Zhengbo Song

Brain Metastases from Esophageal Cancer: Clinical Review of 26 Cases

OBJECTIVE To assess the frequency of brain metastasis in patients with primary esophageal cancer and to describe the clinical characteristics, diagnosis, and prognosis. METHODS Of 1612 patients with primary esophageal carcinoma treated at a single institution from 2000-2010, a retrospective analysis of the medical files of 26 consecutive patients with central nervous system involvement was carried out. The clinical history, imaging, and pathologic findings were analyzed. RESULTS Of the 26 patients, 12 initially presented with a single cerebral metastatic lesion, and 14 had multiple brain lesions. There were 4 patients with adenocarcinoma and 22 with squamous cell carcinoma. Treatments were as follows: 5 patients underwent surgery followed by whole-brain radiation, 5 underwent stereotactic radiosurgery, 13 received whole-brain radiation, and 3 received chemotherapy. The median survival was 4.2 months; 1-year survival rate was 5.8%. CONCLUSIONS In this retrospective study of 1612 patients with esophageal carcinoma at a single medical center, 1.61% (26 of 1612) of the patients had a diagnosis of brain metastasis. The prognosis is poor for patients with brain metastasis from esophageal carcinoma. A solitary brain lesion, surgical treatment, and a good Karnofsky Performance Status may indicate a good prognosis.

Therapeutic efficacy of gefitinib and erlotinib in patients with advanced lung adenosquamous carcinoma

Background: Adenosquamous carcinoma (ASC) of the lung is a rare subtype of nonsmall‐cell lung cancer (NSCLC). To date, the efficacious targeted therapy for advanced ASC remains unclear and the epidermal growth factor receptor (EGFR) mutation rate is not well known. Methods: We retrospectively reviewed clinical information of patients with ASC who were treated with gefitinib or erlotinib at Zhejiang Cancer Hospital between January 2007 and December 2011. Survival analysis was evaluated by the Kaplan‐Meier method. EGFR mutations were assessed in part using direct sequencing methods. Results: In total, 49 patients with a median age of 57 years were used in this study. Thirteen patients achieved a partial response and 19 had disease stabilization. The objective response rate was 26.5%, and the disease control rate was 65.3%. The median progression‐free survival and overall survival were 4.3 and 17.6 months, respectively. In 21 patients with adequate specimens for molecular analysis, 7 (33.3%) had EGFR mutations (4 with deletions within exon 19 and 3 with L858R messenger mutation in exon 21). EGFR mutations were significantly more frequent in women (4/9, 44.4%) than men (3/12, 25%), never‐smokers (6/15, 40%), and smokers (1/6, 16.7%). Conclusion: EGFR‐tyrosine kinase inhibitor (TKI) is an effective treatment for ASC. The frequency of EGFR mutation and clinical characteristics of the EGFR mutants in ASC are similar to those of Asian patients with adenocarcinoma.

A Comparison of ddPCR and ARMS for detecting EGFR T790M status in ctDNA from advanced NSCLC patients with acquired EGFR-TKI resistance

A sensitive and convenient method for detecting epidermal growth factor receptor (EGFR) T790M mutations from circulating tumor DNA (ctDNA) in advanced non–small cell lung cancer (NSCLC) patients with acquired EGFR‐TKI resistance would be desirable to direct patient sequential treatment strategy. A comparison of two platforms for detecting EGFR mutations in plasma ctDNA was undertaken. Plasma samples and tumor samples were collected from patients with acquired EGFR‐TKI resistance in Zhejiang Cancer Hospital from December 2014 to December 2015. Extracted ctDNA was analyzed using two platforms (Droplet Digital PCR and ARMS [dPCR]). A total of 108 patients were enrolled in this study. One hundred and eight patient plasma samples were detected by ddPCR and 75 were detected by ARMS. And 16 patients obtained tissue re‐biopsy, using ARMS assay for detecting EGFR T790M mutation. In all, 43.7% (47/108) had acquired T790M mutation by ddPCR. In 75 patient plasma samples, comparing ddPCR with ARMS, the rates of T790M mutation were 46.7% (35/75) and 25.3% (19/75) by ddPCR and ARMS, respectively. Of all, 16 patients both had tumor and plasma samples, the T790M mutation rates were 56.3% (9/16) by ARMS in tissue and 50.5% (8/16) by ddPCR in plasma ctDNA. The progression mode tended to gradual progression in T790M mutation patients (40.4%), but the T790M negative was inclined to the mode of dramatic progression (39.3%). The patients with T790M‐positive tumors had a longer time to disease progression after treatment with EGFR‐TKIs (median, 13.1 months vs. 10.8 months; P = 0.010) and overall survival (median, 35.3 months vs. 30.3 months; P = 0.214) compared with those with T790M‐negative patients. Our study demonstrates ddPCR assay may provide a highly sensitive method to detect EGFR T790M gene in plasma. And T790M‐positive patients have better clinical outcomes to EGFR‐TKIs than T790M‐negative patients.

Salvage treatment with apatinib for advanced non-small-cell lung cancer

Objective No definitive chemotherapeutic regimen has been established in patients with non-small-cell lung cancer (NSCLC) who failed second- or third-line treatment. The aim of this study was to evaluate apatinib, a VEGFR-2 inhibitor, in advanced NSCLC as salvage treatment. Methods We evaluated the efficacy and toxicity of apatinib in patients with previously treated advanced NSCLC from 2014 to 2015 in Zhejiang Cancer Hospital. Survival analysis was performed by the Kaplan–Meier method. Results Forty-two patients were included in the present study. Four patients achieved partial response, and 22 achieved stable disease, representing a response rate of 9.5% and a disease control rate of 61.9%. Median progression-free survival and overall survival were 4.2 and 6.0 months, respectively. The toxicities associated with apatinib were generally acceptable with a total grade 3/4 toxicity of 50%. Conclusion Apatinib appears to have some activity against advanced NSCLC when utilized as salvage treatment.

Re-administration after the failure of gefitinib or erlotinib in patients with advanced non-small cell lung cancer

OBJECTIVE Few treatment options are available for advanced non-small cell lung cancer (NSCLC) patients who have failed of gefitinib or erlotinib treatment in second/third-line treatment. The aim of this study was to investigate the efficacy of re-administration of the same TKI after failure of gefitinib or erlotinib. PATIENTS AND METHODS The clinical data of 33 patients with advanced NSCLC were retrospectively analyzed. All of the patients were given the same TKI treatment after the failure of gefitinib or erlotinib. Survival analysis was evaluated by Kaplan-Meier method. RESULTS Twenty patients (60.6%) were re-administration with gefitinib as the 2(nd) EGFR-TKI, and thirteen patients (39.4%) received erlotinib. One patient (3.0%) showed partial response (PR), 14 (42.4%) achieved stable disease (SD), and 18 (54.5%) had progressive disease (PD). The disease control rate was 45.5% and the median progression-free survival was 1.5 months (95% CI: 0.6-2.3 months). The PFS in patients who got disease control in the prior TKI was 2.2 and 1.2 months in the progression disease cases (P=0.29), the DCR was 54.5% and 27.3% in two group, respectively (P=0.26). CONCLUSIONS Re-administration of TKI seems to be a potential therapeutic option for treatment of selected advanced NSCLC patients after failure of gefitinib or erlotinib, especially for the patients with NSCLC who once responded from the prior TKI treatment.

Primary tracheobronchial mucoepidermoid carcinoma - a retrospective study of 32 patients

BackgroundThis retrospective study was designed to investigate the clinical characteristics, diagnosis, treatment and prognosis of primary tracheobronchial mucoepidermoid carcinoma (MEC).MethodsClinical data were retrospectively analyzed from 32 patients with pathologically confirmed primary tracheobronchial MEC between January 1990 and December 2010 at Zhejiang Cancer Hospital. The Kaplan-Meier methods were used to estimate and compare survival rates.ResultsThere were 19 males and 13 females ranging in age from 7 to 73 years, with a median age of 28 years. Twenty-six of the 32 patients were treated with surgery alone. The other six patients were treated with surgery plus postoperative radiotherapy or chemotherapy. Six patients died during the follow-up time. The overall five-year survival rates were 81.25%, whereas the five-year survival rate of seven patients with high-grade tumors was only 28.6%. Stage I and II patients experienced better survival than Stage III and IV patients (the five-year survival rate was 100% and 43.6% respectively, P<0.001).ConclusionsPrimary tracheobronchial MEC is a rare disease. Histologic grading and TNM (tumor-node-metastasis)staging are independent prognostic factors. Surgical resection is the primary treatment.

Analysis of the tumor length and other prognosis factors in pT1-2 node-negative esophageal squamous cell carcinoma in a Chinese population

BackgroundTumor length is an important prognostic factor for many carcinomas, but its role in esophageal cancer remained undetermined. The aim of this study was to investigate the effect of tumor length on survival for patients with confined tumors (grade pT1-2) without lymph-node metastases in esophageal squamous cell carcinoma.MethodsWe enrolled 201 patients with esophageal squamous cell carcinoma (SCC) who had undergone surgical resection and been confirmed as pT1-2N0M0. The relationship of tumor length with overall survival was assessed and compared with other factors detailed in the American Joint Committee on Cancer (AJCC) tumor, node, metastasis (TNM) staging system published in 2009.ResultsThe overall survival (OS) rates at 1, 3, and 5 years were 93.0%, 83.7%, and 69.2%, respectively. The tumor length adversely affected OS, with the 5-year rate being 93.5%, 82.0%, 68.6%, 67.9%, 55.3% and 41.1%, respectively for tumor lengths of less than 10 mm, 10 to 20 mm, 20 to 30 mm, 30 to 40 mm, 40 to 50 mm, and greater than 50 mm (P< 0.001). Multivariate analyses showed that the pathologic T classification and grade of tumor was significantly associated with OS. Tumor length of 30 mm or more remained an independent prognostic factor (P = 0.04), as did the other current TNM factors.ConclusionTumor length appears to affect the OS of patients with early-stage esophageal squamous cell carcinoma. It may provide additional prognostic information for the current TNM staging system.

Response to crizotinib in a squamous cell lung carcinoma patient harbouring echinoderm microtubule-associated protein-like 4-anaplastic lymphoma translocation: A case report

Squamous cell lung cancer (SCC) presenting with anaplastic lymphoma kinase (ALK) translocation is rare. We present a case of ALK gene translocation‐SCC in which a remarkable tumor response to crizotinib was achieved after the failure of prior chemoradiotherapy. Considering this remarkable response, we conclude that ALK testing in female non‐smokers or in any patient unresponsive to the initial regimen of chemotherapy, is recommended for SCC patients.

Preoperative elevation of serum C-reactive protein as an indicator of poor prognosis for early-stage esophageal squamous cell carcinoma

Preoperative elevation of serum C‐reactive protein (CRP) is reportedly associated with poor prognosis in several types of cancer. This study investigated the role of serum CRP as a prognostic factor in early‐stage esophageal squamous cell carcinoma (ESCC). The preoperative serum CRP levels were measured in 156 newly diagnosed pT1–2N0M0 patients using an enzyme‐linked immunosorbent assay. Correlations between serum CRP levels and other clinical parameters were analyzed. Multivariate analyses were performed to find prognostic markers using Coxs proportional hazards model. CRP concentrations were within the normal range in 117 (75%) individuals, but were elevated in 39 (25%) patients. Serum CRP levels were significantly correlated with the tumor length (p = 0.032), depth (T classification, p = 0.0157), or histologic grade (p = 0.034). The overall 5‐year survival rates were 76.3% and 50.2% in the low‐ and high‐CRP groups, respectively (p = 0.005). By multivariate analyses, the elevated serum CRP level was found to be an independent prognostic factor for poor survival (hazard ratio = 2.131; p = 0.007), regardless of tumor classification or other prognostic factors. In conclusion, preoperative, high serum CRP is an independent determinant of poor prognosis in early‐stage ESCC.

Clinicopathologic characteristics, genetic variability and therapeutic options of RET rearrangements patients in lung adenocarcinoma.

BACKGROUND RET fusion gene is identified as a novel oncogene in a subset of non-small cell lung cancer (NSCLC). However, few data are available about the prevalence, clinicopathologic characteristics, genetic variability and therapeutic options in RET-positive lung adenocarcinoma patients. PATIENTS AND METHODS For 615 patients with lung adenocarcinoma, RET status was detected by reverse transcription-polymerase chain reaction (RT-PCR). Next-generation sequencing (NGS) and FISH were performed in positive cases. Thymidylate synthetase (TS) mRNA level was assayed by RT-PCR. Overall survival (OS) was evaluated by Kaplan-Meier method and compared with log-rank test. RESULTS Twelve RET-positive patients were identified by RT-PCR. However, one patient failed the detection of RET rearrangement by FISH and NGS. Totally, 11 patients (1.8%) confirmed with RET rearrangements by three methods, including six females and five males with a median age of 54 years. The presence of RET rearrangements was associated with lepidic predominant lung adenocarcinoma subtype in five of 11 patients. RET rearrangements comprised of nine KIF5B-RET and two CCDC6-RET fusions. Four patients had concurrent gene variability by NGS detection,including EGFR(n=1),MAP2K1 (n=1), CTNNB1 (n=1) and AKT1 (n=1). No survival difference existed between RET-positive and negative patients (58.1 vs. 52.0 months, P=0.504). The median progression-free survival of first-line pemetrexed/platinum regimen was 7.5 months for four recurrent cases. And the level of TS mRNA was lower in RET-positive patients than that in those RET-negative counterparts (239±188×10-4 vs. 394±457×10-4, P=0.019). CONCLUSION The prevalence of RET fusion is approximately 1.8% in Chinese patients with lung adenocarcinoma. RET rearrangements are characterized by lepidic predominance and a lower TS level. RET-rearranged patients may benefit more from pemetrexed-based regimen.