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 platinum- based 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.     

Deep diving in the PACIFIC: Practical issues in stage III non-small cell lung cancer to avoid shipwreck

After publication of the PACIFIC trial results, immune checkpoint inhibitor-based immunotherapy was included in the treatment algorithm of locally advanced non-small cell lung cancer (NSCLC). The PACIFIC trial demonstrated that 12 mo of durvalumab consolidation therapy after radical-intent platinum doublet chemotherapy with concomitant radiotherapy improved both progression-free survival and overall survival in patients with unresectable stage III NSCLC. This is the first treatment in decades to successfully improve survival in this clinical setting, with manageable toxicity and without deterioration in quality of life. The integration of durvalumab in the management of locally advanced NSCLC accentuates the need for multidisciplinary, coordinated decision-making among lung cancer specialists, bringing new challenges and controversies as well as important changes in clinical work routines. The aim of the present article is to review—from a practical, multidisciplinary perspective—the findings and implications of the PACIFIC trial. We evaluate the immunobiological basis of durvalumab as well as practical aspects related to programmed cell death ligand 1 determination. In addition, we comprehensively assess the efficacy and toxicity data from the PACIFIC trial and discuss the controversies and practical aspects of incorporating durvalumab into routine clinical practice. Finally, we discuss unresolved questions and future challenges. In short, the present document aims to provide clinicians with a practical guide for the application of the PACIFIC regimen in routine clinical practice.     

Stereotactic body radiation therapy: A good dance partner of oligometastatic non-small cell lung cancer to the sound of SINDAS study

The European Organization for Research on Treatment of Cancer Research published a consensus statement to establish the key criteria to define oligometastatic disease (OMD). According to those criteria, all lesions (both primary and metastatic) should be amenable to radical intent treatment with acceptable toxicity. Several retrospective studies have shown that adding local ablative therapy to the treatment of OMD improves outcomes; however, due to the diverse selection criteria and treatment strategies used in those studies, it is difficult to compare directly results to draw definitive conclusions. In recent years, prospective phase II trials, such as the SABR-COMET and "Oligomez" trials, have shown that stereotactic body radiation therapy (SBRT) improves outcomes in patients with OMD. More recently, interim results of the randomised phase 3 SINDAS trial were reported at the annual meeting of the American Society of Clinical Oncology 2020 demonstrating that upfront SBRT added to systemic treatment with tyrosine kinase inhibitors yielded a significant benefit in both progression-free survival and overall survival in patients with epidermal growth factor receptor-mutant oligometastatic non-small cell lung cancer. In the present editorial, we review the definition and historical context of advanced non-small cell lung cancer with OMD. In addition, we review the scientific evidence for local ablative therapy and SBRT and discuss the results of recently published prospective studies. We also discuss in depth the results of the SINDAS study, including the strengths and weaknesses of the study and the barriers to extrapolating these results to routine clinical practice.     

Practice change in the management of metastatic urothelial carcinoma after ASCO 2020

Metastatic urothelial carcinoma (mUC) is an incurable and aggressive disease. In the past decades there have been few effective treatment options that have impacted the prognosis of mUC patients. However, in the last few years, several drugs have emerged as new treatment choices that are changing the therapeutic landscape of mUC. Immune checkpoint inhibitors (ICIs) and targeted agents are useful treatment strategies that have been incorporated into our clinical practice. Nevertheless, cisplatin-based chemotherapy is still the standard of care in the first-line of metastatic disease. The results of the JAVELIN Bladder 100 phase 3 trial were presented at ASCO 2020, this trial evaluated the role of avelumab, an ICI, as maintenance therapy in patients who had not progressed after first-line platinum-based chemotherapy. The trial met its primary endpoint demonstrating an overall survival benefit with avelumab maintenance. In addition, new drugs and combinations are being evaluated to improve the outcomes of second and subsequent lines. Fibroblast growth factor receptor (FGFR) inhibitors and immunotherapy combinations were some of the strategies presented at ASCO 2020 that have shown promising results. Finally, the development of predictive biomarkers that help us in the decision-making process will be one of the most important challenges in the next years.     

Clinical features and radiological manifestations of COVID-19 disease

Coronavirus disease 2019 (COVID-19) was discovered after unusual cases of severe pneumonia emerged in December 2019 in Wuhan Province (China). Coronavirus is a family of single-stranded RNA viruses. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is transmitted from person to person. Although asymptomatic individuals can transmit the virus, symptomatic patients are more contagious. The incubation period ranges from 3-7 d and symptoms are mainly respiratory, including pneumonia or pulmonary embolism in severe cases. Elevated serum levels of interleukins (IL)-2, IL-6, IL-7 indicate the presence of cytokine release syndrome, which is associated with disease severity. The disease has three main phases: Viral infection, pulmonary involvement, and hyperinflammation. To date, no treatment has proved to be safe or effective. Chest X-ray and computed tomography (CT) are the primary imaging tests for diagnosis of SARS-CoV-2 pneumonia, follow-up, and detection of complications. The main radiological findings are ground-glass opacification and areas of consolidation. The long-term clinical course is unknown, although some patients may develop pulmonary fibrosis. Positron emission tomography-computed tomography (PET-CT) is useful to assess pulmonary involvement, to define the affected areas, and to assess treatment response. The pathophysiology and clinical course of COVID-19 infection remain poorly understood. However, patterns detected on CT and PET-CT may help to diagnose and guide treatment. In this mini review, we analyze the clinical manifestations and radiological findings of COVID-19 infection.     

New challenges in the combination of radiotherapy and immunotherapy in non-small cell lung cancer

Immunotherapy has represented one of the main medical revolutions of recent decades, and is currently a consolidated treatment for different types of tumors at different stages and scenarios, and is present in a multitude of clinical trials. One of the diseases in which it is most developed is non-small cell lung cancer. The combination of radiotherapy and immunotherapy in cancer in general and lung cancer in particular currently represents one of the main focuses of basic and clinical research in oncology, due to the synergy of this interaction, which can improve tumor response, resulting in improved survival and disease control. In this review we present the biochemical and molecular basis of the interaction between radiotherapy and immunotherapy. We also present the current clinical status of this interaction in each of the stages and cases of non-small cell lung cancer, with the main results obtained in the different studies both in terms of tumor response and survival as well as toxicity. Finally, we mention the main studies underway and the challenges of this interaction in the coming years, including how these treatments should be combined to achieve the greatest efficacy with the fewest possible side effects (dose, type of radiotherapy and drugs, sequence of treatments).     

GOECP/SEOR radiotheraphy guidelines for non-small-cell lung cancer

Non-small cell lung cancer (NSCLC) is a heterogeneous disease accounting for approximately 85% of all lung cancers. Only 17% of patients are diagnosed at an early stage. Treatment is multidisciplinary and radiotherapy plays a key role in all stages of the disease. More than 50% of patients with NSCLC are treated with radiotherapy (curative-intent or palliative). Technological advances-including highly conformal radiotherapy techniques, new immobilization and respiratory control systems, and precision image verification systems-allow clinicians to individualize treatment to maximize tumor control while minimizing treatment-related toxicity. Novel therapeutic regimens such as moderate hypofractionation and advanced techniques such as stereotactic body radiotherapy (SBRT) have reduced the number of radiotherapy sessions. The integration of SBRT into routine clinical practice has radically altered treatment of early-stage disease. SBRT also plays an increasingly important role in oligometastatic disease. The aim of the present guidelines is to review the role of radiotherapy in the treatment of localized, locally-advanced, and metastatic NSCLC. We review the main radiotherapy techniques and clarify the role of radiotherapy in routine clinical practice. These guidelines are based on the best available evidence. The level and grade of evidence supporting each recommendation is provided.     

Is hypofractionation acceptable for prostate bed radiotherapy?

Approximately 30% of patients who undergo radical prostatectomy for prostate cancer develop disease progression. The only potentially curative treatment in these patients is postoperative radiotherapy with or without hormonotherapy. One of the standards of care in nonsurgical patients is hypofractionated radiotherapy. However, the current evidence based is insufficient to define the optimal dose and fractionation schedule for postoperative radiotherapy. In this context, the aim of this editorial is to assess the main efficacy and toxicity data for postoperative hypofractionated radiotherapy and discuss the potential to implement this fractionation in routine clinical practice.     

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.