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1.
J Clin Pharmacol ; 62(2): 206-219, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34435684

RESUMO

Population pharmacokinetic (PK) and exposure-safety analyses of alisertib were performed in children enrolled in 2 clinical trials: NCT02444884 and NCT01154816. NCT02444884 was a dose-finding study in children with relapsed/refractory solid malignancies (phase 1) or neuroblastomas (phase 2). Patients received oral alisertib 45 to 100 mg/m2 as powder-in-capsule once daily or twice daily for 7 days in 21-day cycles. Serial blood samples were collected up to 24 hours after dosing on cycle 1, day 1. NCT01154816 was a phase 2 single-arm study evaluating efficacy in children with relapsed/refractory solid malignancies or acute leukemias. Patients received alisertib 80 mg/m2 as enteric-coated tablets once daily for 7 days in 21-day cycles. Sparse PK samples were collected up to 8 hours after dosing on cycle 1, day 1. Sources of alisertib PK variability were characterized and quantified using nonlinear mixed-effects modeling to support dosing recommendations in children and adolescents. A 2-compartment model with oral absorption described by 3 transit compartments was developed using data from 146 patients. Apparent oral clearance and central distribution volume were correlated with body surface area across the age range of 2 to 21 years, supporting the use of body surface area-based alisertib dosing in the pediatric population. The recommended dose of 80 mg/m2 once daily enteric-coated tablets provided similar alisertib exposures across pediatric age groups and comparable exposure to that in adults receiving 50 mg twice daily (recommended adult dose). Statistically significant relationships (P < .01) were observed between alisertib exposures and incidence of grade ≥2 stomatitis and febrile neutropenia, consistent with antiproliferative mechanism-related toxicities.


Assuntos
Antineoplásicos/farmacocinética , Azepinas/farmacocinética , Neoplasias/tratamento farmacológico , Inibidores de Proteínas Quinases/farmacocinética , Pirimidinas/farmacocinética , Adolescente , Antineoplásicos/efeitos adversos , Azepinas/efeitos adversos , Superfície Corporal , Criança , Pré-Escolar , Esquema de Medicação , Feminino , Humanos , Masculino , Dose Máxima Tolerável , Modelos Biológicos , Estadiamento de Neoplasias , Neoplasias/patologia , Inibidores de Proteínas Quinases/efeitos adversos , Pirimidinas/efeitos adversos , Adulto Jovem
2.
Clin. transl. oncol. (Print) ; 24(9): 1744–1754, septiembre 2022.
Artigo em Inglês | IBECS | ID: ibc-JHG-507

RESUMO

PurposeWe conducted a systematic review to analyse the performance of the sentinel lymph-node biopsy (SLNB) after the neoadjuvant chemotherapy, compared to axillary lymph-node dissection, in terms of false-negative rate (FNR) and sentinel lymph-node identification rate (SLNIR), sensitivity, negative predictive value (NPV), need for axillary lymph-node dissection (ALND), morbidity, preferences, and costs.MethodsMEDLINE, Embase, Scopus, and The Cochrane Library were searched. We assessed the quality of the included systematic reviews using AMSTAR2 tool, and estimated the degree of overlapping of the individual studies on the included reviews.ResultsSix systematic reviews with variable quality were selected. We observed a very high overlapping degree across the included reviews. The FNR and the SLNIR were quite consistent (FNR 13–14%; SLNIR ~ 90% or higher). In women with initially clinically node-negative breast cancer, the FNR was better (6%), with similar SLNIR (96%). The included reviews did not consider the other prespecified outcomes.ConclusionsIt would be reasonable to suggest performing an SLNB in patients treated with NACT, adjusting the procedure to the previous marking of the affected lymph node, using double tracer, and biopsy of at least three sentinel lymph nodes. More well-designed research is needed. (AU)


Assuntos
Humanos , Axila , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/cirurgia , Linfonodos/patologia , Linfonodos/cirurgia , Terapia Neoadjuvante/métodos , Estadiamento de Neoplasias , Pacientes
3.
BMC Cancer ; 22(1): 863, 2022 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-35941565

RESUMO

BACKGROUND: There is no clear consensus on the benefits of adjuvant chemotherapy for tumor-node-metastasis (TNM) stage T1 (T1N0M0) breast cancer (BC). Our study investigated the effects of adjuvant chemotherapy on T1N0M0 BC patients. METHODS: Seventy-five thousand one hundred thirty-nine patients diagnosed with T1N0M0 BC were selected from the Surveillance, Epidemiology, and End Results (SEER) database. Multivariate Cox analyses were performed to investigate the effects of adjuvant chemotherapy on T1a, T1b, and T1cN0M0 BC, including various tumor grades, and four molecular subtypes. Propensity score matching (PSM) was used to eliminate confounding factors and further compare the results between adjuvant chemotherapy and no adjuvant chemotherapy. Additionally, 545 T1N0M0 BC patients treated at the Northern Jiangsu People's Hospital were included as an independent external validation cohort. Univariate and multivariate Cox analyses were used to confirm the effects of adjuvant chemotherapy in T1a, T1b, and T1cN0M0 BC. Survival curves for the different tumor grades and molecular subtypes were plotted using the Kaplan-Meier method. RESULTS: Adjuvant chemotherapy demonstrated a statistically significant improvement in overall survival (OS) in T1b and T1c BC, but not in T1a BC. Within T1b BC, adjuvant chemotherapy was found to have effects on grade III, and hormone receptor + (HoR +)/human epidermal growth factor receptor 2 + (HER2 +), HoR-/HER2 + , and HoR-/HER2- molecular subtypes, respectively. Adjuvant chemotherapy was beneficial to OS for grade II/III and T1c BC. Identical results were obtained after PSM. We also obtained similar results with external validation cohort, except that adjuvant chemotherapy made a difference in grade II and T1b BC of the external validation dataset. CONCLUSIONS: Partial T1N0M0 BC patients with grade III T1bN0M0, patients with tumor grade II and III T1cN0M0, and excluding those with HoR + /HER2- subtype tumors, could obtain OS benefits from adjuvant chemotherapy.


Assuntos
Neoplasias da Mama , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/patologia , Quimioterapia Adjuvante/métodos , Estudos de Coortes , Feminino , Humanos , Estadiamento de Neoplasias , Prognóstico , Pontuação de Propensão , Receptor ErbB-2/metabolismo
4.
World J Surg Oncol ; 20(1): 253, 2022 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-35941602

RESUMO

BACKGROUND: Indocyanine green (ICG) is becoming a frequently used sentinel lymph node (SLN) tracer of breast cancer in China. However, there is still a lack of data on its safety. We reported the clinical outcome of ICG as a tracer of SLN over a median 67-month follow-up period to evaluate its feasibility in clinically node-negative patients with breast cancer. METHODS: A total of 194 consecutive patients underwent sentinel lymph node biopsy (SLNB) with ICG, radioisotopes (RI) and methylene blue (MB), or with ICG and MB. The SLN mapping data by each tracer was recorded, and safety outcomes were analyzed through follow-up. RESULTS: With the triad mapping (N = 44), the identification rate of SLN by ICG was 95.5%, slightly higher than that of MB (86.4%) and comparable with RI (95.5%) and combined methods (95.5%, 100%) (p = 0.068). Analysis of all candidates (N = 194) demonstrated that the identification rate of SLN by ICG or by ICG and MB was 99%, significantly higher than that by MB (92.8%) (p < 0.0001). No tracer-related allergic reaction and permanent skin staining of ICG were observed. Local disease progression was reported in 2 of the 194 patients at the ipsilateral axilla. After remedial axillary lymph node dissection, no disease progression was detected at follow-up. CONCLUSIONS: ICG as an SLN tracer is more accurate than MB and comparable to the combined methods and has good clinical safety. ICG can be considered a useful supplement or suitable alternative to traditional tracers.


Assuntos
Neoplasias da Mama , Linfonodo Sentinela , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/patologia , Neoplasias da Mama/cirurgia , Corantes , Feminino , Humanos , Verde de Indocianina , Linfonodos/patologia , Azul de Metileno , Estadiamento de Neoplasias , Linfonodo Sentinela/diagnóstico por imagem , Linfonodo Sentinela/patologia , Linfonodo Sentinela/cirurgia , Biópsia de Linfonodo Sentinela/métodos
5.
Curr Opin Oncol ; 34(5): 490-496, 2022 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-35943438

RESUMO

PURPOSE OF REVIEW: Robot-assisted laparoscopic staging (RALS) is increasingly used for staging epithelial ovarian cancer (EOC). Evidence of its safety is limited. The aim of this review is to compare the efficacy and safety of RALS in clinical early-stage EOC to conventional laparoscopy and laparotomy and to assess the level of evidence that is currently available to adopt this surgical technique. RECENT FINDINGS: Only retrospective studies comparing staging by minimally invasive surgery (MIS) to laparotomy are available. Both RALS and conventional laparoscopic staging shorten length of hospital stay (LHS, mean -2.9 days) and decrease estimated blood loss (EBL, mean -79 ml less) compared to laparotomy. Complication rates and number of lymph nodes collected are similar in all surgical staging techniques. Survival outcomes after staging by MIS cannot be compared to staging by laparotomy because of the lack of evidence but RALS is probably noninferior to conventional laparoscopic staging. SUMMARY: RALS probably improves perioperative outcomes in patients with clinical early stage EOC similar to conventional laparoscopic staging. Whether oncologic outcomes of RALS are comparable to open and conventional approaches is uncertain as there is only level C evidence and randomized controlled trials are urgently needed to confirm the current retrospective findings.


Assuntos
Carcinoma , Laparoscopia , Neoplasias Ovarianas , Robótica , Carcinoma/patologia , Carcinoma Epitelial do Ovário/cirurgia , Feminino , Humanos , Laparoscopia/métodos , Laparotomia , Estadiamento de Neoplasias , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/cirurgia , Estudos Retrospectivos , Resultado do Tratamento
6.
Curr Opin Oncol ; 34(5): 511-517, 2022 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-35943439

RESUMO

PURPOSE OF REVIEW: The management of endometrial cancer has known many evolutions within the last decades. In this review, we aim to summarize recent evolutions (mainly toward less aggressive management) that have occurred in the management of endometrial cancer. RECENT FINDINGS: Enhanced by molecular classification, the determination of lymph node status, in young women, in case of cervical invasion, the treatment is evolving toward a less aggressive strategy. SUMMARY: The predictive value and the safety of sentinel lymph node biopsy explain why most societies propose to abandon systematic pelvic and para aortic lymphadenectomy. For young women, the safety of fertility preservation is now well established and efficient protocols have been validated. In stage II endometrial cancer (stromal cervical invasion), radical hysterectomy appears excessive. The Cancer Genome Atlas classification increases prognostic evaluation in association with the traditional pathological classification and permits to tailor adjuvant treatment more accurately.


Assuntos
Tratamento Conservador , Neoplasias do Endométrio , Neoplasias do Endométrio/genética , Neoplasias do Endométrio/cirurgia , Feminino , Humanos , Histerectomia/métodos , Excisão de Linfonodo/métodos , Linfonodos/patologia , Linfonodos/cirurgia , Metástase Linfática/patologia , Estadiamento de Neoplasias , Biópsia de Linfonodo Sentinela/métodos
7.
Cir Cir ; 90(4): 525-528, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35944435

RESUMO

BACKGROUND: Lymph mapping with sentinel node biopsy is the standard procedure for lymph node staging in patients with cutaneous melanoma with a tumor thickness of 1 mm or greater. Patients who have metastases in sentinel node must undergo complementary lymphadenectomy; however, it has not been shown to improve survival. OBJECTIVE: To know the prevalence in our setting of metastases in the product of complementary lymphadenectomy in patients with metastatic sentinel node. METHOD: Evaluation of a descriptive, retrospective, observational and analytical cohort of patients with metastatic sentinel node submitted to lymphadenectomy. Multivariate analysis of tumor thickness, neural invasion, location, sentinel node number, serum DHL level, lymph nodes dissected and extracapsular spread. RESULTS: 67 patients, 35 women and 32 men with a mean of 66 years, 22% had metastases in lymph nodes from complementary lymphadenectomy, 19% of them with extracapsular spread; no relationship with the Breslow level. Extracapsular spread in the sentinel node, lymphadenectomy time, and perineural invasion in the primary tumor were prognostic factors for non-sentinel node metastasis. CONCLUSIONS: In this series, 22% of the patients with a sentinel node-positive have metastases in the non-sentinel nodes, 19% of them with extracapsular spread, which justifies complementary lymphadenectomy.


ANTECEDENTES: El mapeo linfático con biopsia del ganglio centinela es el procedimiento estándar de estadificación ganglionar en pacientes con melanoma cutáneo con grosor tumoral de 1 mm o mayor. Los pacientes que tienen metástasis en él deben ser sometidos a linfadenectomía complementaria; sin embargo, esta no ha mostrado mejorar la superviviencia. OBJETIVO: Conocer la prevalencia en nuestro medio de metástasis en el producto de linfadenectomía complementaria en pacientes con ganglio centinela metastásico. MÉTODO: Evaluación de una cohorte descriptiva, retrospectiva, observacional y analítica de pacientes con ganglio centinela metastásico sometidos a linfadenectomía, con análisis multivariado de grosor tumoral, invasión neural, localización, número de ganglios centinela, concentración sérica de deshidrogenasa láctica, ganglios disecados en linfadenectomía y ruptura capsular. RESULTADOS: Hubo 67 pacientes (35 mujeres y 32 hombres), con una media de 66 años de edad, en el 22% hubo metástasis en ganglios de linfadenectomía complementaria y en el 19% ruptura capsular; sin relación con el nivel de Breslow. La ruptura capsular en el ganglio centinela, el tiempo de linfadenectomía y la invasión perineural fueron factores pronóstico de metástasis en ganglios no centinela. CONCLUSIONES: En esta serie, el 22% de los pacientes tuvieron metástasis en ganglios no centinela, el 19% de ellos con ruptura capsular, lo cual justifica la linfadenectomía complementaria.


Assuntos
Melanoma , Neoplasias Cutâneas , Feminino , Humanos , Excisão de Linfonodo , Metástase Linfática , Masculino , Melanoma/patologia , Estadiamento de Neoplasias , Estudos Retrospectivos , Biópsia de Linfonodo Sentinela , Neoplasias Cutâneas/patologia
8.
Technol Cancer Res Treat ; 21: 15330338221110673, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35929137

RESUMO

Background: This study aimed to develop a prognostic model based on the Surveillance, Epidemiology, and End Results (SEER) database to predict the overall survival (OS) of small cell carcinoma of the uterine cervix (SmCC). Methods: Between 1975 and 2016, a total of 401 patients were included, and their comprehensive sociodemographic and clinicopathological characteristics were collected. Univariate and multivariate Cox regression models were used to screen for independent prognostic factors. The identified factors were used to conduct a nomogram for predicting the OS of SmCC. The performance of the nomogram was determined using area under the receiver operating characteristic curve (AUC), concordance index (C-index), calibration curve, and decision curve analysis (DCA) metrics. Results: The median survival time of all patients was about 24 months (95% confidence interval [95% CI] [1.50-2.17]). Age (hazard ratio [HR] = 1.693 for 45-59 vs 21-34, 95% CI [1.140-2.513], P = .009; HR = 2.836 for 60-92 vs 21-34, 95% CI [1.851-4.345], P < .001), positive nodes (HR = 2.384, 95% CI [1.437-3.955], P < .001), regional nodes number ≥12 (HR = 0.500, 95% CI [0.282-0.886], P = .018), and treatment method (HR = 0.409 for surgery vs no, 95% CI [0.267-0.628], P < .001; HR = 0.649 for chemotherapy vs no, 95% CI [0.478-0.881)], P = .006) were independent factors of OS. Young patients who had surgical resection or chemotherapy, negative lymph nodes, and regional lymph nodes ≥12 had a longer survival time. These clinical factors were utilized to construct a nomogram for predicting OS. The AUC and C-index were higher than 0.7, indicating the good discriminating ability of the nomogram. The calibrations were all around the 45-degree line, indicating excellent consistency between the prediction of the model and actual observations. The DCA plots supported the clinical utility of the nomogram. Conclusion: The constructed nomogram is expected to help predict the prognosis of SmCC and guide patient treatment.


Assuntos
Carcinoma de Células Pequenas , Neoplasias do Colo do Útero , Fatores Etários , Carcinoma de Células Pequenas/epidemiologia , Carcinoma de Células Pequenas/terapia , Feminino , Humanos , Estadiamento de Neoplasias , Nomogramas , Prognóstico , Programa de SEER , Neoplasias do Colo do Útero/epidemiologia , Neoplasias do Colo do Útero/terapia
9.
Comput Math Methods Med ; 2022: 7442123, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35912154

RESUMO

The value of 320-slice spiral computed tomography (CT) perfusion imaging in staging and long-term dynamic evaluation of breast cancer was explored. 120 breast cancer patients who underwent preoperative CT examination and were confirmed by surgery and pathology were selected. All patients underwent preoperative TNM staging of breast cancer, with 120 cases in each stage. According to the results of 320-slice spiral CT, the postoperative pathology and surgical methods were compared and analyzed. CT diagnosis of breast cancer showed that T1 sensitivity was 71% and accuracy was 61%, T2 sensitivity was 74% and accuracy was 64%, T3 sensitivity was 94% and the accuracy was 84%, and the T4 sensitivity was 100% and the accuracy was 91%. The sensitivity of N1 stage was 71%, and the accuracy was 61%; and the sensitivity of N2 ~ N3 stage was 81%, and the accuracy was 76%. There were 7 cases of M1 with distant metastasis, the sensitivity was 71%, and the accuracy was 71%. At T1 stage, blood flow (BF) was 39.2 ± 16.7 mL/min/100 g, blood volume (BV) was 2.66 ± 1.4 mL/100 g, mean transit time (MTT) was 8.16 ± 2.7 s, and permeability surface (PS) was 16.6 ± 9.7 mL/min/100 g. 320-slice spiral CT perfusion imaging technology provided a new diagnostic mode for everyone, which can quantitatively identify breast cancer with multiple parameters, which was of great significance for clinical auxiliary diagnosis.


Assuntos
Neoplasias da Mama/diagnóstico por imagem , Tomografia Computadorizada Espiral , Neoplasias da Mama/classificação , Neoplasias da Mama/patologia , Feminino , Humanos , Estadiamento de Neoplasias , Imagem de Perfusão/métodos , Tomografia Computadorizada por Raios X/métodos
10.
Clin Nucl Med ; 47(9): e621-e623, 2022 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-35930717

RESUMO

ABSTRACT: A 58-year-old man with large penile wound and enlarged regional lymph node was suspected of having disseminated penile cancer. FDG PET/CT for primary staging showed high FDG uptake on penis and in several enlarged lymph nodes. However, biopsies revealed no signs of malignancy, but ulceration, inflammation, fibrosis, and spirochetes. Furthermore, Wassermann test was positive. The patient was then treated for syphilis. To our knowledge, this is the first report on FDG PET/CT in a patient suspected of having penile cancer that turned out to be syphilis. Thus, syphilis can be added to the list of benign pitfalls in FDG PET/CT.


Assuntos
Neoplasias Penianas , Sífilis , Fluordesoxiglucose F18 , Humanos , Linfonodos/patologia , Metástase Linfática/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias Penianas/diagnóstico por imagem , Neoplasias Penianas/patologia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Compostos Radiofarmacêuticos , Sífilis/complicações , Sífilis/diagnóstico por imagem , Sífilis/patologia
11.
JAMA Netw Open ; 5(8): e2224478, 2022 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-35925606

RESUMO

Importance: The 2017 international PACIFIC trial established a role for immunotherapy after chemoradiation for unresectable stage III non-small cell lung cancer (NSCLC). However, in the US, patients with NSCLC commonly differ from clinical trial populations in terms of age, health, access to care, and treatment course, which may all factor into the efficacy of immunotherapy. Objective: To determine the outcomes of immunotherapy use in unresectable stage III NSCLC in the general US population. Design, Setting, and Participants: This cohort study analyzed the National Cancer Database for patients diagnosed with clinical stage III NSCLC between 2015 and 2017 with follow-up through the end of 2018 who were treated with chemotherapy and radiation. Data were analyzed January 2022. Main Outcomes and Measures: Mortality hazard in a multivariable Cox proportional hazards model and survival among a propensity-matched sample treated with chemotherapy and radiation, with and without immunotherapy. Results: A total of 23 811 patients with clinical stage III NSCLC with median (IQR) age 66 (59-72) years met inclusion criteria (10 454 [43.9%] women; 564 [2.4%] Asian, 2930 [12.3%] Black, 20 077 [84.3%] White patients), including 209 (16.1%) patients with multiple comorbidities and 1297 (5.4%) immunotherapy recipients. Immunotherapy after chemotherapy and radiation was associated with reduced mortality (hazard ratio [HR], 0.74; 95% CI, 0.67-0.82; P < .001). Among a propensity-matched sample, immunotherapy was associated with superior 3-year survival (52% [1297 patients at 0 months, 56 patients at 36 months] vs 44% [2594 patients at 0 months, 173 patients at 36 months]; P < .001). The treatment of 833 patients who received immunotherapy (64.2%) differed from the PACIFIC trial protocol, including 221 patients (17.0%) who received radiation doses outside of the protocol range and 731 patients (56.4%) who started immunotherapy more than 6 weeks after radiation was completed. The survival advantage of immunotherapy persisted when initiated up to 12 weeks after radiation was completed (HR, 0.75; 95% CI, 0.61-0.92). Among patients who received radiation outside the PACIFIC protocol range, the survival advantage of immunotherapy was not significant (HR, 0.87; 95% CI, 0.69-1.01). Conclusions and Relevance: In this cohort study, immunotherapy after chemotherapy and radiation for stage III NSCLC was associated with a survival advantage in the general US population despite two-thirds of patients treated differently than the PACIFIC protocol. The findings suggest there may be flexibility in the timing of immunotherapy initiation after radiation; further study is warranted to clarify the clinical benefits of immunotherapy.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Idoso , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Estudos de Coortes , Feminino , Humanos , Imunoterapia/métodos , Masculino , Estadiamento de Neoplasias
12.
Sci Rep ; 12(1): 13377, 2022 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-35927418

RESUMO

Breast cancer is more common on the left side than the right side. We aim to evaluate differences in clinicopathological and genomic characteristics based on laterality. We analyzed survival outcomes and clinical characteristics of 881,320 patients recorded by the Surveillance, Epidemiology, and End Results (SEER) program. The Cancer Genome Atlas (TCGA) was used to explore genomic and clinical features from 1,062 patients. Gene expression data was used to quantitate cytolytic activity and hallmark gene-sets were used for gene set enrichment analysis. An institutional retrospective review was conducted on 155 patients treated with neoadjuvant chemotherapy (NACT). Patient characteristics were summarized by pathological complete response (pCR). Left sided tumors were found to be more prevalent than right sided tumors. No major clinicopathological differences were noted by laterality. Left sided breast cancer demonstrated poorer outcomes versus right sided tumors (HR 1.05, 95% CI 1.01-1.08; p = 0.011). Cell proliferation gene sets, including E2F Targets, G2M Checkpoint, Mitotic spindle, and MYC Targets, were enriched on the left side compared to the right. Left sided tumors had lower pCR rates versus right sided tumors (15.4% versus 29.9%, p = 0.036). Our findings suggest that left sided breast cancer is associated with aggressive biology and worse outcomes compared to right sided breast cancer.


Assuntos
Neoplasias da Mama , Neoplasias Unilaterais da Mama , Biologia , Neoplasias da Mama/patologia , Feminino , Humanos , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Programa de SEER , Neoplasias Unilaterais da Mama/patologia
15.
BMC Cancer ; 22(1): 855, 2022 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-35931997

RESUMO

BACKGROUND: Colorectal cancer (CRC) is the third most common cancer worldwide. However, limited effective biomarkers are associated with the tumorigenesis and prognosis of CRC. METHODS: The present study identified potential signatures from The Cancer Genome Atlas (TCGA) database and further validated the identified biomarkers in CRC tissues by immunohistochemistry (IHC). RESULTS: The expression of insulin-like growth factor 1 receptor (IGF-1R) and Livin gene was significantly upregulated in CRC samples compared to the adjacent normal samples in the TCGA dataset. IHC indicated that IGF-1R and Livin protein levels are increased in CRC and adenoma tissues compared to normal tissues. Notably, the IGF-1R protein levels differed significantly between adenoma and CRC. The elevated IGF-1R and Livin expression was associated with CRC clinicopathological features, including age, gender, histological subtype, individual cancer stages, nodal metastasis, and TP53-mutant in TCGA. Additionally, the IGF-1R promoter methylation level was closely related to CRC. Consistent with the TCGA study, IHC indicated that overexpressed IGF-1R and Livin proteins were independent risk factors for stage and metastasis. A marked correlation was established between IGF-1R and Livin expression in CRC, while the survival map showed no significant correlation with CRC. Kaplan-Meier survival curves showed that CRC patients with high IGF-1R or Livin expression had a prolonged overall disease-free survival than those with low expression in TCGA. CONCLUSION: IGF-1R and Livin are associated with CRC tumorigenesis and might be valuable for novel biomarker identification and targeted therapeutic strategy development.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Neoplasias Colorretais , Proteínas Inibidoras de Apoptose/metabolismo , Proteínas de Neoplasias/metabolismo , Receptor IGF Tipo 1/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/análise , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Carcinogênese/patologia , Neoplasias Colorretais/patologia , Humanos , Imuno-Histoquímica , Proteínas Inibidoras de Apoptose/análise , Proteínas de Neoplasias/análise , Estadiamento de Neoplasias , Prognóstico , Receptor IGF Tipo 1/análise , Receptor IGF Tipo 1/genética
16.
Lancet ; 400(10350): 431-440, 2022 08 06.
Artigo em Inglês | MEDLINE | ID: mdl-35934006

RESUMO

BACKGROUND: Whole breast irradiation (WBI) after conservative surgery for ductal carcinoma in situ (DCIS) reduces local recurrence. We investigated whether a tumour bed boost after WBI improved outcomes, and examined radiation dose fractionation sensitivity for non-low-risk DCIS. METHODS: The study was an international, randomised, unmasked, phase 3 trial involving 136 participating centres of six clinical trials organisations in 11 countries (Australia, New Zealand, Singapore, Canada, the Netherlands, Belgium, France, Switzerland, Italy, Ireland, and the UK). Eligible patients were women aged 18 years or older with unilateral, histologically proven, non-low-risk DCIS treated by breast-conserving surgery with at least 1 mm of clear radial resection margins. They were assigned to one of four groups (1:1:1:1) of no tumour bed boost versus boost after conventional versus hypofractionated WBI, or randomly assigned to one of two groups (1:1) of no boost versus boost after each centre prespecified conventional or hypofractionated WBI. The conventional WBI used was 50 Gy in 25 fractions, and hypofractionated WBI was 42·5 Gy in 16 fractions. A boost dose of 16 Gy in eight fractions, if allocated, was delivered after WBI. Patients and clinicians were not masked to treatment allocation. The primary endpoint was time to local recurrence. This trial is registered with ClinicalTrials.gov (NCT00470236). FINDINGS: Between June 25, 2007, and June 30, 2014, 1608 patients were randomly assigned to have no boost (805 patients) or boost (803 patients). Conventional WBI was given to 831 patients, and hypofractionated WBI was given to 777 patients. Median follow-up was 6·6 years. The 5-year free-from-local-recurrence rates were 92·7% (95% CI 90·6-94·4%) in the no-boost group and 97·1% (95·6-98·1%) in the boost group (hazard ratio 0·47; 0·31-0·72; p<0·001). The boost group had higher rates of grade 2 or higher breast pain (10% [8-12%] vs 14% [12-17%], p=0·003) and induration (6% [5-8%] vs 14% [11-16%], p<0·001). INTERPRETATION: In patients with resected non-low-risk DCIS, a tumour bed boost after WBI reduced local recurrence with an increase in grade 2 or greater toxicity. The results provide the first randomised trial data to support the use of boost radiation after postoperative WBI in these patients to improve local control. The international scale of the study supports the generalisability of the results. FUNDING: National Health and Medical Research Council of Australia, Susan G Komen for the Cure, Breast Cancer Now, OncoSuisse, Dutch Cancer Society, Canadian Cancer Trials Group.


Assuntos
Neoplasias da Mama , Carcinoma Intraductal não Infiltrante , Neoplasias da Mama/etiologia , Neoplasias da Mama/radioterapia , Neoplasias da Mama/cirurgia , Canadá , Carcinoma Intraductal não Infiltrante/radioterapia , Carcinoma Intraductal não Infiltrante/cirurgia , Fracionamento da Dose de Radiação , Feminino , Humanos , Masculino , Mastectomia Segmentar , Recidiva Local de Neoplasia/etiologia , Estadiamento de Neoplasias , Doses de Radiação
17.
Medicine (Baltimore) ; 101(31): e29929, 2022 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-35945736

RESUMO

OBJECTIVE: We meta-analyzed available evidence on fertility, survival, and cancer recurrence in patients with stage I epithelial ovarian cancer (EOC) after fertility-sparing surgery (FSS). METHODS: We systematically reviewed PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials to identify studies reporting reproductive and oncological outcomes of patients with stage I EOC who underwent FSS. Random-effects models were used to calculate pooled rates of disease outcomes, along with 95% confidence intervals (CIs). Subgroup and sensitivity analyses were conducted to identify sources of heterogeneity in the data. RESULTS: We included 23 observational retrospective studies involving 1126 patients. The pooled pregnancy rate was 30% (95% CI, 0.26-0.34), while the pooled natural conception rate was 26% (95% CI, 0.20-0.33). The pooled live birth rate was 27% (95% CI, 0.22-0.32). The pooled rate of EOC recurrence was 12% (95% CI, 0.09-0.14), which did not differ significantly from the rate among patients who underwent radical surgery (odds ratio, 0.77; 95% CI, 0.45-1.33). CONCLUSIONS: FSS is associated with good oncological outcomes but less than satisfactory reproductive outcomes. All in all, the procedure appears to be a safe alternative to radical surgery for EOC patients who want to preserve fertility.


Assuntos
Preservação da Fertilidade , Neoplasias Ovarianas , Carcinoma Epitelial do Ovário/patologia , Carcinoma Epitelial do Ovário/cirurgia , Feminino , Preservação da Fertilidade/métodos , Humanos , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Neoplasias Ovarianas/patologia , Gravidez , Estudos Retrospectivos
18.
World J Gastroenterol ; 28(23): 2561-2568, 2022 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-35949352

RESUMO

Barcelona clinic liver cancer (BCLC) intermediate stage hepatocellular carcinoma is a heterogenous disease. Transarterial chemoembolization is offered as the first line therapy in this disease stage. Recent advances in systemic therapy have markedly improved outcomes even in advanced stage disease. The use of systemic therapy in BCLC intermediate stage disease may now be of therapeutic benefit in selected patients. We will focus on "the up to seven" criteria and its utility in selecting systemic therapy.


Assuntos
Carcinoma Hepatocelular , Quimioembolização Terapêutica , Neoplasias Hepáticas , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/terapia , Humanos , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/terapia , Estadiamento de Neoplasias , Estudos Retrospectivos , Resultado do Tratamento
19.
Technol Cancer Res Treat ; 21: 15330338221117405, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35950233

RESUMO

Background : The major salivary gland squamous cell carcinoma is a rare head and neck tumor, often accompanied by lymph node metastasis. Even if the patient undergoes surgery, the prognosis remains unsatisfactory. To explore the prognostic factors of postoperative major salivary gland squamous cell carcinoma to establish a prognostic risk stratification model to guide clinical practice. Methods: Patients' information was retrieved from the Surveillance, Epidemiology, and End Results database from 2004 to 2018. Optimal cutoff points were determined using X-tile software, and overall survival and disease-specific survival were calculated by the Kaplan-Meier method. Independent prognostic factors affecting the overall survival and disease-specific survival were identified by multivariate analysis, and corresponding 2 nomogram models were constructed. The discriminative ability and calibration of nomograms were evaluated by the Concordance index, area under curves, and calibration plots. Results: A total of 815 patients with postoperative major salivary gland squamous cell carcinoma were enrolled. The cutoff values for the number of lymph nodes were 2, and the cutoff values for the lymph node ratio were 0.11 and 0.5, respectively. Age, T stage, tumor size, lymph nodes, lymph node ratio, and radiotherapy were prognostic factors for overall survival and disease-specific survival. Nomograms for disease-specific survival and overall survival were established and showed favorable performance with a higher Concordance index and area under curves than that of the tumor-node-metastasis stage and Surveillance, Epidemiology, and End Results stage. The calibration plots of 1-, 3-, and 5-year overall survival and disease-specific survival also exhibited good consistency. What's more, patients were divided into low-, moderate-, and high-risk groups according to the scores calculated by the models. The overall survival and disease-specific survival of patients in the high-risk group were significantly worse than those in the moderate- and low-risk group. Conclusions: Our nomogram integrated clinicopathological features and treatment modality to demonstrate excellent performance in risk stratification and prediction of survival outcomes in patients with major salivary gland squamous cell carcinoma after surgery, with important clinical value.


Assuntos
Carcinoma de Células Escamosas , Nomogramas , Carcinoma de Células Escamosas/patologia , Humanos , Estadiamento de Neoplasias , Prognóstico , Programa de SEER , Glândulas Salivares/patologia
20.
Technol Cancer Res Treat ; 21: 15330338221118188, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35950239

RESUMO

Introduction: In the adjuvant setting for cervical cancer, classical risk factors for postoperative radiochemotherapy have been established. However, data on laboratory changes during therapy and the prognostic value of serological markers are limited and further knowledge is needed to optimize the toxic trimodal regimen. Methods: We retrospectively identified 69 women who underwent weekly postoperative radiochemotherapy with 40 mg/m2 of cisplatin for cervical cancer between 2010 and 2021 at a single center. Laboratory parameters were recorded before, at each cycle and after radiochemotherapy. Kaplan-Meier and log-rank analyses were used to calculate and compare survival, groups were compared using the Mann-Whitney U, χ2, and variance tests. Results: With a median follow-up of 17.7 months, the 1- and 5-year local control rates were 94.0% and 73.7%, respectively, with significantly better rates for more chemotherapy cycles and negative resection margins. Only 68.1% of patients completed all cycles. The most common reasons for early discontinuation were persistent asymptomatic leukopenia in women aged ≤ 50 years, and limiting infections in women aged > 50 years. Leukopenia was more likely to occur after the third cycle. Significantly worse survival was observed for post-radiochemotherapy elevated C-reactive-protein and lactate dehydrogenase levels, low pre-radiochemotherapy nutritional index, and raised C-reactive-protein-levels; the latter were also predictable for local control. The Glasgow prognostic score did not reliably predict survival. Conclusion: Incomplete application of simultaneous chemotherapy leads to inferior local control, and age-dependent limiting factors should be identified at an early stage. In addition to classical risk factors, serological markers (C-reactive-protein, lactate dehydrogenase, nutritional index) show prognostic significance.


Assuntos
Leucopenia , Neoplasias do Colo do Útero , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Quimiorradioterapia/efeitos adversos , Cisplatino , Intervalo Livre de Doença , Feminino , Humanos , Lactato Desidrogenases , Leucopenia/tratamento farmacológico , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Resultado do Tratamento , Neoplasias do Colo do Útero/patologia
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