The number of detected GEP-NET increased about 5-fold in Germany between 1976 and 2006. At the same time, their anatomic distribution changed, and the survival of GEP-NET patients improved significantly. Second malignancies are common and influence the overall survival of GEP-NET patients. Thus, GEP-NET warrant our attention as well as intensive research on their tumorigenesis.
Clinically detected neuroendocrine neoplasms of the rectum have increased 10- to 30-fold in frequency over the past 45 years in Germany. Endoscopic ultrasonography is the method of choice for exact determination of the size of the tumor, depth of infiltration and detection of local lymph node metastases. Well-differentiated neuroendocrine tumors ≤ 10.0 mm in size that do not infiltrate the muscularis propria can be endoscopically resected. In the case of lymphatic or blood vessel invasion or spread to lymph nodes, surgical lymph node dissection is indicated. The management of well-differentiated, neuroendocrine rectal tumors 10.1-20 mm in size is still a matter of debate. Old age and multimorbidity favor a conservative endoscopic approach; however, in the case of fit young patients, surgical management has to be considered. For neuroendocrine rectal neoplasms ≥ 20 mm in size, the risk of metastatic spread increases to 60-80 % indicating that an endoscopic resection is not adequate. Due to the introduction of screening colonoscopy, neuroendocrine rectal tumors are nowadays diagnosed mostly at a prognostically favorable early stage.
Tobacco, alcohol, and betel quid are the main causes of squamous cell cancers of the upper aerodigestive tract. These substances can cause multifocal carcinogenesis leading to multiple synchronous or metachronous cancers of the oesophagus, head and neck region, and lungs (‘field cancerisation’). Globally there are several million people who have survived either head and neck squamous cell cancer (HNSCC) or lung cancer (LC). HNSCC and LC survivors are at increased risk of developing second primary malignancies, including second primary cancers of the oesophagus. The risk of second primary oesophageal squamous cell cancer (OSCC) ranges from 8-30% in HNSCC patients. LC and HNSCC survivors should be offered endoscopic surveillance of the oesophagus. Lugol chromoendoscopy is the traditional and best evaluated screening method to detect early squamous cell neoplasias of the oesophagus. More recently, narrow band imaging combined with magnifying endoscopy has been established as an alternative screening method in Asia. Low-dose chest computed tomography (CT) is the best evidencebased screening technique to detect (second primary) LC and to reduce LC-related mortality. Low-dose chest CT screening is therefore recommended in OSCC, HNSCC, and LC survivors. In addition, OSCC survivors should undergo periodic pharyngolaryngoscopy for early detection of second primary HNSCC. Secondary prevention aims at quitting smoking, betel quid chewing, and alcohol consumption. As field cancerisation involves the oesophagus, the bronchi, and the head and neck region, the patients at risk are best surveilled and managed by an interdisciplinary team.
Introduction: Apatinib, a small molecule oral tyrosine kinase inhibitor (TKI) that mainly targets vascular endothelial growth factor receptor-2, has been approved in the treatment of advanced gastric cancer in China. Whereas, many patients treated with apatinib experienced toxicity necessitating dose reduction. Maintaining adequate dosing and drug levels are essential for optimizing clinical efficacy. Thus, it is urgently needed to explore optimal dosing strategy of apatinib treatment in advanced gastric cancer. Other small molecule TKIs such as sunitinib [J Clin Oncol, 27 (22): 3584-3590], sorafenib [Future Oncol, 13(8): 679-693] and anlotinib [J Hematol Oncol, 9(1): 105] have demonstrated efficacy and acceptable tolerability in advanced cancers via an intermittent dosing schedule. The current study was conducted to compare the efficacy and safety of intermittent (5days on/2 days off schedule) vs continuous apatinib therapy in combination with docetaxel as second-line treatment for advanced gastric cancer. Methods: This study is designed as an open-label, randomized clinical trial. To enroll, patients are required to have pathologically or histologically confirmed advanced gastric cancer and have experienced treatment failure with first-line chemotherapy. Other inclusion criteria include !18 years; Eastern Cooperative Oncology Group performance status of 0-2; life expectancy more than 3 months. Eligible patients are randomized to the treatment arms in a ratio of 1:1. In intermittent dose schedule, patients receive oral apatinib 500 mg/d for 5 days followed by 2 days off treatment. In continuous dose arm, patients received oral apatinib 500 mg/d as a continuous daily dosing. Docetaxel 60 mg/m2 is administered intravenously to patients on day 1 in a 21-day cycle in both groups. Treatment is continued until disease progression, intolerable toxicity or withdraw of consent. The primary outcome is progression free survival. The secondary outcomes include objective response rate, disease control rate, overall survival, quality of life and safety. Tumor response is assessed according to Response Evaluation Criteria in Solid Tumors guideline version 1.1. The incidence and severity of adverse events are defined by the Common Terminology Criteria for Adverse events version 4.0. Approximately 60 patients will be enrolled, with 30 subjects in each arm. Enrollment opened on September, 2017. As the cutoff date of February 27 2018, 19 patients were enrolled: 11 patients in the intermittent dose arm and 8 patients in the continuous dose arm. Clinical trial information: NCT03334591.
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