• EGFR-TKIs
• Non-small cell lung cancer (NSCLC)
• Overall survival
• Primary tumor radiotherapy
• Time

• Humans
• Carcinoma, Non-Small-Cell Lung/radiotherapy
• Carcinoma, Non-Small-Cell Lung/mortality
• Carcinoma, Non-Small-Cell Lung/drug therapy
• Carcinoma, Non-Small-Cell Lung/pathology
• Female
• Male
• Lung Neoplasms/radiotherapy
• Lung Neoplasms/mortality
• Lung Neoplasms/drug therapy
• Lung Neoplasms/pathology
• Lung Neoplasms/therapy
• ErbB Receptors/antagonists & inhibitors
• Aged
• Middle Aged
• Protein Kinase Inhibitors/therapeutic use
• Adult
• Aged, 80 and over
• Kaplan-Meier Estimate
• Retrospective Studies
• Survival Rate
• Time-to-Treatment

• [Qiankehe support (2019) 2795] Guizhou Science and Technology Plan Support Project

• driver gene negative
• metastatic non-small cell lung cancer
• survival
• thoracic radiotherapy
• timing

• Humans
• Lung Neoplasms/genetics
• Lung Neoplasms/radiotherapy
• Small Cell Lung Carcinoma/pathology
• Carcinoma, Non-Small-Cell Lung/genetics
• Carcinoma, Non-Small-Cell Lung/radiotherapy
• Carcinoma, Non-Small-Cell Lung/pathology
• Retrospective Studies
• Treatment Outcome
• Neoplasm Staging

• 320.6750.2020-02-53 Wu Jieping Medical Foundation
• 81972864 National Natural Science Foundation of China
• 82172720 National Natural Science Foundation of China
• ZR2020LZL018 Natural Science Foundation of Shandong Province
• 2-26 Health Field Research Program
• 81972864 Wu Jieping Medical Foundation
• 82172720 Wu Jieping Medical Foundation
• ZR2020LZL018 Wu Jieping Medical Foundation

• Humans
• Carcinoma, Non-Small-Cell Lung/radiotherapy
• Carcinoma, Non-Small-Cell Lung/pathology
• Lung Neoplasms/radiotherapy
• Lung Neoplasms/pathology
• Medical Oncology
• Radiation Oncology/methods
• Radiosurgery/methods
• United States

• ALK-positive (ALK-P)
• EGFR-mutant (EGFR-M)
• malignant pleural effusion (MPE)
• non-small-cell lung cancer (NSCLC)
• overall survival (OS)
• thoracic tumor radiotherapy

• Humans
• Carcinoma, Non-Small-Cell Lung/complications
• Carcinoma, Non-Small-Cell Lung/radiotherapy
• Lung Neoplasms/complications
• Lung Neoplasms/radiotherapy
• Pleural Effusion, Malignant/etiology
• Pleural Effusion, Malignant/drug therapy
• Propensity Score
• ErbB Receptors

• failure pattern
• malignant pleural effusion
• non-small cell lung cancer
• radiotherapy
• targeted therapy

• Humans
• Carcinoma, Non-Small-Cell Lung/drug therapy
• Lung Neoplasms/drug therapy
• Immune Checkpoint Inhibitors/adverse effects
• Chemoradiotherapy/adverse effects
• Combined Modality Therapy

• non-small-cell lung cancer
• targeted therapies

• Humans
• Carcinoma, Non-Small-Cell Lung/drug therapy
• Carcinoma, Non-Small-Cell Lung/genetics
• Carcinoma, Non-Small-Cell Lung/surgery
• Lung Neoplasms/drug therapy
• Lung Neoplasms/genetics
• Lung Neoplasms/surgery
• Cohort Studies
• Retrospective Studies
• Mutation
• Protein Kinase Inhibitors
• ErbB Receptors/metabolism

• local ablation therapy
• non-small cell lung cance
• oligometastasis
• radiation therapy
• stereotactic ablation body radiation therapy
• treatment conditions

• locoregional treatment
• metastatic cancer
• oligometastatic cancer
• primary tumor
• radiotherapy

• controlled malignant pleural effusion
• non-small cell lung cancer
• overall survival
• prognosis
• radiotherapy

• no financial support/funding

• non-small-cell lung cancer
• recurrence
• radiotherapy
• surgery

• Humans
• Carcinoma, Non-Small-Cell Lung/pathology
• Retrospective Studies
• Lung Neoplasms/pathology
• Progression-Free Survival
• Radiosurgery/methods

• Non-small cell lung cancer
• brain metastasis
• immune checkpoint inhibitor
• oligo-metastasis
• radiotherapy

• P30 CA008748 NCI NIH HHS

The incidence of metastatic squamous cell carcinoma of the anus (SCCA) is increasing. Even if systemic docetaxel, cisplatin, and 5-Fluorouracil (DCF) provide a high rate of long-term remission, the role of pelvic chemoradiation (CRT) is unknown in this setting. We reported the safety and efficacy of local CRT in patients with synchronous metastatic SCCA who achieved objective response after upfront DCF.

Patients included in Epitopes HPV01 or Epitopes HPV02 or SCARCE trials and treated with DCF followed by pelvic CRT were included. Concurrent chemotherapy was based on mitomycin (MMC) (10 mg/m² for two cycles) and fluoropyrimidine (capecitabine 825 mg/m² twice a day at each RT treatment day or two cycles of intra-venous 5FU 1000 mg/m² from day 1 to day 4). Primary endpoints were safety, local complete response rate, and local progression-free survival (PFS). Secondary endpoints were PFS, overall survival (OS), and metastasis-free survival (MFS).

From 2013 to 2018, 16 patients received DCF followed by a complementary pelvic CRT for advanced SCCA. Median follow-up was 42 months [range, 11-71]. All patients received the complete radiation dose. Compliance to concurrent CT was poor. Overall, 13/15 of the patients (87%) had at least one grade 1-2 acute toxicity and 11/15 of the patients (73%) had at least one grade 3-4 toxicity. There was no treatment-related death. The most frequent grade 3-4 adverse effects were neutropenia (36%), dermatitis (40%), and anitis (47%). Eleven patients (73%) had at least one chronic grade 1 or 2 toxicity. One patient had a grade 4 chronic rectitis (7%). Complete local response rate was 81% at first evaluation and 62.5% at the end of the follow-up. Median local PFS was not reached and the 3-year local PFS was 77% (95%CI 76.8-77).

In patients with metastatic SCCA who had a significant objective response after upfront DCF, local CRT was feasible with high complete local response rate. The good local control rate, despite interruptions due to toxicities and low CT compliance, underline the role of pelvic RT. The high rate of toxicity prompts the need to adapt CRT regimen in the metastatic setting.

• NSCLC
• SABR
• SRS
• ablative treatment
• non-oncogene addicted NSCLC
• oligometastatic disease

• Lung cancer
• Lung metastases
• Non-small cell lung cancer
• Radiosurgery
• Stereotactic body radiotherapy
• Sterotactic ablative body radiotherapy

• SBRT
• metastasis directed therapy
• oligometastasis
• oligometastatic disease
• radiotherapy

• bone metastases
• lung surgery
• oligometastatic NSCLC
• oncological outcomes
• radiotherapy

• biomarkers
• naïve CD8+ T cells
• oligometastasis
• radiotherapy

• Carcinoma, Non-Small-Cell Lung/radiotherapy
• Humans
• Lung Neoplasms/pathology
• Radiosurgery/methods
• Radium/therapeutic use

The historical standard treatment of metastatic non-small cell lung cancer (NSCLC) consisted of palliative chemotherapy, with limited influence on survival. With the introduction of immuno- and targeted therapy, the prognosis improved largely. A subset of NSCLC patients with limited metastatic disease, called oligometastatic, might obtain long-term survival by adding a local ablative treatment on all visible disease sites, in addition to the standard systemic treatment. The evidence for this combined treatment is still scarce and comes mainly from the pre-immunotherapy era. As radiotherapy might stimulate the immune system making immunotherapy more efficient, here we review the evidence before and in the era of immunotherapy, and discuss the challenges and prospects of the combined treatment.

Oligometastatic cancer is recognized as a separate entity within the spectrum of metastatic disease. It was suggested that patients with oligometastatic disease can obtain long-term survival by giving local ablative therapy (LAT) to all visible disease locations. However, the true extent from which metastatic cancer should be called “oligometastatic” is unknown, although a consensus definition for oligometastatic disease is proposed by research organizations, such as the EORTC (maximum of five metastases in three organs). Different states of the oligometastatic disease are defined, such as synchronous vs. metachronous, oligopersistent vs. oligoprogressive disease. All clinical trials including patients with non-small cell lung cancer (NSCLC) are small and most are not randomized. Two small randomized phase II trials on synchronous disease showed an improvement in progression free survival, with the addition of LAT, and one also demonstrated an overall survival benefit. Immune checkpoint inhibitors (ICI) were not part of the treatment in these trials, while ICI significantly improved long-term outcomes of patients with metastatic NSCLC. Radiotherapy might improve the prognosis of patients treated with ICI because of its immunostimulatory effects and the possibility to eradicate metastatic deposits. Here, we summarize the data for adding ablative radiotherapy to the treatment of oligometastatic NSCLC, especially in the ICI era, and discuss the challenges of combined treatment.

• immune checkpoint inhibitor
• immunotherapy
• non-small cell lung cancer
• oligometastatic
• radiotherapy

The study aimed to assess the efficacy and safety of stereotactic body radiotherapy (SBRT) using CyberKnife (CK) in patients with postoperative thoracic oligo-recurrence/metastasis of non-small-cell lung cancer (NLCLC), and to analyze the prognostic factors affecting overall survival after SBRT.

A total of 44 patients with postoperative thoracic oligo-recurrence/metastatic of NLCLC treated with SBRT were reviewed. Thoracic oligo-recurrence/was defined as 1–3 loco-regional confined to lung lobe, hilar/mediastinal lymph nodes, bronchial stump, or chest wall. Primary endpoints included local control (LC), overall survival (OS), progression-free survival (PFS) and toxicity. Prognostic factors that affected these patients were analyzed by the univariate and multivariate analysis by Kaplan–Meier methods and Cox regression models, respectively.

The median follow-up time after salvage SBRT was 48.5 months. Measuring from the date of salvage SBRT, the median OS of the 44 patients was 52.60 (95% CI: 29.59–75.60) months. 1-,3-and 5-year OS rates were 97.7%, 65.3% and 47.7%, respectively. The 1-,3-year and 5-year LC rates were 97.7%, 85.1% and 80.1%, respectively. At 1, 3 and 5 years, the PFS rates were 77.1%, 28.8% and 5.3%, respectively. Multivariate analysis demonstrated that pre-SBRT neutrophil-to-lymphocyte ratio (NLR) and Charlson comorbidity index (CCI) were independent prognostic factors (p < 0.05). The treatment-related side-effects were well tolerated. No patients developed grade 3 or greater pulmonary toxicity.

SBRT is a promising salvage therapeutic option for postoperative thoracic oligo-recurrence/metastasis of non-small-cell lung cancer with acceptable toxicity. Low pre-SBRT neutrophil-to-lymphocyte ratio (NLR) and low Charlson comorbidity index (CCI) were associated with a better prognosis and longer survival and might be considered as reliable and independent prognostic factors in these patients treated with SBRT.

• CyberKnife
• NSCLC
• oligo-recurrence
• post-surgical recurrence

Radiotherapy, along with other loco-regional interventions, is conventionally utilized as a palliative approach to alleviate symptoms and mitigate oncological emergencies in advanced non-small cell lung cancer (NSCLC). Thanks to the ongoing improvement of medical treatments in the last decade, such as targeted therapy and immunotherapy, the survival of patients with advanced NSCLC has been considerably prolonged, making it feasible and clinically beneficial for radiotherapy to play a more active role in highly selected subpopulations. In this review, we will focus on the evolving roles of radiotherapy in advanced NSCLC. First of all, among patients who are initially unable to tolerate aggressive treatment due to severe symptoms caused by metastases and/or tumor emergencies, timely radiotherapy could significantly improve their performance status (PS) and general condition, thus giving them a chance for intensive treatment and prolonged survival. The efficacy, potential candidates, and optimal dose-fractionation regimens of radiotherapy in this clinical scenario will be discussed. Additionally, radiotherapy can play a curative role as a concurrent therapy, consolidation therapy, and salvage therapy for patients with oligo-metastatic, oligo-residual, and oligo-progressive disease, respectively. Accumulating evidence from recent clinical trials, basic research, and translational investigations regarding the potentially curative roles of radiotherapy in NSCLC patients with oligo-metastatic disease will be summarized. Moreover, with the advent of various small molecular tyrosine kinase inhibitors (TKIs), the treatment efficacy and overall survival of oncogene-addicted NSCLC with brain metastases have been significantly improved, and the clinical value and optimal timing of cranial radiotherapy have become topics of much debate. Finally, synergistic antitumor interactions between radiotherapy and immunotherapy have been repeatedly demonstrated. Thus, the immune sensitizing role of radiotherapy in advanced NSCLC is also highlighted in this review.

• Non-small cell lung cancer (NSCLC)
• palliative cancer
• performance status (PS)
• radiotherapy

• metastasis
• surgical oncology
• radiotherapy

• Epidermal growth factor receptor mutations
• Epidermal growth factor receptor-mutated
• Local ablative therapy
• Non-small cell lung cancer
• Oligometastatic
• SINDAS
• Stereotactic body radiation therapy

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.

• non-small-cell lung cancer
• oligometastatic disease
• pattern of progressive disease
• platinum-based chemotherapy
• threshold number of metastases

• Epidermal growth factor receptor
• Epidermal growth factor receptor-tyrosine kinase inhibitor
• Local ablative therapy
• Lung adenocarcinoma
• Primary tumor resection

Despite recent advances in multimodality treatments such as endocrine therapy, chemotherapy, molecularly targeted therapy, and radiation therapy, it is still very difficult to cure de novo stage IV breast cancer patients completely. The traditional role of radiation therapy for these patients has been a palliative treatment strategy that aims to control tumor progression and suppress tumor related symptoms. Recently, several non-randomized retrospective studies on de novo stage IV breast cancer have revealed that locoregional radiation therapy (LRRT) might confer a survival benefit. However, there is no high level evidence to support the impact of LRRT on survival among patients with de novo metastatic disease so far. This article aimed to summarize the literature and to discuss whether treating the primary lesion with radiation therapy could improve clinical survival outcomes among de novo stage IV breast cancer patients. The issue of patient selection will be discussed because not all de novo stage IV breast cancer patients could benefit from LRRT. This article also explores the clinical evidence regarding LRRT for de novo metastatic disease across various cancers such as prostate, uterine cervical, non-small-cell lung, and head and neck cancers. Many retrospective trials have shown the impact of locoregional treatment (LRT) on survival in de novo metastatic breast cancer. However, since the backgrounds of patients treated with LRRT are quite different from those of patients who did not receive LRRT and the treatment consists of surgery and/or radiation therapy, the role of radiation therapy alone remains unclear. Several reports investigated prognostic factors to detect the benefits of LRRT, which still remains conflicting and no consensus exists. However, selected patients with de novo metastatic disease with better performance status, low tumor burden, and estrogen receptor positivity should be considered for the addition of radiation therapy delivered to the primary site. To explore proper decision-making regarding LRRT, further prospective randomized trials are eagerly awaited.

• Breast cancer
• de novo stage IV
• radiation therapy
• radiotherapy

• Metastasectomy
• Non-small cell lung cancer
• Oligometastases
• Radiosurgery
• Stereotactic ablative radiotherapy
• Stereotactic body radiation therapy