A comparative analysis of EGFR mutation status in association with the efficacy of TKI in combination with WBRT/SRS/surgery plus chemotherapy in brain metastasis from non-small cell lung cancer.

We proposed to identify the efficacy of an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) using whole brain radiotherapy (WBRT)/stereotactic radiosurgery (SRS)/surgery in brain metastases from patients with non-small cell lung cancer (NSCLC) and clarify the association between treatment outcome and EGFR gene mutation status. A total of 282 patients with NSCLC brain metastases who underwent WBRT/SRS/surgery alone or in combination with TKI were enrolled in our study from 2003-2013. Amplification mutation refractory system technology was used to determine the EGFR mutation status in 109 tissue samples. EGFR mutation detection was performed in 109 patients with tumor tissues. The EGFR positive rate was 50 % (55/109), including 26 exon 19 deletions and 24 L858R mutations. The median follow-up time was 28 months. The median overall survival, median progression-free survival of intracranial disease, and median progression-free survival of extracranial disease was significantly longer for patients with TKI treatment (31.9 vs 17.0 months, P < 0.0001; 19.8 vs 12.0 months, P < 0.0001; and 19.6 vs 12.3 months, P < 0.0001; respectively). In subgroup analysis within the TKI group, patients harboring EGFR mutations had better extracranial disease control (20.4 vs 14.1 months, P = 0.032). Administration of TKI agents with conventional therapy compared with conventional therapy alone might be beneficial for overall survival, progression-free survival of intracranial disease and progression-free survival of extracranial disease in patients with brain metastases from NSCLC independent of EGFR mutations.

High plasma fibrinogen concentration and platelet count unfavorably impact survival in non-small cell lung cancer patients with brain metastases.

High expression of fibrinogen and platelets are often observed in non-small cell lung cancer (NSCLC) patients with local regional or distant metastasis. However, the role of these factors remains unclear. The aims of this study were to evaluate the prognostic significance of plasma fibrinogen concentration and platelet count, as well as to determine the overall survival of NSCLC patients with brain metastases. A total of 275 NSCLC patients with brain metastasis were enrolled into this study. Univariate analysis showed that high plasma fibrinogen concentration was associated with age≥65 years (P = 0.011), smoking status (P = 0.009), intracranial symptoms (P = 0.022), clinical T category (P = 0.010), clinical N category (P = 0.003), increased partial thromboplastin time (P < 0.001), and platelet count (P < 0.001). Patients with low plasma fibrinogen concentration demonstrated longer overall survival compared with those with high plasma fibrinogen concentration (median, 17.3 months versus 11.1 months; P≤0.001). A similar result was observed for platelet counts (median, 16.3 months versus 11.4 months; P = 0.004). Multivariate analysis showed that both plasma fibrinogen concentration and platelet count were independent prognostic factors for NSCLC with brain metastases (R2 = 1.698, P < 0.001 and R2 = 1.699, P < 0.001, respectively). Our results suggest that high plasma fibrinogen concentration and platelet count indicate poor prognosis for NSCLC patients with brain metastases. Thus, these two biomarkers might be independent prognostic predictors for this subgroup of NSCLC patients.

Managing esophageal fistulae by endoscopic transluminal drainage in esophageal cancer patients with superior mediastinal sepsis after esophagectomy.

The management of postoperative leaks into the mediastinum after esophagectomy remains a challenge. We describe our clinical management of this complication through endoscopic transluminal drainage. Between 2008 and 2011, 4 patients with esophageal squamous cell carcinoma (ESCC) who underwent McKeown-type esophagectomy with two-field lymphadenectomy experienced complicated anastomotic fistulae in the presence of superior mediastinal sepsis. All 4 patients underwent endoscopic transluminal drainage, and all survived. The mean healing period was 50 days (range, 31 to 58 days), the mean stay in the intensive care unit was 7.3 days (range, 1 to 18 days), and the mean hospital stay was 64.5 days (range, 49 to 70 days). Endoscopically guided transluminal drainage should be considered for ESCC patients with superior mediastinal fistulae after esophagectomy.

The predictive value of histological tumor regression grading (TRG) for therapeutic evaluation in locally advanced esophageal carcinoma treated with neoadjuvant chemotherapy.

Response criteria remain controversial in therapeutic evaluation for locally advanced esophageal carcinoma treated with neoadjuvant chemotherapy. We aimed to identify the predictive value of tumor regression grading (TRG) in tumor response and prognosis. Fifty-two patients who underwent neoadjuvant chemotherapy followed by esophagectomy and radical 2-field lymphadenectomy between June 2007 and June 2011 were included in this study. All tissue specimens were reassessed according to the TRG scale. Potential prognostic factors, including clinicopathologic factors, were evaluated. Survival curves were generated by using the Kaplan-Meier method and compared with the log-rank test. Prognostic factors were determined with multivariate analysis by using the Cox regression model. Our results showed that of 52 cases, 43 (83%) were squamous cell carcinoma and 9 (17%) were adenocarcinoma. TRG was correlated with pathologic T(P = 0.006) and N (P < 0.001) categories. Median overall survival for the entire cohort was 33 months. The 1- and 2-year overall survival rates were 71% and 44%, respectively. Univariate survival analysis results showed that favorable prognostic factors were histological subtype (P = 0.003), pathologic T category (P = 0.026), pathologic N category (P < 0.001), and TRG G0 (P = 0.041). Multivariate analyses identified pathologic N category (P < 0.001) as a significant independent prognostic parameter. Our results indicate that histomorphologic TRG can be considered as an alternative option to predict the therapeutic efficacy and prognostic factor for patients with locally advanced esophageal carcinoma treated by neoadjuvant chemotherapy.

Time distribution of recurrence risk of oesophageal squamous cell carcinoma with complete resection (R0) in a Chinese population.

OBJECTIVES: We aimed to clarify the correlation between clinic-pathological characteristics and the distribution of recurrence probability during follow-up of oesophageal squamous cell carcinoma (OSCC) patients with complete resection analysis by hazard function, and to try to provide evidence-based data for optimal timing for adjuvant therapy. METHODS: A single-institution, retrospective study was conducted on 553 Chinese patients with OSCC who underwent R0 resection between January 2005 and October 2007. Survival curves were generated using the Kaplan-Meier method, and hazard function was used to analyse the annual recurrence hazard. RESULTS: The median recurrence-free survival time of these patients was 3.4 years. In univariate analysis, the favourable prognostic factors were gender, smoking status, a tumour length of ≤4.0 cm, tumour invasion thickness, normal level of squamous cell carcinoma (SCC) antigen, pathological T category and pathological N category. In multivariate analysis, pathological T category and pathological N category were independent prognostic factors. Overall, the recurrence hazard curve for the entire cohort showed that the first major recurrence surge began to increase from the first year at 22.97% and peaked at 1.3 years at 27.4% during follow-up. The second recurrence surge peaked during the seventh year at 13.0%. A lower recurrence risk was observed in patients with the following clinic-pathological characteristics: gender, smoking status and N0. CONCLUSIONS: We identify the presence of two peaks for recurrence risk in Chinese patients with resectable OSCC, which might contribute to choosing the optimal timing for adjuvant therapy after an operation to decrease or delay the recurrence hazard for patients with resectable OSCC.

Time-varying pattern of postoperative recurrence risk of early-stage (T1a-T2bN0M0) non-small cell lung cancer (NSCLC): results of a single-center study of 994 Chinese patients.

BACKGROUND: The aim of this study was to analyze the time-varying pattern of recurrence risk of early-stage (T1a-T2bN0M0) non-small cell lung cancer (NSCLC) after surgery using the hazard function and identify patients who might benefit from adjuvant chemotherapy. PATIENTS AND METHODS: This retrospective study enrolled 994 patients with early-stage NSCLC who underwent radical surgical resection between January 1999 and October 2009. Survival curves were generated using the Kaplan-Meier method, and the annual recurrence hazard was estimated using the hazard function. RESULTS: The median recurrence-free survival (RFS) was 8.8 years. The life table survival analysis showed that the 1-year, 3-year, 5-year and 10-year recurrence rates were 82.0%, 67.0%, 59.0% and 48.0%, respectively. Approximately 256 (25.7%) patients experienced relapse [locoregional: 32 (3.2%) and distant: 224 (22.5%)], and 162 patients died from cancer. The annual recurrence hazard curve for the entire population showed that the first major recurrence surge reached a maximum 1.6 years after surgery. The curve subsequently declined until reaching a nadir at 7.2 years. A second peak occurred at 8.8 years. An analysis of clinical-pathological factors demonstrated that this double-peaked pattern was present in several subgroups. CONCLUSIONS: The presence of a double-peaked pattern indicates that there is a predictable temporal distribution of the recurrence hazard of early-stage NSCLC. The annual recurrence hazard may be an effective method of selecting patients at high risk of recurrence, who may benefit from adjuvant therapy.

Concurrent oncogene mutation profile in Chinese patients with stage Ib lung adenocarcinoma.

Molecular characteristics in lung cancer are associated with carcinogenesis, response to targeted therapies, and prognosis. With concurrent oncogene mutations being reported more often, the adjustment of treatment based on the driver gene mutations would improve therapy. We proposed to investigate the distribution of concurrent oncogene mutations in stage Ib lung adenocarcinoma in a Chinese population and find out the correlation between survival outcome and the most frequently mutated genes in EGFR and KRAS in Chinese population. Simultaneously, we tried to validate the Sequenom method by real time fluoresce qualification reverse transcription polymerase chain reaction (RT-PCR) in oncogene detection. One hundred fifty-six patients who underwent complete surgical resection in our hospital between 1999 and 2007 were retrospectively investigated. Using time-of-flight mass spectrometry, 238 mutation hotspots in 19 oncogenes were examined. Genetic mutations occurred in 86 of 156 patients (55.13%). EGFR was most frequently gene contained driver mutations, with a rate of 44.23%, followed by KRAS (8.33%), PIK3CA (3.84%), KIT (3.20%), BRAF (2.56%), AKT (1.28%), MET (0.64%), NRAS (0.64%), HRAS (0.64%), and ERBB2 (0.64%). No mutations were found in the RET, PDGFRA, FGFR1, FGFR3, FLT3, ABL, CDK, or JAK2 oncogenes. Thirteen patients (8.3%) were detected in multiple gene mutations. Six patients had PIK3CA mutations in addition to mutations in EGFR and KRAS. EGFR mutations can coexist with mutations in NRAS, KIT, ERBB2, and BRAF. Only one case was found to have a KRAS mutation coexisting with the EGFR T790M mutation. Otherwise, mutations in EGFR and KRAS seem to be mutually exclusive. There is no survival benefit in favor of EGFR/KRAS mutation. Several concomitant driver gene mutations were observed in our study. None of EFGR/KRAS mutation was demonstrated as a prognostic factor. Polygenic mutation testing by time-of-flight mass spectrometry was validated by RT-PCR, which can be an alternative option to test for multiple mutations and can be widely applied to clinical practice and help to guide treatment.