High L-Type Amino Acid Transporter 1 Levels Are Associated with Chemotherapeutic Resistance in Gastric Cancer Patients

Introduction: We investigated whether the expression of L-type amino acid transporter 1 (LAT-1) in clinical gastric cancer (GC) patients could predict patient therapeutic response to postoperative adjuvant chemotherapy. Methods: Immunohistochemistry was used to investigate LAT-1, CD98, and phosphorylated-mammalian target of rapamycin (p-mTOR) expression in 111 GC patients. To clarify whether LAT-1 influences the therapeutic effects of chemotherapy, the correlation between disease-free survival rates and LAT-1 was determined in 2 groups: 59 patients who did not undergo postoperative adjuvant chemotherapy and 52 patients who did undergo postoperative adjuvant chemotherapy. Results: LAT-1 was significantly correlated with CD98 and p-mTOR expressions. We did not find any statistically significant correlation between LAT-1 and recurrence in the nontreated group. In contrast, a significant association was found between LAT-1 expression and disease-free survival in the chemotherapy group. Moreover, multivariate regression analysis demonstrated that LAT-1 was an independent predictor of disease-free survival in the postoperative adjuvant chemotherapy group (p = 0.012). Conclusion: Our findings demonstrate that LAT-1 is a useful predictive marker for a successful postoperative adjuvant chemotherapy treatment.

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Randomized Clinical Trial of Adjuvant Mitomycin Plus Tegafur in Patients With Resected Stage III Gastric Cancer

Journal of Clinical Oncology ◽

10.1200/jco.1999.17.12.3810 ◽

1999 ◽

Vol 17 (12) ◽

pp. 3810-3815 ◽

Cited By ~ 82

Author(s):

Lluís Cirera ◽

Anna Balil ◽

Eduard Batiste-Alentorn ◽

Ignasi Tusquets ◽

Teresa Cardona ◽

...

Keyword(s):

Gastric Cancer ◽

Clinical Trial ◽

Overall Survival ◽

Survival Rate ◽

Adjuvant Chemotherapy ◽

Disease Free Survival ◽

Stage Iii ◽

Free Survival ◽

Resected Stage ◽

Disease Free

PURPOSE: The efficacy of adjuvant chemotherapy in gastric cancer is controversial. We conducted a phase III, randomized, multicentric clinical trial with the goal of assessing the efficacy of the combination of mitomycin plus tegafur in prolonging the disease-free survival and overall survival of patients with resected stage III gastric cancer. PATIENTS AND METHODS: Patients with resected stage III gastric adenocarcinoma were randomly assigned, using sealed envelopes, to receive either chemotherapy or no further treatment. Chemotherapy was started within 28 days after surgery according to the following schedule: mitomycin 20 mg/m2 intravenously (bolus) at day 1 of chemotherapy; 30 days later, oral tegafur at 400 mg bid daily for 3 months. Disease-free survival and overall survival were estimated using the Kaplan-Meier analysis and the Cox proportional hazards model. RESULTS: Between January 1988 and September 1994, 148 patients from 10 hospitals in Catalonia, Spain, were included in the study. The median follow-up period was 37 months. The tolerability of the treatment was excellent. The overall survival and disease-free survival were higher in the group of patients treated with chemotherapy (P = .04 for survival and P = .01 for disease-free survival in the log-rank test). The overall 5-year survival rate and the 5-year disease-free survival rate were, respectively, 56% and 51% in the treatment group and 36% and 31% in the control group. CONCLUSION: Our positive results are consistent with the results of recent studies; which conclude that there is a potential benefit from adjuvant chemotherapy in resected gastric cancer.

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Surgery Plus Chemotherapy Compared With Surgery Alone for Localized Squamous Cell Carcinoma of the Thoracic Esophagus: A Japan Clinical Oncology Group Study—JCOG9204

Journal of Clinical Oncology ◽

10.1200/jco.2003.12.095 ◽

2003 ◽

Vol 21 (24) ◽

pp. 4592-4596 ◽

Cited By ~ 432

Author(s):

Nobutoshi Ando ◽

Toshifumi Iizuka ◽

Hiroko Ide ◽

Kaoru Ishida ◽

Masayuki Shinoda ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Lymph Node ◽

Survival Rate ◽

Adjuvant Chemotherapy ◽

Cell Carcinoma ◽

Squamous Cell ◽

Disease Free Survival ◽

Postoperative Adjuvant Chemotherapy ◽

Free Survival ◽

Disease Free

Purpose: We performed a multicenter randomized controlled trial to determine whether postoperative adjuvant chemotherapy improves outcome in patients with esophageal squamous cell carcinoma undergoing radical surgery. Patients and Methods: Patients undergoing transthoracic esophagectomy with lymphadenectomy between July 1992 and January 1997 at 17 institutions were randomly assigned to receive surgery alone or surgery plus chemotherapy including two courses of cisplatin (80 mg/m2 of body-surface area × 1 day) and fluorouracil (800 mg/m2 × 5 days) within 2 months after surgery. Adaptive stratification factors were institution and lymph node status (pN0 versus pN1). The primary end point was disease-free survival. Results: Of the 242 patients, 122 were assigned to surgery alone, and 120 to surgery plus chemotherapy. In the surgery plus chemotherapy group, 91 patients (75%) received both full courses of chemotherapy; grade 3 or 4 hematologic or nonhematologic toxicities were limited. The 5-year disease-free survival rate was 45% with surgery alone, and 55% with surgery plus chemotherapy (one-sided log-rank, P = .037). The 5-year overall survival rate was 52% and 61%, respectively (P = .13). Risk reduction by postoperative chemotherapy was remarkable in the subgroup with lymph node metastasis. Conclusion: Postoperative adjuvant chemotherapy with cisplatin and fluorouracil is better able to prevent relapse in patients with esophageal cancer than surgery alone.

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Effect of Traditional Chinese Medicine Collaborative Model (TCMCM) combined Adjuvant Chemotherapy in IIIb and IIIc Gastric Cancer: Protocol for a Randomized Controlled Trial

10.21203/rs.3.rs-486842/v1 ◽

2021 ◽

Author(s):

zhaoyan li ◽

Jia Li ◽

Nida Cao ◽

Xiaohong Zhu ◽

Yan Xu ◽

...

Keyword(s):

Quality Of Life ◽

Gastric Cancer ◽

Clinical Trial ◽

Adjuvant Chemotherapy ◽

Disease Free Survival ◽

Stage Iiib ◽

Free Survival ◽

Auricular Acupressure ◽

Disease Free

Abstract BackgroundMetastasis and/or recurrence are the primary cause in decreasing the survival time of gastric cancer patients who experienced radical operation. Among whom, patients with stage IIIb and IIIc are especially in high risk of metastasis and recurrence, result in a significant poor survival time than patients with earlier stages. Herbal medicines are natural substances that have been used for centuries in China, auricular acupressure and acupoints has shown promise in reducing side effects of chemotherapy，this traditional Chinese medicine collaborative model（TCMCM）has been studied in cancer, however, the specific effects have not been systematically evaluated. This study was designed to evaluate whether TCMCM can decrease adverse effects after chemotherapy and reduce the recurrence rate and metastasis in stage IIIb and IIIc gastric cancer. Method/designThis prospective，multicenter, randomized, open-label trail will recruit 260 patients with stage IIIb and IIIc gastric cancer who undergo radical surgery with D2 lymphadenectomy. Randomization to usual adjuvant chemotherapy or the intervention (TCMCM) with a 1:1 ratio will be used. Patients in the intervention group received an oral traditional Chinese formula, auricular acupressure and acupoints, all participants will be continuing to receive usual adjuvant chemotherapy. The primary outcome is 3-year disease free survival rate. Secondary outcomes include quality of life，side effects caused by chemotherapy and safety outcome measures. Assessments will be performed at Screening period and 4，8 cycles after adjuvant chemotherapy，9, 12, 18, 24,30 and 36 months after randomization, and adverse events will be recorded.In addition,biological samples will be collected for mechanism exploration studies. DiscussionThis will be the first clinical trial to evaluate the disease-free survival (DFS) and improvements in quality of life in patients of stage IIIb and IIIc gastric cancer receiving TCMCM, which may be used to formulate a standardized TCMCM plan. We are also performing this trial to assess the feasibility of a larger-scale clinical trial in the future. Trail registrationClinicalTrials.gov，NCT03607656. Registered on 1 July 2018.The final protocol version was V1.1.

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Clinical impact of microsatellite instability in patients with stage II and III gastric cancer: Results from the CLASSIC trial.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.4022 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. 4022-4022 ◽

Cited By ~ 9

Author(s):

Yoon Young Choi ◽

Hyunki Kim ◽

Han-Kwang Yang ◽

Woo Ho Kim ◽

Young Woo Kim ◽

...

Keyword(s):

Gastric Cancer ◽

Adjuvant Chemotherapy ◽

Confidence Interval ◽

Microsatellite Instability ◽

Disease Free Survival ◽

Hazard Ratio ◽

Adjusted Hazard Ratio ◽

Stage Ii ◽

Free Survival ◽

Disease Free

4022 Background: The clinical implications of microsatellite instability (MSI) in gastric cancer are unclear. We investigated the usefulness of MSI status as a predictor of prognosis and responsiveness to adjuvant chemotherapy in patients with stage II and III gastric cancer. Methods: Tumor specimens and clinical information were collected from patients enrolled in the CLASSIC trial, a randomized controlled study of capecitabine plus oxaliplatin-based adjuvant chemotherapy. Five mononucleotide markers were used to assess tumor MSI status. Results: Of 592 specimens, 36 (6.1%) were MSI-high (MSI-H), whereas others were MSI-low or microsatellite-stable (MSS). Among 286 patients not treated with adjuvant therapy, those with MSI-H tumors had a better 5-year disease-free survival rate than did those with MSI-low/MSS tumors (hazard ratio adjusted by age, sex, tumor grade, disease stage, tumor location: 0.244 [95% confidence interval, 0.069–0.867]; p = 0.0292). Among 306 patients who received adjuvant chemotherapy, MSI-H status did not correlate with better disease-free survival (adjusted hazard ratio: 0.561 [95% confidence interval, 0.190–1.654]; p = 0.2946). Benefits from adjuvant chemotherapy differed by MSI status; although adjuvant chemotherapy improved disease-free survival among patients with MSI-low/MSS (adjusted hazard ratio: 0.634 [95% confidence interval, 0.485–0.828]; p = 0.0008), no benefit was observed in the MSI-H group (adjusted hazard ratio: 1.877 [95% confidence interval, 0.284–12.390]; p = 0.5130). Conclusions: Among patients with stage II and III gastric cancer, a MSI-H status correlated with a favorable prognosis, and adjuvant chemotherapy benefited those with MSI-L/MSS tumors but not those with MSI-H tumors.

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Efficacy of capecitabine and oxaliplatin versus S-1 as adjuvant chemotherapy in gastric cancer after D2 lymph node dissection.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.4_suppl.160 ◽

2019 ◽

Vol 37 (4_suppl) ◽

pp. 160-160

Author(s):

Kabsoo Shin ◽

In-Ho Kim

Keyword(s):

Gastric Cancer ◽

Lymph Node ◽

Adjuvant Chemotherapy ◽

Lymph Node Ratio ◽

Disease Free Survival ◽

Stage Iiic ◽

Free Survival ◽

D2 Lymph Node Dissection ◽

Node Ratio ◽

Disease Free

160 Background: The aim of this study is to compare capecitabine and oxaliplatin (XELOX) with S-1 based on disease-free survival, and to define the clinical impact of lymph node ratio to select a regimen. Methods: Patients who had curative resection and received either S-1 or XELOX as adjuvant chemotherapy for gastric cancer between Jan. 2011 and Dec. 2015, were analyzed using propensity score matching (PSM). Of the 412 patients enrolled, 301 received S-1 and 111 received XELOX and after PSM, the sample size of each group was 111 patients. And the groups were classified according to stage and lymph node ratio (0, > 0-0.1, > 0.1-025, > 0.25) and three-year disease-free survival (DFS) was evaluated. Results: In post-PSM analysis of all 222 patients, The three-year DFS rates in XELOX group was higher than in the S-1 group in all stage 3 (78% vs. 66.1%, p = 0.036), stage IIIC (64.1% vs. 42.0%, p = 0.038) and LNR > 0.25 (67.7.1% vs. 26.1%, p = 0.002). The hazard ratio of XELOX for recurrence compared with S-1 for stage IIIC and LNR > 0.25 was respectively 0.479 (95% CI 0.238~0.985, p = 0.046) and 0.351 (95% CI 0.162~0.758, p = 0.008). Conclusions: Adjuvant XELOX was more effective than S-1 for stage IIIC and LNR > 0.25 in gastric cancer after D2 dissection.

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To Explore the Effect of NLR and PLR on Prognosis of Rectal Cancer on the basis of T3 substage, and to draw the related nomogram

10.21203/rs.3.rs-627729/v1 ◽

2021 ◽

Author(s):

Donglin Li ◽

Shuang Wang ◽

Yongping Yang ◽

Zeyun Zhao ◽

An Shang ◽

...

Keyword(s):

Risk Factors ◽

Rectal Cancer ◽

Adjuvant Chemotherapy ◽

Area Under The Curve ◽

Disease Free Survival ◽

Postoperative Adjuvant Chemotherapy ◽

Free Survival ◽

N Stage ◽

Independent Risk Factors ◽

Disease Free

Abstract Background: Approximately 50% of patients with rectal cancer are classified into T3 stage, and they are positioned as substage by various criteria. These patients with different neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) develop disparate outcomes. We sought to develop and validate nomograms to predict survival in patients with rectal cancer on the basis of T3 substage.Methods: We conducted a retrospective cohort study by collecting 170 cases from China. Individuals with rectal cancer after 2 or more years of follow up after surgery were eligible for inclusion. Candidate predictors consisted of NLR, PLR, T3 substage and clinical characteristics available at the time of rectal cancer diagnosis. The optimal cut-off values for NLR and PLR were determined using X-Tile (Version 3.6.1) software and were determined before statistical analyses. Variables with P values below 0.1 in the univariable analyses were further evaluated using Cox multivariate analysis. Model discrimination was assessed using receiver operating characteristic (ROC) curve and concordance index (C-index) analysis. Results were internally validated using related software.Results: We analyzed data from 170 patients with T3 rectal cancer. The optimal cut-off value of NLR in relation to overall and disease-free survival were 3.1 and 2.9, and that of PLR were 181.9 and 202.7. Among them, postoperative adjuvant chemotherapy, T3 substage, N stage, CA199 and NLR were independent risk factors affecting overall survival（OS）and disease-free survival (DFS). There was no significant difference in survival rate between T3a and T3b, or between T3c and T3d. The final nomograms of 2-year OS (area under the curve,0.886; The c-index,0.870) and 2-year DFS (area under the curve,0.895; The c-index,0.867) were developed according to independent risk factors analyzed by SPSS 26 (SPSS Inc., Chicago, IL, USA) software. The calibration curves showed negligible optimism.Conclusion: We developed nomograms based on postoperative adjuvant chemotherapy, T3 substage, N stage, CA199 and NLR to help identify patients with poor prognosis and to guide individualized therapy.

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An Immune Cell Signature Is Associated With Disease-Free Survival and Adjuvant Chemosensitivity of Patients With Resectable Gastric Cancer

Frontiers in Immunology ◽

10.3389/fimmu.2020.621623 ◽

2021 ◽

Vol 11 ◽

Author(s):

Hongfei Yan ◽

Yang Chen ◽

Zichang Yang ◽

Zhi Li ◽

Xiaofang Che ◽

...

Keyword(s):

Gastric Cancer ◽

Adjuvant Chemotherapy ◽

Immune Cells ◽

Immune Cell ◽

Disease Free Survival ◽

Tnm Stage ◽

Gene Set Enrichment Analysis ◽

Free Survival ◽

Significant Difference ◽

Disease Free

Increasing evidence has indicated that current tumor-node-metastasis (TNM) stage alone cannot predict prognosis and adjuvant chemotherapy benefits accurately for stages II and III gastric cancer (GC) patients after surgery. In order to improve the predictive ability of survival and adjuvant chemotherapy benefits of GC patients after surgery, this study aimed to establish an immune signature based on the composition of infiltrating immune cells. Twenty-eight types of immune cell fractions were evaluated based on the expression profiles of GC patients from the Gene Expression Omnibus (GEO) database using single-sample gene set enrichment analysis (ssGSEA). The immunoscore (IS) was constructed using a least absolute shrinkage and selection operator (LASSO) Cox regression model. Through the LASSO model, an IS classifier consisting of eight immune cells was constructed. Significant difference was found between high-IS and low-IS groups in the training cohort in disease-free survival (DFS, P < 0.0001) and overall survival (OS, P < 0.0001). Multivariate analysis showed that the IS classifier was an independent prognostic indicator. Moreover, a combination of IS and TNM stage exhibited better prognostic value than TNM stage alone. Further analysis demonstrated that low-IS patients who had more tumor-infiltrating lymphocytes had better response to adjuvant chemotherapy. More importantly, we found that patients with high-IS were more likely to benefit from a Xeloda plus cisplatin regimen after surgery. Finally, we established two nomograms to screen the stage II and III GC patients who benefitted from adjuvant chemotherapy after surgery. The combination of IS classifier and TNM stage could predict DFS and OS of GC patients. The IS model has been proven as a promising tool that can be used to identify the patients with stages II and III GC who may benefit from adjuvant chemotherapy.

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Osteosarcoma

Pediatrics in Review ◽

10.1542/pir.12.11.333 ◽

1991 ◽

Vol 12 (11) ◽

pp. 333-343

Author(s):

Norman Jaffe

Keyword(s):

Differential Diagnosis ◽

Adjuvant Chemotherapy ◽

Primary Tumor ◽

Disease Free Survival ◽

Postoperative Adjuvant Chemotherapy ◽

Surgical Ablation ◽

Free Survival ◽

The Past ◽

Initial Symptoms ◽

Disease Free

Osteosarcoma is principally a disease of the pre-teenager and teenage individual. Pain and swelling of an extremity are the usual initial symptoms. A number of neoplastic and nonneoplastic conditions must be considered in the differential diagnosis. Good quality radiographs complement pathologic material in establishing the diagnosis. Major advances as a consequence of chemotherapy have been achieved during the past decade. Disease-free survival following surgical ablation of the primary tumor and postoperative adjuvant chemotherapy is approximately 60%. The majority of patients undergoing modern forms of treatment are also candidates for limb salvage.

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