Neoadjuvant treatment in non-small cell lung cancer:New perspectives with the incorporation of immunotherapy

The aim of neoadjuvant treatment in non-small cell lung cancer(NSCLC)is to eliminate micrometastatic disease to facilitate surgical resection.Neoadjuvant chemotherapy(ChT)in localised NSCLC has numerous advantages over other therapeutic modalities and is considered standard treatment in resectable disease.Treatment with immune checkpoint inhibitors(ICI)improves long-term survival in advanced disease and has a better toxicity profile than conventional therapies.These immunotherapy agents(anti-PD1/PD-L1),administered with or without ChT,are currently being evaluated in the preoperative setting,with initial results showing better pathological response rates and more long-term benefits.Importantly,these drugs do not appear to increase the rate of severe adverse effects and/or postoperative complications.However,several questions still need to be resolved,including the identification of predictive biomarkers;comparative studies of immunotherapy alone vs combined treatment with ChT and/or radiotherapy;the optimal duration of treatment;the timing of surgery;the need for adjuvant treatment;appropriate radiologic evaluation and mediastinal staging;and the correlation between pathological response and survival outcomes.Here we review the current evidence for immunotherapy from a multidisciplinary perspective and discuss current and future controversies.

Recent advances and new insights in the management of early-stage epidermal growth factor receptor-mutated non-small-cell lung cancer

Patients with early-stage non-small-cell lung cancer(NSCLC)are candidates for curative surgery;however,despite multiple advances in lung cancer management,recurrence rates remain high.Adjuvant chemotherapy has been demonstrated to significantly prolong overall survival(OS),but this benefit is modest and there is an urgent need for effective new therapies to provide a cure for more patients.The high efficacy of tyrosine kinase inhibitors(TKIs)against epidermal growth factor receptor-mutated(EGFR)in patients with advanced EGFR-mutated NSCLC has led to the evaluation of these agents in early stages of the disease.Multiple clinical trials have evaluated the safety and efficacy of EGFR TKIs as an adjuvant treatment,in patients with resected EGFR-mutated NSCLC,and shown that they significantly prolong disease-free survival(DFS),but this benefit does not translate to OS.Recently,an interim analysis of the ADAURA trial demonstrated that,surprisingly,osimertinib improved DFS.This led to the study being stopped early,leaving many unanswered questions about its potential effect on OS and its incorporation as a standard adjuvant treatment in this patient subgroup.These targeted agents are also being evaluated in locally-advanced disease,with promising results,although prospective studies with larger sample sizes are needed to confirm these results.In this article,we review the most relevant studies on the role of EGFR TKIs in the management of early-stage EGFR-mutated NSCLC.

Advances and controversies in the management of early stage nonsmall cell lung cancer

Complete resection continues to be the gold standard for the treatment of earlystage lung cancer.The landmark Lung Cancer Study Group trial in 1995 established lobectomy as the minimum intervention necessary for the management of early-stage non-small cell lung cancer,as it was associated with lower recurrence and metastasis rates than sublobar resection and lower postoperative morbidity and mortality than pneumonectomy.There is a growing tendency to perform sublobar resection in selected cases,as,depending on factors such as tumor size,histologic subtype,lymph node involvement,and resection margins,it can produce similar oncological results to lobectomy.Alternative treatments such as stereotactic body radiotherapy and radiofrequency ablation can also produce good outcomes in inoperable patients or patients who refuse surgery.

Tsunami of immunotherapy reaches mesothelioma

Malignant pleural mesothelioma(MPM) is the most common type of malignant mesothelioma. It is a rare tumor linked to asbestos exposure and is associated with a poor prognosis. Until very recently, patients with advanced or unresectable disease had limited treatment options, primarily based on doublet chemotherapy with cisplatin and pemetrexed. In 2020 and 2021, after more than a decade with no major advances or new drugs, two phase Ⅲ clinical trials published results positioning immunotherapy as a promising option for the first-and second-line treatment of MPM. Immunotherapy has revolutionized the treatment of many cancers and is also showing encouraging results in malignant mesothelioma. Both immune checkpoint inhibition and dual cytotoxic T-lymphocyte–associated antigen 4 and programmed death-ligand 1 pathway blockade resulted in significantly improved overall survival in randomized phase Ⅲ trials. In the Check Mate 743 trial, first-line therapy with nivolumab plus ipilimumab outperformed standard chemotherapy, while in the CONFIRM trial, nivolumab outperformed placebo in patients previously treated with chemotherapy. These two trials represent a major milestone in the treatment of MPM and are set to position immunotherapy as a viable alternative for treatment-naive patients and patients with progressive disease after chemotherapy.

Immunotherapy combinations and chemotherapy sparing schemes in first line non-small cell lung cancer

In recent years,studies have explored different combinations of immunotherapy and chemotherapy.The rationale behind these is the improved survival outcomes of new immunologic therapies used in first-line-treatment of advanced non-small cell lung cancer.Moreover,for the most-studied combinations of anti-programed death-1(PD-1)/programed death ligand-1(PD-L1)with the addition of platinumbased chemotherapy,recent research is investigating whether combining different immunologic antitumoral mechanisms of action,such as anti-PD-1/PD-L1 and anti-CTLA-4,or anti-PD-L1 and anti-TIGIT,with or without chemotherapy,can improve efficacy outcomes compared with more classical combinations,or compared with standard chemotherapy alone.Here,we present the data of the main randomized studies that have evaluated these combinations,focusing on the basic rationale behind the different combinations,and the efficacy and tolerability data available to date.

Lung cancer screening, what has changed after the latest evidence?

Lung cancer(LC)is still one of the most frequent cancers with a high related mortality.Their prognosis is directly proportional to the stage at the time of diagnosis.Seventy percent are currently diagnosed in advanced or locally advanced stage(higher than stage III),making a cure unlikely for the majority of patients.Developments in LC treatment are significant however they do not seem to be enough to reverse the current situation,at least,in a short period of time.Despite recent advances in treatment,primary prevention and early diagnosis appear to be the key to reduce the incidence and mortality of this disease.Many countries have developed LC screening programs based on the results of clinical trials published in recent years.The aim of this paper is to review the latest results of the NEderlands Leuvens Longkanker Screenings Onderzoek and compare them with the findings of the National Lung Screening Trial.We address the question whether it is necessary to continue discussing the evidence regarding LC screening.In both trials,there is a clear impact on LC mortality but,with a modest reduction in over all mortality.Undoubtedly,the benefit of screening can be expected to grow as low-dose computed tomographys are performed over longer periods of time.

Current treatment landscape for oligometastatic non-small cell lung cancer

The management of patients with advanced non-small cell lung carcinoma(NSCLC)has undergone major changes in recent years.On the one hand,improved sensitivity of diagnostic tests,both radiological and endoscopic,has altered the way patients are staged.On the other hand,the arrival of new drugs with antitumoral activity,such as targeted therapies or immunotherapy,has changed the prognosis of patients,improving disease control and prolonging survival.Finally,the development of radiotherapy and surgical and interventional radiology techniques means that radical ablative treatments can be performed on metastases in any location in the body.All of these advances have impacted the treatment of patients with advanced lung cancer,especially in a subgroup of these patients in which all of these treatment modalities converge.This poses a challenge for physicians who must decide upon the best treatment strategy for each patient,without solid evidence for one optimal mode of treatment in this patient population.The aim of this article is to review,from a practical and multidisciplinary perspective,published evidence on the management of oligometastatic NSCLC patients.We evaluate the different alternatives for radical ablative treatments,the role of primary tumor resection or radiation,the impact of systemic treatments,and the therapeutic sequence.In short,the present document aims to provide clinicians with a practical guide for the treatment of oligometastatic patients in routine clinical practice.

Lung Adenocarcinoma Presenting as a Bleeding Sternal Mass

A 53-year-old man with bleeding from a sternal mass associated with a toxic syndrome. Computed tomography (CT) revealed a destructive sternal mass, bilateral pleural effusion and an endobronchial lesion in the right middle lobe bronchus. Immunohistopathological study of an incisional biopsy confirmed metastasic lung adenocarcinoma.