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1.
Front Immunol ; 15: 1312380, 2024.
Article En | MEDLINE | ID: mdl-38726002

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.


Esophageal Neoplasms , Esophageal Squamous Cell Carcinoma , Neoadjuvant Therapy , Tumor Microenvironment , Humans , Tumor Microenvironment/immunology , Esophageal Squamous Cell Carcinoma/therapy , Esophageal Squamous Cell Carcinoma/immunology , Esophageal Squamous Cell Carcinoma/drug therapy , Neoadjuvant Therapy/methods , Esophageal Neoplasms/therapy , Esophageal Neoplasms/immunology , Esophageal Neoplasms/drug therapy , Male , Female , Middle Aged , Retrospective Studies , Prognosis , Aged , Biomarkers, Tumor , Treatment Outcome , Immunotherapy/methods
2.
Sci Rep ; 14(1): 10632, 2024 05 09.
Article En | MEDLINE | ID: mdl-38724585

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.


Anthracyclines , Antineoplastic Combined Chemotherapy Protocols , Breast Neoplasms , Neoadjuvant Therapy , Receptor, ErbB-2 , Trastuzumab , Humans , Breast Neoplasms/drug therapy , Breast Neoplasms/metabolism , Breast Neoplasms/pathology , Breast Neoplasms/mortality , Female , Middle Aged , Neoadjuvant Therapy/methods , Receptor, ErbB-2/metabolism , Anthracyclines/therapeutic use , Anthracyclines/administration & dosage , Adult , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Retrospective Studies , Trastuzumab/therapeutic use , Cyclophosphamide/therapeutic use , Cyclophosphamide/administration & dosage , Docetaxel/therapeutic use , Docetaxel/administration & dosage , Taxoids/therapeutic use , Taxoids/administration & dosage , Doxorubicin/therapeutic use , Doxorubicin/administration & dosage , Bridged-Ring Compounds/therapeutic use , Bridged-Ring Compounds/administration & dosage , Treatment Outcome , Aged , Antibodies, Monoclonal, Humanized
3.
World J Surg Oncol ; 22(1): 126, 2024 May 09.
Article En | MEDLINE | ID: mdl-38725003

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.


Biomarkers, Tumor , Breast Neoplasms , Neoadjuvant Therapy , Receptor, ErbB-2 , Humans , Female , Breast Neoplasms/pathology , Breast Neoplasms/drug therapy , Breast Neoplasms/metabolism , Breast Neoplasms/therapy , Receptor, ErbB-2/metabolism , Neoadjuvant Therapy/methods , Middle Aged , Prognosis , Biomarkers, Tumor/metabolism , Follow-Up Studies , Blood Glucose/analysis , Blood Glucose/metabolism , Adult , Receptors, Estrogen/metabolism , Triglycerides/blood , Triglycerides/metabolism , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Retrospective Studies , Receptors, Progesterone/metabolism , Cholesterol/metabolism , Cholesterol/blood , Aged , Pathologic Complete Response
4.
Clin Respir J ; 18(5): e13756, 2024 May.
Article En | MEDLINE | ID: mdl-38725310

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.


Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Neoadjuvant Therapy , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/surgery , Carcinoma, Non-Small-Cell Lung/pathology , Carcinoma, Non-Small-Cell Lung/mortality , Humans , Lung Neoplasms/drug therapy , Lung Neoplasms/surgery , Lung Neoplasms/pathology , Lung Neoplasms/mortality , Lung Neoplasms/therapy , Neoadjuvant Therapy/methods , Pneumonectomy/methods , Survival Rate , Treatment Outcome , Chemotherapy, Adjuvant/methods , Randomized Controlled Trials as Topic , Length of Stay/statistics & numerical data , Female , Combined Modality Therapy
5.
J Pak Med Assoc ; 74(4 (Supple-4)): S43-S48, 2024 Apr.
Article En | MEDLINE | ID: mdl-38712408

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.


Artificial Intelligence , Breast Neoplasms , Humans , Breast Neoplasms/therapy , Breast Neoplasms/diagnostic imaging , Breast Neoplasms/pathology , Female , Neoadjuvant Therapy/methods , Deep Learning , Chemotherapy, Adjuvant
6.
Front Immunol ; 15: 1355130, 2024.
Article En | MEDLINE | ID: mdl-38742103

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.


B7-H1 Antigen , Immune Checkpoint Inhibitors , Neoadjuvant Therapy , Receptor, ErbB-2 , Triple Negative Breast Neoplasms , Animals , Female , Triple Negative Breast Neoplasms/immunology , Triple Negative Breast Neoplasms/radiotherapy , Triple Negative Breast Neoplasms/therapy , Neoadjuvant Therapy/methods , Mice , Humans , Receptor, ErbB-2/metabolism , Immune Checkpoint Inhibitors/therapeutic use , Immune Checkpoint Inhibitors/pharmacology , Cell Line, Tumor , Receptors, Estrogen/metabolism , Disease Models, Animal , Xenograft Model Antitumor Assays , Breast Neoplasms/immunology , Breast Neoplasms/radiotherapy , Breast Neoplasms/therapy
7.
Minerva Urol Nephrol ; 76(2): 141-147, 2024 Apr.
Article En | MEDLINE | ID: mdl-38742549

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.


Androgen Antagonists , Prostatectomy , Prostatic Neoplasms , Humans , Prostatic Neoplasms/surgery , Prostatic Neoplasms/drug therapy , Prostatic Neoplasms/pathology , Male , Androgen Antagonists/therapeutic use , Neoadjuvant Therapy/methods , Risk Assessment
8.
Clin Respir J ; 18(5): e13761, 2024 May.
Article En | MEDLINE | ID: mdl-38693705

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.


Carcinoma, Non-Small-Cell Lung , Immunotherapy , Lung Neoplasms , Neoadjuvant Therapy , Humans , Carcinoma, Non-Small-Cell Lung/therapy , Carcinoma, Non-Small-Cell Lung/pathology , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/mortality , Neoadjuvant Therapy/methods , Male , Female , Lung Neoplasms/therapy , Lung Neoplasms/pathology , Lung Neoplasms/mortality , Lung Neoplasms/drug therapy , Middle Aged , Aged , Immunotherapy/methods , Neoplasm Staging , Treatment Outcome , Retrospective Studies , Pneumonectomy/methods , Disease-Free Survival , Adult , Antineoplastic Combined Chemotherapy Protocols/therapeutic use
9.
Cancer Cell ; 42(5): 727-731, 2024 May 13.
Article En | MEDLINE | ID: mdl-38701791

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.


Carcinoma, Non-Small-Cell Lung , Immunotherapy , Lung Neoplasms , Humans , Carcinoma, Non-Small-Cell Lung/immunology , Carcinoma, Non-Small-Cell Lung/therapy , Carcinoma, Non-Small-Cell Lung/genetics , Lung Neoplasms/immunology , Lung Neoplasms/genetics , Lung Neoplasms/therapy , Immunotherapy/methods , Circulating Tumor DNA/blood , Circulating Tumor DNA/genetics , Biomarkers, Tumor/genetics , Neoadjuvant Therapy/methods , Clinical Trials as Topic
10.
Clin Transl Med ; 14(5): e1687, 2024 May.
Article En | MEDLINE | ID: mdl-38738791

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.


Breast Neoplasms , Receptor, ErbB-2 , Trastuzumab , Humans , Female , Breast Neoplasms/drug therapy , Middle Aged , Adult , Trastuzumab/therapeutic use , Trastuzumab/pharmacology , Prospective Studies , Aged , Receptor, ErbB-2/metabolism , Albumin-Bound Paclitaxel/therapeutic use , Albumin-Bound Paclitaxel/pharmacology , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/pharmacology , Acrylamides/therapeutic use , Neoadjuvant Therapy/methods , Proto-Oncogene Mas , Sulfinic Acids/therapeutic use , Sulfinic Acids/pharmacology , Aminoquinolines/therapeutic use , Aminoquinolines/pharmacology , Treatment Outcome
11.
Chirurgie (Heidelb) ; 95(6): 495-509, 2024 Jun.
Article De | MEDLINE | ID: mdl-38739162

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.


Neoplasm Recurrence, Local , Rectal Neoplasms , Rectal Neoplasms/therapy , Rectal Neoplasms/pathology , Rectal Neoplasms/surgery , Humans , Neoplasm Recurrence, Local/pathology , Neoadjuvant Therapy/methods , Combined Modality Therapy , Neoplasm Staging
13.
BMC Cancer ; 24(1): 585, 2024 May 13.
Article En | MEDLINE | ID: mdl-38741038

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.


Carcinoma, Squamous Cell , Lung Neoplasms , Neoadjuvant Therapy , Humans , Male , Neoadjuvant Therapy/methods , Female , Lung Neoplasms/therapy , Lung Neoplasms/mortality , Lung Neoplasms/drug therapy , Lung Neoplasms/pathology , Middle Aged , Retrospective Studies , Aged , Carcinoma, Squamous Cell/therapy , Carcinoma, Squamous Cell/mortality , Carcinoma, Squamous Cell/drug therapy , Carcinoma, Squamous Cell/pathology , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Disease-Free Survival , Pneumonectomy , Time-to-Treatment , Adult , Treatment Outcome
15.
Cancer Med ; 13(9): e7176, 2024 May.
Article En | MEDLINE | ID: mdl-38716645

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.


Esophageal Neoplasms , Esophagogastric Junction , Immunotherapy , Neoadjuvant Therapy , Stomach Neoplasms , Humans , Neoadjuvant Therapy/methods , Esophagogastric Junction/pathology , Esophageal Neoplasms/therapy , Esophageal Neoplasms/pathology , Stomach Neoplasms/therapy , Stomach Neoplasms/pathology , Immunotherapy/methods , Treatment Outcome
16.
Genes Chromosomes Cancer ; 63(5): e23240, 2024 May.
Article En | MEDLINE | ID: mdl-38722225

Both primary and secondary breast angiosarcoma (AS) are characterized by multifocal presentation and aggressive behavior. Despite multimodality therapy, local and distant relapse rates remain high. Therefore, neoadjuvant chemotherapy (NACT) is employed to improve the R0 resection rates and survival, but its benefits remain controversial. Herein, we investigate pathologic and molecular correlates to NACT-induced histologic response in a group of 29 breast AS, 4 primary and 25 radiation-associated (RA). The two NACT regimens applied were anthracycline- and non-anthracycline-based. The pathologic response grade was defined as: I: ≤ 50%, II: 51%-90%, III: 91%-99%, and IV: 100%. An additional 45 primary AS and 102 RA-AS treated by surgery alone were included for survival comparison. The genomic landscape was analyzed in a subset of cases and compared to a cohort of AS without NACT on a paired tumor-normal targeted DNA NGS platform. All patients were females, with a median age of 31 years in primary AS and 68 years in RA-AS. All surgical margins were negative in NACT group. The NACT response was evenly divided between poor (Grades I-II; n = 15) and good responders (Grades III-IV; n = 14). Mitotic count >10/mm2 was the only factor inversely associated with pathologic response. By targeted NGS, all 10 post-NACT RA-AS demonstrated MYC amplification, while both primary AS harbored KDR mutations. TMB or other genomic alterations did not correlate with pathologic response. All four patients with Grade IV response remained free of disease. The good responders had a significantly better disease-specific survival (p = 0.04). There was no survival difference with NACT status or the NACT regimens applied. However, NACT patients with MYC-amplified tumors showed better disease-free survival (p = 0.04) compared to MYC-amplified patients without NACT. The overall survival of NACT group correlated with size >10 cm (p = 0.02), pathologic response (p = 0.04), and multifocality (p = 0.01) by univariate, while only size >10 cm (p = 0.03) remained significant by multivariate analysis.


Breast Neoplasms , Hemangiosarcoma , Neoadjuvant Therapy , Humans , Hemangiosarcoma/genetics , Hemangiosarcoma/pathology , Hemangiosarcoma/drug therapy , Female , Neoadjuvant Therapy/methods , Breast Neoplasms/genetics , Breast Neoplasms/drug therapy , Breast Neoplasms/pathology , Aged , Adult , Middle Aged , Aged, 80 and over , Mutation , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Anthracyclines/therapeutic use
17.
Cancer Immunol Immunother ; 73(7): 120, 2024 May 07.
Article En | MEDLINE | ID: mdl-38713243

PURPOSE: The optimal treatment after neoadjuvant chemoimmunotherapy for patients with stage III non-small cell lung cancer (NSCLC) is unclear. This study aimed at comparing the efficacy and safety of chemoradiotherapy and surgery after neoadjuvant chemoimmunotherapy in stage III NSCLC. MATERIALS AND METHODS: We conducted a real-world multicenter retrospective study on patients with stage III NSCLC who received surgery or chemoradiotherapy after neoadjuvant chemoimmunotherapy between October 2018 and December 2022. Progression-free survival (PFS) and overall survival (OS) were assessed from the initiation of neoadjuvant treatment and estimated by the Kaplan‒Meier method. Univariate and multivariate Cox regression models were used to examine potential prognostic factors. One-to-one propensity score matching (PSM) was used to further minimize confounding. RESULTS: A total of 239 eligible patients were enrolled, with 104 (43.5%) receiving surgery and 135 (56.5%) receiving CRT. After 1:1 PSM, 1- and 2-year PFS rates in patients receiving radical surgery (rSurgery group) vs. patients receiving definitive cCRT (dCCRT group) were 80.0% vs. 79.2% and 67.2% vs. 53.1%, respectively (P = 0.774). One- and 2-year OS rates were 97.5% vs. 97.4% and 87.3% vs. 89.9%, respectively (P = 0.558). Patients in the dCCRT group had a numerically lower incidence of distant metastases compared to those in the rSurgery group (42.9% vs. 70.6%, P = 0.119). The incidence of treatment-related adverse events was similar in both groups, except that the incidence of grade 3/4 hematological toxicity was significantly higher in the dCCRT group (30.0% vs. 10.0%, P = 0.025). CONCLUSION: Following neoadjuvant chemoimmunotherapy, definitive concurrent chemoradiotherapy may achieve noninferior outcomes to radical surgery in stage III NSCLC.


Carcinoma, Non-Small-Cell Lung , Chemoradiotherapy , Lung Neoplasms , Neoadjuvant Therapy , Neoplasm Staging , Humans , Carcinoma, Non-Small-Cell Lung/therapy , Carcinoma, Non-Small-Cell Lung/pathology , Carcinoma, Non-Small-Cell Lung/mortality , Female , Male , Retrospective Studies , Lung Neoplasms/therapy , Lung Neoplasms/pathology , Lung Neoplasms/mortality , Neoadjuvant Therapy/methods , Middle Aged , Chemoradiotherapy/methods , Aged , Immunotherapy/methods , Adult , Prognosis , Antineoplastic Combined Chemotherapy Protocols/therapeutic use
18.
J Cancer Res Clin Oncol ; 150(5): 223, 2024 Apr 30.
Article En | MEDLINE | ID: mdl-38691204

OBJECTIVE: To investigate the clinical value of contrast-enhanced computed tomography (CECT) radiomics for predicting the response of primary lesions to neoadjuvant chemotherapy in hepatoblastoma. METHODS: Clinical and CECT imaging data were retrospectively collected from 116 children with hepatoblastoma who received neoadjuvant chemotherapy. Tumor response was assessed according to the Response Evaluation Criteria in Solid Tumors (RECIST). Subsequently, they were randomly stratified into a training cohort and a test cohort in a 7:3 ratio. The clinical model was constructed using univariate and multivariate logistic regression, while the radiomics model was developed based on selected radiomics features employing the support vector machine algorithm. The combined clinical-radiomics model incorporated both clinical and radiomics features. RESULTS: The area under the curve (AUC) for the clinical, radiomics, and combined models was 0.704 (95% CI: 0.563-0.845), 0.830 (95% CI: 0.704-0.959), and 0.874 (95% CI: 0.768-0.981) in the training cohort, respectively. In the validation cohort, the combined model achieved the highest mean AUC of 0.830 (95% CI 0.616-0.999), with a sensitivity, specificity, accuracy, precision, and f1 score of 72.0%, 81.1%, 78.5%, 57.2%, and 63.5%, respectively. CONCLUSION: CECT radiomics has the potential to predict primary lesion response to neoadjuvant chemotherapy in hepatoblastoma.


Contrast Media , Hepatoblastoma , Liver Neoplasms , Neoadjuvant Therapy , Tomography, X-Ray Computed , Humans , Hepatoblastoma/drug therapy , Hepatoblastoma/diagnostic imaging , Hepatoblastoma/pathology , Neoadjuvant Therapy/methods , Female , Male , Liver Neoplasms/diagnostic imaging , Liver Neoplasms/drug therapy , Liver Neoplasms/pathology , Tomography, X-Ray Computed/methods , Retrospective Studies , Child, Preschool , Infant , Child , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Chemotherapy, Adjuvant/methods , Radiomics
20.
Dis Colon Rectum ; 67(6): 782-795, 2024 Jun 01.
Article En | MEDLINE | ID: mdl-38701503

BACKGROUND: A variety of definitions for a clinical near-complete response after neoadjuvant (chemo) radiotherapy for rectal cancer are currently used. This variety leads to inconsistency in clinical practice, long-term outcome, and trial enrollment. OBJECTIVE: The aim of this study was to reach expert-based consensus on the definition of a clinical near-complete response after (chemo) radiotherapy. DESIGN: A modified Delphi process, including a systematic review, 3 surveys, and 2 meetings, was performed with an international expert panel consisting of 7 surgeons and 4 radiologists. The surveys consisted of individual features, statements, and feature combinations (endoscopy, T2-weighted MRI, and diffusion-weighted MRI). SETTING: The modified Delphi process was performed in an online setting; all 3 surveys were completed online by the expert panel, and both meetings were hosted online. MAIN OUTCOME MEASURES: The main outcome was to reach consensus (80% or more agreement). RESULTS: The expert panel reached consensus on a 3-tier categorization of the near-complete response category based on the likelihood of the response to evolve into a clinical complete response after a longer waiting interval. The panelists agreed that a near-complete response is a temporary entity only to be used in the first 6 months after (chemo)radiotherapy. Furthermore, consensus was reached that the lymph node status should be considered when deciding on a near-complete response and that biopsies are not always needed when a near-complete response is found. No consensus was reached on whether primary staging characteristics have to be taken into account when deciding on a near-complete response. LIMITATIONS: This 3-tier subcategorization is expert-based; therefore, there is no supporting evidence for this subcategorization. Also, it is unclear whether this subcategorization can be generalized into clinical practice. CONCLUSIONS: Consensus was reached on the use of a 3-tier categorization of a near-complete response, which can be helpful in daily practice as guidance for treatment and to inform patients with a near-complete response on the likelihood of successful organ preservation. See Video Abstract. UN CONSENSO INTERNACIONAL BASADO EN EXPERTOS ACERCA DE LA DEFINICIN DE UNA RESPUESTA CLNICA CASI COMPLETA DESPUS DE QUIMIORADIOTERAPIA NEOADYUVANTE CONTRA EL CNCER DE RECTO: ANTECEDENTES:Actualmente, se utilizan una variedad de definiciones para una respuesta clínica casi completa después de quimioradioterapia neoadyuvante contra el cáncer de recto. Esta variedad resulta en inconsistencia en la práctica clínica, los resultados a largo plazo y la inscripción en ensayos.OBJETIVO:El objetivo de este estudio fue llegar a un consenso de expertos sobre la definición de una respuesta clínica casi completa después de quimioradioterapia.DISEÑO:Se realizó un proceso Delphi modificado que incluyó una revisión sistemática, 3 encuestas y 2 reuniones con un panel internacional de expertos compuesto por siete cirujanos y 4 radiólogos. Las encuestas consistieron en características individuales, declaraciones y combinaciones de características (endoscopía, T2W-MRI y DWI).AJUSTE:El proceso Delphi modificado se realizó en un entorno en línea; el panel de expertos completó las tres encuestas en línea y ambas reuniones se realizaron en línea.PRINCIPALES MEDIDAS DE RESULTADO:El resultado principal fue llegar a un consenso (≥80% de acuerdo).RESULTADOS:El panel de expertos llegó a un consenso sobre una categorización de tres niveles de la categoría de respuesta casi completa basada en la probabilidad de que la respuesta evolucione hacia una respuesta clínica completa después de un intervalo de espera más largo. Los panelistas coincidieron en que una respuesta casi completa es una entidad temporal que sólo debe utilizarse en los primeros 6 meses después de la quimioradioterapia. Además, se llegó a un consenso en que se debe considerar el estado de los nódulos linfáticos al decidir sobre una respuesta casi completa y que no siempre se necesitan biopsias cuando se encuentra una respuesta casi completa. No se llegó a un consenso sobre si se deben tener en cuenta las características primarias de estadificación al decidir una respuesta casi completa.LIMITACIONES:Esta subcategorización de 3 niveles está basada en expertos; por lo tanto, no hay evidencia que respalde esta subcategorización. Además, no está claro si esta subcategorización puede generalizarse a la práctica clínica.CONCLUSIONES:Se alcanzó consenso sobre el uso de una categorización de 3 niveles de una respuesta casi completa que puede ser útil en la práctica diaria como guía para el tratamiento y para informar a los pacientes con una respuesta casi completa sobre la probabilidad de una preservación exitosa del órgano. (Traducción - Dr. Aurian Garcia Gonzalez).


Consensus , Delphi Technique , Neoadjuvant Therapy , Rectal Neoplasms , Humans , Rectal Neoplasms/therapy , Rectal Neoplasms/pathology , Rectal Neoplasms/radiotherapy , Neoadjuvant Therapy/methods , Chemoradiotherapy/methods , Treatment Outcome , Diffusion Magnetic Resonance Imaging/methods
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