Stereotactic body radiotherapy for lung oligometastases impacts on systemic treatment-free survival: a cohort study

Abstract

To analyze the impact of SBRT on systemic treatment-free survival in patients affected by lung oligometastases. Inclusion criteria of the study were (a) KPS > 70, (b) 1-5 lung oligometastases underwent SBRT with a BED ≥ 100 Gy, (c) absence of extra-thoracic disease, (d) controlled primary tumor, (e) metachronous oligorecurrences for whom SBRT was adopted as primary treatment option, (f) oligoprogressive lung metastases who progressed following a disease remission after a first-line therapy, (g) oligopersistent disease after systemic therapy, and (h) at least 6 months of follow-up post-SBRT. Primary study endpoint was the systemic treatment-free survival for each group, whereas distant progression-free survival (DPFS), local failure-free survival (LFFS), and overall survival (OS) were the secondary endpoints. Seventy-eight patients and 114 lung metastases were analyzed. Of these, 32 patients were treated with SBRT in the oligorecurrence group, whereas the remaining patients underwent SBRT for oligoprogressive disease (n = 35) oligopersistent disease (n = 11). In the whole cohort of patients, the median systemic treatment-free survival was 16 months (3-46 months), the median LFFS was 18 months (12-46 months), the median DPFS was 14 months (3-43 months), and the median OS was 19.6 months (12-47 months). Oligorecurrence group had better clinical outcomes in terms of systemic treatment-free survival (log-rank test p = 0.0035) and DPFS (log-rank test p = 0.0017) compared to the other groups. In the present experience, SBRT allowed to delay the administration of systemic treatments in several settings of lung oligometastasis.

Defining oligometastatic disease from a radiation oncology perspective: An ESTRO-ASTRO consensus document

“…Few lesions progress on a background of widespread but stable metastatic disease [83] + Link with other therapies Progression occurs in a limited number of tumors/metastases while the majority of other metastases are responding or stable while on a systemic treatment strategy [41,48,61] Progression occurs after a cytoreductive treatment [67] Progression while other sites including the primary disease remain stable on systemic treatment or observation [113] Resistant clones can result in isolated progression [42] + Disease load <5 enlarging metastases in an otherwise well-controlled disease state [39] <5 sites of metastatic disease progression while other sites including primary remain stable on systemic treatment [113] 3-5 slowly progressive metastases [36,48] Oligo-Persistence Persistent disease after systemic therapy [67] + Disease load <5 persistent lesions after systemic therapy [39] Statements 7 and 9:…”

“…While there are not sufficient literature data to address dose and BED by primary and in all relevant contexts, the convergence of existing data highlighting improved LC of the targeted metastasis with a minimum of 100 Gy BED 10 makes this a goal when feasible until further evidence emerges [23,35,44,52,63,67,73,78,98]. It is noted however that in sites where normal tissue constraints make this infeasible near the bowel, great vessels or spinal cord, lower BEDs have been associated with control [99,100] and future studies may identify clinical scenarios where lower doses are ade-quate.…”

Oligometastasis and local ablation in the era of systemic targeted and immunotherapy

“…The term oligometastases is referred to a limited tumor burden potentially amenable to local approaches. In this last clinical scenario, high-dose radiation therapy, also known as stereotactic body radiotherapy (SBRT), represents a viable treatment option able to modify the natural history of the oligometastatic disease [1][2][3][4][5].…”

Clonality analysis of pulmonary tumors by genome-wide copy number profiling

“…Therefore, patients with widespread metastatic disease were not included in our study. Patients in our study had only one or a very limited number of tumors, so the degree of metastatic spread at the time of presentation was lower than a random cohort of metastatic lung cancer patients [77,78]. Thus, selection of cases in our study explains the paradox.…”

“…If metastases develop in time, this may be related to one or both initial tumors. The absence of metastatic disease during follow-up does not exclude a clonal relationship between two radically treated tumors either, as radical treatment improves clinical outcomes in oligometastatic disease [76,77]. Therefore, the results of follow-up are not decisive about clonality between tumors.…”