A Multicenter Two-arm,Phase II Trial Assessing the Safety and Efficacy of First-line Lazertinib and Locally Ablative Radiotherapy in Patients With Synchronous Oligo-metastatic EGFR-mutant Non-small Cell Lung Cancer (ABLATE,KCSG-LU21-11)

BackgroundThe current standard treatment of advanced non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutation is upfront EGFR targeted therapy. However, patients invariably experience disease progression at primary tumors or metastatic sites. Adding stereotactic body radiation therapy (SBRT) to systemic therapy can improve progression-free survival (PFS) and overall survival (OS). This multicenter, 2-arm, phase II study aims to evaluate the efficacy and safety of lazertinib, a third generation EGFR tyrosine kinase inhibitor, combined with upfront locally ablative radiotherapy in EGFR-mutant NSCLC patients with synchronous oligometastatic disease (ClinicalTrials.gov: NCT05167851).Patients and MethodsKey inclusion criteria are biopsy-proven EGFR-mutated adenocarcinoma with synchronous, oligometastatic (≤5 metastases) NSCLC. Patients will be randomized 1:1 to receive lazertinib or lazertinib + SBRT to the primary tumor and metastatic sites. The primary endpoint is PFS according to RECIST: Response Evaluation Criteria in Solid Tumor version 1.1, and the secondary endpoints are OS, objective response rate, and safety.ResultsPatient enrolment began in January 2021 and is ongoing at 7 sites in the Republic of Korea.ConclusionThis trial will provide valuable information on the efficacy and safety of lazertinib in combination with SBRT in patients with synchronous, oligometastatic EGFR-mutant NSCLC.     

Long-term Follow-up and Patterns of Recurrence of Patients With Oligometastatic NSCLC Treated With Pulmonary SBRT

IntroductionThis multicenter study aims to analyze outcome as well as early versus late patterns of recurrence following pulmonary stereotactic body radiotherapy (SBRT) for patients with oligometastatic non–small-cell lung cancer (NSCLC).Materials and MethodsThis analysis included 301 patients with oligometastatic NSCLC treated with SBRT for 336 lung metastases. Although treatment of the primary tumor consisted of surgical resection, radiochemotherapy, and/or systemic therapy, pulmonary oligometastases were treated with SBRT.ResultsThe median follow-up time was 16.1 months, resulting in 2-year overall survival (OS), local control (LC), and distant control (DC) of 62.2%, 82.0%, and 45.2%, respectively. Multivariate analysis identified age (P = .019) and histologic subtype (P = .028), as well as number of metastatic organs (P < .001) as independent prognostic factors for OS. LC was superior for patients with favorable histologic subtype (P = .046) and SBRT with a higher biological effective dose at isocenter (P = .037), whereas DC was inferior for patients with metastases in multiple organs (P < .001) and female gender (P = .027). Early (within 24 months) local or distant progression was observed in 15.3% and 36.5% of the patients. After 24 months, the risk of late local failure was low, with 3- and 4-year local failure rates of only 4.0%, and 7.6%. In contrast, patients remained at a high risk of distant progression with 3- and 4-year failure rates of 13.3% and 24.1%, respectively, with no plateau observed.ConclusionSBRT for pulmonary oligometastatic NSCLC resulted in favorable LC and promising OS. The dominant failure pattern is distant with a continuously high risk of disease progression for many years.     

Radical radiation therapy for oligometastatic breast cancer: Results of a prospective phase II trial

Background and purpose

We conducted a prospective phase II multicentric trial to determine if radical radiation therapy to all metastatic sites might improve the progression-free survival (PFS) in oligometastatic breast cancer patients. Secondary endpoints were local control (LC), overall survival (OS) and toxicity.

Five- Versus Ten-Fraction Regimens of Stereotactic Body Radiation Therapy for Primary and Metastatic NSCLC

IntroductionAt our institution, stereotactic body radiotherapy (SBRT) has commonly been prescribed with 50 Gy in 5 fractions and in select cases, 50 Gy in 10 fractions. We sought to evaluate the impact of these 2 fractionation schedules on local control and survival outcomes.MethodsWe reviewed patients treated with SBRT with 50 Gy/5 fraction or 50 Gy/10 fraction for early-stage non–small cell lung cancer (NSCLC) and metastatic NSCLC. Cumulative incidence of local failure (LF) was estimated using competing risk methodology. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method only for patients with stage I disease.ResultsOf the 353 lesions, 300 (85%) were treated with 50 Gy in 5 fractions and 53 (15%) with 10 fractions. LFs at 3 years were 6.5% and 23.9% and Kaplan-Meier estimate of median time to LF was 17.5 months and 26.2 months, respectively. Multivariable analysis revealed increasing planning target volume (hazard ratio 1.01, P = .04) as an independent predictor of increased LF, but tumor size, ultracentral location, and 10 fractions were not. Among patients with stage I NSCLC (n = 298), overall median PFS was 35.6 months and median OS was 42.4 months. There was no difference in PFS or OS between the 2 treatment regimens for patients with stage I NSCLC. Low rates of grade 3+ toxicity were observed, with 1 patient experiencing grade 3 pneumonitis after a 5-fraction regimen of SBRT.ConclusionDose-fractionation schemes with BED₁₀ ≥ 100 Gy provide superior local control and should be offered when meeting commonly accepted constraints. If those regimens appear unsafe, 50 Gy in 10 fractions may provide acceptable compromise between tumor control and safety with relatively durable control, and minimal negative impact on long-term survival.     

A Phase 1 Trial of Concurrent or Sequential Ipilimumab,Nivolumab, and Stereotactic Body Radiotherapy in Patients With Stage IV NSCLC Study

IntroductionPrevious studies have evaluated stereotactic body radiotherapy (SBRT) in oligometastatic patients with NSCLC, including multimodality treatment with anti–programmed cell death protein-1 monotherapy. Questions remain regarding the timing of SBRT and immunotherapy, safety with dual checkpoint blockade, and the utility in widely metastatic patients. This randomized phase 1 trial combined nivolumab and ipilimumab with sequential or concurrent multisite SBRT in patients with stage IV NSCLC to evaluate safety and obtain preliminary activity data.MethodsTreatment-naive patients with metastatic NSCLC were randomized to concurrent (SBRT with immunotherapy) or sequential (SBRT followed by immunotherapy) treatment. A maximum of four treatment fields received SBRT. Nivolumab and ipilimumab were continued until clinical progression, development of toxicity, or after 2 years. Dose-limiting toxicity was defined as greater than or equal to grade 3 toxicity to the relevant organ system attributed to SBRT and immunotherapy occuring within 3 months.ResultsA total of 37 patients were assessable. No dose-limiting toxicity occurred in the concurrent cohort (n = 18). The sequential cohort required a dose reduction in the central lung group owing to two grade 4 pneumonitis events (2 of 19). Overall best response was as follows: 5.4% (2 of 37) complete response, 40.5% (15 of 37) partial response, 16.2% (6 of 37) stable disease, and 37.8% (14 of 37) progressive disease. Median progression-free survival was 5.8 months (95% confidence interval: 3.6–11.4 mo), with median follow-up of 17.0 months. Median overall survival was not reached.ConclusionsConcurrent nivolumab, ipilimumab, and SBRT were not more toxic than sequential therapy, and multisite SBRT was well tolerated in widely metastatic patients. Multimodality therapy resulted in durable metastasis control and encouraging early overall survival.     

Consolidative Local Ablative Therapy Improves the Survival of Patients With Synchronous Oligometastatic NSCLC Harboring EGFR Activating Mutation Treated With First-Line EGFR-TKIs

Introduction

The aim of the current study was to investigate whether consolidative local ablative therapy (LAT) can improve the survival of patients with stage IV EGFR-mutant NSCLC who have oligometastatic disease treated with first-line EGFR–tyrosine kinase inhibitor (TKI) therapy.

寡转移瘤患者体部立体定向放疗的疗效及安全性

目的 探讨小体积寡转移瘤患者局部立体定向放疗（SBRT）的疗效及安全性。方法收集2011年6月至2016年12月85例转移灶≤5个、预计生存期＞3个月、一般状况良好的Ⅳ期寡转移瘤患者,采用3个剂量的SBRT,主要研究终点是局部控制率和毒性反应,次要研究终点是总生存期（OS）和无疾病进展生存期（PFS）。疗效评价采用RECIST 1.1版标准;毒副反应采用RTOG评价标准;Kaplan-Meier法计算生存,Log-rank检验生存差异。结果 85例患者共187处转移灶,中位随访时间为25个月,局部控制率为66.8％（125／187）,其中24、30、36 Gy剂量组局部控制率分别为39.0％、79.0％、84.0％,差异有统计学意义（P＜0.05）。全组中位PFS为7.8个月（1～25个月）,1、2、3年无进展生存率分别为33.3％、25.0％、23.0％;中位OS为25个月,1、2、3年生存率分别为80.5％、75.6％、70.6％。4例患者发生3级以上急性毒副反应,其中2例是肺部转移瘤,2个月后证实为放射性肺炎;另外1例是肝脏转移瘤,放疗时发生严重呕吐、转氨酶升高需入院治疗;还有1例肝、肺、骨多发转移患者发生4级骨髓抑制（白细胞减少为主）。结论 寡转移瘤患者在安全治疗范围内可以从局部SBRT放疗中获得较好的局部控制率,不良反应可耐受。     

Stereotactic Body Radiation Therapy for Salvage Treatment of Recurrent Non-Small Cell Lung Cancer

PurposeThis study analyzes the outcomes and toxicity of stereotactic body radiation therapy (SBRT) as salvage treatment for recurrent non-small cell lung cancer (NSCLC).Methods and MaterialsThis retrospective analysis considered patients treated with thoracic SBRT and a history of prior external beam radiation therapy (EBRT), SBRT, or surgical resection for NSCLC. Follow-up included positron emission tomography and computed tomography imaging at 2- to 3-month intervals. Key outcomes were presented with the Kaplan–Meier method.ResultsForty patients with 52 treatments were included at a mean of 11.82 months after treatment with EBRT (n = 21), SBRT (n = 15), surgical resection (n = 9), and SBRT after EBRT (n = 7). Median imaging and clinical follow-up were 13.39 and 19.01 months, respectively. SBRT delivered a median dose of 40 Gy in 4 fractions. Median biologically effective dose (BED) was 79.60 Gy. Median gross tumor volume and planning target volume were 10.80 and 26.25 cm³, respectively. Local control was 65%, with a median time to local failure of 13.52 months. Local control was 87% after previous SBRT but only 33% after surgery. Median overall survival was 24.46 months, and median progression-free survival (PFS) was 14.11 months. Patients presenting after previous SBRT had improved local control (P = .021), and the same result was obtained including patients with SBRT after EBRT (P = .0037). Treatments after surgical resection trended toward worse local control (P = .061). Patients with BED ≥80 Gy had improved local PFS (P = .032), PFS (P = .021), time without any treatment failure (P = .033), and time to local failure (P = .041). Using the Kaplan–Meier method, BED ≥80 Gy was predictive of improved local PFS (P = .01) and PFS (P < .005). Toxicity consisted of 10 instances of grade <3 toxicity (16%) and no grade ≥3 toxicity.ConclusionsSalvage treatment for recurrent NSCLC with SBRT was effective and well tolerated, particularly after initial treatment with SBRT. When possible, salvage SBRT should aim to achieve a BED of ≥80 Gy.     

Stereotactic Body Radiation Therapy in the Management of Oligometastatic and Oligoprogressive Bladder Cancer and Other Urothelial Malignancies

AimsBladder cancer represents the most common type of urothelial carcinoma, with a median overall survival of 12.5–15 months in the case of metastatic disease. We evaluated the role of stereotactic body radiation therapy (SBRT) in the management oligometastatic urothelial cancer.Materials and methodsData on patients with a maximum of five metastases were collected from three institutions. Concomitant systemic therapy was allowed. End points were the local control of treated metastases, distant progression-free survival (PFS), overall PFS and overall survival.ResultsData for 82 lesions and 61 patients were included. The primary tumour was located in the bladder in 82% of patients, followed by kidney pelvis (11.5%). The most common treated site was lung (40.2%). Twenty-nine (47.5%) and 14 (23%) patients received systemic therapy before and during SBRT, respectively. The median BED10 value was 78.7 Gy. The median follow-up was 17.2 months. Rates of local control at 1 and 2 years were 92% and 88.9%, respectively, with correlation with systemic therapy before SBRT (hazard ratio 2.62, P = 0.034). Overall PFS at 1 and 2 years was 47.9% and 38.1%, respectively. The number of metastases was a predictive factor (hazard ratio 2.65, P = 0.008). The median overall survival was 25.6 months. Total dose (hazard ratio 0.93, P = 0.003) and BED10 (hazard ratio 0.97, P = 0.006) were correlated with overall survival. No grade ≥2 adverse events were reported.ConclusionsSBRT represents an effective and safe treatment in metastatic urothelial carcinoma. Prospective randomised trials are necessary to better evaluate the benefit on delaying the onset of new systemic therapies.     

Clinical Outcomes of Stereotactic Body Radiotherapy With Immediate Versus Delayed Hormone Therapy in Men With Oligometastatic Recurrence of Prostate Cancer

AimsStereotactic body radiotherapy (SBRT) with the delayed option of androgen deprivation therapy (ADT) is the current treatment paradigm in men relapsed with oligometastatic prostate cancer based on the outcome of a phase II randomised controlled study. The immediate (concomitant) use of ADT in this clinical setting potentially augments the efficacy of SBRT by improving systemic disease control. The aim of this study was to compare the clinical outcomes of these two treatment strategies.Materials and methodsEighty-eight patients with up to three oligometastases and controlled primary disease who had been treated using SBRT with immediate or delayed ADT were included in this retrospective analysis. Progression-free survival (PFS), widespread failure-free survival (WFFS) and freedom from further interventions (FFFI) were assessed using Kaplan–Meier and Cox proportional hazard regression methods. Toxicity was evaluated using Common Terminology Criteria for Adverse Events (CTCAE) v4.0.ResultsThirty-nine patients (44.3%) were treated with SBRT and immediate ADT (continuous ADT, n = 7; intermittent ADT, n = 32) and 49 (55.7%) with SBRT and delayed ADT. The median follow-up was 24 months (interquartile range 13.5–37.0 months). PFS in the immediate and delayed ADT groups were 26 months and 16 months, respectively (P < 0.007). The median WFFS in the immediate ADT group was not reached compared with 21 months in the delayed ADT group (P = 0.025). The 1- and 2-year FFFI in the immediate ADT group were 88% and 64.1%, respectively, significantly higher than those in the delayed ADT group (63.8% and 30.2%, respectively, P < 0.002). Acute toxicities of grade 1–2 occurred in 17.9% of the immediate ADT group and 18.4% of the delayed ADT group (P = 0.96). Only one case of grade 3 late toxicity (pelvic insufficiency) was identified in this study.ConclusionsSBRT with concomitant ADT improves PFS, WFFS and FFFI as compared with SBRT with delayed ADT; this finding needs validation in a prospective, randomised study.     

Salvage Stereotactic Body Radiotherapy for Patients With Limited Prostate Cancer Metastases: Deferring Androgen Deprivation Therapy

BackgroundWe investigated whether repeated stereotactic body radiotherapy (SBRT) of oligometastatic disease is able to defer the initiation of palliative androgen deprivation therapy (ADT) in patients with low-volume bone and lymph node metastases.Patients and MethodsPatients with up to 3 synchronous metastases (bone and/or lymph nodes) diagnosed on positron emission tomography, following biochemical recurrence after local curative treatment, were treated with (repeated) SBRT to a dose of 50 Gy in 10 fractions. Androgen deprivation therapy-free survival (ADT-FS) defined as the time interval between the first day of SBRT and the initiation of ADT was the primary end point. ADT was initiated if more than 3 metastases were detected during follow-up even when patients were still asymptomatic or in case of a prostate specific antigen elevation above 50 ng/mL in the absence of metastases. Secondary end points were local control, clinical progression-free survival, and toxicity. Toxicity was scored using the Common Terminology Criteria for Adverse Events.ResultsWe treated 24 patients with a median follow-up of 24 months. Ten patients started with ADT resulting in a median ADT-FS of 38 months. The 2-year local control and clinical progression-free survival was 100% and 42%, respectively. Eleven and 3 patients, respectively, required a second and third salvage treatment for metachronous low-volume metastatic disease. No grade 3 toxicity was observed.ConclusionRepeated salvage SBRT is feasible, well tolerated and defers palliative ADT with a median of 38 months in patients with limited bone or lymph node PCa metastases.     

Lung Metastases Treated With Stereotactic Ablative Radiation Therapy in Oligometastatic Colorectal Cancer Patients: Outcomes and Prognostic Factors After Long-Term Follow-Up

Background

We evaluated a series of oligometastatic colorectal cancer (CRC) patients treated with stereotactic ablative body radiotherapy (SABR) delivered in all active lung metastases.

Impact of Radiotherapy on the Efficacy and Toxicity of anti-PD-1 Inhibitors in Metastatic NSCLC

BackgroundThe impact of radiotherapy (RT) on the efficacy and toxicity of immune checkpoint inhibitors (ICIs) in patients with metastatic non–small-cell lung cancer (NSCLC) is unclear.Materials and MethodsWe identified patients with metastatic NSCLC treated with the anti-programmed death 1 antibodies nivolumab or pembrolizumab between January 2016 and May 2019 at 3 tertiary centers, who were also treated with palliative RT either during or within 3 months of starting anti-programmed death 1 treatment. Patient demographics, tumor characteristics, and treatment history were collected. Response rates, progression-free survival (PFS), and overall survival (OS) were analyzed and correlated with RT use.ResultsA total of 269 patients were identified, with a median follow-up of 19.4 months. The median age was 70 years (range, 35-90 years), and they were 63% male, 60% smokers, and 65% had adenocarcinoma histology. At the commencement of ICI treatment, the majority (86%) had ≥ 1 line of prior therapy and 34% had brain metastases. A total of 102 (38%) patients received RT within 3 months of starting ICI or subsequently during ICI treatment. Of patients that received RT, 86 (84%) received conventional hypofractionated RT, and, in the majority, 81 (79%) the intent of RT was symptom control. The use of RT did not increase grade 3/4 immune-related adverse events. The overall median PFS was 2.0 months (95% confidence interval, 1.3-2.6 months) and the median OS was 9.0 months (95% confidence interval, 6.4-9.5 months). There were no significant differences in median PFS (3.0 vs. 2.0 months; P = .515) and median OS (9.0 vs. 9.0 months; P = .917) in the patients who received RT versus those that did not.ConclusionsIn patients with metastatic NSCLC, the addition of RT to ICI was not associated with increased toxicity or improved survival.     

Metastasis-directed Therapy in Prostate Cancer: Prognostic Significance of the ESTRO/EORTC Classification in Oligometastatic Bone Disease

AimsOligometastatic disease (OMD) represents a spectrum of clinical scenarios and various classification systems have been proposed. Bone-only OMD can occur in patients with advanced prostate cancer and validated decision-making tools are needed to assist patient selection for metastasis-directed therapy. The aim of the present study was to determine the prognostic utility of a classification system for OMD.Materials and methodsA retrospective review was conducted of all patients with bone-only oligometastatic prostate cancer treated with stereotactic body radiotherapy (SBRT) since November 2011. SBRT was delivered using CyberKnife® and gantry-based linear accelerator platforms. All patients were classified into oligometastatic states based on the European Society for Radiotherapy and Oncology/European Organisation for Research and Treatment of Cancer (ESTRO/EORTC) classification system. Kaplan–Meier and Cox regression analyses were carried out to determine the prognostic utility of this classification system.ResultsIn total, 105 patients with 145 osseous metastases were treated over 119 sessions. The median follow-up after SBRT was 23 months (interquartile range 10–39.8). Twelve patients had died after a median time of 31 months. The 3-year metastatic progression-free survival was 23% (95% confidence interval 13–32) and the 3-year overall survival was 88% (95% confidence interval 80–96). Patients in a metachronous oligometastatic state were 4.50 (95% confidence interval 1.19–17.10, P = 0.03) times more likely to experience metastatic progression compared with those with synchronous oligometastases, and 6.69 (95% confidence interval 1.05–42.50, P = 0.04) times more likely to experience any failure. Hazard ratio magnitudes increased for patients in a repeat oligometastatic state. The multivariate model for both metastatic progression-free survival and failure-free survival found prostate-specific antigen doubling time <4 months (P = 0.002; P = 0.05) to independently predict for progression.ConclusionThe ESTRO/EORTC classification of OMD predicts for progression in patients treated with SBRT for bone-only oligometastatic prostate cancer at our institution. Further validation in prospective series over multiple tumour sites is needed. These characterisation factors should be assessed in patients considered for metastasis-directed therapy together with established prognostic features.     

Stereotactic Pelvic Reirradiation for Locoregional Cancer Relapse

AimsUp to 40% of patients who have received radiation for a pelvic malignancy will develop locoregional recurrence in the previously irradiated volume. Stereotactic body radiotherapy (SBRT) has been used in the oligometastatic setting, and provides an ablative approach ideal for reirradiation. The purpose of this study was to evaluate the outcomes after SBRT reirradiation of extraosseous recurrences in the pelvis.Materials and methodsThis single institution retrospective study evaluated patients treated with SBRT reirradiation in the pelvis from January 2011 to February 2018. Patients with more than five oligometastatic lesions, >7 cm in size, and recurrence within the prostate were excluded.ResultsIn total, 30 patients were treated with SBRT with a median follow-up of 29.4 months. The primary tumour sites were most commonly rectum (30.8%) and prostate (30.8%). The median time interval between irradiation for the primary and SBRT reirradiation was 48 months (3–245). The typical reirradiation treatment was 35 Gy in five fractions, the median gross tumour volume size was 10.2 (0.3–110.5) ml and the most common target was the iliac nodes (40%). There were three (10%) acute grade 3 toxicities and no late grade 3 or more toxicities. At 12/24 months, local relapse-free survival, metastasis-free survival, progression-free survival and overall survival were 67.7%/50.7%, 67%/41.7%, 34.8%/14.9% and 83.2%/62.5%, respectively. On univariate analysis, improved local control was associated with low gross tumour volume (<10 ml) (P = 0.003) and prostate primary (P = 0.02), but was no longer significant on multivariate analysis. The proximity of organ at risk to the target did not significantly correlate with worse toxicity (P = 0.14) or tumour coverage (gross tumour volume: P = 0.8, planning target volume: P = 0.4).ConclusionSBRT pelvic reirradiation in oligometastatic patients is a safe and effective treatment modality. Careful consideration should be taken with larger tumour size, as it may be associated with worse oncological and toxicity outcome.     

Survival Impact of Aggressive Treatment and PD-L1 Expression in Oligometastatic NSCLC

Background: Studies have shown that aggressive treatment of non-small cell lung cancer (NSCLC) with oligometastatic disease improves the overall survival (OS) compared to a palliative approach and some immunotherapy checkpoint inhibitors, such as anti-programmed cell death ligand 1 (PD-L1), anti-programmed cell death protein 1 (PD-1), and T-Lymphocyte-associated antigen 4 (CTLA-4) inhibitors are now part of the standard of care for advanced NSCLC. However, the prognostic impact of PD-L1 expression in the oligometastatic setting remains unknown. Methods: Patients with oligometastatic NSCLC were identified from the patient database of the Centre hospitalier de l’Université de Montréal (CHUM). “Oligometastatic disease” definition chosen is one synchronous metastasis based on the M1b staging of the eight IASLC (The International Association for the Study of Lung Cancer) Classification (within sixth months of diagnosis) or up to three cerebral metastasis based on the methodology of the previous major phase II randomized study of Gomez et al. We compared the OS between patients receiving aggressive treatment at both metastatic and primary sites (Group A) and patients receiving non-aggressive treatment (Group B). Subgroup analysis was performed using tumor PD-L1 expression. Results: Among 643 metastatic NSCLC patients, we identified 67 patients with oligometastasis (10%). Median follow-up was 13.3 months. Twenty-nine patients (43%) received radical treatment at metastatic and primary sites (Group A), and 38 patients (57%) received non-aggressive treatment (Group B). The median OS (mOS) of Group A was significantly longer than for Group B (26 months vs. 5 months, p = 0.0001). Median progression-free survival (mPFS) of Group A was superior than Group B (17.5 months vs. 3.4 months, p = 0.0001). This difference was still significant when controlled for primary tumor staging: stage I (p = 0.316), stage II (p = 0.024), and stage III (p = 0.001). In the cohort of patients who were not treated with PD-L1 inhibitors, PD-L1 expression negatively correlated with mOS. Conclusions: Aggressive treatments of oligometastatic NSCLC significantly improve mOS and mPFS compared to a more palliative approach. PD-L1 expression is a negative prognostic factor which suggests a possible role for immunotherapy in this setting.     

EGFR-TKIs plus local therapy demonstrated survival benefit than EGFR-TKIs alone in EGFR-mutant NSCLC patients with oligometastatic or oligoprogressive liver metastases

To investigate whether addition of local therapy to EGFR-TKIs could provide survival benefit than EGFR-TKIs alone in EGFR-mutant NSCLC patients with oligometastatic or oligoprogressive liver metastases (LM). Patients with EGFR-mutant NSCLC and oligometastatic or oligoprogressive LM who met inclusion criteria were retrospectively identified. The primary endpoint was progression-free survival (PFS); secondary endpoints included overall survival (OS) and patterns of failure. Addition of local therapy was associated with a significantly longer PFS (13.8 vs. 8.6 m, p <0.001) and OS (31.2 vs. 18.5 m, p <0.001) in whole group. In oligometastatic cohort, 20 patients received EGFR-TKIs and 23 received EGFR-TKIs plus local therapy as first-line treatment. Addition of local therapy showed a significantly longer PFS (12.9 vs. 7.9 m, p = 0.041) and OS (36.8 vs. 21.3 m, p = 0.034) than EGFR-TKIs alone. In oligoprogressive cohort, 24 patients received continuation of EGFR-TKIs plus local therapy and 25 received switching chemotherapy. Median PFS2 (13.9 vs. 9.2 m, p = 0.007) and OS (28.3 vs. 17.1 m, p = 0.011) was significantly longer in combined group than in switching chemotherapy group. Distant metastatic sites progression was the major pattern of failure in combined group while locoregional recurrence was the major reason in monotherapy or switching chemotherapy group. Our study suggested that EGFR-TKIs plus local therapy showed prolonged survival benefit than EGFR-TKIs alone in EGFR-mutant NSCLC patients with oligometastatic or oligoprogressive LM, indicating addition of local therapy would be alternative choice in this clinical scenario.