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

Tomotherapy plans were produced using a combination of field widths (1 cm, 2.5 cm and 5 cm) and pitches (0.15, 0.30, and 0.45) for seven patients with brain metastases from lung cancer, the plans were compared with dosimetric parameters, protection of organs at risk (OAR) dose and treatment times. All plans were defined that CTV with 30Gy and GTV 50 Gy by ten fraction synchronously. The results showed that the mean dose and CI for GTV was statistical difference (P = 0.002 1, P = 0.012 8), OARs were within the normal range, the treatment time increased inversely proportional to the jaw width, but had lesser impact on the pitch. This study showed plans produced with 5 cm jaw was an effective method for patients with brain metastases from lung cancer.
Aged ; Brain Neoplasms ; diagnostic imaging ; secondary ; Female ; Humans ; Lung Neoplasms ; pathology ; Male ; Middle Aged ; Radiotherapy Planning, Computer-Assisted ; methods ; Radiotherapy, Intensity-Modulated ; methods ; Tomography, Spiral Computed

We retrospectively analyzed the prognostic factors on overall survival (OS) in patients with brain metastasis (BM) and evaluated the role of combined primary tumor and extracranial metastasis (ECM) status as a constituent factor for prognostic index. This study involved 897 patients with BMs who underwent radiotherapy between April 2003 and December 2009. Among the clinical parameters, multivariate analysis showed that age, Karnofsky performance status (KPS), combined primary tumor and ECM status, number of BMs, and treatment group were significant prognostic factors for OS (P < 0.05). To compare the discriminatory ability of 5 prognostic indices, i.e., recursive partitioning analysis (RPA), basic score for BMs (BSBM), score index for radiosurgery (SIR), graded prognostic assessment (GPA), and modified GPA including the combined primary tumor and ECM status (mGPA), the Akaike information criteria (AIC) were calculated. The mGPA showed the lowest AIC value, followed by RPA, GPA, SIR, and BSBM, in that order. It is implicated that modified score of pre-existing factors (i.e., age and KPS) and addition of the combined primary tumor and ECM status to the prognostic index can improve its discriminatory ability and the combined primary tumor and ECM status may be useful as one of constituent factors for prognostic index.
Adult ; Age Factors ; Aged ; Aged, 80 and over ; Brain Neoplasms/*mortality/radiotherapy/secondary ; Breast Neoplasms/pathology ; Female ; Follow-Up Studies ; Humans ; Karnofsky Performance Status ; Lung Neoplasms/pathology ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Multivariate Analysis ; Prognosis ; Retrospective Studies ; Survival Analysis ; Tomography, X-Ray Computed

OBJECTIVETo evaluate the efficacy and prognostic factors of personalized treatment for breast cancer patients who failed chemotherapy.

METHODSSeventy-two patients with breast cancer who failed chemotherapy were treated at the Tumor Hospital of Harbin Medical University from January 2001 to January 2012. Among them, 42 cases received 5.6 cycles (range, 4-8 cycles) of postoperative adjuvant chemotherapy, and 30 cases received 12.2 cycles (range, 6-22 cycles), both postoperative adjuvant and salvage chemotherapy. All of the 72 patients of stage IV were given personalized treatment. Under guidance of the principle that multidisciplinary treatment improves control rate but does not or less damage the normal tissues and host immune function, precise radiotherapy combined with Chinese herbal medicine (CHM), biological agent and others were chosen for the patients.

RESULTSThe median survival time was 20 months. Univariate analysis showed that non-invasive ductal carcinoma, less metastasized organs, without brain, liver and lung metastasis, Karnofsky performance scores ≥ 80, not combined with chemotherapy, and multiple courses of Chinese herbal medicine and biolojical agent treatment had significant impact on survival (P < 0.05). Multivariate analysis showed that no brain metastasis, non-invasive ductal carcinoma, and Chinese herbal medicine and biological agent treatment ≥ 7 courses and not combined with chemotherapy had obvious significance (P < 0.05). The rate of grade 3 and 4 treatment-related hematological toxicity was 8.3% (6/72) and 5.6% (4/72), respectively. All the patients with grade 4 hematological toxicity were the cases of grade 3 at hospital admission. No grade 3 and 4 acute radiation damages of the lung and liver were noticed.

CONCLUSIONChinese herbal medicine combined with biological agents and others prolongs survival time in breast cancer patients who failed chemotherapy, and provides an alternative treatment modality for them.

Adult ; Aged ; Aromatase Inhibitors ; therapeutic use ; Bone Density Conservation Agents ; therapeutic use ; Bone Neoplasms ; drug therapy ; secondary ; Brain Neoplasms ; drug therapy ; secondary ; Breast Neoplasms ; drug therapy ; pathology ; radiotherapy ; surgery ; Carcinoma, Ductal, Breast ; drug therapy ; pathology ; radiotherapy ; secondary ; surgery ; Chemotherapy, Adjuvant ; Diphosphonates ; therapeutic use ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Follow-Up Studies ; Humans ; Imidazoles ; therapeutic use ; Lung Neoplasms ; drug therapy ; secondary ; Medicine, Chinese Traditional ; Middle Aged ; Neoplasm Staging ; Nitriles ; therapeutic use ; Radiotherapy, Adjuvant ; Radiotherapy, Conformal ; methods ; Remission Induction ; Retrospective Studies ; Survival Rate ; Treatment Failure ; Triazoles ; therapeutic use

OBJECTIVETo analyze the clinical features, treatment and prognosis of Stage IV alveolar soft part sarcoma.

METHODSTo analyze the clinical and pathological features, therapeutic methods and follow-up results in 21 patients with stage IV alveolar soft part sarcoma. There were 11 males and 10 females, in the age of 26-57 years (average 37.0 years old). All the 21 patients had metastasis: nine cases had multiple pulmonary metastasis, three cases had multiple pulmonary and brain metastasis, two cases had multiple brain metastasis, two cases had multiple pulmonary and bone metastasis, two cases had single pulmonary metastasis, one case had single bone metastasis, one case had single brain metastasis and one case had single soft tissue metastasis. Eight patients were treated by surgical operation, including five cases of complete resection for the primary and (or) metastatic tumor and 3 cases of palliative operation for the primary tumor. All patients received chemotherapy, including seven cases of CAVD regimen and 14 cases of MAID regimen treatment. One patient with single bone metastasis and five patients with multiple brain metastasis received post-operative whole brain radiation therapy.

RESULTSAll the eight patients with surgical operation had healing by first intention, and pathological examination showed that seven patients achieved R0 surgical margin and one case with R2 status. One patient with single brain metastasis had recurrence after operation. The toxic and adverse reactions of all patients treated with chemotherapy were tolerable. Among them, 17 cases had stable disease and 4 cases had disease progression after chemotherapy. The disease control rate (DCR) was 81.0%. The DCR of patients with CAVD regimen chemotherapy was 85.7% and that of patients treated with MAID regimen was 78.6% (P = 0.862). All patients were followed up for 8 - 86 months (average 32.4 months). The median survival time of all patients was 32.6 months. The 2-year survival rate was 55.1% and the 5-year survival rate was 21.8%. The median survival time in the patients with complete resection was 60.0 months, and that in patients with palliative operation was 27.0, showing a significant difference between them (P = 0.048). The median progression-free survival in patients with complete excision was 57.2 months and that in patients with palliative operation or without operation was 19.6 months, with a significant difference (P = 0.029). The median survival time in patients who received CAVD regimen chemotherapy was 30.0 months, and that in patients with MAID regimen was 51.0 months, with a non-significant difference (P = 0.511). The median progression-free time in patients with CAVD regimen chemotherapy was 13.0 months, and that in patients with MAID regimen was 38.0 months, also with a non-significant difference (P = 0.066).

CONCLUSIONSAlveolar soft part sarcomas are rarely seen and highly malignant tumors, and the prognosis of stage IV ASPS is poor. Complete resection of all tumors is the key of successful treatment of Stage IV ASPS, and the site and number of tumor metastasis are important factors affecting prognosis. The curative effects of radiotherapy and chemotherapy for ASPS need to be further investigated.

Adult ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Bone Neoplasms ; radiotherapy ; secondary ; surgery ; Brain Neoplasms ; radiotherapy ; secondary ; surgery ; Dacarbazine ; therapeutic use ; Disease-Free Survival ; Doxorubicin ; therapeutic use ; Female ; Follow-Up Studies ; Humans ; Ifosfamide ; therapeutic use ; Lower Extremity ; Lung Neoplasms ; secondary ; surgery ; Male ; Mesna ; therapeutic use ; Middle Aged ; Neoplasm Recurrence, Local ; Neoplasm Staging ; Particle Accelerators ; Remission Induction ; Salvage Therapy ; Sarcoma, Alveolar Soft Part ; drug therapy ; radiotherapy ; secondary ; surgery ; Soft Tissue Neoplasms ; drug therapy ; radiotherapy ; surgery ; Survival Rate

OBJECTIVETo evaluate the efficacy, survival and toxicity in patients with brain metastases from non-small cell lung cancer (NSCLC), treated with concurrent systemic chemotherapy and whole brain radiation therapy (WBRT) or sequential systemic chemotherapy/WBRT.

METHODSA total of 60 NSCLC patients with brain metastases were divided into two groups in this prospective clinical study: concurrent systemic chemotherapy and WBRT group (concurrent group) and sequential systemic chemotherapy/WBRT group (sequential group).

RESULTSOf 59 assessable patients, the overall response rate was 22.0%, and the brain response rate was 35.6%; the median progression-free survival time was 3.0 months, and the overall 1- and 2-year survival rates were 55% and 24.4%, respectively, with a median survival time of 16.0 months. The overall response rate was 20.0% in the concurrent group and 24.1% in sequential group (P > 0.05). The brain response rates of 43.3% in concurrent group and 27.6% in sequential group were also not significantly different (P > 0.05). The median progression-free survival time for the patients in the concurrent group was 3.0 months versus 4.0 months in the sequential group, and the median survival time was 16.0 months versus 13.0 months (all P > 0.05). The 1- and 2-year survival rates were 58.5% and 37.2% versus 52.9% and 18.9%, respectively, with a significant difference in the 2-year survival rate between the two groups (P = 0.011). In the sequential group, leukopenia was more frequent during chemotherapy than that in the concurrent group (P = 0.029).

CONCLUSIONConcurrent systemic chemotherapy and WBRT is effective with tolerable adverse events in treating brain metastasis from NSCLC with an encouraging survival, and deserves further large sample and randomized multicenter clinical trials.

Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols ; adverse effects ; therapeutic use ; Brain Neoplasms ; drug therapy ; radiotherapy ; secondary ; Carcinoma, Non-Small-Cell Lung ; drug therapy ; radiotherapy ; secondary ; Cisplatin ; administration & dosage ; Combined Modality Therapy ; Cranial Irradiation ; Deoxycytidine ; administration & dosage ; analogs & derivatives ; Disease-Free Survival ; Female ; Follow-Up Studies ; Humans ; Leukopenia ; chemically induced ; Lung Neoplasms ; pathology ; Male ; Middle Aged ; Prospective Studies ; Survival Rate ; Vinblastine ; administration & dosage ; analogs & derivatives

Although gynecomastia is a well-defined paraneoplastic syndrome in patients with non-small cell lung cancer, the association with pleomorphic carcinoma has not been reported. A 50-yr-old man presented with bilateral gynecomastia and elevated serum beta-human chorionic gonadotropin (beta hCG) level. Chest tomography showed a mass in the right middle lobe. Right middle lobectomy and mediastinal lymph node dissection were performed. beta hCG levels decreased rapidly after surgery. Histological examination revealed pleomorphic carcinoma with positive immunostaining for beta hCG. Serum beta hCG levels began to increase gradually on postoperatively 4th month. Computed tomography detected recurrence and chemotherapy was started. After second cycle of chemotherapy, beta hCG levels decreased dramatically again and tomography showed regression in mass. Patient died 6 months later due to brain metastasis. beta hCG expression may be associated with aggressive clinical course and increased risk of recurrence, also beta hCG levels may be used to evaluate therapy response in patients with pleomorphic carcinoma.
Brain Neoplasms/radiotherapy/secondary ; Carcinoma, Non-Small-Cell Lung/complications/*diagnosis/pathology ; Chorionic Gonadotropin, beta Subunit, Human/*blood ; Gynecomastia/*etiology ; Humans ; Lung Neoplasms/complications/*diagnosis/pathology ; Lymph Nodes/surgery ; Male ; Middle Aged ; Recurrence ; Risk Factors ; Tomography, X-Ray Computed

BACKGROUND AND OBJECTIVEThe brain is one of the most common metastatic sites of breast cancer. Brain metastases develop in 10%-15% of patients with breast cancer and are associated with poor prognosis. The purpose of this retrospective study was to analyze the clinical characteristics and survival of patients with brain metastases due to breast cancer of different subtypes and to identify the prognostic factors that affect clinical outcome.

METHODSA total of 89 patients with breast cancer brain metastases diagnosed between October 1997 and July 2008 at Sun Yat-sen University Cancer Center were included in this study. Among the 89 patients, the number of luminal A, luminal B, human epidermal growth factor receptor 2 (HER-2), and triple-negative (TN) subtypes were 30, 20, 16, and 14, respectively; 9 patients had an unknown subtype. The clinical characteristics, pathologic features, and prognostic factors were analyzed both at the initial diagnosis and at the diagnosis of brain metastases. Endocrine therapy for patients with luminal subtypes was further studied.

RESULTSThe median age of patients was 46 years (range 28-74 years). The median survival time was 8.0 months (range, 0-80 months), the 1-year survival rate was 32% and the 5-year survival rate was 4%. The time to brain metastasis differed according to clinical stage at the initial diagnosis, and the time for patients with the luminal A subtype was the longest (P < 0.001). Multivariate analysis demonstrated that performance status score > 1, multiple brain metastases and without whole brain radiotherapy (WBRT) in combination with chemotherapy were associated with poor prognosis. Compared with the luminal A subtype, features of the HER-2 and TN subtypes included early metastases, rapid progression after first-line treatment (8.0 months vs. 11.0 months), and poor overall survival (25.0 months vs. 63.0 months). The luminal A subtype showed a tendency for good prognosis and slow growth. Tamoxifen could improve the survival of luminal A/B subtypes (median survival 24.0 months vs. 7.0 months, respectively, P = 0.002).

CONCLUSIONSThe prognosis of brain metastases from breast cancer was poor, especially in patients with HER-2 and TN subtypes. Generally, WBRT in combination with chemotherapy was the standard treatment modality. Patients with the luminal subtypes could benefit from tamoxifen.

Adult ; Aged ; Antineoplastic Agents, Hormonal ; therapeutic use ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Brain Neoplasms ; secondary ; therapy ; Breast Neoplasms ; classification ; pathology ; therapy ; Carcinoma, Ductal, Breast ; classification ; pathology ; secondary ; therapy ; Chemotherapy, Adjuvant ; Cranial Irradiation ; methods ; Female ; Follow-Up Studies ; Humans ; Mastectomy ; methods ; Middle Aged ; Neoplasm Staging ; Radiotherapy, Adjuvant ; Receptor, ErbB-2 ; blood ; Receptors, Estrogen ; blood ; Receptors, Progesterone ; blood ; Retrospective Studies ; Survival Rate ; Tamoxifen ; therapeutic use

BACKGROUND AND OBJECTIVEX-ray stereotactic radiotherapy (SRT) is one of the effective treatments for brain metastases (BM). This study was to evaluate the efficacy of SRT on BM, and investigate prognostic factors.

METHODSBetween July 1999 and December 2004, a total of 122 intracranial lesions in 78 patients with BM were treated using SRT in our Center. Forty-nine patients had a solitary lesion and 29 had multiple (2-6) lesions. The median SRT dose was 15 Gy (11-24 Gy) in single fraction for 38 lesions, and 24 Gy (11-40 Gy) in 2-6 fractions for 84 lesions. SRT was combined with whole brain radiotherapy (WBRT) of 30-40 Gy for 39 patients. Progression-free survival (PFS) and overall survival (OS) were estimated by Kaplan-Meier method. Univariate and multivariate analyses were performed by the log-rank test and Cox model, respectively.

RESULTSThe median survival time was 12.9 months (1.7-77.4 months). The 1-year intracranial PFS rate was 87.4%. The 1-and 2-year OS rates were 53.9% and 25.8%, respectively. Univariate analysis showed that the 1-year OS rates were higher in the patients with pretreatment KPS of >/= 70, extracranial lesions controlled, or SRT combined with WBRT than in those with KPS of < 70 (60.7% vs. 29.4%, P = 0.002), extracranial lesions uncontrolled (69% vs. 44.9%, P = 0.005), or SRT alone (64.1% vs. 43.4%, P = 0.03). The benefit of treating with WBRT in combination was mainly achieved in the patients with extracranial lesions controlled or with more than one intracranial lesion. Multivariate analysis showed that KPS score and status of extracranial lesions were independent prognostic factors for OS.

CONCLUSIONSSRT is an effective and safe modality for BM. SRT combined with WBRT may prolong the survival time of the patients with extracranial lesions controlled or multiple intracranial lesions. Independent prognostic factors for OS are KPS score and status of extracranial lesions.

Adult ; Aged ; Brain Neoplasms ; radiotherapy ; secondary ; surgery ; Breast Neoplasms ; pathology ; Cranial Irradiation ; methods ; Disease-Free Survival ; Female ; Follow-Up Studies ; Humans ; Karnofsky Performance Status ; Lung Neoplasms ; pathology ; Male ; Middle Aged ; Neoplasms, Glandular and Epithelial ; radiotherapy ; secondary ; surgery ; Proportional Hazards Models ; Radiosurgery ; methods ; Radiotherapy Dosage ; Survival Rate

OBJECTIVETo study the pattern of blood-brain barrier (BBB) permeability changes during whole brain radiotherapy (WBRT) for metastatic brain tumor.

METHODSTwenty patients with metastatic brain tumors receiving WBRT by 6 MV X-ray underwent (99)mTc-DTPA brain SPECT before and during WBRT (20, 40 Gy) and at 2 weeks after the end of irradiation. A frame of transverse (99)mTc-DTPA brain SPECT image that best displayed the brain metastasis was chosen, and the regions of interest (ROI) were defined in the tumor foci (T), the contralateral normal brain tissue (N) and the background outside the soft tissues around the cranium (B). The radioactive counts of every ROI were measured and the ratios of the total counts (T/B and N/B) before and during WBRT (20 Gy, 40 Gy) and at 2 weeks after the irradiation were calculated.

RESULTSThe average T/B and N/B in the 20 patients with 30 brain metastases was 142.2-/+51.1 and 82.6-/+42.3 before WBRT, 260.3-/+121.5 and 150.7-/+72.5 during 20 Gy WBRT, 251.6-/+118.3 and 161.8-/+68.4 during 40 Gy WBRT, and 250.3-/+117.2 and 158.6-/+73.5 at 2 weeks after the irradiation, respectively. The measurements during WBRT (20 and 40 Gy) and at 2 weeks after the irradiation group underwent no significant variations (P>0.05), but showed significant differences from those before WBRT (P<0.05).

CONCLUSIONSIrradiation causes direct damage of the BBB function, and the permeability of the BBB increases significantly during and within 2 weeks following 20 and 40 Gy WBRT, which provides the optimal time window for interventions with chemotherapy.

Adult ; Aged ; Blood-Brain Barrier ; diagnostic imaging ; physiopathology ; Brain Neoplasms ; diagnostic imaging ; radiotherapy ; secondary ; Capillary Permeability ; physiology ; Cranial Irradiation ; Female ; Humans ; Male ; Middle Aged ; Sodium Pertechnetate Tc 99m ; Tomography, Emission-Computed, Single-Photon