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PURPOSE: Neoadjuvant chemo-immunotherapy is emerging as promising strategy in muscle-invasive bladder cancer (MIBC), yet its perioperative safety remains understudied. This post-hoc analysis of the AURA phase-II trial assesses surgical outcomes following neoadjuvant avelumab with or without chemotherapy. METHODS: We analyzed 88 patients with localized MIBC from the phase 2 multicenter AURA trial (NCT03674424) who underwent radical cystectomy after receiving either avelumab monotherapy (n = 22) or chemo-immunotherapy (n = 66). Surgical complications were classified using Clavien-Dindo criteria. A LASSO regression was used to identify predictors of overall complications, followed by multivariable and mixed-effects models. RESULTS: No increased intra-operative surgical complexity was noted. The overall complication rate was 52%. Major complications occurred significantly more often in the chemo-immunotherapy group compared to monotherapy (21.2% vs. 15.4%, p = 0.03), despite more favorable patient profiles. Neobladder diversion and open surgery were both associated with higher complication rates (81% vs. ileal conduit 40%, p = 0.001; 61% vs. robotic surgery 53%, p = 0.04, respectively). Uretero-enteric stricture occurred in 7.6% of patients, with no significant difference between groups. The predictive model demonstrated high accuracy (AUC 0.851) and identified key risk factors for major complications: neobladder reconstruction (OR 10.9[2.4-48.4], p = 0.002), older age, longer operative time, and low preoperative hemoglobin. Limitations include the non-randomized treatment allocation and small sample size in the monotherapy group, which may limit generalizability. CONCLUSION: Radical cystectomy after neoadjuvant immunotherapy+/-chemotherapy is feasible, safe, and is not associated with increased intra-operative surgical complexity. Neoadjuvant chemo-immunotherapy prior to cystectomy was associated with increased risk of major surgical complications compared to immunotherapy alone.
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Anticorpos Monoclonais Humanizados , Antineoplásicos Imunológicos , Cistectomia , Neoplasias da Bexiga Urinária , Humanos , Neoplasias da Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/cirurgia , Neoplasias da Bexiga Urinária/terapia , Terapia Neoadjuvante , Masculino , Feminino , Idoso , Cistectomia/métodos , Pessoa de Meia-Idade , Anticorpos Monoclonais Humanizados/uso terapêutico , Invasividade Neoplásica , Resultado do Tratamento , Antineoplásicos Imunológicos/uso terapêutico , Complicações Pós-Operatórias/epidemiologia , Quimioterapia AdjuvanteRESUMO
BACKGROUND: Tumor deposits (TDs) may have a worse prognosis in rectal cancer, but their significance in the neoadjuvant era is less certain. Post-treatment TDs might even be a sign of tumor response. The present study aimed to assess the clinical significance of TDs detected before and after neoadjuvant therapy, and to investigate the impact of neoadjuvant therapy-induced TDs changes on oncological outcomes. METHODS: A retrospective cohort analysis using our hospital records from 2017 to 2019 was carried out. All patients received preoperative long-course chemoradiotherapy and part of them received total neoadjuvant therapy. RESULTS: A total of 132 patients with cT3-4N+M0 were included. mrTDs were observed in 40 (30.3%) patients. 40% of the patients had two or more mrTDs. 64.4% of mrTDs located in the mesorectal fat. mrTDs were associated with mrT4 stage, lymph node invasion, threatened mrMRF, and positive mrEMVI. 51.4% of mrTDs positive patients achieved complete response after neoadjuvant therapy. 3-year disease-free survival (DFS) and overall survival (OS) were worse in mrTD positive patients (3y-DFS: 42.5% vs 73.9%, P < 0.001; 3y-OS: 55% vs 82.9%, P < 0.001). Among the patients with mrTDs, those who became ypTDs- after neoadjuvant therapy had better outcome compared to the ypTDs+ patients (3y-DFS: 52.6% vs 22.2%, P = 0.022; 3y-DMFS: 63.2% vs 27.8%, P = 0.025). Distant metastasis occurred earlier and more frequently in ypTDs+ group, and multiple metastasis were more common. ypTDs and TDs' different response to neoadjuvant therapy were prognostic factors of overall survival in multivariate analysis. CONCLUSIONS: The presence of mrTDs and the poor regression of mrTDs in cT3-4N+M0 rectal cancer after neoadjuvant treatment are associated with advanced disease and worse outcome. Patients with ypTDs+ after neoadjuvant therapy have dismal outcome, which call for more innovative treatment.
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Terapia Neoadjuvante , Neoplasias Retais , Humanos , Neoplasias Retais/patologia , Neoplasias Retais/terapia , Neoplasias Retais/mortalidade , Masculino , Feminino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Idoso , Adulto , Intervalo Livre de Doença , Estadiamento de Neoplasias , Resultado do TratamentoRESUMO
Fertility preservation remains a critical concern in young women with early or locally advanced cervical cancer, as standard radical treatments compromise reproductive potential. This study aims to evaluate the feasibility, oncological safety, and reproductive outcomes of fertility-sparing treatment involving neoadjuvant chemotherapy followed by cervical conization and laparoscopic pelvic lymphadenectomy. This single-center, prospective, open-label, single-arm, Phase II interventional study will assess patients with FIGO stage IB2-IB3 cervical cancer (FIGO stage 2018) desiring fertility preservation. Eligible patients will receive three cycles of dose-dense paclitaxel and carboplatin (dd-TC), followed by conization and laparoscopic lymphadenectomy. The primary endpoint is successful uterine preservation. Patients requiring concurrent chemoradiotherapy due to inadequate treatment response will not be considered successful. Secondary endpoints include 2-year recurrence-free survival (RFS), overall survival (OS), quality of life assessments, menstrual and ovulatory resumption, pregnancy, live birth, miscarriage, and preterm birth. Adverse events will be graded according to CTCAE v5.0.
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Protocolos de Quimioterapia Combinada Antineoplásica , Preservação da Fertilidade , Terapia Neoadjuvante , Neoplasias do Colo do Útero , Humanos , Feminino , Neoplasias do Colo do Útero/tratamento farmacológico , Neoplasias do Colo do Útero/cirurgia , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/terapia , Preservação da Fertilidade/métodos , Terapia Neoadjuvante/métodos , Adulto , Carboplatina/administração & dosagem , Paclitaxel/administração & dosagem , Paclitaxel/uso terapêutico , Estudos Prospectivos , Gravidez , Estadiamento de Neoplasias , Excisão de Linfonodo , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Conização , Qualidade de VidaRESUMO
AIM: Standard management with chemoradiotherapy (CRT) or total neoadjuvant therapy (TNT) followed by total mesorectal excision (TME) reduces local recurrence but often is associated with significant long-term functional impairment. Organ preservation (OP) has become a key therapeutic goal in rectal cancer to reduce surgery-related morbidity without compromising oncological outcomes. Three main OP strategies have been developed: Watch and Wait (W&W) strategy, Local Excision (LE) and Contact X-ray Brachytherapy (CXB), both applicable in patients showing a favourable tumour response after neoadjuvant therapy. The current challenge is defining the optimal timing and modalities for response assessment to accurately identify complete clinical response while balancing oncological control, functional outcomes and patient preferences. This trial evaluates whether a structured tumour response surveillance program combined with shared decision-making (SDM) can safely increase OP rates. METHODS: GRECCAR 20 is a multicentre, randomized, open-label, phase III trial enrolling patients with cT2-T3N0-1 rectal adenocarcinoma ≤ 8 cm from the anal verge and ≤ 4 cm in length, without involvement of the anal canal. Across the French GRECCAR and PRODIGE network, 270 patients will be recruited over 36 months. After neoadjuvant treatment (CRT or induction chemotherapy followed by CRT), participants are randomized to either a structured tumour response surveillance strategy with SDM over 8 to 24 weeks (experimental arm) or standard response assessment without SDM at 8 weeks (control arm). In the experimental arm (Arm A), reassessments at 2-, 4- and 6-month post-treatment will guide management decisions-W&W, LE, CXB or TME-through a collaborative process between patient and clinician. In the control arm (Arm B), treatment decisions at 2 months will be made solely by the clinician, between LE or TME, based on clinical, endoscopic and radiological assessment. The primary outcome is the OP rate at 2 years. Secondary endpoints include disease-free survival, TME-free survival, functional outcomes, quality of life (QoL) and patient-reported outcome measures (PROMs). CONCLUSION: GRECCAR 20 is the first randomized trial to assess a structured tumour response surveillance program incorporating SDM in rectal cancer. By prioritizing patient values and QoL, this trial aims to improve OP rates without compromising oncological safety, potentially establishing a new standard of personalized, patient-centred care.
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Adenocarcinoma , Tomada de Decisão Compartilhada , Tratamentos com Preservação do Órgão , Neoplasias Retais , Conduta Expectante , Humanos , Neoplasias Retais/terapia , Neoplasias Retais/patologia , Conduta Expectante/métodos , Terapia Neoadjuvante/métodos , Tratamentos com Preservação do Órgão/métodos , Ensaios Clínicos Fase III como Assunto , Ensaios Clínicos Controlados Aleatórios como Assunto , Adenocarcinoma/terapia , Adenocarcinoma/patologia , Estudos Multicêntricos como Assunto , Masculino , Feminino , Protectomia/métodos , Resultado do Tratamento , Braquiterapia/métodosRESUMO
AIM: This study aimed to assess the prognostic significance of various histologic tumor regression grade (TRG) systems (Becker, American Joint Committee on Cancer (AJCC)/College of American Pathologists (CAP), Japanese Gastric Cancer Association (JGCA), JGCA2017, China, Mandard) and lymph node (LN) regression in patients with locally advanced gastric adenocarcinoma who underwent gastrectomy following neoadjuvant chemotherapy (NACT). METHODS: A retrospective cohort of 134 patients with locally advanced gastric adenocarcinoma from January 2020 to March 2024 who received NACT followed by gastrectomy was analyzed. Due to incomplete records, only the fact that patients received NACT was used, without specific regimen details. Surgical specimens were evaluated by two pathologists according to Becker, AJCC/CAP, JGCA, JGCA2017, China, and Mandard TRG systems. LN regression was categorized as positive/negative and coded as three categories (Code 1: metastasis without regression; Code 2: metastasis with regression; Code 3: regression without metastasis). Clinicopathologic variables, overall survival (OS) and disease-free survival (DFS) were analyzed by Kaplan-Meier curves and log-rank tests. Univariable and multivariable Cox regression models included each TRG subgroup as dummy variables and relevant covariates. Statistical significance was defined as p < 0.05. RESULTS: The median follow-up time was 24 months (range 6-60). The median OS was 18.7 months (95% CI 16.2-21.3), while the median DFS was 16.4 months (95% CI 14.1-18.7). In the univariable analysis, JGCA2017 Score 0 (hazard ratio [HR] 0.28; 95% CI 0.12-0.65; p = 0.003), Score 1a (HR 0.36; 95% CI 0.16-0.83; p = 0.017), and clinical N3 stage (HR 1.95; 95% CI 1.15-3.30; p = 0.013) were significantly associated with both OS and DFS. In multivariable Cox models, independent predictors of OS were JGCA2017 Score 0 (HR 0.25; 95% CI 0.11-0.59; p = 0.002), Score 1a (HR 0.33; 95% CI 0.15-0.76; p = 0.009), cN3 (vs cN1-2; HR 2.05; 95% CI 1.18-3.56; p = 0.010), and positive LN regression (HR 0.42; 95% CI 0.23-0.77; p = 0.005). Regarding DFS, JGCA2017 Score 0 (HR 0.30; 95% CI 0.12-0.75; p = 0.009), cN3 (vs cN1-2; HR 1.90; 95% CI 1.10-3.30; p = 0.020), and positive LN regression (HR 0.50; 95% CI 0.28-0.90; p = 0.018) were independent predictors. Other TRG systems' subgroups did not remain significant in multivariable models. Notably, the JGCA2017 Score 0/1a categories independently predicted better OS and DFS, whereas positive LN regression also emerged as a protective prognostic factor. CONCLUSIONS: JGCA2017 subgroups are the most robust prognostic indicators for OS and DFS in patients with gastric adenocarcinoma following NACT. Positive LN regression is also an independent protective factor. Prospective validation and international standardization of these grading systems are warranted.
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Adenocarcinoma , Terapia Neoadjuvante , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/patologia , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/terapia , Neoplasias Gástricas/cirurgia , Estudos Retrospectivos , Masculino , Feminino , Pessoa de Meia-Idade , Adenocarcinoma/patologia , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/mortalidade , Adenocarcinoma/cirurgia , Adenocarcinoma/terapia , Prognóstico , Gastrectomia , Idoso , Metástase Linfática , Quimioterapia Adjuvante , Adulto , Linfonodos/patologia , Gradação de TumoresRESUMO
INTRODUCTION: Locoregional lymph node involvement significantly worsens the prognosis of muscle invasive urothelial carcinoma of the bladder. Depending on disease burden, systemic chemotherapy is administered preoperatively either as a neoadjuvant treatment for localized cases, or as induction systemic therapy, when radiologic evidence suggests locoregional nodal involvement. Current lymph node assessment relies on CT imaging, but the added value of [18 F]-FDG PET-CT remains unclear. The objective of this study was to evaluate the prognostic value of lymph node assessment using [18 F]-FDG PET-CT performed before and after preoperative chemotherapy. METHODS: We conducted a retrospective single-center study on consecutive patients who received preoperative chemotherapy (neoadjuvant or induction systemic therapy) followed by radical cystectomy for MIBC between 2017 and 2025. Patients who underwent both pre and post-chemotherapy [18 F]-FDG PET-CT were included and categorized into three groups based on nodal metabolic uptake, before and after chemotherapy: (-)/(-), (+)/(-), and (+)/(+). The primary objective was to assess disease-free survival (DFS) according to nodal [18 F]-FDG uptake before and after chemotherapy. RESULTS: Forty-one patients were included, with a median age of 66 years (range 36-78), Preoperative chemotherapy consisted of ddMVAC in 65.9% of cases, with a median of 4 cycles (range 1-6). Seven patients (17.1%) were ypN1 and three (7.3%) were ypN2. At 7 months, all patients with persistent positive uptake experienced disease progression. DFS was significantly lower in the (+)/(+) group (log-rank p < 0.001), followed by (+)/(-), and (-)/(-) groups. In multivariate Cox analysis, persistent lymph node uptake on [18 F]-FDG PET-CT ((+)/(+)) was an independent prognostic factor of worse DFS (HR 6.24; 95% CI 1.64-23.7; p = 0.007), regardless of final T stage and nodal invasion. CONCLUSIONS: Persistent lymph node [18 F]-FDG uptake on PET-CT after chemotherapy is an independent adverse prognostic factor for disease-free survival.
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Carcinoma de Células de Transição , Fluordesoxiglucose F18 , Linfonodos , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Neoplasias da Bexiga Urinária , Humanos , Estudos Retrospectivos , Masculino , Feminino , Terapia Neoadjuvante , Idoso , Pessoa de Meia-Idade , Linfonodos/diagnóstico por imagem , Linfonodos/metabolismo , Intervalo Livre de Doença , Compostos Radiofarmacêuticos , Neoplasias da Bexiga Urinária/diagnóstico por imagem , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/mortalidade , Neoplasias da Bexiga Urinária/terapia , Neoplasias da Bexiga Urinária/metabolismo , Valor Preditivo dos Testes , Metástase Linfática/diagnóstico por imagem , Carcinoma de Células de Transição/diagnóstico por imagem , Carcinoma de Células de Transição/tratamento farmacológico , Prognóstico , Quimioterapia Adjuvante , AdultoRESUMO
Expression of the ß-adrenergic receptors' family has been associated with survival outcomes in multiple different cancer types, showing their potential to act as prognostic factors. No previous work has evaluated these receptors in relation to survival in oesophageal adenocarcinoma. We sought to analyse the expression of ß1 and ß2 adrenergic receptors in oesophageal adenocarcinoma and their association with survival outcomes. The expression of ß1 and ß2 adrenergic receptors was evaluated in a cohort of oesophageal adenocarcinoma patients treated with neo-adjuvant chemotherapy prior to surgical resection at the Northern Ireland Cancer Centre between 2004 and 2012. Immunohistochemical staining for was assessed using a Tissue Microarray with triplicate tumour cores. Cox proportional hazards regression was used to investigate the association of ß1 and ß2 adrenergic receptor expression with survival outcomes, including adjustment for clinical factors. In total, 115 and 122 patients were assessed for ß1 and ß2 adrenergic receptor expression, respectively. In adjusted analysis, high ß2 adrenergic receptor expression was associated with improved recurrence-free [hazard ratio [HR] 0.57, 95% CI 0.33-0.97] and overall survival (HR 0.53, 95% CI 0.30-0.94) with restriction to gastro-oesophageal junction tumours showing a stronger association with improved overall survival (HR 0.27, 95% CI 0.13-0.59). No significant association was observed for ß1 adrenergic receptor expression and any survival outcome. In summary, we found that higher expression of the ß2 adrenergic receptor was associated with a significant improvement in survival in oesophageal adenocarcinoma patients, and gastro-oesophageal junction tumours in particular, treated with neoadjuvant chemotherapy followed by surgical resection.
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Adenocarcinoma , Biomarcadores Tumorais , Neoplasias Esofágicas , Receptores Adrenérgicos beta 1 , Receptores Adrenérgicos beta 2 , Humanos , Neoplasias Esofágicas/mortalidade , Neoplasias Esofágicas/patologia , Neoplasias Esofágicas/metabolismo , Neoplasias Esofágicas/terapia , Masculino , Feminino , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Adenocarcinoma/metabolismo , Adenocarcinoma/terapia , Pessoa de Meia-Idade , Receptores Adrenérgicos beta 2/metabolismo , Receptores Adrenérgicos beta 2/análise , Idoso , Receptores Adrenérgicos beta 1/metabolismo , Receptores Adrenérgicos beta 1/análise , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/metabolismo , Prognóstico , Modelos de Riscos Proporcionais , Terapia Neoadjuvante , Estimativa de Kaplan-Meier , Intervalo Livre de Doença , Imuno-Histoquímica , Análise Serial de Tecidos , AdultoRESUMO
Despite widespread immune profiling in cancer immunotherapy, the antigen-specific responses that drive clinical outcomes remain poorly defined. In a prospective neoadjuvant trial (NCT04013854) of a single-dose anti-PD-1 (nivolumab) in stage III melanoma, we performed antigen-specific profiling of melanoma and viral-specific CD8+ T cells across blood, tumor, and lymph node compartments. Using combinatorial tetramers, we detected melanoma-specific CD8+ T cells in 72% of HLA-A1, -A2, and -A3 patients. These cells displayed distinct phenotypes shaped by tissue and antigen context. Tumor-infiltrating T-bet+ intermediate exhausted CD8+ T cells were strongly associated with pathologic response, while CD39+ terminal exhausted cells marked non-response. T-bet and CD39 expression also stratified responses in uninvolved lymph nodes, suggesting early divergence of therapeutic immune trajectories. Longitudinal profiling revealed that circulating melanoma-specific CD8+ T cell dynamics was antigen-dependent and associated with clinical outcomes. Our findings highlight the clinical value of antigen-specific profiling and identify mechanistic correlates of anti-PD-1 efficacy.
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Linfócitos T CD8-Positivos , Inibidores de Checkpoint Imunológico , Melanoma , Nivolumabe , Receptor de Morte Celular Programada 1 , Neoplasias Cutâneas , Proteínas com Domínio T , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Antígenos de Neoplasias/imunologia , Apirase/metabolismo , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/metabolismo , Inibidores de Checkpoint Imunológico/uso terapêutico , Linfócitos do Interstício Tumoral/imunologia , Melanoma/imunologia , Melanoma/tratamento farmacológico , Melanoma/patologia , Terapia Neoadjuvante/métodos , Nivolumabe/uso terapêutico , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Estudos Prospectivos , Neoplasias Cutâneas/imunologia , Neoplasias Cutâneas/tratamento farmacológico , Neoplasias Cutâneas/patologia , Fator de Transcrição T-bet , Proteínas com Domínio T/metabolismo , Proteínas com Domínio T/imunologiaRESUMO
AIM: Neoadjuvant treatment for rectal cancer has evolved markedly with the growing adoption of total neoadjuvant therapy (TNT), organ-preservation strategies and selective omission of radiotherapy. Recent trials support risk-based personalization, but its application in real-world settings remains poorly documented. The aim was to describe current neoadjuvant treatment practices for mid-low rectal cancer in French expert centres and identify tumour- and patient-related factors influencing decisions. METHOD: This observational study included patients with non-metastatic rectal adenocarcinoma ≤10 cm from the anal verge, discussed in tumour boards (October 2022 to March 2023) across GRECCAR centres. Tumours were classified as early, intermediate-risk or locally advanced rectal cancer (LARC). Neoadjuvant treatments were analysed according to tumour extension, location and age. RESULTS: Among 463 patients from 27 centres, the most frequent regimen was induction chemotherapy, mainly FOLFIRINOX, followed by long-course chemoradiotherapy (CRT) (65%). This approach was used in 51%, 66% and 71% of patients in the early, intermediate-risk and LARC groups, respectively (p = 0.0060). TNT was more frequently administered for low- than mid-rectal cancers, especially in LARC (86% vs. 71%, p = 0.016). In patients >75 years, CRT + consolidation chemotherapy and radiotherapy alone were proportionally more frequent. Among the early rectal cancers, those treated with induction chemotherapy + CRT had more advanced features than those treated with CRT alone (cT3: 80% vs. 43%, cN+: 62% vs. 10%, tumour size: 3.4 vs. 2.3 cm; all p < 0.001). CONCLUSION: TNT with induction chemotherapy is the predominant neoadjuvant approach in French expert centres. Tumour classification, location and patient age significantly influence treatment choices, reflecting a shift towards personalized context-specific care.
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Adenocarcinoma , Terapia Neoadjuvante , Neoplasias Retais , Humanos , Neoplasias Retais/terapia , Neoplasias Retais/patologia , Terapia Neoadjuvante/métodos , Terapia Neoadjuvante/estatística & dados numéricos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , França , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Adenocarcinoma/terapia , Adenocarcinoma/patologia , Fluoruracila/uso terapêutico , Oxaliplatina/uso terapêutico , Quimioterapia de Indução/estatística & dados numéricos , Quimioterapia de Indução/métodos , Leucovorina/uso terapêutico , Irinotecano/uso terapêutico , Adulto , Quimiorradioterapia Adjuvante/estatística & dados numéricos , Quimiorradioterapia Adjuvante/métodos , Quimiorradioterapia/estatística & dados numéricos , Quimiorradioterapia/métodos , Idoso de 80 Anos ou maisRESUMO
It is important to predict response of esophageal squamous cell carcinoma (ESCC) to neoadjuvant immunochemotherapy for treatment decision-making. This study aimed to explore whether dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) derived parameters and MR signal intensity can predict the response. About 82 consecutive ESCC patients undergoing pretherapeutic DCE-MRI, T2WI, and T1WI followed by neoadjuvant immunochemotherapy were prospectively enrolled, among which patients from Institution 1 were randomly stratified into training (n = 52) and internal validation (n = 15) cohorts, and those from Institution 2 were assigned to external validation cohort (n = 15). Ktrans, Kep, and Ve of ESCC and their standard deviation (SD) were generated based on DCE-MRI, mean, and SD of MR signal intensity on T1WI and T2WI were also obtained, and coefficient of variation of these parameters were calculated. In training cohort, all parameters were statistically compared between responders and non-responders. Predictive effectiveness of individual parameters with statistical difference, and the parameters based logistic regression models were evaluated using area under the receiver operating characteristic curve (AUC) in three cohorts. Mean and SD of Kep (Kep_Mean and Kep_SD, respectively) and T2WI signal intensity (T2WI_Mean and T2WI_SD, respectively) in responders were higher than in non-responders (all P-values <0.05), among which, Kep_Mean could best predict the responsiveness with AUCs of 0.858, 0.768, and 0.870; and the model (T2WI_Mean + T2WI_SD + Kep_Mean + Kep_SD) demonstrated superior predictive performance (AUCs: 0.928, 0.911, and 0.907) in training, internal and external validation cohorts, respectively. Combination of mean and SD of Kep, and T2WI signal intensity could well predict immunochemotherapy responsiveness of ESCC.
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Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Imunoterapia , Imageamento por Ressonância Magnética , Terapia Neoadjuvante , Humanos , Masculino , Feminino , Carcinoma de Células Escamosas do Esôfago/diagnóstico por imagem , Carcinoma de Células Escamosas do Esôfago/terapia , Carcinoma de Células Escamosas do Esôfago/tratamento farmacológico , Neoplasias Esofágicas/diagnóstico por imagem , Neoplasias Esofágicas/terapia , Neoplasias Esofágicas/tratamento farmacológico , Pessoa de Meia-Idade , Imageamento por Ressonância Magnética/métodos , Terapia Neoadjuvante/métodos , Meios de Contraste , Idoso , Modelos Logísticos , Valor Preditivo dos Testes , Resultado do Tratamento , Curva ROC , Estudos Prospectivos , Adulto , Área Sob a Curva , Imunoterapia/métodosRESUMO
INTRODUCTION: In early stage non-small cell lung cancer (NSCLC), recurrence is frequent despite surgery and systemic treatments. Observational studies suggest that physical exercise and nutrition could improve outcomes, such as survival and treatment tolerance; however, solid evidence is lacking. The STARLighT trial aims to assess the effects of a telehealth-delivered combined exercise and nutrition intervention on clinical, biological and patient-reported outcomes in early stage NSCLC. METHODS AND ANALYSIS: STARLighT is a multicentre master protocol study conducted in Italy, comprising two cohorts of patients affected by early stage NSCLC (stages IB-IIIA) epidermal growth factor receptor and anaplastic lymphoma kinase wild type. Cohort A will include 46 patients with resectable NSCLC receiving neoadjuvant treatment and will exploit a single-arm phase II design. Cohort B will enrol 268 patients undergoing adjuvant treatment (including as a part of a perioperative strategy) and proposes a randomised controlled phase III design. Patients in Cohort A and those allocated to the interventional arm in Cohort B will receive a tailored telehealth-delivered exercise and nutritional intervention. The control group will receive the usual care plus educational material. For cohort A, two coprimary endpoints are set: pathological complete response and quality of life, whereas the primary endpoint for cohort B is 2-year disease-free survival. Secondary and exploratory endpoints include a series of clinical (eg, overall survival and safety), biological (immune-inflammatory markers, gut microbiota and transcriptomics) and patient-reported outcomes (eg, sleep habits, physical activity, anxiety and depression and distress) evaluations. ETHICS AND DISSEMINATION: The study is approved by the Ethics Committee of the University of Verona (Prot. No. 33979) and registered on ClinicalTrials.gov (NCT07042724). Findings will be disseminated through peer-reviewed journals, scientific meetings, public forums and guideline updates. TRIAL REGISTRATION NUMBER: Clinicaltrial.gov: NCT07042724.
Assuntos
Carcinoma Pulmonar de Células não Pequenas , Terapia por Exercício , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/terapia , Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/terapia , Neoplasias Pulmonares/patologia , Telemedicina , Terapia Neoadjuvante , Terapia por Exercício/métodos , Estudos Multicêntricos como Assunto , Qualidade de Vida , Masculino , Itália , Ensaios Clínicos Fase II como Assunto , Feminino , Estadiamento de Neoplasias , Ensaios Clínicos Fase III como Assunto , Medidas de Resultados Relatados pelo PacienteRESUMO
BACKGROUND: Despite the known benefits of physical activity for women with breast cancer (BC), adherence to recommended guidelines remains low, especially during neo-adjuvant chemotherapy. The Aurora intervention presents a multidimensional approach to improve physical activity adherence, considering the patient's emotional and physical needs and barriers to physical activity. This protocol aims to evaluate Aurora's effects compared to standard care in BC patients. METHODS: In this 9-week randomized controlled trial, 30 female BC patients under 70 years of age, undergoing neo-adjuvant chemotherapy in the Metropolitan Region of Chile, will be recruited. Participants will receive a standard online education class on the benefits of physical activity for BC patients, which includes general information on the importance of exercise during treatment, recommended physical activity guidelines, and tips for safely incorporating movement into daily routines. Afterward, participants will be randomly allocated in a 1:1 ratio to either the 9-week Aurora experimental program (Aurora experimental kit: branded box containing exercise equipment, designed logbook journal, hydration bottle, exercise leaflet, and arm volume measurement tape) or the Aurora control program (Aurora control kit: branded tote bag containing a blank notebook, hydration bottle, and exercise leaflet). The study will employ a mixed-methods approach to assess multidimensional treatment effects through baseline and post-intervention measurements. The primary outcome will be quality of life, which will be assessed using questionnaires and patient perceptions, with thematic analysis of patient-recorded journals and in-depth group interviews to evaluate emotional treatment effects. Secondary outcomes will include (1) functional capacity tests to measure adverse physical effects and (2) biological markers assessed through lipid profiling, inflammation biomarkers, and tumor progression. DISCUSSION: Our conceptual hypothesis is that the Aurora intervention program will positively impact primary and secondary outcomes compared to the control group. Integrating the behavior change COM-B model and a patient-centered design facilitates tailoring interventions to BC patients' multidimensional needs and barriers. Additionally, we expect the Aurora program to promote more significant effects than standard care on physical activity adherence, intensity, and time. TRIAL REGISTRATION: The study was registered at ClinicalTrials.gov, NCT06449417. Registered on May 28, 2024. Unique Protocol ID: 230126002. https://clinicaltrials.gov/study/NCT06449417 .
Assuntos
Neoplasias da Mama , Terapia por Exercício , Exercício Físico , Terapia Neoadjuvante , Qualidade de Vida , Humanos , Feminino , Neoplasias da Mama/terapia , Neoplasias da Mama/psicologia , Neoplasias da Mama/tratamento farmacológico , Terapia Neoadjuvante/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto , Terapia por Exercício/métodos , Pessoa de Meia-Idade , Assistência Centrada no Paciente , Adulto , Resultado do Tratamento , Idoso , Chile , Quimioterapia AdjuvanteRESUMO
BACKGROUND: Triple-negative breast cancer (TNBC) is a subtype of breast cancer with a poor prognosis and limited treatment options. Currently, nonmetastatic TNBC is mostly treated with neoadjuvant chemotherapy, but comparisons between these neoadjuvant regimens are dearth. METHODS: PubMed, Embase, Medline, Cochrane Library, Web of ClinicalTrials.gov, and major international conference databases were systematically searched for randomized controlled trials (RCTs) on the efficacy of various neoadjuvant chemotherapy treatments in patients with TNBC from inception to January 2025. The primary research endpoint was the pathological complete response (pCR) rate. The secondary endpoint was the odds ratios (ORs) at different time points of event-free survival (EFS) and overall survival (OS). The tertiary endpoints were the hazard ratios (HRs) of EFS and OS compared by Bayesian network meta-analysis, as well as corresponding Bayesian network meta-regression analysis with the median follow-up time as the covariate. The above processes were conducted by RStudio 4.2.2 orchestrated with STATA 17.0 MP. RESULTS: For the primary endpoint, compared to regimens containing anthracycline and taxanes (AT), regimens containing anthracycline, taxanes, platinum, and programmed cell death protein-1 (ATPtPD1) showed significant higher pCR rate (ORâ =â 5.68). For the secondary endpoint, compared to AT, ATPtPD1 showed significant longer EFS/OS. For EFS: ORâ =â 2.28 at 18th month; ORâ =â 2.43 at 24th month; ORâ =â 3.21 at 30th month; ORâ =â 4.23 at 36th month; ORâ =â 4.62 at 42nd month; ORâ =â 4.04 at 48th month. For OS: ORâ =â 3.56 at 18th month; ORâ =â 2.23 at 24th month; ORâ =â 2.49 at 30th month; ORâ =â 2.49 at 36th month; ORâ =â 3.17 at 42nd month; ORâ =â 2.97 at 48th month. For the tertiary endpoints, for HR of EFS, compared to AT, ATPtPD1 indicated significant advantage (HRâ =â 2.24, 95% confidence interval [CI]: 1.42-3.59), after meta-regression analysis, shows advantages as well (HRâ =â 2.29, 95% CI: 1.39-3.89). For HR of OS, compared to AT, ATPtPD1 indicated significant advantage (HRâ =â 2.67, 95% CI: 1.03-7.35), after meta-regression analysis, shows advantages as well (HRâ =â 2.70, 95% CI: 1.18-6.33). CONCLUSIONS: Considering efficacy on pCR and OS/EFS together, ATPtPD1 should be considered as the best recommendation in neoadjuvant therapies of TNBC.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Terapia Neoadjuvante , Neoplasias de Mama Triplo Negativas , Humanos , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/mortalidade , Neoplasias de Mama Triplo Negativas/terapia , Terapia Neoadjuvante/métodos , Teorema de Bayes , Feminino , Ensaios Clínicos Controlados Aleatórios como Assunto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Resultado do Tratamento , Taxoides/uso terapêutico , Antraciclinas/uso terapêuticoRESUMO
Neoadjuvant chemotherapy (NACT) is the standard treatment for muscle-invasive bladder carcinoma (MIBC), but its efficacy varies significantly among patients. The aim of this study is the identification of biomarkers and biological processes related to the response to neoadjuvant chemotherapy (NACT) in muscle-invasive bladder carcinoma (MIBC). Fifty-eight transurethral resection (TURBT) samples and thirty cystectomy samples from NACT non-responders were analyzed using mass spectrometry. Samples were classified with sparse k-means and consensus clustering. Protein networks were built using probabilistic graphical models, grouped into functional nodes, and analyzed for activity differences. Gene set enrichment analysis was applied to identify resistance mechanisms, and results were validated using The Cancer Genome Atlas (TCGA) cohort. Proteomic analysis revealed two independent classifications in TURBT samples. The first (Layer1) divided tumors into three groups, including one NACT non-responder subtype not aligned with traditional luminal or basal classifications but characterized by high expression of targetable markers NECTIN4 and Her2. The second (Layer3) separated luminal-papillary tumors from luminal-infiltrated/luminal and basal tumors. While Layer3 groups did not differ in NACT response, they showed distinct disease-free survival outcomes. Importantly, complete response to NACT was linked to improved survival in luminal subgroups but not in basal tumors, suggesting subtype-specific prognostic implications. Finally, analysis of cystectomy samples identified unique mechanisms of resistance for each subgroup, suggesting tailored therapeutic approaches. Two classification systems were defined as follows: one identified a proteomics-based non-responder group with actionable targets, and the other linked tumor subtype to prognosis. Distinct resistance mechanisms suggest opportunities for subtype-specific therapies, supporting improved management and treatment development for MIBC patients.
Assuntos
Biomarcadores Tumorais , Neoplasias da Bexiga Urinária , Humanos , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/metabolismo , Neoplasias da Bexiga Urinária/genética , Terapia Neoadjuvante , Biomarcadores Tumorais/metabolismo , Biomarcadores Tumorais/genética , Feminino , Masculino , Idoso , Pessoa de Meia-Idade , Proteômica/métodos , Regulação Neoplásica da Expressão Gênica , Invasividade Neoplásica , Resistencia a Medicamentos Antineoplásicos , PrognósticoRESUMO
BACKGROUND/AIM: Pathologic complete response (pCR) to neoadjuvant chemotherapy (NACT) is a strong prognostic indicator in triple-negative breast cancer (TNBC). However, reliable predictive biomarkers for pCR remain limited. This study aimed to identify gene expression signatures associated with pCR in TNBC to facilitate more precise treatment stratification. MATERIALS AND METHODS: Tumor samples from 16 TNBC patients treated with NAC at the Kaohsiung Medical University Hospital (KMUH) were analyzed, including 5 pCR and 11 non-pCR cases. RNA sequencing (RNA-seq) was performed, and differentially expressed genes (DEGs) were identified using DESeq2 (|log2FC| ≥2, adjusted p<0.05). Gene expression profiles were compared with a validation cohort of 27 NAC-responsive TNBC cases from The Cancer Genome Atlas (TCGA). Overlapping DEGs were identified using Venn diagram analysis, and drug-gene interaction databases were queried to explore therapeutic relevance. RESULTS: In the KMUH cohort, 175 DEGs were identified, including 146 up-regulated and 29 down-regulated genes in non-pCR tumors. Fifteen DEGs demonstrated consistent differential expression patterns between KMUH and TCGA datasets, showing enrichment in pCR samples. These genes may serve as predictive biomarkers for NAC response. Notably, several of these genes are potentially druggable, suggesting opportunities for targeted therapy in chemoresistant TNBC. CONCLUSION: We identified and validated a 15 gene signature associated with pCR in TNBC across independent cohorts. These findings offer a promising basis for improving patient stratification, guiding treatment decisions, and developing targeted therapies for NAC-resistant TNBC.
Assuntos
Biomarcadores Tumorais , Perfilamento da Expressão Gênica , Transcriptoma , Neoplasias de Mama Triplo Negativas , Humanos , Neoplasias de Mama Triplo Negativas/genética , Neoplasias de Mama Triplo Negativas/patologia , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Feminino , Biomarcadores Tumorais/genética , Perfilamento da Expressão Gênica/métodos , Pessoa de Meia-Idade , Prognóstico , Regulação Neoplásica da Expressão Gênica , Terapia Neoadjuvante , Adulto , IdosoRESUMO
BACKGROUND/AIM: Circumferential resection margin (CRM) has been shown to be a strong predictor of risk of local recurrence (LR) and distant metastases (DM) in patients with rectal cancer treated with total mesorectal excision (TME). However, not all patients with a CRM of zero develop LR or DM. This study aimed to identify factors associated with disease-free survival (DFS) despite non-radical excision (CRM=0 mm). PATIENTS AND METHODS: Patients surgically treated for adenocarcinoma of the rectum between 2005 and 2013 were identified through the Swedish ColoRectal Cancer Registry. RESULTS: Of 8,392 patients included in the study, 159 (1.8%) were found to have CRM 0 mm. The rates of LR (n=27; 17%) and DM (n=62; 39%) were high in the CRM 0 mm group; however, more than half of these patients developed neither (n=84; 52.8%). Stage II disease was associated with a higher DFS [odds ratio (OR)=2.15; 95% confidence interval (CI)=1.11-4.18] compared with stage III disease. Neoadjuvant chemotherapy was a negative prognostic factor of DFS (OR=0.47, 95% CI=0.23-0.97) independent of the stage of disease. CONCLUSION: Over half of the patients with CRM 0 mm after rectal cancer surgery did not develop LR or DM. Lower stage of disease and no neoadjuvant chemotherapy were associated with a better DFS. These findings suggest that other biological or molecular factors may influence prognosis after non-radical excision, highlighting the need for further research to improve postoperative management and follow-up.
Assuntos
Adenocarcinoma , Margens de Excisão , Neoplasias Retais , Humanos , Neoplasias Retais/cirurgia , Neoplasias Retais/patologia , Neoplasias Retais/mortalidade , Masculino , Feminino , Prognóstico , Pessoa de Meia-Idade , Idoso , Fatores de Risco , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Adulto , Intervalo Livre de Doença , Idoso de 80 Anos ou mais , Resultado do Tratamento , Terapia Neoadjuvante , Sistema de Registros , Adenocarcinoma/cirurgia , Adenocarcinoma/patologiaRESUMO
BACKGROUND/AIM: Neoadjuvant therapy enables disease conversion to resectability in selected patients with locally advanced non-small-cell lung cancer (NSCLC) but real-world survival outcomes in this setting are not well defined. This study aimed to evaluate survival outcomes and prognostic factors in patients with initially unresectable, non-metastatic NSCLC in whom complete resection was achieved following neoadjuvant therapy. PATIENTS AND METHODS: This retrospective cohort study included 35 pa tients with initially unresectable NSCLC who underwent R0 resection after neoadjuvant therapy. Demographic, clinical, radiological, and pathological characteristics, treatment details, and survival outcomes were collected. Factors associated with event-free (EFS) and overall (OS) survival were analyzed. RESULTS: The mean age at diagnosis was 67.6 years, and 85.7% of patients were male. Patients received a median of 3 (range=2-6) neoadjuvant therapy cycles (77% with carboplatin and paclitaxel). Postoperative pathology revealed mediastinal lymph node involvement in 37.1% and angiolymphatic invasion in 25.7% of patients. Adjuvant treatment was administered to 51.4% of patients, with no factor significantly associated with this decision. During a median follow-up of 40.6 months, the recurrence rate was 37.1%, and the mortality rate was 40%. The median EFS was 25.4 months, while the median OS was not reached. Two-year EFS and OS rates were 53.9% and 66.3%, respectively. Univariate analysis identified mediastinal lymph node involvement, angiolymphatic invasion, and receiving ≥3 neoadjuvant cycles as significant predictors of shorter EFS, while only mediastinal lymph node involvement significantly affected OS. Multivariate analysis did not reveal independent predictors, likely due to collinearity. CONCLUSION: Complete resection after neoadjuvant therapy yields favorable long-term survival in selected patients with initially unresectable NSCLC. Postoperative mediastinal lymph node status remains a critical prognostic factor.
Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Terapia Neoadjuvante , Humanos , Masculino , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/terapia , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Feminino , Terapia Neoadjuvante/métodos , Idoso , Pessoa de Meia-Idade , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/terapia , Estudos Retrospectivos , Prognóstico , Estadiamento de Neoplasias , Resultado do Tratamento , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Adulto , Terapia CombinadaRESUMO
BACKGROUND: Oligometastasisdisease (OMD) is an intermediate stage between localised disease and widespread metastasis. No standard OMD definition exists for gallbladder cancer (GBC). This review examines OMD definitions in GBC, treatment challenges, current strategies like systemic therapy, immunotherapy, surgery, loco-regional therapy, emerging approaches, and future directions for GBC patients with OMD. MATERIALS AND METHODS: A literature review of GBC and oligometastasiswas conducted using PubMed and Google Scholar through July 2025. RESULTS: Metastatic GBC has a poor prognosis; however, a combination of systemic and immunotherapy can slightly improve survival, ranging from 11.3 to 12.7 months. OMD is a subgroup of patients (with 1-3 liver metastases, para-aortic lymph nodes, metastasis limited to adherent omentum, and/or up to three peritoneal deposits) who experience better survival with consolidative treatment, including neoadjuvant therapy followed by curative resection (such as minor hepatectomy, para-aortic lymphadenectomy) and adjuvant therapy. Reported survival rates at 1, 3, and 5 years range from 20 to 64.0%, 5.7-17%, and 0-23%. Risk factors like extensive hepatic lobectomy and portal vein resection in cholestatic liver increase morbidity and mortality. Elevated preoperative tumour markers (CEA, CA 19 - 9) are associated with poorer survival. CONCLUSION: There is no standard definition of OMD in GBC. Our review emphasises the need to develop a standardised definition of OMD in GBC and for multidisciplinary evaluation and well-designed clinical trials to expand therapeutic options and to optimise patient outcomes.
Assuntos
Neoplasias da Vesícula Biliar , Neoplasias Hepáticas , Humanos , Neoplasias da Vesícula Biliar/terapia , Neoplasias da Vesícula Biliar/patologia , Neoplasias da Vesícula Biliar/mortalidade , Prognóstico , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/terapia , Metástase Linfática , Terapia Combinada , Terapia Neoadjuvante/métodosRESUMO
BACKGROUND: Combined epidural-general anesthesia (TEA+GA) can enhance postoperative recovery after gastrointestinal surgery. However, in patients receiving preoperative neoadjuvant chemotherapy (NACT), a known risk factor for postoperative complications, it remains unclear whether TEA+GA improves postoperative outcomes. METHODS: This retrospective cohort study included 365 patients with NACT followed by radical resection of gastrointestinal cancer at Zhongshan Hospital between January 2020 and December 2022. TEA was initiated before the induction of GA. The primary outcome was the incidence of any postoperative in-hospital complications. Secondary outcomes included intraoperative sufentanil consumption, hypotension, vasopressor use, extubation time, post-anesthesia care unit stay, postoperative hospital length of stay, and intensive care unit admission. Inverse probability of treatment weighting (IPTW) and overlap weighting (OW) were applied to adjust for baseline differences. RESULTS: Of the 365 patients, 152 received TEA+GA, while 213 received GA alone. TEA+GA was associated with a significantly higher rate of postoperative complications (23.7% vs. 15.0%, OR [95% CI]: 1.76 (1.05-2.96), p = 0.036) without subgroup difference. This association remained significant after IPTW (24.1% vs 11.7%, OR [95% CI]: 2.39 [1.24-4.59], p = 0.009) and OW (23.3% vs 10.4%; OR [95% CI]: 2.62 [1.36-5.08], p = 0.004) adjustment. The TEA+GA group had a lower dose of intraoperative sufentanil use and shorter extubation times but showed a higher rate of intraoperative hypotension and increased vasopressor requirements. CONCLUSIONS: In patients who underwent NACT followed by gastrointestinal radical surgery, Combined epidural-general anesthesia was associated with an increased incidence of postoperative in-hospital complications.
Assuntos
Anestesia Epidural , Anestesia Geral , Procedimentos Cirúrgicos do Sistema Digestório , Neoplasias Gastrointestinais , Terapia Neoadjuvante , Complicações Pós-Operatórias , Humanos , Anestesia Geral/efeitos adversos , Anestesia Geral/métodos , Feminino , Masculino , Estudos Retrospectivos , Pessoa de Meia-Idade , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Idoso , Anestesia Epidural/efeitos adversos , Anestesia Epidural/métodos , Neoplasias Gastrointestinais/cirurgia , Neoplasias Gastrointestinais/terapia , Neoplasias Gastrointestinais/tratamento farmacológico , Terapia Neoadjuvante/efeitos adversos , Terapia Neoadjuvante/métodos , Pontuação de Propensão , Procedimentos Cirúrgicos do Sistema Digestório/efeitos adversos , Fatores de Risco , Incidência , Tempo de Internação/estatística & dados numéricos , Quimioterapia Adjuvante/efeitos adversos , Sufentanil/administração & dosagemRESUMO
Neoadjuvant and perioperative therapy have emerged as promising strategies for managing locally advanced gastric cancer (LAGC). Landmark phase III studies, such as PRODIGY and RESOLVE, have established neoadjuvant chemotherapy as a viable therapeutic option in Asia. More recently, the MATTERHORN trial demonstrated the potential of incorporating immune checkpoint inhibitors (ICIs) into perioperative treatment. However, the use of fluorouracil, leucovorin, oxaliplatin, and docetaxel in Asian populations warrants careful consideration, given regional treatment standards and concerns regarding chemotherapy-related toxicities, including neutropenia. This review summarizes key perioperative trials and highlights the evolving role of ICIs while also addressing emerging evidence on targeted therapies in LAGC. Key considerations include assessment of treatment response, as the validity of pathological response as a surrogate endpoint for survival remains unclear; risk- and biomarker-driven patient selection; and unresolved questions regarding the necessity and optimal duration of postoperative therapy. Personalizing postoperative treatment based on prognostic and molecular markers-including clinical stage, pathological response, and circulating tumor DNA status-represents an important next step toward improving outcomes.