Diagnosis and management of patients with stage III non­small cell lung cancer: A joint statement by the Lebanese Society of Medical Oncology and the Lebanese Pulmonary Society (Review).

Proper management of stage III non-small cell lung cancer (NSCLC) might result in a cure or patient long-term survival. Management should therefore be preceded by adequate and accurate diagnosis and staging, which will inform therapeutic decisions. A panel of oncologists, surgeons and pulmonologists in Lebanon convened to establish a set of recommendations to guide and unify clinical practice, in alignment with international standards of care. Whilst chest computerized tomography (CT) scanning remains a cornerstone in the discovery of a lung lesion, a positron-emission tomography (PET)/CT scan and a tumor biopsy allows for staging of the cancer and defining the resectability of the tumor(s). A multidisciplinary discussion meeting is currently widely advised for evaluating patients on a case-by-case basis, and should include at least the treating oncologist, a thoracic surgeon, a radiation oncologist and a pulmonologist, in addition to physicians from other specialties as needed. The standard of care for unresectable stage III NSCLC is concurrent chemotherapy and radiation therapy, followed by consolidation therapy with durvalumab, which should be initiated within 42 days of the last radiation dose; for resectable tumors, neoadjuvant therapy followed by surgical resection is recommended. This joint statement is based on the expertise of the physician panel, available literature and evidence governing the treatment, management and follow-up of patients with stage III NSCLC.

Uterine choriocarcinoma diagnosed 11 years after menopause: A case report.

BACKGROUND: Gestational trophoblastic neoplasms (GTNs) encompass a wide spectrum of diseases, of which choriocarcinoma is one of the most common. Choriocarcinoma occurs mainly in relation to pregnancy and rarely after the menopause. It has the potential to metastasize to organs other than the uterus. CASE REPORT: We describe a 62-year-old woman who presented with postmenopausal bleeding 11 years after the menopause. Pelvic ultrasound and abdominal/pelvic computerized tomography showed an intrauterine mass. Choriocarcinoma was diagnosed by Pipelle endometrial biopsy with positive staining for beta-human chorionic gonadotropin (hCG) and KI 67 along with an elevated serum beta-hCG level. The tumor was managed with multiple cycles of multidrug chemotherapy and follow-up based on serum beta-hCG levels according to the guidelines of the International Federation of Gynecology and Obstetrics (FIGO). CONCLUSION: This case report highlights that choriocarcinoma, a tumor normally associated with pregnancy, can present after the menopause.

Phospho-MEK1/2 and uPAR Expression Determine Sensitivity of AML Blasts to a Urokinase-Activated Anthrax Lethal Toxin (PrAgU2/LF).

In this study, we attempt to target both the urokinase plasminogen activator and the mitogen-activated protein kinase pathway in acute myeloid leukemia (AML) cell lines and primary AML blasts using PrAgU2/LF, a urokinase-activated anthrax lethal toxin. PrAgU2/LF was cytotoxic to five out of nine AML cell lines. Cytotoxicity of PrAgU2/LF appeared to be nonapoptotic and was associated with MAPK activation and urokinase activity because all the PrAgU2/LF-sensitive cell lines showed both uPAR expression and high levels of MEK1/2 phosphorylation. Inhibition of uPAR or desensitization of cells to MEK1/2 inhibition blocked toxicity of PrAgU2/LF, indicating requirement for both uPAR expression and MAPK activation for activity. PrAgU2/LF was also cytotoxic to primary blasts from AML patients, with blasts from four out of five patients showing a cytotoxic response to PrAgU2/LF. Cytotoxicity of primary AML blasts was also dependent on uPAR expression and phos-MEK1/2 levels. CD34(+) bone marrow blasts and peripheral blood mononuclear cells lacked uPAR expression and were resistant to PrAgU2/LF, demonstrating the lack of toxicity to normal hematological cells and, therefore, the tumor selectivity of this approach. Dose escalation in mice revealed that the maximal tolerated dose of PrAgU2/LF is at least 5.7-fold higher than that of the wild-type anthrax lethal toxin, PrAg/LF, further demonstrating the increased safety of this molecule. We have shown, in this study, that PrAgU2/LF is a novel, dual-specific molecule for the selective targeting of AML.