Role of MGMT as biomarker in colorectal cancer

O⁶-methylguanine DNA methyltransferase (MGMT) gene promoter methylation plays an important role in colorectal carcinogenesis, occurring in about 30%-40% of metastatic colorectal cancer. Its prognostic role has not been defined yet, but loss of expression of MGMT, which is secondary to gene promoter methylation, results in an interesting high response to alkylating agents such as dacarbazine and temozolomide. In a phase 2 study on heavily pre-treated patients with MGMT methylated metastatic colorectal cancer, temozolomide achieved about 30% of disease control rate. Activating mutations of RAS or BRAF genes as well as mismatch repair deficiency may represent mechanisms of resistance to alkylating agents, but a dose-dense schedule of temozolomide may potentially restore sensitivity in RAS-mutant patients. Further development of temozolomide in MGMT methylated colorectal cancer includes investigation of synergic combinations with other agents such as fluoropyrimidines and research for additional biomarkers, in order to better define the role of temozolomide in the treatment of individual patients.     

Complete remission in metastatic breast cancer: expecting the unexpected—results of a cross-sectional study

Background

Complete response (CR) in metastatic breast cancer (MBC) is rare. This study aims at analyzing the characteristics and outcome of MBC patients achieving CR.

Methods

We performed a cross-sectional analysis of clinical data from a consecutive series of MBC patients admitted at the Division of Medical Oncology of Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy, achieving CR following treatment for systemic disease and with at least 2 years of follow-up.

Results

Seventy-six MBC patients with CR were identified during a calendar year. 47 patients (61.8%) achieved CR more than once, for a total of 123 cases. Median age at MBC diagnosis was 56 years (range 30–76). 52 patients (68.4%) presented with recurrent disease, 24 (31.6%) with de novo metastatic disease. The majority of patients (80.3%) had hormone receptor (HR) positive and 26 (34.2%) had HER2 overexpressing MBC. 54 patients (71.1%) had only one site of metastatic disease. 33 patients (43.4%) received a local approach as part of their treatment and 67 (54.5%) achieved CR during maintenance therapy. CRs were durable, as after a median follow-up of 8.3 years (interquartile range 5.8–11.0 years) 42 patients (55.3%) were alive with no evidence of disease.

Conclusions

Durable CRs can occur after systemic therapy alone or after combined systemic and local treatments. Most cases presented CR in the presence of limited disease spreading, not necessarily on first-line therapy. Our study highlights the crucial role of multidisciplinary approach to MBC and the benefit of maintenance treatment.

     

Efficacy and Safety of Onartuzumab in Combination With First-Line Bevacizumab- or Pemetrexed-Based Chemotherapy Regimens in Advanced Non-Squamous Non–Small-Cell Lung Cancer

Background

Onartuzumab is a monovalent monoclonal antibody that binds with the extracellular domain of the MET receptor. Given the role of MET in non–small-cell lung cancer (NSCLC), we investigated whether onartuzumab added to first-line chemotherapy efficacy in non-squamous NSCLC.

Patients' and surgeons' perspectives on axillary surgery for breast cancer.

AIMS: The objectives of this study were to compare the postoperative morbidity of Sentinel lymph node biopsy (SLNB) and axillary lymph node dissection (ALND) and to compare the views of surgeons and patients regarding postoperative morbidity. METHODS: A prospective and comparative study was initiated to evaluate, 1 year after surgery, morbidity and sequelae after SLNB in 231 patients. Group I (n=141) underwent SLNB without ALND, group II (n=90) underwent SLNB followed by ALND when SLN where involved. Morbidity analysis was performed, respectively, by surgeons and patients. RESULTS: One hundred and eighty-five patients (80.5%) completed the questionnaire including 113 with SLNB alone, and 72 with ALND. One year after surgery, SLNB produced less morbidity than ALND for symptoms and function. There were significantly different assessments between surgeons and patients for pain, arm mobility and sensitiveness. CONCLUSIONS: One-year postoperative morbidity after SLNB is significantly lower than after ALND but views of surgeons and patients appears to be significantly different. Additional data are required to assess late consequences of axillary surgery.     

CDX-2 should be included in the work-up of patients with lung metastases from unknown primary

Two Cdx homeobox genes have been identified so far in humans[1, 2]. CDX-2 is the product of the Cdx-2 homeobox gene andis expressed in normal colonic epithelia and most colorectaladenocarcinomas. Lung and pleural neoplastic lesions requirethe distinction between primary and metastatic malignancy whenoccurring alone. Colorectal     

Exposure to Multiple Lines of Treatment and Survival of Patients With Metastatic Renal Cell Carcinoma: A Real-world Analysis

Background

The purpose of the present retrospective analysis was to describe the trends in exposure to multiple lines of treatment and overall survival (OS) in patients with metastatic renal cell carcinoma (mRCC) who started therapy in 2 different periods (period 1, 2004-2010; and period 2, 2011-2017).