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

Background: Oligoprogression is defined as cancer progression of a limited number of metastases under active systemic therapy. The role of metastasis-directed therapy, using stereotactic body radiotherapy (SBRT), is controversial as is the continuation versus switch of systemic therapy. We report outcomes of oligoprogressive patients after SBRT, and compare those patients that continued or switched their current line of systemic therapy. Material/Methods: We included patients who developed up to 5 progressive extracranial metastases under systemic therapy for any solid organ malignancy and were treated with SBRT to all lesions at our institution between 01/2014 and 12/2019. Overall survival (OS) and progression-free survival (PFS) were analyzed using the Kaplan-Meier method, and the interval to the next systemic therapy line determined using cumulative incidence functions. Multivariable Cox regression models were used to analyze the influence of baseline and post-progression variables on OS, PFS and survival with the next systemic therapy after SBRT. Results: Among 135 patients with oligoprogressive disease of which the most common primary tumor was lung cancer (n = 46, 34.1 %), 96 continued their current line of systemic therapy after oligoprogression. Among 39 who switched systemic therapy, 28 (71.8 %) paused or discontinued, while 11 (28.2 %) immediately started another systemic treatment. After a median follow-up of 27.2 months, patients that switched and those who continued systemic therapy after oligoprogression had comparable median OS (32.1 vs. 38.2 months, p = 0.47) and PFS (4.3 vs. 3.4 months, p = 0.6). The intervals to the next systemic therapy line were comparable between both cohorts (p = 0.6). An ECOG performance status of 2 and immediately starting a new systemic therapy after oligoprogression were associated with a poorer survival without next systemic therapy, while the de-novo OMD state was associated with better survival without next systemic therapy compared to the induced state. Conclusion: Oncological outcomes of patients that continued or switched systemic therapy after SBRT for oligoprogression were comparable, potentially indicating that further lines of treatment may be safely delayed in selected cases.

Repeat stereotactic body radiotherapy for oligometastatic disease.

BACKGROUND: Patients with oligometastatic disease (OMD) treated with metastasis-directed definitive local therapy such as stereotactic body radiotherapy (SBRT) are at risk of developing new metastases. Here, we compare characteristics and outcomes of patients treated with a single course and repeat SBRT. MATERIALS/METHODS: OMD patients treated with SBRT to 1-5 metastases were included in this retrospective study, and classified as single course or repeat SBRT. Progression-free survival (PFS), widespread failure-free survival (WFFS), overall survival (OS), systemic therapy-free survival (STFS) and cumulative incidence of different first failures were analyzed. Patient and treatment characteristics predicting the use of repeat SBRT were investigated using univariable and multivariable logistic regression. RESULTS: Among the 385 patients included, 129 and 256 received repeat or single course SBRT, respectively. The most common primary tumor and OMD state in both groups were lung cancer and metachronous oligorecurrence. Patients treated with repeat SBRT had shorter PFS (p < 0.0001), while WFFS (p = 0.47) and STFS (p = 0.22) were comparable. Distant failure, particularly with a single metastasis, was more frequently observed in repeat SBRT patients. Repeat SBRT patients had longer median OS (p = 0.01). On multivariable logistic regression, low distant metastases velocity and more previous lines of systemic therapy significantly predicted the use of repeat SBRT. CONCLUSION: Despite shorter PFS and comparable WFFS and STFS, repeat SBRT patients had longer OS. The role of repeat SBRT for OMD patients warrants further prospective investigation, focussing on predictive factors to select patients that might derive a benefit.

Stereotactic body radiotherapy to defer systemic therapy in patients with oligorecurrent disease.

Background: Patients 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/Methods: This 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. Results: Among 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. Conclusion: Selected 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.

Distant Metastasis Velocity as a Novel Prognostic Score for Overall Survival After Disease Progression Following Stereotactic Body Radiation Therapy for Oligometastatic Disease.

PURPOSE: In patients with extracranial oligometastatic disease, distant failure (DF) after local ablative therapies is common. Prognostic scores to guide salvage treatment decision making are currently lacking. Analogous to brain metastasis velocity, we propose distant metastasis velocity (DMV) as a prognostic score for overall survival (OS) and widespread failure-free survival (WFFS) after DF following metastasis-directed stereotactic body radiation therapy (SBRT). METHODS AND MATERIALS: Patients with ≤5 metastases from solid organ malignancies treated with SBRT to all lesions at our institution from 2014 to 2019 were screened, and patients who developed DF were included in this retrospective analysis. DMV was defined as metastases per month, determined at DF, and transformed into a 3-level categorical variable with cut points that minimized the log-rank P value for OS. Simple and multiple linear regression was used to predict DMV based on different patient and treatment variables. The association of DMV and other variables with OS was studied by univariable and multivariable Cox regression. RESULTS: Three hundred eighty-five patients were screened, of which 303 developed DF and were included. The median DMV was 0.7 metastases per month. Patients with <0.5, 0.5 to 1.5, and >1.5 metastases per month were classified as low, intermediate, and high DMV, and had a median OS of 37.1, 26.7, and 16.8 months, respectively (P < .0001). On multivariable analysis, DMV was a strong independent predictor of OS, with a hazard ratio of 0.31 for low (P < .001) compared with high DMV. Lower DMV was significantly associated with longer WFFS (P = .04). The cumulative metastases volume at baseline (regression coefficient ß = 0.03, P = .04) and oligoprogressive/-persistent disease (ß = 1.91, P = .10) predicted higher DMV. CONCLUSIONS: DMV is a novel metric strongly associated with OS and WFFS after DF following SBRT in patients with oligometastatic disease and should be evaluated for decision making about the optimal multimodality salvage treatment strategy. The prognostic value of DMV should be validated in prospective studies.

Evaluation of the prognostic value of the ESTRO EORTC classification of oligometastatic disease in patients treated with stereotactic body radiotherapy: A retrospective single center study.

PURPOSE: To explore the prognostic value of the oligometastatic disease (OMD) states as proposed by the European Society for Radiotherapy and Oncology (ESTRO) European Organisation for Research and Treatment of Cancer (EORTC) classification system. MATERIALS AND METHODS: This retrospective single-institution study included patients with 1-5 extracranial metastases from any solid malignancy treated with SBRT to all metastases. OMD states were defined according to the ESTRO EORTC classification. Overall survival (OS) and progression-free survival (PFS) were analyzed using the Kaplan-Meier method. Discriminatory strength of the classification was assessed by Gönen & Heller's concordance probability estimate (CPE). Univariable and multivariable Cox regression models were used to assess predictors of OS and PFS. RESULTS: In total, 385 patients were included. The median follow-up was 24.1 months. The most frequent OMD states were metachronous oligorecurrence (23.6%) and induced oligoprogression (18.7%). Induced OMD patients had significantly shorter median OS (28.1 months) compared with de-novo (46.3 months, p = 0.002) and repeat OMD (50.3 months, p = 0.002). Median PFS in de-novo OMD patients (8.8 months) was significantly longer than in repeat (5.4 months, p = 0.002) and induced OMD patients (4.3 months, p < 0.001). The classification system had moderate discriminatory strength for OS and PFS. Multivariable analyses confirmed that compared with induced OMD, de-novo OMD was associated with longer PFS and repeat with longer OS. CONCLUSION: All patients were successfully categorized according to the ESTRO EORTC classification system. The discriminatory strength of the classification was confirmed for OMD patients treated with metastases-directed SBRT. Larger multicenter trials are needed to validate the prognostic power for OMD patients irrespective of primary tumor and treatment approach.