BackgroundObesity is a risk factor for malignancy; however, its prognostic role in patients with metastatic melanoma is controversial. We aim to investigate the prognostic role of body mass index (BMI) in patients with metastatic melanoma receiving mitogen-activated pathway kinase inhibitors (MAPKi), immune checkpoint inhibitors (ICIs) alone or their sequence.MethodsData on patients with metastatic melanoma receiving ≥1 line of systemic treatment were retrieved from prospectively collected databases. Progression-free survival (PFS) and overall survival (OS) were analyzed by means of multivariable stratified Cox regression models; disease control rate (DCR) was analyzed by multivariable stratified logistic regression models. Subgroup analyzes according to the type of treatments received, and in BRAF-mutated patients were pre-planned. All multivariable models included BMI, age, gender, American Joint Committee on Cancer stage, performance status, lactate dehydrogenase and treatment sequencing strategy as covariates.ResultsBetween November 2010 and November 2018, 688 patients from three Italian and two Polish centers were enrolled. 379 (57%) patients had M1c/d disease, 273 (41%) were female and the mean BMI was 27.1 (SD=4.9). Considering first-line treatment, 446 patients (66.8%) received ICIs and 222 MAPKi. No impact of BMI on OS was detected either considering the first line of ICIs, or ICIs sequencing (HR=1.02, 95% CI: 0.99 to 1.05, p=0.202, and HR=1.02, 95% CI: 0.99 to 1.04, p=0.237, respectively). A late effect of BMI on OS was found in patients treated with MAPKi: for five units increment, a 51% of risk reduction at 18 months and a 76% of risk reduction at 30 months were observed. No significant effect of BMI on PFS and DCR was found in any of the subgroup analyzes.ConclusionIn patients with metastatic melanoma receiving ICIs, there is no impact of BMI on DCR, PFS and OS. The late prognostic effect of BMI in patients treated with MAPKi should be considered hypothesis generating and needs to be further investigated.
Giant cell tumor of bone (GCTB) is an osteolytic, locally aggressive tumor that rarely metastasizes and typically occurs in the bones. At present, the primary treatment for GCTB is curettage with local adjuvants. Giant cells express receptor activator of nuclear factor-κB ligand (RANKL). Denosumab, a RANKL inhibitor appears to present an effective therapeutic option in advanced cases of GCTB. The aim of the present study was to confirm the efficacy of denosumab in large group of patients with locally advanced GCTB. A total of 35 patients with histologically confirmed GCTB that were treated with denosumab with no participation in clinical trials between May 2013 and September 2015 were included in the present study. Denosumab treatment was administered until complete tumor resection was feasible or tumor progression or unacceptable toxicity had occurred. The mean denosumab treatment duration was 7.4 months. A total of 17 patients received surgery following denosumab treatment: 11 patients underwent wide en bloc resection with prosthesis implantation in 10 cases and 6 patients were treated with intralesional curettage. Tumor progression was observed in 2 patients that underwent intralesional curettage without prosthesis implantation. In addition, tumor progression was observed during denosumab treatment in 2 patients that had previously undergone radiotherapy. The overall 1-year progression-free survival rate was 92.8%. Thus, for patients with advanced, unresectable, progressive or symptomatic pretreated GCTB, denosumab provides a therapeutic option not previously available, which has become the standard therapy in multidisciplinary management of GCTB.
Mucosal melanoma is a rare disease epidemiologically and molecularly distinct from cutaneous melanoma developing from melanocytes located in mucosal membranes. Little is known about its therapy. In this paper, we aimed to evaluate the results of immunotherapy and radiotherapy in a group of patients with advanced mucosal melanoma, based on the experience of five high-volume centers in Poland and Italy. There were 82 patients (53 female, 29 male) included in this retrospective study. The median age in this group was 67.5 (IQR: 57.25–75.75). All patients received anti-PD1 or anti-CTLA4 antibodies in the first or second line of treatment. Twenty-three patients received radiotherapy during anti-PD1 treatment. In the first-line treatment, the median progression-free survival (PFS) reached six months in the anti-PD1 group, which was statistically better than 3.1 months in the other modalities group (p = 0.004). The median overall survival (OS) was 16.3 months (CI: 12.1–22.3) in the whole cohort. Patients who received radiotherapy (RT) during the anti-PD1 treatment had a median PFS of 8.9 months (CI: 7.4–NA), whereas patients treated with single-modality anti-PD1 therapy had a median PFS of 4.2 months (CI: 3.0–7.8); this difference was statistically significant (p = 0.047). Anti-PD1 antibodies are an effective treatment option in advanced mucosal melanoma (MM). The addition of RT may have been beneficial in the selected subgroup of mucosal melanoma patients.
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