Repurposing metformin as anticancer drug: Randomized controlled trial in advanced prostate cancer (MANSMED).

BACKGROUND: The proposal of metformin as an anticancer drug has been explored in many types of cancers. Metformin may act synergistically with standard prostate cancer therapies. However, there is still a debate about the effect of metformin on hormone sensitive prostate cancer (HSPC). PATIENTS AND METHODS: randomized controlled trial. Eligible patients were high risk locally advanced or metastatic HSPC. Patients were randomly assigned to receive either metformin plus standard of care or standard of care alone. The primary endpoint was castration-resistant prostate cancer-free survival (CRPC-FS). The secondary endpoints were overall survival, PSA level and adverse events. RESULTS: A total number of 124 patients underwent randomization where 62 patients were allocated in each arm. Over a median follow up of 22 months, the CRPC-FS was significantly improved with metformin (29 months, 95% CI 25-33 vs. 20 months 95% CI 16-24; P = 0.01). After subgroup analysis, the addition of metformin improved the CRPC-FS in patients with high risk localized disease (median not reached vs. 25 months, 95% CI 18-31; P = 0.02) and in patients with metastatic low tumor volume disease (median not reached vs. 15 months, 95% CI 5-25; P = 0.009). No significant difference in overall survival or PSA response in both treatment arms (P = 0.1 and 0.5, respectively). Metformin was not associated with significant adverse events apart from grade II diarrhea. CONCLUSION: Metformin is a safe and low-cost drug. Combining with androgen deprivation therapy improves the outcome in locally advanced or metastatic prostate cancer. Patients with low volume metastatic prostate cancer seem to drive more benefit.

Clinical Impact of Breast Cancer Stem Cells in Metastatic Breast Cancer Patients.

BACKGROUND: Breast tumors are composed of phenotypically diverse groups of cells; however, it is unclear which of these cells contribute to tumor development. Breast cancer management usually targets proliferating cells, but as breast cancer stem cells are slowly cycling, they may escape these targets whenever they are not actively proliferating. This may explain the occurrence of recurrences and failure of the treatment. AIM: To assess the impact of the BCSC expression on progression-free survival (PFS), overall survival (OS), and tumor response in metastatic breast cancer patients and to correlate the BCSC expression with different clinicopathological parameters. MATERIAL: This prospective study enrolled 76 de novo metastatic breast cancer patients recruited from the Oncology Center, Mansoura University, Egypt, with a minimum age 31 years and a maximum of 70 years. Pretreatment BCSC markers (CD44 and CD24) were assessed by immunohistochemistry on formalin-fixed paraffin-embedded tumor tissues from a primary or metastatic site. Patients received different lines of treatment, hormonal or chemotherapy, according to their biological subtypes. Anti-Her2 was added for Her2-positive patients. RESULTS: Thirty-three patients (43.4%) were premenopausal and 43 patients (56.6%) were postmenopausal. Bone-only metastasis was seen in 12 patients (15.7%), however, visceral ± bone metastasis was seen in 64 patients (84.3%). BCSC markers (CD44+ve and CD24-ve) were expressed in 32 patients (42.1%), while 44 patients (57.9%) were not expressing BCSC markers. Out of 32 patients expressing BCSC, 22 patients (68%) were premenopausal and 28 patients (87.5%) were with high-grade (GIII) disease. BCSC was significantly presented in triple negative subtype breast cancer as there were 32 patients with the BCSC expression, and out of them, 15 patients (46.9%) had triple negative disease, 10 patients (31.3%) had luminal subtype, and seven patients (21.9%) were Her2-amplified, while there were 44 patients without BCSC expression, and out of them, 30 patients (68.2%) were of the luminal subtype, no patient (20.5%) had triple negative disease, and five patients (11.4%) were Her2-amplified (P 0.006). Twenty-four patients (31.5%) presented with visceral crisis; out of them, 17 patients (70.1%) were expressing BCSC which also denoted more aggressive disease. Seventy-four patients were candidates for the response assessment. BCSC-expressing patients showed poor response compared to non-BCSC (16.1% responsive versus 51.2%, respectively), with a significance relation (P 0.003). The BCSC expression was associated with both significant short PFS (median, 18 months vs. 35 months; P=0.001) and short OS (median, 26 months vs. 43 months; P=0.003). In multivariate analysis; BCSC expression was an independent prognostic factor for poor OS (P=0.055) along with the molecular subtype (P=0.012), Her2 status (P=0.011), and histologic grade (P=0.037). CONCLUSION: This study further validates the BCSC expression as a poor prognostic biomarker correlated with poor response, short PFS and OS. So, it could be used as a marker for tailoring treatment with different lines of therapies in further studies. The BCSC expression was highly presented in the triple negative subtype which is an aggressive disease that lacks different targets. So, targeting BCSC may carry a hope in future for this group of patients.

Multidetector computed tomography evaluation of synchronous lymphoma and other solid malignancies.

OBJECTIVE: The objective of this study is to review the multidetector computed tomography (MDCT) findings of synchronous lymphoma and other solid malignancies. PATIENTS AND METHODS: This retrospective study included 18 patients confirmed with diagnosis of lymphoma and other solid malignancies. They were 8 women and 10 men (mean age, 62.5 year; range, 44-73 years). CT scanning was performed on one of the two systems: 64 MDCT in 11 patients and 6 MDCT in 7 patients. All 36 malignancies were underwent pathological evaluation. RESULTS: All cases were confirmed pathologically. Lymphomas were Hodgkin disease ( n = 5 patients) and non-Hodgkin lymphoma ( n = 13 patients). Hepatocellular carcinoma was detected in five patients. Bronchogenic carcinoma was detected in two patients. Renal cell carcinoma was detected in two patients. Breast carcinoma was detected in two patients. Prostatic carcinoma was detected in two patients. Gastric carcinoma was detected in two patients. Endometrial carcinoma was detected in one patient. Colonic carcinoma was detected in one patient. Thyroid carcinoma was detected in one patient. CONCLUSIONS: MDCT scanning is accurately imaging modality for the evaluation of synchronous lymphoma and other solid malignancies. More reports and accumulation of such cases should help to clarify the mechanisms, contribute to a further understanding of this phenomenon, and may lead to a new treatment strategy for synchronous lymphoma and other solid malignancies.

Unusual behavior of diffuse large B-cell lymphoma as cardiac invasion with rapid spontaneous regression after fine needle aspiration cytology.

OBJECTIVE: Spontaneous regression (SR) of lymphoma is a rare phenomenon. While the precise mechanism of SR remains unknown, apoptosis may be associated with its process. Here, we present a case of a 52-year-old woman was admitted to our hospital with cough and orthopnea for 2 weeks. Multi-detector computed tomography of whole body showed anterior and middle mediastinal soft tissue mass with multiple adjacent malignant lymphadenopathy. The mediastinal mass invaded right atrium and pericardium. Another left subphrenic retro-pancreatic mass was detected. This mass surrounded upper pole of left kidney. Fine needle aspiration cytology was done and revealed lymphocytic smear with advised tru-cut biopsy. CT guided tru-cut was taken after 8 days. During CT guided technique; marked regression of left subphrenic mass was detected. Post-contrast MDCT scan was done and revealed partial response of the masses after 8 days. The partial regressive course of this disease suggests the effectiveness of fine needle aspiration cytology in initiating spontaneous regression. Tru-cut biopsy revealed non-Hodgkin lymphoma (diffuse large B-cell type). We report a case of NHL with abnormal location and spontaneous regression.