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1.
Front Immunol ; 15: 1312380, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38726002

RESUMO

Objective: The choice of neoadjuvant therapy for esophageal squamous cell carcinoma (ESCC) is controversial. This study aims to provide a basis for clinical treatment selection by establishing a predictive model for the efficacy of neoadjuvant immunochemotherapy (NICT). Methods: A retrospective analysis of 30 patients was conducted, divided into Response and Non-response groups based on whether they achieved major pathological remission (MPR). Differences in genes and immune microenvironment between the two groups were analyzed through next-generation sequencing (NGS) and multiplex immunofluorescence (mIF). Variables most closely related to therapeutic efficacy were selected through LASSO regression and ROC curves to establish a predictive model. An additional 48 patients were prospectively collected as a validation set to verify the model's effectiveness. Results: NGS suggested seven differential genes (ATM, ATR, BIVM-ERCC5, MAP3K1, PRG, RBM10, and TSHR) between the two groups (P < 0.05). mIF indicated significant differences in the quantity and location of CD3+, PD-L1+, CD3+PD-L1+, CD4+PD-1+, CD4+LAG-3+, CD8+LAG-3+, LAG-3+ between the two groups before treatment (P < 0.05). Dynamic mIF analysis also indicated that CD3+, CD8+, and CD20+ all increased after treatment in both groups, with a more significant increase in CD8+ and CD20+ in the Response group (P < 0.05), and a more significant decrease in PD-L1+ (P < 0.05). The three variables most closely related to therapeutic efficacy were selected through LASSO regression and ROC curves: Tumor area PD-L1+ (AUC= 0.881), CD3+PD-L1+ (AUC= 0.833), and CD3+ (AUC= 0.826), and a predictive model was established. The model showed high performance in both the training set (AUC= 0.938) and the validation set (AUC= 0.832). Compared to the traditional CPS scoring criteria, the model showed significant improvements in accuracy (83.3% vs 70.8%), sensitivity (0.625 vs 0.312), and specificity (0.937 vs 0.906). Conclusion: NICT treatment may exert anti-tumor effects by enriching immune cells and activating exhausted T cells. Tumor area CD3+, PD-L1+, and CD3+PD-L1+ are closely related to therapeutic efficacy. The model containing these three variables can accurately predict treatment outcomes, providing a reliable basis for the selection of neoadjuvant treatment plans.


Assuntos
Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Terapia Neoadjuvante , Microambiente Tumoral , Humanos , Microambiente Tumoral/imunologia , Carcinoma de Células Escamosas do Esôfago/terapia , Carcinoma de Células Escamosas do Esôfago/imunologia , Carcinoma de Células Escamosas do Esôfago/tratamento farmacológico , Terapia Neoadjuvante/métodos , Neoplasias Esofágicas/terapia , Neoplasias Esofágicas/imunologia , Neoplasias Esofágicas/tratamento farmacológico , Masculino , Feminino , Pessoa de Meia-Idade , Estudos Retrospectivos , Prognóstico , Idoso , Biomarcadores Tumorais , Resultado do Tratamento , Imunoterapia/métodos
2.
Sci Rep ; 14(1): 10632, 2024 05 09.
Artigo em Inglês | MEDLINE | ID: mdl-38724585

RESUMO

While some clinics have adopted abbreviated neoadjuvant treatment for HER2-positive breast cancer, there remains a shortage of comprehensive clinical data to support this practice. This is a retrospective, multicenter study. A total of 142 patients were included in the study who are HER2-positive breast cancer, aged ≤ 65 years, with left ventricular ejection fraction ≥ 50%, received neoadjuvant chemotherapy and underwent surgery at 10 different oncology centers in Türkiye between October 2016 and December 2022. The treatment arms were divided into 4-6 cycles of docetaxel/trastuzumab/pertuzumab for arm A, 4 cycles of adriamycin/cyclophosphamide followed by 4 cycles of taxane/TP for arm B. There were 50 patients (35.2%) in arm A and 92 patients (64.8%) in arm B. The median follow-up of all of the patients was 19.9 months (95% CI 17.5-22.3). The 3-year DFS rates for treatment arms A and B were 90.0% and 83.8%, respectively, and the survival outcomes between the groups were similar (p = 0.34). Furthermore, the pathologic complete response rates were similar in both treatment arms, at 50.0% and 51.1%, respectively (p = 0.90). This study supports shortened neoadjuvant treatment of HER2-positive breast cancer, a common practice in some clinics.


Assuntos
Antraciclinas , Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias da Mama , Terapia Neoadjuvante , Receptor ErbB-2 , Trastuzumab , Humanos , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Neoplasias da Mama/mortalidade , Feminino , Pessoa de Meia-Idade , Terapia Neoadjuvante/métodos , Receptor ErbB-2/metabolismo , Antraciclinas/uso terapêutico , Antraciclinas/administração & dosagem , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Estudos Retrospectivos , Trastuzumab/uso terapêutico , Ciclofosfamida/uso terapêutico , Ciclofosfamida/administração & dosagem , Docetaxel/uso terapêutico , Docetaxel/administração & dosagem , Taxoides/uso terapêutico , Taxoides/administração & dosagem , Doxorrubicina/uso terapêutico , Doxorrubicina/administração & dosagem , Hidrocarbonetos Aromáticos com Pontes/uso terapêutico , Hidrocarbonetos Aromáticos com Pontes/administração & dosagem , Resultado do Tratamento , Idoso , Anticorpos Monoclonais Humanizados
3.
World J Surg Oncol ; 22(1): 126, 2024 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-38725003

RESUMO

PURPOSE: This study investigated the changes in the fasting blood glucose (FBG), fasting triglyceride (FTG), and fasting total cholesterol (FTC) levels during neoadjuvant therapy (NAT) for human epidermal growth factor receptor 2 (HER2)-positive breast cancer (BC) and the association with pathologic complete response (pCR). METHODS: Relevant data from Sichuan Cancer Hospital from June 2019 to June 2022 were collected and analyzed, and FBG, FTG, and FTC were divided into baseline, change, and process groups, which were grouped to analyze the changes after receiving NAT and the association with pCR. RESULTS: In the estrogen receptor (ER)-negative subgroup, patients with low levels of FTG in the process group were more likely to achieve pCR compared to high levels, and in the progesterone receptor (PR)-negative subgroup, patients with lower FTG compared to higher FTG after receiving NAT was more likely to achieve pCR. CONCLUSIONS: Patients with HER2-positive BC undergoing NAT develop varying degrees of abnormalities (elevated or decreased) in FBG, FTG, and FTC; moreover, the status of FTG levels during NAT may predict pCR in ER-negative or PR-negative HER2-positive BC.Early monitoring and timely intervention for FTG abnormalities may enable this subset of patients to increase the likelihood of obtaining a pCR along with management of abnormal markers.


Assuntos
Biomarcadores Tumorais , Neoplasias da Mama , Terapia Neoadjuvante , Receptor ErbB-2 , Humanos , Feminino , Neoplasias da Mama/patologia , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/metabolismo , Neoplasias da Mama/terapia , Receptor ErbB-2/metabolismo , Terapia Neoadjuvante/métodos , Pessoa de Meia-Idade , Prognóstico , Biomarcadores Tumorais/metabolismo , Seguimentos , Glicemia/análise , Glicemia/metabolismo , Adulto , Receptores de Estrogênio/metabolismo , Triglicerídeos/sangue , Triglicerídeos/metabolismo , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Estudos Retrospectivos , Receptores de Progesterona/metabolismo , Colesterol/metabolismo , Colesterol/sangue , Idoso , Resposta Patológica Completa
4.
Clin Respir J ; 18(5): e13756, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38725310

RESUMO

INTRODUCTION: This meta-analysis sought to investigate the effect of neoadjuvant chemotherapy (NACT) combined with surgery in patients with nonsmall cell lung cancer (NSCLC). METHODS: With time span from January 2010 to December 2022, PubMed, Web of Science and Embase, China National Knowledge Infrastructure, and WanFang databases were searched for randomized controlled trials on comparison between NACT combined with surgery and surgery alone in patients with NSCLC. Then a meta-analysis was performed in accordance with Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. RESULTS: A total of 1511 studies were retrieved and 12 were finally included. Meta-analysis results showed that compared with surgery alone, a combination of NACT and surgery was associated with higher treatment response rate (odds ratio, OR = 2.459, 95% confidence interval, CI [1.785, 3.388], P < 0.001), 1-year survival rate (OR = 2.185, 95% CI [1.608, 2.970], P < 0.001), and 3-year survival rate (OR = 2.195, 95% CI [1.568, 3.073], P < 0.001) and lower levels of intraoperative blood loss (standardized mean difference, SMD = -0.932, 95% CI [-1.588, -0.275], P = 0.005) and length of hospital stay (SMD = -0.481, 95% CI [-0.933, -0.028], P = 0.037). CONCLUSION: NACT combined with surgery is superior to surgery alone in the treatment of NSCLC and can promote postoperative recovery. Collectively, such combination is a safe and effective treatment for patients with NSCLC.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Terapia Neoadjuvante , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/cirurgia , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/terapia , Terapia Neoadjuvante/métodos , Pneumonectomia/métodos , Taxa de Sobrevida , Resultado do Tratamento , Quimioterapia Adjuvante/métodos , Ensaios Clínicos Controlados Aleatórios como Assunto , Tempo de Internação/estatística & dados numéricos , Feminino , Terapia Combinada
5.
J Pak Med Assoc ; 74(4 (Supple-4)): S43-S48, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38712408

RESUMO

This narrative review explores the transformative potential of Artificial Intelligence (AI) and advanced imaging techniques in predicting Pathological Complete Response (pCR) in Breast Cancer (BC) patients undergoing Neo-Adjuvant Chemotherapy (NACT). Summarizing recent research findings underscores the significant strides made in the accurate assessment of pCR using AI, including deep learning and radiomics. Such AI-driven models offer promise in optimizing clinical decisions, personalizing treatment strategies, and potentially reducing the burden of unnecessary treatments, thereby improving patient outcomes. Furthermore, the review acknowledges the potential of AI to address healthcare disparities in Low- and Middle-Income Countries (LMICs), where accessible and scalable AI solutions may enhance BC management. Collaboration and international efforts are essential to fully unlock the potential of AI in BC care, offering hope for a more equitable and effective approach to treatment worldwide.


Assuntos
Inteligência Artificial , Neoplasias da Mama , Humanos , Neoplasias da Mama/terapia , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/patologia , Feminino , Terapia Neoadjuvante/métodos , Aprendizado Profundo , Quimioterapia Adjuvante
6.
Front Immunol ; 15: 1355130, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38742103

RESUMO

Pre-operative radiation therapy is not currently integrated into the treatment protocols for breast cancer. However, transforming immunological "cold" breast cancers by neoadjuvant irradiation into their "hot" variants is supposed to elicit an endogenous tumor immune defense and, thus, enhance immunotherapy efficiency. We investigated cellular and immunological effects of sub-lethal, neoadjuvant irradiation of ER pos., HER2 pos., and triple-negative breast cancer subtypes in-vitro and in-vivo in humanized tumor mice (HTM). This mouse model is characterized by a human-like immune system and therefore facilitates detailed analysis of the mechanisms and efficiency of neoadjuvant, irradiation-induced "in-situ vaccination", especially in the context of concurrently applied checkpoint therapy. Similar to clinical appearances, we observed a gradually increased immunogenicity from the luminal over the HER2-pos. to the triple negative subtype in HTM indicated by an increasing immune cell infiltration into the tumor tissue. Anti-PD-L1 therapy divided the HER2-pos. and triple negative HTM groups into responder and non-responder, while the luminal HTMs were basically irresponsive. Irradiation alone was effective in the HER2-pos. and luminal subtype-specific HTM and was supportive for overcoming irresponsiveness to single anti-PD-L1 treatment. The treatment success correlated with a significantly increased T cell proportion and PD-1 expression in the spleen. In all subtype-specific HTM combination therapy proved most effective in diminishing tumor growth, enhancing the immune response, and converted non-responder into responder during anti-PD-L1 therapy. In HTM, neoadjuvant irradiation reinforced anti-PD-L1 checkpoint treatment of breast cancer in a subtype -specific manner. According to the "bench to bedside" principle, this study offers a vital foundation for clinical translating the use of neoadjuvant irradiation in the context of checkpoint therapy.


Assuntos
Antígeno B7-H1 , Inibidores de Checkpoint Imunológico , Terapia Neoadjuvante , Receptor ErbB-2 , Neoplasias de Mama Triplo Negativas , Animais , Feminino , Neoplasias de Mama Triplo Negativas/imunologia , Neoplasias de Mama Triplo Negativas/radioterapia , Neoplasias de Mama Triplo Negativas/terapia , Terapia Neoadjuvante/métodos , Camundongos , Humanos , Receptor ErbB-2/metabolismo , Inibidores de Checkpoint Imunológico/uso terapêutico , Inibidores de Checkpoint Imunológico/farmacologia , Linhagem Celular Tumoral , Receptores de Estrogênio/metabolismo , Modelos Animais de Doenças , Ensaios Antitumorais Modelo de Xenoenxerto , Neoplasias da Mama/imunologia , Neoplasias da Mama/radioterapia , Neoplasias da Mama/terapia
7.
Minerva Urol Nephrol ; 76(2): 141-147, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38742549

RESUMO

INTRODUCTION: Patients with high-risk prostate cancer (HRPCa) are prone to have worse pathological features, resulting in early biochemical recurrence after radical prostatectomy (RP). There is an urgent need to develop novel treatment strategies for this group of patients to optimize their outcomes. The purpose of this study is to perform a systematic review of the role of neoadjuvant hormonal therapy (NHT) followed by RP in HRPCa patients. EVIDENCE ACQUISITION: We performed a systematic review of the following databases, MEDLINE (PubMed), EMBASE, Cochrane Library, and clinical Trial.gov; between January 2007 and August 2023, following the PRISMA guidelines. EVIDENCE SYNTHESIS: After screening and deduplication, we included ten studies from an initial pool of 1275. The risk of bias was low in observational studies but ranged from moderate to low in controlled trials. Five studies utilized traditional androgen deprivation treatments (ADT), revealing favorable pathological outcomes but inconsistency in evaluating oncological results. Additionally, four studies focused on RP combined with androgen receptor pathway inhibitors (ARPIs) in the NHT setting, all showing primarily positive pathological outcome, with no clear evidence of an oncological benefit. Limited long-term follow-up data and a shortage of randomized controlled trials were evident among all the studies included in this review, regardless of the type of hormonal treatment used. CONCLUSIONS: Different hormonal treatments, including traditional ADT and ARPIs, yield positive pathology outcomes. Oncological evidence remains limited, echoing older findings predating ARPIs. Definitive conclusions require longer follow-ups and precise patient selection. Currently, insufficient evidence support ARPIs' superiority over conventional therapy before RP.


Assuntos
Antagonistas de Androgênios , Prostatectomia , Neoplasias da Próstata , Humanos , Neoplasias da Próstata/cirurgia , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/patologia , Masculino , Antagonistas de Androgênios/uso terapêutico , Terapia Neoadjuvante/métodos , Medição de Risco
8.
Breast Cancer Res ; 26(1): 77, 2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38745321

RESUMO

BACKGROUND: Early prediction of pathological complete response (pCR) is important for deciding appropriate treatment strategies for patients. In this study, we aimed to quantify the dynamic characteristics of dynamic contrast-enhanced magnetic resonance images (DCE-MRI) and investigate its value to improve pCR prediction as well as its association with tumor heterogeneity in breast cancer patients. METHODS: The DCE-MRI, clinicopathologic record, and full transcriptomic data of 785 breast cancer patients receiving neoadjuvant chemotherapy were retrospectively included from a public dataset. Dynamic features of DCE-MRI were computed from extracted phase-varying radiomic feature series using 22 CAnonical Time-sereis CHaracteristics. Dynamic model and radiomic model were developed by logistic regression using dynamic features and traditional radiomic features respectively. Various combined models with clinical factors were also developed to find the optimal combination and the significance of each components was evaluated. All the models were evaluated in independent test set in terms of area under receiver operating characteristic curve (AUC). To explore the potential underlying biological mechanisms, radiogenomic analysis was implemented on patient subgroups stratified by dynamic model to identify differentially expressed genes (DEGs) and enriched pathways. RESULTS: A 10-feature dynamic model and a 4-feature radiomic model were developed (AUC = 0.688, 95%CI: 0.635-0.741 and AUC = 0.650, 95%CI: 0.595-0.705) and tested (AUC = 0.686, 95%CI: 0.594-0.778 and AUC = 0.626, 95%CI: 0.529-0.722), with the dynamic model showing slightly higher AUC (train p = 0.181, test p = 0.222). The combined model of clinical, radiomic, and dynamic achieved the highest AUC in pCR prediction (train: 0.769, 95%CI: 0.722-0.816 and test: 0.762, 95%CI: 0.679-0.845). Compared with clinical-radiomic combined model (train AUC = 0.716, 95%CI: 0.665-0.767 and test AUC = 0.695, 95%CI: 0.656-0.714), adding the dynamic component brought significant improvement in model performance (train p < 0.001 and test p = 0.005). Radiogenomic analysis identified 297 DEGs, including CXCL9, CCL18, and HLA-DPB1 which are known to be associated with breast cancer prognosis or angiogenesis. Gene set enrichment analysis further revealed enrichment of gene ontology terms and pathways related to immune system. CONCLUSION: Dynamic characteristics of DCE-MRI were quantified and used to develop dynamic model for improving pCR prediction in breast cancer patients. The dynamic model was associated with tumor heterogeniety in prognostic-related gene expression and immune-related pathways.


Assuntos
Neoplasias da Mama , Meios de Contraste , Imageamento por Ressonância Magnética , Humanos , Feminino , Neoplasias da Mama/genética , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/patologia , Neoplasias da Mama/metabolismo , Imageamento por Ressonância Magnética/métodos , Pessoa de Meia-Idade , Adulto , Estudos Retrospectivos , Terapia Neoadjuvante , Prognóstico , Curva ROC , Transcriptoma , Idoso , Resultado do Tratamento
9.
Saudi Med J ; 45(5): 481-489, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38734428

RESUMO

OBJECTIVES: To assess the clinical relevance and prognostic value of changes in the Naples prognostic score (NPS) after neoadjuvant chemoradiotherapy (NACR) among esophageal squamous cell carcinoma (ESCC) patients. METHODS: We studied 232 locally advanced ESCC patients who received NACR before undergoing esophagectomy retrospectively. Categorizing individuals into the elevated NPS group and the non-elevated NPS group based on the change in NPS after NACR (ΔNPS > 0 or ∆NPS ≤ 0), we examined and compared the clinicopathological characteristics, survival rates, and postoperative complications between these 2 groups (∆NPS = post-NACR NPS - pre-NACR NPS). RESULTS: Results: Out of the 232 patients enrolled, 105 exhibited elevated NPS levels, while 127 showed non-elevated NPS levels. Survival analyses indicated inferior overall survival (OS) (p=0.024) and recurrence-free survival (RFS) (p=0.047) in the elevated NPS cohort compared to the non-elevated NPS cohort. Subsequent cox regression analyses identified the post-NACR change in NPS as an independent prognostic indicator for RFS (p=0.029) and OS (p=0.036). CONCLUSION: Elevated NPS post-NACR emerged as a significant indicator of worse prognosis for locally advanced ESCC patients who underwent NACR. This finding has great potential to be useful for recognizing high-risk ESCC patients who received NACR before undergoing esophagectomy and making individualized subsequent therapeutic decisions in clinical practice.


Assuntos
Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Esofagectomia , Terapia Neoadjuvante , Humanos , Feminino , Neoplasias Esofágicas/terapia , Neoplasias Esofágicas/mortalidade , Neoplasias Esofágicas/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Carcinoma de Células Escamosas do Esôfago/terapia , Carcinoma de Células Escamosas do Esôfago/mortalidade , Carcinoma de Células Escamosas do Esôfago/patologia , Estudos Retrospectivos , Idoso , Carcinoma de Células Escamosas/terapia , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/patologia , Taxa de Sobrevida , Quimiorradioterapia/métodos , Intervalo Livre de Doença
10.
Clin Respir J ; 18(5): e13761, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38693705

RESUMO

BACKGROUND: In order to improve survival outcomes in resectable non-small cell lung cancer (NSCLC), strategies for neoadjuvant therapy need to be revisited. We evaluated and compared the efficacy of different neoadjuvant therapeutic modalities in a real-world setting. METHODS: A total of 258 patients with clinical stage IIA to IIIB NSCLC was included. All the patients underwent surgical resection after one to four cycles of neoadjuvant treatment consisting of chemotherapy (83), immunotherapy (23), and immunotherapy plus chemotherapy (152). RESULTS: The radiologic response rate in the combined immunochemotherapy group was 67.8%, higher than that of 48.2% in the chemotherapy group and 4.3% in the immunotherapy group (p < 0.001). An improved major pathological response (MPR) was also achieved in the combined therapy group compared with the chemotherapy group and the immunotherapy group (53.9% vs. 10.8% vs. 8.7%, p < 0.001). Patients in the combined therapy group had a significant trend toward longer disease-free survival than those in the chemotherapy alone group (3-year disease-free survival [DFS] of 68.79% vs. 50.81%; hazard ratio [HR] for progression or death, 0.477; p = 0.003). Multivariate Cox analysis identified radical surgery (HR, 0.328; p = 0.033), ypN0-1 stage (HR, 0.591; p = 0.038) and MPR result (HR, 0.362; p = 0.007) to be independent prognostic factors for DFS. CONCLUSIONS: Neoadjuvant treatment with a combination of immunotherapy plus chemotherapy appears to achieve higher radiological and pathological responses than monotherapy for IIA-IIIB NSCLC. Log-rank analysis showed that a better outcome could be expected in patients with the addition of immunotherapy to neoadjuvant chemotherapy if compared with patients with chemotherapy alone in terms of DFS.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Imunoterapia , Neoplasias Pulmonares , Terapia Neoadjuvante , Humanos , Carcinoma Pulmonar de Células não Pequenas/terapia , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Terapia Neoadjuvante/métodos , Masculino , Feminino , Neoplasias Pulmonares/terapia , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/tratamento farmacológico , Pessoa de Meia-Idade , Idoso , Imunoterapia/métodos , Estadiamento de Neoplasias , Resultado do Tratamento , Estudos Retrospectivos , Pneumonectomia/métodos , Intervalo Livre de Doença , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico
11.
Cancer Med ; 13(9): e7222, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38698687

RESUMO

BACKGROUND: The prognostic predictive tool for patients with colorectal liver metastasis (CRLM) is limited and the criteria for administering preoperative neoadjuvant chemotherapy in CRLM patients remain controversial. METHODS: This study enrolled 532 CRLM patients at West China Hospital (WCH) from January 2009 to December 2019. Prognostic factors were identified from the training cohort to construct a WCH-nomogram and evaluating accuracy in the validation cohort. Receiver operating characteristic (ROC) curve analysis was used to compare the prediction accuracy with other existing prediction tools. RESULTS: From the analysis of the training cohort, four independent prognostic risk factors, namely tumor marker score, KRAS mutation, primary lymph node metastasis, and tumor burden score were identified on which a WCH-nomogram was constructed. The C-index of the two cohorts were 0.674 (95% CI: 0.634-0.713) and 0.655 (95% CI: 0.586-0.723), respectively, which was better than the previously reported predication scores (CRS, m-CS and GAME score). ROC curves showed AUCs for predicting 1-, 3-, and 5-year overall survival (OS) of 0.758, 0.709, and 0.717 in the training cohort, and 0.860, 0.669, and 0.692 in the validation cohort, respectively. A cutoff value of 114.5 points was obtained for the WCH-nomogram total score based on the maximum Youden index of the ROC curve of 5-year OS. Risk stratification showed significantly better prognosis in the low-risk group, however, the high-risk group was more likely to benefit from neoadjuvant chemotherapy. CONCLUSIONS: The WCH-nomogram demonstrates superior prognostic stratification compared to prior scoring systems, effectively identifying CRLM patients who may benefit the most from neoadjuvant chemotherapy.


Assuntos
Neoplasias Colorretais , Hepatectomia , Neoplasias Hepáticas , Nomogramas , Humanos , Neoplasias Colorretais/patologia , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/cirurgia , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/cirurgia , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/tratamento farmacológico , Masculino , Feminino , Pessoa de Meia-Idade , Prognóstico , Idoso , Curva ROC , Terapia Neoadjuvante , Biomarcadores Tumorais , Adulto , Proteínas Proto-Oncogênicas p21(ras)/genética , Fatores de Risco , Estudos Retrospectivos , China , Metástase Linfática , Mutação , Carga Tumoral
12.
BJS Open ; 8(3)2024 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-38747103

RESUMO

BACKGROUND: Neoadjuvant therapy has an established role in the treatment of patients with colorectal cancer. However, its role continues to evolve due to both advances in the available treatment modalities, and refinements in the indications for neoadjuvant treatment and subsequent surgery. METHODS: A narrative review of the most recent relevant literature was conducted. RESULTS: Short-course radiotherapy and long-course chemoradiotherapy have an established role in improving local but not systemic disease control in patients with rectal cancer. Total neoadjuvant therapy offers advantages over short-course radiotherapy and long-course chemoradiotherapy, not only in terms of increased local response but also in reducing the risk of systemic relapses. Non-operative management is increasingly preferred to surgery in patients with rectal cancer and clinical complete responses but is still associated with some negative impacts on functional outcomes. Neoadjuvant chemotherapy may be of some benefit in patients with locally advanced colon cancer with proficient mismatch repair, although patient selection is a major challenge. Neoadjuvant immunotherapy in patients with deficient mismatch repair cancers in the colon or rectum is altering the treatment paradigm for these patients. CONCLUSION: Neoadjuvant treatments for patients with colon or rectal cancers continue to evolve, increasing the complexity of decision-making for patients and clinicians alike. This review describes the current guidance and most recent developments.


Assuntos
Neoplasias Colorretais , Terapia Neoadjuvante , Humanos , Neoplasias Colorretais/terapia , Imunoterapia/métodos , Neoplasias Retais/terapia , Neoplasias Retais/patologia , Quimiorradioterapia/métodos
14.
Cancer Cell ; 42(5): 727-731, 2024 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-38701791

RESUMO

As immunotherapy makes its way into the perioperative setting, a growing number of clinical trials are expanding the evidence base for resectable non-small cell lung cancer (NSCLC) management. Identifying the optimal treatment pattern-whether it's neoadjuvant, adjuvant, or a combination of both-is a crucial next step, particularly in pinpointing which patients benefit the most. This decision-making process requires a multi-disciplinary treatment team capable of utilizing tissue and plasma genomic testing to inform therapeutic choices. Leveraging the perioperative treatment platform, it remains pivotal to integrate circulating tumor DNA (ctDNA) monitoring into clinical trial design efficiently and provide clear guidance on treatment.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Imunoterapia , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/imunologia , Carcinoma Pulmonar de Células não Pequenas/terapia , Carcinoma Pulmonar de Células não Pequenas/genética , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/terapia , Imunoterapia/métodos , DNA Tumoral Circulante/sangue , DNA Tumoral Circulante/genética , Biomarcadores Tumorais/genética , Terapia Neoadjuvante/métodos , Ensaios Clínicos como Assunto
15.
Clin Transl Med ; 14(5): e1687, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38738791

RESUMO

OBJECTIVE: It has been observed that the prognosis of patients with HER2-positive metastatic breast cancer has improved significantly with HER2-targeted agents. However, there is still a lack of evidence regarding first-line anti-HER2 treatment options for patients who have received adjuvant and/or neoadjuvant trastuzumab for HER2-positive metastatic breast cancer. Besides, there are no reliable markers that can predict the efficacy of anti-HER2 treatment in these patients. METHODS: Patients who have received adjuvant and/or neoadjuvant trastuzumab for HER2-positive metastatic breast cancer were enrolled. Pyrotinib plus albumin-bound paclitaxel were used as first-line treatment. The primary endpoint was the objective response rate (ORR). The safety profile was also assessed. In order to explore predictive biomarkers using Olink technology, blood samples were collected dynamically. RESULTS: From December 2019 to August 2023, the first stage of the study involved 27 eligible patients. It has not yet reached the median PFS despite the median follow-up being 17.8 months. Efficacy evaluation showed that the ORR was 92.6%, and the DCR was 100%. Adverse events of grade 3 or higher included diarrhoea (29.6%), leukopenia (11.1%), neutropenia (25.9%), oral mucositis (3.7%), and hand-foot syndrome (3.7%). Toll-like receptor 3 (TLR3) and Proto-oncogene tyrosine-protein kinase receptor (RET) were proteins with significant relevance to PFS in these patients. CONCLUSIONS: This study demonstrates that pyrotinib plus albumin-bound paclitaxel as a first-line treatment regimen shows good efficacy and manageable safety for patients who have received adjuvant and/or neoadjuvant trastuzumab for HER2-positive metastatic breast cancer. Besides, a significant association was identified between the expression levels of TLR3 and RET and the PFS in patients.


Assuntos
Neoplasias da Mama , Receptor ErbB-2 , Trastuzumab , Humanos , Feminino , Neoplasias da Mama/tratamento farmacológico , Pessoa de Meia-Idade , Adulto , Trastuzumab/uso terapêutico , Trastuzumab/farmacologia , Estudos Prospectivos , Idoso , Receptor ErbB-2/metabolismo , Paclitaxel Ligado a Albumina/uso terapêutico , Paclitaxel Ligado a Albumina/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Acrilamidas/uso terapêutico , Terapia Neoadjuvante/métodos , Proto-Oncogene Mas , Ácidos Sulfínicos/uso terapêutico , Ácidos Sulfínicos/farmacologia , Aminoquinolinas/uso terapêutico , Aminoquinolinas/farmacologia , Resultado do Tratamento
16.
Chirurgie (Heidelb) ; 95(6): 495-509, 2024 Jun.
Artigo em Alemão | MEDLINE | ID: mdl-38739162

RESUMO

Multimodal treatment approaches with neoadjuvant radiotherapy and chemotherapy followed by oncological and total mesorectal excision (TME) have significantly reduced the recurrence rate even in locally advanced rectal cancer. Nevertheless, up to 10% of patients develop a local relapse. Surgical R0 resection is the only chance of a cure in the treatment of locally recurrent rectal cancer (LRRC). Due to the altered anatomy and physiology of the true pelvis as a result of the pretreatment and operations as well as the localization and extent of the recurrence, the treatment decision is individualized and remains a challenge for the interdisciplinary team. Even locally advanced tumors with involvement of adjacent structures can be treated in designated centers using multimodal treatment concepts with potentially curative intent.


Assuntos
Recidiva Local de Neoplasia , Neoplasias Retais , Neoplasias Retais/terapia , Neoplasias Retais/patologia , Neoplasias Retais/cirurgia , Humanos , Recidiva Local de Neoplasia/patologia , Terapia Neoadjuvante/métodos , Terapia Combinada , Estadiamento de Neoplasias
18.
BMC Cancer ; 24(1): 585, 2024 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-38741038

RESUMO

OBJECTIVE: The optimal timing for surgery following neoadjuvant immunochemotherapy for lung squamous cell carcinoma appears to be a topic of limited data. Many clinical studies lack stringent guidelines regarding this timing. The objective of this study is to explore the effect of the interval between neoadjuvant immunochemotherapy and surgery on survival outcomes in patients with lung squamous cell carcinoma. METHODS: This study conducted a retrospective analysis of patients with lung squamous cell carcinoma who underwent neoadjuvant immunochemotherapy between January 2019 and October 2022 at The First Affiliated Hospital, Zhejiang University School of Medicine. Patients were divided into two groups based on the treatment interval: ≤33 days and > 33 days. The primary observational endpoints of the study were Disease-Free Survival (DFS) and Overall Survival (OS). Secondary observational endpoints included Objective response rate (ORR), Major Pathological Response (MPR), and Pathological Complete Remission (pCR). RESULTS: Using the Kaplan-Meier methods, the ≤ 33d group demonstrated a superior DFS curve compared to the > 33d group (p = 0.0015). The median DFS for the two groups was 952 days and 590 days, respectively. There was no statistical difference in the OS curves between the groups (p = 0.66), and the median OS was not reached for either group. The treatment interval did not influence the pathologic response of the tumor or lymph nodes. CONCLUSIONS: The study observed that shorter treatment intervals were associated with improved DFS, without influencing OS, pathologic response, or surgical safety. Patients should avoid having a prolonged treatment interval between neoadjuvant immunochemotherapy and surgery.


Assuntos
Carcinoma de Células Escamosas , Neoplasias Pulmonares , Terapia Neoadjuvante , Humanos , Masculino , Terapia Neoadjuvante/métodos , Feminino , Neoplasias Pulmonares/terapia , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Pessoa de Meia-Idade , Estudos Retrospectivos , Idoso , Carcinoma de Células Escamosas/terapia , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/patologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Intervalo Livre de Doença , Pneumonectomia , Tempo para o Tratamento , Adulto , Resultado do Tratamento
20.
Cancer Med ; 13(9): e7176, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38716645

RESUMO

BACKGROUND: In recent years, neoadjuvant immunotherapy (NAIT) has developed rapidly in patients with gastroesophageal junction cancer (GEJC). The suggested neoadjuvant treatment regimens for patients with GEJC may vary in light of the efficacy and safety results. METHODS: A search of the Cochrane Library, PubMed, Embase, and Web of Science was completed to locate studies examining the safety and effectiveness of NAIT for resectable GEJC. We analyzed the effect sizes (ES) and 95% confidence intervals (CI) in addition to subgroups and heterogeneity. Meta-analyses were performed using Stata BE17 software. RESULTS: For these meta-analyses, 753 patients were chosen from 21 studies. The effectiveness of NAIT was assessed using the pathological complete response (pCR), major pathological response (MPR), and nodal downstage to ypN0 rate. The MPR, pCR, and nodal downstage to ypN0 rate values in NAIT were noticeably higher (MPR: ES = 0.45; 95% CI: 0.36-0.54; pCR: ES = 0.26; 95% CI: 0.21-0.32; nodal downstage to ypN0 rate: ES = 0.60; 95% CI: 0.48-0.72) than those of neoadjuvant chemotherapy (nCT) or neoadjuvant chemoradiotherapy (nCRT) (MPR < 30%; pCR: ES = 3%-17%; nodal downstage to ypN0 rate: ES = 21%-29%). Safety was assessed using the treatment-related adverse events (trAEs) incidence rate, surgical delay rate, surgical complications incidence rate, and surgical resection rate. In conclusion, the incidence of trAEs, incidence of surgical complications, and surgical delay rate had ES values of 0.66, 0.48, and 0.09, respectively. These rates were comparable to those from nCT or nCRT (95% CI: 0.60-0.70; 0.15-0.51; and 0, respectively). The reported resection rates of 85%-95% with nCT or nCRT were comparable to the mean surgical resection rate of 90%. CONCLUSION: NAIT is an effective treatment for resectable GEJC; additionally, the level of NAIT toxicity is acceptable. The long-term effects of NAIT require further study.


Assuntos
Neoplasias Esofágicas , Junção Esofagogástrica , Imunoterapia , Terapia Neoadjuvante , Neoplasias Gástricas , Humanos , Terapia Neoadjuvante/métodos , Junção Esofagogástrica/patologia , Neoplasias Esofágicas/terapia , Neoplasias Esofágicas/patologia , Neoplasias Gástricas/terapia , Neoplasias Gástricas/patologia , Imunoterapia/métodos , Resultado do Tratamento
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