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1.
J Natl Compr Canc Netw ; 22(2): 72-81, 2024 03.
Artigo em Inglês | MEDLINE | ID: mdl-38503043

RESUMO

Mesothelioma is a rare cancer that originates from the mesothelial surfaces of the pleura and other sites, and is estimated to occur in approximately 3,500 people in the United States annually. Pleural mesothelioma is the most common type and represents approximately 85% of these cases. The NCCN Guidelines for Mesothelioma: Pleural provide recommendations for the diagnosis, evaluation, treatment, and follow-up for patients with pleural mesothelioma. These NCCN Guidelines Insights highlight significant updates to the NCCN Guidelines for Mesothelioma: Pleural, including revised guidance on disease classification and systemic therapy options.


Assuntos
Mesotelioma Maligno , Mesotelioma , Neoplasias Pleurais , Humanos , Pleura , Mesotelioma/diagnóstico , Mesotelioma/terapia , Neoplasias Pleurais/diagnóstico , Neoplasias Pleurais/terapia
2.
J Natl Compr Canc Netw ; 22(4): 249-274, 2024 05.
Artigo em Inglês | MEDLINE | ID: mdl-38754467

RESUMO

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Non-Small Cell Lung Cancer (NSCLC) provide recommendations for the treatment of patients with NSCLC, including diagnosis, primary disease management, surveillance for relapse, and subsequent treatment. The panel has updated the list of recommended targeted therapies based on recent FDA approvals and clinical data. This selection from the NCCN Guidelines for NSCLC focuses on treatment recommendations for advanced or metastatic NSCLC with actionable molecular biomarkers.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/terapia , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/terapia , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/genética , Biomarcadores Tumorais/genética , Terapia de Alvo Molecular/métodos , Estadiamento de Neoplasias
3.
Acta Haematol ; : 1-15, 2024 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-38768573

RESUMO

INTRODUCTION: This study was designed to compare outcomes among patients by race and ethnicity in the post-covalent Bruton tyrosine kinase inhibitor (cBTKi) treatment era. METHODS: A nationwide electronic health record (EHR)-derived de-identified database was utilized that included patients diagnosed with CLL from 2013 to 2022 who received systemic therapy for their disease. Use of cBTKi therapy, time to next treatment or death (TTNT-D), and overall survival (OS) were compared by race in unadjusted (Kaplan-Meier method) and adjusted analyses (Cox proportional hazards regression). RESULTS: This study included 4,572 White (71.8%) and 558 Black (8.8%) patients with CLL; 270 were Hispanic or Latino (4.2%). Patients who were Black were significantly younger, more were female, had later stage disease, were of lower socioeconomic status (SES), and were more likely to have unmutated immunoglobulin heavy chain gene (IGHV) and to have received cBTKi therapy than White patients (all p ≤ 0.002). SES was also significantly different by ethnicity. TTNT-D and OS were not different by race in either unadjusted or adjusted analyses (all p > 0.05). CONCLUSION: In unadjusted and adjusted analyses, TTNT-D and OS were not different by race. These data did not identify racial healthcare disparities in the era following the introduction of cBTKi therapy despite differences in baseline characteristics.

4.
J Cancer Educ ; 2024 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-38637443

RESUMO

Knowledge related to how oncology treatment trial design influences enrollment of racial and ethnic minorities is limited. Rigorous identification of clinical trial design parameters that associate favorably with minority accrual provides educational opportunities for individuals interested in designing more representative treatment trials. We identified oncology trials with a minimum of 10 patients at an NCI-Designated Comprehensive Cancer Center from 2010 to 2021. We defined a study endpoint of racial and ethnic minority accrual greater than zero. Multivariable logistic regression was used to determine whether co-variables predicted our study endpoint. P-values of less than 0.05 were considered significant. A total of 352 cancer trials met eligibility criteria. These studies enrolled a total of 7981 patients with a total of 926 racial and ethnic minorities leading to a median enrollment of 10%. Trials open in community sites (yes versus no) were more likely to have a minority patient (OR, 2.21; 95% CI, 1.02-4.96) as well as pilot/phase I studies compared to phase II/III (OR, 3.19; 95% CI, 1.34-8.26). Trials incorporating immunotherapy (yes versus no) were less likely to have a minority patient (OR, 0.47; 95% CI, 0.23-0.94). Trials open in community sites as well as early phase treatment studies were more likely to accrue minority patients. However, studies including immunotherapy were less likely to accrue racial and ethnic minorities. Knowledge gained from our analysis may help individuals design oncology treatment trials that are representative of more diverse populations.

5.
J Natl Compr Canc Netw ; 21(9): 961-979, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37673108

RESUMO

Mesothelioma is a rare cancer originating in mesothelial surfaces of the peritoneum, pleura, and other sites. These NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) focus on peritoneal mesothelioma (PeM). The NCCN Guidelines for PeM provide recommendations for workup, diagnosis, and treatment of primary as well as previously treated PeM. The diagnosis of PeM may be delayed because PeM mimics other diseases and conditions and because the disease is so rare. The pathology section was recently updated to include new information about markers used to identify mesothelioma, which is difficult to diagnose. The term "malignant" is no longer used to classify mesotheliomas, because all mesotheliomas are now defined as malignant.


Assuntos
Mesotelioma Maligno , Mesotelioma , Humanos , Oncologia , Mesotelioma/diagnóstico , Mesotelioma/terapia , Peritônio
6.
J Natl Compr Canc Netw ; 21(4): 340-350, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-37015337

RESUMO

The NCCN Guidelines for Non-Small Cell Lung Cancer (NSCLC) provide recommendations for management of disease in patients with NSCLC. These NCCN Guidelines Insights focus on neoadjuvant and adjuvant (also known as perioperative) systemic therapy options for eligible patients with resectable NSCLC.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/terapia , Terapia Neoadjuvante
7.
J Natl Compr Canc Netw ; 20(5): 497-530, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35545176

RESUMO

NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Non-Small Cell Lung Cancer (NSCLC) provide recommended management for patients with NSCLC, including diagnosis, primary treatment, surveillance for relapse, and subsequent treatment. Patients with metastatic lung cancer who are eligible for targeted therapies or immunotherapies are now surviving longer. This selection from the NCCN Guidelines for NSCLC focuses on targeted therapies for patients with metastatic NSCLC and actionable mutations.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/terapia , Humanos , Imunoterapia , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/terapia , Oncologia , Recidiva Local de Neoplasia
9.
J Natl Compr Canc Netw ; 17(12): 1464-1472, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31805526

RESUMO

The NCCN Guidelines for Non-Small Cell Lung Cancer (NSCLC) address all aspects of management for NSCLC. These NCCN Guidelines Insights focus on recent updates in immunotherapy. For the 2020 update, all of the systemic therapy regimens have been categorized using a new preference stratification system; certain regimens are now recommended as "preferred interventions," whereas others are categorized as either "other recommended interventions" or "useful under certain circumstances."


Assuntos
Antineoplásicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Imunoterapia/métodos , Neoplasias Pulmonares/tratamento farmacológico , Guias de Prática Clínica como Assunto/normas , Carcinoma Pulmonar de Células não Pequenas/imunologia , Carcinoma Pulmonar de Células não Pequenas/patologia , Humanos , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/patologia
10.
JTO Clin Res Rep ; 5(3): 100643, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38496377

RESUMO

Introduction: Biomarker testing in oncology is fundamental for targeted therapy use and clinical trial participation. Factors contributing to previously identified racial disparities in biomarker testing remain unclear. This study investigated biomarker testing, clinical trial participation, and targeted therapy by race among patients with metastatic lung cancer with Medicaid coverage in the United States. Methods: The Merative MarketScan Medicaid claims database was used for this study to identify patients diagnosed with having metastatic lung cancer between 2017 and 2019 with at least 121 days of follow-up. Racial differences in biomarker testing, clinical trial enrollment, and targeted therapy use were analyzed using chi-square/t tests followed by logistic regression for confounding covariates. Results: A total of 3845 patients were eligible. A total of 970 (25.2%) patients included in this study were Black. Biomarker testing was observed among 57.0%, targeted therapy among 4.6%, and 2.6% of the study cohort had evidence of clinical trial participation. No significant disparities between Black and White races were identified. Younger age and metastatic disease at initial diagnosis were the strongest independent factors associated with increased biomarker testing. Biomarker testing was positively associated with targeted therapy use (OR = 1.69, p = 0.005). Conclusions: Patients with metastatic lung cancer with Medicaid coverage were found to have exceedingly low biomarker testing rates; only 57% had evidence of any biomarker testing. Although no consistent differences between Black and White races were identified, this study calls attention to care experienced by socioeconomically disadvantaged patients with metastatic lung cancer in the United States.

11.
Diagnostics (Basel) ; 13(6)2023 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-36980426

RESUMO

The treatment of non-small cell lung cancer has dramatically changed over the last decade through the use of targeted therapies and immunotherapies. Implementation of these treatment regimens relies on detailed knowledge regarding each tumor's specific genomic profile, underscoring the necessity of obtaining superior diagnostic tissue specimens. While these treatment approaches are commonly utilized in the metastatic setting, approval among earlier-stage disease will continue to rise, highlighting the importance of early and comprehensive biomarker testing at the time of diagnosis for all patients. Pulmonologists play an integral role in the diagnosis and staging of non-small cell lung cancer via sophisticated tissue sampling techniques. This multifaceted review will highlight current indications for the use of targeted therapies and immunotherapies in non-small cell lung cancer and will outline the quality of various diagnostic approaches and subsequent success of tissue biomarker testing. Pulmonologist-specific methods, including endobronchial ultrasound and guided bronchoscopy, will be examined as well as other modalities such as CT-guided transthoracic biopsy and more.

12.
Clin Lung Cancer ; 24(8): 696-705, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37993218

RESUMO

INTRODUCTION: Extensive-stage small-cell lung cancer (ES-SCLC) continues to have poor survival due to its aggressive behavior, despite improvements with incorporation of immunotherapy with standard chemotherapy. Controversy exists regarding the role of consolidative thoracic radiation therapy (TRT) and prophylactic cranial irradiation (PCI) in ES-SCLC due to high recurrence rates. We report our institutional result of the benefit of PCI and TRT in ES-SCLC. METHODS: Patients with ES-SCLC without intracranial metastasis at diagnosis (N = 163) were included. All patients completed systemic therapy with or without immunotherapy based on time of standard of care. Cohorts were divided by systemic therapy use and further subdivided by treatment with PCI and TRT. Overall survival (OS) and progression-free survival (PFS) were estimated by the Kaplan-Meier method with log-rank test for comparison. The effects of TRT and PCI were estimated by multivariable (MVA) Cox regression. RESULTS: Seventy-four patients (45.4%) received TRT, and 33.1% (n = 54) received PCI. The median follow-up was 11 months (3-85 months). PCI improved median OS to 15 months from 10 months, P = .02) and median PFS to 8.5 months from 5 months (P = .02) which remained significant on MVA, P = .02 and P = .02, respectively. TRT improved OS on UVA (P = 0.002) but was not significant on MVA. TRT did not improve PFS. CONCLUSION: This study including chemotherapy and chemo-immunotherapy suggests improved outcomes with addition of PCI in patients with ES-SCLC while TRT did not show benefit to either OS or PFS. A future trial is needed to evaluate the role of TRT and PCI in the era of chemo-immunotherapy.


Assuntos
Neoplasias Pulmonares , Carcinoma de Pequenas Células do Pulmão , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Carcinoma de Pequenas Células do Pulmão/tratamento farmacológico , Irradiação Craniana/métodos , Imunoterapia
13.
Cancer Manag Res ; 15: 913-927, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37674660

RESUMO

Purpose: Disparities in cancer care delivery remain a pressing health-care crisis within the United States (US). The use of immune checkpoint inhibitors (ICIs) and their management may be a disparity generator that impacts survival. This retrospective study assessed disparities in a cohort of patients with a variety of solid tumors treated with ICIs within a single health-care organization focusing on the impact of race, socioeconomic status (SES) and site of care delivery on survival and the development of severe immune-related adverse events (irAEs). Patients and Methods: Manual chart review was performed on all patients with solid tumors treated with ICIs within a health-care organization from 2012 to 2018. Care delivery was dichotomized as DOP (disease-oriented provider at academic center) and COP (community oncology provider). Primary and secondary outcomes were overall survival (OS) and rates of grade 3-4 irAEs, respectively. Relationships with covariates of interest, including race, socioeconomic status and type of care delivery, were assessed among both outcomes. Results: A total of 1070 eligible patients were identified. Of those, 11.4% were of Black race, 59.7% had either non-small cell lung cancer (NSCLC) or melanoma and 82.8% had stage IV disease. Patients of Black race and lower SES were more likely to be treated by DOPs (p<0.0001). A superior OS was associated with care delivered by DOPs when compared to COPs (HR 0.68; 95% CI 0.56-0.84; p=0.0002), which was durable after accounting for race, SES, histopathologic diagnosis and disease stage. Melanoma patients experienced higher rates of severe irAEs (HR 2.37; 95% CI 1.42-3.97; p=0.001). Race, SES and site of care delivery were not related to rates of severe irAEs. Conclusion: In a large health-care organization, patients treated with checkpoint inhibitors by DOPs benefited from a significant OS advantage that was durable after controlling for racial and socioeconomic factors, providing evidence that disease-oriented care has the potential to mitigate racial and socioeconomic disparities.

14.
JAMA Otolaryngol Head Neck Surg ; 149(12): 1101-1110, 2023 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-37796484

RESUMO

Importance: Cancer survivors are at a higher risk of developing hearing loss (HL) due to older age, chemotherapy, and radiotherapy. However, the prevalence of HL among US cancer survivors remains unknown. Additionally, there is a lack of uniform HL screening guidelines for this enlarging population. Objective: To estimate the prevalence of subjective HL and objective HL by audiometry test among cancer survivors and compare them with the general population as well as to assess the performance of subjective HL questions in detecting true (ie, audiometry-confirmed) HL. Design, Setting, and Participants: In a cross-sectional design, adults between ages 20 and 80 years who had audiometry testing and responded to a hearing questionnaire from the National Health and Nutrition Examination Survey (2011-2012, 2015-2016, and 2017 to March 2020 prepandemic survey cycles) were selected. Data analysis was conducted from August 13, 2022, to July 26, 2023. Main Outcomes and Measures: The weighted prevalence of subjective HL (troublesome hearing and tinnitus) and objective HL (speech-frequency HL and high-frequency HL) by audiometry were calculated. Analyses with χ2 testing and multiadjusted logistic regression models were used to compare HL between cancer survivors and the general population. To evaluate the performance of subjective HL questions as a tool to screen for objective HL by audiometry, areas under the curve were estimated using age- and gender-adjusted logistic regression. Results: Among the total 9337 participants (weighted n = 90 098 441; 51.2% women), 10.3% were cancer survivors. Compared with the general population, cancer survivors had a higher prevalence of troublesome hearing (adjusted odds ratio [AOR], 1.43; 95% CI, 1.11-1.84), tinnitus (AOR, 1.28; 95% CI, 0.94-1.74), speech-frequency HL (AOR, 1.43; 95% CI, 1.11-1.85), and high-frequency HL (AOR, 1.74; 95% CI, 1.29-2.34). When using the subjective HL tool and questioning regarding whether the participants were having troublesome hearing and/or tinnitus in screening for HL, the age- and gender-adjusted area under the curve was 0.88 in detecting speech-frequency HL and 0.90 in detecting high-frequency HL. Conclusion and Relevance: The findings of this study suggest that cancer survivors have a significantly higher prevalence of HL than the general population. Two subjective HL questions could potentially accurately identify those who have true HL and provide a simple and efficient screening tool for health care professionals. Cancer survivors and their families should be educated and encouraged to discuss hearing concerns, and health care professionals should facilitate raising awareness and provide early screening and timely referral when HL is identified.


Assuntos
Sobreviventes de Câncer , Surdez , Neoplasias , Zumbido , Adulto , Humanos , Feminino , Masculino , Zumbido/diagnóstico , Zumbido/epidemiologia , Zumbido/etiologia , Inquéritos Nutricionais , Estudos Transversais , Neoplasias/complicações , Neoplasias/epidemiologia , Perda Auditiva de Alta Frequência , Audiometria de Tons Puros
15.
J Thorac Oncol ; 18(7): 907-921, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-36842467

RESUMO

INTRODUCTION: Sitravatinib, a receptor tyrosine kinase inhibitor targeting TYRO3, AXL, MERTK receptors, and vascular epithelial growth factor receptor 2, can shift the tumor microenvironment toward an immunostimulatory state. Combining sitravatinib with checkpoint inhibitors (CPIs) may augment antitumor activity. METHODS: The phase 2 MRTX-500 study evaluated sitravatinib (120 mg daily) with nivolumab (every 2 or 4 wk) in patients with advanced nonsquamous NSCLC who progressed on or after previous CPI (CPI-experienced) or chemotherapy (CPI-naive). CPI-experienced patients had a previous clinical benefit (PCB) (complete response, partial response, or stable disease for at least 12 weeks then disease progression) or no PCB (NPCB) from CPI. The primary end point was objective response rate (ORR); secondary objectives included safety and secondary efficacy end points. RESULTS: Overall, 124 CPI-experienced (NPCB, n = 35; PCB, n = 89) and 32 CPI-naive patients were treated. Investigator-assessed ORR was 11.4% in patients with NPCB, 16.9% with PCB, and 25.0% in CPI-naive. The median progression-free survival was 3.7, 5.6, and 7.1 months with NPCB, PCB, and CPI-naive, respectively; the median overall survival was 7.9 and 13.6 months with NPCB and PCB, respectively (not reached in CPI-naive patients; median follow-up 20.4 mo). Overall, (N = 156), any grade treatment-related adverse events (TRAEs) occurred in 93.6%; grade 3/4 in 58.3%. One grade 5 TRAE occurred in a CPI-naive patient. TRAEs led to treatment discontinuation in 14.1% and dose reduction or interruption in 42.9%. Biomarker analyses supported an immunostimulatory mechanism of action. CONCLUSIONS: Sitravatinib with nivolumab had a manageable safety profile. Although ORR was not met, this combination exhibited antitumor activity and encouraged survival in CPI-experienced patients with nonsquamous NSCLC.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Nivolumabe/farmacologia , Nivolumabe/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/patologia , Anilidas/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Microambiente Tumoral
16.
JCO Precis Oncol ; 6: e2100427, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35737912

RESUMO

PURPOSE: Comprehensive tumor biomarker testing is a fundamental step in the selection of highly effective molecularly driven therapies for a variety of solid tumors. The primary objective of this study was to examine racial differences in biomarker testing and clinical trial participation in the United States using a real-world database. METHODS: Patients in a real-world deidentified database diagnosed with advanced/metastatic non-small-cell lung cancer (NSCLC), metastatic colorectal cancer (CRC), or metastatic breast cancer were eligible. Biomarker testing and clinical trial participation was compared between Black and White racial groups using chi-squared test and stepwise logistic regression controlling for baseline covariates. RESULTS: A total of 23,488 patients met eligibility criteria. Next-generation sequencing (NGS) testing rates differed significantly between White versus Black race before first-line therapy (36.6% v 29.7%, P < .0001) and at any given time (54.7% v 43.8%, P < .0001) in the nonsquamous NSCLC cohort. Similar disparities in NGS testing rates at any time during the study were observed among patients with CRC (White 51.6%; Black 41.8%, P < .0001). No differences were observed in the breast cancer cohort. Patients of Black race were less likely to be treated in a clinical trial in the overall NSCLC cohort when compared with White counterparts (3.9% v 2.1%, P = .0002). A statistically significant relationship between biomarker/NGS testing and clinical trial enrollment was observed in all cohorts (P < .003) after adjusting for covariates. CONCLUSION: In a real-world database, significant disparities in NGS-based testing rates were observed between Black and White races in NSCLC and CRC. NGS and any biomarker testing were both associated with trial enrollment in all cohorts. There is a need for interventions to promote access to comprehensive testing for patients with advanced/metastatic tumors.


Assuntos
Neoplasias da Mama , Carcinoma Pulmonar de Células não Pequenas , Neoplasias do Colo , Neoplasias Pulmonares , Biomarcadores Tumorais/genética , Neoplasias da Mama/diagnóstico , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Feminino , Humanos , Pulmão , Neoplasias Pulmonares/diagnóstico , Estados Unidos/epidemiologia
17.
JTO Clin Res Rep ; 3(4): 100307, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35400080

RESUMO

Introduction: Lung cancer is the leading cause of cancer-related death and the second most often diagnosed malignancy worldwide. Males have higher incidence of lung cancer and higher mortality. It is hypothesized that the sex differences in survival are primarily driven by a better response of females to treatment. The primary objective of this work is to analyze and describe outcome differences between males and females diagnosed with having lung cancer. Methods: Data were obtained from a large hybrid academic-community practice institution and validated with Surveillance, Epidemiology, and End Results (SEER). The initial cohort included patients aged more than or equal to 18 years diagnosed with having primary malignant lung cancer. Patients were excluded from the analysis if they had an unknown diagnosis date, were missing sex, or had prior history of cancer. Chi-square, t test, and Kruskal-Wallis tests were used to compare characteristics of males and females. Risks were estimated by logistic and Cox regressions. Results: A total of 8909 patients from our institution and 725,018 in SEER were analyzed. Male-to-female ratio was 1.0. Females were more likely to undergo surgery and less likely to be treated with immunotherapy. Females had higher rates of documented psychological affections, depression, anxiety, urinary tract infection, hypothyroidism, and hyperthyroidism, while displaying lower rates of acute kidney injury, myocardial infarction, and myocarditis. Paired multivariable models revealed a lower risk of death for females in SEER (hazard ratio for females = 0.84, confidence interval: 0.69-1.02, p = 0.08) and equal risks in our institution (hazard ratio for females = 0.84, confidence interval: 0.69-1.02, p = 0.08). Conclusions: Female sex was associated with higher surgical rates, lower immunotherapy use rates, higher rates of endocrinologic complications after immunotherapy use, and higher rates of psychological disorders.

18.
Clin Cancer Res ; 28(4): 646-652, 2022 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-34740922

RESUMO

PURPOSE: TRC102, a small-molecule base-excision repair inhibitor, potentiates the cytotoxicity of pemetrexed and reverses resistance by binding to chemotherapy-induced abasic sites in DNA. We conducted a phase I clinical trial combining pemetrexed and TRC102 with cisplatin-radiation in stage III nonsquamous non-small cell lung cancer (NS-NSCLC). PATIENTS AND METHODS: Fifteen patients were enrolled from 2015 to 2019. The primary objective was to determine the dose-limiting toxicity and maximum tolerated dose of TRC102 in combination with pemetrexed, cisplatin, and radiotherapy. Secondary objectives were to assess toxicity, tumor response, and progression-free survival at 6 months. Based on our preclinical experiments, pemetrexed-TRC102 was given on day 1, and cisplatin/radiotherapy was initiated on day 3. This schedule was duplicated in the second cycle. After completion, two additional cycles of pemetrexed-cisplatin were given. Toxicities were assessed using NCI CTACAE versions 4/5. RESULTS: The median age was 69 years (45-79) with the median follow-up of 25.7 months (range, 7.9-47.4). No dose-limiting toxicities and no grade 5 toxicity were seen. Hematologic and gastrointestinal toxicities were the most common side effects. No clinical radiation pneumonitis was seen. Of 15 evaluable patients, three had complete response (20%), and 12 had partial response (80%). The 6-month progression-free survival was 80%, and the 2-year overall survival was 83%. CONCLUSIONS: Pemetrexed-TRC102 combined with cisplatin/radiotherapy in NS-NSCLC is safe and well tolerated. The recommended phase II dose is 200 mg TRC102 along with cisplatin-pemetrexed. No additional safety signal was seen beyond the expected CRT risks. A phase II trial, integrating post-CRT immunotherapy with this aggressive DNA-damaging regimen, is warranted.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Cisplatino , Reparo do DNA , Glutamatos/efeitos adversos , Guanina/efeitos adversos , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Pemetrexede/efeitos adversos , Platina/uso terapêutico
19.
Clin Lung Cancer ; 22(1): 16-22.e1, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33397584

RESUMO

BACKGROUND: Next generation sequencing (NGS) of tumor of patients with advanced non-small cell lung cancer (NSCLC) is now a standard of care that informs the clinician on the best therapeutic approach for their patients. The purpose of our study was to investigate the overall impact of NGS testing on survival as well as potential racial differences in utilization, therapeutic decision, and genomic alterations. METHOD: Using a large institutional database, 928 patients with stage IV NSCLC were identified. NGS testing using Foundation One platform was used. Clinical and genomic characteristics were compared by race. We used a propensity-modeling technique to compare groups that were sequenced or not in terms of overall survival. Time to event data was analyzed using Kaplan-Meier method and Cox model. RESULTS: A total of 295 patients underwent NGS. Patients undergoing NGS testing had significantly longer survival of 25.3 months versus those who did not undergo sequencing with a median survival of 14.6 months (P = .002) irrespective if they received targeted therapy or not. There was no difference in terms of NGS utilization based on race (P = .32). African American individuals had significantly higher rates of ALK rearrangements and mutations in PBRM1, SETD2, TSC2, and FBXW7. CONCLUSION: Our study demonstrates that within a large single institution there is no racial difference in NGS utilization and that NGS testing directly impacts survival. We identify a number of differences in genomic findings between African American and white individuals.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores Tumorais/genética , Negro ou Afro-Americano/estatística & dados numéricos , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Mutação , População Branca/estatística & dados numéricos , Adenocarcinoma de Pulmão/tratamento farmacológico , Adenocarcinoma de Pulmão/etnologia , Adenocarcinoma de Pulmão/mortalidade , Adenocarcinoma de Pulmão/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/etnologia , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/etnologia , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/patologia , Etnicidade/estatística & dados numéricos , Feminino , Seguimentos , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/etnologia , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida
20.
Ann Transl Med ; 8(Suppl 1): S13, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32309417

RESUMO

Obesity is second only to tobacco as a preventable cause of cancer in the US. By multifactorial and often additive mechanisms, obesity leads to the development and promotion of 40% of the cancers diagnosed in this country, including post-menopausal breast, endometrial, colorectal, kidney, liver and pancreatic cancers, among others. Though prevention of obesity should be the ultimate goal of thoughtful and effective healthcare practices, it remains a highly prevalent condition, and morbid obesity (BMI ≥40 Kg/m2) can be refractory to lifestyle interventions in many cases. Currently bariatric surgery is an effective treatment strategy for individuals who suffer from morbid obesity or obesity with associated co-morbidities and fail to lose weight under a medically supervised diet and exercise program. The current review addresses seminal studies that have investigated the potential cancer prevention effects of bariatric surgery, demonstrating a positive impact mostly in post-menopausal breast and endometrial cancers. The controversial association between bariatric surgery and increased colorectal cancer (CRC) risk is also recognized and discussed. Finally, while bariatric surgery should not be routinely recommended as a cancer prevention strategy, it has the potential to decrease the risk for certain types of cancers as a collateral beneficial effect.

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