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1.
BMC Cancer ; 22(1): 957, 2022 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-36068495

RESUMO

BACKGROUND: The presence of mesorectal fascia (MRF) invasion, grade 4 extramural venous invasion (EMVI), tumour deposits (TD) or extensive or bilateral extramesorectal (lateral) lymph nodes (LLN) on MRI has been suggested to identify patients with indisputable, extensive locally advanced rectal cancer (LARC), at high risk of treatment failure. The aim of this study is to evaluate whether or not intensified chemotherapy prior to neoadjuvant chemoradiotherapy improves the complete response (CR) rate in these patients. METHODS: This multicentre, single-arm, open-label, phase II trial will include 128 patients with non-metastatic high-risk LARC (hr-LARC), fit for triplet chemotherapy. To ensure a study population with indisputable, unfavourable prognostic characteristics, hr-LARC is defined as LARC with on baseline MRI at least one of the following characteristics; MRF invasion, EMVI grade 4, enlarged bilateral or extensive LLN at high risk of an incomplete resection, or TD. Exclusion criteria are the presence of a homozygous DPD deficiency, distant metastases, any chemotherapy within the past 6 months, previous radiotherapy within the pelvic area precluding standard chemoradiotherapy, and any contraindication for the planned treatment. All patients will be planned for six two-weekly cycles of FOLFOXIRI (5-fluorouracil, leucovorin, oxaliplatin and irinotecan) prior to chemoradiotherapy (25 × 2 Gy or 28 × 1.8 Gy with concomitant capecitabine). A resection will be performed following radiological confirmation of resectable disease after the completion of chemoradiotherapy. A watch and wait strategy is allowed in case of a clinical complete response. The primary endpoint is the CR rate, described as a pathological CR or a sustained clinical CR one year after chemoradiotherapy. The main secondary objectives are long-term oncological outcomes, radiological and pathological response, the number of resections with clear margins, treatment-related toxicity, perioperative complications, health-related costs, and quality of life. DISCUSSION: This trial protocol describes the MEND-IT study. The MEND-IT study aims to evaluate the CR rate after intensified chemotherapy prior to concomitant chemoradiotherapy in a homogeneous group of patients with locally advanced rectal cancer and indisputably unfavourable characteristics, defined as hr-LARC, in order to improve their prognosis. TRIAL REGISTRATION: Clinicaltrials.gov: NCT04838496 , registered on 02-04-2021 Netherlands Trial Register: NL9790. PROTOCOL VERSION: Version 3 dd 11-4-2022.


Assuntos
Segunda Neoplasia Primária , Neoplasias Retais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Camptotecina/análogos & derivados , Quimiorradioterapia/métodos , Ensaios Clínicos Fase II como Assunto , Fluoruracila/uso terapêutico , Humanos , Leucovorina , Estudos Multicêntricos como Assunto , Terapia Neoadjuvante/métodos , Estadiamento de Neoplasias , Segunda Neoplasia Primária/patologia , Compostos Organoplatínicos , Qualidade de Vida , Neoplasias Retais/patologia , Resultado do Tratamento
2.
Dis Markers ; 2022: 3534433, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36072903

RESUMO

Background: Neoadjuvant chemoradiotherapy (neo-CRT) in combination with surgery increases survival compared to surgery alone, as indicated by the esophageal squamous cell carcinoma (ESCC) treatment recommendations. However, the benefits of neo-CRT are diverse among patients. Consequently, the development of new biomarkers that correlate with neo-CRT might be important for the treatment of ESCC. Methods: The differentially expressed genes (DEG) between responsive and resistant samples from the GSE45670 dataset were obtained. On the TCGA dataset, survival analysis was performed to identify prognosis-related-EMT-genes. For EMT score model construction, lasso regression analysis in the TCGA cohort was used to identify the genes. In the TCGA-ESCC cohort, age, stage, and EMT score were used to construct a nomogram. Results: In total, 10 prognosis-related-EMT-genes were obtained. These 10 genes consisted of 6 risky genes and 4 protective genes. Based on the lasso analysis and univariate Cox regression, an EMT score model consisting of 7 genes (CLEC18A, PIR, KCNN4, MST1R, CAPG, ALDH5A1, and COX7B) was identified. ESCC patients with a high EMT score have a worse prognosis. These genes were differentially expressed between responsive and resistant patients and had a high accuracy for distinguishing resistant and responsive patients. Conclusions: The identified genes have the potential to function as molecular biomarkers for predicting ESCC patients' resistance to neo-CRT. This research may aid in the elucidation of the molecular processes driving resistance and the identification of targets for improving the prognosis for ESCC.


Assuntos
Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Transição Epitelial-Mesenquimal/genética , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/patologia , Neoplasias Esofágicas/terapia , Carcinoma de Células Escamosas do Esôfago/genética , Carcinoma de Células Escamosas do Esôfago/terapia , Humanos , Lectinas Tipo C , Terapia Neoadjuvante , Prognóstico
4.
Zhonghua Wai Ke Za Zhi ; 60(9): 846-852, 2022 Sep 01.
Artigo em Chinês | MEDLINE | ID: mdl-36058711

RESUMO

Objective: To compare the prognostic influence and postoperative pathology of different comprehensive treatment models for adenocarcinoma of esophagogastric junction. Methods: Between January 2012 and December 2017, a total of 219 patients with adenocarcinoma of esophagogastric junction underwent surgery in Gastrointestinal Cancer Center, Peking University Cancer Hospital & Institute and were enrolled in this study. The clinicopathological data of these patients were collected. The patients were categorized into 3 groups according to different treatment models: surgery-first group, neoadjuvant chemotherapy (NAC) group and neoadjuvant chemoradiotherapy (nCRT) group. A trimatch propensity score analysis was applied to control potential confounders among the three groups by using R language software. A total of 7 covariates including gender, age, comorbidity, body mass index, clinical T stage, clinical N stage and Siewert type were included, and the caliper value was taken as 0.2. After matching, a total of 87 patients were included for analysis with 27 patients for each group. There were 82 males and 5 females, with a median age of 63 years (range: 38 to 76 years). The effect of preoperative treatment on postoperative tumor pathology among the three different comprehensive treatment models was explored by χ2 test, ANOVA or Wilcoxon rank sum test. Mann-Whitney U test or χ2 test were used to undergo pairwise comparisons. Kaplan-Meier method and Log-rank test were used to analyze the overall survival and progression-free survival. Results: The proportion of vascular embolism in the surgery-first group was 72.4% (21/29), which was significantly higher than NAC group (37.9% (11/29), χ2=6.971, P=0.008) and nCRT group (6.9% (2/29), χ2=26.696, P<0.01). The proportions of pathological T3-4 stage in nCRT group and NAC group were 55.2% (16/29) and 62.1% (18/29), respectively, which were significantly lower than the surgery-first group (93.1% (27/29), χ2=10.881, P=0.001; χ2=8.031, P=0.005). Compared with the NAC group (55.2% (16/29), χ2=6.740, P=0.009) and nCRT group (31.0% (9/29), χ2=18.196, P<0.01), the proportion of lymph node positivity 86.2% (25/29) were significantly higher in the surgery-first group. The 5-year overall survival rates were 62.1%, 68.6% and 41.4% for the surgery-first group, NAC group and nCRT group, respectively (χ2=4.976, P=0.083). The 5-year progression-free survival rates were 61.7%, 65.1% and 41.1% for the surgery-first group, NAC group and nCRT group, respectively. The differences in overall survival (χ2=4.976, P=0.083) and progression-free survival (χ2=4.332, P=0.115) among the three groups were nonsignificant. Conclusions: Postoperative pathology is significantly different among the three groups. Neoadjuvant chemotherapy and neoadjuvant chemoradiotherapy could decrease the proportions of vascular embolism, pathological T3-4 stage and lymph node positivity to achieve local tumor control. The prognosis of overall survival and progression-free survival are not significantly different among the three groups.


Assuntos
Adenocarcinoma , Junção Esofagogástrica , Adenocarcinoma/patologia , Adulto , Idoso , Estudos de Coortes , Junção Esofagogástrica/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante , Pontuação de Propensão
6.
Gan To Kagaku Ryoho ; 49(8): 893-896, 2022 Aug.
Artigo em Japonês | MEDLINE | ID: mdl-36046977

RESUMO

OBJECTIVE: To examine the potential of peripheral circulating cell-free DNA(cfDNA)as a predictor of response in patients undergoing neoadjuvant chemotherapy(NAC)for advanced colon cancer. METHODS: We compared histological response, background factors, and cfDNA molecular volume changes in cT4 and cT3N+ colon cancer patients. RESULTS: Six of 11 patients responded. The patients with muc and pap histology were non-responders. There was no relationship between CEA or cfDNA levels and response. Responders showed >50% change in DNA integrity index(=cfDNA long fragment/ short fragment ratio), while non-responders showed <50% change(p=0.015). CONCLUSION: Our results suggest that the variability rate in DNA integrity index of peripheral blood cfDNA may be useful in predicting the therapeutic efficacy of colon NAC.


Assuntos
Ácidos Nucleicos Livres , Neoplasias do Colo , Biomarcadores , Biomarcadores Tumorais/genética , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/genética , Neoplasias do Colo/cirurgia , DNA , Humanos , Terapia Neoadjuvante
7.
Chirurgia (Bucur) ; 117(4): 385-398, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36049095

RESUMO

Pancreatic ductal adenocarcinoma (PDAC) represents an aggressive tumor with a low five-year survival rate of less than 10%. Only 20% of patients are estimated to be eligible for upfront curative resection at the time of presentation. The larger group of borderline resectable (BRPC) and locally advanced pancreatic cancers (LAPC) had much poorer outcomes in the past. Although there are improvements for the multimodal therapy of PDAC, surgery remains the single hope for a cure. Combined with adjuvant and/ or neoadjuvant treatment, pancreatic surgery can enhance five-year survival by up to 20%. However, pancreatic resection is widely associated with a high risk of complications and is regarded as one of the most complex surgical procedures. TRIANGLE operation should be added to pancreatic surgery armamentarium as a key procedure, with the potential to increase the number of harvested lymph nodes, reduce the complications rate, and better radical treatment efficacy for BRPC and LAPC be converted to resectability after neoadjuvant treatment (NAT). More and more aggressive pancreatectomy has become justified in the context of NAT. Further technical standardization and optimal neoadjuvant strategy are mandatory for the global dissemination of aggressive pancreatectomies. This review summarizes the surgical treatment for BRPC and potentially resectable LAPC based on the current literature, focusing on the "TRIANGLE "concept of pancreatic surgery.


Assuntos
Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Protocolos de Quimioterapia Combinada Antineoplásica , Carcinoma Ductal Pancreático/cirurgia , Humanos , Terapia Neoadjuvante , Pancreatectomia , Neoplasias Pancreáticas/tratamento farmacológico , Resultado do Tratamento
8.
Chirurgia (Bucur) ; 117(4): 407-414, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36049097

RESUMO

Pancreatic ductal adenocarcinoma (PDAC) is characterized by high heterogeneity; thus, even after a curative intent surgery, there is significant variability in the survival of patients, reflecting different biological behaviors. The selection of proper, personalized therapy for each patient with resectable PDAC, in multimodal therapy, by an experienced multidisciplinary team is of utmost importance to get maximal clinical benefit avoiding potentially harmful treatments. Identifications of patients with resectable PDAC that would benefit from surgical resections in the context of multimodal therapy remain a topic of interest for clinical practice. To improve PDAC patient outcomes, a significant step forward would be the integration of the molecular sub-types in the clinical decision-making between upfront surgery versus neoadjuvant treatment. Successful integration of the preoperative knowledge of the subtype of PDAC can properly guide this treatment selection to further improve patient outcomes. In this review, we present an overview of the current knowledge on the role of molecular subtyping in surgical decisions for PDAC patients.


Assuntos
Adenocarcinoma , Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Adenocarcinoma/cirurgia , Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/cirurgia , Terapia Combinada , Humanos , Terapia Neoadjuvante , Pancreatectomia , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/cirurgia , Resultado do Tratamento
9.
Surg Pathol Clin ; 15(3): 479-490, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36049830

RESUMO

Three recent advances in the surgical approach to pancreatic cancer over the past decade have improved both short- and long-term outcomes for patients with nonmetastatic, operable pancreatic cancer. These include (1) minimally invasive pancreatectomy to reduce operative morbidity while adhering to principles of open oncologic resections, (2) neoadjuvant chemotherapy to treat radiographically occult metastatic disease and improve locoregional control, and (3) applying irreversible electroporation as an adjunct to surgery, allowing a fraction of locally advanced pancreatic cancer to be resected.


Assuntos
Neoplasias Pancreáticas , Humanos , Terapia Neoadjuvante , Pancreatectomia , Neoplasias Pancreáticas/patologia
10.
Surg Pathol Clin ; 15(3): 511-528, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36049833

RESUMO

Examination of pancreatic ductal adenocarcinoma after NAT with the intent of diagnosis and outcome prediction remains a challenging task. The lack of a uniform approach to macroscopically assess these cases along with variations in sampling adds to the complexity. Several TRG systems have been proposed to correlate with an overall survival. In clinical practice, most of these TRG schemes have shown low level of interobserver agreement arguing for a need of larger studies and more innovative ways to assess outcome in this population.


Assuntos
Adenocarcinoma , Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Adenocarcinoma/diagnóstico , Carcinoma Ductal Pancreático/diagnóstico , Humanos , Terapia Neoadjuvante , Neoplasias Pancreáticas/diagnóstico , Ácidos Urônicos
11.
J Natl Compr Canc Netw ; 20(9): 1023-1032.e3, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-36075389

RESUMO

BACKGROUND: Neoadjuvant therapy (NAT) is used in borderline resectable/locally advanced (BR/LA) pancreatic ductal adenocarcinoma (PDAC). Anatomic imaging (CT/MRI) poorly predicts response, and biochemical (CA 19-9) markers are not useful (nonsecretors/nonelevated) in many patients. Pathologic response highly predicts survival post-NAT, but is only known postoperatively. Because metabolic imaging (FDG-PET) reveals primary tumor viability, this study aimed to evaluate our experience with preoperative FDG-PET in patients with BR/LA PDAC in predicting NAT response and survival. METHODS: We reviewed all patients with resected BR/LA PDAC who underwent NAT with FDG-PET within 60 days of resection. Pre- and post-NAT metabolic (FDG-PET) and biochemical (CA 19-9) responses were dichotomized in addition to pathologic responses. We compared post-NAT metabolic and biochemical responses as preoperative predictors of pathologic responses and recurrence-free survival (RFS) and overall survival (OS). RESULTS: We identified 202 eligible patients. Post-NAT, 58% of patients had optimization of CA 19-9 levels. Major metabolic and pathologic responses were present in 51% and 38% of patients, respectively. Median RFS and OS times were 21 and 48.7 months, respectively. Metabolic response was superior to biochemical response in predicting pathologic response (area under the curve, 0.86 vs 0.75; P<.001). Metabolic response was the only univariate preoperative predictor of OS (odds ratio, 0.25; 95% CI, 0.13-0.40), and was highly correlated (P=.001) with pathologic response as opposed to biochemical response alone. After multivariate adjustment, metabolic response was the single largest independent preoperative predictor (P<.001) for pathologic response (odds ratio, 43.2; 95% CI, 16.9-153.2), RFS (hazard ratio, 0.37; 95% CI, 0.2-0.6), and OS (hazard ratio, 0.21; 95% CI, 0.1-0.4). CONCLUSIONS: Among patients with post-NAT resected BR/LA PDAC, FDG-PET highly predicts pathologic response and survival, superior to biochemical responses alone. Given the poor ability of anatomic imaging or biochemical markers to assess NAT responses in these patients, FDG-PET is a preoperative metric of NAT efficacy, thereby allowing potential therapeutic alterations and surgical treatment decisions. We suggest that FDG-PET should be an adjunct and recommended modality during the NAT phase of care for these patients.


Assuntos
Adenocarcinoma , Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/terapia , Carcinoma Ductal Pancreático/diagnóstico por imagem , Carcinoma Ductal Pancreático/terapia , Fluordesoxiglucose F18/uso terapêutico , Humanos , Terapia Neoadjuvante/métodos , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/terapia , Prognóstico , Estudos Retrospectivos
12.
BMJ Open ; 12(9): e060955, 2022 09 17.
Artigo em Inglês | MEDLINE | ID: mdl-36115673

RESUMO

INTRODUCTION: Liver resection is the mainstay of curative-intent treatment for hepatocellular carcinoma (HCC), but the postoperative 5-year recurrence rate reaches 70%, and there are no adjuvant or neoadjuvant therapies recommended by major HCC guidelines that can reduce the risk of recurrence. In the recent decade, significant progress has been achieved in the systemic treatment of HCC, mainly from immune checkpoint inhibitors (ICIs) and targeted therapy. In other malignancies, ICIs in the neoadjuvant setting have shown better outcomes than in the adjuvant setting. On the other hand, the addition of radiation to ICIs incrementally improves the systemic response to ICIs. Neoadjuvant therapy of ICIs plus stereotactic body radiotherapy (SBRT) has shown promising results in several types of solid tumours but not HCC. METHODS AND ANALYSIS: Here, we describe a phase Ib clinical trial of neoadjuvant SBRT plus PD-1 (tislelizumab) prior to hepatic resection in HCC patients. Prior to resection, eligible HCC patients will receive 8 Gy×3 fractions of SBRT together with two cycles of tislelizumab with an interval of 3 weeks. HCC resection is scheduled 4 weeks after the second dose of tislelizumab, followed by adjuvant tislelizumab for 1 year. We plan to enrol 20 participants in this trial. The primary study endpoints include the delay of surgery, tumour response and safety and tolerability of the sequential SBRT/tislelizumab. Other endpoints are the disease-free survival and overall survival rates every 3 or 6 months after the surgery. ETHICS AND DISSEMINATION: This trial was approved by the Ethics Committee of Shandong Cancer Hospital and Institute (SDZLEC2022-021-01). The final results of this trial will be published in a peer-reviewed journal after completion. TRIAL REGISTRATION NUMBER: NCT05185531.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Radiocirurgia , Anticorpos Monoclonais Humanizados , Carcinoma Hepatocelular/patologia , Ensaios Clínicos Fase I como Assunto , Humanos , Inibidores de Checkpoint Imunológico , Terapia Neoadjuvante , Receptor de Morte Celular Programada 1 , Radiocirurgia/métodos
13.
J Clin Invest ; 132(18)2022 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-36106641

RESUMO

Patients with HPV-unrelated head and neck squamous cell carcinoma (HPV-unrelated HNSCC) show only modest benefit from treatment with PD-1 inhibitors (PD-1i). Targeting transforming growth factor ß (TGF-ß) may make PD-1i more effective by inducing T cell responses. In this issue of the JCI, Redman et al. performed a clinical trial in 14 patients with HPV-unrelated HNSCC using bintrafusp alfa, a bifunctional fusion protein that blocks PD-L1 and TGF-ß. Primary tumors displayed pathologic responses with 5 of 14 patients having at least a partial response. While no primary tumor or metastatic lymph node demonstrated a complete pathologic response, the findings suggest that concurrent neoadjuvant inhibition of PD-L1 and TGF-ß may provide a rational strategy to improve pathologic response and clinical outcome in patients with HPV-unrelated HNSCC.


Assuntos
Neoplasias de Cabeça e Pescoço , Infecções por Papillomavirus , Antígeno B7-H1/metabolismo , Ensaios Clínicos como Assunto , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Humanos , Inibidores de Checkpoint Imunológico , Fatores Imunológicos , Imunoterapia , Terapia Neoadjuvante , Infecções por Papillomavirus/etiologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico , Sinapses/metabolismo , Linfócitos T/metabolismo , Fator de Crescimento Transformador beta
14.
Clin. transl. oncol. (Print) ; 24(9): 1744–1754, septiembre 2022.
Artigo em Inglês | IBECS | ID: ibc-206260

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
15.
Breast J ; 2022: 1507881, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36051467

RESUMO

Background: Axillary surgical management in patients with node-positive breast cancer at the time of diagnosis converted to negative nodes through neoadjuvant chemotherapy (NAC) remains unclear. Removal of more than two sentinel nodes (SLNs) in these patients may decrease the false negative rate (FNR) of sentinel lymph node biopsies (SLNBs). We aim to analyse the detection rate (DR) and the FNR of SLNB assessment according to the number of SLNs removed. Methods: A retrospective study was performed from October 2012 to December 2018. Patients with invasive breast cancer who had a clinically node-positive disease at diagnosis and with a complete axillary response after neoadjuvant chemotherapy were selected. Patients included underwent SLNB and axillary lymph node dissection (ALND) after NAC. The SLN was considered positive if any residual disease was detected. Descriptive statistics were used to describe the clinicopathologic features and the results of SLNB and ALND. The DR of SLNB was defined as the number of patients with successful identification of SLN. Presence of residual disease in ALND and negative SLN was considered false negative. Results: A total of 368 patients with invasive breast cancer who underwent surgery after complete NAC were studied. Of them, 85 patients met the eligibility criteria and were enrolled in the study. The mean age at diagnosis was 50.8 years. Systematic lymphadenectomy was performed in all patients, with an average of 10 lymph nodes removed. The DR of SLNB was 92.9%, and the FNR was 19.1. The median number of SLNs removed was 3, and at least, three SLNs were obtained in 42 patients (53.2%). When at least three sentinel nodes were removed, the FNR decreased to 8.7%. Conclusions: In this cohort, the SLN assessment was associated with an adequate DR and a high FNR. Removing three or more SLNs decreased the FNR from 19.1% to 8.7%. Complementary approaches may be considered for axillary lymph node staging after neoadjuvant chemotherapy. The study was approved by our institution's ethics committee (Instituto de Investigacion Sanitaria Hospital 12 de Octubre (imas12), Universidad Complutense de Madrid, Madrid, Spain) (https://clinicaltrials.gov/ct2/show/NCEI:20/0048).


Assuntos
Neoplasias da Mama , Biópsia de Linfonodo Sentinela , Axila/patologia , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Neoplasias da Mama/cirurgia , Feminino , Humanos , Excisão de Linfonodo , Linfonodos/patologia , Linfonodos/cirurgia , Metástase Linfática/patologia , Terapia Neoadjuvante/métodos , Neoplasia Residual/patologia , Estudos Retrospectivos , Biópsia de Linfonodo Sentinela/métodos
16.
Ann Ital Chir ; 92: 263-270, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36052460

RESUMO

AIM: We aimed to evaluate (immunohistochemically) the YAP expression in breast cancer patients undergoing neoadjuvant chemotherapy and to clarify the relationship between the molecular characteristics, treatment response and survival data and the YAP expression, and hence, to clarify the prognostic significance. MATERIAL AND METHODS: One hundred and four patients who were diagnosed with Breast Cancer between 2015-2020 and underwent Neo Adjuvant Chemotherapy were included in the study. Estrogen Receptor(ER), Progesterone Receptor(PR), Human Epidermal Growth Receptor-2(HER2) and Ki-67. Expression are routinely stained immunohistochemically. In this study, existing immunohistochemical markers were reviewed and also, the relationship of YAP with these biological markers was evaluated by using immunohistochemistry and its effect on prognosis has been investigated. RESULTS: The average age of the patients was 52.37. While YAP was positive in 78 patients (75%), it was negative in 26 patients (25%). In the evaluation after neoadjuvant therapy, pathological complete response (MillerPayne Grade5 response) in 28 patients (26.9%), relapse in 6 patients (5.8%), and exitus in 6 patients (5.8%) were detected. In the pathological evaluation, invasive Ductal Carcinoma was the most common one observed in 88 patients (84.6%). As a result of the statistical evaluation, no significant result was obtained between the parameters and YAP negative/positive. CONCLUSION: As a result of staining with additional YAP in patients who were diagnosed with breast cancer and routinely stained with ER, PR, Cerb B2 and Ki-67 in pathology samples, we could not reach a result that would contribute positively to survival. Longer studies to be conducted prospectively will be meaningful. KEY WORDS: Breast Cancer, Chemotherapy, Neoadjuvant, Yes Associated Protein.


Assuntos
Neoplasias da Mama , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores Tumorais , Neoplasias da Mama/patologia , Quimioterapia Adjuvante , Feminino , Humanos , Antígeno Ki-67 , Terapia Neoadjuvante , Recidiva Local de Neoplasia/tratamento farmacológico , Receptor ErbB-2/metabolismo , Receptor ErbB-2/uso terapêutico , Receptores de Estrogênio/metabolismo , Receptores de Estrogênio/uso terapêutico , Receptores de Progesterona/metabolismo , Receptores de Progesterona/uso terapêutico , Estudos Retrospectivos , Proteínas de Sinalização YAP
17.
Adv Surg ; 56(1): 275-286, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36096572

RESUMO

There is growing interest in neoadjuvant endocrine therapy (NET) for the treatment of hormone receptor-positive, human epidermal growth factor receptor 2 -negative (HR + HER2-) breast cancer. Expanding the use of genomic assays demonstrates that many patients with HR + HER2-breast cancer do not benefit from chemotherapy, leading to growing interest in NET as a less toxic alternative. Although NET's ability to downsize breast tumors and achieve breast conservation is well-known, axillary surgery algorithms are not well-defined. Here we review primary endocrine therapy, the landmark NET clinical trials, and management of residual nodal disease following NET.


Assuntos
Neoplasias da Mama , Terapia Neoadjuvante , Axila , Neoplasias da Mama/patologia , Feminino , Humanos , Receptor ErbB-2/genética
19.
JCO Precis Oncol ; 6: e2200197, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36108259

RESUMO

PURPOSE: The prospective Neoadjuvant Breast Registry Symphony Trial compared the 80-gene molecular subtyping signature with clinical assessment by immunohistochemistry and/or fluorescence in situ hybridization in predicting pathologic complete response (pCR) and 5-year outcomes in patients with early-stage breast cancer. METHODS: Standard-of-care neoadjuvant chemotherapy combined with trastuzumab or trastuzumab plus pertuzumab was given to patients with human epidermal growth factor receptor 2 (HER2)-positive tumors (n = 295). pCR was the primary end point, with secondary end points of distant metastasis-free survival and overall survival at 5 years. RESULTS: Among clinically defined HER2-positive (cHER2) tumors, the 80-gene assay identified 29.5% (87 of 295) as Luminal-Type (cHER2/gLuminal), 14.9% (44 of 295) as Basal-Type (cHER2/gBasal), and 55.6% (164 of 295) as HER2-Type (cHER2/genomically classified as HER2 [gHER2]). Patients with cHER2/gHER2 tumors had a higher pCR rate (61.6%) compared with non-gHER2 tumors (26.7%; P < .001). Dual targeting for cHER2/gHER2 tumors yielded a higher pCR rate (75%) compared with those treated with single HER2-targeted therapy (54%; P = .006). For cHER2/gBasal tumors, the 42.9% pCR rate observed with dual targeting was not different from that with trastuzumab alone (46.4%; P = .830). Among those with cHER2/gBasal tumors, 5-year distant metastasis-free survival (68.6%; 95% CI, 49.1 to 81.9) was significantly worse than in patients with cHER2/gLuminal tumors (88.9%; 95% CI, 78.0 to 94.6) and cHER2/gHER2 tumors (87.4%; 95% CI, 80.2 to 92.2; P = .010), with similar corresponding overall survival differences. CONCLUSION: The 80-gene assay identified meaningful genomic diversity in patients with cHER2 disease. Patients with cHER2/gHER2 tumors, who benefitted most from dual HER2-targeted therapy, accounted for approximately half of the cHER2 cohort. Genomically Luminal tumors had low pCR rates but good 5-year outcomes. cHER2/gBasal tumors derived no benefit from dual therapy and had significantly worse 5-year prognosis; these patients merit special consideration in future trials.


Assuntos
Antineoplásicos , Terapia Neoadjuvante , Antineoplásicos/uso terapêutico , Genômica , Humanos , Hibridização in Situ Fluorescente , Estudos Prospectivos , Receptor ErbB-2 , Trastuzumab/farmacologia
20.
J Immunother Cancer ; 10(9)2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36109085

RESUMO

The good pathological response of primary tumors (PTs) to neoadjuvant immunotherapy has been acknowledged in non-small cell lung cancer (NSCLC), however, it remains unclear whether neoadjuvant immunotherapy shows consistent effects in metastatic lymph nodes (LNs). We compared the pathological response of PT and nodal downstaging using a pooled analysis to assess the effect of neoadjuvant immunotherapy on LNs. Original articles reporting the tumor major pathological response (ypT(MPR)), pathological complete response (ypT0) and nodal downstaging following neoadjuvant immunotherapy in NSCLC were retrieved. The OR and 95% CI were calculated by Review Manager V.5.3. Subgroup analysis was performed according to the neoadjuvant therapy regimen used. A total of 209 patients from 6 studies were included in this analysis. The frequency of nodal downstaging was comparable to that of ypT(MPR) (OR 1.31; 95% CI 0.84 to 2.05; p=0.24). Interestingly, ypN0 was observed more frequently than ypT0 (OR 3.26; 95% CI 2.06 to 5.16; p<0.0001). However, this difference was not observed in the subgroup of cN2 patients who underwent immune checkpoint inhibitor monotherapy (OR 1.58; 95% CI 0.56 to 4.48; p=0.39). Neoadjuvant immunotherapy results in satisfactory response in metastatic LN. Patients had a high probability of node clearance when ypT0 was confirmed, especially in patients treated with immunochemotherapy.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/patologia , Humanos , Inibidores de Checkpoint Imunológico , Imunoterapia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Linfonodos/patologia , Metástase Linfática/patologia , Terapia Neoadjuvante , Estadiamento de Neoplasias
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