GOECP/SEOR radiotherapy guidelines for small-cell lung cancer

Small cell lung cancer (SCLC) accounts for approximately 20% of all lung cancers. The main treatment is chemotherapy (Ch). However, the addition of radiotherapy significantly improves overall survival (OS) in patients with non-metastatic SCLC and in those with metastatic SCLC who respond to Ch. Prophylactic cranial irradiation reduces the risk of brain metastases and improves OS in both metastatic and non-metastatic patients. The 5-year OS rate in patients with limited-stage disease (non-metastatic) is slightly higher than 30%, but less than 5% in patients with extensive-stage disease (metastatic). The present clinical guidelines were developed by Spanish radiation oncologists on behalf of the Oncologic Group for the Study of Lung Cancer/Spanish Society of Radiation Oncology to provide a current review of the diagnosis, planning, and treatment of SCLC. These guidelines emphasise treatment fields, radiation techniques, fractionation, concomitant treatment, and the optimal timing of Ch and radiotherapy. Finally, we discuss the main indications for reirradiation in local recurrence.     

Metastatic hormone-sensitive prostate cancer: How should it be treated?

The number of treatment options for metastatic hormone-sensitive prostate cancer has increased substantially in recent years. The classic treatment approach for these patients—androgen-deprivation therapy alone—is now considered suboptimal. Several randomized phase III clinical trials have demonstrated significant clinical benefits—including significantly better overall survival and quality of life—for treatments that combine androgen-deprivation therapy with docetaxel, abiraterone acetate, enzalutamide, apalutamide, and/or radiotherapy to the primary tumour. As a result, these approaches are now included in treatment guidelines and considered standard of care. However, the different treatment strategies have not been directly compared, and thus treatment selection remains at the discretion of the individual physician or, ideally, a multidisciplinary team. Given the range of available treatment approaches with varying toxicity profiles, treatment selection should be individualized based on the patient’s clinical characteristics and preferences, which implies active patient participation in the decision-making process. In the present document, we discuss the changing landscape of the management of patients with metastatic hormone-sensitive prostate cancer in the context of several recently-published landmark randomized trials. In addition, we discuss several unresolved issues, including the optimal sequencing of systemic treatments and the incorporation of local treatment of the primary tumour and metastases.     

Management of oligometastatic non-small cell lung cancer patients: Current controversies and future directions

Oligometastatic non-small cell lung cancer (NSCLC) describes an intermediate stage of NSCLC between localized and widely-disseminated disease. This stage of NSCLC is characterized by a limited number of metastases and a more indolent tumor biology. Currently, the management of oligometastatic NSCLC involves radical treatment (radiotherapy or surgery) that targets the metastatic lesions and the primary tumor to achieve disease control. This approach offers the potential to achieve prolonged survival in patients who, in the past, would have only received palliative measures. The optimal therapeutic strategies for the different scenarios of oligometastatic disease (intracranial vs extracranial disease, synchronous vs metachronous) remain undefined. Given the lack of head-to-head studies comparing radiotherapy to surgery in these patients, the decision to apply surgery or radiotherapy (with or without systemic treatment) must be based on prognostic factors that allow us to classify patients. This classification will allow us to select the most appropriate therapeutic strategy on an individualized basis. In the future, the molecular or microRNA profiles will likely improve the treatment selection process. The objective of the present article is to review the most relevant scientific evidence on the management of patients with oligometastatic NSCLC, focusing on the role of radiotherapy and surgery. We also discuss areas of controversy and future directions.     

Recent developments in radiotherapy for small-cell lung cancer: a review by the Oncologic Group for the Study of Lung Cancer (Spanish Radiation Oncology Society)

Small-cell lung cancer (SCLC) accounts for 13% of all lung tumours. The standard treatment in patients with limited-stage disease is radiotherapy combined with chemotherapy. In extensive SCLC, the importance of consolidation thoracic radiotherapy in patients with a good treatment response has become increasingly recognized. In both limited and extensive disease, prophylactic cranial irradiation is recommended in patients who respond to treatment. New therapeutic approaches such as immunotherapy are being increasingly incorporated into the treatment of SCLC, although more slowly than in non-small cell lung cancer (NSCLC). Diverse radiation dose and fractionation schemes, administered in varying combinations with these new drugs, are being investigated. In the present study we review and update the role of radiotherapy in the treatment of SCLC. We also discuss the main clinical trials currently underway in order to identify future trends.     

New horizons for uncommon mutations in non-small cell lung cancer: BRAF,KRAS, RET,MET, NTRK,HER2

The 2004 discovery of EGFR mutations, followed by ALK rearrangements, ushered in a targeted therapy era for advanced non-small cell lung cancer (NSCLC). Tyrosine kinase inhibitors targeting gene alterations have substantially improved survival and quality of life for patients with NSCLC. In the last decade, rearrangements of the ROS1 oncogene have been incorporated into healthcare practice that are applicable to another small subgroup of patients who benefit from similar targeted strategies. Recent genome studies of lung adenocarcinoma have identified other possible therapeutic targets, including RET, NTRK fusions, c-MET alterations, and activating mutations in KRAS, BRAF, and HER2, all with frequencies greater than 1%. Lung cancers harbouring these genome changes can potentially be treated with agents approved for other indications or under clinical development. This review updates the therapeutic arsenal that especially targets those genes.     

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 CheckMate 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-naïve patients and patients with progressive disease after chemotherapy.     

Single-fraction stereotactic ablative body radiation therapy for primary and metastasic lung tumor: A new paradigm?

Stereotactic ablative body radiotherapy (SABR) is an effective technique comparable to surgery in terms of local control and efficacy in early stages of non-small cell lung cancer (NSCLC) and pulmonary metastasis. Several fractionation schemes have proven to be safe and effective, including the single fraction (SF) scheme. SF is an option cost-effectiveness, more convenience and comfortable for the patient and flexible in terms of its management combined with systemic treatments. The outbreak of the severe acute respiratory syndrome coronavirus 2 pandemic has driven this not new but underutilized paradigm, recommending this option to minimize patients’ visits to hospital. SF SABR already has a long experience, strong evidence and sufficient maturity to reliably evaluate outcomes in peripheral primary NSCLC and there are promising outcomes in pulmonary metastases, making it a valid treatment option; although its use in central locations, synchronous and recurrencies tumors requires more prospective safety and efficacy studies. The SABR radiobiology study, together with the combination with systemic therapies, (targeted therapies and immunotherapy) is a direction of research in both advanced disease and early stages whose future includes SF.     

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.     

Adjuvant versus early salvage radiotherapy for prostate cancer patients: Time to move on

In the management of prostate cancer , few treatments have caused as much controversy as adjuvant radiotherapy (ART) after radical prostatectomy in high-risk patients In the present article, we assess the exclusion and inclusion criteria of the 6 randomised trials and 5-year biochemical relapse-free survival and overall survival rates in order to identify the patient subgroups most likely to benefit from ART. We also evaluate treatment-related toxicity and the indications for androgen deprivation therapy . The main aim of this analysis was to determine whether the available evidence, which previously appeared to support ART, now favours early salvage radiotherapy. If so, perhaps we can finally resolve the controversy surrounding the optimal timing of postoperative radiotherapy