Brain metastasis (BM) is the leading cause of mortality in lung cancer patients. The process of BM (from initial primary tumor development, migration and intravasation, dissemination and survival in the bloodstream, extravasation, to colonization and growth to metastases) is a complex process for which few tumor cells complete the entire process. Recent research on BM of lung cancer has recently stressed the essential role of tumor microenvironment (TME) in assisting tumor cells in the completion of each BM step. This review summarizes recent studies regarding the effects of TME on tumor cells in the entire process of BM derived from lung cancer. The identification of vulnerable targets in the TME and their prospects to provide novel therapeutic opportunities are also discussed.
Brain Neoplasms/pathology* ; Humans ; Lung Neoplasms/drug therapy* ; Neoplasm Metastasis ; Tumor Microenvironment

OBJECTIVE: To retrospectively evaluate the safety and efficacy of percutaneous radiofrequency ablation (RFA) in patients with metachronous hepatic metastases arising from pancreatic adenocarcinoma who had previously received curative surgery.MATERIALS AND METHODS: Between 2002 and 2017, percutaneous RFA was performed on 94 metachronous hepatic metastases (median diameter, 1.5 cm) arising from pancreatic cancer in 60 patients (mean age, 60.5 years). Patients were included if they had fewer than five metastases, a maximum tumor diameter of ≤ 5 cm, and disease confined to the liver or stable extrahepatic disease. For comparisons during the same period, we included 66 patients who received chemotherapy only and met the same eligibility criteria described.RESULTS: Technical success was achieved in all hepatic metastasis without any procedure-related mortality. During follow-up, local tumor progression of treated lesions was observed in 38.3% of the tumors. Overall median survival and 3-year survival rates were 12 months and 0%, respectively from initial RFA, and 14.7 months and 2.1%, respectively from the first diagnosis of liver metastasis. Multivariate analysis showed that a large tumor diameter of > 1.5 cm, a late TNM stage (≥ IIB) before curative surgery, a time from surgery to recurrence of < 1 year, and the presence of extrahepatic metastasis, were all prognostic of reduced overall survival after RFA. Median overall (12 months vs. 9.1 months, p = 0.094) and progression-free survival (5 months vs. 3.3 months, p = 0.068) were higher in the RFA group than in the chemotherapy group with borderline statistical difference.CONCLUSION: RFA is safe and may offer successful local tumor control in patients with metachronous hepatic metastases arising from pancreatic adenocarcinoma. Patients with a small diameter tumor, early TNM stage before curative surgery, late hepatic recurrence, and liver-only metastasis benefit most from RFA treatment. RFA provided better survival outcomes than chemotherapy for this specific group with borderline statistical difference.
Adenocarcinoma ; Catheter Ablation ; Diagnosis ; Disease-Free Survival ; Drug Therapy ; Follow-Up Studies ; Humans ; Liver ; Mortality ; Multivariate Analysis ; Neoplasm Metastasis ; Pancreatic Neoplasms ; Recurrence ; Retrospective Studies ; Survival Rate

metastasis stage, differentiation, invasion depth, and lymph node metastasis (p< 0.005). ProGRP levels were significantly decreased after chemotherapy (p<0.001). Receiver operating characteristic curves revealed a sensitivity and specificity for serum ProGRP in GC of 85.9% and 81.2%, respectively. ProGRP levels were positively correlated with CA72-4 and CEA (r=0.792 and 0.688, p<0.05, respectively). Combined detection of ProGRP, CEA, and CA72-4 showed the best diagnostic power for GC.CONCLUSION: ProGRP may be useful as a potential biomarker for GC diagnosis and therapy.]]>
Carcinoembryonic Antigen ; Diagnosis ; Drug Therapy ; Humans ; Lymph Nodes ; Male ; Neoplasm Metastasis ; ROC Curve ; Sensitivity and Specificity ; Stomach Diseases ; Stomach Neoplasms

OBJECTIVE: Pyrotinib, a novel irreversible pan-ErbB receptor tyrosine kinase inhibitor, showed promising antitumor activity and acceptable tolerability in phase II and phase III randomized clinical trials. We assessed the activity and safety of oral pyrotinib for human epidermal growth factor receptor 2 (HER2) positive metastatic breast cancer patients in the real world. METHODS: We retrospectively analyzed 72 HER2 positive metastatic breast cancer (MBC) patients who received oral pyrotinib based regimens at Beijing Cancer Hospital and other four hospitals (Peking University First Hospital, China-Japan Friendship Hospital, General Hospital of PLA, Peking University Third Hospital) from August 2018 to September 2019. Progression free survival (PFS), objective response rate (ORR), adverse events (AE) of pyrotinib were investigated. RESULTS: Seventy-two patients with HER2 positive MBC were enrolled. The median age of the patients was 55 years (range: 32-79 years). Sixty-nine (95.8%) patients had received anti-HER2 treatment in the metastatic and/or (neo) adjuvant settings; 61 (84.7%) patients had received anti-HER2 treatments in the metastatic setting in terms of trastuzumab 56 (77.8%) patients, lapatinib 36 (50.0%) patients, and T-DM1 4 (5.6%) patients. Among these 72 patients who received oral pyrotinib based regimens, 62 (86.1%) patients received pyrotinib (±trastuzumab) in combination with chemotherapy, 6 (8.3%) patients received pyrotinib (± trastuzumab) in combination with endocrine therapy and 4 (5.6%) patients received pyrotinib (±trastuzumab). Sixty-five (90.3%) patients received 400 mg pyrotinib once daily as initial dose, and 7 (9.7%) patients received 320 mg. OBJECTIVE response and safety to pyrotinib based therapy were evaluable in all the 72 patients. One (1.4%) patient achieved complete response (CR), 18 (25.0%) patients achieved partial response (PR), 41 (56.9%) patients had stable disease (SD), and 12 (16.7%) patients had progressive disease (PD). The ORR (CR+PR) was 26.4% and the median PFS was 7.6 months (95%CI: 5.5-9.7 months). Among the 36 patients with prior lapatinib therapy, the median PFS was 7.9 months (95%CI: 4.1-11.7 months). Among the 15 patients with brain metastasis, the median PFS was 6.0 months (95%CI: 2.2-9.8 months). The main toxicities related to pyrotinib were diarrhea in 57 (79.2%) cases, and 48 (66.7%) cases with grade 1-2 as well as 9 (12.5%) cases with grade 3. CONCLUSION Pyrotinib based therapy is an effective treatment for patients with HER2 positive MBC, including patients with lapatinib treatment failure and brain metastasis, and the toxicities can be tolerated.
Acrylamides/therapeutic use* ; Adult ; Aged ; Aminoquinolines/therapeutic use* ; Antineoplastic Combined Chemotherapy Protocols ; Breast Neoplasms/drug therapy* ; China ; Humans ; Middle Aged ; Neoplasm Metastasis ; Receptor, ErbB-2 ; Retrospective Studies ; Trastuzumab ; Treatment Outcome

Breast cancer (BC) is still the most common cancer among women worldwide. Amongst the subtypes of BC, triple negative breast cancer (TNBC) is characterized by deficient expression of estrogen, progesterone, and human epidermal growth factor receptor 2 receptors. These patients are therefore not given the option of targeted therapy and have worse prognosis as a result. Consequently, much research has been devoted to identifying specific molecular targets that can be utilized for targeted cancer therapy, thereby limiting the progression and metastasis of this invasive tumor, and improving patient outcomes. In this review, we have focused on the molecular targets in TNBC, categorizing these into targets within the immune system such as immune checkpoint modulators, intra-nuclear targets, intracellular targets, and cell surface targets. The aim of this review is to introduce and summarize the known targets and drugs under investigation in phase II or III clinical trials, while introducing additional possible targets for future drug development. This review brings a tangible benefit to cancer researchers who seek a comprehensive comparison of TNBC treatment options.
Breast Neoplasms ; Drug Therapy ; Estrogens ; Female ; Humans ; Immune System ; Neoplasm Metastasis ; Progesterone ; Prognosis ; Receptor, Epidermal Growth Factor ; Triple Negative Breast Neoplasms

metastasis-free survival rates in groups of patients with 1 or without amplifications and with two or more amplifications showed statistically significant differences (P = 0.01).CONCLUSION: Our studies have shown that the presence of clones with two or more amplifications of stem gene in patients with BC T₁N(x)M₀ has a significant prognostic value and determines an unfavorable prognosis for distant metastasis.]]>
Archives ; Breast Neoplasms ; Breast ; Clone Cells ; Drug Therapy ; Ectopic Gene Expression ; Gene Expression ; Humans ; Microarray Analysis ; Neoplasm Metastasis ; Neoplastic Stem Cells ; Oligonucleotide Array Sequence Analysis ; Prognosis ; Survival Rate

therapy-related myelodysplastic syndrome (t-MDS) in breast cancer patients exposed to chemotherapy and/or radiotherapy is significantly high compared to that in other cancer patients. This report reviews the use of hypomethylating agents (HMAs) to treat a 57-year-old woman newly diagnosed with MDS during palliative chemotherapy for metastatic breast cancer. Over a period of 6 years, the patient received several DNA-damaging chemotherapeutics including doxorubicin, cyclophosphamide, and paclitaxel. Repeated thrombocytopenia was the main reason for suspecting secondary hematologic malignancy. She was diagnosed with t-MDS based on bone marrow examination and her treatment history for breast cancer. While azacitidine was originally administered to stabilize MDS, it also stabilized the patient's lung and lymph node metastases without any major toxicity. Therefore, the current case highlights the promising effects of HMAs for treating t-MDS following heavily pretreated breast cancer.]]>
Azacitidine ; Bone Marrow Examination ; Breast Neoplasms ; Breast ; Cyclophosphamide ; DNA Methylation ; Doxorubicin ; Drug Therapy ; Female ; Hematologic Neoplasms ; Humans ; Lung ; Lymph Nodes ; Middle Aged ; Myelodysplastic Syndromes ; Neoplasm Metastasis ; Paclitaxel ; Radiotherapy ; Thrombocytopenia

metastasis and estrogen receptor (ER) negativity were significant prognostic factors for BCSS. Meanwhile, old age, pathologic tumor stage, and ALN metastasis were significant prognostic factors for OS. Subgroup analysis of ER-positive MBC showed that ALN metastasis was a significant prognostic factor for BCSS. Additionally, old age, pathologic tumor stage, and ALN metastasis were prognostic factors for OS. Ultimately, ALN metastasis was the most statistically significant prognostic factor for MBC. However, chemotherapy had no significant effect on BCSS and OS. The Kaplan-Meier curves of BCSS and OS based on pathologic tumor and nodal stages and age revealed that chemotherapy did not statistically significantly improve prognosis, except for the N3 stage.CONCLUSION: Our large retrospective analysis revealed that adjuvant chemotherapy provided little benefit to improve the prognosis of most ER-positive MBC patients. Therefore, chemotherapy can be omitted in the treatment of most ER-positive MBC.]]>
Adenocarcinoma, Mucinous ; Breast Neoplasms ; Breast ; Carcinoma, Ductal ; Chemotherapy, Adjuvant ; Diagnosis ; Drug Therapy ; Estrogens ; Humans ; Lymph Nodes ; Methods ; Mucins ; Multivariate Analysis ; Neoplasm Metastasis ; Prognosis ; Retrospective Studies

PURPOSE: Many patients with cytology proven node-positive breast cancer receive a neoadjuvant chemotherapy (NAC) treatment. We developed a nomogram to predict the breast and axillary pathologic complete responses (pCR) in patients with a cytologically proven axillary node positive breast cancer with NAC. METHODS: We selected 995 patients who were diagnosed with an invasive breast cancer and axillary lymph nodes metastasis, and who were treated with NAC followed by a curative surgery at the Samsung Medical Center between January 2007 and December 2014. The baseline patient and tumor characteristics, chemotherapy regimen, and tumor and nodal responses were thoroughly analyzed and reviewed. A nomogram was developed using a binary logistic regression model with a cross validation. RESULTS: Axillary pCR was achieved in 47.3% and breast pCR was achieved in 24.3% of the patients after NAC. In this case, the both pCR was associated with an initial clinical tumor stage, negative progesterone receptor status, positive human epidermal growth factor receptor 2 status, and clinical radiologic nodal responses. A nomogram was developed based on the clinical and statistically significant predictors. It had good discrimination performance (area under the curve [AUC], 0.868; 95% confidence interval, 0.84–0.89) and calibration fit as noted in that case. The cross validation had an average AUC 0.853 (0.837–0.869). CONCLUSION: Our nomogram might help to predict breast and axillary pCRs after NAC in patients with an initially node-positive breast cancer. Minimal surgery might be acceptable in patients for whom the nomogram indicates a high probability of achieving pCRs.
Area Under Curve ; Breast Neoplasms ; Breast ; Calibration ; Discrimination (Psychology) ; Drug Therapy ; Humans ; Logistic Models ; Lymph Nodes ; Neoadjuvant Therapy ; Neoplasm Metastasis ; Nomograms ; Polymerase Chain Reaction ; Receptor, Epidermal Growth Factor ; Receptors, Progesterone

PURPOSE: Upfront systemic chemotherapy with target agents has been recommended for patients with stage IV colon cancer. Some with partial response are considered for curative resection. There is high risk of developing postoperative complications following upfront systemic chemotherapy. We aimed to evaluate short-term perioperative outcomes of curative surgery after upfront chemotherapy in comparison with upfront surgery in patients with metastatic colon cancer.METHODS: Between January 2010 and October 2015, 146 patients (80 in the surgery first group, 66 in the upfront chemotherapy group) who underwent surgical resection before or after systemic chemotherapy for metastatic colon cancer were included in the present study. All decisions for treatment were made through a multidisciplinary team. Postoperative clinical outcomes and complications were analyzed to compare the groups.RESULTS: There was no difference between the 2 groups in terms of postoperative clinical outcomes. Overall complication rates were not different between the groups (surgery first group: 46.3% vs. upfront chemotherapy group: 60.6%; P = 0.084). When classified according to the Clavien-Dindo method, there was no difference between the 2 groups in terms of major complications (grade 3 or more) (surgery first group: 18.9% vs. upfront chemotherapy group: 27.5%; P = 0.374).CONCLUSION: There was no significant increase in major postoperative complications in metastatic colon cancer patients who received upfront chemotherapy followed by curative surgery. Careful patient selection and treatment planning are important.
Antineoplastic Agents ; Colon ; Colonic Neoplasms ; Drug Therapy ; Humans ; Methods ; Neoplasm Metastasis ; Patient Selection ; Postoperative Complications