Project description: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.

Project description:BackgroundPatients who develop oligorecurrent disease may be treated with metastasis-directed stereotactic body radiotherapy (SBRT) to defer the start of systemic therapy and delay its potential side effects. We report oncological outcomes and patterns of failure in patients with oligorecurrent disease treated with SBRT and determine which factors impact the interval to initiation of systemic therapy.Material/methodsThis retrospective study included patients with oligorecurrent disease (≤5 lesions) from any solid organ malignancy, treated with SBRT to all metastases and no systemic therapy for a minimum one month after SBRT between 01/2014 and 12/2019. The Kaplan-Meier method was used to analyze overall survival (OS) and progression-free survival (PFS), and the cumulative incidence of initiation of systemic therapy was analyzed assuming death without systemic therapy as a competing risk. Univariable and multivariable analyses are used to assess predictors of the systemic therapy-free interval.ResultsAmong 545 patients treated with SBRT for oligometastatic disease, 142 patients were treated with SBRT only for oligorecurrent disease. The most common primary tumors were lung and gastrointestinal cancer in 47 (33.1 %) and 28 (19.7 %) patients, respectively. After a median follow-up of 25 months, the median PFS and OS was 6.1 months and 48.9 months, respectively. Distant metastases were the most common first failure, and oligometastatic distant failure occured in 86 patients (60.6 %). New metastases were treated with repeat SBRT in 48 patients (33.8 %). The 1- and 2-year cumulative incidence of initiation of systemic therapy was 24.6 % and 36.8 %, respectively. In multivariable analysis, the number of previous lines of systemic therapy and the cumulative volume of metastases were significantly associated with the interval to initiation of systemic therapy.ConclusionSelected patients with oligorecurrence achieved favorable OS and low cumulative incidence of initiation of systemic therapy. Prospective studies are warranted to determine how the deferral of systemic therapy impacts OS compared with immediate systemic therapy in combination with SBRT.

Project description:BackgroundMost patients with metastatic cancer eventually develop resistance to systemic therapy, with some having limited disease progression (ie, oligoprogression). We aimed to assess whether stereotactic body radiotherapy (SBRT) targeting oligoprogressive sites could improve patient outcomes.MethodsWe did a phase 2, open-label, randomised controlled trial of SBRT in patients with oligoprogressive metastatic breast cancer or non-small-cell lung cancer (NSCLC) after having received at least first-line systemic therapy, with oligoprogression defined as five or less progressive lesions on PET-CT or CT. Patients aged 18 years or older were enrolled from a tertiary cancer centre in New York, NY, USA, and six affiliated regional centres in the states of New York and New Jersey, with a 1:1 randomisation between standard of care (standard-of-care group) and SBRT plus standard of care (SBRT group). Randomisation was done with a computer-based algorithm with stratification by number of progressive sites of metastasis, receptor or driver genetic alteration status, primary site, and type of systemic therapy previously received. Patients and investigators were not masked to treatment allocation. The primary endpoint was progression-free survival, measured up to 12 months. We did a prespecified subgroup analysis of the primary endpoint by disease site. All analyses were done in the intention-to-treat population. The study is registered with ClinicalTrials.gov, NCT03808662, and is complete.FindingsFrom Jan 1, 2019, to July 31, 2021, 106 patients were randomly assigned to standard of care (n=51; 23 patients with breast cancer and 28 patients with NSCLC) or SBRT plus standard of care (n=55; 24 patients with breast cancer and 31 patients with NSCLC). 16 (34%) of 47 patients with breast cancer had triple-negative disease, and 51 (86%) of 59 patients with NSCLC had no actionable driver mutation. The study was closed to accrual before reaching the targeted sample size, after the primary efficacy endpoint was met during a preplanned interim analysis. The median follow-up was 11·6 months for patients in the standard-of-care group and 12·1 months for patients in the SBRT group. The median progression-free survival was 3·2 months (95% CI 2·0-4·5) for patients in the standard-of-care group versus 7·2 months (4·5-10·0) for patients in the SBRT group (hazard ratio [HR] 0·53, 95% CI 0·35-0·81; p=0·0035). The median progression-free survival was higher for patients with NSCLC in the SBRT group than for those with NSCLC in the standard-of-care group (10·0 months [7·2-not reached] vs 2·2 months [95% CI 2·0-4·5]; HR 0·41, 95% CI 0·22-0·75; p=0·0039), but no difference was found for patients with breast cancer (4·4 months [2·5-8·7] vs 4·2 months [1·8-5·5]; 0·78, 0·43-1·43; p=0·43). Grade 2 or worse adverse events occurred in 21 (41%) patients in the standard-of-care group and 34 (62%) patients in the SBRT group. Nine (16%) patients in the SBRT group had grade 2 or worse toxicities related to SBRT, including gastrointestinal reflux disease, pain exacerbation, radiation pneumonitis, brachial plexopathy, and low blood counts.InterpretationThe trial showed that progression-free survival was increased in the SBRT plus standard-of-care group compared with standard of care only. Oligoprogression in patients with metastatic NSCLC could be effectively treated with SBRT plus standard of care, leading to more than a four-times increase in progression-free survival compared with standard of care only. By contrast, no benefit was observed in patients with oligoprogressive breast cancer. Further studies to validate these findings and understand the differential benefits are warranted.FundingNational Cancer Institute.

Project description:BackgroundImmunotherapy 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.MethodsWe 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.ResultsAmong 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.ConclusionsWe 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.

Project description:AimTo 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 and materialsA 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.ResultsMedian 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.ConclusionsSBRT 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.

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Stereotactic body radiotherapy for oligoprogression with or without switch of systemic therapy

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