Changes in AXL and/or MITF melanoma subpopulations in patients receiving immunotherapy.

Background: Tumor heterogeneity is a hurdle to effective therapy, as illustrated by the 'mixed responses' frequently seen in immunotherapy-treated patients. Previously, AXL+ tumor cells were identified to be highly resistant to targeted therapy, whereas more differentiated MITF+ tumor cells do respond to RAF and MEK inhibitors.

Patients And Methods: In this study, we analyzed tumor heterogeneity and explored the presence of the previously described AXL+ or MITF+ melanoma subpopulations in metastatic tissues by NanoString gene expression analysis, single-cell RNA sequencing and multiplex immunofluorescence.

Sequencing of Checkpoint or BRAF/MEK Inhibitors on Brain Metastases in Melanoma.

Background: The impact of the order of treatment with checkpoint inhibitors or BRAF/MEK inhibitors on the development of brain metastases in patients with metastatic unresectable V600-mutant melanoma is unknown. The SECOMBIT trial examined the impact of the order of receipt of these treatments in such patients.

Methods: In this three-arm trial, we reviewed patients without brain metastases who received the BRAF/MEK inhibitors encorafenib and binimetinib until they had progressive disease followed by the immune checkpoint inhibitors ipilimumab and nivolumab (arm A); or treatment with ipilimumab and nivolumab until they had progressive disease followed by encorafenib and binimetinib (arm B); or treatment with encorafenib and binimetinib for 8 weeks followed by ipilimumab and nivolumab until they had progressive disease followed by retreatment with encorafenib arm binimetinib (arm C).

Final, 10-Year Outcomes with Nivolumab plus Ipilimumab in Advanced Melanoma.

Background: Previous results from this trial showed longer overall survival after treatment with nivolumab plus ipilimumab or with nivolumab monotherapy than with ipilimumab monotherapy in patients with advanced melanoma. Given that patients with advanced melanoma are living longer than 7.5 years, longer-term data were needed to address new clinically relevant questions.

Near-Complete Response to Osimertinib for Advanced Non-Small-Cell Lung Cancer in a Pretreated Patient Bearing Rare Compound Exon 20 Mutation (S768I + V774M): A Case Report.

Third-generation tyrosine kinase inhibitors are the first-line gold standard in treating advanced non-small-cell lung cancer bearing common mutations, but data documenting clinical efficacy in uncommon mutations are currently limited. In this paper, we describe the case of a patient bearing uncommon compound mutations in exon 20, who experienced a near-complete response to third-line Osimertinib, with metabolic complete response of pulmonary, nodal and ostheolytic lesions. This radiological assessment corresponded to an ECOG PS improvement (from three to one) and a substantial clinical benefit for the patients.

ML Models Built Using Clinical Parameters and Radiomic Features Extracted from F-Choline PET/CT for the Prediction of Biochemical Recurrence after Metastasis-Directed Therapy in Patients with Oligometastatic Prostate Cancer.

Unlabelled: Oligometastatic patients at [F]F-Fluorocholine (F-choline) PET/CT may be treated with metastasis-directed therapy (MDT). The aim of this study was to combine radiomic parameters extracted from F-choline PET/CT and clinical data to build machine learning (ML) models able to predict MDT efficacy.

Methods: Oligorecurrent patients (≤5 lesions) at F-choline PET/CT and treated with MDT were collected.

Nivolumab plus ipilimumab in melanoma patients with asymptomatic brain metastases: 7-year outcomes and quality of life from the multicenter phase III NIBIT-M2 trial.

Background: The primary analysis of the phase III NIBIT-M2 study showed a 41% 4-year overall survival (OS) of melanoma patients with asymptomatic brain metastases treated with ipilimumab plus nivolumab.

Methods: Here, we report the 7-year efficacy outcomes and the Health-Related Quality of Life (HRQoL) analyses of the NIBIT-M2 study.

Results: As of May 1, 2023, at a median follow-up of 67 months (mo), the median OS was 8.

Italian nivolumab Expanded Access Programme in melanoma adjuvant setting: patient outcomes and safety profile.

Introduction: The CheckMate 238 randomised study demonstrated the relevant benefit in terms of recurrence-free survival (RFS) of nivolumab versus ipilimumab in resected stage IIIB-C or IV melanoma patients with a tolerable safety profile.

Materials And Methods: From November 2018 to June 2019, 611 patients with stage III and IV resected melanoma were enroled to receive nivolumab as part of an Italian Expanded Access Programme (EAP). According to stages, 77% were stage III while 141 (23%) were stage IV with no evidence of disease (NED).

Outcomes in patients with -mutated melanoma and brain metastases at baseline treated with dabrafenib plus trametinib.

Background: Brain metastases (BM) and lactate dehydrogenase (LDH) levels above the upper limit of normal (ULN) are associated with poor prognosis in patients with melanoma. Although treatment with the BRAF inhibitor dabrafenib and the MEK inhibitor trametinib have demonstrated long-term clinical benefit in patients with melanoma, data on their efficacy in patients with BM are limited.

Methods: DESCRIBE Italy is an observational, retrospective, real-world study evaluating dabrafenib plus trametinib in 499 patients with -mutant stage III unresectable or stage IV melanoma from various sites across Italy.

Conservation agriculture reduces climate change impact of a popcorn and wheat crop rotation.

Urgent action is needed to ensure humanity's future under climate change. Agriculture faces major challenges as it is both influenced by and contributes to climate change. Conservation agriculture sequesters carbon (C) in the soil due to practices such as reduced tillage and planting of cover crops.

Neoadjuvant plus adjuvant combined or sequenced vemurafenib, cobimetinib and atezolizumab in patients with high-risk, resectable BRAF-mutated and wild-type melanoma: NEO-TIM, a phase II randomized non-comparative study.

Background: Following the increased survival of patients with metastatic melanoma thanks to immunotherapy and targeted therapy, neoadjuvant approaches are being investigated to address the unmet needs of unresponsive and intolerant patients. We aim to investigate the efficacy of neoadjuvant plus adjuvant combined or sequenced vemurafenib, cobimetinib and atezolizumab in patients with high-risk, resectable -mutated and wild-type melanoma.

Methods: The study is a phase II, open-label, randomized non-comparative trial in patients with stage IIIB/C/D surgically resectable, -mutated and wild-type melanoma, with three possible treatments: (1) vemurafenib 960 mg twice daily from day 1 to 42; (2) vemurafenib 720 mg twice daily from day 1 to 42; (3) cobimetinib 60 mg once daily from day 1 to 21 and from day 29 to 42; and (4) atezolizumab 840 mg for two cycles (day 22 and day 43).

Comparative efficacy and safety of targeted therapies for BRAF-mutant unresectable or metastatic melanoma: Results from a systematic literature review and a network meta-analysis.

Background: The objective of this study was to estimate the relative efficacy and safety of targeted therapies for the treatment of metastatic melanoma using a network meta-analysis (NMA).

Methods: A systematic literature review (SLR) identified studies in Medline, Embase and Cochrane published until November 2020. Screening used prespecified eligibility criteria.

Sequencing of Ipilimumab Plus Nivolumab and Encorafenib Plus Binimetinib for Untreated -Mutated Metastatic Melanoma (SECOMBIT): A Randomized, Three-Arm, Open-Label Phase II Trial.

Purpose: Limited prospective data are available on sequential immunotherapy and BRAF/MEK inhibition for -mutant metastatic melanoma.

Methods: SECOMBIT is a randomized, three-arm, noncomparative phase II trial (ClinicalTrials.gov identifier: NCT02631447).

Stability Program in Dendritic Cell Vaccines: A "Real-World" Experience in the Immuno-Gene Therapy Factory of Romagna Cancer Center.

Advanced therapy medical products (ATMPs) are rapidly growing as innovative medicines for the treatment of several diseases. Hence, the role of quality analytical tests to ensure consistent product safety and quality has become highly relevant. Several clinical trials involving dendritic cell (DC)-based vaccines for cancer treatment are ongoing at our institute.

Long-Term Outcomes With Nivolumab Plus Ipilimumab or Nivolumab Alone Versus Ipilimumab in Patients With Advanced Melanoma.

Purpose: In the phase III CheckMate 067 trial, durable clinical benefit was demonstrated previously with nivolumab plus ipilimumab and nivolumab alone versus ipilimumab. Here, we report 6.5-year efficacy and safety outcomes.

Radiotherapy and High-Dose Interleukin-2: Clinical and Immunological Results of a Proof of Principle Study in Metastatic Melanoma and Renal Cell Carcinoma.

High-dose interleukin-2 (HD IL-2) has curative potential in metastatic melanoma (MM) and renal cell carcinoma (RCC). Radiotherapy (RT) kills cancer cells and induces immunomodulatory effects. Prospective trials exploring clinical and immunological properties of combined RT/HD IL-2 are still needed.

Retrospective Chart Review of Dabrafenib Plus Trametinib in Patients with Metastatic BRAF V600-Mutant Melanoma Treated in the Individual Patient Program (DESCRIBE Italy).

Background: Real-world data on extended follow-up of patients with BRAF V600-mutant metastatic melanoma are limited. We investigated dabrafenib plus trametinib (dab + tram) outside of a clinical trial setting (Individual Patient Program; DESCRIBE Italy).

Objective: To describe the baseline features, treatment patterns, efficacy, and safety outcomes in patients with BRAF V600-mutant unresectable or metastatic melanoma who had received dab + tram as part of the Managed Access Program (MAP) in Italy.

Primary Analysis and 4-Year Follow-Up of the Phase III NIBIT-M2 Trial in Melanoma Patients With Brain Metastases.

Purpose: Phase II trials have shown encouraging activity with ipilimumab plus fotemustine and ipilimumab plus nivolumab in melanoma brain metastases. We report the primary analysis and 4-year follow-up of the NIBIT-M2 study, the first phase III trial comparing these regimens with fotemustine in patients with melanoma with brain metastases.

Patients And Methods: This phase III study recruited patients 18 years of age and older with wild-type or mutant melanoma, and active, untreated, asymptomatic brain metastases from nine centers, randomized (1:1:1) to fotemustine, ipilimumab plus fotemustine, or ipilimumab plus nivolumab.

Malignant Pleural Mesothelioma: State-of-the-Art on Current Therapies and Promises for the Future.

Malignant pleural mesothelioma (MPM) is a rare, aggressive cancer of the pleural surface associated with asbestos exposure. The median survival of MPM patients is a mere 8-14 months, and there are few biomarkers and no cure available. It is hoped that, eventually, the incidence of MPM will drop and remain low and constant, given that most nations have banned the use of asbestos, but in the meantime, the incidence in Europe is still growing.