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How to optimize the incorporation of immunotherapy in trials for oligometastatic non-small cell lung cancer: a narrative review.

ABSTRACT: Patients with oligometastatic disease (OMD) non-small cell lung cancer (NSCLC) are considered as a subgroup of metastatic NSCLC that can obtain long-term survival or even cure. Oligometastatic refers to a state of a limited number of metastases in a limited number of organs. In clinical guidelines it is stated that patients with oligometastatic NSCLC can benefit from the addition of local radical therapy (LRT) to systemic therapy. With the introduction of minimally invasive surgery, advances in interventional radiology and stereotactic radiotherapy (SRT), LRT is becoming feasible for more and more patients. Furthermore, the introduction of immune checkpoint inhibitors (ICI) in the treatment landscape of advanced NSCLC has improved the survival of these patients. Importantly, the use of ICI in combination with LRT is also of interest in the subgroup of NSCLC patients with OMD. For example, it has been suggested that SRT may synergize with ICI as several preclinical studies reported an increased tumor antigen release, improved antigen presentation, and T-cell infiltration in irradiated tumors. In this narrative review, we describe the current evidence of immunotherapy treatment in OMD NSCLC, with a focus on future trial design and problems that need to be addressed.

SUBMITTER: Remon J

PROVIDER: S-EPMC8350101 | biostudies-literature | 2021 Jul

REPOSITORIES: biostudies-literature

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How to optimize the incorporation of immunotherapy in trials for oligometastatic non-small cell lung cancer: a narrative review.

Remon Jordi J Menis Jessica J Levy Antonin A De Ruysscher Dirk K M DKM Hendriks Lizza E L LEL

Translational lung cancer research 20210701 7

Patients with oligometastatic disease (OMD) non-small cell lung cancer (NSCLC) are considered as a subgroup of metastatic NSCLC that can obtain long-term survival or even cure. Oligometastatic refers to a state of a limited number of metastases in a limited number of organs. In clinical guidelines it is stated that patients with oligometastatic NSCLC can benefit from the addition of local radical therapy (LRT) to systemic therapy. With the introduction of minimally invasive surgery, advances in ...[more]

PMID: 34430382

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Project description:Background and objectiveRole of radiotherapy (RT) in the era of immuno-oncology (IO) in advanced non-small cell lung cancer (NSCLC) is rapidly changing. RT is not only intended for addressing palliation symptoms but also is considered as a potential tool potentializing an immunogenic effect of given drugs. However, the best timing, techniques, doses, volumes, and its use for asymptomatic patients is a subject of research. We performed a review on the role of palliative RT schedules in combination with IO for advanced NSCLC. Indications in symptomatic and asymptomatic patients, outcomes, toxicity, and possible developments are discussed.MethodsA literature search was conducted in MEDLINE and PubMed databases and clinicaltrials.gov using the keywords 'lung cancer' AND "immunotherapy" AND 'radiotherapy' OR "palliative radiotherapy".Key content and findingsBody of evidence indicate that palliative RT used in combination with IO is effective in terms of symptom management and safe; does not increase the risk of serious side effects, including serious pulmonary toxicity. We have limited data evidencing improvement of survival by addition of short ablative RT dose to one site of the disease to IO in oligometastatic NSCLC. Some data indicate that short ablative doses of stereotactic body radiation therapy (SBRT) are more effective with regard to treatment response and survival than protracted RT schedule with lower fractional doses. However, this may be a selection bias of better prognostic patients who underwent SBRT. The use of steroids being a potential concern during IO should not be prohibited if clinically indicated during palliative RT. Its detrimental effect shown in some studies may also be a result of selection bias, because steroids given for not cancer-related causes during IO did not decrease survival.ConclusionsRT for symptom management may be used during, directly before or after IO. This has a potential to ease symptom burdens and improve performance status (PS). However, still more studies are needed to establish optimal guidelines in asymptomatic patients for appropriate timing, volumes, dose, and fractionation schedules of palliative RT use in combination with IO.

Project description:Background and objectiveImmune checkpoint inhibitors and immunotherapy have been shown to improve survival rates, especially in non-small cell lung cancer (NSCLC) patients. More recently, several trials have evaluated the clinical roles of immunotherapy as neoadjuvant settings for NSCLC. There trials suggested that neoadjuvant immunotherapy may effectively reduce the risk of the local recurrence and metastasis of cancer, and significantly improved overall survival and cure rates. Here we conducted a review to summarize the possible mechanism, clinical development, and research progress of neoadjuvant immunotherapy in NSCLC.MethodsRelevant articles for this review were retrieved from Google Scholar, Clinicaltrials.gov., and PubMed using the terms "non-small-cell lung cancer", "NSCLC", "neoadjuvant", "immunotherapy", "immune checkpoint inhibitors", "mechanisms", and "toxicity". The primary focus was placed on clinical studies and conference abstracts measuring the safety and efficacy of neoadjuvant immunotherapy in NSCLC until May 2022.Key content and findingsAfter reviewing the preclinical and clinical trial, the preclinical study showed that neoadjuvant immune checkpoint inhibitor promotes antitumor immunity through the enhancement of T cell effector function and the induction of long-term memory. The initial results of preliminary early-phase trials suggested that neoadjuvant immunotherapy is a promising therapeutic strategy for resectable NSCLC patients, with long-term response and modest toxicity, many of these regimens are currently being evaluated by randomized phase III trials. In addition, the major pathologic response of neoadjuvant immunotherapy ranged up to 45% in these studies when used alone, and up to around 83-86% when used in combination with chemotherapy, therefore it has been seen as a rather potent tumor debulking agent.ConclusionsNeoadjuvant immunotherapy has been shown to be a novel integral component of NSCLC care. However, there are also several research questions that requires further investigation, such as the side effects, the optimally treated patients, and the time of preoperative immunotherapy.

Project description:ObjectiveIn this review, we aim to collect and discuss available data about the role and composition of tumor microenvironment (TME) in oligometastatic (OMD) and oligoprogressive (OPD) non-small cell lung cancer (NSCLC). Furthermore, we aim to summarize the ongoing clinical trials evaluating as exploratory objective the TME composition, through tissue and/or blood samples, in order to clarify whether TME and its components could explain, at least partially, the oligometastatic/oligoprogressive process and could unravel the existence of predictive and/or prognostic factors for local ablative therapy (LAT).BackgroundOMD/OPD NSCLC represent a heterogeneous group of diseases. Several data have shown that TME plays an important role in tumor progression and therefore in treatment response. The crucial role of several types of cells and molecules such as immune cells, cytokines, integrins, protease and adhesion molecules, tumor-associated macrophages (TAMs) and mesenchymal stem cells (MSCs) has been widely established. Due to the peculiar activation of specific pathways and expression of adhesion molecules, metastatic cells seem to show a tropism for specific anatomic sites (the so-called "seed and soil" hypothesis). Based on this theory, metastases appear as a biologically driven process rather than a random release of cancer cells. Although the role and the function of TME at the time of progression in patients with NSCLC treated with tyrosine-kinase inhibitors and immune checkpoint inhibitors (ICIs) have been investigated, limited data about the role and the biological meaning of TME are available in the specific OMD/OPD setting.MethodsThrough a comprehensive PubMed and ClinicalTrials.gov search, we identified available and ongoing studies exploring the role of TME in oligometastatic/oligoprogressive NSCLC.ConclusionsDeepening the knowledge on TME composition and function in OMD/OPD may provide innovative implications in terms of both prognosis and prediction of outcome in particular from local treatments, paving the way for future investigations of personalized approaches in both advanced and early disease settings.

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How to optimize the incorporation of immunotherapy in trials for oligometastatic non-small cell lung cancer: a narrative review.

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How to optimize the incorporation of immunotherapy in trials for oligometastatic non-small cell lung cancer: a narrative review.

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