Objective:To observe the baseline characteristics and clinical efficacy in cancer patients who were treated with immune checkpoint inhibitors (ICIs) and experienced immune-related adverse events (irAEs).Methods:The clinical efficacy in cancer patients experiencing irAEs was retrospectively analyzed, and the objective response rate, progression-free survival, and overall survival were evaluated.Results:The median onset time of irAEs in 23 patients was 3.17 months. There were 47.8% (11/23) patients with multi-system irAEs, 63.3% (7/11) of which were non-simultaneous. The most common irAEs were immune-related pneumonia, hypothyroidism and immune-related liver dysfunction. Complete remission, partial remission and stable disease were respectively achieved in 0, 10 and 11 cases, while the other two patients developed progressive disease. The objective response rate was 43.5% and the disease control rate was 91.3%. With a median follow-up period of 16.5 months, 17 patients (73.9%) had progressive disease and the median progression-free survival was 9.63 months. Eight patients (34.8%) died before reaching the median overall survival. The progression-free survival and overall survival of patients with irAEs ≥grade 3 were significantly shorter than those with irAEs of grade 1-2 ( P<0.01). Conclusions:The occurrence of irAEs might correlate with the short-term efficacy and clinical benefits in patients treated with ICIs.

Objective To analyze the impact of lymphocyte subsets on chemotherapy efficacy and long-term survival of patients with advanced non-small cell lung cancer(NSCLC).Methods Totally 125 NSCLC patients who had received first-line chemotherapy including paclitaxel and pemetrexed with/without platinum were enrolled in this study.Lymphocytes from peripheral blood were collected before and after two cycles of first-line chemotherapy.Flow cytometry was performed to determine the expressions of 21 fluorescence-labeled lymphocyte subsets.Based on the imaging findings,chemotherapy efficacy was evaluated,and impact of the lymphocyte subsets on progression-free survival(PFS)and overall survival(OS)were analyzed.Results The baseline peripheral lymphocyte subsets showed no significant difference among groups receiving different treatment protocols(all P>0.05).After 2 cycles of chemotherapy,the percentage of CD4CD29lymphocytes was(16.87±5.28)% in progressive disease group,which was significantly lower than those in complete remission+partial remission group [(22.42±7.88)%,P=0.013] and stable disease group [(21.88±6.81)%,P=0.009].The median PFS was 7.07 months and median OS was 23.00 months.Cox multivariable regression analysis showed that the percentages of HLA-DR(HR:1.03,95%CI:1.01-1.05,P<0.001) and CDHLA-DRlymphocytes (HR:1.05,95%CI:1.01-1.08,P<0.001)were positively correlated with OS.Conclusions The rise of CD4CD29T lymphocytes in patients after chemotherapy indicates good chemotherapy efficacy.Higher percentage of HLA-DRand CD3HLA-DRlymphocytes in peripheral blood before chemotherapy predicts favorable prognosis.

Brain metastasis, a common complication of non-small cell lung cancer (NSCLC) with an incidence rate of 30%-50%, signiifcantly affects the patients’ quality of life. hTe prognosis of patients of NSCLC with brain metastasis is ex-tremely poor, the average median survival is only 1 m-2 m without treatment. hTe targeted therapy based on lung cancer driven gene is a new treatment. Besides, the immunotherapy which can enhance the effect of anti-cancer by simulating the immune system is a new approach. The combination of targeted therapy and immunotherapy can greatly benefit patients in clinical work.

BACKGROUNDAltered immunoresponse is associated with tumorigenesis and cancer progression. This study assessed the levels of tumor-infiltrating CD3 + or CD8 + T lymphocytes and interleukin-2 (IL-2) protein in radically resected non-small cell lung cancer (NSCLC) tissues to predict overall survival (OS) of the patients.

METHODSParaffin-embedded tissue specimens from 129 NSCLC patients were retrospectively collected for immunostaining of CD8 + , CD3 + , and IL-2 expression. Clinicopathological and survival data were collected and analyzed using the Chi-squared test, Kaplan-Meier curves, and the log-rank test or the Cox regression model.

RESULTSThe data showed a significant inverse association between CD8 + T lymphocyte levels and IL-2 expression (r = -0.927; P = 0.000) and between the levels of CD8 + and CD3 + T lymphocytes (r = -0.722; P = 0.000), but a positive association between CD3 + T lymphocyte levels and IL-2 expression (r = 0.781; P = 0.000) in NSCLC tissues. Furthermore, the levels of CD3 + and CD8 + T lymphocytes and IL-2 expression were associated with tumor stage (P = 0.023, 0.006, and 0.031, respectively) and the level of CD8 + T lymphocytes was associated with the patient gender (P = 0.024). In addition, the levels of CD8 + T lymphocytes were associated with an unfavorable 5-year OS, whereas patients with high levels of CD3 + T lymphocytes in tumor lesions and IL-2-expressing tumors had significantly better 5-year OS rates than patients with low levels.

CONCLUSIONSThe levels of CD8 + T cells in tumor lesions and IL-2 expression were both independent predictors of OS for these NSCLC patients. Thus, the detection of tumor-infiltrating CD3 + or CD8 + T lymphocytes and IL-2 expression could be useful to predict the prognosis of radically resected NSCLC patients.

CD3 Complex ; metabolism ; CD8-Positive T-Lymphocytes ; metabolism ; Female ; Humans ; Immunohistochemistry ; Interleukin-2 ; metabolism ; Lung Neoplasms ; immunology ; metabolism ; Lymphocytes, Tumor-Infiltrating ; metabolism ; Male ; Prognosis

OBJECTIVETo explore the relationship between a proliferation-inducing ligand (APRIL) expression in primary tumor foci of breast cancer and the patients' prognosis.

METHODSParaffin sections of surgical specimens were retrospectively collected from 130 stage I-III breast cancer patients who received surgery between January 2000 and December 2002 in our hospital. Immunohistochemistry was used to assess APRIL expression intensity in the tumor cells and density of interstitial APRIL-positive cells, and their association was analyzed with the density of interstitial CD4⁺ and CD8⁺ cells and with the histopathologic features, overall survival (OS), and disease-free survival (DFS) of the patients.

RESULTSAPRIL positive staining was found in the cytoplasm of the tumor cells, interstitial cells, and the extracellular matrix. APRIL intensity in the tumor cells was positively correlated with the density of interstitial APRIL-positive cells (P=0.009) and Ki67 (P=0.003). The density of interstitial APRIL-positive cells was positively correlated with the density of interstitial CD4⁺ cells (P<0.001) and CD8⁺ cells (P<0.001). In hormone receptor negative patients (ER- and PR-), multivariate COX regression identified the density of interstitial APRIL-positive cells as a positive prognostic factor for DFS (HR=0.313, 95% CI=0.107-0.920, P=0.035). CONCLUSIONSl APRIL is widely expressed in the interstitial immune cells in breast cancer. APRIL staining intensity in the tumor cells is positively correlated with tumor proliferation, indicating that the immune cells might promote tumor proliferation by secreting APRIL. A greater density of interstitial APRIL-positive cells is associated with a good prognosis in hormone receptor-negative patients.

Breast Neoplasms ; diagnosis ; metabolism ; CD4-Positive T-Lymphocytes ; CD8-Positive T-Lymphocytes ; Cell Transformation, Neoplastic ; Cytoplasm ; Disease-Free Survival ; Female ; Humans ; Immunohistochemistry ; Prognosis ; Retrospective Studies ; Tumor Necrosis Factor Ligand Superfamily Member 13 ; metabolism

OBJECTIVETo observe the clinical efficacy of cetuximab plus chemotherapy in the treatment of metastatic colorectal carcinoma.

METHODSClinicopathological data of 128 patients with metastatic colorectal cancer admitted in the Department of Oncology, Chinese PLA General Hospital from 2008 to June 2012 were analyzed retrospectively. Among them, 91 patients received cetuximab as the first-line therapy and 37 in the second-line or more-line therapy. The chemotherapy regimens included oxaliplatin-based therapy (FOLFOX/XELOX), irinotecan-based therapy (FOLFIRI/XELIRI) and fluorouracil-based therapy (Xeloda). The efficacy was evaluated according to RECIST 1.0 criteria. The remission rate, control rate and time to disease progression were compared among patients receiving cetuximab combined with different chemotherapy regimens in different periods.

RESULTSThe disease control rate of cetuximab applied in the first-line treatment was higher than that of the second-line or more-line [85.9% (61/71) vs. 59.3% (16/27), P=0.004]. The disease control rate of the group treated with cetuximab plus oxaliplatin-based chemotherapy was much higher compared to the other two groups [91.1% (41/45) vs. 68.1% (32/47), 4/6, P=0.021]. But there were no significant differences among three regimens in the terms of overall response rate (all P>0.05). The median time to progression of groups with cetuximab plus irinotecan, oxaliplatin or capecitabine was 7.8 months, 8.5 months and 5.2 months respectively. The median time to progression of cetuximab combined with chemotherapy in the first-line treatment and the second-line or more-line was 8.2 and 7.7 months respectively. However, the differences were not statistically significant (P>0.05).

CONCLUSIONSCetuximab in combination with oxaliplatin-based chemotherapy is recommended as the first-line application in the treatment of metastatic colorectal carcinoma patients, because it is helpful to improve the rate of disease control.

Antineoplastic Combined Chemotherapy Protocols ; Camptothecin ; analogs & derivatives ; Cetuximab ; Colorectal Neoplasms ; Deoxycytidine ; analogs & derivatives ; Fluorouracil ; analogs & derivatives ; Humans ; Leucovorin ; Neoplasm Metastasis ; Organoplatinum Compounds ; Retrospective Studies ; Treatment Outcome

Objective To observe the clinical efficacy of cetuximab plus chemotherapy in the treatment of metastatic colorectal carcinoma. Methods Clinicopathological data of 128 patients with metastatic colorectal cancer admitted in the Department of Oncology , Chinese PLA General Hospital from 2008 to June 2012 were analyzed retrospectively. Among them, 91 patients received cetuximab as the first-line therapy and 37 in the second-line or more-line therapy. The chemotherapy regimens included oxaliplatin-based therapy (FOLFOX/XELOX), irinotecan-based therapy (FOLFIRI/XELIRI) and fluorouracil-based therapy (Xeloda). The efficacy was evaluated according to RECIST 1.0 criteria. The remission rate, control rate and time to disease progression were compared among patients receiving cetuximab combined with different chemotherapy regimens in different periods. Results The disease control rate of cetuximab applied in the first-line treatment was higher than that of the second-line or more-line [85.9%(61/71) vs. 59.3%(16/27), P=0.004]. The disease control rate of the group treated with cetuximab plus oxaliplatin-based chemotherapy was much higher compared to the other two groups [91.1%(41/45) vs. 68.1%(32/47), 4/6, P=0.021]. But there were no significant differences among three regimens in the terms of overall response rate (all P>0.05). The median time to progression of groups with cetuximab plus irinotecan, oxaliplatin or capecitabine was 7.8 months, 8.5 months and 5.2 months respectively. The median time to progression of cetuximab combined with chemotherapy in the first-line treatment and the second-line or more-line was 8.2 and 7.7 months respectively. However , the differences were not statistically significant (P>0.05). Conclusions Cetuximab in combination with oxaliplatin-based chemotherapy is recommended as the first-line application in the treatment of metastatic colorectal carcinoma patients, because it is helpful to improve the rate of disease control.

Objective To observe the clinical efficacy of cetuximab plus chemotherapy in the treatment of metastatic colorectal carcinoma. Methods Clinicopathological data of 128 patients with metastatic colorectal cancer admitted in the Department of Oncology , Chinese PLA General Hospital from 2008 to June 2012 were analyzed retrospectively. Among them, 91 patients received cetuximab as the first-line therapy and 37 in the second-line or more-line therapy. The chemotherapy regimens included oxaliplatin-based therapy (FOLFOX/XELOX), irinotecan-based therapy (FOLFIRI/XELIRI) and fluorouracil-based therapy (Xeloda). The efficacy was evaluated according to RECIST 1.0 criteria. The remission rate, control rate and time to disease progression were compared among patients receiving cetuximab combined with different chemotherapy regimens in different periods. Results The disease control rate of cetuximab applied in the first-line treatment was higher than that of the second-line or more-line [85.9%(61/71) vs. 59.3%(16/27), P=0.004]. The disease control rate of the group treated with cetuximab plus oxaliplatin-based chemotherapy was much higher compared to the other two groups [91.1%(41/45) vs. 68.1%(32/47), 4/6, P=0.021]. But there were no significant differences among three regimens in the terms of overall response rate (all P>0.05). The median time to progression of groups with cetuximab plus irinotecan, oxaliplatin or capecitabine was 7.8 months, 8.5 months and 5.2 months respectively. The median time to progression of cetuximab combined with chemotherapy in the first-line treatment and the second-line or more-line was 8.2 and 7.7 months respectively. However , the differences were not statistically significant (P>0.05). Conclusions Cetuximab in combination with oxaliplatin-based chemotherapy is recommended as the first-line application in the treatment of metastatic colorectal carcinoma patients, because it is helpful to improve the rate of disease control.

Objective To explore the relationship between a proliferation-inducing ligand (APRIL) expression in primary tumor foci of breast cancer and the patients' prognosis. Methods Paraffin sections of surgical specimens were retrospectively collected from 130 stage I-III breast cancer patients who received surgery between January 2000 and December 2002 in our hospital. Immunohistochemistry was used to assess APRIL expression intensity in the tumor cells and density of interstitial APRIL-positive cells, and their association was analyzed with the density of interstitial CD4+ and CD8+ cells and with the histopathologic features, overall survival (OS), and disease-free survival (DFS) of the patients. Results APRIL positive staining was found in the cytoplasm of the tumor cells, interstitial cells, and the extracellular matrix. APRIL intensity in the tumor cells was positively correlated with the density of interstitial APRIL-positive cells (P=0.009) and Ki67 (P=0.003). The density of interstitial APRIL-positive cells was positively correlated with the density of interstitial CD4+cells (P<0.001) and CD8+cells (P<0.001). In hormone receptor negative patients (ER-and PR-), multivariate COX regression identified the density of interstitial APRIL-positive cells as a positive prognostic factor for DFS (HR=0.313, 95% CI=0.107-0.920, P=0.035). Conclusions APRIL is widely expressed in the interstitial immune cells in breast cancer. APRIL staining intensity in the tumor cells is positively correlated with tumor proliferation, indicating that the immune cells might promote tumor proliferation by secreting APRIL. A greater density of interstitial APRIL-positive cells is associated with a good prognosis in hormone receptor-negative patients.

Objective To explore the relationship between a proliferation-inducing ligand (APRIL) expression in primary tumor foci of breast cancer and the patients' prognosis. Methods Paraffin sections of surgical specimens were retrospectively collected from 130 stage I-III breast cancer patients who received surgery between January 2000 and December 2002 in our hospital. Immunohistochemistry was used to assess APRIL expression intensity in the tumor cells and density of interstitial APRIL-positive cells, and their association was analyzed with the density of interstitial CD4+ and CD8+ cells and with the histopathologic features, overall survival (OS), and disease-free survival (DFS) of the patients. Results APRIL positive staining was found in the cytoplasm of the tumor cells, interstitial cells, and the extracellular matrix. APRIL intensity in the tumor cells was positively correlated with the density of interstitial APRIL-positive cells (P=0.009) and Ki67 (P=0.003). The density of interstitial APRIL-positive cells was positively correlated with the density of interstitial CD4+cells (P<0.001) and CD8+cells (P<0.001). In hormone receptor negative patients (ER-and PR-), multivariate COX regression identified the density of interstitial APRIL-positive cells as a positive prognostic factor for DFS (HR=0.313, 95% CI=0.107-0.920, P=0.035). Conclusions APRIL is widely expressed in the interstitial immune cells in breast cancer. APRIL staining intensity in the tumor cells is positively correlated with tumor proliferation, indicating that the immune cells might promote tumor proliferation by secreting APRIL. A greater density of interstitial APRIL-positive cells is associated with a good prognosis in hormone receptor-negative patients.