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1.
J Exp Clin Cancer Res ; 41(1): 89, 2022 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-35272688

RESUMO

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is characterized by abundant stroma in which microenvironmental (niche) factors promote PDAC progression. In mouse models, reduction of the stroma increased the proportion of poorly differentiated PDAC with a worse prognosis. Here, we aimed to clarify the effects of stroma on PDAC that may define the PDAC phenotype and induce distinct therapeutic responses. METHODS: The molecular features of PDAC based on differentiation grade were clarified by genome and transcriptome analysis using PDAC organoids (PDOs). We identified the dependency on niche factors that might regulate the differentiation grade. A three-dimensional co-culture model with cancer-associated fibroblasts (CAFs) was generated to determine whether CAFs provide niche factors essential for differentiated PDAC. PDOs were subtyped based on niche factor dependency, and the therapeutic responses for each subtype were compared. RESULTS: The expression profiles of PDOs differed depending on the differentiation grade. Consistent with the distinct profiles, well differentiated types showed high niche dependency, while poorly differentiated types showed low niche dependency. The three-dimensional co-culture model revealed that well differentiated PDOs were strongly dependent on CAFs for growth, and moderately differentiated PDOs showed plasticity to change morphology depending on CAFs. Differentiated PDOs upregulated the expression of mevalonate pathway-related genes correlated with the niche dependency and were more sensitive to simvastatin than poorly differentiated PDOs. CONCLUSIONS: Our findings suggest that CAFs maintain the differentiated PDAC phenotype through secreting niche factors and induce distinct drug responses. These results may lead to the development of novel subtype-based therapeutic strategies.


Assuntos
Adenocarcinoma/tratamento farmacológico , Carcinoma Ductal Pancreático/tratamento farmacológico , Perfilação da Expressão Gênica/métodos , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Animais , Carcinoma Ductal Pancreático/mortalidade , Carcinoma Ductal Pancreático/patologia , Modelos Animais de Doenças , Humanos , Camundongos , Análise de Sobrevida , Microambiente Tumoral
2.
Radiat Oncol ; 17(1): 45, 2022 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-35241109

RESUMO

BACKGROUND: Multimodal therapies based on surgical resection have been recommended for the treatment of adenocarcinoma of the oesophagogastric junction (AEG). We aimed to evaluate prognostic factors in AEG patients receiving neoadjuvant chemoradiotherapy and to build predictive models. METHODS: T3 - T4N + M0 AEG patients with resectable Siewert type II/III tumours were enrolled in this study. All patients underwent neoadjuvant chemoradiation, followed by radical surgery or systemic therapy according to clinical response. Survival analysis was performed using the Kaplan-Meier method; multivariate analysis using the Cox proportional hazards method was also conducted. The Harrell concordance index (C-index) was used to test the prognostic value of models involving prognostic factors, and consistency between actual and predicted survival rates was evaluated by calibration curves. RESULTS: From February 2009 to February 2018, 79 patients were treated with neoadjuvant chemoradiotherapy; 60 patients of them underwent radical surgery. The R0 resection rate was 98.3%, and 46.7% of patients achieved a major pathologic response (MPR), namely, a residual tumour issue less than 10%. The 5-year overall survival (OS) rate was 63%, and the 5-year progression-free survival (PFS) rate was 48%. The incidence of grade 3 complications was 21.5%, and no grade 4 complications were reported. According to the results of univariate and multivariate analyses, we included the neutrophil-lymphocyte ratio (NLR), prognostic nutrition index (PNI), eosinophilic granulocyte (EOS) and postoperative pathologic stage in nomogram analysis to establish prediction models for OS and PFS; the C-index of each model was 0.814 and 0.722, respectively. Both the C-index and calibration curves generated to validate consistency between the actual and predicted survival indicated that the models were well calibrated and of good predictive value. CONCLUSIONS: AEG patients achieved favourable downstaging and pathologic response after neoadjuvant chemoradiation, with acceptable adverse effects. Inflammation-based and nutrition-related factors and postoperative pathologic stage had a significant influence on OS and PFS, and the predictive value was verified through prognostic models.


Assuntos
Adenocarcinoma/mortalidade , Adenocarcinoma/terapia , Quimiorradioterapia Adjuvante , Neoplasias Esofágicas/mortalidade , Neoplasias Esofágicas/terapia , Junção Esofagogástrica , Terapia Neoadjuvante , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/terapia , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Modelos Teóricos , Prognóstico , Taxa de Sobrevida
3.
N Engl J Med ; 386(6): 544-555, 2022 02 10.
Artigo em Inglês | MEDLINE | ID: mdl-35139273

RESUMO

BACKGROUND: Patients with recurrent cervical cancer have a poor prognosis. Cemiplimab, the fully human programmed cell death 1 (PD-1)-blocking antibody approved to treat lung and skin cancers, has been shown to have preliminary clinical activity in this population. METHODS: In this phase 3 trial, we enrolled patients who had disease progression after first-line platinum-containing chemotherapy, regardless of their programmed cell death ligand 1 (PD-L1) status. Women were randomly assigned (1:1) to receive cemiplimab (350 mg every 3 weeks) or the investigator's choice of single-agent chemotherapy. The primary end point was overall survival. Progression-free survival and safety were also assessed. RESULTS: A total of 608 women were enrolled (304 in each group). In the overall trial population, median overall survival was longer in the cemiplimab group than in the chemotherapy group (12.0 months vs. 8.5 months; hazard ratio for death, 0.69; 95% confidence interval [CI], 0.56 to 0.84; two-sided P<0.001). The overall survival benefit was consistent in both histologic subgroups (squamous-cell carcinoma and adenocarcinoma [including adenosquamous carcinoma]). Progression-free survival was also longer in the cemiplimab group than in the chemotherapy group in the overall population (hazard ratio for disease progression or death, 0.75; 95% CI, 0.63 to 0.89; two-sided P<0.001). In the overall population, an objective response occurred in 16.4% (95% CI, 12.5 to 21.1) of the patients in the cemiplimab group, as compared with 6.3% (95% CI, 3.8 to 9.6) in the chemotherapy group. An objective response occurred in 18% (95% CI, 11 to 28) of the cemiplimab-treated patients with PD-L1 expression greater than or equal to 1% and in 11% (95% CI, 4 to 25) of those with PD-L1 expression of less than 1%. Overall, grade 3 or higher adverse events occurred in 45.0% of the patients who received cemiplimab and in 53.4% of those who received chemotherapy. CONCLUSIONS: Survival was significantly longer with cemiplimab than with single-agent chemotherapy among patients with recurrent cervical cancer after first-line platinum-containing chemotherapy. (Funded by Regeneron Pharmaceuticals and Sanofi; EMPOWER-Cervical 1/GOG-3016/ENGOT-cx9 ClinicalTrials.gov number, NCT03257267.).


Assuntos
Adenocarcinoma/tratamento farmacológico , Anticorpos Monoclonais Humanizados/uso terapêutico , Antineoplásicos Imunológicos/uso terapêutico , Carcinoma Adenoescamoso/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Neoplasias do Colo do Útero/tratamento farmacológico , Adenocarcinoma/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Humanizados/efeitos adversos , Antineoplásicos Imunológicos/efeitos adversos , Biomarcadores Tumorais/metabolismo , Carcinoma Adenoescamoso/mortalidade , Progressão da Doença , Feminino , Humanos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/mortalidade , Receptor de Morte Celular Programada 1/metabolismo , Qualidade de Vida , Análise de Sobrevida , Neoplasias do Colo do Útero/mortalidade
4.
Cir Esp (Engl Ed) ; 100(3): 125-132, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35221240

RESUMO

INTRODUCTION: Surgery and chemotherapy have increased the survival of pancreatic cancer. The decrease in postoperative morbidity and mortality and increase in life expectancy, has expanded the indications por cephalic pancreaticoduodenectomy (PDC), although it remains controversial in the geriatric population. METHODS: Retrospective study on a prospective database of patients with ductal adenocarcinoma of pancreas who underwent PDC between 2007-2018. The main objective was to analyse the morbidity-mortality and survival associated with PDC in patients ≥75 years (elderly). RESULTS: 79 patients were included, 21 of them older than 75 years (27%); within this group, 23'9% were over 80 years old. The ASA of both groups was similar. Patients ≥75 years required more transfusions. No differences in operating time were observed, although more vascular resection were performed in the elderly (26 vs. 8.7%; P = .037). Morbidity was higher in the elderly (61.9% vs. 46.6%), although without differences. Patients aged ≥75 years had more non-surgical complications (33.3%, P = .050), being pneumonia the most frequent. Postoperative mortality was higher in the ≥75 years (9 vs. 0%; P = .017). The overall survival and disease-free survival did not show significant differences in both groups. CONCLUSIONS: Elderly patients had higher postoperative mortality and more non-surgical complications. Survival did not show differences, so with an adequate selection of patients, age should not be considered itself as a contraindication for PDC.


Assuntos
Adenocarcinoma/cirurgia , Neoplasias Pancreáticas/cirurgia , Pancreaticoduodenectomia , Adenocarcinoma/mortalidade , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Neoplasias Pancreáticas/mortalidade , Complicações Pós-Operatórias , Estudos Retrospectivos , Resultado do Tratamento
5.
Ann Surg ; 275(3): 415-421, 2022 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-35120060

RESUMO

OBJECTIVE: To evaluate the association between staging concordance, treatment sequencing, and response to neoadjuvant therapy (NAT) on the survival of patients with pancreatic ductal adenocarcinoma (PDAC). SUMMARY OF BACKGROUND DATA: NAT is increasingly utilized in the management of patients with PDAC, but it is unclear whether its benefit is contingent on tumor down-staging. METHODS: This was a cohort study of stage I-III PDAC patients in the National Cancer Database (2006-2015) treated with upfront resection or NAT followed by surgery. We determined staging concordance using patients' clinical and pathological staging data. For NAT patients, we used Bayesian analysis to ascertain staging concordance accounting for down-staging. RESULTS: Among 16,597 patients treated at 979 hospitals, 13,982 had an upfront resection and 2,615 NAT followed by surgery. Overall survival (OS) at 5-years ranged from 26.0% (95% CI 24.9%-27.1%) among cT1-2N0 patients to 18.6% (17.9%-19.2%) among cT1-3N+ ones. Patients with cT3-4 or cN+ tumors had improved OS after NAT compared to upfront surgery (all p< 0.001), while there was no difference among patients with cT1-2N0 (P = 0.16) disease. Relative to accurately staged cT1-2-3N+ or cT4 patients treated with upfront surgery, NAT was associated with a lower risk of death [HR 0.46 (0.37-0.57) for N+; HR 0.56 (0.40-0.77) for T4 disease], even among those without tumor down-staging [HR 0.81 (0.73-0.90) for N+; HR 0.48 (0.39-0.60) for T4]. CONCLUSIONS: NAT is associated with improved survival for PDAC, particularly for patients with more advanced disease and regardless of down-staging. Consideration should be given to recommending NAT for all PDAC patients.


Assuntos
Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Carcinoma Ductal Pancreático/mortalidade , Carcinoma Ductal Pancreático/patologia , Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/patologia , Adenocarcinoma/terapia , Teorema de Bayes , Carcinoma Ductal Pancreático/terapia , Estudos de Coortes , Humanos , Terapia Neoadjuvante , Estadiamento de Neoplasias , Neoplasias Pancreáticas/terapia , Taxa de Sobrevida
6.
Sci Rep ; 12(1): 2059, 2022 02 08.
Artigo em Inglês | MEDLINE | ID: mdl-35136136

RESUMO

The effect of apical lymph node (APN) metastasis on the prognosis of colon cancer is unknown. The present study investigated the impact of APN metastasis on the prognosis of the patients with high-risk stage III colon cancer. This retrospective multi-institutional study included patients with pathological high-risk stage III colon cancer who underwent surgery between April 2009 and December 2014. Clinicopathological factors were examined by univariate and multivariate analyses to clarify independent risk factors for overall survival (OS) and relapse-free survival (RFS). A total of 185 patients were collected. The 5-year OS rates of patients with and without APN metastasis were 35.0% and 72.1%, respectively (p = 0.0014). The 5-year RFS rates of patients with and without APN metastasis was 16.2% and 57.2%, respectively (p = 0.0002). The rate of distant metastasis in patients with APN metastasis was significantly higher than that in patients without APN metastasis (68.8% vs. 36.7%, p = 0.012). The univariate analysis revealed that the differentiation, lymph node ratio, and APN metastasis were significantly associated with 5-year OS, and the preoperative CEA and CA19-9 levels and APN metastasis were significantly associated with 5-year RFS. The multivariate analysis showed that APN metastasis was an independent risk factor for 5-year OS and RFS. APN metastasis may be independently associated with the prognosis of patients with high-risk Stage III colon cancer.


Assuntos
Neoplasias do Colo/mortalidade , Neoplasias do Colo/patologia , Metástase Linfática/patologia , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Idoso , Intervalo Livre de Doença , Feminino , Humanos , Neoplasias Hepáticas/secundário , Linfonodos/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida
7.
BMC Cancer ; 22(1): 139, 2022 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-35120467

RESUMO

BACKGROUND: Gastric cancer is a heterogeneous disease with poorly understood genetic and microenvironmental factors. Mutations in collagen genes are associated with genetic diseases that compromise tissue integrity, but their role in tumor progression has not been extensively reported. Aberrant collagen expression has been long associated with malignant tumor growth, invasion, chemoresistance, and patient outcomes. We hypothesized that somatic mutations in collagens could functionally alter the tumor extracellular matrix. METHODS: We used publicly available datasets including The Tumor Cancer Genome Atlas (TCGA) to interrogate somatic mutations in collagens in stomach adenocarcinomas. To demonstrate that collagens were significantly mutated above background mutation rates, we used a moderated Kolmogorov-Smirnov test along with combination analysis with a bootstrap approach to define the background accounting for mutation rates. Association between mutations and clinicopathological features was evaluated by Fisher or chi-squared tests. Association with overall survival was assessed by Kaplan-Meier and the Cox-Proportional Hazards Model. Gene Set Enrichment Analysis was used to interrogate pathways. Immunohistochemistry and in situ hybridization tested expression of COL7A1 in stomach tumors. RESULTS: In stomach adenocarcinomas, we identified individual collagen genes and sets of collagen genes harboring somatic mutations at a high frequency compared to background in both microsatellite stable, and microsatellite instable tumors in TCGA. Many of the missense mutations resemble the same types of loss of function mutations in collagenopathies that disrupt tissue formation and destabilize cells providing guidance to interpret the somatic mutations. We identified combinations of somatic mutations in collagens associated with overall survival, with a distinctive tumor microenvironment marked by lower matrisome expression and immune cell signatures. Truncation mutations were strongly associated with improved outcomes suggesting that loss of expression of secreted collagens impact tumor progression and treatment response. Germline collagenopathy variants guided interpretation of impactful somatic mutations on tumors. CONCLUSIONS: These observations highlight that many collagens, expressed in non-physiologically relevant conditions in tumors, harbor impactful somatic mutations in tumors, suggesting new approaches for classification and therapy development in stomach cancer. In sum, these findings demonstrate how classification of tumors by collagen mutations identified strong links between specific genotypes and the tumor environment.


Assuntos
Adenocarcinoma/genética , Colágeno Tipo VII/genética , Colágeno/genética , Neoplasias Gástricas/genética , Microambiente Tumoral/genética , Adenocarcinoma/mortalidade , Biologia Computacional , Genótipo , Humanos , Estimativa de Kaplan-Meier , Mutação , Taxa de Mutação , Modelos de Riscos Proporcionais , Neoplasias Gástricas/mortalidade
8.
Anticancer Res ; 42(3): 1455-1463, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35220239

RESUMO

BACKGROUND/AIM: Polymorphous adenocarcinoma (PAC) is a low-grade salivary gland malignancy in contrast to variants with papillary (PAP) or cribriform (CASG) architecture and confers the second most common malignancy of minor salivary glands. Our study aimed to identify prognostic factors and to evaluate histomorphological and molecular diagnostic criteria of PACs. PATIENTS AND METHODS: A series of 155 PACs, including 10 PAPs and 12 CASGs from the population-based Cancer Registry of North Rhine-Westphalia (LKR-NRW) and the Hamburg Salivary Gland Reference Centre (HRC) were analyzed. RESULTS: One fifth of the tumors were located in the major salivary glands and PACS/CASGS invariably lacked p40 expression. Fifty-two percent of PACs showed a PRKD1 E710D mutation. Ordinary PACs had a disease-specific 10-year survival probability of 97% compared to 90% when combining PAPs and CASGs. T-stage at diagnosis was a prognostic factor with 98% for stages T1/T2 versus 75% for T3/T4. CONCLUSION: Diagnostic algorithms for the PAC/CASG spectrum of tumors need to be improved and should include molecular markers.


Assuntos
Adenocarcinoma Papilar , Adenocarcinoma , Biomarcadores Tumorais , Neoplasias das Glândulas Salivares , Adenocarcinoma/química , Adenocarcinoma/genética , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Adenocarcinoma Papilar/química , Adenocarcinoma Papilar/genética , Adenocarcinoma Papilar/mortalidade , Adenocarcinoma Papilar/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/genética , Criança , Feminino , Alemanha , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Estadiamento de Neoplasias , Sistema de Registros , Neoplasias das Glândulas Salivares/química , Neoplasias das Glândulas Salivares/genética , Neoplasias das Glândulas Salivares/mortalidade , Neoplasias das Glândulas Salivares/patologia , Fatores Sexuais , Fatores de Tempo , Carga Tumoral , Adulto Jovem
9.
Anticancer Res ; 42(3): 1541-1546, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35220250

RESUMO

BACKGROUND/AIM: This study aimed to examine the efficacy of surgical intervention after chemotherapy for stage IV gastric cancer and the predictors of survival after surgical intervention. PATIENTS AND METHODS: Forty-three gastric cancer patients who had only one type of incurable factor (e.g., para-aortic lymph node metastasis) and had undergone initial chemotherapy, underwent chemotherapy alone (CX group; n=25), palliative gastrectomy (PS group; n=8), and conversion surgery (CS group; n=10). Their therapeutic outcomes were compared. RESULTS: The CS group had significantly higher 2-year overall survival rates (80%) than the CX group (25%), whose prognosis was similar to that of the PS group (23%; p<0.001). Pathological complete response of para-aortic lymph node or peritoneal metastases was an independent predictor of survival after surgery, as was >6 months of chemotherapy. CONCLUSION: CS may improve the prognosis of patients with stage IV gastric cancer in whom chemotherapy can achieve pathological disappearance of the metastatic lesions.


Assuntos
Adenocarcinoma/cirurgia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Gastrectomia , Terapia Neoadjuvante , Neoplasias Gástricas/cirurgia , Adenocarcinoma/mortalidade , Adenocarcinoma/secundário , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Quimioterapia Adjuvante , Feminino , Gastrectomia/efeitos adversos , Gastrectomia/mortalidade , Humanos , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante/efeitos adversos , Terapia Neoadjuvante/mortalidade , Estadiamento de Neoplasias , Medição de Risco , Fatores de Risco , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/patologia , Fatores de Tempo , Resultado do Tratamento
10.
Sci Rep ; 12(1): 1976, 2022 02 07.
Artigo em Inglês | MEDLINE | ID: mdl-35132098

RESUMO

Lung cancer is one of the most common malignancy worldwide and causes estimated 1.6 million deaths each year. Cancer immunosurveillance has been found to play an important role in lung cancer and may be related with its prognosis. KLRK1, encoding NKG2D, is a homodimeric lectin-like receptor. However, there has not been one research of KLRK1 as a biomarker in lung cancer. Data including patients` clinical characteristics and RNAseq information of KLRK1 from TCGA were downloaded. A total of 1019 patients with lung cancer were included in this study, among which 407 patients were female and 611 patients were male. Evaluations of mRNA expression, diagnostic value by ROC (receiver operating characteristic) curves and prognostic value by survival curve, Cox model and subgroup analysis were performed. The level of KLRK1 expression in lung adenocarcinoma cancer tissues and normal lung tissues was detected by qRT-PCR. The CCK-8 assay investigated the proliferation rate and the wound healing assay assessed the migratory ability in vitro. The expression of KLRK1 in tumor was lower than that in normal tissue. KLRK1 expression was associated with gender, histologic grade, stage, T classification and vital status. Patients with high KLRK1 expression presented an improved overall survival (P = 0.0036) and relapse free survival (P = 0.0031). KLRK1 was found to have significant prognostic value in lung adenocarcinoma (P = 0.015), stage I/II (P = 0.03), older patients (P = 0.0052), and male (P = 0.0047) by subgroup overall survival analysis, and in lung adenocarcinoma (P = 0.0094), stage I/II (P = 0.0076), older patients (P = 0.0072), and male (P = 0.0033) by subgroup relapse free survival analysis. Lung adenocarcinoma cancer patients with high KLRK1 expression presented an improved overall survival (P = 0.015) and relapse free survival (P = 0.0094). In vitro studies indicated that KLRK1 inhibited tumor cell proliferation and migration. KLRK1 was an independent prognostic factor and high KLRK1 expression indicated a better overall and relapse free survival. KLRK1 may be a prognostic biomarker for lung adenocarcinoma cancer.


Assuntos
Adenocarcinoma/diagnóstico , Adenocarcinoma/patologia , Biomarcadores Tumorais/metabolismo , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/patologia , Subfamília K de Receptores Semelhantes a Lectina de Células NK/metabolismo , Células A549 , Adenocarcinoma/mortalidade , Biomarcadores Tumorais/genética , Movimento Celular/genética , Intervalo Livre de Doença , Feminino , Expressão Gênica , Humanos , Neoplasias Pulmonares/mortalidade , Masculino , Subfamília K de Receptores Semelhantes a Lectina de Células NK/genética , Prognóstico , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Curva ROC
11.
BMC Cancer ; 22(1): 210, 2022 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-35216571

RESUMO

BACKGROUND: We collected information on patients with rectal adenocarcinoma in the United States from the Surveillance, Epidemiology, and EndResults (SEER) database. We used this information to establish a model that combined deep learning with a multilayer neural network (the DeepSurv model) for predicting the survival rate of patients with rectal adenocarcinoma. METHODS: We collected patients with rectal adenocarcinoma in the United States and older than 20 yearswho had been added to the SEER database from 2004 to 2015. We divided these patients into training and test cohortsat a ratio of 7:3. The training cohort was used to develop a seven-layer neural network based on the analysis method established by Katzman and colleagues to construct a DeepSurv prediction model. We then used the C-index and calibration plots to evaluate the prediction performance of the DeepSurv model. RESULTS: The 49,275 patients with rectal adenocarcinoma included in the study were randomly divided into the training cohort (70%, n = 34,492) and the test cohort (30%, n = 14,783). There were no statistically significant differences in clinical characteristics between the two cohorts (p > 0.05). We applied Cox proportional-hazards regression to the data in the training cohort, which showed that age, sex, marital status, tumor grade, surgery status, and chemotherapy status were significant factors influencing survival (p < 0.05). Using the training cohort to construct the DeepSurv model resulted in a C-index of the model of 0.824, while using the test cohort to verify the DeepSurv model yielded a C-index of 0.821. Thesevalues show that the prediction effect of the DeepSurv model for the test-cohort patients was highly consistent with the prediction resultsfor the training-cohort patients. CONCLUSION: The DeepSurv prediction model of the seven-layer neural network that we have established can accurately predict the survival rateand time of rectal adenocarcinoma patients.


Assuntos
Adenocarcinoma/mortalidade , Aprendizado Profundo , Neoplasias Retais/mortalidade , Programa de SEER/estatística & dados numéricos , Adulto , Idoso , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Redes Neurais de Computação , Valor Preditivo dos Testes , Prognóstico , Modelos de Riscos Proporcionais , Taxa de Sobrevida , Estados Unidos , Adulto Jovem
12.
BMC Cancer ; 22(1): 211, 2022 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-35219310

RESUMO

BACKGROUND: Immunotherapy is a novel hotspot for the treatment of pancreatic adenocarcinoma (PAAD). However, potential biomarkers which could identify the inflamed tumor microenvironment (TME) are urgently required. METHODS: In the present study, we measured the levels of B7-H3, B7-H4, and major tumor-infiltrating immune cells (TIICs) using bioinformatics analyses and immunohistochemistry (IHC) staining on PAAD samples represented in the tissue microarray (TMA) format. Statistical analysis and figures exhibition were performed using R 4.1.0, SPSS 26.0, and GraphPad Prism 6.0. RESULTS: B7-H3 and B7-H4 were up-regulated in PAAD compared with para-tumor tissues, and their expression exhibited no tight correlation in PAAD tissues. B7-H3 and B7-H4 were lowly expressed in well-differentiated PAAD tissues and correlated with poorly differentiated grades. Besides, single B7-H3 or B7-H4 expression exhibited limited prognostic value, but co-deficiency of B7-H3 and B7-H4 predicted a better prognosis in PAAD. Moreover, co-deficiency of B7-H3 and B7-H4 indicated immuno-hot tumors with high CD8 + T cell infiltration. CONCLUSIONS: Overall, combined B7-H3 and B7-H4 expression is a promising stratification strategy to assess prognosis and immunogenicity in PAAD, which could be used as a novel classifier in clinical practice.


Assuntos
Adenocarcinoma/imunologia , Antígenos B7/deficiência , Linfócitos T CD8-Positivos/metabolismo , Linfócitos do Interstício Tumoral/metabolismo , Neoplasias Pancreáticas/imunologia , Inibidor 1 da Ativação de Células T com Domínio V-Set/deficiência , Adenocarcinoma/mortalidade , Biomarcadores Tumorais/imunologia , Biologia Computacional , Feminino , Humanos , Imuno-Histoquímica , Imunoterapia , Masculino , Pessoa de Meia-Idade , Neoplasias Pancreáticas/mortalidade , Prognóstico , Microambiente Tumoral/imunologia
13.
BMC Cancer ; 22(1): 204, 2022 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-35197014

RESUMO

BACKGROUND: Lung cancer is a leading cause of cancer-related deaths in Uganda. In this study, we aimed to describe the baseline characteristics and survival of patients with lung cancer at the Uganda Cancer Institute (UCI). METHODS: We retrospectively reviewed medical records of all patients with a histological diagnosis of lung cancer registered at UCI between January 2008 and August 2018. Data on demographic, clinical, and treatment characteristics, and vital status were abstracted and analyzed. Patients with undocumented vital status on the medical records were contacted through phone calls. We determined survival as time from histological diagnosis to death. The Kaplan-Meier survival analysis was performed to estimate the median survival time and the 5-year overall survival rate. RESULTS: Of the 207 patients enrolled, 56.5% (n = 117) were female, median age was 60 years (range: 20-94), 78.7% (n = 163) were never-smokers and 18 (8.7%) were living with HIV. Presumptive anti-tuberculosis treatment was given to 23.2% (n = 48). Majority had non-small cell lung cancer (96.6%, n = 200) with 74.5% (n = 149) adenocarcinoma and 19% (n = 38) squamous cell carcinoma. All had advanced (stage III or IV) disease with 96.1% (n = 199) in stage IV. Chemotherapy (44.9%, n = 93) and biological therapy (34.8%, n = 72) were the commonest treatments used. Overall survival at 6 months, 1-, 2- and 5-years was 41.7, 29.7, 11.8, and 1.7%, respectively. The median survival time of 4.4 months was not statistically significantly different between participants with NSCLC or SCLC (4.5 versus 3.9 months, p = .335). CONCLUSION: In Uganda, adenocarcinoma is the predominant histologic subtype of lung cancer and patients are predominantly females, and non-smokers. Patients present late with advanced disease and poor overall survival. Public awareness should be heightened to facilitate early detection and improve outcomes.


Assuntos
Adenocarcinoma/mortalidade , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma de Células Escamosas/mortalidade , Neoplasias Pulmonares/mortalidade , Adenocarcinoma/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma de Células Escamosas/patologia , Feminino , Humanos , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Taxa de Sobrevida , Uganda/epidemiologia , Adulto Jovem
14.
Lancet Oncol ; 23(2): 259-269, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-35038433

RESUMO

BACKGROUND: Trastuzumab is a monoclonal antibody against HER2 (also known as ERBB2). The primary objective of the NRG Oncology/RTOG-1010 trial was to establish whether trastuzumab improves disease-free survival when combined with trimodality treatment (paclitaxel plus carboplatin and radiotherapy, followed by surgery) for patients with untreated HER2-overexpressing oesophageal adenocarcinoma. METHODS: NRG Oncology/RTOG-1010 was an open label, randomised, phase 3 trial for which patients were accrued from 111 NRG-affiliated institutions in the USA. Eligible patients were adults (aged ≥18 years) with newly diagnosed pathologically confirmed oesophageal adenocarcinoma, American Joint Committee on Cancer 7th edition T1N1-2 or T2-3N0-2 stage disease, and a Zubrod performance status of 0-2. Patients were stratified by adenopathy (no vs yes [coeliac absent] vs yes [coeliac present ≤2 cm]) and randomly assigned (1:1) to receive weekly intravenous paclitaxel (50 mg/m2 intravenously over 1 h) and carboplatin (area under the curve 2, intravenously over 30-60 min) for 6 weeks with radiotherapy 50·4 Gy in 28 fractions (chemoradiotherapy) followed by surgery, with or without intravenous trastuzumab (4 mg/kg in week one, 2 mg/kg per week for 5 weeks during chemoradiotherapy, 6 mg/kg once presurgery, and 6 mg/kg every 3 weeks for 13 treatments starting 21-56 days after surgery). The primary endpoint, disease-free survival, was defined as the time from randomisation to death or first of locoregional disease persistence or recurrence, distant metastases, or second primary malignancy. Analyses were done by modified intention to treat. This study is registered with Clinicaltrials.gov, NCT01196390; it is now closed and in follow-up. FINDINGS: 606 patients were entered for HER2 assessment from Dec 30, 2010 to Nov 10, 2015, and 203 eligible patients who were HER2-positive were enrolled and randomly assigned to chemoradiotherapy plus trastuzumab (n=102) or chemoradiotherapy alone (n=101). Median duration of follow-up was 2·8 years (IQR 1·4-5·7). Median disease-free survival was 19·6 months (95% CI 13·5-26·2) with chemoradiotherapy plus trastuzumab compared with 14·2 months (10·5-23·0) for chemoradiotherapy alone (hazard ratio 0·99 [95% CI 0·71-1·39], log-rank p=0·97). Grade 3 treatment-related adverse events occurred in 41 (43%) of 95 patients in the chemoradiotherapy plus trastuzumab group versus 52 (54%) of 96 in the chemoradiotherapy group and grade 4 events occurred in 20 (21%) versus 21 (22%). The most common grade 3 or worse treatment-related adverse events for both groups were haematological (53 [56%] of 95 patients in the chemoradiotherapy plus trastuzumab group vs 55 [57%] of 96 patients in the chemotherapy group) or gastrointestinal disorders (28 [29%] vs 20 [21 %]). 34 (36%) of 95 patients in the chemoradiotherapy plus trastuzumab group and 27 (28%) of 96 patients in the chemoradiotherapy only group had treatment-related serious adverse events. There were eight treatment-related deaths: five (5%) of 95 patients in the chemoradiotherapy plus trastuzumab group (bronchopleural fistula, oesophageal anastomotic leak, lung infection, sudden death, and death not otherwise specified), and three (3%) of 96 in the chemoradiotherapy group (two multiorgan failure and one sepsis). INTERPRETATION: The addition of trastuzumab to neoadjuvant chemoradiotherapy for HER2-overexpressing oesophageal cancer was not effective. Trastuzumab did not lead to increased toxicities, suggesting that future studies combining it with or using other agents targeting HER2 in oesophageal cancer are warranted. FUNDING: National Cancer Institute and Genentech.


Assuntos
Adenocarcinoma/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Esofágicas/tratamento farmacológico , Receptor ErbB-2/análise , Trastuzumab/uso terapêutico , Adenocarcinoma/química , Adenocarcinoma/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Carboplatina/administração & dosagem , Quimiorradioterapia , Neoplasias Esofágicas/química , Neoplasias Esofágicas/mortalidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Paclitaxel/administração & dosagem , Trastuzumab/efeitos adversos
15.
Anticancer Res ; 42(2): 991-1000, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35093899

RESUMO

BACKGROUND/AIM: To compare clinical outcomes following intensified total neoadjuvant therapy (TNT) and intensified neoadjuvant chemoradiotherapy (CRT) in patients with locally advanced rectal cancer (LARC). PATIENTS AND METHODS: Of the 79 patients with LARC admitted to our department, 51 received intensified neoadjuvant CRT (CRT group) and 28 received intensified TNT (TNT group). Intensified TNT was defined as multi-agent chemotherapy, including FOLFOXIRI regimen plus bevacizumab (mutated Ras-BRAF) or panitumumab/cetuximab (wild-type Ras-BRAF) followed by oxaliplatin-5-fluorouracil-based CRT and surgery. Kaplan-Meier and Log rank test were used for survival analysis. Survival rates of the two groups were compared using propensity score matching. RESULTS: Data from 28 TNT patients and 28 CRT patients were analyzed after a 1:1 propensity matching with replacement. Kaplan-Meier curve showed that overall survival (OS), disease-free survival (DFS) and distant metastasis-free survival (DMFS) rates with TNT were comparable to those with CRT. The 5-year DMFS rates for TNT and CRT were 61.5% versus 63.0% (p=0.82), respectively. In the TNT group, 32.1% patients (n=9) achieved pathological complete response (pCR), whereas 21.4% patients (n=6) achieved pCR with CRT (p=0.37). CONCLUSION: Intensified TNT and CRT resulted in similar survival outcomes, while intensified TNT led to higher pCR, albeit not statistically significant.


Assuntos
Adenocarcinoma/terapia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Quimiorradioterapia , Terapia Neoadjuvante/métodos , Neoplasias Retais/terapia , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Quimiorradioterapia/métodos , Progressão da Doença , Relação Dose-Resposta a Droga , Feminino , Seguimentos , Humanos , Itália/epidemiologia , Masculino , Análise por Pareamento , Pessoa de Meia-Idade , Invasividade Neoplásica , Pontuação de Propensão , Neoplasias Retais/mortalidade , Neoplasias Retais/patologia , Análise de Sobrevida , Adulto Jovem
16.
Anticancer Res ; 42(2): 1107-1114, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35093913

RESUMO

BACKGROUND/AIM: We examined the prognostic use of the 3-month prostate-specific antigen (PSA3m) level after androgen-deprivation therapy in patients with de novo metastatic hormone-sensitive prostate cancer (mHSPC). PATIENTS AND METHODS: The present study included 145 patients with mHSPC who received primary androgen-deprivation therapy. RESULTS: The optimal cutoff PSA3m value for prediction of 5-year overall survival was 2.56 ng/ml (area under the receiver operating characteristics curve=0.67) using a time-dependent receiver operating characteristic (survival ROC) curve. In patients with CHAARTED low-volume and LATITUDE low-risk disease, the median overall survival was longer for patients with low PSA3m than that for those with high PSA3m. Multivariate analysis revealed PSA3m (hazard ratio=1.99; p=0.006) and age ≥80 years as independent risk factors for overall survival in patients with mHSPC. CONCLUSION: PSA3m can be a useful prognostic biomarker to avoid excessive upfront combination therapy, particularly in elderly patients with low-volume and low-risk mHSPC.


Assuntos
Adenocarcinoma , Antagonistas de Androgênios/uso terapêutico , Antígeno Prostático Específico/sangue , Neoplasias da Próstata , Adenocarcinoma/diagnóstico , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Idoso , Idoso de 80 Anos ou mais , Seguimentos , Humanos , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Valor Preditivo dos Testes , Prognóstico , Antígeno Prostático Específico/análise , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/mortalidade , Neoplasias da Próstata/patologia , Análise de Sobrevida , Fatores de Tempo , Resultado do Tratamento
17.
Anticancer Res ; 42(2): 1143-1150, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35093918

RESUMO

BACKGROUND/AIM: Locally advanced rectal cancer (LARC) patients are often treated with neoadjuvant long course chemoradiotherapy (NLCCRT) using 45-50.4 Gy conventional fractionated radiotherapy (CFRT). The role of radiotherapy dose escalation is unclear. PATIENTS AND METHODS: We identified LARC patients diagnosed from 2011 to 2016 and treated with NLCCRT using CFRT at high dose (54-60 Gy) or standard dose (45-50.4 Gy). In the primary analyses, we used propensity score (PS) weighting to balance the observable potential confounders. The hazard ratio (HR) of death and other endpoints were compared. We also evaluated these outcomes in supplementary analyses via an alternative approach. RESULTS: Our primary analysis included 459 patients. The HR of death when high dose was compared with standard dose was 0.62 (p=0.51). There were also no statistically significant differences in other endpoints or in the supplementary analyses. CONCLUSION: Overall, survival of LARC patients treated with NLCCT in CFRT was not significantly different between high or standard dose.


Assuntos
Adenocarcinoma/terapia , Quimiorradioterapia/métodos , Neoplasias Retais/terapia , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Adolescente , Adulto , Idoso , Estudos de Coortes , Progressão da Doença , Fracionamento da Dose de Radiação , Esquema de Medicação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante/métodos , Invasividade Neoplásica , Dosagem Radioterapêutica , Neoplasias Retais/mortalidade , Neoplasias Retais/patologia , Estudos Retrospectivos , Padrão de Cuidado , Análise de Sobrevida , Taiwan/epidemiologia , Fatores de Tempo , Adulto Jovem
18.
Dis Colon Rectum ; 65(2): 189-197, 2022 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-34990422

RESUMO

BACKGROUND: Anal adenocarcinoma is a rare clinical entity for which the optimal management is not defined. OBJECTIVE: This study aimed to describe the multidisciplinary management and outcomes of patients with anal adenocarcinoma. DESIGN: This is a retrospective cohort study. SETTING: This study was conducted at a quaternary cancer center. PATIENTS: Men and women with anal adenocarcinoma treated between 1995 and 2016 were selected. INTERVENTIONS: Fifty-two patients were treated with either chemoradiotherapy or trimodality therapy including radiation therapy, chemotherapy, and surgical resection. MAIN OUTCOME MEASURES: Local failure, regional failure, and distant metastasis rates were estimated using the cumulative incidence method. The Kaplan-Meier method was used to estimate progression-free survival and overall survival. The multivariable Cox proportional hazards model was used to evaluate the clinical predictors of outcome. RESULTS: There was a higher 5-year rate of local failure in patients treated with chemoradiotherapy compared with trimodality therapy (53% vs 10%; p < 0.01). The 5-year incidence of distant metastases was 29% (trimodality therapy) versus 30% (chemoradiotherapy; p = 0.9); adjuvant chemotherapy did not reduce the incidence of distant metastases (p = 0.8). Five-year overall survival was 73% (trimodality therapy) versus 49.4% (chemoradiotherapy; p = 0.1). On multivariable analysis, factors associated with worse overall survival were treatment with chemoradiotherapy, cT3-4 category disease, and node-positive disease. LIMITATIONS: This study is limited by its small sample size and retrospective nature. CONCLUSIONS: Although treatment may continue to be tailored to individual patients, better outcomes with a trimodality therapy approach were observed. See Video Abstract at http://links.lww.com/DCR/B708.ADENOCARCINOMA ANAL: UNA ENTIDAD POCO FRECUENTE EN NECESIDAD DE UN MANEJO MULTIDISCIPLINARIO. ANTECEDENTES: El adenocarcinoma anal es una entidad clínica poco frecuente por lo que aún no se define el manejo óptimo. OBJETIVO: Describir el manejo multidisciplinario y los resultados de los pacientes con adenocarcinoma anal. DISEO: Estudio de cohorte retrospectivo. ENTORNO CLINICO: Centro de cáncer cuaternario. PACIENTES: Hombres y mujeres con adenocarcinoma anal tratados entre 1995 y 2016. INTERVENCIONES: Cincuenta y dos pacientes fueron tratados con quimiorradioterapia o terapia trimodal que incluyó: radioterapia, quimioterapia y resección quirúrgica. PRINCIPALES MEDIDAS DE VALORACION: Se estimaron las tasas de falla local, falla regional y metástasis a distancia mediante el método de incidencia acumulada. Se utilizó el método de Kaplan-Meier para estimar la supervivencia libre de progresión y la supervivencia global. Los riesgos proporcionales de multivariable Cox se utilizaron para evaluar los predictores clínicos de los resultados. RESULTADOS: Hubo una mayor tasa de falla local a cinco años en pacientes tratados con quimiorradioterapia en comparación con terapia trimodal (53% vs 10%; p < 0,01). La incidencia a cinco años de metástasis a distancia fue del 29% (terapia trimodal) versus 30% (quimiorradioterapia) (p = 0,9); la quimioterapia adyuvante no redujo la incidencia de metástasis a distancia (p = 0,8). La supervivencia global a cinco años fue del 73% (terapia trimodal) versus 49,4% (quimiorradioterapia); p = 0,1. En el análisis multivariable, los factores asociados con una peor supervivencia general fueron el tratamiento con quimiorradioterapia, enfermedad de categoría cT3-4 y enfermedad con ganglios positivos. LIMITACIONES: Este estudio está limitado por su pequeño tamaño de muestra y su naturaleza retrospectiva. CONCLUSIONES: Aunque el tratamiento puede seguir adaptándose a pacientes individuales, se observaron mejores resultados con un enfoque TTM. Conslute Video Resumen en http://links.lww.com/DCR/B708. (Traducción- Dr. Francisco M. Abarca-Rendon).


Assuntos
Adenocarcinoma/terapia , Neoplasias do Ânus/terapia , Adenocarcinoma/diagnóstico , Adenocarcinoma/mortalidade , Adulto , Idoso , Antineoplásicos/uso terapêutico , Neoplasias do Ânus/diagnóstico , Neoplasias do Ânus/mortalidade , Terapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Padrões de Prática Médica , Protectomia , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do Tratamento
19.
Dis Colon Rectum ; 65(2): 198-206, 2022 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-34990423

RESUMO

BACKGROUND: Short-course radiation followed by chemotherapy as total neoadjuvant therapy has been investigated primarily in Europe and Australia with increasing global acceptance. There are limited data on this regimen's use in the United States, however, potentially delaying implementation. OBJECTIVE: This study aimed to compare clinical performance and oncologic outcomes of 2 rectal cancer neoadjuvant treatment modalities: short-course total neoadjuvant therapy versus standard chemoradiation. DESIGN: This is a retrospective cohort study. SETTING: This study was performed at a National Cancer Institute-designated cancer center. PATIENTS: A total of 413 patients had locally advanced rectal cancers diagnosed from June 2009 to May 2018 and received either short-course total neoadjuvant therapy or standard chemoradiation. INTERVENTIONS: There were 187 patients treated with short-course total neoadjuvant therapy (5 × 5 Gy radiation followed by consolidation oxaliplatin-based chemotherapy) compared with 226 chemoradiation recipients (approximately 50.4 Gy radiation in 28 fractions with concurrent fluorouracil equivalent). MAIN OUTCOME MEASURES: Primary end points were tumor downstaging, measured by complete response and "low" neoadjuvant rectal score rates, and progression-free survival. Secondary analyses included treatment characteristics and completion, sphincter preservation, and recurrence rates. RESULTS: Short-course total neoadjuvant therapy was associated with higher rates of complete response (26.2% vs 17.3%; p = 0.03) and "low" neoadjuvant rectal scores (40.1% vs 25.7%; p < 0.01) despite a higher burden of node-positive disease (78.6% vs 68.9%; p = 0.03). Short-course recipients also completed trimodal treatment more frequently (88.4% vs 50.4%; p < 0.01) and had fewer months with temporary stomas (4.8 vs 7.0; p < 0.01). Both regimens achieved comparable local control (local recurrence: 2.7% short-course total neoadjuvant therapy vs 2.2% chemoradiation, p = 0.76) and 2-year progression-free survival (88.2% short-course total neoadjuvant therapy (95% CI, 82.9-93.5) vs 85.6% chemoradiation (95% CI, 80.5-90.7)). LIMITATIONS: Retrospective design, unbalanced disease severity, and variable dosing of neoadjuvant consolidation chemotherapy were limitations of this study. CONCLUSIONS: Short-course total neoadjuvant therapy was associated with improved downstaging and similar progression-free survival compared with chemoradiation. These results were achieved with shortened radiation courses, improved treatment completion, and less time with diverting ostomies. Short-course total neoadjuvant therapy is an optimal regimen for locally advanced rectal cancer. See Video Abstract at http://links.lww.com/DCR/B724.TERAPIA NEOADYUVANTE TOTAL CON RADIACIÓN DE CORTA DURACIÓN: EXPERIENCIA ESTADOUNIDENSE DE UNA TERAPIA NEOADYUVANTE CONTRA EL CÁNCER DE RECTO. ANTECEDENTES: La radiación de corta duración seguida de quimioterapia como terapia neoadyuvante total se ha investigado principalmente en Europa y Australia con una aceptación mundial cada vez mayor. Sin embargo, datos limitados sobre el uso de este régimen en los Estados Unidos, han potencialmente retrasando su implementación. OBJETIVO: Comparar el desempeño clínico y los resultados oncológicos de dos modalidades de tratamiento neoadyuvante del cáncer de recto: terapia neoadyuvante total de corta duración versus quimioradiación. estándar. DISEO: Cohorte retrospectivo. AJUSTE: Centro oncológico designado por el NCI. PACIENTES: Un total de 413 cánceres rectales localmente avanzados diagnosticados entre junio de 2009 y mayo de 2018 que recibieron cualquiera de los regímenes neoadyuvantes. INTERVENCIONES: Hubo 187 pacientes tratados con terapia neoadyuvante total de ciclo corto (radiación 5 × 5 Gy seguida de quimioterapia de consolidación basada en oxaliplatino) en comparación con 226 pacientes de quimiorradiación (aproximadamente 50,4 Gy de radiación en 28 fracciones con equivalente de fluorouracilo concurrente). PRINCIPALES MEDIDAS DE RESULTADO: Los criterios primarios de valoración fueron la disminución del estadio del tumor, medido por la respuesta completa y las tasas de puntuación rectal neoadyuvante "baja", y la supervivencia libre de progresión. Los análisis secundarios incluyeron las características del tratamiento y las tasas de finalización, conservación del esfínter y recurrencia. RESULTADOS: La terapia neoadyuvante total de corta duración, se asoció con tasas más altas de respuesta completa (26,2% versus 17,3%, p = 0,03) y puntuaciones rectales neoadyuvantes "bajas" (40,1% versus 25,7%, p < 0,01) a pesar de una mayor carga de enfermedad con ganglios positivos (78,6% versus 68,9%, p = 0,03). Los pacientes de ciclo corto también completaron el tratamiento trimodal con mayor frecuencia (88,4% versus 50,4%, p < 0,01) y tuvieron menos meses con estomas temporales (4,8 versus 7,0, p < 0,01). Ambos regímenes lograron un control local comparable (recidiva local: 2,7% de SC-TNT versus 2,2% de TRC, p = 0,76) y supervivencia libre de progresión a 2 años (88,2% de SC-TNT [IC: 82,9 - 93,5] versus 85,6% CRT [CI: 80,5 - 90,7]). LIMITACIONES: Diseño retrospectivo, gravedad de la enfermedad desequilibrada y dosificación variable de quimioterapia neoadyuvante de consolidación. CONCLUSIONES: La terapia neoadyuvante total de ciclo corto se asoció con una mejora en la reducción del estadio y una supervivencia libre de progresión similar en comparación con la quimioradiación. Estos resultados se lograron con ciclos de radiación más cortos, tratamientos mejor finalizados y menos tiempo en ostomías de derivación. La terapia neoadyuvante total de corta duración es un régimen óptimo para el cáncer de recto localmente avanzado. Consulte Video Resumen en http://links.lww.com/DCR/B724. (Traducción- Dr. Fidel Ruiz Healy).


Assuntos
Adenocarcinoma/terapia , Quimiorradioterapia , Terapia Neoadjuvante , Protectomia , Neoplasias Retais/terapia , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias Retais/mortalidade , Neoplasias Retais/patologia , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do Tratamento
20.
Surg Oncol ; 40: 101707, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35030410

RESUMO

BACKGROUND: The aim of this study was to assess the impact of baseline health related quality of life (HRQOL) on the occurrence of postoperative complications and death in patients with resectable esophageal cancer. METHODS: Existing data from a prospective, multicenter, open label, randomized, controlled phase III trial comparing hybrid versus open esophagectomy in patients with resectable esophageal cancer from 2009 to 2012 in France were used. A Cox regression model was used to assess the prognostic value of the baseline HRQOL score on the occurrence of major complications (MC), and major pulmonary complications (MPC) at 30 days post-surgery, as well as on 1-year postoperative overall survival (OS). RESULTS: Every 10-point increase in the baseline role functioning score was associated with a 14% reduction in the risk of MC, while every 10-point increase in fatigue or pain score was associated with an 18% increase in the risk of MC. Similarly, higher scores on fatigue and pain were associated with a higher risk of MPC. Compared with the hybrid procedure, patients undergoing open esophagectomy had a significantly higher risk of MC and MPC. Patients diagnosed with esophageal adenocarcinoma were at significantly lower risk of MC or MPC compared to patients with esophageal squamous cell carcinoma. Higher pain (HR = 1.23, p = 0.035) and insomnia (HR = 1.16, P = 0.031) scores were associated with increased 1-year OS. CONCLUSION: Fatigue, pain, insomnia, and squamous cell pathology were indicators of poor prognosis, and that the presence of these findings might possibly change the management plan towards other forms of treatment and warrant close attention.


Assuntos
Adenocarcinoma/cirurgia , Carcinoma de Células Escamosas/cirurgia , Neoplasias Esofágicas/cirurgia , Esofagectomia/efeitos adversos , Complicações Pós-Operatórias/epidemiologia , Qualidade de Vida , Adenocarcinoma/complicações , Adenocarcinoma/mortalidade , Idoso , Carcinoma de Células Escamosas/complicações , Carcinoma de Células Escamosas/mortalidade , Neoplasias Esofágicas/complicações , Neoplasias Esofágicas/mortalidade , Feminino , França , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Modelos de Riscos Proporcionais , Taxa de Sobrevida , Fatores de Tempo , Resultado do Tratamento
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