Stereotactic ablative radiotherapy and systemic treatments for extracerebral oligometastases, oligorecurrence, oligopersistence and oligoprogression from lung cancer

Kissel, M.; Lequesne, Justine; Faivre, J; Péchoux, C. Le; Stefan, Dinu; Barraux, V.; Loiseau, C.; Grellard, Jean‐Michel; Danhier, S.; Lerouge, D.; Chouaïd, C.; Gervais, Radj; Thariat, Juliette

doi:10.1186/s12885-019-6449-8

Cited by 21 publications

(8 citation statements)

References 25 publications

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“…Since lymph nodes and lung are also very frequent sites of metastatic involvement in NSCLC, it is not surprising that they showed a higher frequency of OPD in our series ( Table 2). On the other hand, liver OPD was rare in our patients (Table 2), which parallels the rarity of hepatic oligoprogression in EGFR-mutated NSCLC [4,5] and is in line with the lower immune reactivity and worse prognosis of hepatic metastases and hepatic oligoprogression in NSCLC [33][34][35].…”

Section: Discussionsupporting

confidence: 81%

Oligoprogressive Non-Small-Cell Lung Cancer under Treatment with PD-(L)1 Inhibitors

Rheinheimer

Heußel

Mayer

et al. 2020

Cancers

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Oligoprogression (OPD) of non-small-cell lung cancer (NSCLC) occurs in approximately half of patients under targeted compounds (TKI) and facilitates use of regional therapies that can prolong survival. In order to characterize OPD in immunotherapy (IO)-treated NSCLC, we analyzed the failure pattern under PD-1/PD-L1 inhibitors (n = 297) or chemoimmunotherapy (n = 75). Under IO monotherapy, OPD was more frequent (20% vs. 10%, p < 0.05), occurred later (median 11 vs. 5 months, p < 0.01), affected fewer sites (mean 1.1 vs. 1.5, p < 0.05), and involved fewer lesions (1.4 vs. 2.3, p < 0.05) in the first compared to later lines. Lymph nodes (42%, mainly mediastinal) and the brain (39%) were mostly affected, followed by the lung (24%) and other organs. Compared to multifocal progression, OPD occurred later (11 vs. 4 months, p < 0.001) and was associated with longer survival (26 vs. 13 months, p < 0.001) and higher tumor PD-L1 expression (p < 0.001). Chemoimmunotherapy showed a similar incidence of OPD as IO monotherapy (13% vs. 11% at 2 years). Local treatments were applied regularly for brain but only in 50% for extracranial lesions. Thus, NSCLC oligoprogression is less common under IO than under TKI, but also favorable. Since its frequency drops later in the disease, regular restaging and multidisciplinary evaluation are essential in order to exploit the full therapeutic potential.

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Section: Discussionsupporting

confidence: 81%

Oligoprogressive Non-Small-Cell Lung Cancer under Treatment with PD-(L)1 Inhibitors

Rheinheimer

Heußel

Mayer

et al. 2020

Cancers

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“…Major exclusion criteria included other previous thoracic radiotherapy or prior TKIs therapy. Oligometastatic disease was defined as the presence of ≤5 lesions in 1 to multiple organs at the initiation of TKIs, while poly-metastatic disease was defined as > 5 metastatic lesions [18]. Oligoprogression was defined as being in a polymetastatic state with progressive lesions, while all other lesions were controlled with TKIs.…”

Section: Patientsmentioning

confidence: 99%

“…Oligoprogression was defined as being in a polymetastatic state with progressive lesions, while all other lesions were controlled with TKIs. Oligopersistence was defined as stable residual disease sites (in five or fewer sites) after systemic treatment [18,19].…”

Section: Patientsmentioning

confidence: 99%

Efficacy and acquired resistance for EGFR-TKI plus thoracic SBRT in patients with advanced EGFR-mutant non–small-cell lung cancer: a propensity-matched retrospective study

et al. 2021

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Background This retrospective study aimed to evaluate the efficacy of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) with stereotactic body radiation therapy (SBRT) and to elucidate potential mechanisms of acquired resistance. Methods Patients with advanced NSCLC harboring positive EGFR mutations after initial TKI therapy for at least 8 weeks were eligible for SBRT between August 2016 and August 2019. Eligible patients were treated with thoracic SBRT, and TKI was continued after SBRT until it was considered ineffective. The control group was treated with TKIs monotherapy. Propensity score matching (PSM, ratio of 1:2) was used to account for differences in baseline characteristics. Overall survival (OS), progression-free survival (PFS), treatment safety and resistance mechanisms were evaluated. Results Three hundred eight patients were included in the study population. Among them, 262 patients received TKIs alone, and 46 patients received TKIs with SBRT. Baseline characteristics were not significantly different between the two cohorts after PSM. The median PFS was 19.4 months in the TKIs +SBRT group compared to 13.7 months in the TKIs group (p = 0.034). An influence on OS has not yet been shown (p = 0.557). Of the 135 patients evaluated after PSM, 28 and 71 patients in the TKIs and TKIs +SBRT cohorts, respectively, had plasma cell-free DNA (cfDNA) next-generation sequencing (NGS) performed at baseline and disease progression. In the TKIs +SBRT cohort, the NGS results showed that T790M mutations were detected in 64.3% (18/28) of patients. Patients in the TKIs cohort exhibited fewer T790M-positive mutations (40.8%, p = 0.035) compared to patients in the TKIs +SBRT cohort. Conclusion Real world data prove that TKIs plus thoracic SBRT significantly extend PFS with tolerable toxicity. The mutation ratio of T790M was increased in the TKIs +SBRT group compared to the TKIs only group. Further randomized studies are warranted.

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“…Over the past 30 years oligometastatic NSCLC has been recognized as a unique clinical entity [3][4][5]11,25]. Several retrospective series and some prospective studies have demonstrated the efficacy and safety of aggressive approaches in selected patients with OMD and supported the use of metastasis-directed ablative radiotherapy alone, or in addition to a primary therapy to consolidate all sites of gross disease [26][27][28][29][30][31][32]. In addition, results from recent Phase II randomized trials have revealed a potential benefit for ablative RT in prolonging PFS [12] and OS [13,14].…”

Section: Discussionmentioning

confidence: 99%

Role of Radiosurgery and Stereotactic Ablative Radiotherapy for Oligometastatic Non-Oncogene Addicted NSCLC

Badellino

Levis

Cuffini

et al. 2022

Cancers

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Local ablative therapy (LAT), intended as stereotactic ablative radiotherapy or stereotactic radiosurgery, is a well-recognized effective treatment for selected patients with oligometastatic NSCLC. Current clinical evidence supports LAT alone or in combination with systemic therapies. Our retrospective mono-institutional study aims to assess the role of LAT with a peculiar focus on the largest series of non-oncogene addicted oligometastatic NSCLC patients to date. We included in this analysis all patients with the mentioned disease characteristics who underwent LAT for intracranial and/or extracranial metastases between 2011 and 2020. The main endpoints were local control (LC), progression free survival (PFS) and overall survival (OS) in the whole population and after stratification for prognostic factors. We identified a series of 245 consecutive patients (314 lesions), included in this analysis (median age 69 years). In 77% of patients, a single metastasis was treated with LAT and intracranial involvement was the most frequent indication (53% of patients) in our series. The overall response rate (ORR) after LAT was 95%. In case of disease progression, 66 patients underwent new local treatments with curative intent. With a median follow-up of 18 months, median PFS was 13 months (1-year PFS 50%) and median OS was 32 months (1-year OS 75%). The median LC was not reached (1-year LC 89%). The presence of brain metastases was the only factor that negatively affected all clinical endpoints, with a 1-year LC, PFS and OS of 82%, 29% and 62% respectively, compared to 95%, 73% and 91%, respectively, for patients without BMs (p < 0.001 for each endpoint). At the multivariate analysis, mediastinal nodal involvement at baseline (p = 0.049), ECOG PS = 1 (p = 0.011), intracranial disease involvement (p = 0.001), administration of chemotherapy in combination with LAT (p = 0.020), and no delivery of further local treatment for progression or delivery of focal treatment for intracranial progression (p < 0.001) were related to a poorer OS. In our retrospective series, which is to our knowledge the largest to date, LAT showed encouraging results and confirmed the safety and effectiveness of focal treatments in non-oncogene addicted oligometastatic NSCLC patients.

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Stereotactic ablative radiotherapy and systemic treatments for extracerebral oligometastases, oligorecurrence, oligopersistence and oligoprogression from lung cancer

Cited by 21 publications

References 25 publications

Oligoprogressive Non-Small-Cell Lung Cancer under Treatment with PD-(L)1 Inhibitors

Oligoprogressive Non-Small-Cell Lung Cancer under Treatment with PD-(L)1 Inhibitors

Efficacy and acquired resistance for EGFR-TKI plus thoracic SBRT in patients with advanced EGFR-mutant non–small-cell lung cancer: a propensity-matched retrospective study

Role of Radiosurgery and Stereotactic Ablative Radiotherapy for Oligometastatic Non-Oncogene Addicted NSCLC

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