Clinical Efficacy Of Neoadjuvant Chemotherapy Research Articles

Pathologic Response Rates in Patients with Gastric Cancer Following FLOT Neoadjuvant Chemotherapy

Background: Gastric adenocarcinoma is among the most prevalent cancers associated with a high mortality rate. The multidrug neoadjuvant chemotherapy administered before and after surgery has attracted attention as a beneficial standard of care for managing this malignancy. Objectives: This study assessed the pathologic response of patients with gastric cancer who were treated with fluorouracil plus leucovorin, oxaliplatin, and docetaxel (FLOT). Methods: Patients with pathologically confirmed gastric adenocarcinoma without distant metastases were enrolled in this retrospective cohort study conducted at Imam Reza and Ghaem hospitals in Mashhad. Data regarding demographics, tumor status, treatment toxicity, and pathology results were collected using a predesigned questionnaire after four cycles of FLOT neoadjuvant chemotherapy. SPSS-26.0 was utilized to analyze the data, and a significance level of P < 0.05 was applied. Results: We evaluated data from 53 cases with a mean age of 51.1 ± 9.7 years. Diffuse adenocarcinoma was the most common finding in histology (54.7%). Pathologic complete response was observed in 16 (30.2%) patients. Most (69.8%) patients received only 7 out of 8 planned cycles. Concerning surgical margin, 46 (86.8%) patients achieved R0 tumor resection. Pathologic complete response was not significantly linked with age (P = 0.91), sex (P = 0.65), performance status (P = 0.2), tumor histology (P = 0.14), tumor grading (P = 0.07), tumor location (P = 0.8), and the number of neoadjuvant chemotherapy cycles (P = 0.9). Conclusions: Our findings demonstrated the relative clinical efficacy of neoadjuvant chemotherapy with the FLOT regimen administered before and after surgery. However, due to chemotherapy-related side effects, patients may not adhere to all eight prescribed cycles of chemotherapy.

Clinical efficacy of Neoadjuvant Chemotherapy combined with Laparoscopic Surgery in patients with Middle and Low Rectal Cancer and its Effect on serum VEGF Levels and quality of life.

To observe the clinical efficacy of neoadjuvant chemotherapy combined with laparoscopic surgery in patients with middle and low rectal cancer and its effect on serum VEGF level and quality of life. Retrospective analysis was performed on 80 patients with middle and low rectal cancer admitted to Baoding No.1 Central Hospital from June 2018 to June 2020.They were randomly divided into two groups. Patients in the control group underwent laparoscopic radical rectal cancer surgery, while those in the experimental group underwent neoadjuvant chemotherapy before surgery. The differences of various surgical indicators between the two groups were compared. The incidence of surgical complications, the serum VEGF levels and the improvement of quality of life were compared. The differences in local recurrence, metastasis and overall survival with in two years after surgery were compared. The various surgical indicators of the experimental group were significantly better than the control group (p<0.05). After treatment, the VEGF levels in the experimental group were significantly lower than those in the control group (p=0.00), while the SF-36 score was significantly higher than that of the control group (p=0.00). The total incidence of surgical complications in experimental group was significantly lower (p=0.03), the local recurrence rate was significantly lower (p=0.02), and the overall survival rate was significantly higher than that in control group (p=0.04). Neoadjuvant chemotherapy combined with laparoscopic surgery is superior to direct surgery alone in the treatment of middle and low rectal cancer and it needs to be promoted.

Clinical Efficacy of Neoadjuvant Chemotherapy with Gemcitabine plus S-1 for Resectable Pancreatic Ductal Adenocarcinoma Compared with Upfront Surgery.

The efficacy of neoadjuvant chemotherapy with gemcitabine plus S-1 (NAC-GS) in the prognosis of patients with resectable pancreatic ductal adenocarcinoma (PDAC) has been reported. NAC-GS is now assumed to be a standard regimen for resectable PDAC in Japan. However, the reason for this improvement in prognosis remains unclear. In 2019, we introduced NAC-GS for resectable PDAC. From 2015 to 2021, 340 patients were diagnosed with resectable PDAC (anatomical and biological [carbohydrate antigen (CA) 19-9 <500U/mL]) and were divided according to the treatment period (upfront surgery [UPS] group, 2015-2019, n = 241; NAC-GS group, 2019-2021, n = 80). We used "intention-to-treat" analysis to compare the clinical outcomes of NAC-GS to those of UPS. Of the 80 patients with NAC-GS, 75 (93.8%) completed two cycles of NAC-GS, and the resection rate of the NAC-GS group was comparable to that of the UPS group (92.5 vs. 91.3%, P = 0.73). The R0 resection rate was significantly higher in the NAC-GS group than in the UPS group (91.3 vs. 82.6%, P = 0.04), even though the surgical burden was smaller. Progression-free survival tended to be better (hazard ratio [HR] = 0.70, P = 0.06), and overall survival was significantly better in the NAC-GS group than in the UPS group (HR 0.55, P = 0.02). NAC-GS provided improvements in microscopic invasion leading to a high R0 rate and smooth administration and completion of adjuvant therapy, which might lead to an improved prognosis in patients with resectable PDAC.

Laparoscopic Radical Hysterectomy Combined with Neoadjuvant Chemotherapy for Cervical Cancer Patients Effectively Improves Immune Function.

Objective To evaluate the clinical efficacy of neoadjuvant chemotherapy plus laparoscopic radical hysterectomy for cervical cancer and the effect on the immune function of patients. Methods Between January 2021 and December 2021, 42 patients with cervical cancer diagnosed and treated at our hospital were recruited and randomly assigned at a 1 : 1 ratio to receive neoadjuvant chemotherapy plus open radical hysterectomy (control group) or neoadjuvant chemotherapy plus laparoscopic radical hysterectomy (treatment group) (study group). Outcome measures included surgical indices, clinical outcomes, and immunological function. Results There were no significant differences in the operative time between the two groups (P > 0.05). Patients receiving laparoscopic surgery had significantly less intraoperative bleeding and shorter time lapse before postoperative anal exhaustion, time lapse before out-of-bed activities, and hospital stay versus patients receiving open surgery (P < 0.05). Laparoscopic surgery resulted in a significantly higher efficacy (90.48%) versus open surgery (57.14%) (P < 0.05). After treatment, patients in the study group showed lower levels of carcinoembryonic antigen (CEA), squamous cell carcinoma antigen (SCC-Ag), and cancer antigen (CA125) than those in the control group (P < 0.05). After treatment, patients given laparoscopic surgery showed significantly lower CD3+, CD4+, and CD8+ levels and higher CD4+/CD8+ levels versus those with open surgery (P < 0.05). The postoperative conditions of the two groups, including recatheterization, postoperative blood transfusion, and secondary anti-inflammation were not significantly different (P > 0.05). The study group showed a significantly lower incidence of complications (19.05%) than the control group (71.43%) (P < 0.05). Patients in the study group had a lower reoperation rate and a higher survival rate (0.00%, 95.24%) than those in the control group (19.05%, 66.67%) (P < 0.05). Conclusion Neoadjuvant chemotherapy plus laparoscopic radical hysterectomy effectively improves clinical efficacy, lowers cancer marker levels, improves patients' immune function, reduces the risk of adverse events, and improves patients' prognosis with less intraoperative bleeding, less trauma, faster postoperative recovery, and shorter hospital stay for cervical cancer patients.

Clinical Value of PLR, MLR, and NWR in Neoadjuvant Chemotherapy for Locally Advanced Gastric Cancer.

Objective The clinical value of platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), and neutrophil-to-white blood cell ratio (NWR) in predicting the prognosis of patients with locally advanced gastric cancer after neoadjuvant chemotherapy (NACT) was studied. Methods A total of 131 patients with locally advanced gastric cancer treated with neoadjuvant chemotherapy in our hospital from May 2015 to June 2018 were selected as the study subjects, and all were treated with neoadjuvant chemotherapy. The relationship between the values of PLR, MLR, and NWR and the efficacy of neoadjuvant chemotherapy and clinical staging was analyzed; all patients were followed up for 3 years. Patients were divided into death group and survival group according to the survival of patients. The predictive value of PLR, MLR, and NWR values for patients' prognosis was analyzed, and the survival rates of patients with different PLR, MLR, and NWR values were compared. Results The effective rate of neoadjuvant chemotherapy in patients with locally advanced gastric cancer was 62.60% (82/131), and the PLR, MLR, and NWR values in the effective group were lower than those in the ineffective group (P < 0.05). The AUC of combined PLR, MLR, and NWR in evaluating the efficacy of neoadjuvant chemotherapy was greater than that of PLR and NWR alone (P < 0.05). The PLR value of patients with stage IIIa, IIIb, and IIIc was greater than that of patients with stage II, the MLR value of patients with stage IIIb and IIIc was greater than that of patients with stage II and IIIa, and the NMR value of patients with stage IIIc was greater than that of patients with stage II, IIIa, and IIIb (P < 0.05). PLR, MLR, and NWR values were positively correlated with clinical stage (P < 0.05). The PLR, MLR, and NWR values in the survival group were lower than those in the death group (P < 0.05). The AUC of combined PLR, MLR, and NWR in predicting the prognosis of patients was greater than that of MLR and NWR alone (P < 0.05). The survival rate of patients with PLR ≥ 162.11 (36.21%) was lower than that of patients with PLR < 162.11 (80.82%), and the survival rate of patients with MLR ≥ 0.31 (42.86%) was lower than that of patients with MLR < 0.31 (74.67%), and the survival rate of patients with NWR ≥ 0.62 (45.00%) was lower than that of patients with NWR < 0.62 (74.65%) (P < 0.05). Conclusions PLR, MLR, and NWR values are correlated with clinical stage, and the combined detection has value in evaluating the clinical efficacy of neoadjuvant chemotherapy and predicting the prognosis of patients with locally advanced gastric cancer.

Effect of Early-Stage Human Breast Carcinoma on Monocyte Programming.

Circulating monocytes are a major source of tumor-associated macrophages (TAMs). TAMs in human breast cancer (BC) support primary tumor growth and metastasis. Neoadjuvant chemotherapy (NAC) is a commonly used treatment for BC patients. The absence of the response to NAC has major negative consequences for the patient: increase of tumor mass, delayed surgery, and unnecessary toxicity. We aimed to identify the effect of BC on the subpopulation content and transcriptome of circulating monocytes. We examined how monocyte phenotypes correlate with the response to NAC. The percentage of CD14-, CD16-, CD163-, and HLA-DR-expressing monocytes was quantified by flow cytometry for patients with T1-4N0-3M0 before NAC. The clinical efficacy of NAC was assessed by RECIST criteria of RECIST 1.1 and by the pathological complete response (pCR). The percentage of CD14+ and СD16+ monocytes did not differ between healthy women and BC patients and did not differ between NAC responders and non-responders. The percentage of CD163-expressing CD14lowCD16+ and CD14+CD16+ monocytes was increased in BC patients compared to healthy women (99.08% vs. 60.00%, p = 0.039, and 98.08% vs. 86.96%, p = 0.046, respectively). Quantitative immunohistology and confocal microscopy demonstrated that increased levels of CD163+ monocytes are recruited in the tumor after NAC. The percentage of CD14lowCD16+ in the total monocyte population positively correlated with the response to NAC assessed by pCR: 8.3% patients with pCR versus 2.5% without pCR (p = 0.018). Search for the specific monocyte surface markers correlating with NAC response evaluated by RECIST 1.1 revealed that patients with no response to NAC had a significantly lower amount of CD14lowCD16+HLA-DR+ cells compared to the patients with clinical response to NAC (55.12% vs. 84.62%, p = 0.005). NGS identified significant changes in the whole transcriptome of monocytes of BC patients. Regulators of inflammation and monocyte migration were upregulated, and genes responsible for the chromatin remodeling were suppressed in monocyte BC patients. In summary, our study demonstrated that presence of BC before distant metastasis is detectable, significantly effects on both monocyte phenotype and transcriptome. The most striking surface markers were CD163 for the presence of BC, and HLA-DR (CD14lowCD16+HLA-DR+) for the response to NAC.

Pretreatment tumour immune microenvironment predicts clinical response and prognosis of muscle-invasive bladder cancer in the neoadjuvant chemotherapy setting.

We examined the relationship between the tumour microenvironment and the clinical efficacy of neoadjuvant chemotherapy in patients with cT2-4aN0M0 bladder cancer using multiplex fluorescence immunohistochemistry. The study retrospectively evaluated 51 patients who underwent radical cystectomy following neoadjuvant chemotherapy for cT2-4aN0M0 muscle-invasive bladder cancer. Patients were divided into responders (<pT2) and non-responders (≥pT2). We assessed the density of each immune cell type in intratumoural and peritumoural areas in both groups via multiplex fluorescence immunohistochemical analysis. The median age was 69 years; 39 patients were male. Twelve (23.5%), 17 (33.3%), 10 (19.7%) and 12 (23.5%) patients were pT0, pT1, pT2 and ≥pT3, respectively. Responders had a significantly higher 5-year cancer-specific survival rate (96.6%) than non-responders (48.4%; p = 0.0018). CD8+ T cell (p = 0.0056) and CD204+ cell (p = 0.0394) densities were significantly higher in the intratumoural area in non-responders than in responders. Patients with higher CD204+ cell densities in cancerous areas had worse prognosis. This comprehensive analysis of the immune microenvironment of a muscle-invasive bladder cancer specimen revealed that preexisting tumour-infiltrating proliferating CD8+ T cells and CD204+ cells are indicators of the response to neoadjuvant chemotherapy and that CD204+ cells can be considered an unfavourable prognostic factor in these patients.

Short-Term Clinical Efficacy of Neoadjuvant Chemotherapy Combined With Laparoscopic Gastrectomy for Locally Advanced Siewert Type II and III Adenocarcinoma of the Esophagogastric Junction: A Retrospective, Propensity Score-Matched Study.

BackgroundLaparoscopic gastrectomy (LG) has been increasingly used for the treatment of locally advanced Siewert type II and III adenocarcinoma of the esophagogastric junction (AEG). However, whether LG can achieve the same short-term efficacy in the treatment of patients who receive neoadjuvant chemotherapy (NACT) remains controversial. Thus, the aim of this study was to investigate the clinical outcomes of NACT combined with LG for Siewert type II and III AEG.MethodsThis retrospective study identified patients with locally advanced Siewert type II and III AEG diagnosed between May 2011 and October 2020 using the clinical tumor-node-metastasis (cTNM) staging system. The short-term outcomes were compared between the matched groups using a 1:3 propensity score matching (PSM) method, which was performed to reduce bias in patient selection.ResultsAfter PSM, 164 patients were selected, including 41 in the NACT group and 123 in the LG group. The baseline characteristics were similar between the two groups. Compared with the LG group, the NACT group exhibit a smaller tumor size and significantly less advanced pathological tumor classification and nodal classification stages. The time to first flatus of the NACT group was significantly shorter, but the hospital stay was significantly longer than that of the LG group. The NACT group showed similar overall (29.3% vs 25.2%, P=0.683), systemic (24.4% vs 21.1%, P=0.663), local (12.2% vs 9.8%, P=0.767), minor (19.5% vs 19.5%, P=1.000) and major (9.8% vs 5.7%, P=0.470) complications as the LG group. Subgroup analyses showed no significant differences in most stratified parameters. Operation time≥ 300 minutes was identified as an independent risk factor for overall complications. Age≥ 60 years was identified as an independent risk factor for major complications.ConclusionNACT combined with LG for AEG does not increase the risk of postoperative morbidity and mortality compared with LG.

Changes of the redox-regulatory system in tumor and its surrounding tissues in patients with soft tissue sarcoma (STS) after neoadjuvant chemotherapy (NC).

e23522 Background: The disruptions in redox homeostasis in the nonmalignant tissues surrounding neoplasm can promote the tumor progression. The aim of this work was to assess the changes of the redox-regulatory system in the tumor and tumor-surrounding tissues in STS patients (pts) under the influence of a mofified metod of NC. Methods: The activity of glutathione S-transferase (GST), glutathione peroxidase (GPx), glutathione reductase (GR), content of reduced glutathione (GSH) and malondialdehyde (MDA) were determined by spectrophotometric methods. All markers were measured in the samples of tumor, peritumoral area and healthy tissues (taken along the line of resection) obtained during the surgery from 42 STS pts (T2a-bN0M0). The control group consisted of 21 primary pts who underwent resection only. Patients of the experimental group (21) received NC comprising systemic and local administration of antitumor drugs. Doxorubicin (40 mg/m2) was injected intravenously on the 1st and 7th days with autologous red blood cells as drug carriers; at the same time, cyclophosphamide (600 mg/m2) and methotrexate (40 mg/m2) were injected along the tumor periphery, on autologous plasma as a carrier. After 14 days, tumor removal surgery performed. All STS pts received standard postoperative chemoradiotherapy. Results: The level of GSH in tumor without NC treatment was higher than in the healthy and peritumoral tissue (by 2.3-2.5 times), and the activity of all glutathione-dependent enzymes was higher by 53.0-147.0 % (p = 0.0413-0.00124). The content of MDA in tumor was lower than in other tissues by 30.0-46.0 % (p = 0.00061). We did not find any differences between the healthy and peritumoral areas. In tumor samples of the experimental group, we also observed statistically significant increase in the level of GSH (by 2.8–3.0 times) and activation of GPO (by 37.3-95.8 %) and GR (by 2.0-3.2 times) vs. other tissues. However, after NC, the studied samples showed an increase in GSH by 3.1–3.8 times (p = 0.0143–0.00112), compared with the corresponding control samples. Also, the activity of GPO (by 54.5 %) and GsT (by 38.9 %) was significantly increased in peritumoral tissue vs similar area in the control group. After NC, the content of MDA was reduced in the healthy and tumor tissues vs control by 52.0 % (p = 0.0074) and 30.6 % (p = 0.04815), respectively. Clinical efficacy of NC was confirmed by reduced tumor volume in most patients by 30-40 %; the 5-year monitoring of STS pts showed that local recurrence and metastasis occurred in 14 of 21 pts in the control group, and in 6 of 21 in the main group (p = 0.0294). Conclusions: The NC treatment modifies the redox balance in the tumor-surrounding tissues and, as a result, decreases the oxidation damages in the healthy tissues. This effect, apparently, is an additional factor that improves the effectiveness of the proposed NC method.

Rs2686344 and serum squamous cell carcinoma antigen could predict clinical efficacy of neoadjuvant chemotherapy for cervical cancer

ObjectiveTo evaluate the predictive value of a single nucleotide polymorphism (SNP) rs2686344 and squamous cell carcinoma antigen (SCCAg) levels in the clinical efficacy of neoadjuvant chemotherapy (NACT) for cervical cancer. MethodsA total of 92 patients with stage IB2-IIIB carcinoma of the uterine cervix who received NACT treatment were enrolled. The relationship between the genotypes of SNP rs2686344 which is located on CAMKK2 on chromosome 12, SCCAg levels and the response to NACT was analyzed. The relationship between the SNP rs2686344 genotypes, SCCAg levels, the response to NACT and the five-year survival rate was evaluated. ResultsThe effective group accounted for 84.85% in patients with low level (≤3.5 ng/mL) of post-treatment SCCAg (post-SCCAg), while the ineffective group accounted for 15.15%. The post-SCCAg levels and the genotypes of rs2686344 were significantly correlated with NACT response (P = 0.003, and P = 0.006). In patients with CC or CT genotype of SNP rs2686344, effective group accounted for 81.18%, while ineffective group accounted for 18.82%; For patients with TT genotype, effective response group accounted for 28.57%, ineffective group accounted for 71.43%. Post-SCCAg level >3.5 ng/mL and TT genotype of SNP rs2686344 showed as independent risk factors for NACT response in the multivariate analysis (P = 0.002, and P = 0.048). There was no significant difference in 5-year overall survival and 5-year disease-free survival between patients with different levels of post-SCCAg, or among different rs2686344 genotypes. ConclusionThe high level of post-SCCAg (>3.5 ng/mL) and TT genotype of rs2686344 may suggest a higher risk of poor response to NACT.

A Retrospective Study of Neoadjuvant Chemotherapy for Locally Advanced Gastric Cancer.

ObjectiveTo explore the efficacy and safety of neoadjuvant chemotherapy in the doublet and triplet regimens of locally advanced gastric cancer.Patients and MethodsA retrospective analysis was conducted on 162 patients with gastric cancer who received neoadjuvant chemotherapy, including 74 patients receiving doublet regimen (fluorouracil/platinum) and 88 patients receiving triplet regimen (fluorouracil/platinum/Taxol). Patients in both groups received neoadjuvant chemotherapy for two cycles, and underwent surgical resection 4 weeks after the end of chemotherapy.ResultsThe total clinical remission rate was 68.6% (105/153), the phase-down rate was 46.4% (71/153), and the pathological response rate was 59.9% (97/162). In the doublet and triplet regimen, the clinical remission rate was 65.7% (44/67) and 70.9% (61/86) (P = 0.708), the descending period rate was 41.8% (28/67) and 50.0% (43/86) (P = 0.485), and the pathological response rate was 51.4% (38/74) and 67.0% (59/88) (P = 0.190). The median disease-free survival (DFS) and overall survival (OS) of 162 patients were 36.0 and 58.5 months. In the doublet and triplet regimen, the median DFS was 38.0 and 34.0 months (P = 0.377), and the median OS was 59.0 and 56.5 months (P = 0.256). The side effects of the doublet group were significantly lower than those of the triplet group, with leucopenia rate of 45.9% (34/74) and 62.5% (55/88) (P = 0.035); thrombocytopenia rate of 18.9% (14/74) and 35.2% (31/88) (P = 0.021); nausea rate of 45.9% (34/74) and 64.8% (57/88) (P = 0.016), and diarrhea rate of 1.4% (1/74) and 9.1% (8/88) (P = 0.032).ConclusionNeoadjuvant chemotherapy is safe and effective for locally advanced gastric cancer. The clinical efficacy of neoadjuvant chemotherapy in the doublet group and the triplet group is equivalent, and the doublet group has better safety and tolerance.

160 - Evaluating the clinical efficacy of neoadjuvant chemotherapy for node-positive upper tract urothelial carcinoma: A multi-center cohort study

160 - Evaluating the clinical efficacy of neoadjuvant chemotherapy for node-positive upper tract urothelial carcinoma: A multi-center cohort study

Abstract OT1-03-01: Inhibiting fatty acid synthase to improve efficacy of neoadjuvant chemotherapy

Abstract Background Human Fatty Acid Synthase (FASN) is the sole cytosolic enzyme responsible for de novo synthesis of long chain fatty acids. Unlike normal tissues, cancer cells require FASN dependent fatty acid synthesis for survival. FASN is overexpressed in 70% of newly diagnosed triple negative breast cancer (TNBC) and associated with significantly shorter disease free and overall survival. In vitro, FASN overexpression induces resistance to multiple DNA damaging agents including doxorubicin and cisplatin. Proton pump inhibitors (PPI), particularly omeprazole can selectively inhibit FASN enzyme activity at a Ki of 3.4umol. Inhibition of FASN activity with PPIs induces apoptosis selectively in cancer cells with minimal effect on non-malignant breast cell lines. PPIs are well tolerated and are FDA approved for a variety of gastro-intestinal disorders. We hypothesize that PPIs will effectively inhibit FASN activity and improve clinical efficacy of neoadjuvant chemotherapy with minimal added toxicity in operable TNBC. Materials and Methods This is a single arm multi -center phase II study of omeprazole 80mg PO BID in combination with standard neoadjuvant anthracycline-weekly taxane chemotherapy (AC-T; Adriamycin 60mg/m2 Cyclophosphamide 600mg/m2 given every q2w with G-CSF or q 3wk x 4 followed by weekly paclitaxel 80mg/m2 x 12) in patients with newly diagnosed clinically stage II or greater TNBC (NCT02595372). Neoadjuvant carboplatin may be offered with weekly paclitaxel at treating physician’s discretion. Patients with prior over the counter or prescription PPI use within 12 months are excluded. An initial core biopsy is performed at baseline, after which patients begin omeprazole monotherapy for a brief period (4-7 days). This is followed by a second research core biopsy and initiation of standard AC-T. PPI is continued until night before definitive surgery. Study follow up ends with definitive surgery and after resolution of known adverse events (&amp;lt;=G1). The primary endpoint is the rate of pCR (defined as no residual invasive disease in breast or axilla) in study patients with FASN expression. Relevant secondary endpoints include rate of pCR in all patients, change in FASN expression, enzymatic activity and downstream target gene expression from baseline to surgery; safety and limited omeprazole PK sampling during the study. Assuming that 70% of newly diagnosed TNBC have FASN expression, a single stage phase II trial to detect a pCR rate of 60% (null= pCR-40%) with 80% power and alpha of 0.10 requires 30 FASN patients (or 42 patients total). This sample size also provides approximately 80% power to identify a change in FASN expression and/or activity of 0.5 SDs using a paired t-test and significance level of 0.05. Conclusion The study enrolled its last participant in May 2019. Six patients are in follow-up who have yet to undergo definitive surgery. Final study patient is anticipated to have surgery in October 2019, with final data analysis planned in the last quarter of 2019. Funding This work has been supported by the Breast Cancer Research Foundation. Citation Format: Sagar Sardesai, Alexandra Thomas, Christopher Gallagher, Filipa Lynce, Yvonne Ottaviano, Tarah Ballinger, Brian P Schneider, Anna Maria Storniolo, Susan Perkins, Jian Tian Zhang, Kathy D Miller. Inhibiting fatty acid synthase to improve efficacy of neoadjuvant chemotherapy [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr OT1-03-01.

Efficacy analysis of neoadjuvant chemotherapy for resectable locally advanced adenocarcinoma of the esophageal-gastric junction

Objective To investigate the clinical efficacy of neoadjuvant chemotherapy (oxaliplatin + capecitabine, XELOX) for the resectable locally advanced adenocarcinoma of esophageal-gastric junction (AEG). Methods The prospective study was conducted. The clinicopathological data of 106 locally advanced AEG patients who were admitted to the Cancer Hospital of Shantou University Medical College from January 2011 to December 2014 were collected. All the patients were divided into the treatment group and control group by single blind, randomized, controlled random number table. Patients underwent preoperative neoadjuvant chemotherapy (XELOX) + surgery + postoperative adjuvant chemotherapy (XELOX) in the treatment group and surgery + postoperative adjuvant chemotherapy (XELOX) in the control group. Total gastrectomy + Roux-en-Y esophagojejunostomy + D2 lymphadenectomy were applied to patients by the same team of doctors. Observation indicators: (1) treatment situations; (2) results of postoperative pathological examination; (3) follow-up and survival situations. Follow-up using outpatient examination was performed to detect the postoperative tumor recurrence or metastasis and patients′ survival up to February 2017. Measurement data with normal distribution were represented as ±s, and comparisons between groups were evaluated with the t test. Measurement data with skewed distribution were described as M (range) and analyzed by the nonparametric test. Comparisons of count data were analyzed using the chi-square test. The ordinal data were compared using the nonparametric test. Survival rate and curve were respectively calculated and drawn by the Kaplan-Meier method and survivals were compared using the Long-rank method. Results One hundred and six patients were screened for eligibility, including 54 in the treatment group and 52 in the control group. (1) Treatment situations: ① preoperative neoadjuvant chemotherapy: 54 in the treatment group received 2-4 cycle neoadjuvant chemotherapy. During the chemotherapy, gastrointestinal reaction, grade 1-2 granulocytopenia, elevated alanine transaminase (ALT) and grade 3 granulocytopenia were detected in 21, 17, 8, 1 patients, and 7 patients had no adverse reaction. The complete response(CR), partial response (PR), stable disease (SD) and progressive disease (PD) of neoadjuvant chemotherapy in the treatment group were detected in 4, 27, 20 and 3 patients, respectively. Of 54 patients in the treatment group, 4, 13, 25 and 12 were in grade 0, 1, 2 and 3 of response to preoperative chemotherapy, respectively. ② Surgical situations: preoperative carcinoembryonic antigen (CEA) in the treatment and control groups were respectively 4.71 μg/L (range, 0.20-36.19 μg/L) and 14.09 μg/L (range, 0.71-178.20 μg/L), with a statistically significant difference between groups (Z=-1.92, P 0.05). ③ Postoperative adjuvant chemotherapy: all the patients completed the postoperative adjuvant chemotherapy. The granulocytopenia, elevated ALT and gastrointestinal reaction occurred in 25, 5, 28 patients in the treatment group and 21, 7, 30 patients in the control group, respectively, with no statistically significant difference between groups (χ2=0.38, 0.47, 0.36, P>0.05). Some of the patients were merged with multiple adverse reactions. (2) Results of postoperative pathological examination: maximum tumor dimension, cases with lymphovascular invasion, perineural invasion, T0, T2, T3, T4 (T stage), stage 0, Ⅰ, Ⅱ and Ⅲ (TNM stage) were respectively (3.6±1.4)cm, 5, 10, 4, 10, 20, 20, 4, 7, 15, 28 in the treatment group and (4.5±1.7)cm, 24, 30, 0, 2, 13, 37, 0, 1, 12, 39 in the control group, with statistically significant differences between groups (t=-2.88, χ2=18.14, 17.30, Z=14.74, 8.13, P 0.05). There was a statistically significant difference in cases with local recurrence between groups (χ2=4.41, P<0.05) The tumor-free survival time and overall survival time in the treatment group were respectively 29 months (range, 8-72 months), 38 months (range, 10-72 months) in 31 patients with CR and PR and 11 months (range, 3-68 months), 18 months (range, 4-68 months) in 23 patients with SD and PD, showing statistically significant differences in tumor-free and overall survival times (χ2=5.27, 7.72, P<0.05). Conclusion Neoadjuvant chemotherapy with oxaliplatin and capecitabine is safe and effective for patients with the resectable locally advanced AEG, it can also decrease tumor stage and reduce local recurrence, but fail to demonstrate a survival benefit. Key words: Adenocarcinoma of esophagogastric junction; Locally advanced; Neoadjuvant chemotherapy

The application of preoperative neoadjuvant chemotherapy in patients with stage IIIA non-small cell lung cancer

Objective To analyze the clinical efficacy of neoadjuvant chemotherapy in patients with stage ⅢA non-small cell lung cancer (NSCLC). Methods From March 2008 to October 2015, there were 92 cases of stage ⅢA NSCLC patients received 2 cycles of neoadjuvant chemotherapy and underwent radical surgery for lung cancer 3-4 weeks late (observation group), and another group of 65 cases of stage ⅢA NSCLC patients (control group) underwent surgery for lung cancer without preoperative chemotherapy. The clinical data as well as early and meddle term surgical outcome of both groups were analyzed retrospectively. Results The neoadjuvant chemotherapy effective rate was 73.9% in the observation group. All surgeries for lung cancer patients were undertaken either with video-assisted thoracotomy or traditional thoracotomy. No operative mortality and the postoperative pathology findings were in accordance with NSCLC. The bleeding amount and operation time of two groups were similar; the resection rate of the observation group was greater than that of the control group. All patients were followed up at least 3 years, and the 2 years and 3 years survival rate of the observation group was slightly higher than that of the control group. Conclusions Preoperative neoadjuvant chemotherapy in patients with NSCLC can improve the resection rate and prolong the survival time, which is worthy of clinical application. Key words: Chemotherapy, adjuvant; Carcinoma, non-small-cell lung/TH

A retrospective clinical study of neoadjuvant chemotherapy for advanced epithelial ovarian cancer

Abstract Objective The aim of this study was to investigate the clinical efficacy of neoadjuvant chemotherapy (NACT) and the prognostic factors for advanced epithelial ovarian cancer (EOC). Methods We enrolled 241 patients with stage III and IV EOC who were diagnosed at the Yunnan Cancer Hospital between October 2006 and December 2015. The observation (NACT-IDS) group (n = 119) received 1-3 courses of platinum-based NACT, followed by interval debulking surgery (IDS) and 6-8 courses of postoperative chemotherapy. The control group underwent primary debulking surgery (PDS) (n = 122) followed by 6-8 courses of postoperative chemotherapy. We analyzed the general conditions of the operations and the survival of both groups. Results Operating time, intraoperative blood loss and postoperative hospitalization were significantly lower in the NACT-IDS group (P &lt; 0.05). The rate of optimal cytoreductive surgery was significantly higher in the NACT-IDS group (P &lt; 0.05). A visible residual lesion was observed in 49 (41.18%) and 48 (40%) cases in the NACT-IDS and PDS groups, respectively, which were not significantly different (P &gt; 0.05). The percentage of International Federation of Gynecology and Obstetrics (FIGO) stage IV tumors and the recurrence rates were significantly higher in the NACT-IDS group (P &lt; 0.05). The mortality rates were 45.19% (47/104) and 35.19% (38/108) in the NACT-IDS and PDS groups, respectively (P &gt; 0.05). Progression-free survival was 23.75 ± 9.98 and 23.57 ± 12.25 months in the NACT-IDS and PDS groups, respectively (P &gt; 0.05). Overall survival (OS) was 31.11 ± 15.66 and 29.63 ± 18.00 months in the NACT-IDS and PDS groups, respectively (P &gt; 0.05). Optimal cytoreductive surgery with or without residual lesion was an independent influencing factor for advanced EOC in multivariate analysis. OS of patients treated with ≥8 courses of chemotherapy was significantly longer than those treated with &lt; 8 courses. Conclusion NACT could improve the intra- and postoperative conditions in advanced EOC patients. Although the percentage of FIGO stage IV cancer was significantly higher in the NACT-IDS group, the prognosis was similar in both the NACT-IDS and PDS groups, suggesting that NACT improves the clinical outcome of advanced EOC. Optimal cytoreductive surgery with no residual lesion is a long-term protective factor in advanced EOC. At least 8 courses of chemotherapy overall or ≥ 6 courses postoperatively improves the OS.

Value of the level of methylation of RASSF1A and WIF-1 in tissue and serum in neoadjuvant chemotherapeutic assessment for advanced breast cancer.

This study assessed the clinical efficacy of the neoadjuvant chemotherapy TAC scheme in treatment of patients with locally advanced breast cancer, and the value of the level of Ras association domain family 1A (RASSF1A) gene methylation and the Wnt inhibitory factor (WIF)-1 gene in tissue and serum of patients in clinical outcome prediction. In total, 126 patients were consecutively selected to receive TAC scheme (docetaxel, pirarubicin/epirubicin and cyclophosphamide) for at least four cycles with the total effective rate. The incidence of complications, progression-free survival and survival rate were recorded. Tumor tissues and peripheral blood samples collected in this study was used to detect methylation positive rate of RASSF1A and WIF-1 by methylation-specific PCR method and the relative level of expression of RASSF1A and WIF-1 mRNA by reverse transcription PCR method. Of the 126 patients, there were 18 cases with complete response (CR), 32 cases with partial response (PR), 50 cases with stable disease (SD), and 26 cases with disease progression (PD) with a total effective rate of 79.37%. Comparison on baseline data of effective group and ineffective group showed no difference (P>0.05), and comparison on adverse reactions occurrence showed no difference (P>0.05). Progression-free survival of the effective group was prolonged with a significant increase in survival rate (P<0.05). Positive rates of RASSF1A methylation and WIF-1 in tissue and serum of the patients in the effective group were significantly lower than those in the ineffective group, but the mRNA of RASSF1A and WIF-mRNA was significantly higher than the ineffective group (P<0.05). The sensitivity of clinical outcome prediction using tissue RASSF1A methylation was 67.0%, the specificity 15.4%, positive predictive value 69.0% and negative predictive value 31.0%. The above-mentioned indexes of tissue WIF-1 were 76.0, 31.4, 72.2 and 27.8, respectively. The indexes of serum RASSF1A were 85.0, 50.0, 76.2 and 23.8%, respectively, and the indexes of serum WIF-1 were 94.0, 75.0, 81.0 and 19.0%, respectively. The receiver operating characteristic curve analysis suggested that the accuracy of clinical outcome prediction using tissue RASSF1A mRNA level was 0.812. The sensitivity 85.2%, the specificity 76.3% and the critical value 0.4256. These indexes of tissue WIF-1 were 0.833, 86.7%, 75.4% and 0.3562 for CR, PR, SD and PD, respectively. These indexes of serum RASSF1A were 0.864, 88.3%, 77.4% and 0.2564, respectively, and for serum WIF-1 were 0.882, 89.4%, 73.5% and 0.1562, respectively. In conclusion, the detection of RASSF1A and WIF-1 gene methylation and level of mRNA expression in tissue and serum of patients with locally advanced breast cancer has an important application value in predicting clinical efficacy of neoadjuvant chemotherapy of the TAC scheme.

Influence of neoadjuvant chemotherapy on prognosis of patients with synovial sarcoma

BackgroundThis study aimed to explore the clinical efficacy of neoadjuvant chemotherapy combined with surgery in primary synovial sarcoma of the limbs and trunk through retrospective analysis of patients with primary synovial sarcoma of the limbs and trunk treated by this treatment in our hospital.MethodsA total of 89 patients diagnosed with synovial sarcoma were enrolled in this study between January 2005 and December 2011 in PLA General Hospital. Most of the patients received neoadjuvant chemotherapy combined with operative treatment (84.3%), 10.1% of them received adjuvant chemotherapy combined with operative treatment, and only 5.6% received merely operative treatment. The influence on the prognosis of patients with synovial sarcoma was analyzed by the statistics overall survival (OS), progression-free survival (PFS), local control (LC), and freedom from distant metastasis (FFDM).ResultsThe median follow-up time was 68.6 months. The 5-year OS, 5-year PFS, 5-year LC, and 5-year FFDM of the patients were 80.2, 60.5, 78.8, and 80.8%, respectively. The OS of the patients with a tumor size >5 cm was lower (91.4 vs 73.1%, P < 0.05). Besides, the OS and FFDM of neoadjuvant chemotherapy were better than those of adjuvant chemotherapy (84.5 vs 55.6%, P = 0.015, and 83.8 vs 55.6%, P = 0.028, respectively). However, there was no significant difference in the LC and PFS.ConclusionsNeoadjuvant chemotherapy was beneficial for patients with synovial sarcoma, and it could improve survival time and control distant metastasis. Tumor size was an important factor influencing patients’ prognosis.

Clinical efficacy of neoadjuvant chemotherapy combined with radical gastrectomy for advanced gastric cancer

Objective To investigate the clinical efficacy of neoadjuvant chemotherapy combined with radical gastrectomy for advanced gastric cancer. Methods The retrospective cross-sectional study was conducted. The clinicopathological data of 73 patients who underwent neoadjuvant chemotherapy combined with radical gastrectomy for advanced gastric cancer at the First Affiliated Hospital of Zhejiang University between June 2004 and December 2009 were collected. Neoadjuvant chemotherapy regimens included XELOX and FOLFOX. Patients received radical gastrectomy within 2 weeks after the completion of the last cycle of neoadjuvant chemotherapy and then continued to undergo postoperative neoadjuvant chemotherapy. Observation indicators: (1) adverse event of neoadjuvant chemotherapy; (2) surgical and postoperative situations; (3) follow-up situations. Follow-up using outpatient examination and telephone interview was performed to detect survival of patients up to December 2014. Measurement data with skewed distribution were described as M (range). Overall survival time was from the beginning of treatment to death or end of follow-up (patients with loss to follow-up). Progression-free survival time was from the beginning of treatment to tumor progression, recurrence and metastasis or death. The survival curve was drawn by the Kaplan-Meier method. Results (1) Adverse event of neoadjuvant chemotherapy: of 73 patients, 38 received XELOX regimens and 35 received FOLFOX regimens, with a median cycle of 3 (range, 1-7 cycles). There were 55 adverse events during neoadjuvant chemotherapy, including 47 with grade 1-2 and 8 with grade 3-4. (2) Surgical and postoperative situations: all the 73 patients underwent successful D2 radical gastrectomy for gastric cancer, including 40 receiving total gastrectomy, 31 receiving distal gastrectomy, 1 receiving total gastrectomy with transverse colon resection and 1 receiving distal gastrectomy with cholecystectomy. Of 73 patients, 10 with postoperative complications were improved by conservative treatment, including 3 with pleural effusion, 2 with peritoneal effusion, 2 with anastomotic bleeding, 2 with cholecystitis and 1 with lympha fistula. No patient received reoperations or died within 30 days postoperatively. Pathological TNM staging: 22 patients were detected in stageⅠ-Ⅱ, 45 in stage Ⅲ, 4 in stage Ⅳ and 2 in stage T0N1M0. Three patients (in stage T0N0M0) had complete remission. Forty-three patients underwent postoperative chemotherapy. (3) Follow-up: all the 73 patients were followed up for 8-125 months, with a median time of 51 months. The median survival time, 5-year overall survival rate and 5-year disease-free survival rate of 73 patients were 52 months, 41.1% and 34.2%, respectively. Conclusion XELOX and FOLFOX regimens of neoadjuvant chemotherapy combined with radical gastrectomy for advanced gastric cancer are safe and effective. Key words: Gastric neoplasms; Gastrectomy; Neoadjuvant chemotherapy

The clinical efficacy of neoadjuvant chemotherapy on urothelial carcinoma of the bladder: A retrospective analysis from a single-center in Taiwan

The clinical efficacy of neoadjuvant chemotherapy on urothelial carcinoma of the bladder: A retrospective analysis from a single-center in Taiwan