Tumor-reactive T cell clonotype dynamics underlying clinical response to TIL therapy in melanoma.

Adoptive cell therapy (ACT) using in vitro expanded tumor-infiltrating lymphocytes (TILs) has inconsistent clinical responses. To better understand determinants of therapeutic success, we tracked TIL clonotypes from baseline tumors to ACT products and post-ACT blood and tumor samples in melanoma patients using single-cell RNA and T cell receptor (TCR) sequencing. Patients with clinical responses had baseline tumors enriched in tumor-reactive TILs, and these were more effectively mobilized upon in vitro expansion, yielding products enriched in tumor-specific CD8 cells that preferentially infiltrated tumors post-ACT.

Primary prophylaxis with mTOR inhibitor enhances T cell effector function and prevents heart transplant rejection during talimogene laherparepvec therapy of squamous cell carcinoma.

The application of mammalian target of rapamycin inhibition (mTORi) as primary prophylactic therapy to optimize T cell effector function while preserving allograft tolerance remains challenging. Here, we present a comprehensive two-step therapeutic approach in a male patient with metastatic cutaneous squamous cell carcinoma and heart transplantation followed with concomitant longitudinal analysis of systemic immunologic changes. In the first step, calcineurin inhibitor/ mycophenolic acid is replaced by the mTORi everolimus to achieve an improved effector T cell status with increased cytotoxic activity (perforin, granzyme), enhanced proliferation (Ki67) and upregulated activation markers (CD38, CD69).

Melanoma neoantigen vaccines: Are we getting more personal now?

KEYNOTE-942 is a randomized phase II adjuvant study in patients with resected stage III melanoma investigating a personalized neoantigen mRNA vaccine in combination with anti-PD-1. The study gave a clear signal of superiority for the vaccine plus anti-PD-1 in relapse-free and distant-metastasis-free survival but is not yet conclusive, and important questions remain.

[Oncology: what's new in 2023].

The oncology field continues its remarkable evolution over the years, with promising advances leading to innovative and individualized treatments. The development of new molecules, the identification of new therapeutic targets and the search for new sequences or combinations promise to revolutionize cancer treatments and contribute to improving survival rates, patients' quality of life and to open new perspective in oncology research. In this article, the newest data released in 2023 are reviewed.

Immune checkpoint inhibitor-related myositis and myocarditis: diagnostic pitfalls and imaging contribution in a real-world, institutional case series.

Background: Immune checkpoint inhibitors (ICIs) are reshaping the prognosis of many cancers, but often cause immune-related adverse events (irAEs). Among neurological irAEs, myositis is the most frequently reported. Our aim is to describe clinical and non-clinical characteristics, treatment and outcome of all irMyositis (skeletal limb-girdle and/or ocular myositis) and irMyocarditis cases in our reference center.

Development of an eHealth-enhanced model of care for the monitoring and management of immune-related adverse events in patients treated with immune checkpoint inhibitors.

Purpose: The use of electronic patient-reported outcome (ePRO) data in routine care has been tied to direct patient benefits such as improved quality of care and symptom control and even overall survival. The modes of action behind such benefits are seldom described in detail. Here, we describe the development of a model of care leveraging ePRO data to monitor and manage symptoms of patients treated with immune checkpoint inhibitors.

Modeling tumor size dynamics based on real-world electronic health records and image data in advanced melanoma patients receiving immunotherapy.

The development of immune checkpoint inhibitors (ICIs) has revolutionized cancer therapy but only a fraction of patients benefits from this therapy. Model-informed drug development can be used to assess prognostic and predictive clinical factors or biomarkers associated with treatment response. Most pharmacometric models have thus far been developed using data from randomized clinical trials, and further studies are needed to translate their findings into the real-world setting.

[Endometrial cancer in the crossroads of modernity and immunotherapy].

Frequent and with an increasing incidence in some territories, endometrial cancer is a complex disease leading to significant morbidity among affected patients. After years of research and the implementation of state-of-the-art molecular and gene assays significant breakthroughs were made. Through a better understanding of the underlying mechanisms of uterine carcinogenesis, a more precise and personalized risk stratification and the incorporation of immunotherapy, the treatment of endometrial cancer is experiencing significant improvements.

Semiautomated Pipeline to Quantify Tumor Evolution From Real-World Positron Emission Tomography/Computed Tomography Imaging.

Purpose: A semiautomated pipeline for the collection and curation of free-text and imaging real-world data (RWD) was developed to quantify cancer treatment outcomes in large-scale retrospective real-world studies. The objectives of this article are to illustrate the challenges of RWD extraction, to demonstrate approaches for quality assurance, and to showcase the potential of RWD for precision oncology.

Methods: We collected data from patients with advanced melanoma receiving immune checkpoint inhibitors at the Lausanne University Hospital.

Interactive process mining of cancer treatment sequences with melanoma real-world data.

The growing availability of clinical real-world data (RWD) represents a formidable opportunity to complement evidence from randomized clinical trials and observe how oncological treatments perform in real-life conditions. In particular, RWD can provide insights on questions for which no clinical trials exist, such as comparing outcomes from different sequences of treatments. To this end, process mining is a particularly suitable methodology for analyzing different treatment paths and their associated outcomes.

[Oncology: what's new in 2022].

The past year has brought several innovations in medical oncology, opening up promising new options for many solid tumors, both localized and metastatic. Immunotherapy, a real spearhead of emerging therapies in metastatic diseases, is seeing its use extend to adjuvant and neoadjuvant modalities, particularly in colon and lung cancers. 2022 also sees a great deal of focus on targeted therapies, as well as on antibody-drug conjugates, which creates new standards in both breast and lung cancers.

Systematic comparison with autoimmune liver disease identifies specific histological features of immune checkpoint inhibitor-related adverse events.

Background: Immune checkpoint inhibitors (ICIs) have become a mainstay of cancer treatment. Their immune-boosting quality has one major drawback, their proclivity to induce a broad array of immune-related adverse events (irAEs) affecting, among others, the liver and sharing some similarities with classic autoimmune liver diseases (AILD).We aimed to compare clinical, laboratory and histological features of patients with liver-related irAEs and AILD.

Ga-DOTATOC PET/CT to detect immune checkpoint inhibitor-related myocarditis.

Background: Immune checkpoint inhibitor (ICI)-related myocarditis is a rare but potentially fatal adverse event that can occur following ICI exposure. Early diagnosis and treatment are key to improve patient outcomes. Somatostatin receptor-based positron emission tomography-CT (PET/CT) showed promising results for the assessment of myocardial inflammation, yet information regarding its value for the diagnosis of ICI-related myocarditis, especially at the early stage, is limited.

[Immunotherapy for bladder cancer in 2021].

Intravesical immunotherapy with Calmette-Guerin bacillus (BCG) have been used since decades for the treatment of non-muscle invasive bladder cancer and is a proof of principle that immunotherapy works for this malignancy. Since 2016, immune checkpoint inhibitors (ICI) demonstrated clinical benefits in locally advanced or metastatic bladder cancer, providing potentially durable tumor control in first line therapy or upon relapse after standard treatments. Ongoing clinical trials aim to demonstrate the efficiency of ICI for the treatment of localized disease.

Real-life use of talimogene laherparepvec (T-VEC) in melanoma patients in centers in Austria, Switzerland and Germany.

Background: Talimogene laherparepvec (T-VEC) is a licensed therapy for use in melanoma patients of stage IIIB-IVM1a with injectable, unresectable metastatic lesions in Europe. Approval was based on the Oncovex Pivotal Trial in Melanoma study, which also included patients with distant metastases and demonstrated an overall response rate (ORR) of 40.5% and a complete response (CR) rate of 16.

Mucosal Melanoma of the Head and Neck: A Retrospective Review and Current Opinion.

Head and Neck Mucosal Melanoma (HNMM) is an uncommon malignancy that arises in decreasing order in the nasal cavity, the paranasal sinuses, and the oral cavity. Although radical surgery followed by eventual radiotherapy is acknowledged as the mainstay treatment, patients with advanced stages or multi-focal tumors benefit from new systemic therapies. We wish to share our experience with these treatments and review the current literature.

Cancer Care of Children, Adolescents and Adults With Autism Spectrum Disorders: Key Information and Strategies for Oncology Teams.

Delivering optimal cancer care to children, adolescents and adults with ASD has recently become a healthcare priority and represents a major challenge for all providers involved. In this review, and after consideration of the available evidence, we concisely deliver key information on this heterogenous group of neurodevelopmental disorders, as well as recommendations and concrete tools for the enhanced oncological care of this vulnerable population of patients.

Physical approaches to treat glioblastoma.

Purpose Of Review: Glioblastoma (GBM) patients have a poor prognosis despite the use of modern synergistic multimodal treatment strategies, with a progression-free survival estimated at 7-8 months, a median survival of 14-16 months and 5-year overall survival of 9.8%.

Recent Findings: Physical methods hold the promise to act synergistically with classical treatments to improve the outcome of GBM patients.

[Locally advanced and metastatic melanoma : novelties].

The standard of care of melanoma patients has evolved at a rapid pace with the advent of immune checkpoint inhibitors and BRAF and MEK inhibitors. ESMO guidelines were revised in September 2019 to integrate the results of recent studies that broaden the indication of these treatments to the adjuvant setting and validated new limitations to completion lymph node dissection in the case of a positive sentinel lymph node biopsy in locally advanced melanoma. We hereby detail the main novelties of the revised ESMO 2019 guidelines.

Adverse effects of immune-checkpoint inhibitors: epidemiology, management and surveillance.

Immune-checkpoint inhibitors (ICIs), including anti-cytotoxic T lymphocyte antigen 4 (CTLA-4), anti-programmed cell death 1 (PD-1) and anti-programmed cell death 1 ligand 1 (PD-L1) antibodies, are arguably the most important development in cancer therapy over the past decade. The indications for these agents continue to expand across malignancies and disease settings, thus reshaping many of the previous standard-of-care approaches and bringing new hope to patients. One of the costs of these advances is the emergence of a new spectrum of immune-related adverse events (irAEs), which are often distinctly different from the classical chemotherapy-related toxicities.

[Oncology, what's new in 2018].

The year 2018 has been incredibly prolific regarding novelties. Several studies have given impressive results and offer new anticancer perspectives. Immunotherapy is gaining more and more place defining a new standard of care for different types of cancer.

Targeting immune checkpoints in breast cancer: an update of early results.

The immune tumour microenvironment has been shown to play a crucial role in the development and progression of cancer. Expression of gene signatures, reflecting immune activation, and the presence of tumour-infiltrating lymphocytes were associated with favourable outcomes in HER2-positive and triple-negative breast cancer. Recently, immunotherapy with immune checkpoint blockade induced long-lasting responses and improved survival in hard-to-treat malignancies (ie, melanoma and non-small cell lung cancer) and are changing treatment paradigms in a variety of neoplastic diseases.