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Definitive chemoradiotherapy (CRT) has been a standard of care for patients with unresectable stage III non-small cell lung cancer (NSCLC). However, locoregional recurrence occurs in about 30% of patients after definitive CRT. Recently, the addition of durvalumab as maintenance therapy has shown to improve the outcome of these patients. However, locoregional recurrence will still remain. https://www.selleckchem.com/products/tabersonine.html "Salvage surgery" has been performed to achieve local control in clinical practice, although its clinical significance is unclear. In this review, we define salvage surgery as lung resection for local control of the tumor which was not planned initially, after failure or insufficient treatment effect of the initial CRT for locally advanced cancer and evaluated nine studies to gain some insights on its role in the treatment of lung cancer. The time from radiotherapy (RT) to salvage surgery varied considerably (range, 3 to 282 weeks). Salvage surgery was performed for persistent disease (47%) and locoregional recurrence (52%). Lobectomy (63%) and mediastinal lymph node dissections (90%) were the most common procedures. However, the rate of pneumonectomy was higher in salvage surgery (28%) compared to that in lung resection in general. The median morbidity was 41% (range, 15% to 62%) and the mortality was 4% (range, 0 to 11%) which appeared acceptable. The median recurrence-free survival and overall survival (OS) after salvage surgery ranged from 10 to 22 months and 13 to 76 months, respectively. Favorable prognostic factors of salvage surgery were longer period from RT to salvage surgery and radiological downstaging. The pathological response was also prognostic, although this information cannot be obtained preoperatively. We conclude that salvage surgery can be considered especially for those with late local recurrence or those with the metabolic response. Given the condition where phase III trials are difficult, the accumulation of real-world evidence in a prospective fashion will be necessary.Stage III non-small cell lung cancer (NSCLC) comprises a highly heterogeneous group of patients defined according to the extent and localization of disease. Patients with discrete N2 involvement identified preoperatively with resectable disease are candidates for multimodal therapy either with definitive chemoradiation therapy, induction chemotherapy, or chemoradiotherapy (CTRT) followed by surgery. Neoadjuvant chemotherapy has yielded comparable survival benefit to adjuvant chemotherapy in patients with stage II-III disease and may allow for downstaging the tumor or the lymph nodes, an earlier delivery of systemic treatment, and better compliance to systemic therapy. The use of immune checkpoint inhibitors (ICIs) as induction therapy shows encouraging activity and a favorable safety profile in patients with resectable early stage or locally advanced NSCLC. An unprecedented rate of pathological response and downstaging has been reported in single-arm clinical trials, especially when immunotherapy is combined with neoadjuvant chemotherapy. Ongoing randomized phase II/III clinical trials assessing the efficacy and safety of induction with immunotherapy plus chemotherapy have the potential to establish this therapeutic approach as a novel standard of care. These trials aim to validate pathological response as a surrogate marker of survival benefit and to demonstrate that this therapeutic strategy can improve the cure rate in patients with stage II-III NSCLC.Despite adequate treatment, 50% of stage III locally advanced inoperable non-small cell lung cancer (NSCLC) patients have a locoregional relapse. Local control on early stages on the contrary, is as high as 85-90% with stereotactic body radiotherapy (SBRT). The addition of SBRT to conventional chemoradiation or its use in monotherapy in stage III NSCLC is a novel strategy to decrease local failure that has been explored by various authors. This is a systematic review of studies using SBRT in inoperable stage III NSCLC. Search results obtained 141 articles of which only 6 original studies were pointed as relevant. Three of these studies were prospective, of which 2 were phase I dose-scalation studies and remaining 3 were retrospective. In summary, SBRT outcomes on 134 patients were included. Median dose in the SBRT treatment was 22.5 Gy in 2 to 7 fractions. Obtained global toxicity was 3.7% grade 5 and 14.17% grade 3. Dose-escalation studies proposed a 2 fraction SBRT schedule of 20-24 Gy, obtaining a 78% local control rate at 1 year and an OS of 67%. Initial improvement in local control with this innovative therapeutic strategy has led to ongoing phase II and III clinical trials that will evaluate the efficiency of SBRT in stage III NSCLC clinical scenario.Locally advanced lung cancer, defined by nodal involvement in upper mediastinal stations (N2) (stage IIIA-N2), includes a wide spectrum of patients with multiple therapeutic alternatives. Such heterogeneity is explained, at least in part, by tumor size and magnitude of mediastinal nodal involvement. In this setting, many variants can influence the prognosis, such as the specific nodal stations compromised, the burden of mediastinal disease, and the presence of skip metastasis. In the surgical field, the advent of minimally invasive techniques, including video-assisted thoracoscopic and robotic surgery, have revolutionized the management of early-stage lung cancer, but implementations of these approaches in the locally advanced setting have been erratic. This review attempts to highlight the most relevant scientific data of the surgical management of locally advanced lung cancer patients, analyzing not only the medical evidence but also the cost-effectiveness and accessibility.Stage III non-small cell lung cancer (NSCLC) includes a highly heterogeneous group of patients with differences in the extent and localization of disease. Many aspects of stage III disease are controversial. The data supporting treatment approaches are often subject to a number of limitations, due to the heterogeneous patient populations involved in the trials. Furthermore, the definition of stage III disease has changed over time, and early studies were frequently inadequately powered to detect small differences in therapeutic outcome, were not randomized, or had a limited follow-up times. Major improvements in therapy, including the use of more active chemotherapy agents and refinements in radiation and surgical techniques, also limit the interpretation of earlier clinical trials. Lastly, improvements in pretreatment staging have led to reclassification of patients with relatively minimal metastatic disease as stage IV rather than stage III, leading to an apparent increase in the overall survival of both stage III and IV patients.
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