BACKGROUND: Advanced epidermal growth factor receptor (EGFR)-mutant lung adenocarcinoma had a high overall incidence of brain metastasis during the full course, and local brain radiotherapy combined with systemic targeted therapy may be a better strategy. This study aimed to identify the prognostic factors of EGFR-mutant brain-metastatic lung adenocarcinoma patients who received EGFR-tyrosine kinase inhibitors (EGFR-TKIs) in combination with gamma knife radiosurgery. METHODS: Retrospective analysis of EGFR-mutant lung adenocarcinoma patients with brain metastases which developed at initial diagnosis or during EGFR-TKIs treatment period were performed. Intracranial progression free survival (PFS) was statistically analyzed between different subgroups to find out the prognostic factors including gender, age, smoking history, extracranial metastasis, EGFR mutation type, size and number of intracranial lesions, carcino-embryonic antigen (CEA) level, lung-molGPA score and so on. RESULTS: A total of 74 EGFR-mutant brain-metastatic lung adenocarcinoma patients were enrolled in this study, with median intracranial PFS of 14.7 months. One-year intracranial-progression-free rate was 58.5%, and two-year rate was 22.2%. Univariate survival analysis showed that patients with lower CEA level at initial diagnosis (<10 ng/L)(16.9 months vs 12.6 months, P=0.012) and smaller intracranial lesions (<2 cm)(15.4 months vs 10.8 months, P=0.021) and higher lung-molGPA score (>3)(15 months vs 12.6 months, P=0.041) were prone to have a superior intracranial PFS. Multivariate analysis showed that CEA≥10 ng/mL and intracranial lesion≥2 cm were the independent risk factors of intracranial PFS. CONCLUSIONS EGFR-TKIs in combination with gamma knife radiosurgery was an efficient treatment option to control the cranial tumor lesion. CEA≥10 μg/L at initial diagnosis and intracranial lesion≥2 cm were the risk factors of EGFR-mutant brain-metastatic lung adenocarcinoma patients receiving EGFR-TKIs in combination with gamma knife radiosurgery.
Adenocarcinoma of Lung ; drug therapy ; pathology ; radiotherapy ; therapy ; Adult ; Aged ; Brain Neoplasms ; secondary ; Combined Modality Therapy ; ErbB Receptors ; antagonists & inhibitors ; genetics ; Female ; Humans ; Male ; Middle Aged ; Mutation ; Prognosis ; Protein Kinase Inhibitors ; pharmacology ; therapeutic use ; Radiosurgery ; Retrospective Studies

OBJECTIVES: This study evaluated the predictive factors for survival of patients with oral squamous cell carcinoma (OSCC) and investigated the overall and disease-specific survival (DSS) outcomes. MATERIALS AND METHODS: A total of 67 consecutive patients who underwent surgery for OSCC from January 2006 to November 2014 were included in this study. Patients were classified according to age, sex, pTNM stages, primary sites, smoking and alcohol drinking habits, depth of invasion, perineural and lymphovascular invasion, cell differentiation and postoperative radiotherapy. Kaplan-Meier methods were used to estimate the survival categorized by patient groups. Cox regression methods were used to investigate the main independent predictors of survival. RESULTS: Nineteen patients died of OSCC during follow-up periods. Another five patients died of other diseases including lung adenocarcinoma (n=1), cerebral infarction (n=1), general weakness (n=2), and pneumonia (n=1). The tongue (n=16) was the most common site for primary origin, followed by buccal mucosa (n=15), mandibular gingiva (n=15), maxillary gingiva (n=9), floor of mouth (n=9), retromolar trigone (n=2), and palate (n=1). Eleven patients had pTNM stage I disease, followed by stage II (n=22) and stage IV (n=34). No patients had pTNM stage III disease in this study. The overall survival of all patients was 64.2% and the DSS was 71.6%. DSS of patients with stage I and II disease was 100%. Stepwise Cox regression showed the two predictors for DSS were pTNM stage (P<0.0001, odds ratio=19.633) and presence of metastatic lymph nodes (P=0.0004, odds ratio=0.1039). CONCLUSION: OSCC has been associated with poor prognosis; however, there were improved survival outcomes compared with past studies. Advanced-stage disease and presence of metastatic lymph nodes were associated with poorer survival compared with early-stage OSCC and absence of neck node metastasis. Stage I and II OSCC were associated with excellent survival results in this study.
Adenocarcinoma ; Alcohol Drinking ; Carcinoma, Squamous Cell ; Cell Differentiation ; Cerebral Infarction ; Epithelial Cells ; Follow-Up Studies ; Gingiva ; Humans ; Lung ; Lymph Nodes ; Lymphatic Metastasis ; Mouth Floor ; Mouth Mucosa ; Neck ; Neoplasm Metastasis ; Neoplasm Staging ; Palate ; Pneumonia ; Prognosis ; Radiotherapy ; Smoke ; Smoking ; Tongue

OBJECTIVE: This is a retrospective study aimed at clarifying the details of recurrence patterns and sites in patients with cervical cancer treated with definitive radiation therapy (RT). METHODS: Data were analyzed from consecutive patients, admitted to the University of Tokyo Hospital (Tokyo, Japan) between 2001 and 2013, who had received definitive RT, with or without chemotherapy, for International Federation of Gynecology and Obstetrics stages IB-IVA cervical cancer. RESULTS: One hundred and thirty-seven patients formed the patient cohort. The median follow-up period for surviving patients was 57.0 months. A complete response was achieved in 121 patients (88%). Of these, 36 (30%) developed a cancer recurrence during follow-up. The first sites of recurrence were located in intra-RT fields in nine, outside RT fields in 20, and both in seven patients. In the intra-RT field group, all patients showed a local recurrence, while no one experienced an isolated pelvic lymph node (PLN) recurrence. In the outside RT field group, the most frequent site of recurrence was lung (60%), and three-quarters of patients were free from intra-RT field recurrence until the last follow-up. Of the entire cohort, including 48 PLN-positive patients, only seven patients (5.1%) developed PLN persistence or recurrence, all in the common iliac, internal iliac, and/or obturator nodes, and all with another synchronous relapse. CONCLUSION: Local disease was a major type of intra-RT field recurrence, while PLN control was favorable even in initially PLN-positive patients. The predominance of outside RT field recurrence alone highlights issues concerning distant control, including the intensity enhancement of systematic therapy.
Adenocarcinoma/drug therapy/*radiotherapy/secondary ; Adult ; Aged ; Aged, 80 and over ; Antineoplastic Agents/therapeutic use ; Brachytherapy ; Carcinoma, Squamous Cell/drug therapy/*radiotherapy/secondary ; Chemoradiotherapy ; Disease-Free Survival ; Dose Fractionation ; Female ; Follow-Up Studies ; Humans ; Lung Neoplasms/*secondary ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Recurrence, Local/*diagnosis ; Pelvis ; Retrospective Studies ; Survival Rate ; Uterine Cervical Neoplasms/drug therapy/pathology/*radiotherapy

Gastric cancer is the most common cancer in Korean males and can easily spread to distant organs such as the liver, lungs, brain, or bones. However, skin metastasis, particularly of the eye, is rare. Metastatic eyelid cancer is extremely rare; metastases from internal organs have not been reported so far. We recently experienced a patient with metastatic eyelid cancer from adenocarcinoma of the stomach. A 62-year-old female was admitted with a right upper eyelid mass and foreign body sensation. She had a history of stomach cancer of 3 years. She was treated by chemotherapy and radiotherapy for pathologic fracture. After receiving supportive care for 2 years, the mass appeared on her right pupil. Punch-biopsy of the mass was performed and histological examination revealed adenocarcinoma, the same as the initial histological result. We report this case with a review of related literature.
Adenocarcinoma* ; Brain ; Drug Therapy ; Eyelid Neoplasms ; Eyelids* ; Female ; Foreign Bodies ; Fractures, Spontaneous ; Humans ; Liver ; Lung ; Male ; Middle Aged ; Neoplasm Metastasis ; Pupil ; Radiotherapy ; Sensation ; Skin ; Stomach ; Stomach Neoplasms

OBJECTIVETo investigate the factors in the disease-free interval (DFI) of metachronous pulmonary metastasis from rectal cancer.

METHODSClinical data of 92 patients with metachronous pulmonary metastasis from rectal cancer in the Department of Colorectal Surgery at the Changhai Hospital of the Second Military Medical University from January 2001 to December 2013 were analyzed retrospectively. Univariate and multivariate analysis were performed to find the factors affecting disease-free interval of metachronous pulmonary metastasis from rectal cancer using Log-rank test and Cox proportional hazards model, respectively.

RESULTSThe median age of all the cases was 61 (range, 26-81) years. Of the 92 cases, 59 were males and 33 were females. Thirty-six cases were confirmed to have <5 cm distance from lower margin to dentate line. Forty-four cases were examined to have 5 μg/L carcinoembryonic antigen(CEA) level. Of these cases reviewed pathologically, 69 cases were adenocarcinoma, 23 were mucinous adenocarcinoma; 19 cases had stage T1-2 lesions, 73 had stage T3-4 lesions; 43 cases had stage N0 metastasis, 49 had stage N1-2 metastasis. Thirty cases received preoperative radiotherapy, 63 cases received postoperative chemotherapy. The median follow up time of all the cases was 62(range, 3-140) months. The DFI of all the cases was (25.9±21.0) months. Univariate Log-rank test indicated that the factors associated with the disease-free interval of metachronous pulmonary metastasis of rectal cancer were location of the tumor(χ(2)=4.496, P=0.034), preoperative CEA level (χ(2)=5.553, P=0.018), T stage (χ(2)=5.796, P=0.016), N stage (χ(2)=6.780, P=0.009), preoperative neoadjuvant radiotherapy (χ(2)=11.718, P=0.001) and postoperative adjuvant chemotherapy (χ(2)=9.214, P=0.002). A shorter distance from lower margin to dentate line(<5 cm), a lower preoperative CEA level(<5 μg/L), advanced T stage lesions(T3-4), advanced N stage metastasis(N1-2), no use of preoperative radiotherapy and use of postoperative chemotherapy were associated with shorter DFI of patients with metachronous pulmonary metastasis from rectal cancer. Multivariate analysis showed that N stage(OR=0.525, 95% CI: 0.309-0.891, P=0.017), location of the tumor (OR=1.770, 95% CI:1.115-2.812, P=0.016) and preoperative neoadjuvant radiotherapy (OR=1.976, 95% CI:1.228-3.401, P=0.006) were the independent risk factors associated with the disease-free interval of metachronous pulmonary metastasis from rectal cancer.

CONCLUSIONSAdvanced N stage, low location of the tumor and no use of preoperative neoadjuvant radiotherapy are risk factors of shorter disease-free interval of metachronous pulmonary metastasis from rectal cancer.

Adenocarcinoma ; diagnosis ; secondary ; Adult ; Aged ; Aged, 80 and over ; Chemotherapy, Adjuvant ; Disease-Free Survival ; Female ; Humans ; Lung Neoplasms ; diagnosis ; secondary ; Male ; Middle Aged ; Multivariate Analysis ; Neoadjuvant Therapy ; Postoperative Period ; Proportional Hazards Models ; Rectal Neoplasms ; pathology ; radiotherapy ; Retrospective Studies ; Risk Factors

We report of a patient with metastatic adenocarcinoma of the esophagus and stomach from lung cancer. The patient was a 68-year-old man receiving radiotherapy and chemotherapy for stage IV lung cancer, without metastases to the gastrointestinal (GI) tract at the time of the initial diagnosis. During the treatment period, dysphagia and melena newly developed. Upper GI endoscopy revealed geographic erosion at the distal esophagus and multiple volcano-shaped ulcers on the stomach body. Endoscopic biopsy was performed for each lesion. To determine whether the lesions were primary esophageal and gastric cancer masses or metastases from the lung cancer, histopathological testing including immunohistochemical staining was performed, and metastasis from lung cancer was confirmed. The disease progressed despite chemotherapy, and the patient died 5 months after the diagnosis of lung cancer. This is a case report of metastatic adenocarcinoma in the esophagus and stomach, which are very rare sites of spread for lung cancer.
Adenocarcinoma ; Aged ; Biopsy ; Deglutition Disorders ; Diagnosis ; Drug Therapy ; Endoscopy ; Esophageal Neoplasms ; Esophagus ; Humans ; Lung Neoplasms* ; Melena ; Neoplasm Metastasis* ; Radiotherapy ; Stomach ; Stomach Neoplasms ; Ulcer

Primary thymic adenocarcinoma is a very rare malignancy of the anterior mediastinum with no standardized treatment. A 36-year-old male patient presented with hoarseness over the past 3 months. A chest computed tomography (CT) scan showed an infiltrative mass to the proximal vessels and aortic arch in left upper mediastinum (4.1x3.1x5.4 cm). Brain magnetic resonance imaging (MRI) showed focal lesions, suggesting metastasis in the left frontal lobe. A thoracoscopic biopsy of the mediastinal mass confirmed a primary thymic adenocarcinoma forming a glandular structure with atypia of tumor cells. The patient received four cycles of systemic chemotherapy, consisting of etoposide and cisplatin, with concurrent radiotherapy (6,000 cGy/30 fractions) to the mediastinal lesion and the metastatic brain lesion (4,200 cGy/12 fractions). A follow-up chest CT scan and brain MRI showed a decrease in the size of the left upper mediastinal mass and brain lesion. We report a rare case of the primary thymic adenocarcinoma with a literature review.
Adenocarcinoma* ; Adult ; Aorta, Thoracic ; Biopsy ; Brain ; Chemoradiotherapy ; Cisplatin ; Drug Therapy ; Etoposide ; Follow-Up Studies ; Frontal Lobe ; Hoarseness ; Humans ; Magnetic Resonance Imaging ; Male ; Mediastinum ; Neoplasm Metastasis ; Radiotherapy ; Small Cell Lung Carcinoma* ; Thorax ; Thymus Gland ; Tomography, X-Ray Computed

Sorafenib is an emerging therapeutic option for radioactive iodine (RAI)-refractory differentiated thyroid carcinoma. However, the effects of sorafenib as an adjuvant treatment following surgery or radiation on brain metastases from poorly differentiated thyroid carcinoma (PDTC) have never been reported. A 52-year-old patient underwent total thyroidectomy for follicular thyroid carcinoma. Despite high-dose RAI therapy, a neck mass and lung metastases were developed. PDTC was diagnosed by neck mass removal. During adjuvant external beam radiation therapy (EBRT) to the neck, brain metastases developed. After palliative EBRT for brain metastases, the brain tumor size decreased but lung metastases markedly progressed. Off-label sorafenib was used to treat progressive multiple metastatic lesions. Over five months of sorafenib treatment, the sum of the longest diameters for target lesions was decreased by 45% in brain and 13% in lung. Sorafenib can be considered a new adjuvant therapeutic option for metastatic brain lesions from PDTC after EBRT.
Adenocarcinoma, Follicular ; Brain Neoplasms ; Brain* ; Humans ; Iodine ; Lung ; Middle Aged ; Neck ; Neoplasm Metastasis* ; Radiotherapy* ; Thyroid Gland* ; Thyroid Neoplasms* ; Thyroidectomy

OBJECTIVETo explore the combined anti-tumor effect of radiation therapy and gene-targeted suppression of tumor neovasculature in lung adenocarcinoma in vivo, and to explore the feasibility of micro-PET/CT in dynamic evaluation of treatment effectiveness.

METHODSThirty 5-6-week old male BALB/c nude mice were used in this study. The mouse models of xenotransplanted human lung adenocarcinoma were divided into 5 groups at random, six mice in each group: the control group, radiation treatment alone group and three groups of recombinant baculovirus plus radiation treatment (intratumoral injection, tail vein injection, and intramuscular injection). The tumor volume was measured every 2 days. Growth delay time (GD) and growth inhibition rate was calculated. FDG metabolism was evaluated by micro-PET-CT before and after treatment. The expressions of VEGF, CD31 and Ki-67 were detected by immunohistochemistry (IHC).

RESULTSThe tumor growth delay was >12 days, and the tumor inhibition rate was >45% in the recombinant baculovirus combined with radiotherapy groups, significantly higher than that of the radiotherapy alone group (P < 0.05). Immunohistochemical analysis showed that the expressions of VEGF, CD31 and Ki-67 were significantly lower than that in other groups (P < 0.05). The micro-PET-CT assessment showed that the FDG-metabolism in the recombinant baculovirus combined with radiotherapy groups was significantly reduced (P < 0.05), and the SUVmax (FDG metabolism) of transplanted tumors after treatment was also markedly decreased in comparison with that of the control group. The tumor volume after treatment was significantly correlated with SUVmax in the recombinant baculovirus intratumoral injection + radiotherapy group(r = 0.976), recombinant baculovirus intravenous injection + radiotherapy group (r = 0.954), recombinant baculovirus intramuscular injection + radiotherapy group (r = 0.929), and radiotherapy alone group (r = 0.871, P < 0.05).

CONCLUSIONSThe recombinant baculovirus containing Egr1 promoter and K5 gene combined with radiotherapy enhances the suppressing effect on the growth of lung adenocarcinoma in the tumor-bearing nude mice. The inducibility of Egr1 promoter by radiation allows the targeting and controllability of treatment. Micro-PET-CT results have a good correlation with the treatment effectiveness. Therefore, it can be used in real-time evaluation of tumor metabolic function in vivo.

Adenocarcinoma ; metabolism ; pathology ; radiotherapy ; Animals ; Baculoviridae ; genetics ; Cell Line, Tumor ; Combined Modality Therapy ; Early Growth Response Protein 1 ; genetics ; physiology ; Fluorodeoxyglucose F18 ; Genetic Therapy ; Genetic Vectors ; Humans ; Ki-67 Antigen ; metabolism ; Lung Neoplasms ; metabolism ; pathology ; radiotherapy ; Male ; Mice, Inbred BALB C ; Mice, Nude ; Molecular Targeted Therapy ; Neoplasm Transplantation ; Peptide Fragments ; genetics ; physiology ; Plasminogen ; genetics ; physiology ; Platelet Endothelial Cell Adhesion Molecule-1 ; metabolism ; Positron-Emission Tomography ; Promoter Regions, Genetic ; Random Allocation ; Recombinant Proteins ; genetics ; Tomography, X-Ray Computed ; Tumor Burden ; Vascular Endothelial Growth Factor A ; metabolism

OBJECTIVETo explore the optimal management and analyze the prognostic factors for follicular thyroid carcinoma.

METHODSThe clinicopathological data of 119 patients with well-differentiated follicular thyroid carcinoma treated in our hospital from 1970 to 2008 were retrospectively reviewed. The overall survival (OS) rate was estimated by Kaplan-Meier method. Log rank and Cox regression analyses were used to identify the prognostic factors.

RESULTSThe 5- and 10-year OS rates were 81.1% and 66.7%, respectively. The 3- , 5- and 10-year cumulative distant metastasis rates were 27.4%, 29.6% and 35.9%, respectively. The age of ≥ 45 years old was one of the most important factors affecting survival rate (P < 0.05) and an independent factor for distant matastasis.

CONCLUSIONSFollicular thyroid carcinoma has some special features such as diffuse growth and vascular tumors thrombosis and with a relatively poor prognosis. The key measure to improve local control and prognosis is radical resection. Some aggressive management such as total thyroidectomy combined with (13)1I therapy and regular follow-up should be performed to improve the survival rate and to control postoperative distant metastasis for patients ≥ 45 years old.

Adenocarcinoma, Follicular ; pathology ; radiotherapy ; secondary ; surgery ; Adolescent ; Adult ; Age Factors ; Aged ; Aged, 80 and over ; Bone Neoplasms ; secondary ; Child ; Female ; Follow-Up Studies ; Humans ; Iodine Radioisotopes ; therapeutic use ; Lung Neoplasms ; secondary ; Lymph Node Excision ; Lymphatic Metastasis ; Male ; Middle Aged ; Neoplasm Recurrence, Local ; Neoplasm Staging ; Radiotherapy, Adjuvant ; Retrospective Studies ; Survival Rate ; Thyroid Neoplasms ; pathology ; radiotherapy ; surgery ; Thyroidectomy ; Young Adult