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3.
J Exp Child Psychol ; 242: 105888, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38430869

RESUMO

The current study investigated the association of children's age, gender, ethnicity, Big Five personality traits, and self-efficacy with their academic cheating behaviors. Academic cheating is a rampant problem that has been documented in adolescents and adults for nearly a century, but our understanding of the early development and factors influencing academic cheating is still weak. Using Zoom, the current study recruited children aged 4 to 12 years (N = 388), measured their cheating behaviors through six tasks simulating academic testing scenarios, and assessed their Big Five personality traits and self-efficacy through a modified Berkeley Puppet Interview paradigm, as well as age and gender. We found that children cheated significantly less with increased age and that boys cheated significantly more than girls. However, neither Big Five personality traits nor self-efficacy were significantly correlated with children's cheating. These findings suggest that academic cheating is a developing issue from early to middle childhood and that factors such as gender socialization may play a role in such development. Personal characteristics such as personality traits and self-efficacy may undergo additional development before their associations with cheating become robust, as reported in the adult literature.


Assuntos
Personalidade , Autoeficácia , Masculino , Adulto , Feminino , Adolescente , Humanos , Pré-Escolar , Criança , Enganação
5.
Neurosurgery ; 95(2): 380-391, 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-38456696

RESUMO

BACKGROUND AND PURPOSE: A retrospective single-center analysis of the safety and efficacy of reirradiation to 40 Gy in 5 fractions (reSBRT) in patients previously treated with stereotactic body radiotherapy to the spine was performed. METHODS: We identified 102 consecutive patients treated with reSBRT for 105 lesions between 3/2013 and 8/2021. Sixty-three patients (61.8%) were treated to the same vertebral level, and 39 (38.2%) to overlapping immediately adjacent levels. Local control was defined as the absence of progression within the treated target volume. The probability of local progression was estimated using a cumulative incidence curve. Death without local progression was considered a competing risk. RESULTS: Most patients had extensive metastatic disease (54.9%) and were treated to the thoracic spine (53.8%). The most common regimen in the first course of stereotactic body radiotherapy was 27 Gy in 3 fractions, and the median time to reSBRT was 16.4 months. At the time of simulation, 44% of lesions had advanced epidural disease. Accordingly, 80% had myelogram simulations. Both the vertebral body and posterior elements were treated in 86% of lesions. At a median follow-up time of 13.2 months, local failure occurred in 10 lesions (9.5%). The 6- and 12-month cumulative incidences of local failure were 4.8% and 6%, respectively. Seven patients developed radiation-related neuropathy, and 1 patient developed myelopathy. The vertebral compression fracture rate was 16.7%. CONCLUSION: In patients with extensive disease involvement, reSBRT of spine metastases with 40 Gy in 5 fractions seems to be safe and effective. Prospective trials are needed to determine the optimal dose and fractionation in this clinical scenario.


Assuntos
Radiocirurgia , Reirradiação , Terapia de Salvação , Neoplasias da Coluna Vertebral , Humanos , Radiocirurgia/métodos , Masculino , Feminino , Neoplasias da Coluna Vertebral/radioterapia , Neoplasias da Coluna Vertebral/cirurgia , Neoplasias da Coluna Vertebral/secundário , Idoso , Pessoa de Meia-Idade , Estudos Retrospectivos , Reirradiação/métodos , Terapia de Salvação/métodos , Idoso de 80 Anos ou mais , Adulto , Fracionamento da Dose de Radiação , Resultado do Tratamento
6.
Foot Ankle Orthop ; 9(1): 24730114231224727, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38298264

RESUMO

Background: Lisfranc fracture-dislocation is an uncommon but serious injury that currently lacks universal consensus on optimal operative treatment. Two common fixation methods are open reduction and internal fixation (ORIF) and primary arthrodesis (PA). The objective of this study is to analyze the cost difference between ORIF and PA of Lisfranc injuries, along with the contribution of medical services to overall costs. Methods: This was a retrospective cost analysis of the MarketScan database from 2010 to 2020. MarketScan is an insurance and commercial claims database that integrates deidentified patient information. It captures person-specific clinical utilization, expenditures, and enrollment across inpatient and outpatient services. Patients undergoing primary ORIF (CPT code 28615) vs PA (28730 and 28740) for Lisfranc fracture-dislocation were identified. The primary independent variable was ORIF vs PA of Lisfranc injury. Total costs due to operative management was the primary objective. The utilization of and costs contributed by medical services was a secondary outcome. Results: From 2010 to 2020, a total of 7268 patients underwent operative management of Lisfranc injuries, with 5689 (78.3%) ORIF and 1579 (21.7%) PA. PA was independently associated with increased net and total payment and coinsurance, clinic visits, and imaging, and patients attended significantly more PT sessions. Conclusion: Using this large database that does not characterize severity or extent of injury, we found that treatment of Lisfranc fracture-dislocation with ORIF was associated with substantially lower initial episode of treatment costs compared with PA. Specific excessive cost drivers for PA were clinic visits, PT sessions, and imaging. Level of Evidence: Level III, retrospective cohort study.

7.
Adv Radiat Oncol ; 9(2): 101355, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38405315

RESUMO

Purpose: Recurrent or new primary breast cancer requiring comprehensive regional nodal irradiation after prior radiation therapy (RT) to the supraclavicular area and upper axilla is challenging due to cumulative brachial plexus (BP) dose tolerance. We assessed BP dose sparing achieved with pencil beam scanning proton therapy (PBS-PT) and photon volumetric modulated arc therapy (VMAT). Methods and Materials: In an institutional review board-approved planning study, all patients with ipsilateral recurrent breast cancer treated with PBS-PT re-RT (PBT1) with at least partial BP overlap from prior photon RT were identified. Comparative VMAT plans (XRT1) using matched BP dose constraints were developed. A second pair of proton (PBT2) and VMAT (XRT2) plans using standardized target volumes were created, applying uniform prescription dose of 50.4 per 1.8 Gy and a maximum BP constraint <25 Gy. Incidence of brachial plexopathy was also assessed. Results: Ten consecutive patients were identified. Median time between RT courses was 48 months (15-276). Median first, second, and cumulative RT doses were 50.4 Gy (range, 42.6-60.0), 50.4 Gy relative biologic effectiveness (RBE) (45.0-64.4), and 102.4 Gy (RBE) (95.0-120.0), respectively. Median follow-up was 15 months (5-33) and 18 months for living patients (11-33) Mean BP max was 37.5 Gy (RBE) for PBT1 and 36.9 Gy for XRT1. Target volume coverage of V85% (volume receiving 85% of prescription dose), V90%, and V95% were numerically lower for XRT1 versus PBT1. Similarly, axilla I-III and supraclavicular area coverage were significantly higher for PBT2 than XRT2 at dose levels of V55%, V65%, V75%, V85%, and V95%. Only axilla I V55% did not reach significance (P = .06) favoring PBS-PT. Two patients with high cumulative BPmax (95.2 Gy [RBE], 101.6 Gy [RBE]) developed brachial plexopathy symptoms with ulnar nerve distribution neuropathy without pain or weakness (1 of 2 had symptom resolution after 6 months without intervention). Conclusions: PBS-PT improved BP sparing and target volume coverage versus VMAT. For patients requiring comprehensive re-RT for high-risk, nonmetastatic breast cancer recurrence with BP overlap and reasonable expectation for prolonged life expectancy, PBT may be the preferred treatment modality.

8.
Clin Orthop Relat Res ; 482(2): 313-322, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-37498201

RESUMO

BACKGROUND: Out-of-pocket (OOP) costs can be substantial financial burdens for patients and may even cause patients to delay or forgo necessary medical procedures. Although overall healthcare costs are rising in the United States, recent trends in patient OOP costs for foot and ankle orthopaedic surgical procedures have not been reported. Fully understanding patient OOP costs for common orthopaedic surgical procedures, such as those performed on the foot and ankle, might help patients and professionals make informed decisions regarding treatment options and demonstrate to policymakers the growing unaffordability of these procedures. QUESTIONS/PURPOSES: (1) How do OOP costs for common outpatient foot and ankle surgical procedures for commercially insured patients compare between elective and trauma surgical procedures? (2) How do these OOP costs compare between patients enrolled in various insurance plan types? (3) How do these OOP costs compare between surgical procedures performed in hospital-based outpatient departments and ambulatory surgical centers (ASCs)? (4) How have these OOP costs changed over time? METHODS: This was a retrospective, comparative study drawn from a large, longitudinally maintained database. Data on adult patients who underwent elective or trauma outpatient foot or ankle surgical procedures between 2010 and 2020 were extracted using the MarketScan Database, which contains well-delineated cost variables for all patient claims, which are particularly advantageous for assessing OOP costs. Of the 1,031,279 patient encounters initially identified, 41% (427,879) met the inclusion criteria. Demographic, procedural, and financial data were recorded. The median patient age was 50 years (IQR 39 to 57); 65% were women, and more than half of patients were enrolled in preferred provider organization insurance plans. Approximately 75% of surgical procedures were classified as elective (rather than trauma), and 69% of procedures were performed in hospital-based outpatient departments (rather than ASCs). The primary outcome was OOP costs incurred by the patient, which were defined as the sum of the deductible, coinsurance, and copayment paid for each episode of care. Monetary data were adjusted to 2020 USD. A general linear regression, the Kruskal-Wallis test, and the Wilcoxon-Mann-Whitney test were used for analysis, as appropriate. Alpha was set at 0.05. RESULTS: For foot and ankle indications, trauma surgical procedures generated higher median OOP costs than elective procedures (USD 942 [IQR USD 150 to 2052] versus USD 568 [IQR USD 51 to 1426], difference of medians USD 374; p < 0.001). Of the insurance plans studied, high-deductible health plans had the highest median OOP costs. OOP costs were lower for procedures performed in ASCs than in hospital-based outpatient departments (USD 645 [IQR USD 114 to 1447] versus USD 681 [IQR USD 64 to 1683], difference of medians USD 36; p < 0.001). This trend was driven by higher coinsurance for hospital-based outpatient departments than for ASCs (USD 391 [IQR USD 0 to 1136] versus USD 337 [IQR USD 0 to 797], difference of medians USD 54; p < 0.001). The median OOP costs for common outpatient foot and ankle surgical procedures increased by 102%, from USD 450 in 2010 to USD 907 in 2020. CONCLUSION: Rapidly increasing OOP costs of common foot and ankle orthopaedic surgical procedures warrant a thorough investigation of potential cost-saving strategies and initiatives to enhance healthcare affordability for patients. In particular, measures should be taken to reduce underuse of necessary care for patients enrolled in high-deductible health plans, such as shorter-term deductible timespans and placing additional regulations on the implementation of these plans. Moreover, policymakers and physicians could consider finding ways to increase the proportion of procedures performed at ASCs for procedure types that have been shown to be equally safe and effective as in hospital-based outpatient departments. Future studies should extend this analysis to publicly insured patients and further investigate the health and financial effects of high-deductible health plans and ASCs, respectively. LEVEL OF EVIDENCE: Level III, economic and decision analysis.


Assuntos
Gastos em Saúde , Ortopedia , Adulto , Humanos , Feminino , Estados Unidos , Pessoa de Meia-Idade , Masculino , Estudos Retrospectivos , Pacientes Ambulatoriais , Tornozelo/cirurgia , Custos de Cuidados de Saúde
9.
Int J Radiat Oncol Biol Phys ; 118(2): 468-473, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-37791937

RESUMO

PURPOSE: HER2-positive (HER2+) breast cancer historically exhibited the most adverse local outcomes and, consequently, has had limited representation among trials of partial breast irradiation (PBI). We hypothesized that with contemporary HER2-targeted agents, patients may now exhibit excellent disease control outcomes after adjuvant PBI. METHODS AND MATERIALS: Using a prospectively maintained institutional database, we identified patients with HER2+ breast cancer treated with breast conserving surgery (BCS) and PBI from 2000 to 2022. Salient clinicopathologic and treatment parameters were collected. All patients received external beam PBI to 40 Gy in 10 daily fractions. Cumulative incidence functions were calculated to estimate the incidence of local recurrence (LR) with the competing risk of death. RESULTS: We identified 1248 patients who underwent PBI at our institution, of whom the study cohort comprised 52 (4%) with HER2+ breast cancer (median age, 64 years; range, 44-87). Nearly all had T1 tumors (98%; median size, 12 mm [range, 1-21 mm]). Most had estrogen receptor positive disease (88%), and all patients had negative surgical margins. Nearly all underwent sentinel node biopsy (94%), with the remainder undergoing no surgical axillary evaluation. Forty-two (81%) received chemotherapy; 40 (77%), hormone therapy; and 42 (81%), HER2-directed therapy, most commonly trastuzumab. At 143.8 person-years of follow-up (range, 7-226 months for each patient), we observed 2 LR events at 14 and 26 months, respectively, yielding a 2-year LR rate of 3.8%. No regional or distant recurrences were observed, nor were any breast-specific mortality events. Two deaths were observed, both without evidence of disease. CONCLUSIONS: Among a cohort of patients with HER2+ early-stage breast cancer managed with BCS and PBI, we observed a 2-year LR rate of 3.8%, with no regional or distant recurrences and excellent overall survival. These findings require confirmation with longer follow-up among larger cohorts but appear consistent with the excellent results of contemporary randomized trials of PBI unselected for HER2 status.


Assuntos
Antineoplásicos , Neoplasias da Mama , Humanos , Pessoa de Meia-Idade , Feminino , Neoplasias da Mama/radioterapia , Neoplasias da Mama/cirurgia , Neoplasias da Mama/patologia , Mama/efeitos da radiação , Mastectomia Segmentar , Trastuzumab , Recidiva Local de Neoplasia/patologia
10.
Cancers (Basel) ; 15(24)2023 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-38136268

RESUMO

Radiotherapy is an integral component of multidisciplinary breast cancer care. Given how commonly radiotherapy is used in the treatment of breast cancer, many patients with recurrences have received previous radiotherapy. Patients with new primary breast cancer may also have received previous radiotherapy to the thoracic region. Curative doses and comprehensive field photon reirradiation (reRT) have often been avoided in these patients due to concerns for severe toxicities to organs-at-risk (OARs), such as the heart, lungs, brachial plexus, and soft tissue. However, many patients may benefit from definitive-intent reRT, such as patients with high-risk disease features such as lymph node involvement and dermal/epidermal invasion. Proton therapy is a potentially advantageous treatment option for delivery of reRT due to its lack of exit dose and greater conformality that allow for enhanced non-target tissue sparing of previously irradiated tissues. In this review, we discuss the clinical applications of proton therapy for patients with breast cancer requiring reRT, the currently available literature and how it compares to historical photon reRT outcomes, treatment planning considerations, and questions in this area warranting further study. Given the dosimetric advantages of protons and the data reported to date, proton therapy is a promising option for patients who would benefit from the added locoregional disease control provided by reRT for recurrent or new primary breast cancer.

11.
Artigo em Inglês | MEDLINE | ID: mdl-37973033

RESUMO

INTRODUCTION: There has been a trend toward performing arthroplasty in the ambulatory setting. The primary purpose of this study was to compare outpatient and inpatient total shoulder arthroplasties (TSAs) for postoperative medical complications, healthcare utilization outcomes, and surgical outcomes. METHODS: Patients who underwent outpatient TSA or inpatient TSA with a minimum 5-year follow-up were identified in the PearlDiver database. These cohorts were propensity-matched based on age, sex, Charlson Comorbidity Index, smoking status, and obesity (body mass index > 30). All outcomes were analyzed using chi square and Student t-tests where appropriate. RESULTS: Outpatient TSA patients had markedly lower rates of various 90-day medical complications. Outpatient TSA patients had lower risk of aseptic loosening at 2 years postoperation and lower risk of periprosthetic joint infection at 5 years postoperation relative to inpatient TSA patients. Outpatient TSA reimbursements were markedly lower than inpatient TSA reimbursements at the 30-day, 90-day, and 1-year postoperative intervals. CONCLUSION: This study found patients undergoing outpatient TSA to be at lowers odds for both postoperative medical and surgical complications compared with those undergoing inpatient TSA. Despite increased risk of postoperative healthcare utilization for readmissions and emergency department visits, outpatient TSA was markedly less expensive at every postoperative time point assessed.


Assuntos
Artroplastia do Ombro , Humanos , Artroplastia do Ombro/efeitos adversos , Pacientes Ambulatoriais , Pacientes Internados , Estudos de Coortes , Complicações Pós-Operatórias/etiologia , Resultado do Tratamento
12.
JAMA ; 330(18): 1791-1792, 2023 11 14.
Artigo em Inglês | MEDLINE | ID: mdl-37889498

RESUMO

This JAMA Clinical Guidelines Synopsis summarizes the American Academy of Dermatology's 2023 guidelines for topical-therapy management of adults with atopic dermatitis.


Assuntos
Dermatite Atópica , Fármacos Dermatológicos , Humanos , Administração Tópica , Inibidores de Calcineurina , Dermatite Atópica/tratamento farmacológico , Fármacos Dermatológicos/administração & dosagem , Fármacos Dermatológicos/uso terapêutico
13.
Curr Rev Musculoskelet Med ; 16(11): 563-574, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37789169

RESUMO

PURPOSE OF REVIEW: First metatarsophalangeal joint sprains or turf toe (TT) injuries occur secondary to forceful hyperextension of the great toe. TT injuries are common among athletes, especially those participating in football, soccer, basketball, dancing, and wrestling. This review summarizes the current treatment modalities, rehabilitation protocols, and return-to-play criteria, as well as performance outcomes of patients who have sustained TT injuries. RECENT FINDINGS: Less than 2% of TT injuries require surgery, but those that do are typically grade III injuries with damage to the MTP joint, evidence of bony injury, or severe instability. Rehabilitation protocols following non-operative management consist of 3 phases lasting up to 10 weeks, whereas protocols following operative management consist of 4 phases lasting up 20 weeks. Athletes with low-grade injuries typically achieve their prior level of performance. However, among athletes with higher grade injuries, treated both non-operatively and operatively, about 70% are expected to maintain their level of performance. The treatment protocol, return-to-play criteria, and overall performance outcomes for TT injuries depend on the severity and classification of the initial sprain. For grade I injuries, players may return to play once they experience minimal to no pain with normal weightbearing, traditionally after 3-5 days. For grade II injuries, or partial tears, players typically lose 2-4 weeks of play and may need additional support with taping when returning to play. For grade III injuries, or complete disruption of the plantar plate, athletes lose 4-6 weeks or more depending upon treatment strategy.

14.
Biomacromolecules ; 24(11): 4771-4782, 2023 11 13.
Artigo em Inglês | MEDLINE | ID: mdl-37815312

RESUMO

Complex coacervation refers to the liquid-liquid phase separation (LLPS) process occurring between charged macromolecules. The study of complex coacervation is of great interest due to its implications in the formation of membraneless organelles (MLOs) in living cells. However, the impacts of the crowded intracellular environment on the behavior and interactions of biomolecules involved in MLO formation are not fully understood. To address this knowledge gap, we investigated the effects of crowding on a model protein-polymer complex coacervate system. Specifically, we examined the influence of sucrose as a molecular crowder and polyethylene glycol (PEG) as a macromolecular crowder. Our results reveal that the presence of crowders led to the formation of larger coacervate droplets that remained stable over a 25-day period. While sucrose had a minimal effect on the physical properties of the coacervates, PEG led to the formation of coacervates with distinct characteristics, including higher density, increased protein and polymer content, and a more compact internal structure. These differences in coacervate properties can be attributed to the effects of crowders on individual macromolecules, such as the conformation of model polymers, and nonspecific interactions among model protein molecules. Moreover, our results show that sucrose and PEG have different partition behaviors: sucrose was present in both the coacervate and dilute phases, while PEG was observed to be excluded from the coacervate phase. Collectively, our findings provide insights into the understanding of crowding effects on complex coacervation, shedding light on the formation and properties of coacervates in the context of MLOs.


Assuntos
Polímeros , Proteínas , Polímeros/química , Proteínas/química , Polietilenoglicóis/química , Substâncias Macromoleculares/química , Sacarose
15.
Orthop Clin North Am ; 54(4): 485-494, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37718087

RESUMO

There remains a high prevalence and substantial risks of opioid utilization amongst orthopedic patients. The goal of this review is to discuss strategies for responsible opioid use in the perioperative setting following foot and ankle orthopedic surgeries. We will highlight 1) education interventions, 2) risk identification, and 3) non-opioid alternatives for postoperative pain management.


Assuntos
Analgesia , Ortopedia , Humanos , Tornozelo/cirurgia , Manejo da Dor , Extremidade Inferior , Analgésicos Opioides/uso terapêutico
16.
World J Surg ; 47(12): 3051-3059, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37735223

RESUMO

BACKGROUND: Global perceptions of barriers to women in orthopaedics have not been assessed. The purpose of this study was to determine the importance of international barriers to women entering and advancing within orthopaedic surgery. METHODS: An anonymous, online survey was distributed to women medical students, trainees, and practicing surgeons via Women in Orthopaedics Worldwide, the "Women in Ortho" Facebook page, and individual programmes. Participants were asked to rate perceived barriers to (1) pursuing training and (2) career advancement on a scale of 1-5, with 5 being the most important and relative to other barriers. Descriptive statistics and univariate analyses were employed. RESULTS: The survey yielded 237 US (84.0%) and 45 international (16.0%) respondents. Per entering orthopaedic surgery, the most important barriers were male-dominated culture, lack of a strong women mentor, and lack of female representation at home institution. Compared with the US surgeons/trainees, international respondents cited greater societal disapproval (2.8 ± 1.2 vs. 3.4 ± 1.3, P = 0.01). Medical students assigned less importance to lack of exposure, more to lack of resources for creating competitive applications (P < 0.05). Regarding career advancement, lack of women leadership, family responsibilities, and gender-biased selection for promotion were the most important. International surgeons/trainees noted greater concern for societal disapproval (3.5 ± 1.5 vs. 2.6 ± 1.3, P = 0.003) and were more likely to rank sexual harassment in their top three (17.6 vs. 4.2%, P = 0.02). CONCLUSION: While notable differences exist, there is striking similarity across countries and position levels in perceived barriers to women entering and advancing in orthopaedic surgery. LEVEL OF EVIDENCE: III.


Assuntos
Procedimentos Ortopédicos , Ortopedia , Médicas , Cirurgiões , Humanos , Masculino , Feminino , Escolha da Profissão , Inquéritos e Questionários
18.
J Phys Chem B ; 127(39): 8344-8357, 2023 10 05.
Artigo em Inglês | MEDLINE | ID: mdl-37751332

RESUMO

Monoclonal antibodies (mAbs) make up a major class of biotherapeutics with a wide range of clinical applications. Their physical stability can be affected by various environmental factors. For instance, an acidic pH can be encountered during different stages of the mAb manufacturing process, including purification and storage. Therefore, understanding the behavior of flexible mAb molecules in acidic solution environments will benefit the development of stable mAb products. This study used small-angle X-ray scattering (SAXS) and complementary biophysical characterization techniques to investigate the conformational flexibility and protein-protein interactions (PPI) of a model mAb molecule under near-neutral and acidic conditions. The study also characterized the interactions between Fab and Fc fragments under the same buffer conditions to identify domain-domain interactions. The results suggest that solution pH significantly influences mAb flexibility and thus could help mAbs remain physically stable by maximizing local electrostatic repulsions when mAbs become crowded in solution. Under acidic buffer conditions, both Fab and Fc contribute to the repulsive PPI observed among the full mAb at a low ionic strength. However, as ionic strength increases, hydrophobic interactions lead to the self-association of Fc fragments and, subsequently, could affect the aggregation state of the mAb.


Assuntos
Anticorpos Monoclonais , Imunoglobulina G , Anticorpos Monoclonais/química , Espalhamento a Baixo Ângulo , Imunoglobulina G/química , Difração de Raios X , Cloreto de Sódio , Ácidos , Fragmentos Fc das Imunoglobulinas/química , Concentração de Íons de Hidrogênio
19.
Radiother Oncol ; 187: 109839, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37536378

RESUMO

BACKGROUND AND PURPOSE: The addition of cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) to endocrine therapy in hormone receptor-positive (HR+) human epidermal growth factor 2-negative (HER2-) breast cancer has led to practice-changing improvements in overall survival. However, there are conflicting data concerning the safety of CDK4/6i combination with radiotherapy, and no consensus guidelines exist to guide practice. We conducted a meta-analysis to assess the safety and feasibility of CDK4/6i treatment with radiotherapy. MATERIALS AND METHODS: A comprehensive search was performed in PubMed/MEDLINE, Web of Science, and Scopus, for studies in advanced/metastatic breast cancer receiving CDK4/6i and radiotherapy with the provided safety data on the occurrence of toxicity. The main outcomes were safety (grade 3-5 adverse events), CDK 4/6i dose reduction, and the discontinuation rate due to toxicity. RESULTS: Fifteen studies comprising 1133 patients with HR+/HER2- breast cancer patients were included. Among them, 617 pts received CDK4/6i and radiotherapy; the median follow-up was 17.0 months (IQR 9.2 - 18.0), and the median age was 58.8 years (IQR 55.5---62.5). The pooled prevalence of severe hematologic toxicity was 29.4% (95% CI 14.0% - 47.4%; I2 = 93%; τ2 = 0.084; p < 0.01 and severe non-hematologic toxicity was 2.8% (95% CI 1.1% - 4.8%; I2 = 0%; τ2 = 0.0; p = 0.67). The pooled prevalence of CDK4/6i dose reduction was 24.0% (95% CI 11.1% - 39.4%; I2 = 90%; τ2 = 0.052; p < 0.01) with no difference between CDK4/6i plus RT vs. CDK4/6i (odds ratio of 0.934; 95% CI 0.66 - 1.33; I2 = 0%; τ2 = 0.0; p = 0.56). The pooled prevalence of CDK4/6i discontinuation due to toxicity was 2.3% (95% CI 0.4% - 5.2%; I2 = 23%; τ2 = 0.002; p = 0.24). CONCLUSION: The findings of this study suggest that radiotherapy in addition to CDK4/6i treatment in breast cancer patients is generally safe and well tolerated and remains a viable treatment option.


Assuntos
Neoplasias da Mama , Feminino , Humanos , Pessoa de Meia-Idade , Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/radioterapia , Consenso , Quinase 4 Dependente de Ciclina , Fator de Crescimento Epidérmico , Estudos de Viabilidade , Inibidores de Proteínas Quinases/efeitos adversos , Radioterapia
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