UNASSIGNED: No standardized treatment strategy exists for managing oligoprogression during maintenance therapy in driver-negative advanced non-small cell lung cancer (NSCLC). Similarly, a uniform response to oligoprogression during maintenance therapy using immune checkpoint inhibitors (ICIs) has not been established. Consequently, our investigation focused on assessing the efficacy and safety of employing stereotactic total body radiotherapy in conjunction with ICIs to address oligoprogression in advanced NSCLC.
UNASSIGNED: We conducted a retrospective analysis of patients diagnosed with driver-negative advanced NSCLC who received stereotactic body radiotherapy (SBRT) in combination with ICIs to manage oligoprogressive lesions within the period from October 2018 to October 2023 at our institution. Oligoprogression, defined as progression occurring in three or fewer disease sites, was the focus of our investigation. Our assessment encompassed various parameters including the local control rate (LCR), progression-free survival post-oligoprogression (PFS-P), overall survival post-oligoprogression (OS-P), progression-free survival (PFS), overall survival (OS), and the safety profile associated with SBRT followed by sequential ICIs after oligoprogression.
UNASSIGNED: A total of 15 patients were enrolled in this study, all at stage IV, with 12 (80%) receiving a diagnosis of adenocarcinoma. Before oligoprogression, 11 (73.3%) patients had undergone immunotherapy. Following the treatment of oligoprogressed lung cancer with SBRT sequential ICIs, the median PFS-P and OS-P were 8 months (95% CI: 2.7-13.3) and 12 months (95% CI: 7.3-16.7), respectively. Additionally, the median PFS and OS were 26 months (95% CI: 8.0-44.0) and 30 months (not reached), respectively. The median local control (LC) of 15 oligoprogressed lesions was 13 months (95% CI: 5.3-20.2), with a 1-year LCR of 77.9%. Notably, patients with a performance status (PS) score of less than 2 demonstrated a more favorable survival benefit.
UNASSIGNED: Stereotactic systemic radiation therapy, combined with sequential ICIs, enhances both LC and survival in advanced NSCLC characterized by oligoprogression and negative driver gene mutations. This approach also exhibits the potential to postpone the transition between systemic chemotherapy regimens. Manageable adverse reactions were observed, with the absence of grade 4 reactions.

Stereotactic ablative radiotherapy (SABR) may improve survival in patients with inoperable pulmonary oligometastases. However, the impact of pulmonary oligometastatic status after systemic therapy on SABR outcomes remains unclear. Hence, we investigated the outcomes of SABR in 45 patients with 77 lung tumors and the prognostic value of pulmonary oligoprogression. Eligibility criteria were pulmonary oligometastases (defined as ≤5 metastatic lung tumors), controlled extrapulmonary disease (EPD) after front-line systemic therapy, SABR as primary local treatment for inoperable pulmonary metastases, and consecutive imaging follow-up. Oligometastatic lung tumor was classified into controlled or oligoprogressive status. Overall survival (OS), in-field progression-free survival (IFPFS), out-field progression-free survival (OFPFS), and prognostic variables were evaluated. With 21.8 months median follow-up, the median OS, IFPFS, and OFPFS were 28.3, not reached, and 6.5 months, respectively. Two-year OS, IFPFS, and OFPFS rates were 56.0%, 74.2%, and 17.3%, respectively. Oligoprogressive status (p = 0.003), disease-free interval < 24 months (p = 0.041), and biologically effective dose (BED10) < 100 Gy (p = 0.006) were independently associated with inferior OS. BED10 ≥ 100 Gy (p = 0.029) was independently correlated with longer IFPFS. Oligoprogressive status (p = 0.017) and EPD (p = 0.019) were significantly associated with inferior OFPFS. Grade ≥ 2 radiation pneumonitis occurred in four (8.9%) patients. Conclusively, SABR with BED10 ≥ 100 Gy could provide substantial in-field tumor control and longer OS for systemic therapy respondents with inoperable pulmonary oligometastases. Oligoprogressive lung tumors exhibited a higher risk of out-field treatment failure and shorter OS. Hence, systemic therapy should be tailored for patients with oligoprogression to reduce the risk of out-field treatment failure. However, in the absence of effective systemic therapy, SABR is a reasonable alternative to reduce resistant tumor burden.

UNASSIGNED: Oligoprogressive disease is recognized as the overall umbrella term; however, a small number of progressions on imaging can represent different clinical scenarios. This study aims to explore the optimal treatment strategy after immunotherapy (IO) resistance in advanced non-small-cell lung cancer (NSCLC), especially in personalized therapies for patients with different oligoprogressive patterns.
UNASSIGNED: Based on European Society for Radiotherapy and Oncology/European Organization for Research and Treatment of Cancer consensus, metastatic NSCLC patients with cancer progression after IO resistance were divided into four patterns, repeat oligoprogression (REO, oligoprogression with a history of oligometastatic disease), induced oligoprogression (INO, oligoprogression with a history of polymetastatic disease), de-novo polyprogression (DNP, polyprogression with a history of oligometastatic disease), and repeat polyprogression (REP, polyprogression with a history of polymetastatic disease). Patients with advanced NSCLC who received programmed cell death-1/programmed cell death ligand-1 inhibitors between January 2016 and July 2021 at Shanghai Chest Hospital were identified. The progression patterns and next-line progression-free survival (nPFS), overall survival (OS) were investigated stratified by treatment strategies. nPFS and OS were calculated using the Kaplan-Meier method.
UNASSIGNED: A total of 500 metastatic NSCLC patients were included. Among 401 patients developed progression, 36.2% (145/401) developed oligoprogression and 63.8% (256/401) developed polyprogression. Specifically, 26.9% (108/401) patients had REO, 9.2% (37/401) patients had INO, 27.4% (110/401) patients had DNP, and 36.4% (146/401) patients had REP, respectively. The patients with REO who received local ablative therapy (LAT) had significant longer median nPFS and OS compared with no LAT group (6.8 versus 3.3 months; p = 0.0135; OS, not reached versus 24.5 months; p = 0.0337). By contrast, there were no nPFS and OS differences in INO patients who received LAT compared with no LAT group (nPFS, 3.6 versus 5.3 months; p = 0.3540; OS, 36.6 versus 45.4 months; p = 0.8659). But in INO patients, there were significant longer median nPFS and OS using IO maintenance by contrast with IO halt treatment (nPFS, 6.1 versus 4.1 months; p = 0.0264; OS, 45.4 versus 32.3 months; p = 0.0348).
UNASSIGNED: LAT (radiation or surgery) is more important for patients with REO while IO maintenance plays a more dominant role in patients with INO.

Nonsmall cell lung cancer (NSCLC) is treated by various therapies such as surgical intervention, radiotherapy, chemotherapy, molecular targeted therapy, and immunotherapy. Currently, molecular targeted therapy, including epidermal growth factor receptor (EGFR) inhibitors and Anaplastic Lymphoma Kinase (ALK) and Kirsten Rat Sarcoma viral Oncogene (KRAS) inhibitors, has received much attention and improved the prognosis of NSCLC. Nevertheless, the terminal point of molecular targeted drugs is resistance. Drug resistance has been classified into oligoprogression and extensive progression based on the tumor lesion progression after drug resistance. There is extensive research demonstrating that local therapy (surgical resection, radiotherapy, and thermal ablation) can prolong the survival of patients with drug resistance. This review is intended to determine the efficacy of image-guided thermal ablation in patients with NSCLC with EGFR mutation.

Epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC) develops resistance to tyrosine kinase inhibitors (TKIs). Here, we evaluated the efficacy of radiotherapy and continuation of TKIs in patients with advanced NSCLC with oligoprogression after EGFR-TKIs.
From January 2011 to January 2019, 33 patients with EGFR-mutated NSCLC on TKIs were treated by radiotherapy and continuation of TKIs for oligoprogressive disease. The primary endpoints were median progression-free survival 1 (mPFS1), mPFS2, and median overall survival (mOS). PFS1 was measured from the start of EGFR-TKIs therapy to the oligoprogression of the disease. PFS2 was measured from the date of oligoprogression to the further progression of the disease, while OS was calculated from oligoprogression to death from any cause or was censored at the last follow-up date.
The mPFS1, mPFS2, and mOS were 11.0 (95% CI, 4.4-17.6), 6.5 (95% CI, 1.4-11.6) and 21.8 (95% CI, 14.8-28.8) months, respectively. Univariate analysis showed that EGFR mutation type (p = 0.024), radiotherapy method (p = 0.001), and performance status (p = 0.017) were significantly correlated with PFS2. Univariate analysis showed that sex (p = 0.038), smoking history (p = 0.031), EGFR mutation type (p = 0.012), and radiotherapy method (p = 0.009) were significantly correlated with OS. Multivariate analysis suggested that radiotherapy method (p = 0.001) and performance status (p = 0.048) were prognostic factors for PFS2, and radiotherapy method (p = 0.040) was a prognostic factor for OS.
Radiotherapy with continued TKIs is effective for EGFR-mutated NSCLC with oligoprogression, and it should be conducted as soon as possible. T790M+ patients have higher sensitivity to radiotherapy, and patients with good performance status and stereotactic body radiation therapy have better PFS2 and OS.

BACKGROUND: Immunotherapy has brought substantial benefit for patients with advanced non-small cell lung cancer (NSCLC); however, resistance may occur, of which oligoprogression is most common. There are no standard strategies to overcome acquired resistance, thus exploring potential effective approaches is critical. Our study evaluated the clinical outcome of combing stereotactic body radiotherapy (SBRT) with checkpoint inhibitors (CPIs) in oligoprogressive NSCLC.
METHODS: We retrospectively reviewed patients with advanced NSCLC who received SBRT for oligoprogressive lesions after acquired resistance to CPIs in our hospital between January 2015 and January 2021. Acquired resistance was defined as initial complete/partial response (CR/PR) followed by progression/death. Oligo patterns of acquired resistance were defined as progression in ≤2 sites of disease. We evaluated the local control rate (LR), progression-free survival (PFS-PO), overall survival (OS-PO), and safety of combing SBRT after oligoprogression.
RESULTS: Among 177 patients reviewed, 24 patients were included. Fifteen (62.5%) were diagnosed with adenocarcinoma, and 20 (83.3%) were with stage IV. Before oligoprogression, immunotherapy was used as first-line treatment in 16 (66.7%) patients, and 4 (16.7%) received monotherapy. After combing SBRT with CPIs, the median PFS-PO and OS-PO were 11 months (95% CI: 8-NA) and 34 months (95% CI: 19-NA). The median LC of 34 oligoprogressed lesions was 43 months (95% CI: 7.7-78.3). The 1- and 2-year LC rates were 100% and 81.8%, respectively. Patients with adenocarcinoma, lung immune prognostic index (LIPI) (≥1), and positive PD-L1 tended to achieve favorable survival benefits.
CONCLUSIONS: We observed considerable benefit of local control and survival by combing SBRT in patients with oligoprogression after required resistance to CPIs in NSCLC. The adverse events are well managed. Our results suggest that combing SBRT with CPIs could be a potential strategy to overcome acquired resistance.

UNASSIGNED: Immune checkpoint inhibitors (ICIs) have changed the management of non-small cell lung cancer (NSCLC). However, resistance is inevitable. The disease progression patterns, sequential treatment, and prognosis beyond ICI resistance are not completely understood.
UNASSIGNED: We retrospectively analyzed stage IV NSCLC patients who underwent ICI treatment at Zhejiang Cancer Hospital between January 2016 and January 2020 and who suffered disease progression after at least stable disease on immunotherapy for more than 3 months (at least two cycles). Oligoprogression and systematic progression were defined as previous reports. The main outcome measures were progression-free survival (PFS), second PFS (PFS2), and overall survival (OS). Survival curves were plotted using the Kaplan-Meier method. The Cox proportional hazards model was used for multivariate analysis.
UNASSIGNED: Totally 1,014 NSCLC patients were administered immunotherapy. Of them, 208 NSCLC patients were included in this retrospective study. The estimated PFS, PFS2 and OS were 6.3 months (95% CI 5.6-7.0 months), 10.7 months (95% CI 10.1-12.7 months), and 21.4 months (95% CI 20.6-26.4 months), respectively. After resistance, 55.3% (N = 115) patients developed oligoprogression, and 44.7% (N = 93) systemic progression. For patients with systemic progression, chemotherapy (N = 35, 37.6%), best supportive care (N = 30, 32.3%), and antiangiogenic therapy alone (N = 11, 11.8%) were the major strategies. A combination of local radiotherapy (N = 38, 33.0%) with continued ICIs was the most common treatment used in oligoprogression group, followed by continued immunotherapy with antiangiogenic therapy (N = 19, 16.5%) and local radiotherapy only (N = 17, 14.9%). For patients with oligoprogression, continued immunotherapy plus local radiotherapy can lead to a significantly longer PFS2 (12.9 vs. 10.0 months; p = 0.006) and OS (26.3 vs. 18.5 months, p = 0.001). The PFS2 and OS of patients with oligoprogression were superior to those of patients with systemic progression (PFS2: 13.1 vs. 10.0 months, p = 0.001; OS: 25.8 vs. 19.1 months, p = 0.003).
UNASSIGNED: The major progression pattern after acquired resistance from immunotherapy is oligoprogression. Local radiotherapy with continued immunotherapy beyond oligoprogression in responders was feasible and led to prolonged PFS2 and OS in advanced NSCLC patients.

OBJECTIVE: To evaluate the clinical outcomes of metastatic colorectal cancer (mCRC) patients with oligometastases, oligoprogression, or local control of dominant tumors after stereotactic body radiotherapy (SBRT) and establish a nomogram model to predict the prognosis for these patients.
METHODS: A cohort of 94 patients with 162 mCRC metastases was treated with SBRT at a single institution. Treatment indications were oligometastases, oligoprogression, and local control of dominant tumors. End points of this study were the outcome in terms of progression-free survival (PFS), overall survival (OS), local progression (LP), and cumulative incidence of starting or changing systemic therapy (SCST). In addition, univariate and multivariable analyses to assess variable associations were performed. The predictive accuracy and discriminative ability of the nomogram were determined by concordance index (C-index) and calibration curve.
RESULTS: Median PFS were 12.6 months, 6.8 months, and 3.7 months for oligometastases, oligoprogression, and local control of dominant tumors, respectively. 0-1 performance status, < 10 ug/L pre-SBRT CEA, and ≤ 2 metastases were significant predictors of higher PFS on multivariate analysis. Median OS were 40.0 months, 26.1 months, and 6.5 months for oligometastases, oligoprogression, and local control of dominant tumors, respectively. In the multivariate analysis of the cohort, the independent factors for survival were indication, performance status, pre-SBRT CEA, and PTV, all of which were selected into the nomogram. The calibration curve for probability of survival showed the good agreement between prediction by nomogram and actual observation. The C-index of the nomogram for predicting survival was 0.848.
CONCLUSIONS: SBRT for metastases derived from colorectal cancer offered favorable survival and symptom palliation without significant complications. The proposed nomogram could provide individual prediction of OS for patients with mCRC after SBRT.

Purpose: To analyze the prognostic factors and optimal response interval for stereotactic body radiotherapy (SBRT) in patients with lung oligometastases (OM) or oligoprogression (OP) from colorectal cancer (CRC). Method: Patients with lung OM or OP from CRC treated by SBRT at our hospital were included in this retrospective review. The local control (LC), response to SBRT in different evaluation interval and regional metastases (RM) was analyzed. The risk factor for LC and RM was calculated using the Kaplan-Meier method and compared using the Log-rank test. Multivariate analysis with a Cox proportional hazards model was used to test independent significance. Results: A total of 53 patients with 105 lung metastases lesions treated from 2012 to 2018 were involved in this retrospective study. The median biologically effective dose (BED) for these patients was 100 Gy (range: 75-131.2 Gy). Complete response (CR) increased from 27 (25.7%) to 46 (43.8%) lesions at 1.8 and 5.3 months following SBRT, and at the last follow-up, 52 (49.5%) lesions achieved CR. The median follow-up duration for all patients was 14 months (range: 5-63 months), and 1-year LC was 90.4%. During the follow-up, 10 lesions suffered local relapse after SBRT (9 of them occurred within 8 months after SBRT). The univariate analysis shows BED ≥ 100 Gy (P = 0.003) and gross tumor volume (GTV) < 1.6 cm3 (P = 0.011) were better predictors for 1-year LC. The patients with lung oligoprogression had higher 1-year RM when compared with patients with lung oligometastases (hazard ratio 2.78; 95% confidence interval [CI] 1.04-7.48, P = 0.042). Until the last follow up, 4 (7.5%) patients suffered grade 2 radiation pneumonitis, and no grade 3-4 toxicity was observed. Conclusions: SBRT provides favorable LC in CRC patients with lung OM or OP, and the GTV and BED can affect the LC. Radiology examinations nearly 5-6 months following SBRT appear to represent the final local effect of SBRT, and the patients with oligoprogression has higher RM.

OBJECTIVE: To evaluate the outcome and toxicities of stereotactic ablative radiotherapy (SABR) for skeletal metastasis in a tertiary cancer center.
METHODS: This is a retrospective review of 22 patients treated with SABR for skeletal metastases for oligometastases (OM) or oligoprogression (OP) since October 2012. There are a total of 27 treatments with 20 spinal and seven non-spinal metastases. Treatment outcome including local control (LC), progression-free survival (PFS), overall survival (OS), pain control, treatment-related toxicity and failure pattern are described. Patients are assessed by interval computed tomography (CT), positron emission tomography-CT, magnetic resonance imaging or bone scintigraphy by physicians\' discretion. Toxicities are graded by common toxicities criteria version 4.03.
RESULTS: The median age of the patients is 64 years. Primary sites include lung (50%), breast (32%), nasopharynx (9%), prostate (4.5%) and colon (4.5%). Twelve patients with OM and 10 with OP are included. Dose to most spinal and non-spinal metastases is 35 and 50 Gy, respectively, in five fractions. With a median follow up of 15.6 months, there are three local failures (1-year LC 91.2%). The median PFS and OS are 10.1 and 37.3 months, while PFS of OP and OM group is 6.6 and 10.6 months, respectively. Two-third of symptomatic patients have at least 1-year complete pain control. There are two vertebral fractures and one grade 3 esophagitis.
CONCLUSIONS: Our series shows excellent LC of SABR to skeletal metastases with limited toxicities in OM and OP diseases. However, its benefit of survival warrants further studies.