Project description:BackgroundLittle evidence has been generated for how best to manage patients with non-small-cell lung cancer (nsclc) presenting with rarer clinical scenarios, including oligometastases, oligoprogression, and pseudoprogression. In each of those scenarios, oncologists have to consider how best to balance efficacy with quality of life, while maximizing the duration of each line of therapy and ensuring that patients are still eligible for later options, including clinical trial enrolment.MethodsAn expert panel was convened to define the clinical questions. Using case-based presentations, consensus practice recommendations for each clinical scenario were generated through focused, evidence-based discussions.ResultsTreatment strategies and best-practice or consensus recommendations are presented, with areas of consensus and areas of uncertainty identified.ConclusionsIn each situation, treatment has to be tailored to suit the individual patient, but with the intent of extending and maximizing the use of each line of treatment, while keeping treatment options in reserve for later lines of therapy. Patient participation in clinical trials examining these issues should be encouraged.
Project description:Despite the importance of accurate disease definitions for effective management and treatment decisions, there is currently no consensus on what constitutes oligometastatic non-small-cell lung cancer (NSCLC). Predominant patterns of initial progressive disease (PD) after first-line systemic therapy have been shown to be a substantial basis for local ablative therapy (LAT) for all disease sites in patients with oligometastatic NSCLC, suggesting that these patterns could be helpful in defining synchronous oligometastatic NSCLC. Therefore, this retrospective study aimed to propose a threshold number of metastases for synchronous oligometastatic NSCLC, based on the pattern of initial PD after first-line systemic therapy. The cut-off threshold number of metastases compatible with synchronous oligometastatic NSCLC was determined using receiver operating characteristic (ROC) curve analyses of PD at the initially involved sites alone. ROC analysis of 175 patients revealed that the presence of 1-3 metastases before first-line treatment (sensitivity, 85.9%; specificity, 97.3%; area under the curve, 0.91) was compatible with oligometastatic NSCLC, therefore we divided patients into oligometastatic NSCLC and non-oligometastatic NSCLC groups. Multivariate logistic regression analyses revealed oligometastatic NSCLC to be the only independent predictor of PD at initially involved sites alone (odds ratio 165.7; P < .001). The median survival times in patients with oligometastatic or non-oligometastatic NSCLC were 23.0 and 10.9 mo (hazard ratio, 0.51; P = .002), respectively. Based on these findings, we propose synchronous oligometastatic NSCLC as 1-3 metastases in accordance with patterns of initial progression. The result of our study might be contributory to provide a common definition of synchronous oligometastatic NSCLC.
Project description:BackgroundIn the past decade, major developments have improved the survival of patients with oligometastatic non-small cell lung cancer (NSCLC). About 20% - 50% of patients with NSCLC present with oligometastases at diagnosis. For this group of patients, it seems that an increase in survival would justify aggressive local therapies. The development of minimally invasive surgery and advanced radiotherapy techniques like stereotactic body radiation therapy (SBRT) makes local control possible for selected patients with metastatic NSCLC. The advantage of SBRT over surgery is that it is a non-invasive technique, with minimum side effects, and is more suitable for fragile and elderly patients, non-candidates for surgery, or patients who refuse surgery.AimThe purpose of this review is to summarize the latest scientific evidence on the management of oligometastatic NSCLC, focusing on the role of radiotherapy.Relevance for patientsThe initial treatment recommended for patients with oligometastatic NSCLC is systemic therapy. Patients should be considered for radical treatment to both the primary tumor and oligometastases. Aggressive local therapy comprises surgery and/or definitive radiotherapy such as SRS or SBRT, and may be preceded or followed by systemic treatment. Recent clinical evidence from Phase II trials reports benefits in terms of PFS in patients with good performance status and long disease-free periods, with good response to systemic therapy, especially in EGFR wild-type tumors. Phase I and II trials have shown that radiotherapy combined with immunotherapy can improve tumor response rate and possibly overall survival. The recommendation is also to include OM patients in ongoing clinical trials.
Project description:Stage IV non-small cell lung cancer (NSCLC) accounts for 35 to 40% of newly diagnosed cases of NSCLC. The oligometastatic state-≤5 extrathoracic metastatic lesions in ≤3 organs-is present in ~25% of patients with stage IV disease and is associated with markedly improved outcomes. We retrospectively identified patients with extrathoracic oligometastatic NSCLC who underwent primary tumor resection at our institution from 2000 to 2018. Event-free survival (EFS) and overall survival (OS) were estimated using the Kaplan-Meier method. Factors associated with EFS and OS were determined using Cox regression. In total, 111 patients with oligometastatic NSCLC underwent primary tumor resection; 87 (78%) had a single metastatic lesion. Local consolidative therapy for metastases was performed in 93 patients (84%). Seventy-seven patients experienced recurrence or progression. The five-year EFS was 19% (95% confidence interval (CI), 12-29%), and the five-year OS was 36% (95% CI, 27-50%). Factors independently associated with EFS were primary tumor size (hazard ratio (HR), 1.15 (95% CI, 1.03-1.29); p = 0.014) and lymphovascular invasion (HR, 1.73 (95% CI, 1.06-2.84); p = 0.029). Factors independently associated with OS were neoadjuvant therapy (HR, 0.43 (95% CI, 0.24-0.77); p = 0.004), primary tumor size (HR, 1.18 (95% CI, 1.02-1.35); p = 0.023), pathologic nodal disease (HR, 1.83 (95% CI, 1.05-3.20); p = 0.033), and visceral-pleural invasion (HR, 1.93 (95% CI, 1.10-3.40); p = 0.022). Primary tumor resection represents an important treatment option in the multimodal management of extrathoracic oligometastatic NSCLC. Encouraging long-term survival can be achieved in carefully selected patients, including those who received neoadjuvant therapy and those with limited intrathoracic disease.
Project description: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.
Project description:In metastatic non-small cell lung cancer (NSCLC), the role of radiotherapy (RT) has been limited to palliation to alleviate the symptoms. However, with the development of advanced RT techniques, recent advances in immuno-oncology therapy targeting programmed death 1 (PD-1) and programmed death ligand 1 (PD-L1) and targeted agents for epidermal growth factor receptor (EGFR) mutation or anaplastic lymphoma kinase (ALK) translocation allowed new roles of RT in these patients. Within this metastatic population, there is a subset of patients with a limited number of sites of metastatic disease, termed as oligometastasis that can achieve long-term survival from aggressive local management. There is no consensus on the definition of oligometastasis; however, most clinical trials define oligometastasis as having 3 to 5 metastatic lesions. Recent phase II randomized clinical trials have shown that ablative RT, including stereotactic ablative body radiotherapy (SABR) and hypofractionated RT, to primary and metastatic sites improved progression-free survival (PFS) and overall survival (OS) in patients with oligometastatic NSCLC. The PEMBRO-RT study, a randomized phase II study comparing SABR prior to pembrolizumab therapy and pembrolizumab therapy alone, revealed that the addition of SABR improved the overall response, PFS, and OS in patients with advanced NSCLC. The efficacy of RT in oligometastatic lung cancer has only been studied in phase II studies; therefore, large-scale phase III studies are needed to confirm the benefit of local ablative RT in patients with oligometastatic NSCLC. Local intensified RT to primary and metastatic lesions is expected to become an important treatment paradigm in the near future in patients with metastatic lung cancer.
Project description:BackgroundLocal consolidative therapy (LCT) has emerged as a treatment option in patients with oligometastatic non-small cell lung cancer (NSCLC) undergoing chemotherapy or targeted therapy. However, the current literature lacks evidence as to whether LCT improves survival in NSCLC patients receiving immunotherapy. Our study aimed to assess whether LCT combined with pembrolizumab ± chemotherapy could improve the survival of patients with synchronous oligometastatic NSCLC.MethodsPatients with NSCLC, without EGFR or ALK genetic aberrations, who were treated with first-line pembrolizumab ± chemotherapy, were included in the study. Survival analysis of the LCT and non-LCT groups was compared.ResultsA total of 231 patients were included in the study. The median follow-up time was 15.24 months. Median progression-free survival (PFS) and overall survival (OS) of the entire cohort were 12.00 and 23.43 months, respectively. Of the 231 patients included, 76 patients received LCT combined with pembrolizumab ± chemotherapy (LCT group) while 155 patients received pembrolizumab ± chemotherapy alone (non-LCT group). Of note, the PFS of the LCT and non-LCT groups was 13.97 and 10.08 months (p = 0.016), respectively. The OS were 30.67 and 21.97 months (p = 0.011), respectively. The PFS and OS were significantly improved with LCT for patients with brain or lung metastases but not bone metastases. No significant increase in treatment-related toxicity was observed in the LCT group.ConclusionsThe present study shows that LCT to metastatic sites is an option for consideration in patients with synchronous oligometastatic NSCLC during first-line pembrolizumab treatment, with significantly improved PFS and OS compared with systemic treatment alone.
Project description:Non-small cell lung cancer (NSCLC) is an aggressive malignancy with close to half of all patients presenting with metastatic disease. A proportion of these patients with limited metastatic disease, termed oligometastatic disease, have been shown to benefit from a definitive treatment approach. Synchronous and metachronous presentation of oligometastatic disease have prognostic significance, with current belief that metachronous disease is more favorable. Surgical excision of intracranial and extracranial oligometastatic disease has been shown to improve survival, especially in patients with lymph node-negative disease, adenocarcinoma histology and smaller thoracic tumors. Definitive radiation to sites of oligometastatic disease and initial thoracic disease has also been shown to have a similar impact on survival for both intracranial and extracranial disease. Recent studies have reported on the use of targeted agents combined with ablative doses of radiation in the oligometastatic setting with promising outcomes. In this review, we present the historical and current literature describing surgical and radiation treatment options for patients with oligometastatic NSCLC.
Project description:Standard treatments for patients with metastatic non-small cell lung cancer (NSCLC) include palliative chemotherapy and radiotherapy, but with limited survival rates. With the development of improved immunotherapy and targeted therapy, NSCLC prognoses have significantly improved. In recent years, the concept of oligometastatic disease has been developed, with randomized trial data showing survival benefits from local ablation therapy (LAT) in patients with oligometastatic NSCLC (OM-NSCLC). LAT includes surgery, stereotactic ablation body radiation therapy, or thermal ablation, and is becoming an important treatment component for OM-NSCLC. However, controversy remains on specific management strategies for the condition. In this review, we gathered current randomized trial data to analyze prognostic factors affecting patient survival, and explored ideal treatment conditions for patients with OM-NSCLC with respect to long-term survival.