scholarly journals M2 Macrophage-based Prognostic Nomogram for Gastric Cancer After Surgical Resection: Original Article

2020 ◽  
Author(s):  
Jianwen Hu ◽  
Yongchen Ma ◽  
Ju Ma ◽  
Yanpeng Yang ◽  
Yingze Ning ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Overall Survival ◽  
Curative Resection ◽  
Patient Survival ◽  
Tnm Staging ◽  
M2 Macrophage ◽  
Concordance Index ◽  
Age And Gender ◽  
Cd163 Expression ◽  
And Gender

Abstract Background: A good prediction model is useful to accurately predict patient prognosis. Tumor–node–metastasis (TNM) staging often cannot accurately predict prognosis when used alone. Some researchers have shown infiltration of M2 macrophages in many tumors, which indicates poor prognosis. This approach has the potential to predict prognosis more accurately when used in combination with TNM staging. The present study aimed to develop and validate a nomogram to predict survival in patients with gastric cancer by combining TNM staging and the degree of M2 macrophage infiltration.Methods: Patients undergoing curative resection for gastric cancer between 2008 and 2013 at our hospital were enrolled and assigned into either the training set or the validation set. M2 macrophage markers were evaluated by immunohistochemical staining. A stepwise method was applied to screen variables associated with patient survival time, and a nomogram was constructed to predict patient survival. Concordance index, calibration curve, and decision curve analysis were used to evaluate the discrimination, calibration, and clinical benefit of the model.Results: A multivariate analysis demonstrated that CD163 expression, TNM staging, age, and gender were independent risk factors for overall survival. Thus, these parameters were assessed to develop the nomogram. In the training, validation, and overall datasets, the concordance index was >0.6. The model showed a high degree of discrimination in all three datasets. The five-year survival calibration curves were a very good fit with standard curves in all three datasets, and the model demonstrated good clinical benefit. The prognostic abilities had threshold probabilities of 10%–38% for one-year survival, 10%–75% for three-year survival, and 35%–80% for five-year survival.Conclusions: We combined CD163 expression in macrophages, TNM staging, age, and gender to develop a nomogram to predict five-year overall survival after curative resection for gastric cancer. This model has the potential to provide further diagnostic and prognostic value for patients with gastric cancer.

scholarly journals M2 Macrophage-Based Prognostic Nomogram for Gastric Cancer After Surgical Resection

2021 ◽  
Vol 11 ◽  
Author(s):  
Jianwen Hu ◽  
Yongchen Ma ◽  
Ju Ma ◽  
Yanpeng Yang ◽  
Yingze Ning ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Tnm Staging ◽  
Training Data ◽  
M2 Macrophage ◽  
Data Sets ◽  
Good Prediction ◽  
Data Set ◽  
Age And Gender ◽  
Cd163 Expression ◽  
And Gender

A good prediction model is useful to accurately predict patient prognosis. Tumor–node–metastasis (TNM) staging often cannot accurately predict prognosis when used alone. Some researchers have shown that the infiltration of M2 macrophages in many tumors indicates poor prognosis. This approach has the potential to predict prognosis more accurately when used in combination with TNM staging, but there is less research in gastric cancer. A multivariate analysis demonstrated that CD163 expression, TNM staging, age, and gender were independent risk factors for overall survival. Thus, these parameters were assessed to develop the nomogram in the training data set, which was tested in the validation and whole data sets. The model showed a high degree of discrimination, calibration, and good clinical benefit in the training, validation, and whole data sets. In conclusion, we combined CD163 expression in macrophages, TNM staging, age, and gender to develop a nomogram to predict 3- and 5-year overall survivals after curative resection for gastric cancer. This model has the potential to provide further diagnostic and prognostic value for patients with gastric cancer.

Randomized Trial of Adjuvant Chemotherapy With Mitomycin, Fluorouracil, and Cytosine Arabinoside Followed by Oral Fluorouracil in Serosa-Negative Gastric Cancer: Japan Clinical Oncology Group 9206–1

2003 ◽  
Vol 21 (12) ◽  
pp. 2282-2287 ◽  
Author(s):  
Atsushi Nashimoto ◽  
Toshifusa Nakajima ◽  
Hiroshi Furukawa ◽  
Masatsugu Kitamura ◽  
Taira Kinoshita ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Overall Survival ◽  
Adjuvant Chemotherapy ◽  
Survival Benefit ◽  
Curative Resection ◽  
Cancer Recurrence ◽  
Phase Iii ◽  
Relapse Free Survival ◽  
Free Survival ◽  
Significant Difference

Purpose: To evaluate the survival benefit of adjuvant chemotherapy after curative resection in serosa-negative gastric cancer patients (excluding patients who were T1N0), we conducted a multicenter phase III clinical trial in which 13 cancer centers in Japan participated. Patients and Methods: From January 1993 to December 1994, 252 patients were enrolled into the study and allocated randomly to adjuvant chemotherapy or surgery alone. The chemotherapy comprised intravenous mitomycin 1.33 mg/m2, fluorouracil (FU) 166.7 mg/m2, and cytarabine 13.3 mg/m2 twice weekly for the first 3 weeks after surgery, and oral FU 134 mg/m2 daily for the next 18 months for a total dose of 67 g/m2. The primary end point was relapse-free survival. Overall survival and the site of recurrence were secondary end points. Results: Ninety-eight percent of patients underwent gastrectomy with D2 or greater lymph node dissection. There were no treatment-related deaths and few serious adverse events. There was no significant difference in relapse-free and overall survival between the arms (5-year relapse-free survival 88.8% chemotherapy v 83.7% surgery alone; P = .14 and 5-year survival 91.2% chemotherapy v 86.1% surgery alone; P = .13, respectively). Nine patients (7.1%) in the chemotherapy arm and 17 patients (13.8%) in the surgery-alone arm had cancer recurrence. Conclusion: There was no statistically significant relapse-free or overall survival benefit with this adjuvant chemotherapy for patients with macroscopically serosa-negative gastric cancer after curative resection, and there was no statistical difference between the two arms relating to the types of cancer recurrence. We do not recommend adjuvant chemotherapy with this regimen for this population in clinical practice.

A prospective randomized trial comparing 5-fluorouracil (5-FU), mitomycin-C (MMC), and polysaccharide-K (PSK) versus UFT and PSK as adjuvant chemoimmunotherapy (CITX) for patients with locally advanced gastric cancer with curative resection

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 15074-15074
Author(s):  
J. Choi ◽  
S. Kang ◽  
J. Park ◽  
H. Lee ◽  
Y. Cho ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Overall Survival ◽  
Randomized Trial ◽  
Advanced Gastric Cancer ◽  
Curative Resection ◽  
Locally Advanced ◽  
Disease Free Survival ◽  
Target Number ◽  
Stage Ib ◽  
Locally Advanced Gastric Cancer

15074 Background: Adjuvant chemotherapy has demonstrated small but significant survival benefit in locally advanced gastric cancer in several meta-analyses, while adjuvant CITX showed improved outcome of patients (pts) compared to chemotherapy alone in a few trials. However, optimal chemotherapy regimen remains to be determined. We conducted a randomized trial comparing oral (PO) CITX with intravenous (IV) CITX in gastric cancer pts with curative resection. Methods: All enrolled pts underwent radical surgery with at least D2 dissection. After stratification for pathologic stage (IB or II vs. III) and primary tumor size (=5 cm vs. >5 cm), pts were randomized to IV CITX (5-FU 500 mg/m2 weekly for 24 weeks, MMC 8 mg/m2 every 6 weeks x 4) or PO CITX (UFT 400–600 mg/day for 12 months). Pts in both arms received PSK 3 g/day PO for 4 months. The planned target number of pts was 368 to prove the non-inferiority of PO CITX compared to IV CITX in overall survival. Results: A total of 82 pts (stage IB: 6, II: 29, IIIA: 30, IIIB: 17; 44 in IV arm, 38 in PO arm) were enrolled between May 2002 and October 2005, when the trial was closed due to poor accrual. Pts characteristics were well balanced. With a median follow-up of 39 months (14–55 months) in survivors, there were no significant differences in 3-year disease-free survival (82% vs. 61%, p=0.302) and overall survival (84% vs. 79%, p=0.838) between IV and PO arms. No grade 4 toxicity was observed in both arms. IV arm demonstrated higher incidence of grade 2 or 3 neutropenia (79% vs. 52%, p=0.025), thrombocytopenia (19% vs. 0%, p=0.008), and vomiting (36% vs. 9%, p=0.013). Conclusions: Although accrual was well below that planned, the results of this trial suggest that PO CITX with UFT might have similar efficacy with lower toxicity profile compared with 5-FU and MMC CITX in adjuvant treatment for gastric cancer. No significant financial relationships to disclose.

scholarly journals Development and external validation of a nomogram predicting overall survival after curative resection of colon cancer

2021 ◽  
Vol 49 (5) ◽  
pp. 030006052110150
Author(s):  
Shuanhu Wang ◽  
Yakui Liu ◽  
Yi Shi ◽  
Jiajia Guan ◽  
Mulin Liu ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Overall Survival ◽  
Curative Resection ◽  
Predictive Accuracy ◽  
External Validation ◽  
Tnm Staging ◽  
Cox Proportional Hazards ◽  
Calibration Plot ◽  
Metastatic Colon Cancer ◽  
Validation Set

Objective To develop and externally validate a prognostic nomogram to predict overall survival (OS) in patients with resectable colon cancer. Methods Data for 50,996 patients diagnosed with non-metastatic colon cancer were retrieved from the Surveillance, Epidemiology, and End Results (SEER) database. Patients were assigned randomly to the training set (n = 34,168) or validation set (n = 16,828). Independent prognostic factors were identified by multivariate Cox proportional hazards regression analysis and used to construct the nomogram. Harrell’s C-index and calibration plots were calculated using the SEER validation set. Additional external validation was performed using a Chinese dataset (n = 342). Results Harrell’s C-index of the nomogram for OS in the SEER validation set was 0.71, which was superior to that using the 7th edition of the American Joint Committee on Cancer TNM staging (0.59). Calibration plots showed consistency between actual observations and predicted 1-, 3-, and 5-year survival. Harrell’s C-index (0.72) and calibration plot showed excellent predictive accuracy in the external validation set. Conclusions We developed a nomogram to predict OS after curative resection for colon cancer. Validation using the SEER and external datasets revealed good discrimination and calibration. This nomogram may help predict individual survival in patients with colon cancer.

scholarly journals Development and Validation a Nomogram for Predicting Overall Survival in Patients With Intrahepatic Cholangiocarcinoma

2021 ◽  
Vol 8 ◽  
Author(s):  
Chen Yuan ◽  
Zhigang Hu ◽  
Kai Wang ◽  
Shubing Zou
Keyword(s):  
Overall Survival ◽  
Intrahepatic Cholangiocarcinoma ◽  
Calibration Curve ◽  
Staging System ◽  
Tnm Staging ◽  
Concordance Index ◽  
Discrimination Ability ◽  
Probability Of Survival ◽  
External Data ◽  
Staging Systems

Background: This study aims to establish an effective nomogram to predict the overall survival of patients with intrahepatic cholangiocarcinoma (ICC).Patients and Methods: Data used to build the nomogram comes from the Surveillance, Epidemiology, and End Results (SEER) database. Patients diagnosed with ICC between 2005 and 2016 were retrospectively collected. Prediction accuracy and discrimination ability of the nomogram was evaluated by concordance index (C-index) and calibration curve. The area under receiver operating characteristic (ROC) curve (AUC) and decision curve analysis (DCA) were used to compare the precision of the 1-, 3-, and 5-year survival of the nomogram with 8th American Joint Commission on Cancer (AJCC) tumor–node–metastasis (TNM) staging system. Finally, it was verified in a prospective study of patients diagnosed with ICC in the Second Affiliated Hospital of Nanchang University from 2013 to 2020 by bootstrap resampling.Result: The study contains two parts of data; we establish a nomogram using external data, and we conducted internal verification and external verification. The nomogram that we have established has good calibration, with a concordance index (C-index) of 0.75 (95% CI, 0.74–0.76) for overall survival (OS) prediction. The AUC value of the nomogram predicting 1-, 3-, and 5-year OS rates were 0.821, 0.828, and 0.836, which were higher than those of the 8th AJCC TNM staging systems. The calibration curve for the probability of survival between prediction by nomogram and actual observation shows good agreement. The nomogram showed better accuracy than the 8th edition AJCC TNM staging.Conclusion: The nomogram established can provide a more accurate prognosis for patients with intrahepatic cholangiocarcinoma.

scholarly journals Muscle Mass in Elderly Patients with DLBCL Treated with RCHOP

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 3044-3044
Author(s):  
Iuliana Vaxman ◽  
Agata Schlesinger ◽  
Natalia Goldberg ◽  
Meir Lahav ◽  
Anat Gafter ◽  
...  
Keyword(s):  
Overall Survival ◽  
Platelet Count ◽  
Elderly Patients ◽  
Muscle Mass ◽  
Cox Regression ◽  
Dose Intensity ◽  
Age And Gender ◽  
Chemotherapy Dose ◽  
Pre Treatment ◽  
And Gender

Abstract Sarcopenia is defined as reduced muscle mass and loss of strength or function and can be part of normal aging as well as a component of cachexia. Multiple studies found correlation between reduced muscle mass and negative outcomes in chronic diseases and solid tumors. Little research exist on similar relationship in hematological malignancies and no studies investigated impact of longitudinal muscle mass changes on clinical outcomes in elderly lymphoma patients undergoing treatment. To evaluate the muscle mass during the course of chemotherapy in patients 70 years or older with DLBCL and its effect on survival and toxicity, we performed a retrospective cohort study. We included patients diagnosed between the years 2007-2014, and treated with RCHOP at the Rabin Medical Center. We collected data on age, sex, performance status (PS), number of extranodal involvement sites, Ann Arbor stage, international prognostic index (IPI), Charlson comorbidity index (CCI), hemoglobin (Hb), LDH, neutrophil, lymphocyte, monocyte, and platelet count, creatinine, albumin, CRP, treatment date, response and survival. We evaluated muscle mass by adding bilateral psoas muscle cross-sectional areas measured at the level of the third lumbar vertebra in a semi-automated manner on standard PET CT images. The ratio of the total psoas area normalized to height square (expressed in cm2/m2) was defined as muscle index. The change in muscle index after vs. before treatment was estimated. Correlation was estimated in a non-parametric test. The effect of pre-treatment muscle mass index and the above mentioned variables was estimated in a univariate Cox regression analysis. Variables potentially associated with mortality were entered into a Cox regression multivariate analysis. Results: Ninety three patients treated with RCHOP with baseline PETCT were included in the cohort. Median age was 78 years (range 70-90). Half of patients were female. Sixty percent had an IPI score of 3 or more. Mean muscle index before treatment was 4.66 cm2/m2, median 4.4 cm2/m2. End of treatment PETCT was available for 76 patients. Mean post treatment index was 4.2 cm2/m2, median 3.92 cm2/m2. A decrease in muscle index was observed in 76% of patients. The change in index ranged from -7.5 to 0.8, with a mean change of -0.58, SE0.12. No statistically significant correlation between pre treatment index and dose intensity was shown (p = 0.46). A negative correlation was shown between pre treatment index and days of hospitalization in cycles 1-2 (p=0.007, r=-0.28). Pre-treatment muscle index was not associated with overall survival (p = 0.43). In a sub-group analysis by sex a higher muscle index was associated with a longer overall survival among men (HR 0.59, 95% CI 0.44 to 78, p<0.001), while such an association was not demonstrated among women. Factors associated with overall survival (p<0.05 unless otherwise specified) were dose of adriamycin and cyclophosphamide in the first cycle, low hemoglobin, albumin, lymphocyte count (p=0.08), and platelet count (p=0.052) and LDH level. In a multivariate model that included these variables, albumin and chemotherapy dose remained statistically significant. In a second model with these variables as well as age and gender, the variables that were associated with overall survival were albumin, age, and gender, while chemotherapy dose became of borderline significance (p=0.08). Conclusion: based on our data including 93 elderly patients with DLBCL a higher muscle mass before RCHOP was associated with longer overall survival among men, but not among women. No association was found between muscle mass measured as total psoas area corrected to height and dose intensity and infection. During the course of chemotherapy we observed a loss of muscle mass in most of the patients. Disclosures No relevant conflicts of interest to declare.

M2 Macrophage Infiltration Is Closely Associated with Poor Prognosis for Adult T-Cell Leukemia/Lymphoma (ATLL),

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 3672-3672 ◽  
Author(s):  
Daisuke Niino ◽  
Yoshihiro Komohara ◽  
Yoshizo Kimura ◽  
Masanori Takeuchi ◽  
Hiroaki Miyoshi ◽  
...  
Keyword(s):  
Overall Survival ◽  
T Cell ◽  
Poor Prognosis ◽  
M2 Macrophage ◽  
M2 Macrophages ◽  
Macrophage Phenotype ◽  
M1 Macrophages ◽  
Adult T Cell Leukemia ◽  
Cd163 Expression ◽  
Tumor Area

Abstract Abstract 3672 Background: Adult T-cell leukemia/lymphoma (ATLL) is a peripheral T-cell lymphoma caused by a retrovirus, human T-cell lymphotropic virus type I, and characterized by an aggressive clinical course and poor prognosis. Although several factors associated with this poor prognosis have been identified, including high-level Ki67 antigen expression and high serum levels of calcium, parathyroid hormone-related protein, soluble interleukin-2 receptor, β2-microglobulin, and neuron-specific enolase, the accuracy of current prognostic models for prediction of the outcome of treatment is inadequate, and clinically relevant biomarkers have not been established. Tumor-associated macrophages, which are known to possess the immunosuppressive M2 macrophage phenotype, contribute to tumor growth, invasion, and metastasis by producing various mediators. Macrophage polarization is divided into types M1 and M2 based on the expression of membrane receptors, cytokines, and chemokines. M1 expresses CD80, interleukin (IL)-6, IL-12, and chemokine receptor 7, while M2 expresses CD163, IL10, and chemokine ligand 22. The classically activated M1 macrophages exhibit antitumor functions and the alternatively activated M2 macrophages protumor functions, which contribute to the development and progression of tumors. CD163 is a monocyte/macrophage-restricted membrane protein belonging to the scavenger receptor cysteine-rich domain family and it functions as an endocytic receptor for a hemoglobin-haptoglobin complex. CD163 expression has been associated with an anti-inflammatory M2 macrophage phenotype and is believed to be useful for distinguishing M2 macrophages from pro-inflammatory M1 macrophages. Macrophages, especially M2 polarized macrophages, preferentially express CD163, but no studies have investigated macrophage phenotypes in ATLL. The aim of our study was therefore to investigate CD163 expression, which has been used as a marker for M2 macrophages, and the relationship between macrophage activation and prognosis for ATLL in order to gain new information about the therapeutic implications of this relationship for ATLL. Methods: Between 1985 and 2003, 75 cases of ATLL were examined. The male-to-female ratio was 1.34:1 and the median age 63 years (range: 35–87 years). Advanced clinical stages were identified in 75% of the patients, and lactic dehydrogenase was elevated in 25%. Most patients were treated with combination chemotherapy and the median survival period was 271 days (range: 4–3, 807 days). We performed a retrospective study on the immunohistochemical expression of macrophage markers (CD68, CD163) and their correlation with overall survival for the 75 ATLL patients. Paraffin sections were examined immunohistochemically by using anti-CD68 (PGM1) and anti-CD163 antibodies, and the absolute number of intratumoral macrophages in the ATLL specimens was determined. Kaplan-Meier survival estimates were subjected to comparative univariate analyses using the log-rank test. Cox proportional-hazard regression test was used for the multivariate analysis. P-values of less than 0.05 were considered significant. Results: The number of CD68-positive macrophages in ATLL tissues did not correlate with overall survival (P =0.25), whereas patients with a large number of CD163-positive macrophages (>250 cells/mm2 tumor area; n=37) had worse outcomes than those with a small number (<250 cells/mm2 tumor area; n=36) (P =0.05). Meanwhile, a higher ratio of CD163-positive to CD68-positive macrophages in ATLL significantly correlated with worse overall survival (P =0.039). Multivariate analysis confirmed that high CD163/CD68 ratio was an independent prognostic factor. Conclusions: Considering that high CD163/CD68 ratio reflects the proportion of macrophages polarized to the M2 phenotype, our findings further indicate that activation of macrophages towards the M2 phenotype correlates with worse prognosis. They also suggest that immunohistochemical analysis of M2 macrophages at the time of diagnosis can provide additional relevant prognostic information. However, these findings need to be further explored in future studies. Disclosures: No relevant conflicts of interest to declare.

The role of adjuvant chemoradiotherapy (CRT) in Turkish patients with gastric carcinoma

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 15159-15159
Author(s):  
M. Gumus ◽  
F. Dane ◽  
S. Kaya ◽  
M. A. Ozturk ◽  
P. F. Yumuk ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Overall Survival ◽  
Curative Resection ◽  
Gastroesophageal Junction ◽  
Prognostic Significance ◽  
Disease Free Survival ◽  
Adjuvant Chemoradiotherapy ◽  
Cox Regression Analysis ◽  
Turkish Patients ◽  
Disease Free

15159 Background: Increased disease free and overall survivals were seen in curatively resected patients with gastric and gastroesophageal adenocarcinoma treated with postoperative adjuvant CRT compared to surgery alone. There is no study analyzing the outcome of gastric cancer patients who received adjuvant CRT after curative resection in Turkish patients. Thus, we aimed to analyze the treatment outcome of postoperative CRT, and the prognostic significance of various parameters in these patients. Material Metod: Overall 130 patients with gastric cancer staged IB to IV(M0) were treated with chemoradiotherapy after curative resection, in two outpatient clinics in Istanbul. The chemotherapy consisted of fluorouracil 425 mg/m2 plus leucovorin 20 mg/m2 for 5 days, followed by 4500 cGy of radiotherapy for 5 weeks with fluorouracil (400 mg/m2) and leucovorin (20 mg/m2) on the first 4 days and the last 3 days of radiotherapy. Two 5-day cycles of chemotherapy with the doses used in the first cycle were given 4 weeks after the completion of radiotherapy. The demographic features and histopathological characteristics of the patients were analyzed as prognostic factors. Results: The median follow up was 13 months (range: 1–77) starting from surgery date. The median age was 58 years (range:33–75). About 28 % of the patients were female. ECOG performance score (PS) was =1 in 92.9 %, whereas it was 2 in the remaining 7.1%. Twenty-one patients had gastroesophageal junction and 109 had gastric primaries. The rates of T1, T2, T3, and T4 tumors were 3.8%, 26.9%, 61.5%, and 7.7%, respectively. A hundred and nine (83.8%) patients had regional node involvement. The 3 year disease free survival and overall survival for all patients were 50.1%, and 61.7%, respectively. The median overall survival was 54 months. In multivariate Cox regression analysis; nodal status (p: 0.003) was the only independent prognostic factor for overall survival. Tolerance was acceptable, and the main toxicity was related to gastrointestinal system. Conclusion: The adjuvant CRT after curative resection of gastric cancer was feasible, with acceptable toxicities in our Turkish patient population. No significant financial relationships to disclose.

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