Neoadjuvant fluorouracil plus leucovorin, oxaliplatin, and docetaxel (FLOT) has shown significant benefits for gastric cancer patients. However, it has not been well accepted in Asian countries. We ...conducted a prospective study on the safety and feasibility of the FLOT regimen in Chinese patients.
Patients with adenocarcinoma of the stomach or esophagogastric junction received four cycles of neoadjuvant chemotherapy (NAC) and four cycles of adjuvant chemotherapy (AC) with the FLOT regimen. The completion status of chemotherapy, adverse events, postoperative morbidities, and pathological tumor regression were analyzed. The 2-year overall survival (OS) and relapse-free survival are presented.
Altogether, 10 patients were enrolled, and all patients completed four cycles of neoadjuvant chemotherapy. There were no severe hematological adverse events (grade 3 or above), except for a case of grade 3 anemia. All 10 patients underwent radical gastrectomy. Nine patients had R0 resection, and three patients had complete or subtotal pathological tumor regression. Nine patients completed four cycles of adjuvant chemotherapy, but only one patient completed the full dose of adjuvant chemotherapy. The dose of adjuvant chemotherapy was reduced by 25% or less in the other patients. The median follow-up time was 23.13 months, eight patients achieved the overall survival endpoint, and seven patients had relapse-free survival for this period. Two patients died of disease progression.
Our study demonstrates that the neoadjuvant FLOT regimen is safe and effective for Chinese patients. Dose adjustment is necessary for adjuvant chemotherapy. The pathological regression and survival rates need reevaluation in a larger cohort. The trial is registered with ClinicalTrials.gov (number NCT03646591).
Introduction
As neoadjuvant chemotherapy (NCT) has been successfully introduced in gastric cancer (GC), more biomarkers are needed to evaluate the efficacy. Cancer-associated fibroblasts (CAFs) is ...associated with chemoresistance and prognosis. Three biomarkers, CD10, fibroblast activation protein-α (FAP) and G-protein-coupled receptor 77 (GPR77), have been proved to express in CAFs. However, their predictive values for efficacy of NCT and prognosis in gastric cancer is unknown.
Methods
Totally, specimens of 171 locally advanced gastric cancer patients who underwent NCT and D2 radical gastrectomy and matched preoperative biopsy specimens were retrospectively analyzed. Tumor regression grade (TRG) is reevaluated according to Mandard TRG. Expressions of CD10, FAP and GPR77 in CAFs before NCT (pre-) and after NCT (post-) were evaluated by immunohistochemistry. Survival curves on overall survival (OS) were obtained by Kaplan-Meier method, and differences were analyzed by log-rank test. Associations between categorical variables were explored by chi-square test or Fisher’s exact method. Univariable and multivariate analyses were performed by logistic regression model and Cox proportional hazard regression model.
Results
High expressions of post-CD10, post-FAP, post-GPR77 and pre-CD10 were related to worse TRG (all p<0.05). In multivariable analysis, post- and pre-FAP were independent predictive factors to TRG (p<0.010). Post-CD10 (p=0.032) and post-FAP (p=0.013) were related to OS in univariable analysis, but none of biomarkers were independent prognostic factors in multivariable analysis.
Conclusions
Expressions of CD10, FAP and GPR77 in CAFs were related to chemoresistance and overall survival, and these biomarkers have predictive values for tumor regression and prognosis in locally advanced gastric cancer patients.
Magnetic resonance imaging (MRI) with the help of MRI-based tumor regression grade (mrTRG) score has been used as a tool to predict pathological tumor regression grade (pTRG) in patients of rectal ...cancer post-neoadjuvant chemoradiation. Our study aims to evaluate the ability of MRI in assessing treatment response comparing an objective mrTRG score and a subjective Likert score, with a focus on the ability to predict pathologic complete response (pCR).
Post-treatment MRI studies were retrospectively reviewed for 170 consecutive cases of histopathologically proven rectal cancer after receiving neoadjuvant chemoradiation and prior to surgery by two oncoradiologists blinded to the eventual postoperative histopathology findings. An objective (mrTRG) and a subjective Likert score were assigned to all the cases. Receiver operating characteristic curves were constructed to determine the ability of Likert scale and mrTRG to predict pCR, with postoperative histopathology being the gold standard. The optimal cutoff points on the scale of 1 to 5 were obtained for mrTRG and Likert scale with the greatest sum of sensitivity and specificity using the Youden Index.
The most accurate cutoff point for the mrTRG to predict complete response was 2.5 (using Youden index), with a sensitivity of 69.2%, specificity of 69.6%, positive predictive value (PPV) of 85.6%, negative predictive value (NPV) of 46.4%, and accuracy of 69.3%. The most accurate cutoff for the Likert scale to predict complete response was 3.5, with a sensitivity of 47.5%, specificity of 89.1%, PPV of 91.9%, NPV of 39.4%, and accuracy of 59%. mrTRG had a lower cutoff and was more accurate in predicting pCR compared to Likert score.
An objective mrTRG was more accurate than a subjective Likert scale to predict complete response in our study.
Accumulated studies have verified that tumor regression is associated with the prognosis of rectal cancer. However, stratified analysis within a certain stage is still unknown. The purpose of our ...study was to assess the impact of pathologic response on the survival of stageII and III rectal cancer patients after neoadjuvant chemoradiotherapy (nCRT).
Clinicopathologic characteristics and tumor regression scores (TRS) were assessed in 236 rectal cancer patients who treated with nCRT followed by surgery. Survival analysis was performed using Cox proportional hazards models.
Among these patients, the stage of 88 patients was ypII, and 91 patients were with the stage of ypIII. The median follow-up time was 59.8 months. TRS was not an independent prognostic factor in ypII patients while it was significantly associated with the prognosis of ypIII patients (5-year survival rate 67.2% vs. 42.5%,
< 0.001). Furthermore, ypIII patients with the response to nCRT had similar survival to that of ypII patients (5-year survival rate 67.2% vs. 70.5%,
= 0.56). For ypIII patients, multivariable analysis showed that well differentiation, negative surgical margin, and the administration of adjuvant chemotherapy were associated with better survival. The surgical margin and differentiation were prognostic factors for ypII patients.
ypIII rectal cancer patients with poor response to preoperative treatment are at high risk of worse oncological outcomes.
Immune checkpoint inhibitors are increasingly used in neoadjuvant therapy for locally advanced gastric cancer. However, the effect of body composition on the efficacy of neoadjuvant therapy has not ...been reported.
The computed tomography (CT) images and clinicopathological data of 101 patients with locally advanced gastric cancer who received neoadjuvant chemotherapy combined with immunotherapy (NCI) from 2019 to 2021 were collected. The CT image of L3 vertebral body section was selected, and the body composition before and after the neoadjuvant treatment was calculated using the SliceOmatic software, mainly including skeletal muscle index (SMI), subcutaneous adipose index (SAI), and visceral adipose index (VAI). The relationship between body composition and the efficacy and adverse events of NCI was analyzed.
Of the 101 patients, 81 with evaluable data were included in the analysis. Of the included patients, 77.8% were male; the median age of all the patients was 62 years, and the median neoadjuvant therapy cycle was three. After the neoadjuvant therapy, 62.9% of the tumors were in remission (residual tumor cells ≤ 50%), and 37.1% of the tumors had no remission (residual tumor cells>50%). Moreover, 61.7% of the patients had treatment-related adverse events (TRAEs), and 18.5% had immune-related adverse events (irAEs). After neoadjuvant therapy, the body mass index (from 23 to 22.6 cm
/m
, p=0.042), SAI (from 34.7 to 32.9 cm
/m
, p=0.01) and VAI (from 32.4 to 26.8 cm
/m
, p=0.005) were significantly lower than those before treatment, while the SMI had no significant change (44.7 vs 42.5 cm
/m
, p=0.278). The multivariate logistics regression analysis revealed that low SMI (odds ratio OR: 3.23,95% confidence interval CI: 1.06-9.81, p=0.047), SMI attenuation (△SMI) ≥ 1.8(OR: 1.45,95%CI: 1.20-3.48, p=0.048), and clinical node positivity (OR: 6.99,95%CI: 2.35-20.82, p=0.001) were independent risk factors for non-remission. Additionally, high SAI is an independent risk factor for irAEs (OR: 14, 95%CI: 1.73-112.7, p=0.013).
Low SMI and △SMI≥1.8 are independent risk factors for poor tumor regression in patients with advanced gastric cancer receiving NCI. Patients with a high SAI are more likely to develop irAEs.
Glioblastoma is one of the most fatal diseases in human central nerve system. However, the prognosis and treatment of glioblastoma still call for steady improvement. In recent years, increasing ...studies have revealed that the abnormal expression of long non-coding RNA (lncRNA) is closely related to carcinogenesis and prognosis. Unfortunately, many lncRNAs still need further research in their function and molecule mechanism. LncRNA TRG-AS1 hasn’t been detected in any types of cancers before. TRG-AS1 is associated with poor prognosis and is upregulated in glioblastoma tissues and cells. TRG-AS1 can also accelerate glioblastoma cell proliferation in return. On the other hand, miRNA-877-5p expresses low in glioblastoma and contains binding sites with both TRG-AS1 and SUZ12. Furthermore, TRG-AS1 suppresses the expression of miR-877-5p while miR-877-5p suppresses SUZ12 expression. Overexpression of TRG-AS1 could promote the expression of SUZ12.Rescue assays demonstrates that overexpression of SUZ12 can counteract the decline of glioblastoma cell proliferation induced by knockdown of TRG-AS1. Based on all these assays, TRG-AS1 promotes glioblastoma cell proliferation by acting as a ceRNA of miR-877-5p to regulate SUZ12 expression. TRG-AS1 might serve as a new target in glioblastoma treatment.
This study was designed to observe the efficacy and safety of albumin-bound paclitaxel plus nedaplatin as neoadjuvant therapy in patients with esophageal squamous cell carcinoma (ESCC). From April ...2019 to Dec 2020, patients with ESCC who underwent Mckeown surgery at our center were analyzed retrospectively. All patient received 2 to 3 cycles of albumin-bound paclitaxel combined with nedaplatin before surgery, tumor regression grade (TRG) and American National Cancer Institute Common Toxicity Criteria version 5.0 were used to evaluate its efficacy and safety. TRG grades from TRG 2 to TRG 5are considered effective in chemotherapy, TRG 1 stands for pathological complete response (pCR). A total of 41 patients were included in this study. All patients achieved R0 resection. According to the TRG classification, the number of patients assessed for TRG 1-TRG 5 were: 7 cases, 12 cases, 3 case, 12 cases and 7 cases. Its objective response rate and pCR were 82.9% (34/41) and 17.1% (7/41), respectively. We found that hematological toxicity is the most common adverse events of this regimen, with an incidence of 24.4%, followed by digestive tract reactions, with an incidence of 17.1%. Hair loss, neurotoxicity and hepatological disorder are the others, their incidence was 12.2%, 7.3%, and 2.4%; and chemotherapy related deaths were no found. Notably, 7 patients achieved pCR without recurrence or death. Survival analysis showed that patients with pCR may have longer disease-free survival (P = .085) and overall survival (P = .273), although the difference was not statistically significant. As neoadjuvant therapy for patients with ESCC, albumin-bound paclitaxel combined with nedaplatin has a higher pCR rate and less side effects. It is a reliable choice for ESCC patients as neoadjuvant therapy.
The lncRNA TRG-AS1 and its co-expressed gene P2RY10 are important for colorectal cancer (CRC) occurrence and development. The purpose of our research was to explore the roles of TRG-AS1 and P2RY10 in ...CRC progression.
The abundance of TRG-AS1 and P2RY10 in CRC cell lines (HT-29 and LoVo) and normal colon cells FHC was determined and difference between CRC cells and normal cells was compared. LoVo cells were transfected with si-TRG-AS1 and si-P2RY10 constructs. Subsequently, the viability, colony formation, and migration of the transfected cells were analyzed using cell counting kit-8, clonogenicity, and scratch-wound/Transwell® assays, respectively. Cells overexpressing GNA13 were used to further explore the relationship between TRG-AS1 and P2RY10 along with their downstream functions. Finally, nude mice were injected with different transfected cell types to observe tumor formation
.
TRG-AS1 and P2RY10 were significantly upregulated in HT-29 and LoVo compared to FHC cells. TRG-AS1 knockdown and P2RY10 silencing suppressed the viability, colony formation, and migration of LoVo cells. TRG-AS1 knockdown downregulated the expression of P2RY10, GNA12, and GNA13, while P2RY10 silencing downregulated the expression of TRG-AS1, GNA12, and GNA13. Additionally, GNA13 overexpression reversed the cell growth and gene expression changes in LoVo cells induced by TRG-AS1 knockdown or P2RY10 silencing.
experiments revealed that CRC tumor growth was suppressed by TRG-AS1 knockdown and P2RY10 silencing.
TRG-AS1 knockdown repressed the growth of HT-29 and LoVo by regulating P2RY10 and GNA13 expression.
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