Temporal evolution of CT imaging features in oligometastatic lung lesions after stereotactic body radiation therapy: a multicenter retrospective study of early tumor response as a predictor of favorable local control

Introduction

Patients diagnosed with extrapulmonary primary malignancies often confront the challenge of lung metastasis, which occurs in about 20–50% of cases as their disease progresses (1,2). Traditionally, the management of metastatic disease has predominantly relied on systemic therapy; however, there is a growing interest in incorporating metastasis-directed therapy into the treatment regimen for patients with oligometastatic disease, with the goal of improving progression-free and overall survival outcomes (3-6). Although surgery has historically served as the cornerstone of local therapy for metastases, less invasive alternatives such as stereotactic body radiation therapy (SBRT) or stereotactic ablative body radiation (SABR) are becoming more widely accepted (4-9). SBRT, as a noninvasive and safe alternative to surgery, enables the delivery of highly ablative radiation doses using conformal techniques. This approach minimizes exposure to nearby critical tissues, ensuring excellent local control with minimal toxicity (4-9).

In the post-SBRT follow-up of patients, accurate interpretation of computed tomography (CT) scans, the primary imaging modality, is imperative to differentiate potential local recurrences from benign changes post-treatment. Radiologists and oncologists must be familiar with these changes to be able to assess response and avoid the misclassification of benign changes as local recurrence of the tumor, which bears the risk of unnecessary biopsies or surgery, and avoid missing the opportunity to diagnose local relapse early when patients can benefit from salvage therapy (10-12). The early identification of patients who fail to respond to lung SBRT is vital as they can benefit from salvage therapy. However, there remains a significant gap in the comprehensive evaluation of evolving CT characteristics in lung metastases (13,14). Furthermore, there is an urgent need to identify early predictive indicators for patient outcomes, as this could significantly enhance our ability to tailor personalized treatment strategies and improve overall prognosis.

Although oligometastatic disease is typically defined as comprising up to five lesions occurring separately and distributed in up to three organs, previous studies on definitive radiotherapy for oligometastases have primarily focused on one to three metastases (3,15). For patients with four or more metastatic lesions, intensive systemic treatments such as chemotherapy and targeted therapy are often administered (4). However, the upper limit in the number of metastases remains a subject of ongoing debate and research. Reflecting this evolving paradigm, recent prospective clinical trials have explored the efficacy of definitive local therapy, such as SBRT, in patients with a higher burden of disease. For instance, the RISE trial is currently evaluating the integration of SBRT for extensive-stage small-cell lung cancer with up to 10 metastases (16). These patients may also receive prolonged systemic therapies, such as maintenance chemotherapy, even though they still fall within the oligometastatic spectrum. To precisely evaluate CT findings in lung metastases post-SBRT, it is critical to select patients carefully to avoid the confounding effects of high-intensity and long-term systemic treatments. Therefore, the selection should specifically include individuals who have a limited number of lung metastases and have received SBRT without undergoing high-intensity or long-term systemic therapies. The primary objective of this study was to investigate the temporal evolution of follow-up chest CT images post-SBRT in patients with up to three lung metastases, including solitary metastasis, and to identify the early predictive indicators of local control and prognosis, thereby significantly informing personalized treatment or follow-up strategies. We present this article in accordance with the STROBE reporting checklist (available at https://qims.amegroups.com/article/view/10.21037/qims-2025-1695/rc).

Methods

Patient population and inclusion criteria

This retrospective study was conducted across five centers: the Qingchun, Yuhang, and Zhijiang Centers Affiliated with the First Affiliated Hospital, Zhejiang University School of Medicine, and the Linhai and Enze Centers Affiliated with Taizhou Hospital of Zhejiang Province, Affiliated with Wenzhou Medical University. The study included patients with up to three pulmonary oligometastases who underwent SBRT between May 2018 and December 2022. Patients were eligible if they had no metastases in other organs, an Eastern Cooperative Oncology Group (ECOG) performance status of 0–2, and complete follow-up CT imaging data at the required intervals. For thoracic malignancies, including lung cancer, only patients who developed new pulmonary lesions after definitive treatment of the primary tumor were included, ensuring the diagnosis of metastasis rather than multiple primary tumors. For non-lung primary cancers (such as esophageal or breast cancer), both synchronous and metachronous pulmonary oligometastases were eligible, as these represent distinct metastatic disease patterns. All cases were reviewed by a multidisciplinary tumor board to confirm the diagnosis. Patients with diffuse metastatic disease, uncontrolled primary tumors, or incomplete follow-up imaging were excluded from the study. This study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. Ethical approval was obtained from the Institutional Review Boards of the First Affiliated Hospital, Zhejiang University School of Medicine and Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University (Nos. 2024-0513 and K20240740). The requirement for informed consent was waived by the Institutional Review Board of the First Affiliated Hospital, Zhejiang University School of Medicine because no identifying detail of the participants was included in this research. All participating institutions were also informed and agreed the study.

Imaging acquisition and evaluation

All non-contrast chest CT scans were performed with the patient in the supine position during end-inspiration to minimize respiratory motion artifacts. The scanning was conducted using Philips Brilliance 64 (Philips, Amsterdam, the Netherlands) at Center 1, Philips Incisive 32 at Center 2, GE Frontier 64 (GE Healthcare, Chicago, IL, USA) at Center 3, United Imaging uCT530 (United Imaging, Shanghai, China) at Center 4, and BrightSpeed Elite 16 (GE Healthcare) at Center 5. To ensure consistency across institutions, CT images were reconstructed as axial slices with a thickness of 5.0 mm and an interval of 5.0 mm. Tube voltage was set at 120 kVp, and adaptive tube current modulation was employed to reduce radiation exposure while maintaining high image quality. The reconstructed images were reviewed on lung and mediastinal window settings, optimized for evaluating both pulmonary lesions and surrounding tissues. This standardized acquisition protocol ensured reliable and comparable imaging data across all participating centers. CT imaging was conducted at baseline, 1 month, and every 3 months in the first year after SBRT, followed by every 6 months in the second year, and annually thereafter. To ensure robust and reliable outcome evaluation, all included patients were required to have a minimum follow-up period of 2 years within our hospitals.

CT images were independently reviewed by two thoracic radiologists (with 8 years and 18 years of respective experience in oncologic imaging) to ensure high diagnostic accuracy. Both radiologists were blinded to patient outcomes and clinical data during the initial assessment to minimize interpretation bias. Any discrepancies in findings were resolved through consensus meetings to maintain uniformity in data classification. Radiological changes following SBRT were assessed based on temporal evolution. Ground-glass opacity (GGO) was defined as hazy areas of increased lung attenuation that preserved bronchovascular margins and often represented subacute inflammatory or radiation-induced changes (13,14,17,18). Loose consolidation, characterized by increased density and obscured bronchovascular markings, was considered indicative of early radiation-induced pneumonitis or alveolar inflammation (13,14,18,19). Scar-like fibrosis manifested as linear opacities accompanied by volume loss within the irradiated field, representing the later stage of radiation-induced changes (13,14,18,19). Mass-like consolidation refers to well-circumscribed focal consolidation limited to the area surrounding the tumor, with the abnormality being larger than the original tumor (13,14,18,19). Local recurrence was radiologically defined as a progressive increase in lesion size within the irradiated field on sequential imaging (13,14,18,19).

Treatment evaluation and prognostic factors

To assess treatment efficacy, the 2-year local control rate was selected as the primary endpoint, as this period represents a critical window during which most local recurrences after SBRT are observed. This measure provides a reliable indicator of long-term treatment effectiveness. Patients who survived for at least 2 years after SBRT had follow-up imaging data covering this period, whereas those who experienced disease progression or death within 2 years were included in the analysis up to their last follow-up. This approach ensured comprehensive utilization of available patient data while minimizing selection bias.

Tumor response was evaluated dynamically throughout the follow-up period, with a particular focus on early response at 1-month post-SBRT. Tumor response was assessed using the Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) (20,21), classifying lesions into four categories—partial response (PR): a reduction in the longest diameter of the treated lesion by at least 30% compared to baseline. Complete response (CR): complete disappearance of the treated lesion with no residual abnormality on imaging. Stable disease (SD): neither sufficient shrinkage to qualify as PR nor sufficient increase to qualify as PD, typically representing changes of less than 30% in either direction. Progressive disease (PD): an increase in the longest diameter of the treated lesion by at least 20% or the appearance of new lesions within the treated region. PD was used as the primary radiological indicator of local recurrence. Based on the 1-month evaluation, PR and CR were grouped as a favorable early response, whereas SD and PD were considered a poor early response. Biologically effective dose, α/β=10 (BED10), was used to quantify the radiobiological effect of SBRT, accounting for both total dose and fractionation. Additionally, adverse events (AEs) related to SBRT were recorded from medical records using the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 to evaluate treatment toxicity and its potential impact on tumor control.

To identify potential prognostic factors for recurrence, clinical and imaging characteristics were compared between the recurrence and non-recurrence groups. Variables analyzed included sex, age, primary tumor site and histology, tumor location, tumor size, BED10, early tumor response at 1-month, and AEs related to SBRT. The goal was to determine whether factors such as metastasis diameter, BED10 dose, tumor location, and early response were associated with recurrence within 2 years.

Statistical analysis

All statistical analyses were performed using SPSS 22.0 for Windows (IBM Corp., Armonk, NY, USA). The prevalence of clinical and CT features was compared between the recurrence and non-recurrence groups at 2 years. Continuous variables were analyzed using Student’s t-test, whereas categorical variables were compared using the Chi-squared test or Fisher’s exact test, as appropriate. Actuarial local control rates were calculated using the Kaplan-Meier method, and comparisons between groups were performed using the log-rank test. The local control rate was defined as the proportion of patients who remained free of local recurrence at the specified time points.

Results

A total of 191 patients were enrolled from a multi-center network to secure a representative cohort. This cohort included 117 patients from one major institution and 71 from another, with five participating sub-centers contributing 68, 27, 22, 49, and 22 cases, respectively. With respect to the burden of oligometastatic disease, 151 patients had a single lesion, 25 had two lesions, and 15 had three lesions.

As shown in Table 1, among the 246 nodules analyzed, 30 experienced local recurrence within 2 years, whereas 216 did not. No significant differences were observed between the recurrence and non-recurrence groups in terms of sex, age, or follow-up time (all P>0.05). Primary tumor sites, including head and neck, thorax, and abdomen and pelvis, were not significantly associated with recurrence (P=0.119). Similarly, primary tumor histology, such as adenocarcinoma or squamous cell carcinoma, showed no significant impact on local recurrence (P=0.459). Tumor location, whether in different lung lobes or classified as central versus peripheral, also had no significant effect on recurrence (P=0.557 and P>0.99, respectively). Additionally, AEs related to SBRT were not significantly associated with recurrence risk (P=0.35). In contrast, tumor diameter, BED10 [dose to the planning target volume (PTV)], and early tumor response at 1-month follow-up were significantly associated with local recurrence (all P<0.05). Nodules ≤20 mm had significantly lower recurrence rates compared to those ≥30 mm (P<0.001). A higher BED10 (≥100 Gy) was associated with improved local control compared to doses <100 Gy (P=0.022). Furthermore, a favorable tumor response at 1-month follow-up CT was strongly predictive of lower recurrence rates compared to a bad response (P=0.001). As shown in Figure 1, the 2-year local control rate was 87.8% for all nodules, 95.0% for those with a favorable early response, and 81.1% for those with a bad early response.

Figure 1 Local control rate (%) for patients with pulmonary oligo-metastasis following SBRT. All patients had at least 2 years of follow-up, yet data beyond this period were incomplete for some, potentially limiting the observation of late recurrences. Therefore, the 2-year local control rate was chosen as a reliable measure of treatment effectiveness, with rates of 87.8% for all patients, 95.0% for those with a favorable early response, and 81.1% for those with a bad early response. SBRT, stereotactic body radiation therapy.

CT imaging revealed temporal evolution patterns of pulmonary oligometastatic nodules following SBRT (Figures 2-5). In nodules without recurrence (Figures 2,3), significant tumor shrinkage was frequently observed on 1-month post-SBRT CT scans (Figures 2B,3B). By 3 months, this was often followed by the development of loose consolidation with patchy GGO (Figures 2C,3C), which commonly aligned with the 50% isodose curve of the SBRT plan (Figures 2G,3H), suggesting treatment-induced effects. Over time, loose consolidation gradually resolved (Figures 2D,3D) and transitioned into scar-like fibrosis by 12 months (Figures 2E,3E). During long-term follow-up (18–36 months), fibrosis continued to regress (Figures 2F,3F,3G), reflecting stable local control. In contrast, recurrent nodules followed a different imaging trajectory (Figure 4). At 1-month post-SBRT, the lesion exhibited only slight shrinkage (19–16 mm), indicative of a poor early response (Figure 4B). By 3 months, persistent loose consolidation with patchy GGO was observed (Figure 4C). At 6 months, loose consolidation remained with minimal reduction in size (Figure 4D). A notable transition occurred at 9 months, when loose consolidation evolved into mass-like consolidation (Figure 4E). This mass-like consolidation raised suspicion of local recurrence, given its increasing density and size. By 12 months, further enlargement confirmed recurrence (Figure 4F).

Figure 2 Temporal evolution of CT images of a pulmonary oligometastatic nodule in a 60-year-old male patient with esophageal cancer, following SBRT. (A) The axial CT scan prior to SBRT reveals a solitary oligometastatic lung nodule (arrow) located in the right upper lobe, measuring 8 mm in diameter. (B) 1-month after SBRT, the CT scan demonstrates significant reduction in size of the solitary nodule (arrow), measuring 4 mm in diameter. (C) Three months post-SBRT, the CT scan exhibits loose consolidation (arrowheads) with patchy GGO (red arrowhead). (D) Six months post-SBRT, there is further shrinkage of the loose consolidation observed on CT scan (arrowheads). (E) At 12-month follow-up after SBRT, CT images reveal scar-like fibrosis (curved arrow). (F) At 18-month follow-up after SBRT, CT images reveal continued shrinkage of scar-like fibrosis (curved arrow). (G) SBRT isodose distribution with an axial slice of simulation CT. The distribution of the 50% isodose curve is similar to the region of loose consolidation and ground-glass opacity distribution presented at 3 months post-SBRT. CT, computed tomography; GGO, ground-glass opacity; SBRT, stereotactic body radiation therapy.

Figure 3 CT progression of a pulmonary oligometastatic nodule in a 39-year-old female patient with nasopharynx cancer, following SBRT. (A) The axial CT scan prior to SBRT reveals a solitary oligometastatic lung nodule (white arrow) with a small intracavitary lesion (red arrow) located in the right lower lobe. (B) 1-month after SBRT, the CT scan demonstrates that the nodule (white arrow) has slightly reduced in size, while the intracavitary lesion (red arrow) has become larger. (C) Three months post-SBRT, the CT scan exhibits loose consolidation (white arrowheads) with patchy GGO (red arrowhead). (D) Six months post-SBRT, there is further shrinkage of the loose consolidation observed on CT scan (arrowheads). (E) At 12-month follow-up after SBRT, CT images reveal scar-like fibrosis (curved arrow). (F) At 24-month follow-up after SBRT, CT images reveal continued shrinkage of scar-like fibrosis (curved arrow). (G) At 36-month follow-up after SBRT, CT images reveal continued shrinkage of scar-like fibrosis (curved arrow). (H) SBRT Isodose distribution with in axial slice of simulation CT. The distribution of the 50% isodose curve is similar to the region of loose consolidation and ground-glass opacity distribution presented at three months post-SBRT. CT, computed tomography; GGO, ground-glass opacity; SBRT, stereotactic body radiation therapy.

Figure 4 CT progression of a pulmonary oligometastatic nodule in a 48-year-old female patient with breast cancer, following SBRT. (A) The axial CT scan prior to SBRT reveals a solitary oligometastatic lung nodule (arrow) located in the right middle lobe, measuring 19 mm in diameter. (B) 1-month after SBRT, the CT scan demonstrates slightly reduction in size of the solitary nodule (arrow), measuring 16 mm in diameter. (C) Three months post-SBRT, the CT scan exhibits loose consolidation (arrowheads) with patchy ground-glass opacity (red arrowheads). (D) Six months post-SBRT, the CT scan exhibits loose consolidation (arrowheads). (E) At the 9-month follow-up after SBRT, CT images reveal a mass-like consolidation (star) with surrounding loose consolidation (arrowheads). At this time, we initially suspected that this mass-like consolidation represented local recurrence. (F) At 12-month follow-up after SBRT, CT images reveal continued enlargement of mass-like consolidation (star). At this time, we believed this mass-like consolidation represented local recurrence. CT, computed tomography; GGO, ground-glass opacity; SBRT, stereotactic body radiation therapy.

Figure 5 Temporal evolution of CT features following SBRT in pulmonary oligometastases. (A) Evolution of CT features in patients without recurrence. GGO (yellow circles) and loose consolidation (blue squares) were predominant in the early phase (3–6 months), followed by the resolution of loose consolidation and the gradual emergence of scar-like fibrosis (green triangles) after 9–12 months. Mass-like consolidation (gray triangles) was rarely observed in this group. (B) Evolution of CT features in patients with recurrence. GGO and loose consolidation initially appeared in a pattern similar to that seen in non-recurrent cases. However, mass-like consolidation became the dominant finding after 6–9 months, progressively increasing over time, indicating recurrent tumor progression. Scar-like fibrosis was less prominent compared to the non-recurrence group. This figure serves as a summarized comparison of the characteristic temporal trajectories between recurrent and non-recurrent lesions, reflecting the cohort-level evolution patterns observed in this study. CT, computed tomography; GGO, ground-glass opacity; M, month; SBRT, stereotactic body radiation therapy.

A distinct comparison between recurrent and non-recurrent cases is illustrated in Figure 5. In patients without recurrence (Figure 5A), early post-SBRT changes were characterized by transient GGO and loose consolidation, peaking at 3–6 months before gradually resolving. By 9–12 months, scar-like fibrosis emerged as the predominant feature, increasing steadily and remaining stable at long-term follow-up (18–24 months). Mass-like consolidation was rarely observed in non-recurrent nodules. In contrast, patients with recurrence (Figure 5B) exhibited a different trajectory. Although early-phase GGO and loose consolidation were present at 3–6 months, mass-like consolidation progressively increased from 6–9 months, becoming the dominant radiological feature. Unlike non-recurrent nodules, where scar-like fibrosis stabilized over time, recurrent lesions demonstrated a continuous increase in mass-like consolidation, indicative of progressive tumor regrowth.

Discussion

This multicenter retrospective study explored the temporal evolution of CT imaging features in pulmonary oligometastatic nodules following SBRT and identified critical predictors of local control, including early tumor response, tumor diameter, and BED10 (dose to the PTV). The efficacy of SBRT is well-established, not only in the oligometastatic setting but also as a definitive, standard-of-care treatment for medically inoperable patients with early-stage (N0M0) non-small cell lung cancer (NSCLC) with tumors up to 4 cm in size. This underscores the broad and central role of SBRT across the continuum of thoracic oncology (22,23). Our findings provide valuable insights into the dynamic post-SBRT changes observed on CT imaging and highlight their potential to guide clinical decision-making and personalized patient management.

One of the key findings of this study is the significant predictive value of early tumor response for long-term (2-year) local control. Patients with a favorable early response at 1-month follow-up CT demonstrated a markedly higher 2-year local control rate (95.0%) compared to those with a bad early response (81.1%). Our 2-year local control rate is consistent with existing literature, which reports a 2-year local control rate of 80–95% for pulmonary oligometastasis, with low rates of severe AEs, even when targeting up to four lesions (3,6,15,24). The strength of this study lies in its stratification approach, which identified valuable early predictors. Most prior studies recommend the first follow-up CT at 3 months post-SBRT as a standard practice for evaluating treatment response (7,14,19,25). However, our study found that 3-month follow-up CT often showed loose consolidation, which could confound the assessment of treatment efficacy. Therefore, we propose that early CT imaging at 1-month post-SBRT is a valuable supplement, aiding in the early prediction of treatment efficacy. Moreover, it is important to note that early shrinkage was not exclusive to non-recurrent nodules, as a subset of recurrent nodules also demonstrated initial reduction in size. This finding suggests that although early response is an important prognostic marker, it should not be used in isolation to determine long-term outcomes. Continuous imaging follow-up remains essential for detecting subtle changes indicative of recurrence. Similarly, Herman et al. cautioned against using early imaging alone to predict recurrence, recommending more frequent and prolonged follow-up CT (6).

In this study, we identified tumor diameter as a significant predictor of local control. Smaller tumors (≤20 mm) showed superior control rates compared to larger tumors (≥30 mm), consistent with previous studies (15,25,26). This is likely due to the more effective dose distribution in smaller lesions and the reduced heterogeneity within the tumor, which allows for more uniform targeting by SBRT. Meanwhile, larger tumors often pose greater challenges in dose coverage and may harbor radioresistant regions, contributing to the increased likelihood of recurrence.

In our study, BED10 emerged as a significant predictor of local control, underscoring the importance of radiation dose escalation in achieving optimal treatment outcomes. This study aligns with previous studies that have demonstrated that higher BED10 values, typically above 100 Gy, are associated with better local control rates in pulmonary oligometastatic lesions (8,25,26). Beyond its direct oncologic outcomes, the toxicity profile of SBRT, particularly its impact on the immune system, warrants careful consideration. A growing body of evidence indicates that low-dose radiation exposure to large volumes of healthy lung parenchyma is a key predictor of treatment-related lymphopenia (27,28). This is of paramount clinical significance, as lymphopenia has been consistently identified as a powerful independent prognostic factor across multiple cancer types, including lung cancer. Severe lymphopenia can compromise immune surveillance and is associated with reduced tolerance to subsequent systemic therapies, such as chemotherapy and consolidation immunotherapy, which are now standard in the management of NSCLC (29). Therefore, treatment planning strategies that minimize integral lung dose may not only reduce the risk of classic radiation pneumonitis but also preserve lymphocyte counts, potentially improving a patient’s capacity to complete planned multimodal treatment and thereby impacting overall survival. Furthermore, although higher BED10 values correlate with improved local control, it is essential to balance dose escalation with the risk of normal tissue toxicity (3). The challenge lies in maximizing the tumoricidal effects of SBRT while minimizing damage to adjacent healthy lung tissue.

The temporal evolution of CT imaging after SBRT plays a crucial role in predicting treatment response and detecting recurrence in pulmonary oligometastatic lesions. In our study, the early changes observed at 1-month post-SBRT, including significant tumor shrinkage, were predictive of favorable long-term outcomes. Such early responses can guide clinical decision-making by identifying patients who are more likely to achieve durable local control, further supporting the role of early follow-up imaging in assessing treatment efficacy. In our study, GGO and loose consolidation were commonly observed in non-recurrent patients, typically localized within the 50% isodose curve. These changes are consistent with previous studies (18,30), which noted that these imaging changes represent early radiation-induced inflammatory responses. Such changes are generally considered benign, as they resolve over time and progress into scar-like fibrosis. This evolution from GGO to fibrosis aligns with the observations of Guerreiro et al. (31), who noted that post-SBRT changes in non-recurrent lesions generally evolve into stable fibrosis without further progression or recurrence. Our study corroborates this, showing that long-term follow-up demonstrated continued fibrosis shrinkage with no evidence of recurrence, supporting the notion that fibrosis represents a stable post-treatment response rather than malignant progression.

In contrast, recurrent lesions exhibited a markedly different imaging progression. Although some lesions showed slight shrinkage, this partial reduction in size in SD, categorized as bad early response, was not sustained. Over time, these lesions developed into mass-like consolidation. Mass-like consolidation, characterized by dense and well-circumscribed focal consolidation exceeding the original tumor margins, is a hallmark feature of local recurrence, as noted in Halpenny et al. (32) and Guerreiro et al. (31). This shift from early slight shrinkage to mass-like changes underscores the need for continuous follow-up imaging, as early tumor shrinkage, though predictive in most cases, is not an absolute guarantee of long-term control. This finding emphasizes the importance of continuous follow-up imaging to differentiate between benign post-treatment changes and recurrence.

The observed imaging patterns have significant implications for clinical practice. The observed temporal evolution of lesions post-SBRT provides valuable insights into treatment response and long-term prognosis. Familiarity with typical post-SBRT changes, such as loose consolidation and GGO, can help radiologists and oncologists differentiate benign findings from recurrence, reducing the risk of unnecessary interventions such as biopsies or additional imaging. Conversely, recognizing atypical features, such as persistent consolidation or mass-like changes, can raise clinical suspicion for recurrence, prompting timely diagnostic evaluations. Early identification of recurrence enables the initiation of personalized salvage treatments, including repeat SBRT, surgery, or systemic therapy, potentially improving patient outcomes and prolonging survival.

Strengths and limitations of the study

This study benefits from a multicenter design, which enhances the generalizability of the findings. The inclusion of patients with a limited metastatic burden (up to 3 lung metastases) reduces confounding effects from extensive systemic disease and allows for a more focused evaluation of SBRT outcomes. The correlation between early post-treatment imaging changes and long-term prognosis underscores the importance of early treatment response assessment in guiding patient management. However, several limitations should be noted. First, the retrospective nature of the study introduces the potential for selection bias, as patients with incomplete follow-up imaging were excluded. Second, the absence of histopathological confirmation for all suspected recurrences may limit the accuracy of recurrence classification. Future research should focus on validating these findings in larger patient cohorts. Additionally, prospective studies with standardized imaging and reporting protocols are needed to validate these findings and further refine the criteria for differentiating recurrence from benign post-SBRT changes.

Conclusions

This study emphasizes the prognostic value of early tumor response, tumor diameter, and BED10 in predicting local control in pulmonary oligometastatic nodules treated with SBRT. The temporal evolution of CT imaging provides critical insights into treatment outcomes, with two key phases being particularly important. The first phase, occurring at 1-month post-treatment, reveals whether tumor shrinkage has occurred, which serves as an early predictor of potential recurrence. The second phase, as the lesion transitions from consolidation to fibrosis, is crucial for identifying recurrence-related features, particularly in cases where consolidation persists or evolves into mass-like changes. Recognizing these patterns and deviations is essential for facilitating timely interventions, optimizing patient management, and improving clinical outcomes.

Acknowledgments

None.

Footnote

Reporting Checklist: The authors have completed the STROBE reporting checklist. Available at https://qims.amegroups.com/article/view/10.21037/qims-2025-1695/rc

Data Sharing Statement: Available at https://qims.amegroups.com/article/view/10.21037/qims-2025-1695/dss

Funding: This study was partially supported by the National Natural Science Foundation of China (Nos. 82171890 and 81701683), and Taizhou Science and Technology Bureau, Taizhou Science and Technology Program Project (No. 24ywb36).

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://qims.amegroups.com/article/view/10.21037/qims-2025-1695/coif). F.Z. serves as an unpaid editorial board member of Quantitative Imaging in Medicine and Surgery, and he reports funding of National Natural Science Foundation of China (Nos. 82171890 and 81701683). J.P. reports funding of Taizhou Science and Technology Bureau, Taizhou Science and Technology Program Project (No. 24ywb36). The other authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. The retrospective research was approved by the Institutional Review Boards of the First Affiliated Hospital, Zhejiang University School of Medicine and Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University (Nos. 2024-0513 and K20240740) and was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. Informed consent was waived by the Institutional Review Board of the First Affiliated Hospital, Zhejiang University School of Medicine because no identifying detail of the participants was included in this research. All participating institutions were also informed and agreed the study.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

References

1. Mohammed TL, Chowdhry A, Reddy GP, Amorosa JK, Brown K, Dyer DS, Ginsburg ME, Heitkamp DE, Jeudy J, Kirsch J, MacMahon H, Parker JA, Ravenel JG, Saleh AG, Shah RDExpert Panel on Thoracic Imaging. ACR Appropriateness Criteria® screening for pulmonary metastases. J Thorac Imaging 2011;26:W1-3. [Crossref] [PubMed]
2. Franquet T, Rosado-de-Christenson ML, Marchiori E, Abbott GF, Martínez-Jiménez S, López L. Uncommon thoracic manifestations from extrapulmonary tumors: Computed tomography evaluation - Pictorial review. Respir Med 2020;168:105986. [Crossref] [PubMed]
3. Chmura S, Winter KA, Robinson C, Pisansky TM, Borges V, Al-Hallaq H, et al. Evaluation of Safety of Stereotactic Body Radiotherapy for the Treatment of Patients With Multiple Metastases: Findings From the NRG-BR001 Phase 1 Trial. JAMA Oncol 2021;7:845-852. [Crossref] [PubMed]
4. Palma DA, Olson R, Harrow S, Gaede S, Louie AV, Haasbeek C, et al. Stereotactic ablative radiotherapy versus standard of care palliative treatment in patients with oligometastatic cancers (SABR-COMET): a randomised, phase 2, open-label trial. Lancet 2019;393:2051-8. [Crossref] [PubMed]
5. Palma DA, Olson R, Harrow S, Gaede S, Louie AV, Haasbeek C, et al. Stereotactic Ablative Radiotherapy for the Comprehensive Treatment of Oligometastatic Cancers: Long-Term Results of the SABR-COMET Phase II Randomized Trial. J Clin Oncol 2020;38:2830-8. [Crossref] [PubMed]
6. Gits HC, Khosravi Flanigan MA, Kapplinger JD, Reisenauer JS, Eiken PW, Breen WG, et al. Sublobar Resection, Stereotactic Body Radiation Therapy, and Percutaneous Ablation Provide Comparable Outcomes for Lung Metastasis-Directed Therapy. Chest 2024;165:1247-59. [Crossref] [PubMed]
7. Navarria P, Ascolese AM, Cozzi L, Tomatis S, D'Agostino GR, De Rose F, De Sanctis R, Marrari A, Santoro A, Fogliata A, Cariboni U, Alloisio M, Quagliuolo V, Scorsetti M. Stereotactic body radiation therapy for lung metastases from soft tissue sarcoma. Eur J Cancer 2015;51:668-74. [Crossref] [PubMed]
8. Antonoff MB, Sofocleous CT, Callstrom MR, Nguyen QN. The roles of surgery, stereotactic radiation, and ablation for treatment of pulmonary metastases. J Thorac Cardiovasc Surg 2022;163:495-502. [Crossref] [PubMed]
9. Das A, Giuliani M, Bezjak A. Radiotherapy for Lung Metastases: Conventional to Stereotactic Body Radiation Therapy. Semin Radiat Oncol 2023;33:172-80. [Crossref] [PubMed]
10. Willmann J, Adilovic S, Vlaskou Badra E, Christ SM, Ahmadsei M, Tanadini-Lang S, Mayinger M, Guckenberger M, Andratschke N. Repeat stereotactic body radiotherapy for oligometastatic disease. Radiother Oncol 2023;184:109671. [Crossref] [PubMed]
11. Sharma A, Duijm M, Oomen-de Hoop E, Aerts JG, Verhoef C, Hoogeman M, Nuyttens JJ. Factors affecting local control of pulmonary oligometastases treated with stereotactic body radiotherapy. Acta Oncol 2018;57:1031-7. [Crossref] [PubMed]
12. Fodor A, Mori M, Tummineri R, Broggi S, Deantoni CL, Mangili P, Baroni S, Villa SL, Dell'Oca I, Del Vecchio A, Fiorino C, Di Muzio N. CT radiomic predictors of local relapse after SBRT for lung oligometastases from colorectal cancer: a single institute pilot study. Strahlenther Onkol 2023;199:477-84. [Crossref] [PubMed]
13. Kim TH, Woo S, Halpenny DF, Kim YJ, Yoon SH, Suh CH. Can high-risk CT features suggest local recurrence after stereotactic body radiation therapy for lung cancer? A systematic review and meta-analysis. Eur J Radiol 2020;127:108978. [Crossref] [PubMed]
14. Huang K, Senthi S, Palma DA, Spoelstra FO, Warner A, Slotman BJ, Senan S. High-risk CT features for detection of local recurrence after stereotactic ablative radiotherapy for lung cancer. Radiother Oncol 2013;109:51-7. [Crossref] [PubMed]
15. Virbel G, Le Fèvre C, Noël G, Antoni D. Stereotactic Body Radiotherapy for Patients with Lung Oligometastatic Disease: A Five-Year Systematic Review. Cancers (Basel) 2021;13:3623. [Crossref] [PubMed]
16. Kuncman Ł, Fijuth J, Tworek D, Sierko E, Cisek P, Masłowski M, Lisik-Habib M, Orzechowska M, Galwas-Kliber K, Antczak A, Chmielewska I, Ziółkowska B, Kurczewska-Michalak M, Kuźnicki W, Jędrzejczak N, Ranoszek K, Bilski M. Radiotherapy(R) Integration(I) Strategy for Small(S)-Cell Lung Cancer in Extensive(E) Stage (RISE) with up to 10 metastases- a study protocol of a randomized phase II trial. BMC Cancer 2025;25:142. [Crossref] [PubMed]
17. Bankier AA, MacMahon H, Colby T, Gevenois PA, Goo JM, Leung ANC, Lynch DA, Schaefer-Prokop CM, Tomiyama N, Travis WD, Verschakelen JA, White CS, Naidich DP. Fleischner Society: Glossary of Terms for Thoracic Imaging. Radiology 2024;310:e232558. [Crossref] [PubMed]
18. Yang Y, Li G, Li S, Wang Y, Zhao Y, Dong B, Wang J, Zhu R, Chen M. CT Appearance Pattern After Stereotactic Body Radiation Therapy Predicts Outcomes in Early-Stage Non-Small-Cell Lung Cancer. Front Oncol 2021;11:746785. [Crossref] [PubMed]
19. Dahele M, Palma D, Lagerwaard F, Slotman B, Senan S. Radiological changes after stereotactic radiotherapy for stage I lung cancer. J Thorac Oncol 2011;6:1221-8. [Crossref] [PubMed]
20. Yang D, Woodard G, Zhou C, Wang X, Liu Z, Ye Z, Li K. Significance of different response evaluation criteria in predicting progression-free survival of lung cancer with certain imaging characteristics. Thorac Cancer 2016;7:535-42. [Crossref] [PubMed]
21. He LN, Chen T, Fu S, Jiang Y, Zhang X, Chen C, Du W, Luo L, Li A, Wang Y, Yu H, Zhou Y, Wang Y, Yang Y, Huang Y, Zhao H, Fang W, Zhang L, Hong S. Tumor response assessment by measuring the single largest lesion per organ in advanced non-small cell lung cancer patients treated with PD-1/PD-L1 inhibitor. Ther Adv Med Oncol 2023;15:17588359231200463. [Crossref] [PubMed]
22. Wujanto C, Vellayappan B, Siva S, Louie AV, Guckenberger M, Slotman BJ, Onishi H, Nagata Y, Liu M, Lo SS. Stereotactic Body Radiotherapy for Oligometastatic Disease in Non-small Cell Lung Cancer. Front Oncol 2019;9:1219. [Crossref] [PubMed]
23. Sebastian NT, Xu-Welliver M, Williams TM. Stereotactic body radiation therapy (SBRT) for early stage non-small cell lung cancer (NSCLC): contemporary insights and advances. J Thorac Dis 2018;10:S2451-64. [Crossref] [PubMed]
24. Hurmuz P, Cengiz M, Esen CSB, Yedekci Y, Yildiz Z, Ozyigit G, Zorlu F, Akyol F. Factors affecting post-treatment radiation-induced lung disease in patients receiving stereotactic body radiotherapy to lung. Radiat Environ Biophys 2021;60:87-92. [Crossref] [PubMed]
25. García-Cabezas S, Bueno C, Rivin E, Roldán JM, Palacios-Eito A. Lung metastases in oligometastatic patients: outcome with stereotactic body radiation therapy (SBRT). Clin Transl Oncol 2015;17:668-72. [Crossref] [PubMed]
26. Kimura T, Fujiwara T, Kameoka T, Adachi Y, Kariya S. Stereotactic body radiation therapy for metastatic lung metastases. Jpn J Radiol 2022;40:995-1005. [Crossref] [PubMed]
27. Kuncman Ł, Pajdziński M, Smółka K, Bilski M, Socha J, Stando R, Peszyńska-Piorun M, Korab K, Jereczek-Fossa BA, Fijuth J. Early lymphocyte levels and low doses radiation exposure of lung predict lymphopenia in radiotherapy for lung cancer. Front Immunol 2024;15:1426635. [Crossref] [PubMed]
28. Ray-Coquard I, Cropet C, Van Glabbeke M, Sebban C, Le Cesne A, Judson I, Tredan O, Verweij J, Biron P, Labidi I, Guastalla JP, Bachelot T, Perol D, Chabaud S, Hogendoorn PC, Cassier P, Dufresne A, Blay JY. Lymphopenia as a prognostic factor for overall survival in advanced carcinomas, sarcomas, and lymphomas. Cancer Res 2009;69:5383-91. [Crossref] [PubMed]
29. Anichini A, Tassi E, Grazia G, Mortarini R. The non-small cell lung cancer immune landscape: emerging complexity, prognostic relevance and prospective significance in the context of immunotherapy. Cancer Immunol Immunother 2018;67:1011-22. [Crossref] [PubMed]
30. Huang K, Dahele M, Senan S, Guckenberger M, Rodrigues GB, Ward A, Boldt RG, Palma DA. Radiographic changes after lung stereotactic ablative radiotherapy (SABR)--can we distinguish recurrence from fibrosis? A systematic review of the literature. Radiother Oncol 2012;102:335-42. [Crossref] [PubMed]
31. Guerreiro NFC, Araujo-Filho JAB, Horvat N, Lee HJ, Oliveira BSP, Ynoe de Moraes F, Castro I, Miranda Degrande FA, Abreu CEV, Giassi KS. Interobserver Variability in the Computed Tomography Assessment of Pulmonary Injury and Tumor Recurrence After Stereotactic Body Radiotherapy. J Thorac Imaging 2020;35:302-8. [Crossref] [PubMed]
32. Halpenny D, Ridge CA, Hayes S, Zheng J, Moskowitz CS, Rimner A, Ginsberg MS. Computed tomographic features predictive of local recurrence in patients with early stage lung cancer treated with stereotactic body radiation therapy. Clin Imaging 2015;39:254-8. [Crossref] [PubMed]