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INTRODUCTION: Checkpoint inhibitors (CPI) have significantly improved survival among patients with various cancer types. Prior studies have shown a correlation between immune cell infiltration and poorly differentiated cancers. This study evaluated the impact of poorly differentiated histology on survival in patients with advanced gastrointestinal cancers treated with immunotherapy. METHODS: This study was a retrospective, single-center analysis of patients with gastrointestinal cancers treated with CPIs between 2016 and 2021. Univariate and multivariable analyses were performed to identify factors associated with patient outcome. Kaplan-Meier analysis and Cox proportional hazards models were used to assess the association between tumor and patient characteristics, progression-free survival, and overall survival. RESULTS: A total of 123 patients were eligible and included in the analysis. Median age was 66 years (23-88 years). Majority had stage IV disease (89%), were white (65.5%), and were male (64.5%). Most common diagnoses were hepatocellular carcinoma (30.5%), gastric adenocarcinoma (16.5%), esophageal adenocarcinoma (17%), and colorectal cancer (19.8%). About 32% of the tumors were microsatellite instability-high (MSI-High/dMMR), with BRAF V600E mutation rate of 10%. About 25% of the patients received CPIs as initial treatment, while 35.5% had received two or more prior lines of therapy. Compared with well and moderately differentiated histology, patients with poorly differentiated tumors had a shorter median overall survival (mOS) (not reached [NR] vs. NR vs. 9.3 months, p = 0.0264). There was no statistically significant difference in median progression-free survival (mPFS) between histology types (2.5 vs. 4.2 vs. 2 months, p = 0.1314). On univariate survival analysis, moderately differentiated tumors correlated with a significantly longer mOS (HR: 0.48, CI: 0.24-0.93, p = 0.030) and mPFS (HR: 0.62, 95% CI: 0.38-1.00, p = 0.048) compared to poorly differentiated histology. Female patients (HR: 0.55, 95% CI: 0.34-0.90, p = 0.018) and the Eastern Cooperative Oncology Group (ECOG) of 1 (vs. ≥2) had significantly longer mPFS (HR: 0.58, 95% CI: 0.35-0.97, p = 0.036). ECOG of 1 also correlated with longer mOS (HR: 0.47, 95% CI: 0.23-0.94, p = 0.034). Microsatellite stable (MSS) tumors had significantly shorter mPFS (HR: 5.74, 95% CI: 2.41-13.63, p < 0.001) and mOS (HR: 5.45, 95% CI: 1.64-18.12, p = 0.006). The number of prior systemic therapies was also associated with shorter mPFS (HR: 1.19, 95% CI: 1.03-1.39, p = 0.022) and mOS (HR: 1.23, 95% CI: 1.01-1.50, p = 0.045). On multivariable analyses, ECOG status of 0/1 versus ≥2 and MSI-High/dMMR versus MSS remained significantly associated with longer mPFS and mOS. There was no correlation with histologic differentiation status, race, or mutations such as BRAF V600E or KRAS. CONCLUSION: Results from this study demonstrate that poorly differentiated histology was associated with shorter mOS but was not associated with improved PFS in patients treated with CPI. Treatment-naïve patients, moderately differentiated tumors, female gender, ECOG 1, and MSI-High/dMMR were most likely to benefit from CPI.
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Adenocarcinoma , Neoplasias Colorretais , Neoplasias Gastrointestinais , Humanos , Masculino , Feminino , Idoso , Neoplasias Colorretais/patologia , Prognóstico , Proteínas Proto-Oncogênicas B-raf/genética , Estudos Retrospectivos , Adenocarcinoma/patologia , Neoplasias Gastrointestinais/tratamento farmacológico , Neoplasias Gastrointestinais/genética , Instabilidade de Microssatélites , ImunoterapiaRESUMO
BACKGROUND: CheckMate 040 assessed the efficacy and safety of nivolumab in patients with advanced hepatocellular carcinoma (HCC). Understanding the safety profile of nivolumab is needed to support the management of treatment-related adverse events (TRAEs). This analysis assessed the safety of nivolumab monotherapy in the phase I/II, open-label CheckMate 040 study. MATERIALS AND METHODS: Select TRAEs (sTRAEs; TRAEs with potential immunologic etiology requiring more frequent monitoring) occurring between first dose and 30 days after last dose were analyzed in patients in the dose-escalation and -expansion phases. Time to onset (TTO), time to resolution (TTR), and recurrence of sTRAEs were assessed, and the outcome of treatment with immune-modulating medication (IMM) was evaluated. RESULTS: The analysis included 262 patients. The most common sTRAE was skin (35.5%), followed by gastrointestinal (14.5%) and hepatic (14.1%) events; the majority were grade 1/2, with 10.7% of patients experiencing grade 3/4 events. One patient had grade 5 pneumonitis. Median (range) TTO ranged from 3.6 (0.1-59.9) weeks for skin sTRAEs to 47.6 (47.1-48.0) weeks for renal sTRAEs. Overall, 68% of sTRAEs resolved, with median (range) TTR ranging from 3.7 (0.1-123.3+) weeks for gastrointestinal sTRAEs to 28.4 (0.1-79.1) weeks for endocrine sTRAEs. Most gastrointestinal and all hepatic events resolved with treatment in accordance with established toxicity management algorithms. In 57 patients (40%), sTRAEs were managed with IMM. Reoccurrence of sTRAEs was uncommon following rechallenge with nivolumab. CONCLUSION: Nivolumab demonstrated a manageable safety profile in this analysis of patients with advanced HCC. A majority of sTRAEs resolved with treatment. IMPLICATIONS FOR PRACTICE: Nivolumab is a viable treatment option for patients with previously treated advanced hepatocellular carcinoma as it has demonstrated durable tumor responses and promising survival. Nivolumab has a manageable safety profile. The most common select treatment-related adverse events (sTRAEs) in this analysis were skin related (35%). Gastrointestinal and hepatic sTRAEs were observed in approximately 14% of patients. The majority of sTRAEs resolved (68%). Safety events are easier to manage if addressed early. Patient education on signs and symptoms to watch out for and the importance of early reporting and consultation should be emphasized.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Carcinoma Hepatocelular/tratamento farmacológico , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Recidiva Local de Neoplasia , Nivolumabe/efeitos adversosRESUMO
BACKGROUND: Early detection and management of treatment-related adverse events (TRAEs) in patients receiving immune checkpoint inhibitors may improve outcomes. In CheckMate 142, nivolumab (3 mg/kg) plus low-dose ipilimumab (1 mg/kg) provided durable clinical benefit (objective response rate [ORR] 55%, median duration of response not reached, 12-month overall survival [OS] rate 85%) and manageable safety for previously treated microsatellite instability-high and/or mismatch repair-deficient (MSI-H/dMMR) metastatic colorectal cancer (mCRC). In-depth safety and additional efficacy outcomes from CheckMate 142 are presented. MATERIALS AND METHODS: Safety assessments included frequency of TRAEs, select TRAEs (sTRAEs), and immune-mediated adverse event incidences; time to onset (TTO); time to resolution (TTR); immune-modulating medication (IMM) use; dose delay; and sTRAE occurrence after resuming therapy. Efficacy assessments included ORR and survival analyses in patients with sTRAEs with or without concomitant IMM treatment and patients without sTRAEs. RESULTS: Among 119 patients, 25%, 23%, 19%, 5%, 5%, and 29% experienced an endocrine, gastrointestinal, hepatic, pulmonary, renal, or skin sTRAE, respectively; the majority (57%) were grade 1/2. sTRAEs occurred early (median TTO, 5.2-12.6 weeks). Nonendocrine sTRAEs resolved in most (>71%) patients (median TTR, 1.5-9.0 weeks). IMMs were used to manage sTRAEs in 22%-56% of patients (most resolved). Of patients with dose delay because of sTRAEs, 25 of 29 resumed treatment. Patients with or without sTRAEs had comparable ORR (57% vs. 52%) and 12-month OS rates (93% vs. 75%). Similar results were observed in patients with or without sTRAEs regardless of IMM use (ORR 52% vs. 57%; OS rates 87% vs. 82%). CONCLUSION: The benefit-risk profile of nivolumab plus low-dose ipilimumab provides a promising treatment option for patients with previously treated MSI-H/dMMR mCRC. IMPLICATIONS FOR PRACTICE: Nivolumab (NIVO) plus low-dose (1 mg/kg) ipilimumab (IPI) received U.S. Food and Drug Administration approval for patients with microsatellite instability-high and/or mismatch repair-deficient (MSI-H/dMMR) metastatic colorectal cancer (mCRC) that progressed following treatment with a fluoropyrimidine, oxaliplatin, and irinotecan based on results from CheckMate 142. In this safety analysis, the majority of select treatment-related adverse events (sTRAEs) occurred early, were managed using evidence-based treatment algorithms, and resolved. Efficacy outcomes were comparable between patients with or without sTRAEs regardless of the use of concomitant immune-modulating medications. The benefit-risk profile of NIVO + low-dose IPI provides a promising treatment option for MSI-H/dMMR mCRC.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Reparo de Erro de Pareamento de DNA/genética , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Instabilidade de Microssatélites , Recidiva Local de Neoplasia/tratamento farmacológico , Terapia de Salvação , Idoso , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Gerenciamento Clínico , Feminino , Seguimentos , Humanos , Ipilimumab/administração & dosagem , Masculino , Metástase Neoplásica , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/patologia , Nivolumabe/administração & dosagem , Prognóstico , Estudos Retrospectivos , Taxa de SobrevidaRESUMO
BACKGROUND: Neuroendocrine tumors (NETs) metastasize to the liver. Everolimus and selective internal radioembolization (SIRT) are approved treatments. Pasireotide is a somatostatin analogue with an affinity for somatostatin receptors 1, 2, 3, and 5. Everolimus and pasireotide may potentiate SIRT radiosensitization and inhibit rebound angiogenesis. This study evaluated the safety of pasireotide, everolimus, and SIRT. METHODS: This 3 + 3 phase 1 trial evaluated 3 dose levels of everolimus (2.5, 5, and 10 mg/day), pasireotide (600 µg twice daily), and SIRT (SIR-Spheres dose on days 9 and 37). Eligibility criteria included well or moderately differentiated NETs, bilobar liver metastases, and progression on long-acting octreotide. Toxicities and responses were evaluated with the Common Terminology Criteria for Adverse Events and the Response Evaluation Criteria in Solid Tumors (version 1.1). Dose-limiting toxicities (DLTs) were defined in the first 28 days. Correlative markers-angiopoietin 1, angiopoietin 2, basic fibroblast growth factor, collagen V, insulin-like growth factor binding protein 1, insulin-like growth factor binding protein 1, interleukin 8, M30, M65, placenta growth factor, and vascular endothelial growth factor receptor 2-were assessed. The Norfolk Quality of Life-Neuroendocrine Tumor Questionnaire was used to assess the quality of life (QOL). RESULTS: Thirteen patients were enrolled; 1 was not evaluable for the primary endpoint. Eleven patients had well-differentiated tumors. The primary sites included small bowel (4), pancreas (3), lung (2), colon (1), gastric (1), and unknown primary (2) were unknown. Four had liver-only disease; 12 completed the planned treatment. No DLTs were observed. There was no treatment-related mortality. The most common toxicity was hyperglycemia. Clinically significant liver toxicity was not observed. One patient had liver progression. QOL improved on treatment. The median progression-free survival and overall survival were 18.6 and 46.3 months, respectively. CONCLUSIONS: The recommended phase 2 dose of everolimus is 10 mg daily in combination with pasireotide and SIRT. The regimen is well tolerated. Preliminary activity appears promising. Cancer 2018;124:1992-2000. © 2018 American Cancer Society.
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Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Braquiterapia/métodos , Everolimo/administração & dosagem , Neoplasias Hepáticas/terapia , Tumores Neuroendócrinos/terapia , Somatostatina/análogos & derivados , Idoso , Braquiterapia/efeitos adversos , Quimiorradioterapia/métodos , Relação Dose-Resposta a Droga , Embolização Terapêutica/efeitos adversos , Embolização Terapêutica/métodos , Feminino , Humanos , Estimativa de Kaplan-Meier , Fígado/irrigação sanguínea , Fígado/efeitos dos fármacos , Fígado/efeitos da radiação , Neoplasias Hepáticas/irrigação sanguínea , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/cirurgia , Masculino , Pessoa de Meia-Idade , Neovascularização Patológica/tratamento farmacológico , Neovascularização Patológica/etiologia , Tumores Neuroendócrinos/mortalidade , Tumores Neuroendócrinos/patologia , Intervalo Livre de Progressão , Qualidade de Vida , Critérios de Avaliação de Resposta em Tumores Sólidos , Somatostatina/administração & dosagemRESUMO
BACKGROUND: Standard adjuvant treatment for pancreatic adenocarcinoma (PDAC) is gemcitabine [Gem(CONKO-001: Gem vs. placebo DFS:13.4 vs. 6.7 mo; P < 0.001; OS:22.8 vs. 20.2 mo; P = 0.01)]. Addition of cisplatin (Cis) to Gem has resulted in increased PFS for advanced and metastatic disease, which may be predicted by low expression of excision repair cross-complementing group-1 (ERCC1), the key enzyme in nucleotide excision repair. This Phase II prospective trial assesses outcomes of patients treated with adjuvant Gem/Cis, stratifying results by tumor ERCC1 expression. METHODS: Patients with resected PDAC were enrolled (2010-2013) and received Gem(1,000 mg/m(2) )/Cis(50 mg/m(2) ). Tumor ERCC1 expression was evaluated by immunohistochemistry and dichotomized into low or high expression. Primary outcomes were recurrence-free and overall survival (RFS/OS). RESULTS: Of 22 pts, 16(73%) were Stage IIB, 5(23%) Stage IIA, and 1(4%) Stage IA. Grade 3/4 toxicity occurred in 13 pts (59%); neutropenia was most common (n = 9;41%). Median follow-up was 37.5 months. Median RFS was 16.7 mo; OS was 35.5 mo. Low ERCC1 (n = 15;75%) compared to high ERCC1 (n = 5;25%) was not associated with improved RFS (12.4 vs. 16.7 mo; P = 0.68) or OS (Median not reached vs. 21.6 mo; P = 0.22). CONCLUSIONS: Adjuvant Gem/Cis is feasible in patients with resected pancreatic adenocarcinoma. RFS and OS for Gem/Cis appear promising compared to historic control. Tumor ERCC1 expression can be reliably evaluated, and low expression is present in most patients. J. Surg. Oncol. 2016;114:336-341. © 2016 Wiley Periodicals, Inc.
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Adenocarcinoma/terapia , Antineoplásicos/toxicidade , Cisplatino/uso terapêutico , Proteínas de Ligação a DNA/metabolismo , Desoxicitidina/análogos & derivados , Endonucleases/metabolismo , Neoplasias Pancreáticas/terapia , Adenocarcinoma/metabolismo , Adenocarcinoma/mortalidade , Idoso , Biomarcadores/metabolismo , Quimioterapia Adjuvante , Desoxicitidina/uso terapêutico , Quimioterapia Combinada , Estudos de Viabilidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pancreatectomia , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/mortalidade , Valor Preditivo dos Testes , Estudos Prospectivos , Resultado do Tratamento , GencitabinaRESUMO
PURPOSE: Appendiceal mucinous neoplasms (AMN) are a rare heterogeneous group of diseases. In the absence of randomized trials, AMN management is controversial. The goal of this study was to evaluate the impact of hyperthermic intraperitoneal chemotherapy (HIPEC) after cytoreductive surgery on survival in AMN patients. PATIENTS AND METHODS: Patient data including demographics, pathology, type of therapy, and outcomes were collected from Emory University, the Ohio State University, and Wayne State University databases. One of the three centers did not use HIPEC. Statistical analysis evaluating overall survival (OS) of AMN patients was performed. RESULTS: Between 1990 and 2010, 163 AMN patients were identified. Histology showed 60 patients had diffuse peritoneal adenomucinosis, 88 had peritoneal mucinous carcinomatosis (PMCA), and 15 had PMCA with indeterminate or discordant features. Complete surgical resection was achieved in 76 patients. HIPEC was used in 79 patients. The median OS was 77 months for patients who received HIPEC compared with 25 months for patients who did not (p < .001). In multivariable analysis, histopathologic subtype (p < .001), complete surgical resection (p < .001), and HIPEC (p < .001) were independent predictors for improved OS. A survival advantage for AMN patients treated at HIPEC-treating centers was observed (p = .0026). After adjusting for HIPEC therapy, no significant survival difference was observed between the non-HIPEC-treating center and the HIPEC-treating centers (p = .094). CONCLUSION: The addition of HIPEC to cytoreductive surgery likely provides a survival advantage and should be considered in the treatment strategy for AMN.
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Adenocarcinoma Mucinoso/tratamento farmacológico , Neoplasias do Apêndice/tratamento farmacológico , Procedimentos Cirúrgicos de Citorredução/métodos , Febre/terapia , Adenocarcinoma Mucinoso/cirurgia , Adulto , Idoso , Neoplasias do Apêndice/cirurgia , Feminino , Humanos , Injeções Intraperitoneais , Masculino , Pessoa de Meia-Idade , Centros de Atenção Terciária , Resultado do TratamentoRESUMO
BACKGROUND: Ampullary (AMP-A) and duodenal adenocarcinomas (DA) are rare tumors. The literature regarding treatment and outcome is very limited. The objective of this project is to compare the outcomes of AMP-A and DA. METHODS: The records for AMP-A and DA patients between July 1995 and July 2012 at Emory University were reviewed for demographics, pathology, treatment, and survival. Survival rates were estimated by Kaplan-Meier method and compared with log-rank test. A Cox proportional hazard model was fitted to estimate the adjusted effect of AMP-A versus DA on overall survival (OS). RESULTS: Ninety-five AMP-A and 66 DA patients were identified. No significant difference between patients with DA and AMP-A was observed for age, gender, or grade. DA presented with larger tumors and higher stages. Treatment included surgery, surgery followed by adjuvant therapy or chemotherapy alone. No OS difference was observed when controlled for stage. AMP-A was sub-classified into intestinal (IAMP), pancreaticobiliary (PBAMP), and unspecified types. IAMP tended to present at a higher grade (P = 0.045) than PBAMP. No OS difference between the IAMP and PBAMP was observed. CONCLUSIONS: After accounting for stage, OS was not significantly different for AMP-A and DA patients. There was no OS difference comparing PBAMP with IAMP.
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Adenocarcinoma/mortalidade , Adenocarcinoma/terapia , Neoplasias do Ducto Colédoco/mortalidade , Neoplasias do Ducto Colédoco/terapia , Neoplasias Duodenais/mortalidade , Neoplasias Duodenais/terapia , Adenocarcinoma/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Ampola Hepatopancreática/patologia , Ampola Hepatopancreática/cirurgia , Quimioterapia Adjuvante/estatística & dados numéricos , Neoplasias do Ducto Colédoco/patologia , Neoplasias Duodenais/patologia , Feminino , Humanos , Linfonodos/patologia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Gradação de Tumores , Invasividade Neoplásica , Recidiva Local de Neoplasia , Estadiamento de Neoplasias , Neoplasias do Sistema Nervoso Periférico/patologia , Modelos de Riscos Proporcionais , Grupos Raciais/estatística & dados numéricos , Radioterapia Adjuvante/estatística & dados numéricos , Estudos Retrospectivos , Neoplasias Vasculares/patologiaRESUMO
Pancreatic ductal adenocarcinoma remains a highly aggressive disease, with a 5-year relative survival rate of 10%. Numerous barriers to treatment exist, such as dense desmoplasia, infiltration of immune suppressor cells, inhibitory cytokines, low effector T-cell infiltration, and low tumor mutational burden. These factors help form a highly suppressive tumor microenvironment unique to pancreatic ductal adenocarcinoma. This review outlines barriers to treatment of pancreatic ductal adenocarcinoma by discussing the unique characteristics of the pancreatic tumor microenvironment and the factors that contribute to making pancreatic ductal adenocarcinoma such a challenging disease to treat.
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Recent studies have identified durable responses with the use of immune checkpoint inhibitors in patients with mismatch repair-deficient (MMR-D)/microsatellite instability-high (MSI-H) metastatic colorectal cancer (CRC). The dramatic improvement in clinical outcomes led to the US Food and Drug Administration approval of pembrolizumab, nivolumab, and nivolumab in combination with ipilimumab in metastatic patients with MSI-H/MMR-D CRC who previously experienced progression on cytotoxic therapies. In the clinical trials investigating these agents, HIV-seropositive patients were not included and therefore the clinical efficacy of these agents in patients with metastatic MSI-H/MMR-D CRC living with HIV is unclear. On the basis of growing evidence, immune checkpoint blockade therapies seem to be a safe approach in patients with well-controlled HIV infection. Research on immunotherapeutic approaches in patients living with HIV and cancer is an area of unmet medical need that can be addressed by clinical trial designs that are inclusive of patients with well-controlled seropositive HIV and trials that specifically evaluate immune therapies in patients living with HIV.
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Neoplasias Colorretais , Infecções por HIV , Neoplasias Colorretais/tratamento farmacológico , Infecções por HIV/tratamento farmacológico , Humanos , Inibidores de Checkpoint Imunológico , Ipilimumab/efeitos adversos , Instabilidade de Microssatélites , Estados UnidosRESUMO
BACKGROUND: Uncommon early-onset severe toxicities from 5-fluorouracil (5-FU) and capecitabine can be fatal if early warning signs are not recognized and treated promptly. OBJECTIVES: This article delineates the differences between expected side effects and uncommon early-onset severe toxicities from 5-FU and capecitabine. It also provides background for understanding the reasons patients may develop these toxicities and reviews the efficacy of standard supportive care against a novel therapy (uridine triacetate). METHODS: A panel of nurses convened to review the literature about toxicities associated with 5-FU and capecitabine administration and determined methods to educate nurses about toxicities and treatment. FINDINGS: Standard supportive care for 5-FU and capecitabine toxicities is associated with high fatality rates. Uridine triacetate treatment within 96 hours of administration is associated with survival.
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Antimetabólitos Antineoplásicos/toxicidade , Capecitabina/toxicidade , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/mortalidade , Fluoruracila/análogos & derivados , Neoplasias/tratamento farmacológico , Acetatos/uso terapêutico , Adulto , Idoso , Antimetabólitos Antineoplásicos/administração & dosagem , Capecitabina/administração & dosagem , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/tratamento farmacológico , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/toxicidade , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/mortalidade , Neoplasias/parasitologia , Segurança do Paciente , Medição de Risco , Índice de Gravidade de Doença , Análise de Sobrevida , Uridina/análogos & derivados , Uridina/uso terapêuticoRESUMO
This is a pilot study aimed at evaluating the prevalence of zinc deficiency and how zinc levels affect the quality of life (QOL) of patients with upper gastrointestinal (GI) cancers receiving systemic chemotherapy. The data collection was completed on 40 patients. Although the primary objective of a positive prevalence of zinc deficiency in upper GI cancer patients at diagnosis and after receiving chemotherapy is not statistically significant, we found a statistically significant association between zinc level and certain QOL factors. There is a significantly positive association with satisfaction of social contact at baseline only, sexual pleasure at baseline and at 2 months, QOL at baseline only, and troublesome sweating at baseline, and from baseline to 2 months corresponding with change in other skin problems. Conversely, there is a significantly negative association corresponding changes in enjoyment of physical activities, how the patient usually feels, sexual pleasure, the way in which the patient approaches food, QOL, rashes on the face, and other skin problems. Neutropenia grades were reflective of decreased zinc at baseline but did not show decreased zinc correlating with a weakened immune system.
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OBJECTIVES: The aim of this study is to characterize the changes in the incidence, presentation, surgical treatment, and survival of patients with appendiceal mucinous neoplasm (AMN) over the past 4 decades using nationwide cancer surveillance data. METHODS: Patients with the diagnosis of AMN were identified in the Surveillance Epidemiology and End Results (SEER) database. Information on demographics, disease characteristics, and surgical treatment was collected. Temporal changes in AMN incidence, characteristics of cases, and survival were analyzed from 1973 to 2011. Determinants of overall survival (OS) were examined using both crude and multivariable Cox proportional hazard models. RESULTS: The overall incidence rate of AMN increased on average 3.1%/1,000,000 persons-years (P<0.001). A significant decline in the age at diagnosis was observed (P=0.014). The proportion of patients presenting with distant disease at diagnosis also significantly increased (P=0.004). Five-year survival of patients with distant stage AMN increased at a rate of 3.5%/y between 1984 and 2006 (P<0.001). Median OS was not reached for localized and regional stage disease. Median OS for distant stage disease was 42 months. CONCLUSIONS: There has been an increase in the overall incidence of AMN with an observed increase in the proportion of younger age and distant stage at diagnosis. The OS has improved over time.
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Adenocarcinoma Mucinoso/epidemiologia , Neoplasias do Apêndice/epidemiologia , Adenocarcinoma Mucinoso/mortalidade , Adenocarcinoma Mucinoso/patologia , Adenocarcinoma Mucinoso/cirurgia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Apendicectomia , Neoplasias do Apêndice/mortalidade , Neoplasias do Apêndice/patologia , Neoplasias do Apêndice/cirurgia , Colectomia , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Gradação de Tumores , Estadiamento de Neoplasias , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Programa de SEER , Taxa de Sobrevida , Adulto JovemRESUMO
PURPOSE: Appendiceal tumors are a heterogeneous group of diseases that include typical neuroendocrine tumors (TNET), goblet cell carcinoids (GCC), and atypical GCC. Atypical GCC are classified into signet-ring cell cancers (SRCC) and poorly differentiated appendiceal adenocarcinoids. The prognosis and management of these diseases is unclear because there are no prospective studies. The aim of this study is to assess the characteristics and outcome of appendiceal TNET, GCC, and SRCC patients. MATERIALS AND METHODS: Appendiceal TNET, GCC, and SRCC patients diagnosed between 1973 and 2011 were identified in the Surveillance Epidemiology and End Results (SEER) database. Demographics, type of surgery, and clinicopathologic characteristics were collected. Survival functions were estimated by the Kaplan-Meier method, and log-rank test was used to assess the difference in overall survival (OS) among the three histologies. RESULTS: The SEER database yielded 1,021 TNET patients, 1,582 with GCC, and 534 SRCC patients. TNET presented at a younger age (p < 0.001). Patients with SRCC presented with advanced stage disease (p < 0.001). The median OS (mOS) for GCC and TNET patients was not reached; mOS for SRCC was 24 months. Multivariate analysis stratified for stage revealed significantly longer survival for TNET and GCC than SRCC (p < 0.001). CONCLUSION: This is the largest report to date for appendiceal neuroendocrine tumor patients, suggesting a spectrum of diseases with different characteristics and outcomes. In this report, we present a treatment approach for this complex spectrum of disease, based on the experience of Ohio State and Emory Universities investigators.
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Neoplasias do Apêndice/diagnóstico , Tumor Carcinoide/diagnóstico , Carcinoma de Células em Anel de Sinete/diagnóstico , Tumores Neuroendócrinos/diagnóstico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias do Apêndice/patologia , Tumor Carcinoide/patologia , Carcinoma de Células em Anel de Sinete/patologia , Criança , Bases de Dados Factuais , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Tumores Neuroendócrinos/patologia , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do Tratamento , Adulto JovemRESUMO
PURPOSE: A challenge in borderline resectable pancreatic cancer (BRPC) management is the high rate of positive posterior margins (PM). Stereotactic body radiation therapy (SBRT) allows for higher radiation delivery dose with conformity. This study evaluated the maximal tolerated dose with a dose escalation plan level up to 45 Gy using SBRT in BRPC. METHODS AND MATERIALS: A single-institution, 3 + 3 phase 1 clinical trial design was used to evaluate 4 dose levels of SBRT delivered in 3 fractions to the planning target volume (PTV) with a simultaneous in-field boost (SIB) to the PM. Dose level (DL) 1 was 30 Gy to the PTV, and for dose levels 2 through 4 (DL2-DL4) the dose was 36 Gy. The SIB dose to the PM was 6, 6, 7.5, and 9 Gy for DL-1, DL-2, DL-3, and DL-4, respectively. All patients received 4 treatments of modified FOLFIRINOX (fluorouracil, leucovorin, irinotecan, oxaliplatin) before SBRT. RESULTS: Thirteen patients with a median age of 64 years were enrolled. The median follow-up time was 18 months. The locations of the cancer were head (n=12) and uncinate/neck (n=1). One patient did not undergo SBRT. There were no grade 3 or 4 toxicities. Five patients did not undergo resection because of disease progression (1 local, 4 distant); 8 had R0 resection in the PM, and 5 of 8 had vessel reconstruction. Two patients had disease downstaged to T1 and T2 from T3 disease. Four patients are still alive, and 3 are disease free. The median overall survival for resected patients was not reached (9.3: not reached). CONCLUSION: The SBRT dose of 36 Gy with a 9-Gy SIB to the PM (total 45 Gy) delivered in 3 fractions is safe and well tolerated. The dose-limiting toxicity for a 45-Gy dose was not reached, and further dose escalations are needed in future trials.
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Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Fracionamento da Dose de Radiação , Neoplasias Pancreáticas/terapia , Lesões por Radiação/etiologia , Radiocirurgia/efeitos adversos , Radiocirurgia/métodos , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Camptotecina/administração & dosagem , Camptotecina/efeitos adversos , Camptotecina/análogos & derivados , Quimiorradioterapia/efeitos adversos , Quimiorradioterapia/métodos , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/efeitos adversos , Humanos , Irinotecano , Leucovorina/administração & dosagem , Leucovorina/efeitos adversos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Compostos Organoplatínicos/administração & dosagem , Compostos Organoplatínicos/efeitos adversos , Oxaliplatina , Pancreatectomia , Neoplasias Pancreáticas/diagnóstico , Lesões por Radiação/diagnóstico , Radioterapia Adjuvante/métodos , Resultado do TratamentoRESUMO
PURPOSE: Colorectal cancer has a distinct clinicopathologic presentation in younger patients. The aim of this paper was to evaluate the outcome of younger (age below 50 y) and older patients with stage IV (advanced) colorectal cancer in the modern era of combination chemotherapy. METHODS: Cases of metastatic colorectal cancer reported in Surveillance, Epidemiology, and End Results registry (1973 to 2008) were reviewed. Demographics, tumor characteristics, and overall and cancer-specific survivals in patients below 50 and above 50 years of age were compared by Cox proportional hazard analyses. Joinpoint regression analysis was used to evaluate secular trends in 2-year survival. RESULTS: Younger patients had a greater proportion of negative clinicopathologic features (male sex, African American ethnicity, and signet ring or mucinous histology). In multivariate analysis, older age, male sex, African American ethnicity, right-sided tumors, and signet ring histology were associated with higher mortality risk. Younger patients had improved survival (hazard ratio 0.72; 95% confidence interval: 0.70-0.75) compared with older patients, whereas all patients experienced increased 2-year survival by joinpoint analysis beginning in 1999-2000. CONCLUSIONS: The results confirm decreased mortality from advanced colorectal cancer in the era of modern combination chemotherapy in younger and older patients. Younger age, non-right-sided tumors, and absence of signet ring histology significantly associate with better survival.
Assuntos
Adenocarcinoma Mucinoso/mortalidade , Adenocarcinoma/mortalidade , Negro ou Afro-Americano/estatística & dados numéricos , Carcinoma de Células em Anel de Sinete/mortalidade , Neoplasias Colorretais/mortalidade , População Branca/estatística & dados numéricos , Adenocarcinoma/patologia , Adenocarcinoma Mucinoso/patologia , Adulto , Fatores Etários , Carcinoma de Células em Anel de Sinete/patologia , Neoplasias Colorretais/patologia , Humanos , Pessoa de Meia-Idade , Análise Multivariada , Estadiamento de Neoplasias , Prognóstico , Modelos de Riscos Proporcionais , Fatores de Risco , Programa de SEER , Fatores Sexuais , Resultado do TratamentoRESUMO
OBJECTIVES: FOLFIRINOX (5-fluorouracil [5-FU], oxaliplatin, and irinotecan) as compared with gemcitabine in pancreatic cancer (PC) has superior activity and increased toxicity. The bolus 5-FU contributes to the toxicity. We hypothesized that the elimination of bolus 5-FU and use of hematopoietic growth factor will improve the safety profile without compromising the activity of FOLFIRINOX. METHODS: Sixty patients with PC treated with modified FOLFIRINOX (no bolus 5-FU) were reviewed. Patients were divided into metastatic or nonmetastatic (locally advanced or borderline resectable) disease. Toxicity, response rate, progression-free survival, and overall survival were evaluated. RESULTS: Nonmetastatic and metastatic disease were present in 24 (40%) and 36 (60%) patients, respectively. The incidence of grade 4 neutropenia, grade 3/4 diarrhea, and fatigue were 3%, 13%, and 13%, respectively. Response rate was 30%. The median progression-free survival for nonmetastatic disease was 13.7 months (95% confidence interval [CI], 9.6-24.6 months), and that for metastatic disease was 8.5 months (95% CI, 3.7-11.0 months), respectively. The median overall survival for nonmetastatic disease was 17.8 months (95% CI, 9.9 months to not estimable), and that for metastatic disease was and 9.0 months (95% CI, 7.1 months to not estimable), respectively. CONCLUSIONS: Modified FOLFIRINOX has an improved safety profile with maintained efficacy in metastatic PC. Modified FOLFIRINOX has promising activity in nonmetastatic disease.