Adjuvant crizotinib in high-risk uveal melanoma following definitive therapy.

Introduction: Approximately 40% of patients with uveal melanoma (UM) will develop metastatic disease. Tumors measuring at least 12mm in basal diameter with a class 2 signature, as defined by a widely used gene expression-profiling test, are associated with significantly higher risk of metastasis, with a median time to recurrence of 32 months. No therapy has been shown to reduce this risk.

Axitinib in combination with pembrolizumab in patients with advanced renal cell cancer: a non-randomised, open-label, dose-finding, and dose-expansion phase 1b trial.

Background: Previous studies combining PD-1 checkpoint inhibitors with tyrosine kinase inhibitors of the VEGF pathway have been characterised by excess toxicity, precluding further development. We hypothesised that axitinib, a more selective VEGF inhibitor than others previously tested, could be combined safely with pembrolizumab (anti-PD-1) and yield antitumour activity in patients with treatment-naive advanced renal cell carcinoma.

Methods: In this ongoing, open-label, phase 1b study, which was done at ten centres in the USA, we enrolled patients aged 18 years or older who had advanced renal cell carcinoma (predominantly clear cell subtype) with their primary tumour resected, and at least one measureable lesion, Eastern Cooperative Oncology Group performance status 0-1, controlled hypertension, and no previous systemic therapy for renal cell carcinoma.

Metastatic melanoma patients' sensitivity to ipilimumab cannot be predicted by tumor characteristics.

Unlabelled: Immune checkpoint inhibitors have dramatically changed the prognosis for patients with metastatic melanoma. However, not all patients respond to therapy and toxicities can be severe leaving need for reliable clinical predictive markers.

Methods: We examined primary tumor characteristics including ulceration, BRAF mutation status, and Breslow depth in patients who subsequently developed stage IV disease and were treated with ipilimumab at 3 institutions.

Surveillance strategies in the follow-up of melanoma patients: too much or not enough?

Background: After appropriate initial therapy for patients with stage II-III melanoma, there is no consensus regarding surveillance. Thus, follow-up is highly variable among institutions and individual providers. The National Comprehensive Cancer Network recommends routine clinical examination and consideration of imaging for stage IIB-IIIC every 3-12 mo with no distinction between stages.

The Raf Kinase Inhibitor Sorafenib Inhibits JAK-STAT Signal Transduction in Human Immune Cells.

Sorafenib is an oral multikinase inhibitor that was originally developed as a Raf kinase inhibitor. We hypothesized that sorafenib would also have inhibitory effects on cytokine signaling pathways in immune cells. PBMCs from normal donors were treated with varying concentrations of sorafenib and stimulated with IFN-α or IL-2.

Cutaneous keratoacanthomas/squamous cell carcinomas associated with neutralization of transforming growth factor β by the monoclonal antibody fresolimumab (GC1008).

Fresolimumab is an antibody capable of neutralizing all human isoforms of transforming growth factor beta (TGFβ) and has demonstrated anticancer activity in investigational studies. Inhibition of TGFβ by fresolimumab can potentially result in the development of cutaneous lesions. The aim of this study was to investigate the clinical, histological, and immunohistochemical characteristics of cutaneous neoplasms associated with fresolimumab.

Phase I study of GC1008 (fresolimumab): a human anti-transforming growth factor-beta (TGFβ) monoclonal antibody in patients with advanced malignant melanoma or renal cell carcinoma.

Background: In advanced cancers, transforming growth factor-beta (TGFβ) promotes tumor growth and metastases and suppresses host antitumor immunity. GC1008 is a human anti-TGFβ monoclonal antibody that neutralizes all isoforms of TGFβ. Here, the safety and activity of GC1008 was evaluated in patients with advanced malignant melanoma and renal cell carcinoma.

The role of local therapy in the management of lung and liver oligometastases.

Despite recent advances in oncologic therapy, an important proportion of patients with primary cancer will develop distant metastasis. The standard therapy for metastatic cancer is systemic therapy, which typically does not yield excellent response rates for most solid tumors. Data in the literature support the existence of a state of limited metastasis or oligometastasis.

Stereotactic body radiation therapy for oligometastases.

There are data in the literature to suggest the presence of an oligometastatic state, and local aggressive therapy of the oligometastases may improve outcomes including survival. Stereotactic body radiation therapy has emerged as one of the local therapy options for oligometastases in various body sites, most commonly in the lung and the liver. Retrospective studies and clinical trials have demonstrated promising results with the use of stereotactic body radiation therapy for oligometastases.

Stereotactic radiosurgery alone for patients with 1-4 radioresistant brain metastases.

Brain metastases from radioresistant histologies are perceived to be less responsive to WBRT compared to other histologies, and stereotactic radiosurgery (SRS) may provide better local control. The aim of this study was to examine the outcomes of patients with 1-4 brain metastasis from radioresistant histologies (renal cell carcinoma and melanoma) treated with SRS alone. Thirty-eight patients with 1-4 radioresistant brain metastases (66 lesions) were treated with SRS alone.

A pilot study of bevacizumab and interferon-α2b in ocular melanoma.

Objectives: We hypothesized that administration of bevacizumab, a monoclonal antibody that neutralizes vascular endothelial growth factor, in combination with high-dose interferon-alpha2b (IFN-α2b), an inhibitor of basic fibroblast growth factor, would have clinical activity in patients with metastatic ocular melanoma.

Methods: Patients with metastatic ocular melanoma received bevacizumab (15 mg/kg intravenously every 2 weeks) plus IFN-α2b (5 MU/m subcutaneously 3 times weekly for 2 weeks followed by a dose of 10 MU/m subcutaneously thereafter). Patients exhibiting a clinical response or stabilization of disease were treated until disease progression.

Stereotactic radiosurgery with or without whole brain radiotherapy for patients with a single radioresistant brain metastasis.

Purpose: To examine the outcomes of patients with a single brain metastasis from radioresistant histologies (renal cell carcinoma and melanoma) treated with stereotactic radiosurgery (SRS) with or without whole brain radiotherapy (WBRT).

Methods And Materials: We reviewed the medical records of 27 patients treated at our institution between 2000 and 2007 with a single radioresistant brain metastasis. Patients were treated with Gamma Knife based SRS.

Phase I trial of continuous infusion recombinant human interleukin-4 in patients with cancer.

Background: A phase I study using recombinant human interleukin-4 (rhuIL-4) administered as a continuous intravenous infusion was conducted in patients with advanced cancer to study the toxicity profile and to determine the maximum tolerated dose (MTD) of this cytokine.

Methods: Twenty-six patients with non-hematologic malignancies were treated with escalating doses of rhuIL-4 administered as 24-hour continuous intravenous infusion on days 1-5 and 15-19 every 28 days. The dose levels of rhuIL-4 were: dose level I-0.

Results of whole brain radiotherapy and recursive partitioning analysis in patients with brain metastases from renal cell carcinoma: a retrospective study.

Purpose: To determine the benefit of whole brain radiotherapy (WBRT) and the use of the Radiation Therapy Oncology Group (RTOG) recursive partitioning analysis (RPA) classification system in patients with brain metastases from renal cell carcinoma.

Methods And Materials: We identified 46 consecutive patients with brain metastases from renal cell carcinoma who were treated with WBRT at the Cleveland Clinic Foundation between 1983 and 2000. We reviewed their charts for patient and tumor characteristics and categorized them according to the RTOG RPA classes.

F-18 fluorodeoxyglucose positron emission tomography in the evaluation of distant metastases from renal cell carcinoma.

Purpose: We conducted a study to evaluate the role of F-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) in the detection of distant metastases from renal cell carcinoma (RCC).

Materials And Methods: Twenty-four patients with histologically proven clear-cell RCC undergoing surgical evaluation for possible resection of recurrent disease were investigated. All patients had suspected distant metastases based on conventional anatomic imaging techniques (computed tomography and magnetic resonance imaging).