Locally advanced NSCLC is a heterogenous group of bronchogenic malignancies that are traditionally thought to be unresectable without overt distant metastasis or malignant pleural effusion. The mainstay of treatment for this class of diseases until the early 1990s was radiation alone, which resulted in a dismal outcome. The new technologies in radiation therapy (e.g. 3D-CRT) and the shift in paradigm (e.g. omission of ENI) have enabled the dose-escalation, which translated to improved outcome compared to the conventional radiotherapy using 2-D planning. The trials combining chemotherapy with radiotherapy, first sequentially, then concurrently, have changed the standard of care for patients with good functional status to concurrent chemoradiation. Some studies have shown survival benefits to adding consolidative systemic therapy with concurrent chemoradiation. We will outline the development of the current treatment standard of locally advanced NSCLC and present selected topics undergoing active research to forecast the next generation of NSCLC therapy
Carcinoma, Non-Small-Cell Lung* ; Drug Therapy ; Humans ; Neoplasm Metastasis ; Pleural Effusion, Malignant ; Radiotherapy ; Standard of Care

Locally advanced Non-small cell lung cancer (NSCLC) is a commonly encountered diagnosis. Historically the treatment of locally advanced NSCLC has involved radiation therapy. Clinical trials have shown a benefit to the addition of chemotherapy. In recent years studies have further defined the role of chemotherapy by provided data showing the benefit of concurrent chemotherapy and radiation therapy followed by consolidation with more chemotherapy. Technological advances in radiation therapy have made dose escalation feasible and the current treatment paradigm is now evolving further as dose escalation data becomes available.
Carcinoma, Non-Small-Cell Lung ; Combined Modality Therapy

Locally advanced non-small cell lung cancer (NSCLC) is a heterogeneous disease, and we have embarked on an era where patients will benefit from individualized therapeutic strategies based on identifiable molecular characteristics of the tumor. The landmark studies demonstrating the importance of molecular characterization of tumors for NSCLC patients, the promising molecular pathways, and the potential molecular targets/agents for treatment of this disease will be reviewed. Understanding these issues will aid in the development of rationally designed clinical trials, so as to determine best means of appropriately incorporating these molecular strategies, to the current standard of radiation and chemotherapy regimens, for the treatment of locally advanced NSCLC.
Carcinoma, Non-Small-Cell Lung ; Combined Modality Therapy ; Humans ; Precision Medicine ; Lung Neoplasms ; Receptor, Epidermal Growth Factor

The majority of non-small cell lung cancer patients present with locally advanced disease that may not be resectable. A single modality treatment such as thoracic radiotherapy often results in an inferior outcome when compared to combined modality treatment. Various combinations of radiotherapy, chemotherapy, and surgery have been tested in patients with locally advanced non-small-celllung cancer with promising results. The favorable results of the combined modality treatment are accompanied by a corresponding increase in treatment related morbidity. In this article, the results of the application of combined modality treatments in the management of locally advanced non-small cell lung cancer are reviewed.
Carcinoma, Non-Small-Cell Lung* ; Combined Modality Therapy* ; Drug Therapy ; Humans ; Radiotherapy