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

Brain metastasis was a common metastasis site and leading cause of death in non-small cell lung cancer (NSCLC). Tyrosine kinase inhibitors had improved survival of NSCLC patients with positive drive gene. It also brings good news to NSCLC patients with positive drive gene and brain metastases. However, there is still no effective treatment for NSCLC patients with drive gene-negative and brain metastases. In recent years, immunotherapy has made breakthrough progress and become important first and second line treatment options of NSCLC especially in patients with drive gene-negative. The role of immunotherapy in specific populations of NSCLC-brain metastasis patients, especially drive gene-negative patients has become the focus of attention. In this report, we review the research progress of immunotherapy in NSCLC with brain metastases, especially in driver-negative patients, analyze the limitations of existing research and future challenge.
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Brain Neoplasms ; immunology ; secondary ; therapy ; Carcinoma, Non-Small-Cell Lung ; genetics ; pathology ; Humans ; Immunotherapy ; methods ; Lung Neoplasms ; genetics ; pathology ; Patient Selection

BACKGROUND: Bevacizumab combined with platinum-based chemotherapy has been recommended as the first-line agent in advanced nonsquamous non-small cell lung cancer (NSCLC) without driven gene, but this regimen is not common in the second-line or later-line treatment of non-squamous NSCLC. The aim of this study is to investigate the efficacy and safety of bevacizumab combined with chemotherapy as second-line or later-line treatment in advanced non-squamous NSCLC. METHODS: We retrospectively reviewed the clinical data of advanced nonsquamous NSCLC patients who were treated with bevacizumab after first-line treatment failure and they were hospitalized in the Affiliated Cancer Hospital of Zhengzhou University from January 2014 to June 2017, and Kaplan-Meier method, Log-rank test and Cox model were used for analysis. RESULTS: A total of 62 patients were included in the analysis. The total objective response rate (ORR) was 32.2%, and the disease control rate (DCR) was 96.8%. The median progression-free survival (PFS) was 6.4 months (95%CI: 6.05-6.83), and the median overall survival (OS) was 20.4 months (95%CI: 12.98-27.76). In the subgroup analysis, there was no significant difference in median PFS between patients with brain metastases and those without brain metastases (6.2 months vs 6.4 months, P=0.052). Cycles of bevacizumab (>6 or ≤6 cycles) was an independent influencing factor of PFS (P=0.004). The most common adverse events were leukopenia, fatigue, nausea, thrombocytopenia and hypertension. CONCLUSIONS In the second-line or later-line treatment, bevacizumab combined with chemotherapy is an effective and safe regimen for advanced non-squamous NSCLC.
Aged ; Bevacizumab ; adverse effects ; therapeutic use ; Brain Neoplasms ; secondary ; Carcinoma, Non-Small-Cell Lung ; drug therapy ; pathology ; Disease-Free Survival ; Female ; Humans ; Lung Neoplasms ; drug therapy ; pathology ; Male ; Middle Aged ; Retrospective Studies ; Safety ; Treatment Outcome

The NCCN has recently released its 2017 version 1.0 guideline for colorectal cancer. There are several updates from this new version guideline which are believed to change the current clinical practice. Update one, low-dose aspirin is recommended for patients with colorectal cancer after colectomy for secondary chemoprevention. Update two, biological agents are removed from the neoadjuvant treatment regimen for resectable metastatic colorectal cancer (mCRC). This update is based on lack of evidence to support benefits of biological agents including bevacizumab and cetuximab in the neoadjuvant setting. Both technical criteria and prognostic information should be considered for decision-making. Currently biological agents may not be excluded from the neoadjuvant setting for patients with resectable but poor prognostic disease. Update three, panitumumab and cetuximab combination therapy is only recommended for left-sided tumors in the first line therapy. The location of the primary tumor can be both prognostic and predictive in response to EGFR inhibitors in metastatic colorectal cancer. Cetuximab and panitumumab confer little benefit to patients with metastatic colorectal cancer in the primary tumor originated on the right side. On the other hand, EGFR inhibitors provide significant benefit compared with bevacizumab-containing therapy or chemotherapy alone for patients with left primary tumor. Update four, PD-1 immune checkpoint inhibitors including pembrolizumab or nivolumab are recommended as treatment options in patients with metastatic deficient mismatch repair (dMMR) colorectal cancer in second- or third-line therapy. dMMR tumors contain thousands of mutations, which can encode mutant proteins with the potential to be recognized and targeted by the immune system. It has therefore been hypothesized that dMMR tumors may be sensitive to PD-1 inhibitors.
Antibodies, Monoclonal ; pharmacology ; therapeutic use ; Antibodies, Monoclonal, Humanized ; therapeutic use ; Antineoplastic Agents ; therapeutic use ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Aspirin ; administration & dosage ; therapeutic use ; Bevacizumab ; therapeutic use ; Biological Products ; therapeutic use ; Brain Neoplasms ; drug therapy ; genetics ; Cetuximab ; therapeutic use ; Clinical Decision-Making ; methods ; Colorectal Neoplasms ; drug therapy ; genetics ; pathology ; prevention & control ; therapy ; Contraindications ; Humans ; Mutation ; physiology ; Neoadjuvant Therapy ; standards ; Neoplasm Metastasis ; drug therapy ; Neoplastic Syndromes, Hereditary ; drug therapy ; genetics ; Practice Guidelines as Topic ; Prognosis ; Secondary Prevention ; methods ; standards

Fibromyalgia syndrome after comprehensive treatment of breast cancer is rare and seldom reported. Here we present a case of a 50-year-old female patient,who was admitted to the hospital because of generalized fibromyalgia for 3 months and brain metastasis after the right breast carcinoma surgery for 1 month, and the clinical diagnosis was brain metastasis from breast carcinoma combined with fibromyalgia syndrome. The fibromyalgia were relieved with proper symptomatic treatment but the patient eventually died of tumor progression.
Brain Neoplasms ; mortality ; secondary ; Breast Neoplasms ; complications ; mortality ; therapy ; Carcinoma ; mortality ; therapy ; Female ; Fibromyalgia ; diagnosis ; etiology ; therapy ; Humans ; Middle Aged

OBJECTIVEThe aim of this study was to analyze the clinical features and prognostic factors in patients with brain metastasis from colorectal cancer (CRC).

METHODSClinical materials of 45 colorectal cancer patients who developed brain metastasis were collected, and the data and follow-up data of those patients were retrospectively analyzed.

RESULTSMost brain metastases were from rectal cancer (64.4%), and 80.0% of the 45 cases had extracranial metastases. The most common extracranial metastatic site was the lung (57.8%), followed by the liver (35.6%). All the brain metastases in patients with liver metastases were supratentorial, while in contrast, 44.8% of the patients without liver metastasis had subtentorial metastasis, showing a significant difference between them (P<0.05). The interval time from diagnosis of CRC to the development of brain metastases in case of Dukes D stage was 12.0 months, significantly shorter than that in the cases of Dukes A stage (24.0 months), B (36.0 months) and C (29.0 months) (P<0.05). The interval time was also shorter in the patients who developed extracranial metastasis within one year than those more than one year (12.0 months vs. 38.0 months)( P<0.05). The median survival time of patients with brain metastasis from colorectal was 6.0 months, with a 1-year survival rate of 21.1% and 2-year survival rate of 3.3% only. Univariate analysis showed that the median survival of patients with a KPS score of ≥70 was 8.0 months, significantly higher than 2.0 months in those with a KPS score of <70 (P<0.05). The median survival of patients with one or two brain metastases was 8.0 months, significantly higher than 4.0 months of those with >2 brain metastases (P<0.05). The median survival time after diagnosis of brain metastasis was 4.0 months for those who received monotherapy (only steroids, only chemotherapy or only radiotherapy), significantly shorter than 10.0 months of patients who received chemoradiotherapy, and 12.0 months of those who underwent surgery (P<0.05). Comparing each two differently treated groups, the survival time of surgery combined with chemotherapy or radiotherapy group was significantly different from that of all of other groups (P<0.05). The median survival time of chemoradiotherapy group was longer than that of monotherapy, but the difference was not significant (P>0.05). Multivariate analysis showed that brain metastases >2 and treatment modality type are independent prognostic factors for survival.

CONCLUSIONSPatients initially diagnosed with a Dukes D stage primary colorectal tumor and occurrence of extracranial metastasis (especially, pulmonary metastasis) within one year are associated to an increased risk of brain metastases and have a shorter survival time. Most brain metastases in patients with liver metastases are supratentorial, while many patients without liver metastasis have subtentorial metastasis. Brain metastases >2 and the type of treatment modality are independent prognostic factors for survival. The prognosis of patients who received chemoradiotherapy is better than those treated only with chemotherapy or radiotherapy. Some subsets of patients may benefit from surgery plus chemotherapy/radiotherapy.

Brain Neoplasms ; mortality ; secondary ; therapy ; Chemoradiotherapy ; Colorectal Neoplasms ; Humans ; Liver Neoplasms ; secondary ; Lung Neoplasms ; secondary ; Neoplasm Staging ; Prognosis ; Rectal Neoplasms ; pathology ; Retrospective Studies ; Survival Rate ; Time Factors

Cervical cancer is one of the most common cancers in women worldwide. The outcome of patients with metastatic cervical cancer is poor. We reviewed the relevant literature concerning the treatment and diagnosis of metastatic cervical cancer. There are two types of metastasis related to different treatments and survival rates: hematogenous metastasis and lymphatic metastasis. Patients with hematogenous metastasis have a higher risk of death than those with lymphatic metastasis. In terms of diagnosis, fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) and PET-computed tomography are effective tools for the evaluation of distant metastasis. Concurrent chemoradiotherapy and subsequent chemotherapy are well-tolerated and efficient for lymphatic metastasis. As for lung metastasis, chemotherapy and/or surgery are valuable treatments for resistant, recurrent metastatic cervical cancer and chemoradiotherapy may be the optimal choice for stage IVB cervical cancer. Chemotherapy and bone irradiation are promising for bone metastasis. A better survival is achieved with multimodal therapy. Craniotomy or stereotactic radiosurgery is an optimal choice combined with radiotherapy for solitary brain metastases. Chemotherapy and palliative brain radiation may be considered for multiple brain metastases and other organ metastases.
Bone Neoplasms/secondary/therapy ; Brain Neoplasms/secondary/therapy ; Chemoradiotherapy ; Female ; Fluorodeoxyglucose F18 ; Humans ; Lung Neoplasms/secondary/therapy ; Lymphatic Metastasis ; Positron-Emission Tomography ; Uterine Cervical Neoplasms/diagnostic imaging/*pathology/therapy

Cervical cancer is one of the most common cancers in women worldwide. The outcome of patients with metastatic cervical cancer is poor. We reviewed the relevant literature concerning the treatment and diagnosis of metastatic cervical cancer. There are two types of metastasis related to different treatments and survival rates: hematogenous metastasis and lymphatic metastasis. Patients with hematogenous metastasis have a higher risk of death than those with lymphatic metastasis. In terms of diagnosis, fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) and PET-computed tomography are effective tools for the evaluation of distant metastasis. Concurrent chemoradiotherapy and subsequent chemotherapy are well-tolerated and efficient for lymphatic metastasis. As for lung metastasis, chemotherapy and/or surgery are valuable treatments for resistant, recurrent metastatic cervical cancer and chemoradiotherapy may be the optimal choice for stage IVB cervical cancer. Chemotherapy and bone irradiation are promising for bone metastasis. A better survival is achieved with multimodal therapy. Craniotomy or stereotactic radiosurgery is an optimal choice combined with radiotherapy for solitary brain metastases. Chemotherapy and palliative brain radiation may be considered for multiple brain metastases and other organ metastases.
Bone Neoplasms/secondary/therapy ; Brain Neoplasms/secondary/therapy ; Chemoradiotherapy ; Female ; Fluorodeoxyglucose F18 ; Humans ; Lung Neoplasms/secondary/therapy ; Lymphatic Metastasis ; Positron-Emission Tomography ; Uterine Cervical Neoplasms/diagnostic imaging/*pathology/therapy

This study analyzes the clinical characteristics of the brain metastasis (BM) of gynecologic cancer based on the type of cancer. In addition, the study examines the factors influencing the survival. Total 61 BM patients of gynecologic cancer were analyzed retrospectively from January 2000 to December 2012 in terms of clinical and radiological characteristics by using medical and radiological records from three university hospitals. There were 19 (31.1%) uterine cancers, 32 (52.5%) ovarian cancers, and 10 (16.4%) cervical cancers. The mean interval to BM was 25.4 months (21.6 months in ovarian cancer, 27.8 months in uterine cancer, and 33.1 months in cervical cancer). The mean survival from BM was 16.7 months (14.1 months in ovarian cancer, 23.3 months in uterine cancer, and 8.8 months in cervical cancer). According to a multivariate analysis of factors influencing survival, type of primary cancer, Karnofsky performance score, status of primary cancer, recursive partitioning analysis class, and treatment modality, particularly combined therapies, were significantly related to the overall survival. These results suggest that, in addition to traditional prognostic factors in BM, multiple treatment methods such as neurosurgery and combined chemoradiotherapy may play an important role in prolonging the survival for BM patients of gynecologic cancer.
Adult ; Aged ; Brain/*pathology ; Brain Neoplasms/*mortality/*secondary/therapy ; Chemoradiotherapy ; Female ; Genital Neoplasms, Female/*mortality/pathology/therapy ; Humans ; Middle Aged ; Multivariate Analysis ; Ovarian Neoplasms/mortality/pathology/therapy ; Prognosis ; Retrospective Studies ; Uterine Cervical Neoplasms/mortality/pathology/therapy ; Uterine Neoplasms/mortality/pathology/therapy ; Young Adult

Gefitinib is regarded as a relatively safe agent for the treatment of an advanced non-small cell lung cancer (NSCLC). Pulmonary toxicity such as interstitial lung disease associated with gefitinib is uncommon with an estimated all time incidence around 1% worldwide. Moreover, a case of gefitinib associated with pulmonary cystic changes has not been reported yet. In this report we present a case of progressive multiple air cystic changes in both lungs in a patient with NSCLC and intrapulmonary metastases who underwent a gefitinib therapy.
Antineoplastic Agents/*adverse effects ; Brain Neoplasms/secondary ; Carcinoma, Non-Small-Cell Lung/*drug therapy/secondary ; Cysts/*chemically induced ; Female ; Humans ; Lung/pathology ; Lung Diseases/*chemically induced ; Lung Diseases, Interstitial ; Lung Neoplasms/*drug therapy ; Middle Aged ; Quinazolines/*adverse effects