Denosumab in patients with giant-cell tumour of bone: a multicentre, open-label, phase 2 study.

Background: Giant-cell tumour of bone (GCTB) is a rare, locally aggressive osteoclastogenic stromal tumour of the bone. This phase 2 study aimed to assess the safety and activity of denosumab in patients with surgically salvageable or unsalvageable GCTB.

Methods: In this multicentre, open-label, phase 2 study done at 30 sites in 12 countries we enrolled adults and skeletally mature adolescents (aged ≥12 years) weighing at least 45 kg with histologically confirmed and radiographically measurable GCTB, Karnofsky performance status 50% or higher (Eastern Cooperative Oncology Group status 0, 1, or 2), and measurable active disease within 1 year of study enrolment.

Functional outcome of surgical treatment of adults with extremity osteosarcoma after megaprosthetic reconstruction-single-center experience.

Background: Osteosarcoma is the most common primary malignant bone tumor in adults and is usually located in the long bones. Standard treatment consists of perioperative chemotherapy and radical surgical resection. Limb-sparing surgery using a variety of reconstructive techniques remains the gold standard.

Principles of prophylactic and therapeutic management of skin toxicity during treatment with checkpoint inhibitors.

The introduction of immunotherapy into the treatment of cancer patients has revolutionised the oncological approach and significantly improved patient survival. The key drugs are immune checkpoint inhibitors (CPIs), whose mechanism of action is to elicit immune response against cancer cell antigens. Three types of CPIs are currently used and approved: an anti-CTLA-4 antibody, ipilimumab; anti-PD-1 antibodies, nivolumab and pembrolizumab; and anti-PD-L1 antibodies: atezolizumab, avelumab and durvalumab.

Five-Year Survival with Combined Nivolumab and Ipilimumab in Advanced Melanoma.

Background: Nivolumab plus ipilimumab or nivolumab alone resulted in longer progression-free and overall survival than ipilimumab alone in a trial involving patients with advanced melanoma. We now report 5-year outcomes in the trial.

Methods: We randomly assigned patients with previously untreated advanced melanoma to receive one of the following regimens: nivolumab (at a dose of 1 mg per kilogram of body weight) plus ipilimumab (3 mg per kilogram) every 3 weeks for four doses, followed by nivolumab (3 mg per kilogram every 2 weeks); nivolumab (3 mg per kilogram every 2 weeks) plus ipilimumab-matched placebo; or ipilimumab (3 mg per kilogram every 3 weeks for four doses) plus nivolumab-matched placebo.

Prognostic value of the pretreatment neutrophil-to-lymphocyte ratio in patients with advanced gastrointestinal stromal tumors treated with sunitinib after imatinib failure.

The neutrophil-to lymphocyte ratio (NLR) has been proven to be correlated with outcomes in various cancer types, including gastrointestinal stromal tumors (GIST). There is limited data regarding the clinical value of NLR during second line therapy after failure of imatinib and there is an urgent need for more precise predictive factors for therapy. The aim of this study was to assess the association of the pretreatment NLR with progression free survival (PFS) and overall survival (OS) in patients with unresectable/metastatic GIST treated with sunitinib in a second line of treatment.

Safety and efficacy of nivolumab in patients with rare melanoma subtypes who progressed on or after ipilimumab treatment: a single-arm, open-label, phase II study (CheckMate 172).

Background: Nivolumab has been widely studied in non-acral cutaneous melanoma; however, limited data are available in other melanoma subtypes. We report outcomes by melanoma subtype in patients who received nivolumab after progression on prior ipilimumab.

Patients And Methods: CheckMate 172 was a phase II, single-arm, open-label, multicentre study that evaluated nivolumab in patients with advanced melanoma who progressed on or after ipilimumab.

Comparison of seventh and eighth edition of AJCC staging system in melanomas at locoregional stage.

Background: The eighth edition of the American Joint Committee on Cancer (AJCC) staging system has been effective since January 2018. It has introduced some major changes in the localized/locoregional melanoma classification. However, it has not been demonstrated how this classification was validated on external, clinical data.

NBTXR3, a first-in-class radioenhancer hafnium oxide nanoparticle, plus radiotherapy versus radiotherapy alone in patients with locally advanced soft-tissue sarcoma (Act.In.Sarc): a multicentre, phase 2-3, randomised, controlled trial.

Background: Pathological complete response to preoperative treatment in adults with soft-tissue sarcoma can be achieved in only a few patients receiving radiotherapy. This phase 2-3 trial evaluated the safety and efficacy of the hafnium oxide (HfO) nanoparticle NBTXR3 activated by radiotherapy versus radiotherapy alone as a pre-operative treatment in patients with locally advanced soft-tissue sarcoma.

Methods: Act.

Molecular Comparison of Imatinib-Naïve and Resistant Gastrointestinal Stromal Tumors: Differentially Expressed microRNAs and mRNAs.

Despite the success of imatinib in advanced gastrointestinal stromal tumor (GIST) patients, 50% of the patients experience resistance within two years of treatment underscoring the need to get better insight into the mechanisms conferring imatinib resistance. Here the microRNA and mRNA expression profiles in primary (imatinib-naïve) and imatinib-resistant GIST were examined. Fifty-three GIST samples harboring primary KIT mutations (exon 9; n = 11/exon 11; n = 41/exon 17; n = 1) and comprising imatinib-naïve (IM-n) (n = 33) and imatinib-resistant (IM-r) (n = 20) tumors, were analyzed.

Plasma lncRNA expression profile as a prognostic tool in mutant metastatic melanoma patients treated with BRAF inhibitor.

Long non-coding RNAs (lncRNA) are dysregulated in many cancer types. Abnormal baseline levels of these lncRNAs display diagnostic and prognostic potential in cancer patients. The aim of this study was to evaluate the prognostic value of plasma lncRNAs in -mutant advanced melanoma patients treated with a BRAF inhibitor.

Prognostic and predictive value of AJCC-8 staging in the phase III EORTC1325/KEYNOTE-054 trial of pembrolizumab vs placebo in resected high-risk stage III melanoma.

Background: The American Joint Committee on Cancer-8 (AJCC) classification of melanoma was implemented in January 2018. It was based on data gathered when checkpoint inhibitors were not used as adjuvant therapy in stage III melanoma. The European Organization for Research and Treatment of Cancer (EORTC) 1325/KEYNOTE-054 double-blind phase III trial evaluated pembrolizumab vs placebo in AJCC-7 stage IIIA (excluding lymph node metastasis ≤1 mm), IIIB or IIIC (without in-transit metastasis) patients after complete lymphadenectomy.

Natural history of well-differentiated liposarcoma of the extremity compared to patients treated with surgery.

Background: Patients with well-differentiated liposarcoma (WDLPS) of the extremity are mostly treated surgically, thereby possibly inducing severe morbidities. Despite the excellent prognosis, the natural history is barely studied. The aim of this study was to evaluate the natural history of extremity WDLPS by evaluating the outcome of patients treated with active surveillance (AS), who thereby exhibited the natural history of extremity WDLPS, and of patients treated surgically.

Five-Year Outcomes with Dabrafenib plus Trametinib in Metastatic Melanoma.

Background: Patients who have unresectable or metastatic melanoma with a V600E or V600K mutation have prolonged progression-free survival and overall survival when receiving treatment with BRAF inhibitors plus MEK inhibitors. However, long-term clinical outcomes in these patients remain undefined. To determine 5-year survival rates and clinical characteristics of the patients with durable benefit, we sought to review long-term data from randomized trials of combination therapy with BRAF and MEK inhibitors.

Use of extracellular vesicles from lymphatic drainage as surrogate markers of melanoma progression and mutation.

Liquid biopsies from cancer patients have the potential to improve diagnosis and prognosis. The assessment of surrogate markers of tumor progression in circulating extracellular vesicles could be a powerful non-invasive approach in this setting. We have characterized extracellular vesicles purified from the lymphatic drainage also known as exudative seroma (ES) of stage III melanoma patients obtained after lymphadenectomy.

Detection of SS18-SSX1/2 fusion transcripts in circulating tumor cells of patients with synovial sarcoma.

A recent study on 15 patients with synovial sarcoma demonstrated very low prevalence of tumor-specific fusion transcripts in peripheral blood specimens. Our results in an independent cohort of 38 patients with synovial sarcoma support these findings. Synovial sarcoma patients could greatly benefit from a non-invasive monitoring of tumor burden by liquid biopsies.

Defining Tumor Rupture in Gastrointestinal Stromal Tumor.

Tumor rupture is an important risk factor predictive of recurrence after macroscopically complete resection of gastrointestinal stromal tumors (GISTs), and an indication for defined interval or even lifelong adjuvant therapy with imatinib according to guidelines. However, there is no consensus or universally accepted definition of the term 'tumor rupture', and, consequently, its incidence varies greatly across reported series. Without predefined criteria, the clinical significance of rupture has also been difficult to assess on multivariate analysis of retrospective data.

Evaluation of Two Dosing Regimens for Nivolumab in Combination With Ipilimumab in Patients With Advanced Melanoma: Results From the Phase IIIb/IV CheckMate 511 Trial.

Purpose: Nivolumab 1 mg/kg plus ipilimumab 3 mg/kg (NIVO1+IPI3) is approved for first-line treatment of patients with advanced melanoma in several countries. We conducted a phase IIIb/IV study (CheckMate 511) to determine if nivolumab 3 mg/kg plus ipilimumab 1 mg/kg (NIVO3+IPI1) improves the safety profile of the combination.

Patients And Methods: Patients (N = 360) age 18 years or older with previously untreated, unresectable stage III or IV melanoma were randomly assigned 1:1 to NIVO3+IPI1 or NIVO1+IPI3 once every 3 weeks for four doses.

Predicting Survival in Patients Undergoing Resection for Locally Recurrent Retroperitoneal Sarcoma: A Study and Novel Nomogram from TARPSWG.

Purpose: The role of surgery for first relapse locally recurrent retroperitoneal sarcoma (RPS-LR1) is uncertain. We report outcomes of the largest RPS-LR1 series and propose a new prognostic nomogram.

Experimental Design: Patients with consecutive RPS-LR1 without distant metastases who underwent resection at 22 centers (2002-2011) were included.

Five-year outcomes from a phase 3 METRIC study in patients with BRAF V600 E/K-mutant advanced or metastatic melanoma.

Background: Primary findings from the METRIC (TMT212A2301) study demonstrated that trametinib improved progression-free survival (PFS) and overall survival (OS) compared with chemotherapy in patients with unresectable or metastatic cutaneous melanoma with a BRAF V600 E/K mutation. However, clinical data characterising the long-term use of these therapies in combination with BRAF inhibitors or as monotherapies are limited.

Methods: In this open-label, phase 3 study, 322 patients with BRAF V600 E/K-mutant metastatic melanoma were randomised in a 2:1 ratio to receive trametinib (2 mg orally, once daily; n = 214) or chemotherapy (dacarbazine [1000 mg/m] or paclitaxel [175 mg/m] intravenously, every 3 weeks; n = 108).

Radiotherapy for retroperitoneal liposarcoma: A report from the Transatlantic Retroperitoneal Sarcoma Working Group.

Background: The current study investigated the role of radiotherapy (RT) in patients with primary nonmetastatic retroperitoneal liposarcomas.

Methods: A total of 607 patients with localized retroperitoneal well-differentiated liposarcomas (WDLPS) and dedifferentiated liposarcomas (DDLPS) underwent surgical resection with or without RT at 8 high-volume sarcoma centers (234 patients with WDLPS, 242 patients with grade 1 to 2 DDLPS, and 131 patients with grade 3 DDLPS; grading was performed according to the National Federation of Centers for the Fight Against Cancer [Federation Nationale des Centres de Lutte Contre le Cancer; FNCLCC]). RT was administered in 19.

Pigmented/melanocytic malignant perivascular epithelioid cell tumor with TFE3-SFPQ(PSF) rearrangement - a challenging diagnosis of PEComa family of tumors.

We here report a case of a distinct subtype of pigmented/melanocytic malignant PEComa with TFE3-SFPQ(PSF) rearrangement. The tumor involved the iliac region and clinically mimicked metastatic melanoma. The immunohistochemical assessment was supplemented with molecular studies including fluorescence in situ hybridization (FISH) and next-generation sequencing sarcoma panel (NGS).