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1.
Clin Cancer Res ; 29(4): 723-730, 2023 02 16.
Artigo em Inglês | MEDLINE | ID: mdl-36595540

RESUMO

PURPOSE: Neoadjuvant targeted therapy provides a brief, preoperative window of opportunity that can be exploited to individualize cancer care based on treatment response. We investigated whether response to neoadjuvant therapy during the preoperative window confers survival benefit in patients with operable head and neck squamous cell carcinoma (HNSCC). PATIENTS AND METHODS: A pooled analysis of treatment-naïve patients with operable HNSCC enrolled in one of three clinical trials from 2009 to 2020 (NCT00779389, NCT01218048, NCT02473731). Neoadjuvant regimens consisted of EGFR inhibitors (n = 83) or anti-ErbB3 antibody therapy (n = 9) within 28 days of surgery. Clinical to pathologic stage migration was compared with disease-free survival (DFS) and overall survival (OS) while adjusting for confounding factors using multivariable Cox regression. Circulating tumor markers validated in other solid tumor models were analyzed. RESULTS: 92 of 118 patients were analyzed; all patients underwent surgery following neoadjuvant therapy. Clinical to pathologic downstaging was more frequent in patients undergoing neoadjuvant targeted therapy compared with control cohort (P = 0.048). Patients with pathologic downstage migration had the highest OS [89.5%; 95% confidence interval (CI), 75.7-100] compared with those with no stage change (58%; 95% CI, 46.2-69.8) or upstage (40%; 95% CI, 9.6-70.4; P = 0.003). Downstage migration remained a positive prognostic factor for OS (HR, 0.22; 95% CI, 0.05-0.90) while adjusting for measured confounders. Downstage migration correlated with decreased circulating tumor markers, SOX17 and TAC1 (P = 0.0078). CONCLUSIONS: Brief neoadjuvant therapy achieved pathologic downstaging in a subset of patients and was associated with significantly better DFS and OS as well as decreased circulating methylated SOX17 and TAC1.


Assuntos
Neoplasias de Cabeça e Pescoço , Terapia Neoadjuvante , Humanos , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Intervalo Livre de Doença , Biomarcadores Tumorais
2.
Laryngoscope Investig Otolaryngol ; 7(3): 757-765, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35734044

RESUMO

Objectives: Data on the efficacy of including definitive local therapy to the primary site for head and neck squamous cell carcinoma (HNSCC) patients with synchronous distant metastasis are lacking. In multiple different solid tumor types, there has been benefit when using systemic therapy followed by local consolidative therapy (stereotactic ablative radiotherapy or surgery) directed at metastases. We proposed to retrospectively evaluate patients at our institution that received definitive treatment to the primary. Methods: Single institution retrospective study evaluating 40 patients with metastatic HNSCC treated with definitive surgery (55%) or chemoradiation (45%) to the primary site from 2000 to 2020. The major endpoints were overall survival (OS) and progression-free survival (PFS) for the total population and multiple sub-groups. Some variables were evaluated with multiple covariates Cox model. Results: The median PFS was 8.6 months (95% CI, 6.4-11.6), and OS was 14.2 months (95% CI, 10.9-27.5). In 28% of patients that received induction therapy, there was a twofold increase in median overall survival to 27.5 months. In the 33% of patients that received anti-PD-1 mAb as part of their treatment course, the median OS was significantly increased to 41.7 months (95% CI, 8.7-NR) versus 12.1 months (95% CI, 8.4-14.4) with a 5-year OS of 39%. Multivariate analysis for OS showed significance for age at diagnosis, use of IO, and number of metastatic sites. Conclusion: We observed impressive survival outcomes in metastatic HNSCC patients treated with definitive local therapy to the primary site in addition to induction and/or immunotherapy. Further study is warranted.Level of Evidence: 3.

3.
J Natl Compr Canc Netw ; 18(7): 873-898, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32634781

RESUMO

Treatment is complex for patients with head and neck (H&N) cancers with specific site of disease, stage, and pathologic findings guiding treatment decision-making. Treatment planning for H&N cancers involves a multidisciplinary team of experts. This article describes supportive care recommendations in the NCCN Guidelines for Head and Neck Cancers, as well as the rationale supporting a new section on imaging recommendations for patients with H&N cancers. This article also describes updates to treatment recommendations for patients with very advanced H&N cancers and salivary gland tumors, specifically systemic therapy recommendations.


Assuntos
Neoplasias de Cabeça e Pescoço , Neoplasias de Cabeça e Pescoço/diagnóstico , Neoplasias de Cabeça e Pescoço/terapia , Humanos , Oncologia , Guias de Prática Clínica como Assunto
4.
Eur J Cancer ; 107: 142-152, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30576970

RESUMO

BACKGROUND: Patients with recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC) progressing on platinum-based chemotherapy have poor prognoses and limited therapeutic options. Programmed cell death-1 (PD-1) and its ligand 1 (PD-L1) are frequently upregulated in HNSCC. The international, multi-institutional, single-arm, phase II HAWK study (NCT02207530) evaluated durvalumab monotherapy, an anti-PD-L1 monoclonal antibody, in PD-L1-high patients with platinum-refractory R/M HNSCC. PATIENTS AND METHODS: Immunotherapy-naïve patients with confirmed PD-L1-high tumour cell expression (defined as patients with ≥25% of tumour cells expressing PD-L1 [TC ≥ 25%] using the VENTANA PD-L1 [SP263] Assay) received durvalumab 10 mg/kg intravenously every 2 weeks for up to 12 months. The primary end-point was objective response rate; secondary end-points included progression-free survival (PFS) and overall survival (OS). RESULTS: Among evaluable patients (n = 111), objective response rate was 16.2% (95% confidence interval [CI], 9.9-24.4); 29.4% (95% CI, 15.1-47.5) for human papillomavirus (HPV)-positive patients and 10.9% (95% CI, 4.5-21.3) for HPV-negative patients. Median PFS and OS for treated patients (n = 112) was 2.1 months (95% CI, 1.9-3.7) and 7.1 months (95% CI, 4.9-9.9); PFS and OS at 12 months were 14.6% (95% CI, 8.5-22.1) and 33.6% (95% CI, 24.8-42.7). Treatment-related adverse events were 57.1% (any grade) and 8.0% (grade ≥3); none led to death. At data cut-off, 24.1% of patients remained on treatment or in follow-up. CONCLUSION: Durvalumab demonstrated antitumour activity with acceptable safety in PD-L1-high patients with R/M HNSCC, supporting its ongoing evaluation in phase III trials in first- and second-line settings. In an ad hoc analysis, HPV-positive patients had a numerically higher response rate and survival than HPV-negative patients.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Antineoplásicos Imunológicos/uso terapêutico , Antígeno B7-H1/metabolismo , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Terapia de Salvação , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/metabolismo , Feminino , Seguimentos , Neoplasias de Cabeça e Pescoço/metabolismo , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Agências Internacionais , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/metabolismo , Recidiva Local de Neoplasia/patologia , Prognóstico , Carcinoma de Células Escamosas de Cabeça e Pescoço/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço/secundário , Taxa de Sobrevida , Adulto Jovem
5.
Clin Genitourin Cancer ; 16(6): e1171-e1179, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30206026

RESUMO

INTRODUCTION: Current real-world data regarding treatment patterns in advanced bladder cancer in the community setting are limited. This study describes patient characteristics, treatment patterns, and effectiveness outcomes for stage IV bladder cancer in the community setting. METHODS: Medical records data of adults diagnosed with stage IV bladder cancer between January 1, 2008 and June 1, 2015 were retrospectively collected from a network of United States community oncology practices. Patient characteristics, treatment patterns, and efficacy outcomes were assessed. Across-group comparisons were conducted using bivariate analyses. Kaplan-Meier and Cox regression analyses of progression-free survival and overall survival (OS) were conducted. RESULTS: Of 508 patients (mean age, 70 ± 11 years), 75.2% were male, 79.1% white, 15.4% black, and 71.5% were ≥ 65 years. The most prevalent comorbidities were diabetes (23.4%) and renal disease (16.5%). Overall, 56% of patients received first-line platinum-based chemotherapy; the most common regimen was gemcitabine/carboplatin (23.6%), followed by gemcitabine/cisplatin (17%). The median OS was 9.4 months from stage IV bladder cancer diagnosis and 8.4 months from start of first-line therapy. Cox regression analysis of OS from diagnosis showed a higher risk of death for patients with no treatment (hazard ratio [HR], 2.06; P < .0001) or other treatment (HR, 1.83; P = .002) versus cisplatin and for patients with impaired performance (HR, 2.05; P < .0001). CONCLUSION: Platinum-based chemotherapy was the most prescribed treatment for stage IV bladder cancer in the community setting. Several patients were not treated with any chemotherapy, although we did not observe the reason for no treatment. This study highlights an unmet need in this population, particularly in a relapsed/refractory setting, and the need for improvement in outcomes.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Serviços de Saúde Comunitária/estatística & dados numéricos , Avaliação de Resultados em Cuidados de Saúde/estatística & dados numéricos , Padrões de Prática Médica/estatística & dados numéricos , Neoplasias da Bexiga Urinária/terapia , Idoso , Idoso de 80 Anos ou mais , Quimioterapia Adjuvante/métodos , Quimioterapia Adjuvante/estatística & dados numéricos , Cistectomia/estatística & dados numéricos , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prostatectomia/estatística & dados numéricos , Estudos Retrospectivos , Estados Unidos/epidemiologia , Neoplasias da Bexiga Urinária/mortalidade , Neoplasias da Bexiga Urinária/patologia
6.
Clin Ther ; 40(9): 1522-1537, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-30150077

RESUMO

PURPOSE: The purpose of this study was to provide an understanding of the effectiveness of existing therapies in patients with advanced head and neck cancer (HNC), particularly in clinical practice. METHODS: Data from the electronic medical records of adult patients diagnosed with locally advanced or metastatic (Stage III-IVc) HNC between January 1, 2007, and October 1, 2015, were retrospectively collected from a network of community oncology practices in the United States. Eligible patients experienced disease progression despite having received prior systemic therapy. Kaplan-Meier and Cox regression analyses of progression-free survival (PFS) and overall survival (OS) were conducted. Patient-reported outcomes were also collected. FINDINGS: The study included 462 patients (median age 61.0 years; 80.7% male; 77.1% white). Most patients had a history of tobacco use (41.8% current, 41.8% past), and human papillomavirus testing was infrequent overall (11.0%). The median overall duration of follow-up was 16.4 months (range, 2.3-85.2 months). Median PFS values were 8.45 months with first-line treatment and 5.33 months with second-line treatment. PFS with first-line treatment was significantly associated with primary tumor location, performance status, and tobacco use. Performance status was a predictor of PFS in second-line treatment. Median OS values were 21.04 and 9.53 months from the start of the first and second lines of therapy, respectively. Abuse/excessive use of alcohol, older age, and impaired performance status were associated with a significantly increased risk for death in outcomes analyses. Outcomes were worse among patients initially diagnosed with Stage IVc disease versus those who progressed to Stage IVc. Past tobacco use and alcohol abuse were associated with worse patient-reported symptoms such as dry mouth and sore throat (smoking) and trouble swallowing (alcohol). IMPLICATIONS: This study of data from clinical practice shows that there remains a large unmet need for effective therapeutic options in advanced HNC. Patients' characteristics such as alcohol use and performance status were statistically significant predictors of PFS and OS in Stage III-IVc HNC.


Assuntos
Neoplasias de Cabeça e Pescoço/patologia , Neoplasias de Cabeça e Pescoço/terapia , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Alcoolismo/complicações , Bases de Dados Factuais , Progressão da Doença , Intervalo Livre de Doença , Feminino , Nível de Saúde , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Estadiamento de Neoplasias , Intervalo Livre de Progressão , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Risco , Fumar Tabaco
7.
JAMA Oncol ; 4(11): 1583-1588, 2018 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-29931076

RESUMO

Importance: Immunotherapy for recurrent and/or metastatic (R/M) squamous cell carcinoma of the head and neck (SCCHN) is promising. The toll-like receptor 8 (TLR8) agonist motolimod may stimulate innate and adaptive immunity. Objective: To determine whether motolimod improves outcomes for R/M SCCHN when combined with standard therapy. Design, Setting, and Participants: The Active8 study was a multicenter, randomized, double-blind, placebo-controlled clinical trial enrolling adult patients (age ≥18 years) with histologically confirmed R/M SCCHN of the oral cavity, oropharynx, hypopharynx, or larynx between October 2013 and August 2015. Follow-up ended September 2016. Analysis for the present report was conducted between June 2016 and December 2017. Interventions: Combination treatment with platinum (carboplatin or cisplatin), fluorouracil, cetuximab (the EXTREME regimen), and either placebo or motolimod, each administered intravenously every 3 weeks. Patients received a maximum of 6 chemotherapy cycles, after which patients received weekly cetuximab with either placebo or motolimod every 4 weeks. Main Outcomes and Measures: Progression-free survival (PFS) as determined by independent central review using immune-related RECIST (Response Evaluation Criteria in Solid Tumors). Key secondary end points included overall survival (OS) and safety. Results: Of 195 patients enrolled, 85% were men (n = 166); 82% were white (n = 159); median age was 58 years (range 23-81 years). Median PFS was 6.1 vs 5.9 months (hazard ratio [HR], 0.99; 1-sided 90% CI, 0.00-1.22; P = .47), and median OS was 13.5 vs 11.3 months (HR, 0.95; 1-sided 90% CI, 0.00-1.22; P = .40) for motolimod vs placebo. Increased incidence of injection site reactions, pyrexia, chills, anemia, and acneiform rash were noted with motolimod. Of 83 cases oropharyngeal cancer, 52 (63%) were human papillomavirus (HPV) positive. In a prespecified subgroup analysis of HPV-positive participants, motolimod vs placebo resulted in significantly longer PFS (7.8 vs 5.9 months; HR, 0.58; 1-sided 90% CI, 0.00-0.90; P = .046) and OS (15.2 vs 12.6 months; HR, 0.41; 1-sided 90% CI, 0.00-0.77; P = .03). In an exploratory analysis, patients with injection site reactions had longer PFS and OS (median PFS, 7.1 vs 5.9 months; HR, 0.69; 1-sided 90% CI, 0.00-0.93; P = .06; and median OS, 18.7 vs 12.6; HR, 0.56; 1-sided 90% CI, 0.00-0.81; P = .02). Conclusions and Relevance: Adding motolimod to the EXTREME regimen was well tolerated but did not improve PFS or OS in the intent-to-treat population. Significant benefit was observed in HPV-positive patients and those with injection site reactions, suggesting that TLR8 stimulation may benefit subset- and biomarker-selected patients. Trial Registration: ClinicalTrials.gov identifier: NCT01836029.


Assuntos
Antineoplásicos Imunológicos/uso terapêutico , Benzazepinas/uso terapêutico , Cetuximab/uso terapêutico , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos Imunológicos/farmacologia , Benzazepinas/farmacologia , Cetuximab/farmacologia , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Intervalo Livre de Progressão , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Adulto Jovem
8.
J Natl Compr Canc Netw ; 16(5): 479-490, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29752322

RESUMO

The NCCN Guidelines for Head and Neck (H&N) Cancers provide treatment recommendations for cancers of the lip, oral cavity, pharynx, larynx, ethmoid and maxillary sinuses, and salivary glands. Recommendations are also provided for occult primary of the H&N, and separate algorithms have been developed by the panel for very advanced H&N cancers. These NCCN Guidelines Insights summarize the panel's discussion and most recent recommendations regarding evaluation and treatment of nasopharyngeal carcinoma.


Assuntos
Neoplasias de Cabeça e Pescoço , Guias como Assunto , História do Século XXI , Humanos
9.
Clin Ther ; 40(4): 562-573, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29530457

RESUMO

PURPOSE: The goal of this study was to describe patient characteristics, health resource utilization (HRU), and costs associated with treating recurrent or refractory head and neck cancer (HNC) among patients with disease progression in the community oncology setting. METHODS: This retrospective observational study was conducted by using data from the Vector Oncology Data Warehouse. Patients had been diagnosed with locally advanced or metastatic (stage III-IVc) HNC between January 1, 2007, and October 1, 2015. Patients also had evidence of at least 1 systemic anticancer therapy regimen following the diagnosis of advanced HNC, with at least 1 disease progression. Costs, treatment patterns, and HRU were evaluated beginning with diagnosis of advanced HNC through 3 lines of therapy. Costs of surgery or radiation were not available for inclusion in the analysis. Total cost for the study period and cost per month were analyzed by using a generalized linear regression model. FINDINGS: The study included 462 patients (median age, 61 years; range, 26-99 years); of these, 81% were male, 77% were white, and 21% were black. At initial diagnosis, the most frequent tumor locations were the hypopharynx/larynx (31%) and the oropharynx (31%). Human papilloma virus testing was most frequent among the oropharynx group (22% tested, 52% positive). Overall, 42% were current tobacco users and 22% were current or past alcohol abusers/excessive users. Platinum-based combination therapies were the most frequently administered chemotherapy in both first (42%) and second (40%) lines of treatment. Through the overall study period (mean, 20.5 months), 74% of patients were hospitalized, 19% had an emergency department visit, and 100% had an office visit. The overall mean (SD) duration of hospital stay was 12.6 days, and the median number of office visits per patient was 35. The mean monthly health care cost for the overall study period was $14,391 (95% CI, 12,739-16,044). Hospitalization costs represented ~57% of the total expenditures. Statistically significant predictors of higher overall cost included primary tumor location in the oral cavity, history of alcohol abuse/excess use, use of cetuximab, and higher comorbidity index. Older age and being stage IV versus other stages of disease at diagnosis were associated with lower overall cost. IMPLICATIONS: These data suggest that costs of care in patients with recurrent or refractory HNC are related to patient characteristics and treatment patterns. Identification of factors contributing to the costs of care in HNC may provide a useful foundation for developing strategies to control rising costs.


Assuntos
Neoplasias de Cabeça e Pescoço/terapia , Custos de Cuidados de Saúde , Hospitalização/economia , Adulto , Idoso , Idoso de 80 Anos ou mais , Terapia Combinada , Bases de Dados Factuais , Feminino , Neoplasias de Cabeça e Pescoço/economia , Recursos em Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
10.
J Natl Compr Canc Netw ; 15(6): 761-770, 2017 06.
Artigo em Inglês | MEDLINE | ID: mdl-28596256

RESUMO

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Head and Neck Cancers provide treatment recommendations for cancers of the lip, oral cavity, pharynx, larynx, ethmoid and maxillary sinuses, and salivary glands. Recommendations are also provided for occult primary of the head and neck (H&N), and separate algorithms have been developed by the panel for very advanced H&N cancers. These NCCN Guidelines Insights summarize the panel's discussion and most recent recommendations regarding the increase in human papillomavirus-associated oropharyngeal cancer and the availability of immunotherapy agents for treatment of patients with recurrent or metastatic H&N cancer.


Assuntos
Neoplasias de Cabeça e Pescoço/diagnóstico , Neoplasias de Cabeça e Pescoço/terapia , Neoplasias de Cabeça e Pescoço/etiologia , Humanos
11.
Med Oncol ; 34(7): 126, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28573640

RESUMO

While conventional organization of EGFR mutations in non-small cell lung cancer (NSCLC) includes classic lesions sensitive to tyrosine kinase inhibitors (TKI) and variants localized to the tyrosine kinase domain (TKD) in exons 18-21, next-generation sequencing (NGS) raises the prospect of identifying clinically relevant variants in extra-TKD regulatory regions. NSCLC patients at our institution who received tumor profiling with NGS from 2013 to 2015 were identified. EGFR mutations were arranged based upon their distribution relative to the TKD. In silico analysis was performed to predict non-synonymous single nucleotide polymorphism (nsSNP) pathogenicity. Of 247 patients, 43 EGFR variants were seen in 39 patients (16%). While 32 had TKD lesions demonstrable through standard testing, 7 had extra-TKD nsSNPs (7/43), of which 5 were extracellular domain (ECD), 1 juxtamembrane (JM) and 1 carboxy-terminal (CT). Aside from known pathogenic ECD mutation G598V, 5/6 extra-TKD nsSNPs were predicted damaging with in silico analysis. Seven of 7 extra-TKD nsSNP+ patients smoked and were stage IV; 5/7 were adenocarcinoma. An adenocarcinoma patient with JM R675Q had erlotinib, 150 mg daily, added following progression of disease on carboplatin and paclitaxel and had a partial response for 4 months. No other extra-TKD nsSNP+ patient received EGFR-directed therapy. >2% NSCLC cases in our cohort had EGFR nsSNPs located outside of the TKD, representing >16% of all EGFR mutations. Extra-TKD variants should be characterized collaboratively to determine TKI sensitivity and additional therapeutic targets.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/genética , Receptores ErbB/genética , Neoplasias Pulmonares/genética , Mutação , Inibidores de Proteínas Quinases/uso terapêutico , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Algoritmos , Carboplatina/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Simulação por Computador , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/genética , Cloridrato de Erlotinib/uso terapêutico , Feminino , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Paclitaxel/uso terapêutico , Polimorfismo de Nucleotídeo Único , Domínios Proteicos
12.
Case Rep Surg ; 2015: 424650, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26236536

RESUMO

Primary squamous cell carcinoma (SCC) of the gallbladder is a rare malignancy of the gallbladder, accounting for less than 5% of gallbladder pathology. Initial presentation is often similar to adenocarcinoma of the gallbladder. SCC tends to be more locally aggressive, however, and possesses a worse prognosis than adenocarcinoma. We report a case of locally advanced SCC of the gallbladder.

13.
J Natl Compr Canc Netw ; 13(6): 719-28; quiz 728, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26085388

RESUMO

The NCCN Guidelines for Rectal Cancer begin with the clinical presentation of the patient to the primary care physician or gastroenterologist and address diagnosis, pathologic staging, surgical management, perioperative treatment, posttreatment surveillance, management of recurrent and metastatic disease, and survivorship. The NCCN Rectal Cancer Panel meets at least annually to review comments from reviewers within their institutions, examine relevant new data from publications and abstracts, and reevaluate and update their recommendations. These NCCN Guidelines Insights summarize major discussion points from the 2015 NCCN Rectal Cancer Panel meeting. Major discussion topics this year were perioperative therapy options and surveillance for patients with stage I through III disease.


Assuntos
Neoplasias Retais/terapia , Terapia Combinada , Humanos , Guias de Prática Clínica como Assunto , Neoplasias Retais/diagnóstico
14.
Oncol Res ; 22(2): 117-21, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25706398

RESUMO

Chondroitin sulfate proteoglycan-4 (CSPG4), a membrane-bound proteoglycan known to be expressed on the surface of malignant cells, has a restricted distribution in normal tissues. CSPG4 is a potential candidate tumor marker. We investigate CSPG4 expression on blasts in newly diagnosed acute myeloid leukemia (AML) patients and its relation with cytogenetic abnormalities and molecular markers known to have prognostic significance in this disease. Using hybridoma technology, we generated a specific monoclonal antibody (mAb), mAb 225.28, reactive with CSPG4. Blast samples obtained from the peripheral blood of newly diagnosed AML patients were analyzed for CSPG4 expression using the CSPG4-specific mAb and multiparameter flow cytometry. The results were correlated with cytogenetic and molecular characteristics of AML. CSPG4 was found to be expressed on a variable fraction of leukemic blasts in all AML patients with different leukemia morphology, including monoblastic cases. Reactivity of CSPG4-specific mAb with leukemic blasts was not limited to those with the rearranged MLL gene. CSPG4 was also expressed on AML blasts with a complex karyotype, FLT3 mutation, or NPM1 mutation. The results indicate that CSPG4 is expressed and detectable by flow cytometry using the mAb 225.28 on a proportion of blasts of all subtypes of AML irrespective of cytogenetic and molecular abnormalities. mAb 225.28 could be useful in detecting AML blasts by flow cytometry.


Assuntos
Anticorpos Monoclonais/metabolismo , Proteoglicanas de Sulfatos de Condroitina/metabolismo , Leucemia Mieloide Aguda/metabolismo , Leucemia Mieloide Aguda/patologia , Proteínas de Membrana/metabolismo , Anticorpos Monoclonais/imunologia , Especificidade de Anticorpos/imunologia , Antígenos de Superfície/metabolismo , Biomarcadores Tumorais , Proteoglicanas de Sulfatos de Condroitina/imunologia , Aberrações Cromossômicas , Humanos , Imunofenotipagem , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/imunologia , Proteínas de Membrana/imunologia , Gradação de Tumores , Nucleofosmina
15.
J Natl Compr Canc Netw ; 12(7): 1028-59, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24994923

RESUMO

The NCCN Guidelines for Colon Cancer address diagnosis, pathologic staging, surgical management, perioperative treatment, posttreatment surveillance, management of recurrent and metastatic disease,and survivorship. This portion of the guidelines focuses on the use of systemic therapy in metastatic disease. The management of metastatic colorectal cancer involves a continuum of care in which patients are exposed sequentially to a variety of active agents, either in combinations or as single agents. Choice of therapy is based on the goals of treatment, the type and timing of prior therapy, the different efficacy and toxicity profiles of the drugs, the mutational status of the tumor, and patient preference.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/cirurgia , Neoplasias Hepáticas/secundário , Inibidores da Angiogênese/efeitos adversos , Inibidores da Angiogênese/uso terapêutico , Anticorpos Monoclonais Humanizados/efeitos adversos , Anticorpos Monoclonais Humanizados/uso terapêutico , Antineoplásicos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bevacizumab , Camptotecina/efeitos adversos , Camptotecina/análogos & derivados , Camptotecina/uso terapêutico , Capecitabina , Cetuximab , Neoplasias do Colo/patologia , Desoxicitidina/efeitos adversos , Desoxicitidina/análogos & derivados , Desoxicitidina/uso terapêutico , Progressão da Doença , Fluoruracila/efeitos adversos , Fluoruracila/análogos & derivados , Fluoruracila/uso terapêutico , GTP Fosfo-Hidrolases/genética , Humanos , Leucovorina/efeitos adversos , Leucovorina/uso terapêutico , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/cirurgia , Proteínas de Membrana/genética , Compostos Organoplatínicos/efeitos adversos , Compostos Organoplatínicos/uso terapêutico , Oxaloacetatos , Proteínas Proto-Oncogênicas/genética , Proteínas Proto-Oncogênicas B-raf/genética , Proteínas Proto-Oncogênicas p21(ras) , Resultado do Tratamento , Proteínas ras/genética
16.
J Natl Compr Canc Netw ; 11(5): 519-28, 2013 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-23667203

RESUMO

The NCCN Clinical Practice Guidelines in Oncology for Colon Cancer begin with the clinical presentation of the patient to the primary care physician or gastroenterologist and address diagnosis, pathologic staging, surgical management, perioperative treatment, patient surveillance, management of recurrent and metastatic disease, and survivorship. The NCCN Colon Cancer Panel meets annually to review comments from reviewers within their institutions and to reevaluate and update their recommendations. In addition, the panel has interim conferences as new data necessitate. These NCCN Guidelines Insights summarize the NCCN Colon Cancer Panel's discussions regarding the treatment of localized disease for the 2013 update of the guidelines.


Assuntos
Neoplasias do Colo/diagnóstico , Neoplasias do Colo/terapia , Detecção Precoce de Câncer , Humanos , Terapia Neoadjuvante , Estadiamento de Neoplasias
17.
J Natl Compr Canc Netw ; 11(2): 141-52; quiz 152, 2013 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-23411381

RESUMO

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Colon Cancer begin with the clinical presentation of the patient to the primary care physician or gastroenterologist and address diagnosis, pathologic staging, surgical management, perioperative treatment, patient surveillance, management of recurrent and metastatic disease, and survivorship. The NCCN Colon Cancer Panel meets annually to review comments from reviewers within their institutions and to reevaluate and update their recommendations. In addition, the panel has interim conferences as new data necessitate. These NCCN Guidelines Insights summarize the NCCN Colon Cancer Panel's discussions surrounding metastatic colorectal cancer for the 2013 update of the guidelines. Importantly, changes were made to the continuum of care for patients with advanced or metastatic disease, including new drugs and an additional line of therapy.


Assuntos
Neoplasias do Colo/terapia , Oncologia/normas , Neoplasias do Colo/patologia , Humanos , Oncologia/educação , Metástase Neoplásica , Guias de Prática Clínica como Assunto
18.
Blood ; 119(13): 3132-41, 2012 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-22323446

RESUMO

Hematologic maligancies exhibit a growth advantage by up-regulation of components within the molecular apparatus involved in cell-cycle progression. The SCF (Skip-Cullin1-F-box protein) E3 ligase family provides homeostatic feedback control of cell division by mediating ubiquitination and degradation of cell-cycle proteins. By screening several previously undescribed E3 ligase components, we describe the behavior of a relatively new SCF subunit, termed FBXL2, that ubiquitinates and destabilizes cyclin D2 protein leading to G(0) phase arrest and apoptosis in leukemic and B-lymphoblastoid cell lines. FBXL2 expression was strongly suppressed, and yet cyclin D2 protein levels were robustly expressed in acute myelogenous leukemia (AML) and acute lymphoblastic leukemia (ALL) patient samples. Depletion of endogenous FBXL2 stabilized cyclin D2 levels, whereas ectopically expressed FBXL2 decreased cyclin D2 lifespan. FBXL2 did not bind a phosphodegron within its substrate, which is typical of other F-box proteins, but uniquely targeted a calmodulin-binding signature within cyclin D2 to facilitate its polyubiquitination. Calmodulin competes with the F-box protein for access to this motif where it bound and protected cyclin D2 from FBXL2. Calmodulin reversed FBXL2-induced G(0) phase arrest and attenuated FBXL2-induced apoptosis of lymphoblastoid cells. These results suggest an antiproliferative effect of SCF(FBXL2) in lymphoproliferative malignancies.


Assuntos
Proliferação de Células , Ciclina D2/metabolismo , Proteínas F-Box/fisiologia , Leucemia/patologia , Animais , Apoptose/genética , Apoptose/fisiologia , Calmodulina/metabolismo , Calmodulina/fisiologia , Células Cultivadas , Regulação para Baixo/fisiologia , Proteínas F-Box/genética , Proteínas F-Box/metabolismo , Regulação Leucêmica da Expressão Gênica , Humanos , Células K562 , Leucemia/genética , Leucemia/metabolismo , Camundongos , Proteólise , Transfecção , Células U937 , Ubiquitinação/genética
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