Kunli Zhu

Circulating lymphocytes as predictors of sensitivity to preoperative chemoradiotherapy in rectal cancer cases.

OBJECTIVE The objective of this study was to identify clinical predictive factors for tumor response after neoadjuvant chemoradiotherapy (nCRT) in locally advanced rectal cancer (LARC). METHODS All factors were evaluated in 88 patients with LARC treated with nCRT. After a long period of 4-8 weeks of chemoradiotherapy, 3 patients achieved clinical complete response (cCR) and thus aggressive surgery was avoided, and the remaining 85 patients underwent a curative-intent operation. The response to nCRT was evaluated by tumor regression grade (TRG) system. RESULTS There were 32 patients (36.4%) with good tumor regression (TRG 3-4) and 56 (63.6%) with poor tumor regression (TRG 0-2). Lymphocyte counts and ratios were higher in good response cases (P=0.01, 0.03, respectively) while neutrophil ratios and N/L ratios were higher in poor response cases (P=0.04, 0.02, respectively). High lymphocyte ratios before nCRT and good tumor regression (TRG3-4) were significantly associated with improved 5-year disease-free survival (P<0.05). Pretreatment nodal status was also significantly associated with 5-year disease-free survival and 5-year overall survival (P<0.05). Multivariate analysis confirmed that the pretreatment lymphocyte ratio and lymph nodal status were independent prognostic factors. CONCLUSION Our study suggested that LARC patients with high lymphocyte ratios before nCRT would have good tumor response and high 5-year DFS and OS.

Measurement of tumor volume by PET to evaluate prognosis in patients with advanced non-small cell lung cancer treated by non-surgical therapy

Background Patients with advanced non-small cell lung cancer (NSCLC) seem to have disparity in prognosis. Accurate prediction of prognosis could be useful in the future to predict individual risk and to develop more aggressive or alternative treatment strategies. Purpose To evaluate the prognostic value of metabolic tumor volume (MTV) measured by 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) in patients with NSCLC. Material and Methods We retrospectively reviewed 120 patients with pathologically proven NSCLC (61 squamous cell carcinomas and 59 adenocarcinomas) who underwent pretreatment 18F-FDG PET. MTV and maximum standardized uptake value (SUVmax) for the primary tumors were measured by 18F-FDG PET. Pretreatment variables (age, sex, American Joint Committee on Cancer [AJCC] stage, histological type, SUVmax, and MTV) were analyzed to identify their correlation with two-year survival. To further evaluate and compare the predictive value of PET parameters, MTV, and SUVmax, time-dependent receiver-operating characteristic curve (ROC) analysis was used. Results In the univariate analysis, AJCC stage, histological type, MTV, and SUVmax of primary tumor were significant predictors of survival. On multivariate analysis, independent prognostic factors associated with decreased two-year survival were AJCC stage (hazard ratio [HR] 2.236, P = 0.003), histological type (HR 2.038, P = 0. 004), and MTV (HR 1.016, P = 0.001). SUVmax was not a significant factor (HR 0.96, P = 0.490). On time-dependent ROC analysis, MTV showed good predictive performance for two-year survival consistently better than SUVmax. Conclusion MTV, a volumetric parameter of 18F-FDG PET, is an important independent prognostic factor for survival and a better predictor of survival than SUVmax for the primary tumor in patients with advanced NSCLC.

Prognostic Significance of CYFRA21-1, CEA and Hemoglobin in Patients with Esophageal Squamous Cancer Undergoing Concurrent Chemoradiotherapy

PURPOSE To evaluate the prognostic value of serum CYFRA21-1, CEA and hemoglobin levels regarding long-term survival of patients with esophageal squamous cell carcinoma (ESCC) treated with concurrent chemoradiotherapy (CRT). METHODS Age, gender, Karnofsky Performance Status (KPS), tumor location, tumor length, T stage, N stage and serum hemoglobin, and CYFRA21-1 and CEA levels before concurrent CRT were retrospectively investigated and related to outcome in 113 patients receiving 5-fluorouracil and cisplatin combined with radiotherapy for ESCC. The Kaplan-Meier method was used to analyze prognosis, the log-rank to compare groups, the Cox proportional hazards model for multivariate analysis, and ROC curve analysis for assessment of predictive performance of biologic markers. RESULTS The median survival time was 20.1 months and the 1-, 2-, 3-, 5- year overall survival rates were 66.4%, 43.4%, 31.9% and 15.0%, respectively. Univariate analysis showed that factors associated with prognosis were KPS, tumor length, T-stage, N-stage, hemoglobin, CYFRA21-1 and CEA level. Multivariate analysis showed T-stage, N-stage, hemoglobin, CYFRA21-1 and CEA level were independent predictors of prognosis. By ROC curve, CYFRA21-1 and hemoglobin showed better predictive performance for OS than CEA (AUC= 0.791, 0.704, 0.545; P=0.000, 0.000, 0.409). CONCLUSIONS Of all clinicopathological and molecular factors, T stage, N stage, hemoglobin, CYFRA21-1 and CEA level were independent predictors of prognosis for patients with ESCC treated with concurrent CRT. Among biomarkers, CYFRA21-1 and hemoglobin may have a better predictive potential than CEA for long-term outcomes.

Predictors of sensitivity to preoperative chemoradiotherapy of rectal adenocarcinoma.

OBJECTIVES The purpose of the study was to identify predictive factors of tumor response to preoperative chemoradiotherapy for rectal adenocarcinoma. METHODS Ninety-eight patients with nonmetastatic rectal adenocarcinoma received preoperative concurrent chemoradiotherapy and underwent mesorectal excision. After treatment, tumor response according to tumor regression grade were evaluated. The correlation of clinicopathologic factors to tumor response was analyzed. RESULTS The results from a univariate analysis indicated that pretreatment carcinoembryonic antigen level ≤3.0 ng/ml (P = 0.002), non-fixed tumor (P = 0.001), and tumor circumferential extent ≤50% (P = 0.001) were associated significantly with a good tumor response. They also indicated that pretreatment positive lymph nodes (P = 0.032) were associated significantly with a poor tumor response. In multivariate analysis, the results indicated that pretreatment carcinoembryonic antigen level (hazard ratio, 2.930; P = 0.003), tumor mobility (hazard ratio, 2.651; P = 0.002) and circumferential extent of tumor (hazard ratio, 2.394; P = 0.019) independently predicted a good pathologic response rate. Pretreatment positive lymph nodes were not significantly associated with a good response (hazard ratio, 0.361; P = 0.191). CONCLUSIONS Pretreatment carcinoembryonic antigen level, tumor mobility and circumferential extent of tumor may be helpful in predicting responsiveness in rectal adenocarcinoma to preoperative chemoradiotherapy, although the results should be confirmed in larger, more homogeneous studies.

The prognostic role of EZH2 expression in rectal cancer patients treated with neoadjuvant chemoradiotherapy

BackgroundNeoadjuvant chemoradiotherapy (nCRT) combined with surgery has been implemented as a standard treatment strategy in locally advanced rectal cancer (LARC). However, there is a wide spectrum of response to nCRT. The aim of this study was to determine whether enhancer of zeste homologue 2 (EZH2 ) expression could predict response to nCRT and outcomes for patients in LARC.MethodThe study examined the EZH2 expression in 112 biopsies by immohistochemistry. The associations between EZH2 and clinical characters were analyzed.ResultsEZH2 expression in biopsy tissue was significantly related to increased tumor cell proliferation, as assessed by Ki-67 expression with a cutoff value of 37% (p <0.001). High EZH2 expression was correlated closely with low differentiation (p = 0.029), high CEA level (p = 0.041), T4 status (p = 0.011) and node metastasis (p =0.045). By univariate and multivariate analysis, we observed low EZH2 expression could reliably and independently predict the good response to nCRT ( p = 0.026 and p = 0.023) and down-staging ( p = 0.021 and p = 0.027). In univariate analysis, high EZH2 expression was significantly associated with poor 5-year disease-free survival (p = 0.025) and 5-year overall survival (p = 0.032). In multivariate analysis, EZH2 was a prognostic factor for 5-year DFS (HR = 2.287; 95% CI 1.137-4.602, p = 0.020) but not for 5-year OS (HR = 2.182; 95% CI 0.940-5.364, p = 0.069).ConclusionOur study revealed that low EZH2 expression in biopsy tissue might be a useful predictive factor of good tumor response to nCRT and longer 5-year DFS in patients with LARC. However this is a relatively small retrospective study, to further validate the role of EZH2 in rectal cancer, large consistent cohort studies are needed.

Human epidermal growth factor receptor-2 expression in locally advanced rectal cancer: Association with response to neoadjuvant therapy and prognosis

The aim of this study was to determine whether pretreatment status of human epidermal growth factor receptor‐2 (HER‐2) could predict pathologic response to neoadjuvant chemoradiotherapy (nCRT) and outcomes for patients with locally advanced rectal cancer (LARC). A total of 119 patients diagnosed with LARC received standardized multimodal treatment. Their HER‐2 status was determined in pretreatment biopsies by immunohistochemistry (IHC) and FISH. Tumor response was assessed in resected regimens using the tumor regression grade system and TNM staging system. Twenty‐two cases in 119 patients assessed as IHC3+ or IHC2+ plus gene‐amplified were determined as HER‐2 positive. Positive HER‐2 status was not associated with any pretreatment clinicopathologic parameters (P > 0.05). HER‐2 status could not predict pathologic response to nCRT based on downstaging (P = 0.210) and tumor regression grade (P = 0.085) but it provides us with a trend that HER‐2‐positive tumors may be resistant to nCRT. Positive HER‐2 status was significantly associated with poor 5‐year disease‐free survival (P = 0.015) and 5‐year overall survival (P = 0.026). It can act as a worse prognostic factor for LARC patients.

PDCD4 as a Predictor of Sensitivity to Neoadjuvant Chemoradiotherapy in Locally Advanced Rectal Cancer Patients

OBJECTIVE The purpose of this study was to examine the role of programmed cell death 4 (PDCD4) expression in predicting tumor response to neoadjuvant chemoradiotherapy and outcomes for patients with locally advanced rectal cancer. METHODS Clinicopathological factors and expression of PDCD4 were evaluated in 92 patients with LARC treated with nCRT. After the completion of therapy, 4 cases achieved clinical complete response (cCR), and thus the remaining 88 patients underwent a standardized total mesorectal excision procedure. There were 38 patients (41.3%) with a good response (TRG 3-4) and 54 (58.7%) with a poor one (TRG 0-2). RESULTS Immunohistochemical staining analyses showed that patients with high expression of PDCD4 were more sensitive to nCRT than those with low PDCD4 expression (P=0.02). High PDCD4 expression before nCRT and good response (TRG3-4) were significantly associated with improved 5-year disease-free survival and 5-year overall survival (P<0.05). Multivariate analysis demonstrated that the pretreatment PDCD4 expression was an independent prognostic factor. CONCLUSION Our study demonstrated that high expression of PDCD4 protein is a useful predictive factor for good tumor response to nCRT and good outcomes in patients with LARC.

GOLPH3 overexpression correlates with poor response to neoadjuvant therapy and prognosis in locally advanced rectal cancer

Neoadjuvant chemoradiotherapy (nCRT) combined with surgery is a standard therapy for locally advanced rectal cancer (LARC). The aim of this study was to assess the expression of GOLPH3 (Golgi phosphoprotein 3), a newly found oncogene, in LARC as well as its relationship with nCRT sensitivity and prognosis. We retrospectively analyzed 148 LARC cases receiving nCRT and total mesorectal excision (TME). Immunohistochemistry was used to assess GOLPH3 and mTOR (mammalian target of rapamycin) in tumor tissues. Then, the associations of GOLPH3 with pathological characteristics and prognosis of rectal cancer were assessed. The 148 cases included 77 with high GOLPH3 expression (52.03%), which was associated with tumor invasive depth and lymphatic metastasis. Cases with high GOLPH3 expression had 2.58 and 2.71 fold higher local relapse and distant metastasis rates compared with the low expression group. Correlation analyses showed that GOLPH3 was an independent indicator for judging tumor down-staging and postoperative TRG (tumor regression grade), indicating it could predict nCRT sensitivity. In addition, GOLPH3 expression was associated with mTOR levels. Multiple-factor analysis indicated that GOLPH3 was an independent prognosis indicator for 5 year-DFS (disease free survival) and OS (overall survival) in LARC. These results reveal that GOLPH3 is an independent predictive factor for nCRT sensitivity and prognosis in LARC, with a mechanism related to mTOR.

Comparison of intra-arterial chemoembolization with and without radiotherapy for advanced hepatocellular carcinoma with portal vein tumor thrombosis: a meta-analysis

Purpose Numerous studies have tried to combine transarterial chemoembolization (TACE) or hepatic arterial infusion chemotherapy (HAIC) with radiotherapy (RT) for the treatment of hepatocellular carcinoma (HCC) patients with portal vein tumor thrombus (PVTT). However, the efficacy of TACE or HAIC combined with RT versus TACE or HAIC alone remains controversial. Thus, we performed a meta-analysis to compare the efficacy and safety of intra-arterial chemoembolization combined with RT versus intra-arterial chemoembolization alone for the treatment of HCC patients with PVTT. Methods PubMed, Embase, and Cochrane Library databases were systematically searched for eligible studies. Two authors independently reviewed the abstracts, extracted relevant data and rated the quality of studies. The major end points were objective response rate (ORR), overall survival (OS), and adverse events. Results Eight studies with a total of 1,760 patients were included in this meta-analysis. The pooled results showed that intra-arterial chemoembolization combined with RT significantly improved ORR of PVTT (OR, 4.22; 95% CI, 3.07–5.80; P<0.001) and OS (HR, 0.69; 95% CI, 0.57–0.83; P=0.001), but did not affect ORR of primary liver tumor (OR, 1.37; 95% CI, 0.67–2.79; P=0.390). The incidence of grade 3 or 4 leukopenia (OR, 5.80; 95% CI, 2.478–13.56; P<0.001) and thrombocytopenia (OR, 3.77; 95% CI, 1.06–13.43; P=0.041) was higher in the intra-arterial chemoembolization plus RT group than in the intra-arterial chemoembolization group. Conclusion Combination therapy of intra-arterial chemoembolization and RT for HCC patients with PVTT could bring higher ORR of PVTT and better survival benefits. This combination therapy was also associated with a significantly increased risk of adverse events. However, they were mostly mild to moderate and successfully treated with conservative treatment.

Prognostic value of serum γ‑glutamyl transferase in unresectable hepatocellular carcinoma patients treated with transcatheter arterial chemoembolization combined with conformal radiotherapy

The detection of γ-glutamyl transferase (GGT) has previously been reported to be useful in the diagnosis in hepatocellular carcinoma (HCC). The aim of the present study was to investigate the baseline serum GGT levels in patients with intermediate HCC (Barcelona Clinic Liver Cancer stage B) following treatment with transcatheter arterial chemoembolization (TACE) combined with three-dimensional conformal radiotherapy (3DCRT). A total of 154 intermediate HCC patients with Child-Pugh grade A were retrospectively investigated. Receiver operating characteristic (ROC) analysis was used to determine the optimal threshold for the GGT serum levels, and univariate and multivariate analyses were used to establish the prognostic factors. The median overall survival (OS) time was 24.3 months. The optimal threshold for GGT was 85 U/L (sensitivity, 75.13%; specificity, 69.81%; and area under the ROC curve, 0.763). The one-, three- and five-year OS rates were 79.9, 49.7 and 17.2%, respectively, for patients with low GGT levels (≤85 U/l) and 52.3, 22.1 and 8.5%, respectively, for patients with high GGT levels (>85 U/l) (P=0.007). The results indicated that the serum GGT level was an independent prognostic factor (hazard ratio=2.32; P=0.007) for OS. Furthermore, in subgroups stratified according to serum α-fetoprotein, gross tumor volume and radiation dose, serum GGT was also found to correlate with OS (P<0.05). Therefore, the baseline GGT level may be a significant prognostic factor for intermediate HCC patients with Child-Pugh grade A following TACE combined with 3DCRT.