Marios P. Decatris

Melanoma of the gallbladder: appropriate surgical management and review of the literature

Melanomas of the gallbladder (GB) are extremely rare with a very poor prognosis. They feature in the literature as a few case reports and the method of their management is not clear. We report a case of patient with metastatic cutaneous melanoma to the GB, and our treatment suggestion.

Immune checkpoint inhibitors as first-line and salvage therapy for advanced non-small-cell lung cancer.

Advanced non-small-cell lung cancer (NSCLC) has a poor prognosis with few treatment options available for patients after failure of first-line therapy. Nivolumab is the first immune checkpoint inhibitor targeting the PD-1 to be approved in recurrent NSCLC with squamous and nonsquamous histology. More recently, pembrolizumab has also been approved as salvage therapy in PD-L1-positive recurrent NSCLC. The success of immunotherapy in malignant melanoma, previously a disease with no effective treatment, has generated optimism and expectation that some of the checkpoint inhibitors currently in clinical development will soon become available as first-line therapy and hence improve outcomes for the vast majority of patients with advanced NSCLC. This article summarizes the progress accomplished in the field and discusses controversies surrounding the use of immune checkpoint inhibitors.

Management of endocrine resistant breast cancer.

Metastatic breast cancer (MBC) may present de novo but more commonly develops in women initially presenting with early breast cancer despite the widespread use of adjuvant hormonal and cytotoxic chemotherapy. MBC is incurable. Hormone sensitive MBC eventually becomes resistant to endocrine therapy in most women. Anthracyclines are the agents of choice in the treatment of endocrine resistant MBC. With the widespread use of anthracyclines in the adjuvant setting, taxanes have become the agents of choice for many patients. Recently capecitabine has become established as a standard of care for patients pretreated with anthracyclines and taxanes. However, a range of agents have activity as third line treatment. These include gemcitabine, vinorelbine and platinum analogues. The sequential use of non-cross resistant single agents rather than combination therapy is preferable in most women with MBC. Even though combination therapy can improve response rates and increase progression free interval, there is no robust evidence to indicate an advantage in terms of overall survival. Moreover, combination therapy is associated with a higher toxicity rate and poor quality of life. There is no role for dose-intense therapy, high dose therapy or maintenance chemotherapy outside the context of a clinical trial. The introduction of trastuzumab, monoclonal antibody targeting growth factor receptors, has improved the therapeutic options for women with tumours overexpressing HER2/neu. DNA micro-array profiles of tumours can potentially help to individualise therapy in future. Molecular targeted therapy has the potential to revolutionise the management of MBC.