RESUMO
INTRODUCTION: Information about survival outcomes in metastatic biliary tract cancer (BTC) is sparse, and the numbers often quoted are based on reports of clinical trials data that may not be representative of patients treated in the real world. Furthermore, the impact of more widespread adoption of a standardized combination chemotherapy regimen since 2010 on survival is unclear. METHODS: We performed an analysis of the Surveillance, Epidemiology, and End Results database to determine the real-world overall survival trends in a cohort of patients with metastatic BTC diagnosed between the years 2000 and 2017 with follow-up until 2018. We analyzed data for the entire cohort, evaluated short-term and long-term survival rates, and compared survival outcomes in the pre-2010 and post-2010 periods. Survival analysis was performed using the Kaplan-Meier method, and Cox proportional hazard models were used to evaluate factors associated with survival. RESULTS: Among 13, 287 patients, the median age was 68 years. There was a preponderance of female (57%) and white (77%) patients. Forty-one percent died within 3 months of diagnosis (short-term survivors) and 20% were long-term survivors (12 months or longer). The median overall survival (OS) for the entire cohort was 4.5 months. Median OS improved post-2010 (4.5 months) compared to pre-2010 (3.5 months) (P < .0001). On multivariate analysis, age <55 years, intrahepatic cholangiocarcinoma, surgical resection, and diagnosis post-2010 were associated with lower hazard of death. CONCLUSION: The real-world prognosis of metastatic BTC is remarkably poorer than described in clinical trials because a large proportion of patients survive less than three months. Over the last decade, the improvement in survival has been minimal.
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Neoplasias dos Ductos Biliares , Colangiocarcinoma , Estados Unidos/epidemiologia , Humanos , Feminino , Idoso , Pessoa de Meia-Idade , Neoplasias dos Ductos Biliares/terapia , Bases de Dados Factuais , Análise Multivariada , Ductos Biliares Intra-HepáticosRESUMO
INTRODUCTION: Despite aggressive surgical care and systemic therapy, patients with pancreatic ductal adenocarcinoma (PDAC) have a poor prognosis. Recent studies show that racial disparities in outcome also exist. We sought to investigate the association lymph node (LN) metastases had with survival between Black and White patients with PDAC after resection. METHODS: Retrospective analysis of 226 PDAC patients who underwent resection at a single institution from 2010 to 2018 was performed with attention to LN metastasis and patient race. The number of patients who received chemotherapy was also evaluated. RESULTS: One Hundred Seventy Five (77.4%) PDAC patients were White and 51 (22.6%) were Black. 130 (59.3%) patients had LN metastasis (LN+). LN+ and LN- groups were similar in race (P = 0.93), sex (P = 0.10) and age at the time of diagnosis (P = 0.45). Patients with LN + disease were more likely to present with larger tumors (3.4 versus 2.8 cm, P = 0.02) and higher T status (P = 0.001). White and Black patients had similar rates of LN metastasis (59% versus 58.8%, P = 1.0). The median survival for LN- Black and White patients were similar (43.2 versus 30.2 mo, P = 0.82). LN + Black patients trended towards receiving more systemic therapy than White LN + patients (55% versus 42%, P = 0.10). The median survival for LN + Black patients was significantly less than LN + White patients (17.5 versus 24.6 mo, P = 0.04). CONCLUSIONS: Black LN + PDAC patients have an inferior survival rate after resection when compared to their White counterparts. Our disparity in outcome cannot be solely explained by a difference in systemic treatment. Further investigation is warranted to determine racial differences in tumor biology or response to chemotherapy.
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Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Humanos , Estudos Retrospectivos , Metástase Linfática/patologia , Neoplasias Pancreáticas/cirurgia , Carcinoma Ductal Pancreático/cirurgia , Linfonodos/cirurgia , Linfonodos/patologia , Prognóstico , Estadiamento de Neoplasias , Taxa de Sobrevida , Neoplasias PancreáticasRESUMO
BACKGROUND: Despite recent advances in cancer, racial disparities in treatment outcomes persist, and their mechanisms are still not fully understood. The objective of this study was to examine racial differences in frailty and geriatric assessment impairments in an unselected cohort of older adults with newly diagnosed gastrointestinal (GI) malignancies. METHODS: This study used data from the Cancer and Aging Resilience Evaluation Registry, a prospective cohort study that enrolled older adults (≥60 years) with GI malignancies who were presenting for their initial consultation. Participants who had a geriatric assessment completed before chemotherapy initiation and self-reported as either White or Black were included. Frailty was defined with a frailty index based on the deficit accumulation method. The differences in the prevalence and adjusted odds ratios for frailty and geriatric assessment impairments between Black and White participants were examined. RESULTS: Of the 710 eligible patients who were seen, 553 consented with sufficient data for analyses. The mean age at enrollment was 70 ± 7.1 years, 58% were male, and 23% were Black. Primary cancer diagnoses included colorectal cancer (32%), pancreatic cancer (27%), and hepatobiliary cancer (18%). Black participants were more likely to be frail (50.0% vs 32.7%; P < .001) and report limitations in activities of daily living (27.3% vs 14.1%; P = .001), instrumental activities of daily living (64.8% vs 47.3%; P = .002), and walking 1 block (62.5% vs 48.2%; P = .004). These associations persisted even after adjustments for age, sex, education, cancer type, cancer stage, and comorbidity. CONCLUSIONS: Black participants were frailer and reported more limitations in function in comparison with White participants. These findings may partially explain disparities in cancer outcomes and warrant further examination.
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Fragilidade , Neoplasias Gastrointestinais , Atividades Cotidianas , Idoso , Feminino , Fragilidade/diagnóstico , Fragilidade/epidemiologia , Neoplasias Gastrointestinais/epidemiologia , Avaliação Geriátrica/métodos , Humanos , Masculino , Estudos Prospectivos , Sistema de RegistrosRESUMO
BACKGROUND: Poor self-rated health (SRH) is a known predictor of frailty and mortality in the general population; however, its role among older adults with cancer is unknown. We evaluated the role of SRH as a potential screening tool to identify frailty and geriatric assessment (GA)-identified impairments. MATERIALS AND METHODS: Adults ≥60 years diagnosed with cancer in the UAB Cancer & Aging Resilience Evaluation (CARE) registry underwent a GA at the time of initial consultation. We measured SRH using a single-item from the Patient-Reported Outcomes Measurement Information System global health scale and dichotomized responses as poor (poor, fair) and good (good, very good, and excellent). We evaluated the diagnostic performance of SRH in measuring frailty, and GA impairment (≥2 deficits among a set of seven GA domains). We examined the impact of SRH with survival using a Cox model adjusting for confounders, exploring the mediating role of frailty. RESULTS: Six hundred and three older adults with cancer were included, with a median age of 69 years. Overall, 45% (n = 274) reported poor SRH. Poor SRH demonstrated high sensitivity and specificity for identifying frailty (85% and 78%, respectively) and GA impairment (75% and 78%, respectively). In a Cox regression model, poor SRH was associated with inferior survival (HR = 2.26; 95% CI 1.60-3.18) after adjusting for confounders; frailty mediated 69% of this observed relationship. CONCLUSION: Self-rated health may be used as a screening tool to identify older adults with cancer with frailty and GA impairments. Poor SRH is associated with inferior survival, which is mediated by frailty.
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Fragilidade , Neoplasias , Idoso , Fragilidade/diagnóstico , Fragilidade/epidemiologia , Avaliação Geriátrica , Nível de Saúde , Humanos , Neoplasias/complicações , Neoplasias/epidemiologia , Modelos de Riscos Proporcionais , Sistema de RegistrosRESUMO
BACKGROUND: The NCCN Guidelines for Older Adult Oncology recommend that, when possible, older adults with cancer undergo a geriatric assessment (GA) to provide a comprehensive health appraisal to guide interventions and appropriate treatment selection. However, the association of age with GA-identified impairments (GA impairments) remains understudied and the appropriate age cutoff for using the GA remains unknown. PATIENTS AND METHODS: We designed a cross-sectional study using the Cancer and Aging Resilience Evaluation (CARE) registry of older adults with cancer. We included adults aged ≥60 years diagnosed with gastrointestinal malignancy who underwent a patient-reported GA prior to their initial consultation at the gastrointestinal oncology clinic. We noted the presence of GA impairments and frailty using Rockwood's deficit accumulation approach. We studied the relation between chronologic age and GA impairments/frailty using Spearman rank correlation and chi-square tests of trend. RESULTS: We identified 455 eligible older adults aged ≥60 years with gastrointestinal malignancies; the median age was 68 years (range, 64-74 years) and colorectal (33%) and pancreatic (24%) cancers were the most common cancer type. The correlation between chronologic age and number of geriatric impairments was weak and did not reach statistical significance (Spearman ρ, 0.07; P=.16). Furthermore, the prevalence of domain-specific impairments or frailty was comparable across the 3 age groups (60-64 years, 65-74 years, ≥75 years) with the exception of comorbidity burden. Notably, 61% of patients aged 60 to 64 years had ≥2 GA impairments and 35% had evidence of frailty, which was comparable to patients aged 65 to 74 years (66% and 36%, respectively) and ≥75 years (70% and 40%, respectively). CONCLUSIONS: Using chronologic age alone to identify which patients may benefit from GA is problematic. Future studies should identify screening tools that may identify patients at high risk of frailty and GA impairments.
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Fragilidade , Neoplasias Gastrointestinais , Neoplasias , Idoso , Estudos Transversais , Fragilidade/diagnóstico , Fragilidade/epidemiologia , Neoplasias Gastrointestinais/diagnóstico , Neoplasias Gastrointestinais/epidemiologia , Avaliação Geriátrica , Humanos , Pessoa de Meia-Idade , Neoplasias/complicações , Neoplasias/diagnóstico , Neoplasias/epidemiologia , Sistema de RegistrosRESUMO
Identifying individuals with hereditary syndromes allows for timely cancer surveillance, opportunities for risk reduction, and syndrome-specific management. Establishing criteria for hereditary cancer risk assessment allows for the identification of individuals who are carriers of pathogenic genetic variants. The NCCN Guidelines for Genetic/Familial High-Risk Assessment: Colorectal provides recommendations for the assessment and management of patients at risk for or diagnosed with high-risk colorectal cancer syndromes. The NCCN Genetic/Familial High-Risk Assessment: Colorectal panel meets annually to evaluate and update their recommendations based on their clinical expertise and new scientific data. These NCCN Guidelines Insights focus on familial adenomatous polyposis (FAP)/attenuated familial adenomatous polyposis (AFAP) syndrome and considerations for management of duodenal neoplasia.
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Polipose Adenomatosa do Colo , Neoplasias Colorretais , Polipose Adenomatosa do Colo/diagnóstico , Polipose Adenomatosa do Colo/genética , Polipose Adenomatosa do Colo/terapia , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/genética , Heterozigoto , Humanos , Fatores de RiscoRESUMO
PURPOSE: Fatigue is a component of frailty and may undermine functional well-being and independent living. The prevalence of fatigue and its impact on functional limitations among older adults with cancer remains understudied. METHODS: Using participants enrolled in the Cancer and Aging Resilience Evaluation (CARE), a prospective registry of patients (≥ 60 years) with cancer, who underwent a geriatric assessment (GA) at the first visit with oncology, we examined the presence of fatigue based on self-report of moderate to severe fatigue on PROMIS global health 10-item instrument at the time of GA. We examined the association of fatigue with impairments in instrumental activities of daily living (IADL) and activities of daily living (ADL) adjusting for age, sex, race/ethnicity, education, cancer type and stage, pain, comorbidities, and time from cancer. RESULTS: We included 374 older adults with cancer with a median age of 70 years; 56% were male and 23% black. Diagnoses included colorectal (33%) and pancreatic cancers (25%), with most patients with advanced stage disease (71% stage III/IV). Overall, 210 (58%) patients reported significant fatigue. Patients reporting significant fatigue had an increased odds of IADL (adjusted odds ratio, aOR 1.9; 95% CI 1.1-3.2) or ADL impairment (aOR 3.6; 95% CI 1.4-9.3), as compared to those without, after adjusting for aforementioned confounders. CONCLUSIONS: Over half of older adults with cancer reported moderate to severe fatigue that was independently associated with functional status limitations. Further understanding of the multifaceted aspects of fatigue and development of interventions combating fatigue in this population is urgently needed.
Assuntos
Atividades Cotidianas , Neoplasias Gastrointestinais , Idoso , Fadiga/epidemiologia , Fadiga/etiologia , Estado Funcional , Neoplasias Gastrointestinais/complicações , Neoplasias Gastrointestinais/epidemiologia , Avaliação Geriátrica , Humanos , Recém-Nascido , Masculino , Sistema de RegistrosRESUMO
BACKGROUND: A majority of older adults with cancer develop malnutrition; however, the implications of malnutrition among this vulnerable population are poorly understood. The goal of this study was to quantify the prevalence of nutrition related-symptoms and malnutrition among older adults with gastrointestinal (GI) malignancies and the association of malnutrition with geriatric assessment (GA) impairment, health-related quality of life (HRQoL), and health care utilization. METHODS: We performed a cross-sectional study of older adults (≥60 years) who were referred to the GI Oncology clinic at the University of Alabama at Birmingham. Participants underwent the Cancer & Aging Resilience Evaluation survey that includes the abbreviated Patient-Generated Subjective Global Assessment of nutrition. Nutrition scores were dichotomized into normal (0-5) and malnourished (≥6), and multivariate analyses adjusted for demographics, cancer type, and cancer stage were used to examine associations with GA impairment, HRQoL, and health care utilization. RESULTS: A total of 336 participants were included (men, 56.8%; women, 43.2%), with a mean age of 70 years (standard deviation, ±7.2 years) and colorectal cancer (33.6%) and pancreatic cancer (24.4%) being the most common diagnoses. Overall, 52.1% of participants were identified as malnourished. Malnutrition was associated with a higher prevalence of several GA impairments, including 1 or more falls (adjusted odds ratio [aOR], 2.1), instrumental activities of daily living impairment (aOR, 4.1), and frailty (aOR, 8.2). Malnutrition was also associated with impaired HRQoL domains; both physical (aOR, 8.7) and mental (aOR, 5.0), and prior hospitalizations (aOR, 2.2). CONCLUSION: We found a high prevalence of malnutrition among older adults with GI malignancies that was associated with increased GA impairments, reduced HRQoL, and increased health care utilization.
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Neoplasias Gastrointestinais/complicações , Desnutrição/epidemiologia , Desnutrição/etiologia , Qualidade de Vida , Idoso , Idoso de 80 Anos ou mais , Alabama , Estudos Transversais , Pessoas com Deficiência , Feminino , Idoso Fragilizado , Avaliação Geriátrica , Hospitalização , Humanos , Masculino , Pessoa de Meia-Idade , Estado Nutricional , PrevalênciaRESUMO
BACKGROUND: Only a few patients with pancreatic ductal adenocarcinoma (PDAC) recurring after curative resection and peri-operative (neoadjuvant and adjuvant) therapy are included in clinical trials of metastatic PDAC. As such, there is a paucity of data to guide treatment after relapse, and patients are treated similarly to those with de novo metastatic PDAC (mPDAC). We evaluated the patterns of chemotherapy use and over-all survival (OS) in patients with recurrent PDAC (rPDAC) following curative therapy. METHODS: In this retrospective study, the Indiana University pancreatic cancer database was used to identify patients with PDAC who underwent curative resection and subsequently developed recurrence. Demographics, tumor and treatment characteristics were collected. Patients were broadly divided into those who received chemotherapy for rPDAC and those who did not. Patients in the former category were further subdivided into those who received single agent therapy, any standard combination therapy (5-fluorouracil/irinotecan/oxaliplatin combination or gemcitabine/nab-paclitaxel) and those who received non-standard combinations. Survival analysis was performed by the Kaplan-Meier method. Log rank tests were used to determine differences in survival between treated rPDAC patients and those not treated. Cox regression analysis was employed to evaluate factors associated with OS. RESULTS: We identified 435 patients with resected PDAC treated between 2008 and 2014. Two hundred and twenty-three patients (51.2%) were diagnosed with rPDAC. Of these, 140 patients (63%) received chemotherapy whereas 71 patients (32%) did not receive chemotherapy. The 74 patients (53%) who received any standard, approved multiagent combination regimen had a median OS of 14 months compared to 8 months for the 47 patents (34%) who received other non-standard combinations and the 19 (13%) who received single agent therapy (P = 0.029). Multivariate cox regression analysis showed that margin negative resection, peri-operative therapy, radiotherapy and the use of any chemotherapy for rPDAC were associated with improved OS. CONCLUSION: Our findings support the use of standard approved multi-agent therapy in rPDAC. Patients derive significant benefit from these standard combination therapies with median OS that is comparable to what is observed with treatment for de novo mPDAC.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Ductal Pancreático/tratamento farmacológico , Neoplasias Pancreáticas/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Ductal Pancreático/mortalidade , Carcinoma Ductal Pancreático/secundário , Carcinoma Ductal Pancreático/cirurgia , Terapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/cirurgia , Estudos Retrospectivos , Análise de Sobrevida , Resultado do TratamentoRESUMO
Management of advanced intrahepatic cholangiocarcinoma (iCCA) is challenging and overall survival is poor. Progress in the development of new therapeutic options for metastatic cholangiocarcinoma (CCA) has been slow; hence, to date, there are no approved second-line agents in this setting. Although the development of immune checkpoint inhibitors has significantly improved overall survival in a variety of malignancies, there has not been a clinically important impact in CCA. This report presents a 66-year-old patient with chemotherapy-refractory iCCA who experienced a prolonged response to immunotherapy. Tumor genome profiling revealed a high tumor mutation burden of 17 mutations per megabase in the absence of microsatellite instability. He was started on immunotherapy with nivolumab and has experienced an ongoing response for 16 months without clinical symptoms and only minimal radiologic disease.
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Antineoplásicos Imunológicos/uso terapêutico , Neoplasias dos Ductos Biliares/terapia , Colangiocarcinoma/terapia , Neoplasias Hepáticas/terapia , Metástase Linfática/terapia , Nivolumabe/uso terapêutico , Idoso , Antineoplásicos Imunológicos/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias dos Ductos Biliares/genética , Neoplasias dos Ductos Biliares/imunologia , Neoplasias dos Ductos Biliares/patologia , Ductos Biliares Intra-Hepáticos/patologia , Ductos Biliares Intra-Hepáticos/cirurgia , Capecitabina/farmacologia , Capecitabina/uso terapêutico , Quimiorradioterapia Adjuvante/métodos , Colangiocarcinoma/genética , Colangiocarcinoma/imunologia , Colangiocarcinoma/secundário , Análise Mutacional de DNA , Resistencia a Medicamentos Antineoplásicos/genética , Fluoruracila/farmacologia , Fluoruracila/uso terapêutico , Humanos , Canal Inguinal/patologia , Leucovorina/farmacologia , Leucovorina/uso terapêutico , Fígado/diagnóstico por imagem , Fígado/patologia , Neoplasias Hepáticas/secundário , Metástase Linfática/diagnóstico por imagem , Masculino , Instabilidade de Microssatélites , Neoplasia Residual , Nivolumabe/farmacologia , Compostos Organoplatínicos/farmacologia , Compostos Organoplatínicos/uso terapêutico , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Resultado do TratamentoRESUMO
Intensive chemotherapeutic protocols and allogeneic stem cell transplantation continue to represent the mainstay of acute myeloid leukemia (AML) treatment. Although this approach leads to remissions in the majority of patients, long-term disease control remains unsatisfactory as mirrored by overall survival rates of approximately 30%. The reason for this poor outcome is, in part, due to various toxicities associated with traditional AML therapy and the limited ability of most patients to tolerate such treatment. More effective and less toxic therapies therefore represent an unmet need in the management of AML, a disease for which therapeutic progress has been traditionally slow when compared to other cancers. Several studies have shown that leukemic blasts elicit immune responses that could be exploited for the development of novel treatment concepts. To this end, early phase studies of immune-based therapies in AML have delivered encouraging results and demonstrated safety and feasibility. In this review, we discuss opportunities for immunotherapeutic interventions to enhance the potential to achieve a cure in AML, thereby focusing on the role of monoclonal antibodies, hypomethylating agents and the leukemic microenvironment.
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Antineoplásicos Imunológicos/uso terapêutico , Imunoterapia/métodos , Leucemia Mieloide Aguda , Microambiente Tumoral , Animais , Humanos , Leucemia Mieloide Aguda/imunologia , Leucemia Mieloide Aguda/patologia , Leucemia Mieloide Aguda/terapia , Microambiente Tumoral/efeitos dos fármacos , Microambiente Tumoral/imunologiaRESUMO
Importance: The association of adjuvant chemotherapy (AC) with survival in the general population of patients with resected biliary tract cancer (BTC) remains controversial. As such, the role of this treatment in the treatment of older adult patients (aged ≥70 years) needs to be evaluated. Objective: To describe the patterns of use of AC and compare survival outcomes of AC and observation in older adult patients following resection of BTC. Design, Setting, and Participants: This retrospective cohort study included 8091 older adult patients with resected BTC with data available in the National Cancer Database from January 1, 2004, to December 31, 2019. Patients were divided into 2 cohorts: AC and observation. The AC cohort was subdivided into single-agent and multiagent AC treatment. Exposures: Adjuvant chemotherapy vs observation following BTC resection. Main Outcomes and Measures: The primary outcome was overall survival (OS) of patients who received AC compared with observation following resection of BTC as evaluated using Kaplan-Meier estimates and multivariable Cox proportional hazards regression models. Inverse probability of treatment weighting and propensity score matching were performed to address indication bias. Results: Between 2004 and 2019, of 8091 older adult patients with resected BTC identified (median [range] age, 77 [70-90] years; 5136 women [63.5%]; 2955 men [36.5%]), only one-third (2632 [32.5%]) received AC. There was an increase in the use of AC across the study period from 20.7% (n = 495) in 2004 to 2009 to 41.2% (n = 856) in 2016 to 2019. Age 80 years or older (odds ratio, 0.29; 95% CI, 0.25-0.33; P < .001) and gallbladder primary site (odds ratio, 0.71; 95% CI, 0.61-0.83; P < .001) were associated with a lower odds of AC. Following inverse probability of treatment weighting, as a composite, AC was not associated with improved survival (median OS, 20.5 months; 95% CI, 19.2-21.7 months) compared with observation (median OS, 19.0 months; 95% CI, 18.1-20.3 months). A longer median OS was associated with single-agent AC (21.5 months; 95% CI, 19.9-24.0 months) but not multiagent AC (19.1 months; 95% CI, 17.5-21.1 months) compared with observation (median OS, 17.3 months; 95% CI, 16.1-18.4 months). This improvement in OS with single-agent AC was not apparent on multivariable analysis (hazard ratio [HR], 0.97; 95% CI, 0.89-1.05; P = .44). However, age at diagnosis of 80 years or older (HR, 1.35; 95% CI, 1.28-1.42; P < .001) and treatment at nonacademic centers (HR, 1.14; 95% CI, 1.07-1.20, P < .001) were associated with worse OS. Conclusions and Relevance: In this cohort study of older adult patients, AC was not associated with an improvement in survival compared with observation following BTC resection. These findings suggest the need for further study of AC for older adult patients who may benefit after curative intent surgery for BTC.
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Neoplasias do Sistema Biliar , Masculino , Humanos , Feminino , Idoso , Estudos de Coortes , Estudos Retrospectivos , Neoplasias do Sistema Biliar/tratamento farmacológico , Neoplasias do Sistema Biliar/cirurgia , Quimioterapia Adjuvante , Pontuação de PropensãoRESUMO
Gastroenteropancreatic high-grade (HG) neuroendocrine carcinoma (GEP-NEC) is an aggressive malignancy with limited treatment options and increasing incidence in the United States. Due to the rarity of the cancer and heterogeneity of the primary tumor location, data on GEP-NEC oncogenesis and its interaction with the host immune system are limited. A greater understanding of GEP-NEC and its tumor microenvironment (TME) would benefit efforts to develop more effective targeted therapies and rationally adapt immunotherapy to this disease. In this study, we profiled the expression of 770 unique genes using 21 biopsy samples from patients with GEP-NEC using the NanoString nCounter PanCancer IO 360 platform. Our results show several trends evident within the GEP-NEC TME. Greater expression of genes indicative of immune cell infiltration was present within the TME of patients <60 years of age and in patients with greater overall survival (OS). Tumors from patients with non-pancreatic NEC had diminished MHCII expression compared to pancreatic NEC, suggesting more prominent adaptive immune responses in the pancreatic GEP-NEC subtype. Patients with a >6 months OS had tumors with elevated NK cell gene signatures compared to patients with poor survival. Further, the analysis revealed numerous differentially expressed genes based on patient age, tumor location, response to treatment, and OS, which warrant future validation for assessing the relationship with clinical outcomes in patients.
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Carcinoma Neuroendócrino , Microambiente Tumoral , Humanos , Microambiente Tumoral/imunologia , Projetos Piloto , Masculino , Feminino , Carcinoma Neuroendócrino/imunologia , Carcinoma Neuroendócrino/genética , Carcinoma Neuroendócrino/patologia , Pessoa de Meia-Idade , Idoso , Neoplasias Pancreáticas/imunologia , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/patologia , Adulto , Neoplasias Gastrointestinais/imunologia , Neoplasias Gastrointestinais/genética , Neoplasias Gastrointestinais/patologia , Neoplasias Intestinais , Neoplasias Gástricas , Tumores NeuroendócrinosRESUMO
Background: Gallbladder cancer is one of the highest fatal malignancy. We conducted a retrospective analysis to study the outcomes of gallbladder malignancy in an academic care setting. Methods: Data was collected retrospectively on patients treated at University of Alabama at Birmingham between January 2005 and June 2015 from the electronic medical record using a standardized data collection tool (Redcap). We evaluated for predictors of overall survival (OS) and progression-free survival (PFS). Results: Of the 93 patients in this study, 66.7% were female. Adjuvant chemotherapy (CT) was given to 11% and adjuvant chemoradiation (CRT) to 14%. On multivariate analysis, albumin >3.5 g/dL, uninvolved margins, absence of lymphovascular invasion, and peri-neural invasion were independent predictors of OS and PFS. The overall median survival time was 24.3 months with a 5-year survival rate at 23.7%. Surgery with CRT for the full cohort had a median OS of 54.4 vs. 15.6 months (P=0.0048) compared to surgery CT alone. The OS in stage 3-4 patients with surgery alone vs. surgery & CT was 5.5 vs. 28.7 months, respectively (P=0.0061). The PFS for the same group was 4.6 vs. 17.5 months (P=0.0052). Conclusions: The dismal survival rates of gallbladder cancer made adjuvant therapy (CT or CRT) critically important. Concurrent CRT needs to be evaluated in randomized clinical trials for potential improvement in clinical outcomes compared to currently approved standard of care, adjuvant CT alone.
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BACKGROUND: Given the dearth of data regarding the time to treatment initiation (TTI) in the palliative setting, and its impact on survival outcomes, we sought to determine TTI in a real-world cohort of metastatic colorectal cancer (mCRC) and metastatic pancreatic cancer (mPC) patients and evaluate the impact of TTI on real-world survival outcomes. METHODS: We collected survival and treatment data for mCRC and mPC from the Flatiron Health electronic health records (EHR) derived database. We divided TTI into 3 categories: < 2 weeks, 2-< 4 weeks, and 4-8 weeks, from diagnosis to first-line therapy. Outcome measures were median TTI, real-world overall survival (RW-OS) based on TTI categories by Kaplan-Meier method, and impact of TTI on survival using cox proportional hazard models. RESULTS: Among 7108 and 3231 patients with mCRC and mPC treated within 8 weeks of diagnosis, the median TTI were 28 days and 20 days. Median RW-OS for mCRC was 24 months; 26.9 months versus 22.6 and 18.05 months in the 4-8-week, 2-< 4 week (control) and < 2-week groups, respectively (p < 0.0001). For mPC, median RW-OS was 8 months, without significant difference in RW-OS among the groups (p = 0.05). The 4-8-week group was associated with lower hazard of death (HR 0.782, 95% CI 0.73-0.84, p < 0.0001) and the < 2-week group was associated with a higher hazard of death (HR 1.26, 95% CI 1.15-1.38, p < 0.0001) in mCRC. The 4-8-week group was associated with lower hazard of death for mPC (HR 0.88, 95% CI 0.8-0.97, p = 0.0094). CONCLUSION: In a real-world cohort of patients treated within 8 weeks of diagnosis, and with the limitations of a retrospective study, later TTI did not have a negative impact on survival outcomes in mCRC and mPC.
Assuntos
Neoplasias do Colo , Neoplasias Colorretais , Neoplasias Pancreáticas , Neoplasias Retais , Humanos , Neoplasias Colorretais/patologia , Estudos Retrospectivos , Tempo para o TratamentoRESUMO
BACKGROUND: PD-1/PD-L1 immune checkpoint inhibitors (ICIs) are widely used in the treatment of metastatic malignancies. Judiciously balancing disease control (DC) against development of immune-related adverse events (irAE) remains a crucial aspect of treatment. The effect of treatment discontinuation after sustained disease control (SDC) is unknown. The purpose of this analysis was to evaluate outcomes of responders to ICI who discontinue treatment after a minimum of 12 months (SDC). METHODS: We retrospectively reviewed the database of the University of New Mexico Comprehensive Cancer Center (UNMCCC) between 2014 and 2021 and identified patients who had received ICI. Patients with metastatic solid tumors who had stopped ICI therapy after achieving SDC [stable disease, partial response, complete response (SD, PR, CR)] were selected and outcomes reviewed from their electronic health records. RESULTS: We identified 204 patients who were treated with ICI for various solid cancers. Forty-four patients (21.6%) met the criteria, of whom 35 with follow-up data were included in the final analysis; including 11 melanoma, 5 non-small cell lung, 4 head & neck, 8 renal, 4 urothelial, 1 anal, 1 Merkel cell carcinoma, and 1 liposarcoma. Patients were divided into two groups: those who stopped ICI due to an irAE [irAE group, n = 14, median treatment time (MTT), 16.6 mo] and those who stopped due to other reasons (eg completion of 2 years of therapy, n = 20, non-cancer related surgery, n = 1) (non-irAE group, n = 21, MTT, 23.7 mo). Among the irAE group, the most common irAE included pneumonitis, rash, transaminitis, and fatigue. As of data cutoff date, 9 of 14 (64%) patients continued to show SDC. Only 5 of 14 (36%) patients in this group experienced progression of disease (PD), with 1 of 2 patients achieving DC (median follow-up of 19.2 mo after last dose of treatment, range 3-50.2 mo). Among the non-irAE group, 13 of 21 (62%) continued to have SDC. Eight of 21 (38%) experienced PD after stopping treatment, 7 of whom received ICI rechallenge, with 2 of 7 achieving DC (median follow-up of 22.2 mo, range 3.6-54.8 mo). At a median follow-up of 21.3 mo from stopping ICI therapy (range, 3-54.8 mo), 10 patients (71%) from the irAE group and 13 (61.9%) from the non-irAE group are in DC and have not experienced PD. CONCLUSIONS: We demonstrate that 22 (66%) patients experienced SDC, regardless of cancer type or development of irAE. After including patients who were re-challenged with ICI due to PD, 25 (71%) remain in DC. Future prospective malignancy-specific trials are warranted to evaluate optimal treatment duration.
Assuntos
Antineoplásicos Imunológicos , Neoplasias Renais , Humanos , Inibidores de Checkpoint Imunológico/efeitos adversos , Receptor de Morte Celular Programada 1 , Estudos Retrospectivos , Antineoplásicos Imunológicos/efeitos adversos , Neoplasias Renais/patologiaRESUMO
To evaluate the safety and efficacy of combining yttrium-90 radioembolization (Y90-RE) with immune checkpoint inhibitor therapy, consecutive advanced unresectable hepatocellular carcinoma (HCC) patients treated between 2016 and 2022 with atezolizumab/bevacizumab or nivolumab within three-months pre- and post-Y90-RE were retrospectively evaluated. Tumor response and treatment-related clinical/laboratory adverse events (AE) were assessed at 1 and 6 months, as well as differences in clinical and laboratory variables and median overall survival (OS) from initial treatment (whether it was Y90-RE or systemic therapy) between the two cohorts. A total of 19 patients (10 atezolizumab/bevacizumab; 9 nivolumab), comprising 84% males with median age 69 years, met the inclusion criteria. Compared to the atezolizumab/bevacizumab group, there were less males (100% vs. 67%; p = 0.02) and more ECOG ≥ 2 patients in the nivolumab group (0% vs. 33%; p = 0.02). Baseline characteristics or incidence of 6-month post-treatment any-grade AE (60% vs. 56%; p = 0.7), grade ≥ 3 AE (0% vs. 11%; p = 0.3), objective response (58% total, 60% vs. 56%; p = 0.7), and complete response (16% total; 10% vs. 22%; p = 0.8) were similar between the atezolizumab/bevacizumab and the nivolumab cohorts. Median OS was 12.9 months for the whole cohort, 16.4 months for nivolumab, and 10.7 months for atezolizumab/bevacizumab. Among patients with advanced unresectable HCC, the utilization of Y90-RE concurrently or within 90 days of nivolumab or atezolizumab/bevacizumab immunotherapy, appears to be well-tolerated and with a low incidence of severe AE.
Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Masculino , Humanos , Idoso , Feminino , Carcinoma Hepatocelular/tratamento farmacológico , Bevacizumab/uso terapêutico , Nivolumabe/uso terapêutico , Estudos Retrospectivos , Neoplasias Hepáticas/tratamento farmacológicoRESUMO
BACKGROUND: Older adults with cancer are at increased risk of treatment-related toxicities and excess mortality. We evaluated whether a patient-reported geriatric assessment (GA) based frailty index can identify those at risk of adverse outcomes. METHODS: Older adults (≥60 years) enrolled in a single-institutional prospective registry underwent patient-reported GA at initial evaluation in our medical oncology clinic. Using deficit accumulation method, we constructed a 44-item frailty index (CARE-FI), categorizing patients as robust, pre-frail, and frail. The primary outcome was overall survival (OS). Secondary outcomes included (a) functional decline at 3 months post-therapy (b) incident grade ≥3 treatment-related toxicities at six-month post-treatment. We used multivariate Cox and logistic regression models respectively to study the impact of frailty on primary and secondary outcomes. RESULTS: We identified 589 older adults with a median age of 69 years; 55% males and 73% Whites. Overall, 168 (29%) were pre-frail and 230 (39%) frail. Being frail (vs. robust) was associated with worse OS (Hazards Ratio, HR 1.83, 95% Confidence Interval, CI 1.34-2.49, p < 0.001) after adjusting for age, sex, race/ethnicity, cancer type, cancer stage, and line of therapy. Similarly, frailty was associated with increased risk of functional decline (OR 3.01; 95% CI 1.33-6.81; p = 0.008) and grade ≥3 non-hematologic toxicities (OR 3.65; 95% CI 1.54-8.69; p = 0.003) but not hematologic toxicities (OR 1.01; 95% CI 0.46-2.22; p = 0.97). CONCLUSIONS: Our frailty index using a patient-reported GA is a robust predictor of survival, functional decline, and treatment related toxicity among older adults with GI malignancies.
Assuntos
Fragilidade , Neoplasias Gastrointestinais , Masculino , Idoso , Humanos , Feminino , Fragilidade/epidemiologia , Idoso Fragilizado , Avaliação Geriátrica/métodos , Medidas de Resultados Relatados pelo PacienteRESUMO
OBJECTIVES: Pancreatic cancer continues to be a major cause of cancer-related mortality. There has been a greater implementation of up-front chemotherapy for pancreatic adenocarcinoma patients. Although there are many theoretical benefits to neoadjuvant chemotherapy, its clinical impact is uncertain. We sought to understand the outcomes of patients with resectable and borderline-resectable pancreatic adenocarcinoma who underwent neoadjuvant chemotherapy. METHODS: Patients were collected in a secure database from September 2018 to May 2020. Patients were excluded if they presented with locally advanced or metastatic disease, inability to complete chemotherapy, or if they were not a surgical candidate. RESULTS: Sixty-six patients with resectable disease underwent chemotherapy. Folinic acid/5-fluorouracil/irinotecan/oxaliplatin was used in 41 patients (62.1%) and gemcitabine-based regimens in 28 patients (42.4%, greater than 100% as some patients underwent both regimens). After restaging, 47 patients (71.2%) were thought to have resectable disease. Of these patients, 36 have been successfully resected to date. Metastatic disease was found in 12 patients (18.2%) and 6 patients (9.1%) had locally advanced disease. CONCLUSIONS: Most patients with resectable pancreatic cancer are resected after neoadjuvant chemotherapy, but a subset will develop local or distant progression. Further studies will be needed to determine which patients will progress locally and may benefit from an up-front surgical approach.
Assuntos
Terapia Neoadjuvante , Neoplasias Pancreáticas/tratamento farmacológico , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bases de Dados Factuais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde , Neoplasias Pancreáticas/cirurgia , Neoplasias PancreáticasRESUMO
Curcumin inhibits UDP-glucuronyltransferases, a primary metabolic pathway for cancer chemotherapeutic agents like irinotecan. Concurrent administration of both agents may exacerbate irinotecan toxicity. We conducted this phase I study to determine the safety of concurrent curcumin and irinotecan administration. Ten participants with advanced solid tumors received one of four doses (1, 2, 3, and 4 g) of a curcumin phosphatidylcholine complex (PC) orally daily, and 200 mg/m2 of i.v. infusion irinotecan on days 1 and 15 of a 28-day cycle, to determine the maximum tolerated dose (MTD) of PC. Thirteen participants received 4 g of PC (MTD) to assess the effect on the pharmacokinetic (PK) properties of irinotecan and its metabolites, SN-38 and SN-38G. Irinotecan, SN-38, and SN-38G exposure equivalence with and without curcumin was assessed using area under the plasma concentration-time curves from 0 to 6 h (AUC0-6h ). Safety assessments and disease responses were also evaluated. The combination of irinotecan and PC was well-tolerated. Because there was no dose limiting toxicity, the maximum dose administered (4 g) was defined as the recommended phase II dose of PC. PC did not significantly alter the plasma exposure and other PK properties of irinotecan and its metabolites. There was no apparent increase in the incidence of irinotecan-associated toxicities. The objective response rate was 3/19 (22%, 95% confidence interval [CI]: 5-39%), median progression free survival and overall survival (n = 23) were 4 months (95% CI: 2.9-8.9 months) and 8.4 months (95% CI: 3.7 - not evaluable [NE]), respectively. Future studies are required to evaluate the efficacy of this combination.