Circulating activated lymphocyte subsets as potential blood biomarkers of cancer progression.

The objective of this study was to predict the value of lymphocyte subsets in cancer progression. Peripheral blood was obtained from 327 untreated patients with cancer and 158 healthy volunteers. Levels of lymphocyte subsets were determined by flow cytometry. There were decreased levels of natural killer (NK) cells, CD8+ T cells, and naïve CD4+ /CD4+ T cells in untreated patients with cancer compared to those in healthy controls. Inversely, there were elevated levels of the following T-cell percentages in cancer patients compared to those in healthy controls: memory CD4+ /CD4+ , CD8+ T cells, HLA-DR/CD8+ , CD8+ CD38+ /CD8+ , and CD4+ /CD8+ . In addition, there are a decreasing trend in terms of CD4+ T-cell counts and an increase CD8+ HLA-DR/CD8+ T-cell and CD8+ CD38+ /CD8+ T-cell percentages in the advanced stage. An increasing trend with advanced tumor stage and the percentages of CD8+ HLA-DR/CD8+ T cells and CD8+ CD38+ /CD8+ T cells was shown in this study. There are a negative correlation for CD4+ T-cell counts and positive correlation for percentages of CD8+ HLA-DR/CD8+ T cell and CD8+ CD38+ /CD8+ T cells with the lymph node metastasis. In the presence of distant metastatic spread, we observed higher NK-cell counts, CD8+ HLA-DR/CD8+ T-cell percentages, CD8+ CD38+ /CD8+ T-cell percentages, as well as lower CD4+ T-cell counts than those in the absence of distant metastases spread. Abnormal levels of NK cell, CD8+ T cells, memory CD4+ /CD4+ , naïve CD4+ / CD4+ , CD8+ HLA-DR/CD8+ , CD8+ CD38+ /CD8+ , and CD4+ /CD8+ can be a potential blood biomarkers of cancer development. CD4+ T-cell counts and percentages of CD8+ HLA-DR/ CD8+ and CD8+ CD38+ / CD8+ can predict the cancer progression.

Effect of Endostar combined with chemotherapy in advanced well-differentiated pancreatic neuroendocrine tumors.

The aim of the present study was to assess the effect of Endostar and temozolomide or dacarbazine plus 5-fluorouracil (5-FU) in patients with advanced pancreatic neuroendocrine tumors (pNETs).Phase II study of 14 patients with locally advanced or metastatic well-differentiated pNETs treated between April 2013 and September 2016. Patients received temozolomide or dacarbazine plus 5-FU, and Endostar. The primary outcome was the radiographic response rate.All 14 patients had nonfunctional pNETs. Six patients received temozolomide and 8 received dacarbazine + 5-FU, combined with Endostar. Thirteen patients were assessable for treatment response: 1(7%) with complete response, 5 (39%) with partial response, 5 (39%) with stable disease, and 2 (15%) with progression. The median progression-free survival was 12 months. The most common grade 1/2 toxicities were neutropenia (43%) and leucopenia (21%).Endostar combined with temozolomide or dacarbazine + 5-FU was effective in the treatment of advanced pNETs. The combinations were well tolerated.

Efficacy of Gemcitabine and S-1 for Patients with Advanced Pancreatic Cancer.

Objective To explore the efficacy and toxicities of gemcitabine combined with S-1 in treating locally advanced and metastatic pancreatic ductal adenocarcinoma and prognostic factors. Methods We retrospectively analyzed the clinical data of patients with locally advanced and metastatic pancreatic cancer receiving gemcitabine and S-1 as first-line therapy in the Department of Medical Oncology,Peking Union Medical College Hospital from January 2014 to January 2017.Gemcitabine was administered at a dose of 1000 mg/m2 over 30 min-utes on days 1 and 8,and oral S-1 at a dose of 40-60 mg twice daily from days 1 to 14,repeated every 3 weeks.All patients received at least two cycles of chemotherapy. Results A total of 60 patients were included,13(22%) achieved partial remission,37(61%) had stable disease,and 10(17%) experienced progressive disease.The median progression-free survival was 7 months(95% CI=6-10 months) and the median overall survival was 12 months(95% CI=9-20 months).Both univariate and multivariate analyses of prognostic factors showed primary resection was significant in predicting shorter progression-free survival and lung metastasis was significant for shorter overall survival.The most common grade 3-4 toxicities were neutropenia(27%) and leukopenia(18%). Conclusion Gemcitabine combined with S-1 is an effective regimen with manageable toxicities in the treatment of advanced pancreatic cancer and can be used as first-line therapy.

Efficiency of Sunitinib in Chinese Patients with Advanced Progressive Pancreatic Neuroendocrine Tumor.

Objective To explore the efficiency of sunitinib in Chinese pancreatic neuroendocrine tumors (pNET) patients. Methods Advanced pNET patients who had accepted sunitinib treatment in the oncology department of PUMC Hospital from January 2009 to June 2015 after disease progression were enrolled in this study. Data collection included clinicopathological characteristics,medical therapies and outcomes. Results Eighteen pNET patients were collected. The overall response rate (ORR) was 27.7% and the disease control rate (DCR) was 83.3%. Nine patients received sunitinib as the first-line therapy and 9 as the second/post-second line. The median progression-free survival (mPFs)(12 month vs. 12 month;HR:0.92,95%CI:0.31-2.75,P=0.88),ORR (22.2% vs.33.3%;Χ(2)=0.055,P=0.98),and DCR (88.9% vs.77.8%;Χ(2)=0.4,P=0.98)showed no significant difference between first-line therapy and post-second line therapy. The mPFS of Ki-67≥10% and Ki-67<10% group patients was not significantly different (8 months vs. 13 months;HR:1.13,95% CI:0.34-3.77,P=0.845). The commonly reported adverse events included bone marrow suppression,diarrhea,roteinuria,hypertension,and rash. Conclusions First-line or second/post-second line sunitinib treatment has certain antitumor activity in Chinese patients with advanced pNET. The efficiency and commonly reported adverse events of Sunitinib are consistent with the known Western data.

Chromogranin A is a reliable serum diagnostic biomarker for pancreatic neuroendocrine tumors but not for insulinomas.

BACKGROUND: Pancreatic neuroendocrine tumors (PNETs) are a group of rare tumors. Chromogranin A (CgA) was considered as the most practical and useful serum tumor marker in PNET patients. But peripheral blood levels of CgA are not routinely tested in Chinese patients with PNETs. This study was to assess the diagnostic value of CgA in Chinese patients with PNETs especially in patients with insulinomas. METHODS: Eighty-nine patients with PNETs including 57 insulinomas and 32 non-insulinoma PNETs as well as 86 healthy participants were enrolled in this study between September 2003 and June 2013. Serum levels of CgA were measured by ELISA method. Expression of CgA protein was detected in 26 PNET tissues including 14 insulinomas by immunohistochemical staining. RESULTS: Serum levels of CgA in 89 PNET patients were significantly higher than that in healthy controls (P = 7.2 × 10-9). Serum levels of CgA in 57 patients with insulinomas (median 64.8 ng/ml, range 25-164) were slightly higher than the levels in healthy controls (median 53.4 ng/ml, range 39-94) but much lower than the levels in 32 patients with non-insulinoma PNETs (median 193 ng/ml, range 27-9021), P = 0.001. The serum CgA levels were reduced in 16 of 17 patients with insulinomas after tumor resection. ROC curve showed that CgA values at 60 ng/ml distinguished patients with insulinomas from healthy controls but its sensitivity and specificity were 66.7% and 73.3%, respectively. In contrast, CgA values at 74 ng/ml distinguished patients with non-insulinoma PNETs from healthy controls, and the sensitivity and specificity were 65.6% and 91.9%, respectively. Except for two insulinomas with negative staining of CgA, 12 insulinoma tissues showed positive staining of CgA. CONCLUSION: CgA is a reliable serum diagnostic biomarker for PNETs but not for insulinomas.

[Treatment and prognosis of 77 cases of small cell lung cancer].

OBJECTIVE: To investigate the clinical treatment modality and prognosis of small cell lung cancer(SCLC). METHOD: We retrospectively analyzed the clinical data of 77 SCLC patients who were admitted to our department after 2002. RESULTS: The disease was limited in 43 patients and extensive in 34 patients. For patients with limited SCLC, the 1-year, 2-year, and 5-year survival rate was 80%, 56%, and 21%, respectively. Four patients who had undergone surgical resection were all alive. Among patients who underwent adjuvant chemotherapy followed by radiotherapy, salvage chemotherapy, and salvage chemotherapy followed by radiotherapy, the median of survival period was 51 months, 12 months, and 28 months, respectively. For patients with extensive SCLC, the 1-year and 2-year survival rate was 56% and 25%, respectively. The median of survival period was 14.3 months. Stage was an independent factor in multifactor COX regression. Monofactor COX regression showed that radiotherapy and resection were factors correlated with survival. Brain metastasis had no impact on survival. CONCLUSIONS: Chemotherapy followed by radiotherapy is preferred for limited SCLC, while surgical resection remains questionable for early-stage patients. For extensive SCLC, multi-line chemotherapy may be helpful to improve the overall survival. Stage is an independent factor for predicting the prognosis.