to novel SCSs. Risk of bias was assessed with the Risk of Bias in Nonrandomized Studies of Interventions (ROBINS-I) tool. The strength of evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) criteria. RESULTS A total of 6 studies with 137 patients with FBSS were identified. Studies were published between 2013 and 2021. The mean ± SD age of the pooled patient sample was 55 ± 10.5 years. All patients who underwent treatment with conventional SCSs were identified. Two studies evaluated the efficacy of high-density spinal cord stimulation, 3 studies evaluated burst spinal cord stimulation, and 1 study assessed multimodal waveforms. The mean difference in back pain scores after conversion from a standard SCS to a novel waveform SCS was 2.55 (95% CI 1.59–4.08), demonstrating a significant reduction in back pain after conversion to novel stimulation. The authors also performed a subgroup analysis to compare burst stimulation to tonic waveforms. In this analysis, the authors found no significant difference in the average reductions in back pain between the 2 groups (p = 0.534).The authors found an I2 statistic equivalent to 98.47% in the meta-regression model used to assess the effect of follow-up duration on study outcome; this value implied that the variability in the data can be attributed to the remaining between-study heterogeneity. The overall certainty was moderate, with a high risk of bias across studies. CONCLUSIONS Rescue therapy with novel waveform spinal cord stimulation is a potential option for pain reduction in patients who become refractory to conventional SCSs. Conversion to novel waveform SCSs may potentially mitigate expenses and complications.

Abstract Introduction: The ALTERNATE trial randomized postmenopausal women with ER Allred 6-8 HER2- breast cancer to 6 months of NET with anastrozole (A), fulvestrant (F) or the combination (A+F). Biopsies were taken preNET and after 4-weeks(wks). Patients with Ki67 values >10% at 4-wks were offered triage to neoadjuvant chemotherapy. Patients with on-treatment Ki67 ≤ 10% who completed NET underwent surgery and Ki67 was reassessed. The primary endpoint was endocrine-sensitive disease rate (ESDR). ESD is defined as pCR or PEPI-0 residual disease (pT1-2, pN0, Ki67 ≤ 2.7%). We previously reported that the ESDR difference between the F-containing arms and the A arm was not >10% (ASCO 2020) and that baseline RNA-seq-based intrinsic subtypes predicted outcomes overall (SABCS 2021). Herein we describe relationships between PAM50 intrinsic subtype and Ki67 values by treatment arm because comparative drug effectiveness in adjuvant endocrine therapy studies in ER+ HER2- breast cancer can be predicted by the degree of Ki67 suppression (PMC3518447). Methods: 743 of the 1297 eligible patients (A: 264; F: 231; A+F: 248) had RNA extracted from preNET frozen tumor biopsies with >50% tumor content and subjected to RNA seq. Intrinsic subtypes were then assigned as LumA, LumB, and NonLum (Basal or HER2-E) using open-source PAM50-based informatics. Differences in the proportion with wk4 Ki67 > 10%, % change in wk4 ki67, and surgical CCCA (Ki67 ≤ 2.7%) rate (sxCCCA) between treatments and by intrinsic subtype was assessed using stratified logistic regression, Wilcoxon rank sum test, and Fisher’s exact test, respectively. Analysis of sxCCCA excluded those who failed to complete NET for reasons other than disease progression or early Ki67 >10%. Results: Amongst the 358 LumA cases there were no significant differences in Ki67-based endpoints between treatments. Among the 292 LumB cases, the wk4 ki67 > 10% rate was lower with A+F (19.4%) than A (43%) (P=0.0002) and was somewhat lower in F (31%) versus A (P=0.076). The % change in wk4 Ki67 in LumB cases, adjusted for baseline Ki67, showed markedly superior suppression for A+F versus A (-90% vs. -77%; P=<0.0001) and versus F (-90% vs. -80%; P=0.0026). Furthermore sxCCCA rates were significantly higher with A+F than A (53% vs. 25% P = <0.0001) and somewhat higher for F (37%) than A (p=0.068), indicating that superior antiproliferative effects for A+F persist after 6 months on therapy. Lack of Ki67 suppression in response to treatment was observed in the majority of 43 NonLum samples regardless of treatment. Conclusion: The combination of A+F was significantly more effective than either drug alone for the control of LumB breast cancer cell proliferation. This suggests that A+F may be a more effective adjuvant endocrine therapy than A alone in LumB disease. The lower Ki67 suppression with A alone also suggests that poorer outcome in some LumB tumors may be due to insufficient ER targeting rather than ER-independent tumor growth Support: U10CA180821, U10CA180882, U24CA196171, UG1CA189856, U10CA180868 (NRG), NCI BIQSFP, BCRF, Genentech, AstraZeneca. https://acknowledgments.alliancefound.org. (MJE) CPRIT RR140033, P50-CA186784, P50-CA58223, U01-CA214125, U24-CA210954, Gift from Ralph and Lisa Eads, McNair Scholarship. ClinicalTrials.gov Identifier: NCT01953588 Citation Format: Matthew J. Ellis, Meenakshi Anurag, Jeremy Hoog, Aranzazu Fernandez-Martinez, Cheng Fan, Richard Gibbs, Souzan Sanati, Kiran Vij, Mark Watson, Travis Dockter, Olwen Hahn, Joseph Guenther, Abigail Caudle, Erica Crouch, Amy Tiersten, Monica Mita, Wajeeha Razaq, Tina J. Hieken, Yang Wang, A. Marilyn Leitch, Gary W. Unzeitig, Eric Winer, Anna Weiss, Kelly Hunt, Ann H. Partridge, Charles M. Perou, Vera Suman, Cynthia X. Ma, Lisa A. Carey. The effect of intrinsic subtype on inhibition of tumor growth by anastrozole vs. fulvestrant vs. the combination: Results from the Alliance neoadjuvant endocrine therapy (NET) ALTERNATE trial [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr CT026.

Renal transplant anastomotic pseudoaneurysms (RTAPs) are a rare vascular postoperative complication. The etiology of these pseudoaneurysms is attributed to infection or surgical vessel damage. RTAPs can lead to allograft dysfunction, allograft loss, or patient mortality due to rupture or sepsis. Because of these serious complications, expedient diagnosis is imperative for initiating surgical intervention and medical management. Sonography is a useful imaging modality for diagnosing and characterizing RTAPs. The sonographic findings, although not often described in detail in the literature, are definitive and unique. This case report describes the sonographic findings of a patient 22 days post renal autotransplant, who presented with excruciating abdominal pain. Sonographic examination identified multiple classic pseudoaneurysm findings and demonstrated intrarenal and extrarenal vascular abnormalities.

Abstract There is great interest in expanding the use of ultrasound (US), but new challenges exist with its application to lumbar facet–targeted procedures. The primary aim of this systematic review and meta-analysis was to determine the risk of incorrect needle placement associated with US–guided lumbar medial branch blocks (MBB) and facet joint injections (FJI) as confirmed by fluoroscopy or computerized tomography (CT). An a priori protocol was registered, and a database search was conducted. Inclusion criteria included all study types. Risk of bias was assessed using the Cochrane risk of bias tool for randomized controlled trials and the National Heart, Lung, and Blood tool for assessing risk bias for observational cohort studies. Pooled analysis of the risk difference (RD) of incorrect needle placement was calculated. Pooled analysis of 7 studies demonstrated an 11% RD (P < 0.0009) of incorrect needle placement for US-guided MBB confirmed using fluoroscopy with and without contrast. Pooled analysis of 3 studies demonstrated a 13% RD (P < 0.0001) of incorrect needle placement for US-guided FJI confirmed using CT. The time to complete a single-level MBB ranged from 2.6 to 5.0 minutes. The certainty of evidence was low to very low. Ultrasound-guided lumbar MBB and FJI are associated with a significant risk of incorrect needle placement when confirmed by fluoroscopy or CT. The technical limitations of US and individual patient factors could contribute to the risk of incorrect needle placement.

AbstractThe development of new technology to treat unmet clinical needs is an important component of modern cardiovascular disease. The need for this has been emphasized in the past several years beginning with the Food and Drug Administration (FDA) guidance document on Early Feasibility Studies in 2012 and then the 21st Century Cures legislation. A number of steps need to be considered in this process by the stakeholders involved including physician innovators and scientists, professional societies such as Society for Cardiovascular Angiography & Interventions, regulatory agencies, and medical device companies. This article focuses on the early iterative steps required to optimize the process and achieve the goal of timely efficient innovation and device development in cardiovascular disease.

Abstract Background Neuropathic pain is a complex condition that can be refractory to conventional management and can cause persistent suffering in patients. Current pharmacologic treatments can provide temporary symptomatic relief; however, the mechanism of these therapies does not address the underlying cause of neuropathic pain. The use of injectable biologics for neuropathic pain has multiple proposed mechanisms for analgesia including attenuation of inflammatory mediated processes, arrest or delay of the degenerative process, inhibition of apoptotic pathways, and augmentation of the survival and recovery of injured and uninjured nerves. Study Design A systematic review of human studies involving the use of injectable biologics for neuropathic pain. Methods A comprehensive search of several data bases including Ovid MEDLINE ® and Epub Ahead of Print, In Process & Other Non-Indexed Citations and Daily, and Ovid Embase from inception to November 24, 2020. Results The initial search yielded 3,450 studies with an additional 6 studies identified through other resources. Twenty-seven studies were included after independent review by two of the investigators. The included studies assessed the efficacy of injectable biologics for the treatment of neuropathic pain defined as pain reduction. Secondary outcome measures included functional improvement as well as safety of the procedures. A qualitative assessment of the literature without meta-analysis was performed due to the heterogeneity of the data. Conclusion According to the GRADE criteria, there is very low certainty of evidence in support of the efficacy of injectable biologics for treatment of neuropathic pain. Future efforts should focus on creating a standardized methodology and study design with respect to preparation, dosage and route of administration of biologics. This will serve as a catalyst for higher quality randomized trials with generation of more useful data to help drive informed clinical decision making.

Abstract Background: There is debate regarding the benefit of breast surgery in women with stage IV breast cancer, especially among those with oligometastatic disease and good response to systemic therapy. Although some retrospective studies have suggested that locoregional therapy may improve survival, this finding has not been universally replicated in randomized controlled trials (RCT) in India, Turkey, and recently the US. To assess need for dissemination of trial results by members of the Alliance/American College of Surgeons Clinical Research Program Dissemination and Implementation (ACS CRP D&I) committee, we sought to determine trends in surgical resection and other therapies for stage IV breast cancer in response to these findings. Methods: The National Cancer Database (NCDB) was queried to identify women diagnosed with clinical stage IV breast cancer of ductal, lobular, or metaplastic histology between 2004-2017. Trends in the rate of women who underwent surgery with breast-conserving surgery (BCS) or mastectomy, radiation, and/or systemic treatments were compared. Possible predictors of breast surgery were examined in univariable and multivariable analysis. Results: We identified 87,331 cases meeting inclusion criteria and assessed demographics for surgery versus no surgery. Of the 87,331 cases, 7,718 (9%) underwent BCS and 17,625 (20%) underwent mastectomy. Rates of breast surgical resection for women with clinically diagnosed stage IV breast cancer rose until 2009, reaching a peak at 37%, followed by a decline to a rate of 18% in 2017 (Table). The largest decline was seen in the hormone receptor positive (HR+) and HER2- subgroup with 71% of patients undergoing surgery in 2007 down to 15% in 2017. Concurrently, the mean number of days between chemotherapy initiation and definitive surgery has been on the rise, ranging from 52 days in 2004 up to 94 days in 2017. In 2004, the rate of systemic therapy alone was slightly more common than locoregional therapy (surgery and/or radiation) with or without systemic therapy (48% vs 37%). By 2017, systemic therapy alone was by far more frequently utilized (69% vs 20%, p&lt;0.001). On multivariable analysis, factors associated with reduced odds of receiving surgery were older age, black race, higher comorbidity index, being uninsured, smaller tumors, lower histologic grade, multiple sites of metastasis, and treatment with chemo-endocrine therapy (all group p values ≤0.001). Factors associated with increased odds of receiving surgery were metaplastic histology, TN subtype, and radiation therapy (all group p values ≤0.001). Conclusions: Rates of surgical resection of the breast primary for stage IV breast cancer have been on the decline in recent years, especially for HR+/HER2- disease, suggesting that providers are responding to the lack of benefit demonstrated in RCTs. Higher rates of surgery in patients with HR-/HER2+ disease and the concurrent rise in the time interval between initiation of systemic therapy and definitive surgical intervention suggest that providers may still be selecting surgery for patients with certain subtypes or those with a durable response to systemic therapy. These areas of continued clinical equipoise could be a target for future studies or de-implementation strategies. OverallHR+/HER2-HER2+TNUnknownSurgery/Total%Surgery/Total%Surgery/Total%Surgery/Total%Surgery/Total%20041189/351334-55-30-50-3420051202/353834-65-35-23-3420061268/375834-54-36-31-3420071571/433636-71-41-32-3620081992/54203754/925926/544820/41491892/52333620092194/592437172/3604883/1525556/106531883/53063520102318/6419361162/331835554/134841352/80144250/9522620112322/6921341220/378932532/144137384/91542186/7762420122238/7110311177/393830587/163536339/85340135/6842020132147/7579281173/423128534/172831334/92536106/6951520142013/8033251086/442825496/185227306/99831125/7551720151805/794323914/434321517/198126288/9962986/6231420161609/819420829/464018459/196823247/10122474/5741320171477/813618722/467815421/190522256/10372578/51615Percent of women with stage IV breast cancer undergoing surgery by year and receptor subtype. Rows containing any number &lt;10 are not reported by subtype to maintain confidentiality, per NCDB guidelines. Citation Format: Sasha R Douglas, Ingrid Lizarraga, Judy C Boughey, Anna Weiss, Kelly Hunt, Diana Dickson-Witmer, Preeti D Subhedar, Ko Un Park, Beiqun Zhao, Sarah Blair. Trends in surgical resection for stage IV breast cancer: Less surgery more systemic treatment [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr PD7-06.

Abstract Background: Neoadjuvant ET (NET) offers an opportunity to assess ET sensitivity for ER+ HER2- BC and potentially to tailor therapy. Ki67 &gt;10% on biopsy after 2-4 weeks (wks) of NET identifies patients (pts) with intrinsic ET resistance; while pathologic complete response (pCR) and modified preoperative endocrine prognostic index of 0 (mPEPI 0: pT1-2N0, Ki67 ≤2.7%) at surgery indicates sensitivity to ET. However, on-NET biopsy is not always acceptable or feasible and delays the ET sensitivity determination. PAM50 ROR score and intrinsic subtypes by tumor RNA profiling are prognostic in pts with early stage ER+ HER2- BC, and predict pCR rates to neoadjuvant chemotherapy (NCT) (PMC2667820). We therefore hypothesized that PAM50 analysis on pre-NET biopsies could predict the likelihood of a) a high on-NET Ki67, b) mPEPI-0 or pCR at surgery and, c) pCR for pts triaged to NCT. Methods: The ALTERNATE trial is a phase III study that randomized postmenopausal pts with clinical stage II/III ER+ (Allred score 6-8) HER2- BC to receive neoadjuvant anastrozole, fulvestrant, or both for 6 months before surgery. Research biopsy was required at pre-NET and wk 4, then optional at wk 12. Pts with Ki67 &gt;10% on biopsy at wk 4 or 12 discontinued NET and were offered NCT. PAM50 intrinsic subtype and ROR-P values were generated from mRNA sequencing (RNASeq) analysis on pre-NET biopsies using open-source informatics (PMC7723687) and evaluated for prediction of on-NET Ki67 &gt;10% at wk 4 or 12, pCR or mPEPI-0 post NET, and pCR post NCT. Results: 749 of 1,297 eligible trial pts were included in the analyses, after excluding 548 pts due to insufficient pre-NET tumor for RNASeq (n=511) or PAM50 normal subtype (n=37). Similar to the entire ALTERNATE population, the rate of Ki67 &gt;10% at wk 4 or 12 was 24.4% (95% CI: 21.4-27.7%) and the rate of mPEPI-0/pCR post NET was 19.8% (95% CI: 17.0-22.8%). There were 393 (52.5%) Lum A, 302 (40.3%) Lum B, and 54 (7.2%) non-Lum (9 Basal, 45 HER2-E) BCs. These included 196 (26.2%) ROR-P low, 354 (47.3%) ROR-P medium and 199 (26.6%) ROR-P high BCs. Both the rates of Ki67 &gt;10% at wk 4 or 12 and mPEPI-0/pCR differed significantly with respect to PAM50 subtype or ROR-P category, such that Lum A or ROR-P low BCs were least likely to have a Ki67 &gt;10% at wk 4 or 12 and most likely to achieve mPEPI-0/pCR (Table). 93 of 168 (55.4%) pts triaged to NCT had RNA-seq results, yielding 26 Lum A, 49 Lum B, 4 Basal and 14 HER2-E, with the pCR rates of 0%, 6.1%, 0%, and 21.4%, respectively. There were 10 ROR-P low, 39 medium, and 44 high tumors, with a pCR rate of 0%, 5.1% and 9.1%, respectively. Conclusion: These data indicate that both baseline ROR-P and intrinsic subtype are predictive of early on-NET Ki67 &gt; 10% and mPEPI 0/pCR at surgery after NET. For pts triaged to NCT based on an early on-NET Ki67 &gt;10%, the HER2-E group had the highest pCR rate (20%) and no pCRs were observed in Lum A. These data may be useful for directing neoadjuvant therapy in postmenopausal pts with ER+ HER2- BC. Support: U10CA180821, U10CA180882, U24CA196171, UG1CA189856, U10CA180868 (NRG), NCI BIQSFP, BCRF, Genentech, AstraZeneca. https://acknowledgments.alliancefound.org. (MJE) CPRIT RR140033, P50CA186784, P50-CA58223, U01 CA214125, U24CA210954, Gift from Ralph and Lisa Eads, McNair Scholarship. Trials.gov Identifier: NCT01953588. Table 1.Rates of Ki67 &gt;10% and mPEPI-0/pCR post NET by PAM50 subtype and ROR-P categoryKi67 &gt;10% at wk 4 or 12mPEPI 0/pCR post NETPAM50 SubtypenYes, n (%)PnNo, n (%)PLum A37251 (13.7%) 95% CI: 10.4-17.6%&lt;0.0001393104 (26.5%) 95%CI: 22.2-31.1%&lt;0.0001Lum B29394 (32.1%) 95% CI: 26.8-37.8%30243 (14.2%) 95%CI: 10.5-18.7%Non-luminal (Basal and HER2-E)5338 (71.7%) 95%CI: 57.6-83.2%541 (1.9%) 95%CI: 0.05-9.9%ROR-P CategorynYes, n (%)PnNo, n (%)PLow18018 (10.0%) 95%CI: 6.0-15.3%&lt;0.000119660 (30.6%) 95%CI: 24.2-37.6%&lt;0.0001Intermediate34474 (21.5%) 95%CI: 17.3-26.2%35471 (20.1%) 95%CI: 16.0-24.6%High19491 (46.9%) 95%CI: 39.7-54.2%19917 (8.5%) 95%CI: 5.1-13.3% Citation Format: Cynthia X Ma, Meenakshi Anurag, Travis Dockter, Jeremy Hoog, Aranzazu Fernandez-Martinez, Cheng Fan, Richard Gibbs, Souzan Sanati, Kiran Vij, Mark Watson, Olwen Hahn, Joseph Guenther, Abigail Caudle, Erika Crouch, Amy Tiersten, Monica Mita, Wajeeha Razaq, Tina J Hieken, Yang Wang, A. Marilyn Leitch, Gary W Unzeitig, Anna Weiss, Eric P Winer, Kelly Hunt, Ann H Partridge, Lisa A Carey, Charles M Perou, Matthew J Ellis, Vera Suman. Pam50 intrinsic subtype and risk of recurrence score (ROR) for the prediction of endocrine (ET) sensitivity and pathologic response to chemotherapy in postmenopausal women with clinical stage II/III estrogen receptor positive (ER+) and HER2 negative (HER2-) breast cancer (BC) in the alternate trial (Alliance A011106) [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr PD9-03.