Stage-IV melanoma and pulmonary metastases: factors predictive of survival.
ABSTRACT We reviewed a contemporary, single-institution experience to evaluate the natural history of stage-IV melanoma metastatic to the lung and identify factors predictive of survival.
A search of our prospective database was performed to identify patients with stage-IV melanoma and pulmonary metastases as the initial disease site; only patients seen at our institution prior to developing stage-IV disease and in whom treatment response was available were included. Patients' demographic, clinical, and treatment variables were recorded. Cox regression was used to identify factors independently predictive of survival.
The study cohort was comprised of 122 patients. Median survival was 14 months (5-year survival of 8%). Clinical factors at time of diagnosis of stage IV independently predictive of survival were a solitary pulmonary metastasis (HR 2.7, CI 1.6-4.4, P<0.0005) and absence of extra-pulmonary disease (HR 1.9, CI 1.2-3.1, P = 0.01). Among treatment factors, only metastasectomy was independently predictive of survival (HR 0.42, CI 0.21-0.87, P = 0.02). Of the patients, 26 (21%) underwent metastasectomy, with a median survival of 40 months compared with 13 months in patients not selected for surgical treatment. Of these 26, 23 (88%) experienced recurrence at a median of 5 months after the procedure. No survival difference was seen between responders and non-responders to systemic therapy (P = 0.55).
In stage-IV melanoma with pulmonary metastases, a solitary metastasis and absence of extra-pulmonary disease are predictive of survival. While these factors are often present in patients selected for pulmonary metastasectomy, this independently predicts survival. However, response to systemic therapy does not correlate with a survival difference.
Article: Pulmonary metastasectomy[Show abstract] [Hide abstract]
ABSTRACT: BACKGROUND: The major obstacle in curing cancer is the limited ability to prevent and treat metastatic disease. Pulmonary metastasectomy is now a standard treatment option in carefully selected cases. With the lung being frequently the only site of metastasis, a complete resection of all tumor masses poses a potentially curative treatment option. METHODS: This review article gives an outline of the basics of pulmonary metastasectomy and reviews the latest research in this field. RESULTS AND CONCLUSIONS: Technical advances in thoracic surgery during the past decades made pulmonary metastasectomy a safe procedure with a low morbidity. However, surgical resection must be embedded in an individualized oncological concept.European Surgery 10/2011; 43(5). · 0.26 Impact Factor
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ABSTRACT: The fourth ¿Melanoma Bridge Meeting¿ took place in Naples, December 5 to 8th, 2013. The four topics discussed at this meeting were: Diagnosis and New Procedures, Molecular Advances and Combination Therapies, News in Immunotherapy, and Tumor Microenvironment and Biomarkers.Until recently systemic therapy for metastatic melanoma patients was ineffective, but recent research in tumor biology and immunology has led to the development of new targeted and immunotherapeutic agents that prolong progression-free survival (PFS) and overall survival (OS). New therapies, such as mitogen-activated protein kinase (MAPK) pathway inhibitors, like BRAF and MEK inhibitors, as well as other signaling pathways inhibitors, are being tested in metastatic melanoma either as monotherapy or in combination, and have yielded promising results.Improved survival rates have also been observed with immune therapy for patients with metastatic melanoma. Immune-modulating antibodies came to the forefront with anti-CTLA-4, programmed cell death-1 (PD-1) and PD-1 ligand 1 (PD-L1) pathway blocking antibodies that result in durable responses in a subset of melanoma patients. Agents targeting other immune inhibitory (e.g., Tim-3) or immune stimulating (e.g., CD137) receptors and other approaches such as adoptive cell transfer demonstrate clinical benefit in melanoma as well.This meeting¿s specific focus was on advances in targeted therapy and immunotherapy. Both combination targeted therapy approaches and different immunotherapies were discussed. Similarly to the previous meetings, the importance of biomarkers for clinical application as markers for diagnosis, prognosis and prediction of treatment response was an integral part of the meeting. Significant consideration was given to issues surrounding the development of novel therapeutic targets as further study of patterns of resistance to both immunologic and targeted drugs are paramount to future drug development to guide existing and future therapies. The overall emphasis on biomarkers supports novel concepts toward integrating biomarkers into contemporary clinical management of patients with melanoma across the entire spectrum of disease stage. Translation of the knowledge gained from the biology of tumor microenvironment across different tumors represents a bridge to impact on prognosis and response to therapy in melanoma.Journal of Translational Medicine 10/2014; 12(1):277. · 3.99 Impact Factor
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ABSTRACT: Background:Interleukin-2 (IL-2) treatment for patients with metastatic melanoma has shown remarkable durable responses. Systemic administration of IL-2 may cause severe side effects, whereas local administration is considered to be a safe alternative. The lungs are common sites of metastases in melanoma patients causing considerable respiratory problems. We sought to evaluate the potential antitumoral effect of a low-dose inhalative IL-2 (lh-IL-2) regimen for patients with melanoma lung metastases. In addition, we explored the prophylactic potential of Ih-IL-2 after surgical removal of lung metastases in a study carried out in an outpatient setting.Methods:Twenty patients with American Joint Committee on Cancer stage-IV (M1b and M1c) melanoma were enrolled in this study and treated with 3 × 3 million IU inhalative IL-2 q.d. together with monthly dacarbazine bolus injections. Five patients received lh-IL-2 after surgical resection of lung metastases to prevent recurrence of the disease (prophylaxis group, N=5). All other patients were enrolled in the treatment group (N=15). Clinical evaluations were carried out monthly and radiological follow-up was performed every third month.Results:Nine patients in the treatment group had a clinical benefit with partial regression (27%) or stable disease (33%). Four patients had progression of lung metastases (26.7%) and two patients were not evaluable (13.3%). In the prophylaxis group, none of the patients developed new lung metastases during lh-IL-2 therapy. The median follow-up period was 7.8 months in the treatment group and 25.7 months in the prophylaxis group. In the majority of patients, treatment was well tolerated.Conclusions:Low-dose IL-2 inhalation might offer an effective and safe treatment option for lung metastases in melanoma patients. In addition, lh-IL-2 may have a prophylactic potential to prevent recurrence in the lungs after pulmonary melanoma metastasectomy. Administration can easily be performed in an outpatient setting, thus offering an attractive treatment option.British Journal of Cancer advance online publication, 11 February 2014; doi:10.1038/bjc.2014.62 www.bjcancer.com.British Journal of Cancer 02/2014; 110(6). · 5.08 Impact Factor