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1.
Zhonghua Wei Chang Wai Ke Za Zhi ; 27(4): 395-402, 2024 Apr 25.
Article Zh | MEDLINE | ID: mdl-38644245

Objective: To explore the efficacy of immune checkpoint inhibitors combined with adjuvant chemotherapy in patients with phase III gastric cancer and esophagogastric junction cancer. Methods: This study used a retrospective cohort study method based on real-world data. Clinical data of 403 patients with stage III gastric/esophagogastric junction cancer who underwent gastrectomy followed by adjuvant therapy in the Department of Gastric Surgery at Sun Yat-sen University Cancer Center from January 2020 to December 2023 were retrospectively collected. The study cohort comprised 147 (36.5%) patients with stage IIIA, 130 (32.3%) with stage IIIB, and 126 (31.3%) with stage IIIC gastric/esophagogastric junction cancer. Of them, 15 (3.7%) were HER-2 positive, 25 (6.2%) dMMR, and 22 (5.5%) patients Epstein-Barr virus encoding RNA (EBER) positive. Based on treatment plans, the patients were divided into immune checkpoint inhibitor combined with chemotherapy group (immune therapy group, n=110, 71 males and 39 females, median age 59 years old) and chemotherapy alone group (chemotherapy group, n=293, 186 males and 107 females, median age 60 years old). All patients in the immunotherapy group received immune checkpoint inhibitors targeting the programmed cell death protein-1 (PD-1) and its ligand (PD-L1). Of them, 85 received pembrolizumab, 10 received sintilimab, 8 received tislelizumab, 4 received camrelizumab, 2 received toripalimab, and 1 received pabocizumab. The adjuvant chemotherapy regimens used among the chemotherapy alone group includes SOX regimen (132 cases), XELOX (102 cases), S-1 monotherapy (44 cases), and other regimens (15 cases). The 3-year DFS rate of the two groups was compared, and subgroup analysis was conducted based on different ages, molecular phenotypes, pTNM staging, extranodal infiltration, and tumor length. Results: The median follow-up was 20.5 months (range 3.1~46.3), with a 3-year overall DFS rate of 61.4% for the entire 403 patients. The 3-year DFS rate for the immunotherapy group was 82.7%, higher than the chemotherapy alone group (58.8%), with a statistically significant difference (P=0.021). Multivariate analysis showed that postoperative immunotherapy was a protective factor for DFS (HR=0.352, 95%CI: 0.180~0.685). Subgroup analysis showed that stage IIIC (HR=0.416, 95%CI: 0.184~0.940), aged ≥60 years (HR=0.336, 95%CI: 0.121~0.934) and extranodal invasion (HR=0.378, 95%CI: 0.170~0.839) were associated with benefit from the combined immune adjuvant chemotherapy, while no association was observed for MMR, HER-2 or EBER status. Conclusion: Stage III gastric/esophagogastric junction cancer patients may benefite from postoperative immune checkpoint inhibitor combined with adjuvant chemotherapy in real-world settings.


Esophagogastric Junction , Gastrectomy , Immune Checkpoint Inhibitors , Neoplasm Staging , Stomach Neoplasms , Humans , Male , Female , Retrospective Studies , Stomach Neoplasms/drug therapy , Stomach Neoplasms/pathology , Middle Aged , Immune Checkpoint Inhibitors/therapeutic use , Chemotherapy, Adjuvant , Esophagogastric Junction/pathology , Aged , Esophageal Neoplasms/drug therapy , Esophageal Neoplasms/pathology , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Antibodies, Monoclonal, Humanized/therapeutic use
2.
World J Surg Oncol ; 22(1): 106, 2024 Apr 20.
Article En | MEDLINE | ID: mdl-38643188

BACKGROUND: The survival outcomes in HER2-low versus HER2-zero breast cancer (BC) after neoadjuvant chemotherapy (NACT) remain unclear. The meta-analysis was conducted to summarize current evidence about the survival outcomes in HER2-low versus HER2-zero BC. METHODS: We conducted a systematic search in PubMed and EMBASE databases to identify relevant studies. RESULTS: A total of 14 studies with 53,714 patients were included. Overall, 34,037 patients (63.37%) were HER2-low, and 19,677 patients (36.63%) were HER2-zero. Patients with HER2-low tumors had a significantly lower pathological complete response (pCR) rate than patients with HER2-zero tumors, regardless of the hormone receptor status. Compared with HER2-zero breast cancer, the overall survival (OS) and disease-free survival (DFS) of HER2-low BC were longer in the overall cohort (HR = 0.72; 95% CI = 0.61-0.85; P < 0.0001; HR = 0.83; 95% CI = 0.75-0.92; P = 0.0002); however, no differences were observed in terms of OS and DFS between HER2-low and HER2-zero BC in the HR-negative group. In the HR-positive group, HER2-low status had no significant impact on OS, while significantly associated with increased DFS (HR = 0.85; 95% CI = 0.76-0.96; P = 0.007). CONCLUSION: These results suggest that although HER2-low BC has a poor response to NACT, it is correlated with favorable OS and DFS after NACT in the overall cohort as well as longer DFS in the HR-positive group.


Breast Neoplasms , Humans , Female , Breast Neoplasms/pathology , Neoadjuvant Therapy , Receptor, ErbB-2 , Disease-Free Survival , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Chemotherapy, Adjuvant
3.
Ann Diagn Pathol ; 70: 152301, 2024 Jun.
Article En | MEDLINE | ID: mdl-38581761

INTRODUCTION: Despite screening, the incidence of breast cancer is increasing worldwide. Neoadjuvant chemotherapy (NAC) response is one of the most important parameters taken into consideration in surgery, optimal adjuvant chemotherapy planning and prognosis prediction. Research on predictive markers for the response to NAC is still ongoing. In our study, we investigated the relationship between tumor-infiltrating neutrophils/mast cells/lymphocytes and NAC response in breast carcinomas. MATERIAL AND METHOD: Study included 117 patients who were diagnosed with invasive breast carcinoma using core needle biopsy. In these biopsies tumor-infiltrating neutrophils/mast cells/lymphocytes were evaluated and Miller Payne Score was used for NAC response. RESULT: 53 patients exhibited high TILs, 36 had high TINs, and 46 showed high TIMs. While pathological complete response was 27 % in all patients, it was 38 % in high TINs patients, 35 % in high TILs patients, and 28 % in high TIMs patients. High TIMs were observed to be statistically associated with survival. TILs, TINs, nuclear grade, ER, PR and HER2 expression, Ki-67 proliferation index were found to be associated with the Miller - Payne score. In multivariate analysis, TINs, nuclear grade, pathological stage, and molecular subtype were found to be independent risk factors for treatment response. CONCLUSION: TINs have better prognostic value to predict neoadjuvant treatment than TILs. High TIMs are associated with increased overall survival. The inclusion of TINs in NAC response and TIMs in overall survival in pathology reports and treatment planning is promising in breast carcinomas as they are simple to use and reproducible markers.


Breast Neoplasms , Lymphocytes, Tumor-Infiltrating , Neoadjuvant Therapy , Neutrophils , Humans , Breast Neoplasms/pathology , Breast Neoplasms/drug therapy , Breast Neoplasms/immunology , Female , Neoadjuvant Therapy/methods , Middle Aged , Adult , Lymphocytes, Tumor-Infiltrating/immunology , Neutrophils/pathology , Neutrophils/metabolism , Aged , Prognosis , Chemotherapy, Adjuvant/methods , Lymphocytes/pathology , Lymphocytes/metabolism
4.
Rev Assoc Med Bras (1992) ; 70(3): e20231215, 2024.
Article En | MEDLINE | ID: mdl-38656005

OBJECTIVE: Patients with residual disease after neoadjuvant chemotherapy have a relative risk of developing recurrence. This study investigates the risk factors for recurrence in locally advanced breast cancer patients with residual disease and evaluates survival analysis. METHODS: This is a retrospective, single-center study. Breast cancer patients who failed to achieve a pathological complete response after neoadjuvant chemotherapy were included. Demographic, clinicopathological, and treatment characteristics were evaluated to identify predictive factors of recurrence and survival analysis. RESULTS: We included 205 patients in this study. After a median of 31 months of follow-up, 10 patients died, and 20 developed distant metastasis. Disease-free survival and disease-specific survival were 73.8% and 83.1%, respectively. Lymphovascular invasion and non-luminal subtype were independent predictors of locoregional recurrence. In situ carcinoma, lymphovascular invasion, ypTIII stage, and non-luminal molecular subtypes were independent predictors of disease-free survival. The only independent factor affecting disease-specific survival was cNII-III. The number of involved lymph nodes was an independent predictor of disease-free survival in patients without complete axillary response. CONCLUSION: Factors affecting disease-specific survival and disease-free survival were cNII-III and the number of involved lymph nodes, respectively. Patients with non-luminal, large residual tumors with in situ carcinoma, lymphovascular invasion, clinically positive axilla, and residual nodal involvement have a high relative risk for recurrence and may benefit from additional treatments.


Breast Neoplasms , Neoadjuvant Therapy , Neoplasm Recurrence, Local , Neoplasm, Residual , Humans , Female , Breast Neoplasms/pathology , Breast Neoplasms/mortality , Neoplasm Recurrence, Local/pathology , Retrospective Studies , Middle Aged , Risk Factors , Adult , Neoplasm, Residual/pathology , Disease-Free Survival , Aged , Neoplasm Staging , Lymphatic Metastasis , Chemotherapy, Adjuvant
5.
Rev Assoc Med Bras (1992) ; 70(3): e20231377, 2024.
Article En | MEDLINE | ID: mdl-38656011

OBJECTIVE: The aim of this study was to evaluate depression and sleep quality in Turkish women receiving neoadjuvant or adjuvant chemotherapy for breast cancer and investigate their relationship. METHODS: This cross-sectional, descriptive, and analytical study included 183 patients who received chemotherapy for non-metastatic breast cancer. Data were collected using the Beck Depression Inventory-II, the Pittsburgh Sleep Quality Index, and a disease-related/sociodemographic information form. RESULTS: The mean age of the participants was 50.2 years, and 50.3% were in menopause. The mean Beck Depression Inventory-II score was 19.64±10.4. Mild depression was detected in 25.7% (n=47) of the women, and moderate or severe depression in 55.2% (n=101). The mean global score of sleep quality was found to be 8.28±2.62, and the majority of the participants (79.7%, n=146) had poor sleep quality. There was a positive correlation (p<0.001, r=0.43) between depression and sleep quality scores. While a negative correlation was found between depression scores and age (p<0.001, r=0.26), the surgical procedure performed did not significantly affect depression scores (p=0.705). Additionally, depression scores were positively correlated with sleep duration (p<0.001, r=0.42) and sleep latency (p=0.01, r=0.48). CONCLUSION: Very high rates of depression and poor sleep quality were detected among Turkish women receiving neoadjuvant or adjuvant chemotherapy for breast cancer. The entire healthcare team involved in the treatment process should take this relationship into consideration and use the necessary preventive and therapeutic methods.


Breast Neoplasms , Depression , Sleep Quality , Humans , Female , Breast Neoplasms/drug therapy , Middle Aged , Cross-Sectional Studies , Turkey/epidemiology , Adult , Depression/epidemiology , Chemotherapy, Adjuvant/adverse effects , Sleep Wake Disorders/epidemiology , Aged , Psychiatric Status Rating Scales , Surveys and Questionnaires , Socioeconomic Factors , Severity of Illness Index , Neoadjuvant Therapy/adverse effects
6.
Br J Surg ; 111(4)2024 Apr 03.
Article En | MEDLINE | ID: mdl-38659247

BACKGROUND: The clinical impact of adjuvant chemotherapy after resection for adenocarcinoma arising from intraductal papillary mucinous neoplasia is unclear. The aim of this study was to identify factors related to receipt of adjuvant chemotherapy and its impact on recurrence and survival. METHODS: This was a multicentre retrospective study of patients undergoing pancreatic resection for adenocarcinoma arising from intraductal papillary mucinous neoplasia between January 2010 and December 2020 at 18 centres. Recurrence and survival outcomes for patients who did and did not receive adjuvant chemotherapy were compared using propensity score matching. RESULTS: Of 459 patients who underwent pancreatic resection, 275 (59.9%) received adjuvant chemotherapy (gemcitabine 51.3%, gemcitabine-capecitabine 21.8%, FOLFIRINOX 8.0%, other 18.9%). Median follow-up was 78 months. The overall recurrence rate was 45.5% and the median time to recurrence was 33 months. In univariable analysis in the matched cohort, adjuvant chemotherapy was not associated with reduced overall (P = 0.713), locoregional (P = 0.283) or systemic (P = 0.592) recurrence, disease-free survival (P = 0.284) or overall survival (P = 0.455). Adjuvant chemotherapy was not associated with reduced site-specific recurrence. In multivariable analysis, there was no association between adjuvant chemotherapy and overall recurrence (HR 0.89, 95% c.i. 0.57 to 1.40), disease-free survival (HR 0.86, 0.59 to 1.30) or overall survival (HR 0.77, 0.50 to 1.20). Adjuvant chemotherapy was not associated with reduced recurrence in any high-risk subgroup (for example, lymph node-positive, higher AJCC stage, poor differentiation). No particular chemotherapy regimen resulted in superior outcomes. CONCLUSION: Chemotherapy following resection of adenocarcinoma arising from intraductal papillary mucinous neoplasia does not appear to influence recurrence rates, recurrence patterns or survival.


Neoplasm Recurrence, Local , Pancreatectomy , Pancreatic Neoplasms , Aged , Female , Humans , Male , Middle Aged , Adenocarcinoma/pathology , Adenocarcinoma/drug therapy , Adenocarcinoma/mortality , Adenocarcinoma/therapy , Adenocarcinoma, Mucinous/pathology , Adenocarcinoma, Mucinous/drug therapy , Adenocarcinoma, Mucinous/therapy , Adenocarcinoma, Mucinous/mortality , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Capecitabine/administration & dosage , Capecitabine/therapeutic use , Carcinoma, Pancreatic Ductal/pathology , Carcinoma, Pancreatic Ductal/mortality , Carcinoma, Pancreatic Ductal/drug therapy , Carcinoma, Pancreatic Ductal/therapy , Carcinoma, Pancreatic Ductal/surgery , Chemotherapy, Adjuvant , Gemcitabine , Neoplasm Recurrence, Local/epidemiology , Pancreatic Intraductal Neoplasms/pathology , Pancreatic Intraductal Neoplasms/therapy , Pancreatic Intraductal Neoplasms/mortality , Pancreatic Intraductal Neoplasms/surgery , Pancreatic Neoplasms/pathology , Pancreatic Neoplasms/drug therapy , Pancreatic Neoplasms/mortality , Pancreatic Neoplasms/therapy , Pancreatic Neoplasms/surgery , Propensity Score , Retrospective Studies
7.
Front Immunol ; 15: 1359302, 2024.
Article En | MEDLINE | ID: mdl-38646542

Objective: At present, several important trials have been published show that perioperative immunotherapy combined with chemotherapy can improve the prognosis of patients with resectable non-small cell lung cancer, which further optimizes treatment options. Therefore, we conducted a systematic review and meta-analysis to evaluate the efficacy and safety of perioperative immunotherapy combined with chemotherapy in resectable non-small cell lung cancer. Methods: The following databases were searched for relevant studies: PubMed, EMBASE, Cochrane library (updated 12 October 2023). All randomized trials comparing perioperative immunotherapy combined with chemotherapy versus chemotherapy alone in resectable non-small cell lung cancer were eligible for inclusion. Data were analyzed using Review Manager 5.4.1 (Cochrane collaboration software). Primary outcomes and measures included overall survival (OS), event-free survival (EFS), pathological complete response (pCR), major pathological response (MPR), R0 resection rate, rate of underwent surgery and adverse events (AEs). Results: A total of 2912 patients (1453 receiving perioperative immunotherapy plus chemotherapy and 1459 receiving chemotherapy alone) were included in this systematic review and meta-analysis. The result showed that compared with chemotherapy alone, combined therapy significantly improved OS (HR = 0.68;95% CI: 0.56-0.83), EFS (HR = 0.58;95% CI: 0.51-0.65), pCR (OR = 7.53;95% CI: 4.63-12.26), MPR (OR = 5.03;95% CI: 3.40-7.44), R0 resection (OR = 1.58;95% CI: 1.152.18) and rate of underwent surgery (OR = 1.25;95% CI: 1.04-1.49). However, combination therapy was associated with higher risk of severe adverse event (OR = 1.46;95% CI: 1.19-1.78; P=0.0002), grade 3 and higher treatment-related adverse event (TRAE) (OR = 1.25;95% CI: 1.06-1.49; P=0.010), TRAE that led to interruption (OR = 1.90;95% CI: 1.34-2.68; P=0.0003) and immune-related adverse event (OR = 2.78;95% CI: 2.18-3.55; P<0.00001). Significant benefits were observed across most subgroups of EFS and pCR. However, no statistical differences were observed for EFS of never smoked (HR = 0.73;95% CI: 0.51-1.05) and EGFR-mutation positive (HR = 0.35;95% CI: 0.04-3.03). Conclusion: This systematic review and meta-analysis found superior efficacy associated with perioperative immunotherapy plus chemotherapy compared with chemotherapy alone in both tumor regression and prolonged survival in resectable NSCLC, but increased the risk of TRAE, so monitoring for adverse events is warranted. Systematic review registration: https://www.crd.york.ac.uk/prospero, identifier (CRD42023476786).


Carcinoma, Non-Small-Cell Lung , Immunotherapy , Lung Neoplasms , Neoadjuvant Therapy , Humans , Carcinoma, Non-Small-Cell Lung/therapy , Carcinoma, Non-Small-Cell Lung/mortality , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/immunology , Lung Neoplasms/therapy , Lung Neoplasms/drug therapy , Lung Neoplasms/mortality , Neoadjuvant Therapy/methods , Immunotherapy/methods , Immunotherapy/adverse effects , Clinical Trials, Phase III as Topic , Chemotherapy, Adjuvant , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Treatment Outcome , Combined Modality Therapy
8.
J Hematol Oncol ; 17(1): 17, 2024 04 08.
Article En | MEDLINE | ID: mdl-38589926

Evidence from Europe shows that perioperative chemotherapy may be beneficial for the treatment of locally advanced gastric cancer, but reliable and robust data is lacking. To rectify this, the phase 3 RESONANCE trial investigated the efficacy and safety of S-1 plus oxaliplatin (SOX) as a perioperative chemotherapy regimen for gastric cancer. This randomized, open-label trial enrolled patients from 19 medical centers with stage II/III resectable gastric cancer who were centrally randomly assigned to either perioperative chemotherapy (PC) arm or adjuvant chemotherapy (AC) arm. Patients in the PC arm received two to four cycles of SOX followed by surgery and four to six cycles of SOX. Patients in the AC arm received upfront surgery and eight cycles of SOX. 386 patients in each group were enrolled and 756 (382 in PC and 374 in AC) were included in the mITT population. The three-year DFS rate was 61.7% in the PC arm and 53.8% in the AC arm (log-rank p = 0.019). The R0 resection rate in the PC arm was significantly higher than that in the AC arm (94.9% vs. 83.7%, p < 0.0001). There was no difference between two arms in surgical outcomes or postoperative complications. Safety-related data were like the known safety profile. In conclusion, from a clinical perspective, this trial indicated a trend towards higher three-year disease-free survival rate with perioperative SOX in stage II/III resectable gastric cancer with well-tolerated toxicity compared to adjuvant SOX, which might provide a theoretical basis for applying perioperative SOX in advanced gastric cancer patients. (ClinicalTrials.gov NCT01583361).


Stomach Neoplasms , Humans , Stomach Neoplasms/drug therapy , Stomach Neoplasms/surgery , Oxaliplatin/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Chemotherapy, Adjuvant , Disease-Free Survival , Neoadjuvant Therapy
9.
JCO Precis Oncol ; 8: e2300390, 2024 Mar.
Article En | MEDLINE | ID: mdl-38564683

PURPOSE: Results from the TAILORx trial revealed that the use of adjuvant chemotherapy along with endocrine therapy had no survival advantage in patients with estrogen receptor (ER)-positive, human epidermal growth factor receptor 2-negative (HER2-), node-negative (N0) breast cancer (BC) with an intermediate (11-25) 21-gene recurrence score (RS) in the overall population. However, in patients under age 50 years, adjuvant chemotherapy demonstrated a progression-free survival benefit when the RS ranged from 16-25. We studied this cohort with the population-based national database. METHODS: The 2010-2018 National Cancer Database was used to include patients with BC age 18-50 years, N0, M0, RS 16-25, ER+/progesterone receptor±, and HER2-. Patients were divided into two groups on the basis of adjuvant chemotherapy use, and the survival between them was compared. RESULTS: Adjuvant chemotherapy use was noted in 4,808/15,792 (30.45%) patients. Median RS was 18 and 21 in patients without and with adjuvant chemotherapy, respectively. Factors associated with adjuvant chemotherapy use were higher T stage, poor and moderately differentiated tumors, age <40 years, care at an academic center, Caucasian race, patients undergoing mastectomy, regional lymph node surgery, and radiation therapy. Kaplan-Meier survival at 10 years was better with adjuvant chemotherapy (96.2% v 91.6%). Patients without adjuvant chemotherapy had more adverse outcomes (hazard ratio [HR], 1.683 [95% CI, 1.392 to 2.036]; P < .0001). Subgroup analysis showed that the benefit was significant in patients with RS scores 21-25 (HR, 1.953 [95% CI, 1.295 to 2.945]), ductal histology (HR, 1.521 [95% CI, 1.092 to 2.118]), Caucasian race (HR, 1.655 [95% CI, 1.180 to 2.322]), and 41-50 years age group (HR, 1.732 [95% CI, 1.244 to 2.411]). CONCLUSION: Our study showed an overall survival benefit for adjuvant chemotherapy use in patients with ER-positive, N0 premenopausal BC patients, age less than 50 years, with an intermediate RS score, particularly 21-25.


Breast Neoplasms , Humans , Middle Aged , Adolescent , Young Adult , Adult , Female , Breast Neoplasms/drug therapy , Breast Neoplasms/genetics , Breast Neoplasms/metabolism , Retrospective Studies , Mastectomy , Receptor, ErbB-2/genetics , Receptor, ErbB-2/metabolism , Prognosis , Receptors, Estrogen/metabolism , Hormones/therapeutic use , Chemotherapy, Adjuvant/methods
10.
Hum Vaccin Immunother ; 20(1): 2342133, 2024 Dec 31.
Article En | MEDLINE | ID: mdl-38659098

Hepatoid adenocarcinoma of the lung (HAL) is a rare and aggressive subtype of lung cancer. The prognosis for patients with HAL is generally poor and currently, there are only limited treatment options. Here, we present a case of a 47-year-old male diagnosed with locally advanced-stage HAL who achieved a remarkably long disease-free survival after receiving neoadjuvant and adjuvant camrelizumab plus chemotherapy and surgery. This case highlights the potential of immunochemotherapy plus surgery in improving outcomes for patients with HAL.


Adenocarcinoma of Lung , Antibodies, Monoclonal, Humanized , Lung Neoplasms , Neoadjuvant Therapy , Humans , Male , Middle Aged , Antibodies, Monoclonal, Humanized/therapeutic use , Antibodies, Monoclonal, Humanized/administration & dosage , Lung Neoplasms/drug therapy , Lung Neoplasms/therapy , Adenocarcinoma of Lung/drug therapy , Adenocarcinoma of Lung/therapy , Adenocarcinoma of Lung/pathology , Neoadjuvant Therapy/methods , Chemotherapy, Adjuvant/methods , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Disease-Free Survival , Adenocarcinoma/therapy , Adenocarcinoma/drug therapy , Treatment Outcome
11.
Breast Cancer ; 31(3): 519-528, 2024 May.
Article En | MEDLINE | ID: mdl-38564089

PURPOSE: Higher pre-diagnosis physical activity (PA) is associated with lower all-cause mortality in breast cancer (BCa) patients. However, the association with pathological complete response (pCR) is unclear. We investigated the association between pre-diagnosis PA level and chemotherapy completion, dose delay, and pCR in BCa patients receiving neoadjuvant chemotherapy (NACT). METHODS: 180 stage I-III BCa patients receiving NACT (mean [SD] age of diagnosis: 60.8 [8.8] years) in the Sister Study were included. Self-reported recreational and total PA levels were converted to metabolic equivalent of task-hours per week (MET-hrs/wk). The pCR was defined as no invasive or in situ residual in breast or lymph node (ypT0 ypN0). Multivariable logistic regression analyses estimated odds ratios (ORs) and 95% confidence intervals (CIs) for treatment outcomes. RESULTS: In this sample, 45 (25.0%) BCa patients achieved pCR. Higher pre-diagnosis recreational PA was not associated with lower likelihood of chemotherapy completion (highest vs. lowest tertile: OR = 0.87, 95% CI = 0.30-2.56; Ptrend = 0.84), greater dose delay (OR = 1.45, 95% CI = 0.54-3.92; Ptrend = 0.46), or greater odds of pCR (OR = 1.28, 95% CI = 0.49-3.34; Ptrend = 0.44). Associations were similar for pre-diagnosis total PA. Meeting the recommended level of recreational PA was not associated with pCR overall (≥ 7.5 vs. < 7.5 MET-hrs/wk: OR = 1.33, 95% CI = 0.59-3.01). CONCLUSIONS: Although small sample size and limited information on exercise closer to time of diagnosis limit interpretation, pre-diagnosis PA was not convincingly associated with treatment tolerance or treatment efficacy in BCa patients receiving NACT. Future investigations are needed to better understand the impact of pre-diagnosis PA on BCa treatment.


Breast Neoplasms , Exercise , Neoadjuvant Therapy , Humans , Female , Breast Neoplasms/drug therapy , Breast Neoplasms/pathology , Breast Neoplasms/therapy , Breast Neoplasms/mortality , Neoadjuvant Therapy/methods , Middle Aged , Aged , Exercise/physiology , Treatment Outcome , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Chemotherapy, Adjuvant/methods , Adult
12.
Int J Mol Sci ; 25(7)2024 Apr 06.
Article En | MEDLINE | ID: mdl-38612893

Cancer continues to pose a significant global health challenge, as evidenced by the increasing incidence rates and high mortality rates, despite the advancements made in chemotherapy. The emergence of chemoresistance further complicates the effectiveness of treatment. However, there is growing interest in the potential of metformin, a commonly prescribed drug for type 2 diabetes mellitus (T2DM), as an adjuvant chemotherapy agent in cancer treatment. Although the precise mechanism of action of metformin in cancer therapy is not fully understood, it has been found to have pleiotropic effects, including the modulation of metabolic pathways, reduction in inflammation, and the regulation of cellular proliferation. This comprehensive review examines the anticancer properties of metformin, drawing insights from various studies conducted in vitro and in vivo, as well as from clinical trials and observational research. This review discusses the mechanisms of action involving both insulin-dependent and independent pathways, shedding light on the potential of metformin as a therapeutic agent for different types of cancer. Despite promising findings, there are challenges that need to be addressed, such as conflicting outcomes in clinical trials, considerations regarding dosing, and the development of resistance. These challenges highlight the importance of further research to fully harness the therapeutic potential of metformin in cancer treatment. The aims of this review are to provide a contemporary understanding of the role of metformin in cancer therapy and identify areas for future exploration in the pursuit of effective anticancer strategies.


Diabetes Mellitus, Type 2 , Metformin , Neoplasms , Humans , Metformin/pharmacology , Metformin/therapeutic use , Diabetes Mellitus, Type 2/drug therapy , Cell Proliferation , Chemotherapy, Adjuvant , Hyperplasia , Neoplasms/drug therapy
13.
Zhonghua Zhong Liu Za Zhi ; 46(4): 335-343, 2024 Apr 23.
Article Zh | MEDLINE | ID: mdl-38644269

Objectives: To assess the prognostic impact of the neoadjuvant rectal (NAR) score following neoadjuvant short-course radiotherapy and consolidation chemotherapy in locally advanced rectal cancer (LARC), as well as its value in guiding decisions for adjuvant chemotherapy. Methods: Between August 2015 and August 2018, patients were eligible from the STELLAR phase III trial (NCT02533271) who received short-course radiotherapy plus consolidation chemotherapy and for whom the NAR score could be calculated. Based on the NAR score, patients were categorized into low (<8), intermediate (8-16), and high (>16) groups. The Kaplan-Meier method, log rank tests, and multivariate Cox proportional hazard regression models were used to evaluate the impact of the NAR score on disease-free survival (DFS). Results: Out of the 232 patients, 24.1%, 48.7%, and 27.2% had low (56 cases), intermediate (113 cases), and high NAR scores (63 cases), respectively. The median follow-up period was 37 months, with 3-year DFS rates of 87.3%, 68.3%, and 53.4% (P<0.001) for the low, intermediate, and high NAR score groups. Multivariate analysis demonstrated that the NAR score (intermediate NAR score: HR, 3.10, 95% CI, 1.30-7.37, P=0.011; high NAR scores: HR=5.44, 95% CI, 2.26-13.09, P<0.001), resection status (HR, 3.00, 95% CI, 1.64-5.52, P<0.001), and adjuvant chemotherapy (HR, 3.25, 95% CI, 2.01-5.27, P<0.001) were independent prognostic factors for DFS. In patients with R0 resection, the 3-year DFS rates were 97.8% and 78.0% for those with low and intermediate NAR scores who received adjuvant chemotherapy, significantly higher than the 43.2% and 50.6% for those who did not (P<0.001, P=0.002). There was no significant difference in the 3-year DFS rate (54.2% vs 53.3%, P=0.214) among high NAR score patients, regardless of adjuvant chemotherapy. Conclusions: The NAR score is a robust prognostic indicator in LARC following neoadjuvant short-course radiotherapy and consolidation chemotherapy, with potential implications for subsequent decisions regarding adjuvant chemotherapy. These findings warrant further validation in studies with larger sample sizes.


Consolidation Chemotherapy , Neoadjuvant Therapy , Rectal Neoplasms , Humans , Rectal Neoplasms/pathology , Rectal Neoplasms/therapy , Chemotherapy, Adjuvant , Prognosis , Disease-Free Survival , Proportional Hazards Models , Male , Female , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Middle Aged , Survival Rate , Rectum
14.
Breast Cancer ; 31(3): 507-518, 2024 May.
Article En | MEDLINE | ID: mdl-38573438

BACKGROUND: In breast cancer patients receiving neoadjuvant chemotherapy (NAC), immediate breast reconstruction (IBR) as a breast cancer treatment option remains controversial. We assessed the impact of NAC on surgical and oncological outcomes of patients undergoing IBR. METHODS: This was a retrospective multicenter study of 4726 breast cancer cases undergoing IBR. The rate of postoperative complications and survival data were compared between IBR patients who received NAC and those who did not receive NAC. Propensity score matching analysis was performed to mitigate selection bias for survival. RESULTS: Of the total 4726 cases, 473 (10.0%) received NAC. Out of the cases with NAC, 96 (20.3%) experienced postoperative complications, while 744 cases (17.5%) without NAC had postoperative complications. NAC did not significant increase the risk of complications after IBR (Odds ratio, 0.96; 95%CI 0.74-1.25). At the median follow-up time of 76.5 months, 36 patients in the NAC group and 147 patients in the control group developed local recurrences. The 5-year local recurrence-free survival rate was 93.1% in the NAC group and 97.1% in the control group. (P < 0.001). After matching, there was no significant difference between the two groups. CONCLUSION: IBR after NAC is a safe procedure with an acceptable postoperative complication profile.


Breast Neoplasms , Mammaplasty , Mastectomy , Neoadjuvant Therapy , Postoperative Complications , Humans , Female , Breast Neoplasms/surgery , Breast Neoplasms/drug therapy , Breast Neoplasms/pathology , Breast Neoplasms/mortality , Neoadjuvant Therapy/adverse effects , Neoadjuvant Therapy/methods , Middle Aged , Retrospective Studies , Mammaplasty/adverse effects , Mammaplasty/methods , Mastectomy/adverse effects , Adult , Postoperative Complications/etiology , Postoperative Complications/epidemiology , Chemotherapy, Adjuvant/adverse effects , Chemotherapy, Adjuvant/methods , Neoplasm Recurrence, Local , Aged , Follow-Up Studies , Treatment Outcome , Propensity Score , Disease-Free Survival
15.
J Gastrointest Surg ; 28(4): 365-374, 2024 Apr.
Article En | MEDLINE | ID: mdl-38583885

BACKGROUND: Adjuvant chemotherapy (CT) constitutes the primary approach for treating resectable advanced gastric cancer (GC). However, the effectiveness of postoperative CT can differ across various patient groups. This retrospective study aimed to examine how variances in clinical and pathologic factors affect postoperative CT. METHODS: This study enrolled 2060 patients with GC who underwent curative gastrectomy at Zhejiang Cancer Hospital between January 2008 and December 2017, with 1277 receiving postoperative CT. This study used Kaplan-Meier to determine the effect of clinical and pathology factors on CT benefits. In addition, univariate and multivariate Cox regression analyses were used to identify independent prognosis risk factors. RESULTS: Both univariate and multivariate analyses demonstrated that the absence of postoperative CT is an independent factor associated with a poor prognosis in patients with GC. The Kaplan-Meier univariate analysis revealed that specific subgroups, including males, those with a normal body mass index (BMI), the elderly, individuals with gastric adenocarcinoma, cases of nerve invasion by the tumor, vascular invasion by the tumor, tumor size ≥ 5 cm, and Tumor, Node, Metastasis (TNM) stage III, exhibited improved treatment outcomes with the administration of postoperative CT. The creation of nomograms using Cox regression and the rms package holds significant clinical relevance. CONCLUSION: Postoperative CT is advantageous for prolonging the survival of advanced patients undergoing D2 gastrectomy, particularly in male patients, the elderly, individuals with a normal BMI score, those diagnosed with gastric adenocarcinoma, cases, in which the tumor invades nerves or blood vessels, patients with a tumor size of ≥5 cm, and those with a TNM stage of III, as it results in improved treatment outcomes within these subgroups.


Adenocarcinoma , Stomach Neoplasms , Humans , Male , Aged , Retrospective Studies , Neoplasm Staging , Prognosis , Stomach Neoplasms/drug therapy , Stomach Neoplasms/surgery , Chemotherapy, Adjuvant , Adenocarcinoma/drug therapy , Adenocarcinoma/surgery , Gastrectomy/methods
16.
J Gastrointest Surg ; 28(4): 375-380, 2024 Apr.
Article En | MEDLINE | ID: mdl-38583886

PURPOSE: This study aimed to investigate the correlation between sarcopenia and adverse events (AEs) of postoperative imatinib therapy through computed tomography (CT) quantitative body composition for intermediate- and high-risk gastrointestinal stromal tumors (GISTs). METHODS: The study retrospectively analyzed the clinical data of 208 patients with intermediate- and high-risk GIST treated surgically and treated with imatinib afterward at the First Affiliated Hospital of Wenzhou Medical University between October 2011 and October 2021. Images of preoperative CT scans within 1 month were used to determine the body composition of the patients. On the basis of the L3 skeletal muscle index, patients were classified into sarcopenia and nonsarcopenia groups. In 2 groups, AEs related to imatinib were analyzed. RESULTS: The proportion of AEs related to imatinib in the sarcopenia group was higher, and this disparity had a significant statistical significance (P = .013). Sarcopenia was significantly associated with hemoglobin reduction compared with nonsarcopenia (P = .015). There was a significant difference between the sarcopenia group and the nonsarcopenia group in the ratio of severe AEs (grades 3-4). Hemoglobin content (odds ratio [OR], 0.981; 95% CI, 0.963-1.000; P = .045), sex (OR, 0.416; 95% CI, 0.192-0.904; P = .027), and sarcopenia (OR, 5.631; 95% CI, 2.262-14.014; P < .001) were the influential factors of imatinib severe AEs in patients with intermediate- and high-risk GIST within 1 year after imatinib treatment. CONCLUSION: Patients with preoperative sarcopenia have a higher incidence and severity of AEs during adjuvant imatinib therapy.


Antineoplastic Agents , Gastrointestinal Stromal Tumors , Sarcopenia , Humans , Imatinib Mesylate/adverse effects , Gastrointestinal Stromal Tumors/diagnostic imaging , Gastrointestinal Stromal Tumors/drug therapy , Gastrointestinal Stromal Tumors/surgery , Retrospective Studies , Sarcopenia/chemically induced , Sarcopenia/diagnostic imaging , Chemotherapy, Adjuvant , Hemoglobins , Tomography , Antineoplastic Agents/adverse effects
17.
Acta Oncol ; 63: 125-136, 2024 Apr 08.
Article En | MEDLINE | ID: mdl-38587062

BACKGROUND AND PURPOSE: Tamoxifen remains an important adjuvant treatment in premenopausal patients with hormone receptor-positive breast cancer. Thus, determination of hormone receptors is important. Here, we compare cytosol-based methods, immunohistochemistry (IHC), and gene expression (GEX) analysis for determining hormone receptor status in premenopausal breast cancer patients from a randomised tamoxifen trial, to evaluate their performance in identifying patients that benefit from tamoxifen. PATIENTS AND METHODS: Premenopausal patients (n=564) were randomised to 2 years of tamoxifen or no systemic treatment. Estrogen receptor (ER) and progesterone receptor (PR) status by protein expression measured by cytosol-based methods and IHC, and mRNA by GEX analysis were compared in 313 patients with available data from all methods. Kaplan Meier estimates and Cox regression were used to evaluate the treatment-predictive value for recurrence-free interval (RFi) and overall survival (OS). Median follow-up for event-free patients was 26 (RFi) and 33 (OS) years. RESULTS: The mRNA data of ESR1 and PGR distributed bimodally, patterns confirmed in an independent cohort. Kappa-values between all methods were 0.76 and 0.79 for ER and PR, respectively. Tamoxifen improved RFi in patients with ER-positive (ER+) or PR-positive (PR+) tumours (Hazard Ratio [HR] and 95% confidence interval [CI]), cytosol-ER+ 0.53 [0.36-0.79]; IHC-ER+ 0.55 [0.38-0.79]; GEX-ER+ 0.54 [0.37-0.77]; cytosol-PR+ 0.49 [0.34-0.72]; IHC-PR+ 0.58 [0.40-0.85]; GEX-PR+ 0.55 [0.38-0.80]). Results were similar for OS. INTERPRETATION: These methods can all identify patients that benefit from 2 years of tamoxifen with equal performance, indicating that GEX data might be used to guide adjuvant tamoxifen therapy.


Breast Neoplasms , Tamoxifen , Humans , Female , Tamoxifen/therapeutic use , Antineoplastic Agents, Hormonal/therapeutic use , RNA, Messenger/genetics , Chemotherapy, Adjuvant , Breast Neoplasms/drug therapy , Breast Neoplasms/genetics , Breast Neoplasms/metabolism , Receptors, Estrogen/metabolism , Hormones/therapeutic use , Receptors, Progesterone/metabolism , Treatment Outcome
18.
Cancer Med ; 13(7): e7146, 2024 Apr.
Article En | MEDLINE | ID: mdl-38581118

BACKGROUND: De-escalation strategies for newly-diagnosed p16-positive oropharyngeal squamous cell carcinoma (p16+ OPSCC), aim to reduce treatment-related morbidity without compromising disease control. One strategy is neoadjuvant cisplatin and docetaxel chemotherapy (NAC + S) before transoral robotic surgery, with pathology-based risk-adapted adjuvant treatment. METHODS: We examined the recurrence-free survival (RFS) for patients who received NAC + S. RESULTS: Comparing outcomes in 103 patients between 2008 and 2023, 92% avoided adjuvant treatment and showed significantly higher 2-year recurrence-free survival (RFS) compared to those with adjuvant treatment (95.9% vs. 43.8%, p = 0.0049) CONCLUSION: Our findings suggest that pathology-based risk-adapted omission of adjuvant treatment following NAC + S does not appear to elevate recurrence risk and that NAC may identify patients with favorable tumor biology, yielding a 2-year RFS probability exceeding 95% without adjuvant treatment. Further, the study identifies a patient subset experiencing disease recurrence despite triple modality therapy. Despite limitations, including a retrospective design and modest sample size, the data advocate for controlled NAC + S studies.


Carcinoma, Squamous Cell , Head and Neck Neoplasms , Oropharyngeal Neoplasms , Robotic Surgical Procedures , Humans , Neoadjuvant Therapy , Retrospective Studies , Robotic Surgical Procedures/adverse effects , Carcinoma, Squamous Cell/surgery , Neoplasm Recurrence, Local/prevention & control , Oropharyngeal Neoplasms/surgery , Chemotherapy, Adjuvant , Head and Neck Neoplasms/etiology
19.
Breast Cancer Res ; 26(1): 59, 2024 Apr 08.
Article En | MEDLINE | ID: mdl-38589932

INTRODUCTION: Patients with hormone receptor positive breast cancer are recommended at least five years of adjuvant endocrine therapy, but adherence to this treatment is often suboptimal. We investigated longitudinal trends in adjuvant endocrine therapy (AET) adherence among premenopausal breast cancer patients and identified clinical characteristics, including baseline comorbidities and non-cancer chronic medication use, associated with AET adherence. METHODS: We included stage I-III premenopausal breast cancer patients diagnosed during 2002-2011 and registered in the Danish Breast Cancer Group clinical database who initiated AET. We used group-based trajectory modeling to describe AET adherence patterns. We also linked patients to Danish population-based registries and fit multinomial logistic models to compute odds ratios (ORs) and 95% confidence intervals (95% CIs) associating clinical characteristics with AET adherence patterns. RESULTS: We identified three adherence patterns among 4,353 women-high adherers (57%), slow decliners (36%), and rapid decliners (6.9%). Women with stage I disease (vs. stage II; OR: 1.9, 95% CI 1.5, 2.5), without chemotherapy (vs. chemotherapy; OR: 4.3, 95% CI 3.0, 6.1), with prevalent comorbid disease (Charlson Comorbidity Index score ≥ 1 vs. 0; OR: 1.6, 95% CI 1.1, 2.3), and with a history of chronic non-cancer medication use (vs. none; OR: 1.3, 95% CI 1.0, 1.8) were more likely to be rapid decliners compared with high adherers. CONCLUSIONS: Women with stage I cancer, no chemotherapy, higher comorbidity burden, and history of chronic non-cancer medication use were less likely to adhere to AET. Taking steps to promote adherence in these groups of women may reduce their risk of recurrence.


Breast Neoplasms , Humans , Female , Breast Neoplasms/drug therapy , Breast Neoplasms/epidemiology , Chemotherapy, Adjuvant , Antineoplastic Agents, Hormonal/therapeutic use , Medication Adherence , Retrospective Studies
20.
Medicine (Baltimore) ; 103(16): e37841, 2024 Apr 19.
Article En | MEDLINE | ID: mdl-38640302

BACKGROUND: While survival rates among cardiac allograft recipients have improved, there has been a rise in post-transplant malignancies, with gastric cancer being less commonly reported. This study presented a successful treatment of gastric cancer in an individual 10 years after undergoing a heart transplant. CASE PRESENTATION: A 66-year-old Chinese man presented to the gastrointestinal clinic with a complaint of diagnosis of gastric cancer for 4 months and treated with neoadjuvant therapy for 1 month. He has undergone orthotopic heart transplantation 10 years earlier due to a myocardial infarction. Physical examination and laboratory tests did not reveal any significant abnormalities. Abdominal contrast-enhanced computed tomography (CT) imaging indicated a gastric mass near the greater curvature, with gastroscopy suggesting a carcinoma at the esophagogastric junction, Siewert III. An echocardiogram indicated left atrial enlargement with mild mitral and tricuspid regurgitation. The diagnosis suggested that his gastric cancer at the esophagogastric junction was a consequence of long-term immunosuppressive therapy. A multidisciplinary team (MDT) consultation recommended a proximal radical gastrectomy. Postoperatively, the patient received 4 cycles of adjuvant chemotherapy with XELOX combined with Herceptin, initiated a month after surgery. During the 1-year follow-up, the patient showed commendable recovery, with no signs of tumor recurrence or metastasis. CONCLUSION: This case underscores the potential risk of malignancy from immunosuppressive agents in transplant recipients. The successful management of this complex scenario underscores the indispensable role of an MDT approach in treating such unique and challenging cases.


Heart Transplantation , Stomach Neoplasms , Male , Humans , Aged , Stomach Neoplasms/surgery , Neoplasm Recurrence, Local , Heart Transplantation/adverse effects , Echocardiography , Chemotherapy, Adjuvant , Gastrectomy/methods
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