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1.
Ann Surg ; 2024 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-38814074

RESUMO

OBJECTIVE: An expert panel made recommendations to optimize surgical education and training based on the effects of contemporary challenges. BACKGROUND: The inaugural Blue Ribbon Committee (BRC I) proposed sweeping recommendations for surgical education and training in 2004. In light of those findings, a second BRC (BRC II) was convened to make recommendations to optimize surgical training considering the current landscape in medical education. METHODS: BRC II was a panel of 67 experts selected on the basis of experience and leadership in surgical education and training. It was organized into subcommittees which met virtually over the course of a year. They developed recommendations, along with the Steering Committee, based on areas of focus and then presented them to the entire BRC II. The Delphi Method was chosen to obtain consensus, defined as>80% agreement amongst the panel. Cronbach alpha was computed to assess the internal consistency of three Delphi rounds. RESULTS: Of 50 recommendations, 31 obtained consensus in the following aspects of surgical training (# consensus recommendation /# proposed): Workforce (1/5), Medical Student Education (3/8), Work Life Integration (4/6), Resident Education (5/7), Goals, Structure and Financing of Training (5/8), Education Support and Faculty Development (5/6), Research Training (7/9), and Educational Technology and Assessment (1/1). The internal consistency was good in Rounds 1 and 2 and acceptable in Round 3. CONCLUSIONS: BRC II used the Delphi approach to identify and recommend 31 priorities for surgical education in 2024. We advise establishing a multidisciplinary surgical educational group to oversee, monitor and facilitate implementation of these recommendations.

2.
Ann Surg ; 277(5): e1006-e1017, 2023 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-35796435

RESUMO

OBJECTIVE: To propose a framework for quantification of surgical team familiarity. BACKGROUND: Operating room (OR) teamwork quality is associated with familiarity among team members and their individual specialization. We describe novel measures of OR team familiarity and specialty experience. METHODS: Surgeon-scrub (SS) and surgeon-circulator (SC) teaming scores, defined as the pair's proportion of interactions relative to the surgeon's total cases in the preceding 6 months were calculated between 2017 and 2021 at an academic medical center. Nurse service-line (SL) experience scores were defined as the proportion of a nurse's cases performed within the given specialty. SS, SC, and nurse-SL scores were analyzed by specialty, case urgency, robotic approach, and surgeon academic rank. Two-sample Kolmogorov-Smirnov tests were used to determine heterogeneity between distributions. RESULTS: A total of 37,364 operations involving 150 attending surgeons and 222 nurses were analyzed. Median SS and SC scores were 0.08 (interquartile range: 0.03-0.19) and 0.06 (interquartile range: 0.03-0.13), respectively. Higher margin SLs, senior faculty rank, elective, and robotic cases were associated with greater SS, SC, and nurse-SL scores ( P <0.001). CONCLUSIONS: These novel measures of teaming and specialization illustrate the low levels of OR team familiarity and objectively highlight differences that necessitate a deliberate evaluation of current OR scheduling practices.


Assuntos
Medicina , Robótica , Cirurgiões , Humanos , Equipe de Assistência ao Paciente , Centros Médicos Acadêmicos , Especialização
3.
Ann Surg ; 277(1): 66-72, 2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-35997268

RESUMO

OBJECTIVE: The aim of this review was to review the ethical and multidisciplinary clinical challenges facing trauma surgeons when resuscitating patients presenting with penetrating brain injury (PBI) and multicavitary trauma. BACKGROUND: While there is a significant gap in the literature on managing PBI in patients presenting with multisystem trauma, recent data demonstrate that resuscitation and prognostic features for such patients remains poorly described, with trauma guidelines out of date in this field. METHODS: We reviewed a combination of recent multidisciplinary evidence-informed guidelines for PBI and coupled this with expert opinion from trauma, neurosurgery, neurocritical care, pediatric and transplant surgery, surgical ethics and importantly our community partners. RESULTS: Traditional prognostic signs utilized in traumatic brain injury may not be applicable to PBI with a multidisciplinary team approach suggested on a case-by-case basis. Even with no role for neurosurgical intervention, neurocritical care, and neurointerventional support may be warranted, in parallel to multicavitary operative intervention. Special considerations should be afforded for pediatric PBI. Ethical considerations center on providing the patient with the best chance of survival. Consideration of organ donation should be considered as part of the continuum of patient, proxy and family-centric support and care. Community input is crucial in guiding decision making or protocol establishment on an institutional level. CONCLUSIONS: Support of the patient after multicavitary PBI can be complex and is best addressed in a multidisciplinary fashion with extensive community involvement.


Assuntos
Lesões Encefálicas Traumáticas , Traumatismos Cranianos Penetrantes , Obtenção de Tecidos e Órgãos , Humanos , Criança , Ressuscitação/métodos , Procedimentos Neurocirúrgicos
4.
Ann Surg ; 273(6): 1042-1048, 2021 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-33914482

RESUMO

OBJECTIVE: Our goal was to evaluate the relationship between surgeon representation on NIH study sections and success in grant funding. SUMMARY OF BACKGROUND DATA: NIH funding for surgeon-scientists is declining. Prior work has called for increased surgeon participation in the grant review process as a strategy to increase receipt of funding by surgeon-scientists. METHODS: A retrospective review of surgeon (primary department: General, Urology, Orthopedic, Ophthalmology, Otolaryngology, Neurosurgery) representation on NIH study sections and receipt of funding was performed using NIH Research Portfolio Online Reporting Tools Expenditures and Results (RePORTER) and 2019 Blue Ridge Institute for Medical Research data. NIH chartered study section panels and ad hoc reviewers for each 2019 review date were also obtained. RESULTS: In 2019, 9239 individuals reviewed in at least 1 of the 168 study sections [190 (2.1%) surgeons, 64 (0.7%) standing members, 126 (1.4%) ad-hoc]. Most surgeons on study sections were male (65%) professors (63%). Surgeons most commonly served on bioengineering, technology, and surgical sciences (29.6% surgeons), diseases and pathophysiology of the visual system (28.3%), and surgery, anesthesiology and trauma (21%). In 2019, 773 surgeons received 1235 NIH grants (>$580 M) out of a total of 55,012 awards (2.2%). Funded surgeons were predominantly male (79%), White (68%), non-Hispanic (97%), full professors (50%), and 43% had additional advanced degrees (MPH/PhD/MBA). surgery, anesthesiology and trauma, diseases and pathophysiology of the visual system, and bioengineering, technology, and surgical sciences were the most common study sections that reviewed funded grants to surgeon-scientists. Ninety-two surgeons both received grant funding and served on study section. Study sections with higher surgeon representation were more likely to fund surgeon-scientists (P < 0.001). CONCLUSIONS: Surgeon representation on NIH study sections is strongly associated with receipt of funding by surgeon-scientists. Increasing NIH study section representation by surgeons may help to preserve the surgeon-scientist phenotype.


Assuntos
Distinções e Prêmios , Pesquisa Biomédica/economia , National Institutes of Health (U.S.)/economia , Especialidades Cirúrgicas/economia , Estudos Retrospectivos , Estados Unidos
5.
J Vasc Surg ; 74(2S): 2S-5S, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34303457

RESUMO

Healthcare disparities are a serious problem that shorten the lives of many Americans, even after accounting for social, cultural, and economic factors and correcting for confounders such as the lack of medical insurance and access to healthcare, black Americans and other minority groups receive worse medical care and experience worse outcomes as a result. Healthcare does not occur in a vacuum; surgeons cannot serve our patients' needs isolated in a bubble and cocooned from larger societal concerns. Although disparities rooted in race likely have the greatest negative effects on our patients' health, plenty of groups exist that have not historically received equal opportunities and acceptance within the surgical world. Despite now accounting for more than one half of all medical graduates, women remain underrepresented in leadership positions, and the gender pay gap has remained significant in all branches of medicine. It will require active, multifaceted, and sustained effort to increase diversity, equity, and inclusion in academic surgery. We have described the steps that can be taken within surgical departments and in national surgical societies to recruit, retain, and foster a diverse surgical workforce and to develop a more inclusive culture within surgery and surgical training.


Assuntos
Diversidade Cultural , Equidade de Gênero , Princípios Morais , Seleção de Pessoal , Médicas , Racismo , Sexismo , Cirurgiões , Procedimentos Cirúrgicos Vasculares , Assistência à Saúde Culturalmente Competente/etnologia , Feminino , Disparidades em Assistência à Saúde/etnologia , Direitos Humanos , Humanos , Liderança , Masculino , Mentores , Fatores Raciais , Fatores Sexuais , Sociedades Médicas , Cirurgiões/educação , Procedimentos Cirúrgicos Vasculares/educação
6.
Pediatr Surg Int ; 37(10): 1383-1392, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34245339

RESUMO

BACKGROUND: Chronic pancreatitis (CP) and acute recurrent pancreatitis (ARP) in pediatric patients are strongly associated with genetic mutations and lead to pan-parenchymal disease refractory to medical and endoscopic treatment. Our aim was to assess pain resolution and glucose control in patients with CP and ARP following total pancreatectomy with islet auto-transplantation (TPIAT). METHODS: We retrospectively analyzed prospectively collected clinical data of 12 children who developed CP and ARP and underwent TPIAT when 21 years old or younger at the University of Chicago between December 2009 and June 2020. Patients with recurrent or persistent abdominal pain attributed to acute or chronic pancreatic inflammation and a history of medical interventions attempted for the relief of pancreatic pain were selected by a multi-disciplinary team for TPIAT. We followed patients post-operatively and reported data for pre-TPIAT, post-operative day 75, and yearly post-TPIAT. RESULTS: All 12 patients experienced complete resolution of pancreatic pain. The overall insulin-independence rate after 1 year was 66% (8/12) and 50% (3/6) at 4 years. Shorter duration of CP/ARP pre-TPIAT, higher mass of islets infused, and lower BMI, BMI percentile, and BSA were associated with insulin-independence post-TPIAT. CONCLUSIONS: TPIAT is a viable treatment option for pediatric patients with CP and ARP. Pediatric patients undergoing TPIAT for CP achieved resolution of pancreatic-type pain and reduced opioid requirements. The majority were able to achieve insulin-independence which was associated with lower pre-TPIAT BMI and higher islet mass transplanted (i.e., over 2000 IEQ/kg), the latter of which can be achieved by earlier TPIAT. LEVEL OF EVIDENCE: Treatment study, Level IV.


Assuntos
Glicemia , Pancreatite Crônica , Dor Abdominal , Criança , Humanos , Pancreatectomia , Pancreatite Crônica/cirurgia , Estudos Retrospectivos , Transplante Autólogo , Resultado do Tratamento
7.
Transpl Int ; 32(3): 280-290, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30353611

RESUMO

We investigated six indices based on a single fasting blood sample for evaluation of the beta-cell function after total pancreatectomy with islet autotransplantation (TP-IAT). The Secretory Unit of Islet Transplant Objects (SUITO), transplant estimated function (TEF), homeostasis model assessment (HOMA-2B%), C-peptide/glucose ratio (CP/G), C-peptide/glucose creatinine ratio (CP/GCr) and BETA-2 score were compared against a 90-min serum glucose level, weighted mean C-peptide in mixed meal tolerance test (MMTT), beta score and the Igls score adjusted for islet function in the setting of IAT. We analyzed values from 32 MMTTs in 15 patients after TP-IAT with a follow-up of up to 3 years. Four (27%) individuals had discontinued insulin completely prior to day 75, while 6 out of 12 patients (50%) did not require insulin support at 1-year follow-up with HbA1c 6.0% (5.5-6.8). BETA-2 was the most consistent among indices strongly correlating with all reference measures of beta-cell function (r = 0.62-0.68). In addition, it identified insulin independence (cut-off = 16.2) and optimal/good versus marginal islet function in the Igls score well, with AUROC of 0.85 and 0.96, respectively. Based on a single fasting blood sample, BETA-2 score has the most reliable discriminant value for the assessment of graft function in patients undergoing TP-IAT.


Assuntos
Jejum/sangue , Células Secretoras de Insulina/fisiologia , Transplante das Ilhotas Pancreáticas , Pancreatectomia , Adolescente , Adulto , Glicemia/análise , Peptídeo C/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Transplante Autólogo , Adulto Jovem
8.
Ann Surg ; 266(3): 411-420, 2017 09.
Artigo em Inglês | MEDLINE | ID: mdl-28650359

RESUMO

OBJECTIVE: To determine whether concurrently performed operations are associated with an increased risk for adverse events. BACKGROUND: Concurrent operations occur when a surgeon is simultaneously responsible for critical portions of 2 or more operations. How this practice affects patient outcomes is unknown. METHODS: Using American College of Surgeons' National Surgical Quality Improvement Program data from 2014 to 2015, operations were considered concurrent if they overlapped by ≥60 minutes or in their entirety. Propensity-score-matched cohorts were constructed to compare death or serious morbidity (DSM), unplanned reoperation, and unplanned readmission in concurrent versus non-concurrent operations. Multilevel hierarchical regression was used to account for the clustered nature of the data while controlling for procedure and case mix. RESULTS: There were 1430 (32.3%) surgeons from 390 (77.7%) hospitals who performed 12,010 (2.3%) concurrent operations. Plastic surgery (n = 393 [13.7%]), otolaryngology (n = 470 [11.2%]), and neurosurgery (n = 2067 [8.4%]) were specialties with the highest proportion of concurrent operations. Spine procedures were the most frequent concurrent procedures overall (n = 2059/12,010 [17.1%]). Unadjusted rates of DSM (9.0% vs 7.1%; P < 0.001), reoperation (3.6% vs 2.7%; P < 0.001), and readmission (6.9% vs 5.1%; P < 0.001) were greater in the concurrent operation cohort versus the non-concurrent. After propensity score matching and risk-adjustment, there was no significant association of concurrence with DSM (odds ratio [OR] 1.08; 95% confidence interval [CI] 0.96-1.21), reoperation (OR 1.16; 95% CI 0.96-1.40), or readmission (OR 1.14; 95% CI 0.99-1.29). CONCLUSIONS: In these analyses, concurrent operations were not detected to increase the risk for adverse outcomes. These results do not lessen the need for further studies, continuous self-regulation and proactive disclosure to patients.


Assuntos
Readmissão do Paciente/estatística & dados numéricos , Complicações Pós-Operatórias/etiologia , Reoperação/estatística & dados numéricos , Procedimentos Cirúrgicos Operatórios/métodos , Adulto , Idoso , Bases de Dados Factuais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/epidemiologia , Pontuação de Propensão , Melhoria de Qualidade , Risco Ajustado , Fatores de Risco , Procedimentos Cirúrgicos Operatórios/mortalidade
12.
Surg Innov ; 23(6): 586-592, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27507575

RESUMO

Background Complex procedures often have numerous acceptable approaches; it is unclear how surgical fellows choose between techniques. We used pancreaticoduodenectomy as a model to catalogue variability between surgeons and investigate factors that affect fellows' acquisition of techniques. Materials and methods Semistructured interviews and operative note analysis were conducted to determine techniques of 5 attending surgeons, and these data were mapped to identify variations. Identical interviews and questioning were completed with 4 fellowship graduates whose practice includes pancreaticoduodenectomy. Results All surgeons performed a different operation, both in order and techniques employed. Based on minor variations, there were 21 surgical step data points that differed. Of 5 surgeons, 4 were unable to identify colleagues' techniques. Fellows reported adopting techniques from mentors who had regimented techniques, teaching styles they related to, and with whom they frequently operated. Residency training did not strongly influence their choice of technique; however, senior partners after fellowship did influence technique. Conclusions The number of variants of pancreaticoduodenectomy based on granular, step-by-step differences is larger than previously described. Results hint that variation may be furthered by the fact that surgeons are not aware of the techniques used by colleagues. Fellows choose techniques based on factors not directly related to their own outcomes but rather mentor factors. Whether fellows adopt techniques that will be optimal given their abilities is worthy of further investigation, as are changes in technique over time. Better codification of variation is needed to facilitate these investigations as well as matching of technical variations to patient outcomes.


Assuntos
Competência Clínica , Corpo Clínico Hospitalar/educação , Pancreaticoduodenectomia/métodos , Inquéritos e Questionários , Anastomose Cirúrgica/educação , Anastomose Cirúrgica/métodos , Educação de Pós-Graduação em Medicina/métodos , Avaliação Educacional , Feminino , Pesquisas sobre Atenção à Saúde , Humanos , Entrevistas como Assunto , Masculino , Pancreaticoduodenectomia/efeitos adversos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/fisiopatologia
16.
Ann Surg ; 259(5): 960-5, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24096757

RESUMO

OBJECTIVE: To prospectively evaluate the additional value of geriatric assessment (GA) for predicting surgical outcomes in a cohort of older patients undergoing a pancreaticoduodenectomy (PD) for pancreatic tumors. BACKGROUND: Older patients are less often referred for possible PD. Standard preoperative assessments may underestimate the likelihood of significant adverse outcomes. The prospective utility of validated GA has not been studied in this group. METHODS: PD-eligible patients were enrolled in a prospective outcome study. Standard preoperative assessments were recorded. Elements of validated GA were also measured, including components of Fried's model of frailty, the Vulnerable Elders Survey (VES-13), and the Short Physical Performance Battery (SPPB). All postoperative adverse events were recorded, systematically reviewed, and graded using the Clavien-Dindo system by a surgeon blinded to the GA results. Multivariate regression analyses were conducted. RESULTS: Seventy-six older patients underwent a PD. Significant unrecognized vulnerability was identified at the baseline: Fried's "exhaustion" (37.3%), SPPB <10 (28.5%), and VES-13 >3 (15.4%). Within 30 days of PD, 46% experienced a severe complication (Clavien-Dindo grade ≥III). In regression analyses controlling for age, the body mass index, the American Society of Anesthesiologists score, and comorbidity burden, Fried's "exhaustion" predicted major complications [odds ratio (OR) = 4.06; P = 0.01], longer hospital stays (ß = 0.27; P = 0.02), and surgical intensive care unit admissions (OR = 4.30; P = 0.01). Both SPPB (OR = 0.61; P = 0.04) and older age predicted discharge to a rehabilitation facility (OR = 1.1; P < 0.05) and age correlated with a lower likelihood of hospital readmission (OR = 0.94; P = 0.02). CONCLUSIONS: Controlling for standard preoperative assessments, worse scores on GA prospectively and independently predicted important adverse outcomes. Geriatric assessment may help identify older patients at high risk for complications from PD.


Assuntos
Avaliação Geriátrica/métodos , Neoplasias Pancreáticas/cirurgia , Pancreaticoduodenectomia , Complicações Pós-Operatórias/epidemiologia , Medição de Risco/métodos , Idoso , Idoso de 80 Anos ou mais , Intervalo Livre de Doença , Feminino , Idoso Fragilizado , Humanos , Illinois/epidemiologia , Incidência , Tempo de Internação/tendências , Masculino , Pessoa de Meia-Idade , Neoplasias Pancreáticas/mortalidade , Readmissão do Paciente/tendências , Prognóstico , Estudos Prospectivos , Fatores de Risco , Taxa de Sobrevida/tendências
17.
Ann Surg ; 260(4): 659-65; discussion 665-7, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25203883

RESUMO

OBJECTIVE: Total pancreatectomy and islet cell autotransplantation (TPIAT) has been increasingly utilized for the management of chronic pancreatitis (CP) with early success. However, the long-term durability of this operation remains unclear. METHODS: All patients undergoing TPIAT for the treatment of CP with 5-year or greater follow-up were identified for inclusion in this single-center observational study. End points included narcotic requirements, glycemic control, islet function, quality of life (QOL), and survival. RESULTS: Between 2000 and 2013, 166 patients underwent TPIAT; 112 of these patients had 5-year follow-up data to analyze. All patients underwent successful IAT with a mean of 6027 ± 595 islet equivalents per body weight. There was no perioperative mortality and actuarial survival at 5 years was 94.6%. The narcotic independence rate at 1 year was 55% and continued to improve to 73% at 5-year follow-up (P < 0.05). The insulin independence rate declined over time (38% at 1 year vs 27% at more than 5 years), but insulin requirements remained similar (21.4 vs 24.3 units per day, P = 0.6). All patients achieved stable glycemic control with a median hemoglobin A1C (HgA1C) of 6.9% (range: 5.85%-8.3%). The short form 36-item QOL assessment of a subset of patients available for contact demonstrated continued improvements in all tested modules in patients with at least 5-year follow-up. Two patients developed diabetic complications requiring whole organ pancreas transplant for salvage. CONCLUSIONS: This represents one of the largest series examining long-term outcomes after TPIAT. This operation produces durable pain relief and improvement in QOL parameters. Insulin independence rates decline over time, but most patients maintain stable glycemic control.


Assuntos
Transplante das Ilhotas Pancreáticas , Pancreatectomia , Pancreatite Crônica/cirurgia , Dor Abdominal/tratamento farmacológico , Adolescente , Adulto , Feminino , Seguimentos , Hemoglobinas Glicadas/metabolismo , Humanos , Hipoglicemiantes/uso terapêutico , Insulina/uso terapêutico , Masculino , Pessoa de Meia-Idade , Entorpecentes/uso terapêutico , Pancreatite Crônica/complicações , Pancreatite Crônica/mortalidade , Qualidade de Vida , Análise de Sobrevida , Transplante Autólogo , Resultado do Tratamento , Adulto Jovem
18.
Pancreatology ; 14(1): 27-35, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24555976

RESUMO

DESCRIPTION: Total pancreatectomy with islet autotransplantation (TPIAT) is a surgical procedure used to treat severe complications of chronic pancreatitis or very high risk of pancreatic cancer while reducing the risk of severe diabetes mellitus. However, clear guidance on indications, contraindications, evaluation, timing, and follow-up are lacking. METHODS: A working group reviewed the medical, psychological, and surgical options and supporting literature related to TPIAT for a consensus meeting during PancreasFest. RESULTS: Five major areas requiring clinical evaluation and management were addressed: These included: 1) indications for TPIAT; 2) contraindications for TPIAT; 3) optimal timing of the procedure; 4) need for a multi-disciplinary team and the roles of the members; 5) life-long management issues following TPIAP including diabetes monitoring and nutrition evaluation. CONCLUSIONS: TPIAT is an effective method of managing the disabling complications of chronic pancreatitis and risk of pancreatic cancer in very high risk patients. Careful evaluation and long-term management of candidate patients by qualified multidisciplinary teams is required. Multiple recommendations for further research were also identified.


Assuntos
Transplante das Ilhotas Pancreáticas , Pancreatectomia , Pancreatite Crônica/cirurgia , Contraindicações , Humanos , Transplante das Ilhotas Pancreáticas/métodos , Neoplasias Pancreáticas/etiologia , Neoplasias Pancreáticas/cirurgia , Risco , Transplante Autólogo
19.
Adv Surg ; 48: 223-33, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25293618

RESUMO

The goal of IAT is the preservation of beta-cell mass at the time of pancreatectomy. The majority of recipients have significant endogenous beta-cell function with positive blood C-peptide after surgery, even if only approximately one third achieve insulin independence. In appropriately selected patients, total pancreatectomy combined with IAT achieves relief of pain and improves quality of life with relatively easier-to-manage glycemic control and avoidance of hyper- and hypoglycemic episodes. Current research is focused on improving techniques of islet isolation and engraftment as well as long-term survival of autografted islets.


Assuntos
Transplante das Ilhotas Pancreáticas , Pancreatectomia/métodos , Pancreatite Crônica/cirurgia , Dor Abdominal/prevenção & controle , Doença Aguda , Glicemia/metabolismo , Contraindicações , Terapia de Reposição Hormonal , Humanos , Hormônios Pancreáticos/uso terapêutico , Pancreatite Crônica/sangue , Pancreatite Crônica/dietoterapia , Seleção de Pacientes , Qualidade de Vida , Recidiva , Transplante Autólogo
20.
Clin Cancer Res ; 30(4): 729-740, 2024 02 16.
Artigo em Inglês | MEDLINE | ID: mdl-38109213

RESUMO

PURPOSE: The neutralizing peptibody trebananib prevents angiopoietin-1 and angiopoietin-2 from binding with Tie2 receptors, inhibiting angiogenesis and proliferation. Trebananib was combined with paclitaxel±trastuzumab in the I-SPY2 breast cancer trial. PATIENTS AND METHODS: I-SPY2, a phase II neoadjuvant trial, adaptively randomizes patients with high-risk, early-stage breast cancer to one of several experimental therapies or control based on receptor subtypes as defined by hormone receptor (HR) and HER2 status and MammaPrint risk (MP1, MP2). The primary endpoint is pathologic complete response (pCR). A therapy "graduates" if/when it achieves 85% Bayesian probability of success in a phase III trial within a given subtype. Patients received weekly paclitaxel (plus trastuzumab if HER2-positive) without (control) or with weekly intravenous trebananib, followed by doxorubicin/cyclophosphamide and surgery. Pathway-specific biomarkers were assessed for response prediction. RESULTS: There were 134 participants randomized to trebananib and 133 to control. Although trebananib did not graduate in any signature [phase III probabilities: Hazard ratio (HR)-negative (78%), HR-negative/HER2-positive (74%), HR-negative/HER2-negative (77%), and MP2 (79%)], it demonstrated high probability of superior pCR rates over control (92%-99%) among these subtypes. Trebananib improved 3-year event-free survival (HR 0.67), with no significant increase in adverse events. Activation levels of the Tie2 receptor and downstream signaling partners predicted trebananib response in HER2-positive disease; high expression of a CD8 T-cell gene signature predicted response in HR-negative/HER2-negative disease. CONCLUSIONS: The angiopoietin (Ang)/Tie2 axis inhibitor trebananib combined with standard neoadjuvant therapy increased estimated pCR rates across HR-negative and MP2 subtypes, with probabilities of superiority >90%. Further study of Ang/Tie2 receptor axis inhibitors in validated, biomarker-predicted sensitive subtypes is warranted.


Assuntos
Neoplasias da Mama , Proteínas Recombinantes de Fusão , Feminino , Humanos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Teorema de Bayes , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Terapia Neoadjuvante , Paclitaxel/efeitos adversos , Receptor ErbB-2/metabolismo , Receptor TIE-2 , Trastuzumab/efeitos adversos
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