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1.
Ann Surg Oncol ; 30(2): 1184-1193, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36331660

RESUMO

BACKGROUND: The Multicenter Selective Lymphadenectomy Trial-II (MSLT-II) revealed completion lymph node dissection (CLND) after positive sentinel lymph node biopsy (SLNB) did not improve melanoma-specific survival compared with surveillance. Given these findings and the morbidity associated with CLND, this study investigated trends in rates and predictors of CLND after MSLT-II. METHODS: Analysis of the National Cancer Database was performed for all patients aged ≥18 years with melanoma and a positive SLNB for 2012-2019. Rates of CLND before and after publication of MSLT-II were identified and logistic regression used to identify factors associated with CLND. RESULTS: Patients undergoing CLND declined from 55.9% pre-MSLT-II (n = 9725) to 19.5% post-MSLT-II (n = 9419) (odds ratio [OR] 0.32, 95% confidence interval [CI] 0.29-0.35). CLND was less likely in females (OR 0.83; 95% CI 0.78-0.89), older patients (vs. 18-39 yr; 40-64 yr OR 0.80, 95% CI 0.65-0.98; 65-79 yr OR 0.67, 95% CI 0.53-0.84; >80 yr OR 0.38, 95% CI 0.30-0.49), sicker patients (Deyo category ≥2 OR 0.85, 95% CI 0.73-0.99), thinner primary lesions (vs. 0.01-0.79 mm; 1.01-4.00 mm OR 1.16, 95% CI 1.01-1.33; ≥4.01 mm OR 1.31, 95% CI 1.08-1.59), patients from metro areas (Rural OR 1.31, 95% CI 1.00-1.70; Urban OR 1.15, 95% CI 1.03-1.29), and those treated at lower-volume centers (vs. lowest-volume; highest-volume OR 1.31, 95% CI 1.14-1.50; high-volume OR 1.40, 95% CI 1.24-1.57). CONCLUSIONS: MSLT-II has impacted clinical care; however, male gender, thicker lesions, rural/urban residence, younger age, fewer comorbidities, and treatment at higher-volume centers confer a greater likelihood of undergoing CLND. Further investigations should focus on whether these populations benefit from more aggressive surgical care.


Assuntos
Melanoma , Linfonodo Sentinela , Neoplasias Cutâneas , Feminino , Humanos , Masculino , Estados Unidos/epidemiologia , Adolescente , Adulto , Melanoma/patologia , Excisão de Linfonodo , Biópsia de Linfonodo Sentinela , Bases de Dados Factuais , Probabilidade , Neoplasias Cutâneas/patologia , Linfonodo Sentinela/patologia
3.
Surg Oncol Clin N Am ; 32(1): 13-25, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36410913

RESUMO

Investigator-initiated trials (IITs) are designed by principal investigators who identify important, unaddressed clinical gaps and opportunities to answer these questions through clinical trials. Surgical oncologists are poised to lead IITs due to their multidisciplinary clinical practice and substantial research background. The process of developing, organizing, and implementing IITs is multifaceted and involves important steps including (but not limited to) navigating regulatory requirements, obtaining funding, and meeting enrollment targets. Here, the authors explore the steps, methodology, and barriers of IIT development by surgical oncologists and highlight the importance of IITs in oncology.


Assuntos
Oncologistas , Oncologia Cirúrgica , Humanos , Pesquisadores , Oncologia
4.
Am Surg ; 86(4): 377-385, 2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-32391763

RESUMO

Appalachian Kentucky (AK) has a disproportionally high breast cancer mortality rate. Postmastectomy radiotherapy (PMRT) in N2/N3 nodal disease improves survival and locoregional recurrence. We evaluated Kentucky patient compliance to the quality measure of PMRT received within one year of diagnosis. A population-based retrospective review of patients who received mastectomy with N2/N3 nodal disease from 2006 to 2015 was obtained through the Kentucky Cancer Registry. A total of 1489 patients met the inclusion criteria. Of these, 1104 (66.6%) received PMRT. AK patients were less likely to receive PMRT (58.3%) than non-AK patients (70%, P < 0.001). After adjusting for significant factors, private insurance, education level, treatment center, and receipt of adjuvant chemotherapy were independently associated with PMRT compliance. Patients who received PMRT had improved overall survival (OS, P < 0.0001) and disease-free survival (DFS, P < 0.0001). Appalachian status was not a major factor in OS (P= 0.1929) or DFS (P = 0.5840). Nearly two decades after the recommendation of PMRT, compliance remains poor in Kentucky. PMRT continues to be a major factor in survival and recurrence in this population. Interventions focusing on improving insurance coverage, education level, and guideline adherence in nonacademic centers are needed to improve compliance.


Assuntos
Neoplasias da Mama/radioterapia , Cooperação do Paciente , Radioterapia Adjuvante , Adulto , Idoso , Análise de Variância , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/cirurgia , Quimioterapia Adjuvante , Feminino , Humanos , Cobertura do Seguro , Seguro Saúde , Kentucky , Metástase Linfática , Mastectomia , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/prevenção & controle , Estudos Retrospectivos , Fatores Socioeconômicos , Análise de Sobrevida
5.
Cells ; 8(9)2019 08 30.
Artigo em Inglês | MEDLINE | ID: mdl-31480338

RESUMO

Unlike other breast cancer subtypes, patients with triple negative breast cancer (TNBC) have poor outcomes and no effective targeted therapies, leaving an unmet need for therapeutic targets. Efforts to profile these tumors have revealed the PI3K/AKT/mTOR pathway as a potential target. Activation of this pathway also contributes to resistance to anti-cancer agents, including microtubule-targeting agents. Eribulin is one such microtubule-targeting agent that is beneficial in treating taxane and anthracycline refractory breast cancer. In this study, we compared the effect of eribulin on the PI3K/AKT/mTOR pathway with other microtubule-targeting agents in TNBC. We found that the phosphorylation of AKT was suppressed by eribulin, a microtubule depolymerizing agent, but activated by paclitaxel, a microtubule stabilizing agent. The combination of eribulin and everolimus, an mTOR inhibitor, resulted in an increased reduction of p-S6K1 and p-S6, a synergistic inhibition of cell survival in vitro, and an enhanced suppression of tumor growth in two orthotopic mouse models. These findings provide a preclinical foundation for targeting both the microtubule cytoskeleton and the PI3K/AKT/mTOR pathway in the treatment of refractory TNBC.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Everolimo/farmacologia , Furanos/farmacologia , Cetonas/farmacologia , Fosfatidilinositol 3-Quinases/metabolismo , Inibidores de Proteínas Quinases/farmacologia , Proteínas Proto-Oncogênicas c-akt/antagonistas & inibidores , Serina-Treonina Quinases TOR/antagonistas & inibidores , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Animais , Antineoplásicos/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinogênese/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Everolimo/uso terapêutico , Feminino , Furanos/uso terapêutico , Humanos , Cetonas/uso terapêutico , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos NOD , Camundongos SCID , Inibidores de Proteínas Quinases/uso terapêutico
6.
J Surg Res ; 214: 79-85, 2017 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-28624063

RESUMO

BACKGROUND: The role of systemic chemotherapy in early-stage, estrogen receptor (ER)-positive, and Her2-negative breast cancer remains an area of active investigation. The decision to recommend chemotherapy is multifactorial, and some patients decline recommended chemotherapy. We sought to identify patient factors leading to refusal of adjuvant therapy. MATERIALS AND METHODS: Data were collected from National Comprehensive Cancer Network Outcomes database and used to identify patients with primary, unilateral, T1-T2, N0, ER+, Her2-disease diagnosed from 2005-2011. Patient and clinical characteristics were analyzed for associations with physician recommendation for chemotherapy and patient acceptance of chemotherapy. A logistic regression model was used to identify patient and tumor characteristics associated with recommendation for and acceptance of chemotherapy. RESULTS: A total of 329 patients were identified. Chemotherapy was recommended in 191 patients (58.1%) and not in 138 (41.9%). Young age (odds ratio [OR]: 3.9, 95% confidence interval [CI]: 1.2-12.7), large tumor size (6.69, 95% CI: 3.31-13.5), and high Oncotype DX scores (11.2, 95% CI: 4.5-27.9) were more likely to receive a recommendation. About 71 patients (37.1%) refused chemotherapy. Patients younger than age 50 (20.9, 95% CI: 2.5-172.0), larger tumor size (3.4, 95% CI: 1.3-8.7), Oncotype DX score > 31 (31.3, 95% CI: 3.3-295.0), privately insured (8.2, 95% CI: 1.9-34.7), and Hispanic ethnicity (5.2, 95% CI: 1.6-16.8) were more likely to accept chemotherapy. CONCLUSIONS: Physician recommendations for adjuvant chemotherapy for early-stage ER + breast cancer varied by commonly considered factors. Patient acceptance varied by similar factors but was also influenced by race and insurance status. This may be explained by cultural or social factors not well understood or not overcome by physician guidance.


Assuntos
Antineoplásicos/uso terapêutico , Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/tratamento farmacológico , Mastectomia , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Padrões de Prática Médica/estatística & dados numéricos , Receptores de Estrogênio/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Neoplasias da Mama/cirurgia , Quimioterapia Adjuvante , Bases de Dados Factuais , Feminino , Humanos , Modelos Logísticos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Receptor ErbB-2/metabolismo , Estados Unidos
7.
J Natl Compr Canc Netw ; 14(9): 1081-90, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-27587621

RESUMO

BACKGROUND: Antiestrogen (anti-e) use in estrogen receptor-positive (ER+) ductal carcinoma in situ (DCIS) has been shown to reduce the incidence of noninvasive and invasive breast cancer. Few studies have evaluated factors associated with anti-e recommendation in ER+ DCIS. METHODS: The California Cancer Registry was queried for female patients diagnosed with ER+ DCIS and treated with lumpectomy or unilateral mastectomy from 2004 to 2011. Patient demographics, comorbidities, and clinical characteristics were analyzed for association with anti-e recommendation. RESULTS: Of 5,527 patients identified, 76.4% patients underwent lumpectomy and 23.6% underwent unilateral mastectomy. Of the total cohort, 31.6% patients were recommended anti-e therapy, 60.4% were not, and the remaining 8.0% were recommended anti-e, but administration was not documented. Performance of lumpectomy predicted anti-e use compared with mastectomy (odds ratio [OR], 2.08; 95% CI, 1.77-2.43). Asian/Pacific Islanders were more often recommended anti-e therapy when compared with whites (OR, 1.28; 95% CI, 1.10-1.49). Patients younger than 70 years were more often recommended anti-e (age, 18-49 years: OR, 1.38; CI, 1.12-1.71; and age, 50-69 years: OR, 1.43; CI, 1.20-1.71). CONCLUSIONS: Despite current guidelines to consider the use of anti-e therapy, recommendation of anti-e after surgical treatment of DCIS is low, having been recommended to 40% of patients, and used by fewer than one-third. Significant predictors include lumpectomy compared with unilateral mastectomy, Asian/Pacific Islander race, younger age, and number of comorbidities. Further work is merited to understand patterns of anti-e therapy recommendation by providers in patients with DCIS.


Assuntos
Neoplasias da Mama/tratamento farmacológico , Carcinoma Ductal de Mama/tratamento farmacológico , Moduladores de Receptor Estrogênico/administração & dosagem , Receptores de Estrogênio/metabolismo , Adolescente , Adulto , Idoso , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/metabolismo , Carcinoma Ductal de Mama/patologia , Estudos de Coortes , Feminino , Humanos , Pessoa de Meia-Idade , Adulto Jovem
8.
Ann Surg Oncol ; 23(10): 3392-402, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-27503492

RESUMO

BACKGROUND: To optimize breast cancer care, several organizations have crafted guidelines to define best practices for treating breast cancer. In addition to recommended therapies, 'timeliness of treatment' has been proposed as a quality metric. Our study evaluates time to surgical treatment and its effect on overall survival (OS). METHODS: The National Cancer Data Base (NCDB) was used to identify women diagnosed with invasive breast cancer between 2004 and 2012. Time from diagnosis to surgical treatment was calculated and grouped according to predetermined time intervals. Univariate and multivariate Cox proportional hazard models were used to assess patient and treatment factors related to OS. RESULTS: Overall, 420,792 patients initially treated with surgery were identified. Increased time to surgical treatment >12 weeks was associated with decreased OS [hazard ratio (HR) 1.14, 95 % confidence interval (CI) 1.09-1.20]. When stratified by pathologic stage, stage I patients treated at 8 to <12 weeks (HR 1.07, 95 % CI 1.02-1.13) and >12 weeks (HR 1.19, 95 % CI 1.11-1.28), as well as stage II patients treated at >12 weeks (HR 1.16, 95 % CI 1.08-1.25), had decreased OS compared with patients treated at <4 weeks. Other variables associated with decreased survival were treatment at a community cancer program, Medicaid or Medicare insurance, Black race, increasing age, mastectomy, moderately and poorly differentiated tumor grade, increasing T and N stage, and higher Charlson Index Group. CONCLUSION: The survival benefit of expedited time to initial surgical treatment varies by stage and appears to have the greatest impact in early-stage disease. Prior to establishing standard metrics, further quantification of the impact on patient outcomes is needed.


Assuntos
Neoplasias da Mama/mortalidade , Neoplasias da Mama/terapia , Indicadores de Qualidade em Assistência à Saúde , Tempo para o Tratamento/estatística & dados numéricos , Adolescente , Adulto , Negro ou Afro-Americano/estatística & dados numéricos , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/patologia , Comorbidade , Bases de Dados Factuais , Feminino , Humanos , Mastectomia/estatística & dados numéricos , Medicaid/normas , Medicare/estatística & dados numéricos , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Modelos de Riscos Proporcionais , Taxa de Sobrevida , Tempo para o Tratamento/normas , Estados Unidos/epidemiologia , Adulto Jovem
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