Imaging-guided adaptive radiation therapy in limited-stage small cell lung cancer: Current evidence and clinical perspectives

Abstract

Small cell lung cancer (SCLC) remains among the most aggressive thoracic malignancies and continues to present major therapeutic challenges despite advances in multimodality treatment. Limited-stage SCLC (LS-SCLC), representing approximately one-third of cases, is conventionally managed with concurrent chemoradiotherapy delivered with curative intent. Radiation therapy (RT) is central to treatment; however, rapid treatment related anatomical and volumetric changes may alter target geometry and reduce the accuracy of plans generated from baseline imaging. Adaptive RT (ART) has emerged as an imaging-guided strategy that enables treatment modification according to evolving anatomy during RT delivery. This narrative review examines the rationale and current evidence supporting imaging-guided ART in LS-SCLC, with emphasis on imaging-informed decision-making and contemporary implementation considerations. LS-SCLC represents a biologically compelling setting for adaptive treatment because of its rapid treatment responsiveness; however, important uncertainties remain regarding patient selection, imaging schedules, adaptive triggers, and workflow standardization. Prospective studies incorporating standardized adaptive workflows and clinically meaningful endpoints are required to determine whether observed dosimetric advantages translate into measurable clinical benefit.

Key Words: Adaptive radiation therapy; Limited-stage small cell lung cancer; Image-guided radiotherapy; Cone-beam computed tomography; Adaptive replanning; Thoracic radiotherapy

Core Tip: Adaptive radiation therapy (ART) is a viable treatment strategy accounting for changes in tumor size and anatomy during the course of irradiation. Limited-stage small cell lung cancer (LS-SCLC) may be well suited for ART since it responds well to both chemotherapy and radiation therapy. Despite paucity of high level evidence, several studies have investigated ART for LS-SCLC and have reported promising results. Changes that could be accounted for by ART may include tumor regression or progression, atelectasis, pleural effusion, anatomical shifts, and infiltrative changes.

INTRODUCTION

Cancer remains a leading cause of morbidity and mortality worldwide, with thoracic malignancies accounting for a substantial proportion of cancer-related deaths[1-3]. Pulmonary malignancies are broadly classified into non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC), the latter characterized by aggressive biological behavior, including rapid proliferation, short doubling time, and early metastatic dissemination[4]. Despite representing a smaller proportion of lung cancers, SCLC is associated with poor outcomes and considerable therapeutic challenges. According to current staging systems, SCLC is categorized into limited-stage (LS-SCLC) and extensive-stage SCLC (ES-SCLC)[5-7]. LS-SCLC accounts for approximately one-third of cases and refers to disease that can reasonably be encompassed within a tolerable radiation therapy (RT) volume[6,7].

Optimization of RT delivery for LS-SCLC remains challenging because improvements in disease control must be balanced against treatment related toxicity. Advances in treatment planning, image guidance, and adaptive techniques have shifted thoracic radiation oncology from static treatment delivery toward increasingly individualized approaches. Image guided radiation therapy (IGRT) uses imaging to verify patient positioning and treatment delivery. Verification imaging confirms the accuracy of treatment setup. Adaptive RT (ART) may be described as planned modification of treatment during the course of RT in response to anatomical or dosimetric changes identified on repeated imaging. Adaptive replanning involves contour revision, dose recalculation, and generation of a new treatment plan when evolving anatomy is expected to compromise target coverage or organ at risk (OAR) constraints. Although adaptive strategies have gained increasing attention across multiple disease sites, evidence specific to LS-SCLC remains limited and heterogeneous, consisting predominantly of anatomical and dosimetric studies.

This narrative review is aimed to provide an overview of imaging-guided ART in LS-SCLC. A focused literature search was performed using the PubMed/MEDLINE, EMBASE, Scopus, and Web of Science databases for studies published between January 2000 and January 2026. Search strategies incorporated combinations of relevant keywords and Medical Subject Headings (MeSH), including “small cell lung cancer”, “limited-stage small cell lung cancer”, “adaptive radiation therapy”, “adaptive radiotherapy”, “image-guided radiation therapy”, “image-guided radiotherapy”, “cone beam computed tomography”, “computed tomography”, “magnetic resonance imaging”, “positron emission tomography”, and “thoracic radiotherapy”, together with related terms. Studies were selected based on their relevance to imaging-guided ART, anatomical changes during thoracic RT, adaptive treatment strategies, and clinical or dosimetric outcomes in LS-SCLC. When direct evidence specific to LS-SCLC was limited, selected studies involving mixed thoracic malignancies or broader ART populations were included to provide clinically relevant contextual information. Conference abstracts, duplicate publications, studies unrelated to thoracic RT or adaptive treatment, reports lacking sufficient methodological detail, and non-English publications were excluded. Owing to the limited quantity and heterogeneity of the available evidence, a quantitative meta-analysis was not performed. Instead, the literature was synthesized qualitatively, with emphasis on the biological rationale, imaging methodologies, adaptive workflow implementation, dosimetric findings, clinical interpretation, and emerging research directions.

CONTEMPORARY MANAGEMENT OF LS-SCLC AND THE EMERGENCE OF ART

Concurrent chemoradiotherapy remains the standard of care for LS-SCLC and provides superior outcomes compared with systemic therapy alone[8-14]. Earlier integration of thoracic RT within multimodality treatment has further improved clinical outcomes[11-14]. Recent advances have further expanded the standard management of LS-SCLC. The phase III ADRIATIC trial demonstrated that consolidation durvalumab administered after completion of concurrent chemoradiotherapy significantly improved both overall survival and progression free survival compared with placebo, establishing consolidation immunotherapy as a new component of standard treatment for appropriately selected patients[15]. The incorporation of consolidation immunotherapy may also have implications for adaptive treatment strategies because treatment related radiographic changes, inflammatory responses, and pulmonary toxicity may complicate imaging interpretation during RT and follow-up. In this context, contemporary adaptive workflows may require consideration of both anatomical evolution and treatment related immunologic effects when determining the need and timing for adaptive reassessment. More broadly, systemic treatment should be considered an important modifier of interval imaging findings, because chemotherapy, immunotherapy, and targeted therapies may produce different patterns and kinetics of tumor regression, inflammation, edema, or treatment-related pulmonary changes that can complicate distinction between true disease response and treatment-related radiographic alterations.

Multiple randomized trials and meta-analyses have consistently demonstrated superior outcomes with concurrent chemoradiotherapy compared with systemic therapy alone, establishing thoracic RT as an indispensable component of standard treatment[8-14,16-18]. This strategy reflects the aggressive biological behavior of SCLC, characterized by rapid proliferation, accelerated repopulation, and early metastatic dissemination, which necessitates simultaneous control of both locoregional and systemic disease[19,20]. Concurrent chemotherapy and RT not only target complementary disease compartments but also exploit radiosensitization to improve local control[19,20].

Despite the established role of thoracic RT, optimization of treatment delivery remains an active area of investigation[21-25]. Studies evaluating dose fractionation have refined the balance between disease control and treatment related toxicity, although no single approach fully eliminates this tradeoff[21-25]. Consequently, treatment decisions increasingly incorporate tumor extent, anticipated toxicity, treatment feasibility, and institutional expertise in addition to prescription dose[26-28]. Parallel advances in treatment planning, image guidance, respiratory motion management, and conformal RT have shifted the focus from dose escalation toward optimization of the therapeutic ratio, emphasizing maintenance of treatment accuracy throughout the RT course[16].

Conventional RT planning is based on pretreatment simulation imaging and assumes relative anatomical stability throughout treatment. However, treatment related anatomical changes may alter target geometry, organ relationships, and the delivered dose distribution. ART was developed to address this limitation by integrating repeated anatomical assessment into RT delivery[29-31]. Rather than relying solely on baseline imaging, adaptive strategies allow for treatment reassessment and replanning when evolving anatomy results in clinically meaningful geometric or dosimetric changes. Adaptation may be performed using either offline or online workflows. Offline adaptation, the most widely implemented approach in thoracic RT, incorporates interval imaging followed by contour revision, replanning, quality assurance, and implementation during subsequent fractions. Online adaptation integrates imaging, contour modification, optimization, and treatment delivery within the same treatment session. Although online workflows may provide greater anatomical accuracy immediately before irradiation, they can be operationally demanding.

The biological characteristics of LS-SCLC make it particularly suitable for adaptive treatment strategies. Rapid tumor regression during concurrent chemoradiotherapy is frequently accompanied by dynamic anatomical changes, including resolution of obstructive atelectasis, pleural fluid variation, airway re-expansion, mediastinal repositioning, and altered respiratory geometry. These changes may influence target coverage and OAR exposure, making repeated imaging valuable not only for treatment verification but also for identifying clinically relevant anatomical changes that may justify replanning. Importantly, radiographic tumor regression should not automatically prompt reduction of treatment volumes because residual microscopic disease and uncertainties in response assessment remain important oncologic considerations. The rationale for ART in LS-SCLC extends beyond geometric optimization alone. Adaptive treatment seeks to preserve oncologic intent while accounting for evolving anatomy. This biological rationale, together with increasing technological capability, has driven growing interest in imaging-guided adaptive approaches in contemporary thoracic radiation oncology.

ADAPTIVE RADIATION THERAPY IN LS-SCLC: CURRENT EVIDENCE AND CLINICAL INTERPRETATION

The growing interest in ART for LS-SCLC reflects a broader transition in thoracic radiation oncology from static treatment delivery toward response-adaptive strategies. Because LS-SCLC frequently undergoes substantial anatomical changes during concurrent chemoradiotherapy, ART represents a logical extension of contemporary IGRT. Table 1 summarizes data from selected studies relevant to imaging-guided ART in LS-SCLC.

Table 1 Critical appraisal of available evidence supporting adaptive radiation therapy relevant to limited-stage small cell lung cancer.

Ref.	Design	Population	Adaptive strategy	Principal observation	Translational relevance	Comment
Sager et al[16]	Retrospective dosimetric analysis	24 LS-SCLC patients	Repeat CT simulation with offline adaptive replanning	Median decrease in GTV and PTV volumes was 66.99% and 44.37%, respectively. Median decrease in MLD and V20 was 14.88% and 10.5%, respectively. Median decrease in MHD, MED, and spinal cord maximum dose was 23.4%, 37.79%, and 29.1%, respectively	Suggests that adaptation may preserve treatment feasibility and maintain OAR constraints in anatomically evolving patients	Significant reductions in GTV and PTV with improved OAR dosimetry; adaptive replanning enabled completion of curative-intent treatment in selected patients
Yee et al[32]	Prospective observational study	10 LS-SCLC patients	Serial volumetric assessment	Median shrinkage in GTV was 52.8% (range: 13.3%-83.6%) with the majority of shrinkage occurring by the end of the initial week of RT	Suggests that timing of adaptive reassessment may influence effectiveness of adaptive workflows	Early and substantial tumor regression was observed during treatment
Ozdemir et al[33]	Retrospective dosimetric analysis	10 LS-SCLC patients	Repeat CT simulation with offline adaptive replanning	3.7% daily tumor shrinkage rate was observed. The benefits of ART were the greatest for tumor volumes ≥ 30 cm3 and were directly dependent on GTV reduction during treatment	ART for SCLC achieved a significant benefit in terms of OAR sparing and dose escalation	The average GTV reduction observed over 13 fractions was 58.5% and over 23 fractions was 70%. Compared with the plan without adaptation, ART resulted in reduced OAR exposure
Elsayad et al[34]	Retrospective observational study	71 thoracic RT patients including LS-SCLC (6 patients), ES-SCLC (7 patients), and NSCLC (58 patients)	Serial CBCT-guided reassessment	Frequent treatment-related anatomical changes requiring consideration of plan modification. Patients in the SCLC group experienced a marked GTV reduction, ranging from -23% to -83% (mean -46%; median -36%)	Supports routine imaging as a mechanism for identifying potential adaptive indications	SCLC patients were more likely to obtain a high/very high adaptation priority score (6/13 patients; 46.5%) than NSCLC patients (12/58 patients, 20.6%; P = 0.01)
Møller et al[35]	Retrospective cohort study	173 patients with NSCLC and 60 with SCLC	Reassessment following anatomical alterations during RT	Pleural and atelectatic changes frequently altered treatment geometry	Highlights importance of non-tumoral adaptive triggers beyond simple tumor regression	Cohort heterogeneity; limited disease-specific analysis
Spoelstra et al[36]	Imaging feasibility study	Thoracic RT cohort (21 NSCLC patients, 3 SCLC patients)	Serial 4D-CT assessment	Dynamic changes in target geometry and respiratory motion characteristics identified during treatment	Supports motion-aware adaptive concepts	Role of ART may be limited when respiratory-gated RT is used to reduce concomitant chemoradiotherapy induced adverse effects. Use of more conformal treatment techniques might provide the rationale for repeat imaging as a method to identify patients at risk of dosimetric miss

LS-SCLC: Limited-stage small cell lung cancer; CT: Computed tomography; GTV: Gross tumor volume; PTV: Planning target volume; MLD: Mean lung dose; MHD: Mean heart dose; MED: Mean esophageal dose; OAR: Organ at risk; RT: Radiation therapy; ES-SCLC: Extensive-stage small cell lung cancer; NSCLC: Non-small cell lung cancer; SCLC: Small cell lung cancer; 4D-CT: Four-dimensional computed tomography; ART: Adaptive radiation therapy.

Sager et al[16] provided a focused evaluation of adaptive treatment using repeat computed tomography (CT) simulation and offline replanning during concurrent chemoradiotherapy of LS-SCLC. Significant median reductions were noted for both volumetric and dosimetric parameters. Gross tumor volume (GTV) decreased by 66.99% and planning target volume (PTV) by 44.37%. Mean lung dose (MLD) and V20 fell by 14.88% and 10.5%, respectively. Mean heart dose, mean esophageal dose, and spinal cord maximum dose showed median reductions of 23.4%, 37.79%, and 29.1%, respectively[16]. Notably, ART also allowed for treating one-third of the study group who would otherwise be ineligible for curative intent irradiation due to unfavorable critical organ dosimetry at the outset[16].

Yee et al[32] observed marked early tumor regression during definitive chemoradiotherapy for LS-SCLC, suggesting that the timing of reassessment may influence the effectiveness of adaptive workflows. A total of 104 CT scans of 10 patients acquired at different time points were analyzed. Median shrinkage in GTV was 52.8%, with the majority of shrinkage occurring by the end of the initial week of RT[32].

Ozdemir et al[33] also studied on 10 patients with LS-SCLC to assess the role of ART during concomitant chemoradiotherapy for LS-SCLC. In their study, average GTV reduction was 58.5% and 70% over 13 and 23 fractions, respectively[33]. ART resulted in relative decreases of 8.7%, 5%, 10%, 19%, and 13% in MLD, lung V20, lung V5, esophagus V50, and heart V42 parameters, respectively, with a relative decrease of 21 cGy in mean medulla spinalis dose[33]. Of note, benefits of ART were the greatest for tumor volumes ≥ 30 cm³ and were directly dependent on GTV reduction during treatment[33].

In addition to these studies including patients with LS-SCLC only, some other studies also addressed ART of thoracic malignancies with mixed SCLC and NSCLC patient populations[34-36]. Elsayad et al[34] demonstrated that serial cone-beam CT frequently identified treatment related anatomical and volumetric changes during thoracic RT. While interpretation is subject to cohort heterogeneity, the study supported routine interval imaging as a practical means of recognizing anatomical changes that may warrant treatment reassessment[34]. As a notable finding of their study, patients in the SCLC group experienced a marked GTV reduction, ranging from -23% to -83%, and SCLC patients were more likely to obtain a high/very high adaptation priority score (6/13 patients; 46.5%) than NSCLC patients (12/58 patients, 20.6%; P = 0.01)[34].

In a retrospective cohort study of 173 patients with NSCLC and 60 with SCLC, Møller et al[35] showed that atelectatic changes, pleural fluid variation, and inflammatory processes might substantially alter treatment geometry and create adaptive indications independent of direct tumor response.

Spoelstra et al[36] demonstrated dynamic changes in target geometry and respiratory motion using serial four-dimensional CT (4D-CT), supporting the potential value of motion-aware adaptive strategies. Their thoracic RT cohort included 21 NSCLC patients and 3 SCLC patients[36]. They concluded that the role of ART could be limited when respiratory-gated RT is utilized to reduce toxicity of concomitant chemoradiotherapy[36]. The use of more conformal treatment techniques might provide the rationale for repeat imaging as a method to identify patients at risk of dosimetric miss.

Overall, studies addressing ART collectively indicate that treatment related anatomical evolution during thoracic RT is not uncommon, and may include tumor regression, atelectatic resolution, pleural fluid changes, respiratory motion alterations, and shifts in target-organ relationships[16,32-36]. Such changes may cause delivered dose distributions to diverge from the original treatment plan, although the need for adaptation depends on the magnitude, timing, and dosimetric consequences of these anatomical changes. Notably, interpretation of available evidence also requires consideration of differences in disease stage, histology, and concurrent systemic therapy. Systemic therapy can substantially influence tumor regression, thoracic anatomy, toxicity, and imaging appearances during RT. The limited direct evidence supporting ART originates from patients undergoing curative-intent chemoradiotherapy for LS-SCLC, whereas additional insights are frequently extrapolated from studies involving NSCLC. Patient populations with mixed tumor histologies and disease settings (relapse, primary tumor, consolidation, curative or palliative intent, etc.) might differ substantially in tumor biology, treatment objectives, systemic therapy, and patterns of anatomical response. For example, the phase III ADRIATIC trial established consolidation durvalumab as part of contemporary management for LS-SCLC following concurrent chemoradiotherapy, highlighting the evolving interaction between systemic therapy and thoracic RT[15]. Nevertheless, subgroup analyses from the ALTER 1202 trial demonstrated that prior thoracic RT influenced outcomes in patients with relapsed SCLC receiving anlotinib, illustrating how previous irradiation, disease stage, and systemic treatment may affect subsequent response and imaging findings[37]. Although these studies do not directly establish the efficacy of ART in LS-SCLC, they provide important contextual evidence regarding how disease stage, histology, prior thoracic irradiation, and systemic therapy may influence tumor evolution, treatment response, imaging interpretation, and subsequent treatment decision-making[15,37]. More broadly, systemic therapies can influence the magnitude and timing of tumor regression, inflammatory and treatment-related radiographic changes, toxicity profiles, and the interpretation of interval imaging. Evidence from other thoracic oncology settings should therefore be interpreted cautiously when considering adaptive strategies in LS-SCLC. In this context, a meta-analysis of randomized trials evaluating anlotinib as third-line treatment for advanced NSCLC reported its efficacy and safety profile in a different disease setting, providing additional contextual evidence regarding the effects of systemic targeted therapy on tumor evolution and treatment-related outcomes[38]. However, these findings should not be extrapolated to establish a role for anlotinib or other targeted therapies in ART for LS-SCLC. Rather, they underscore the importance of considering concurrent and sequential systemic therapies when interpreting anatomical and radiographic changes during thoracic cancer treatment[38].

Currently, evidence base remains dominated by retrospective analyses, feasibility studies, and dosimetric investigations. Most studies include small patient cohorts, heterogeneous imaging schedules, poorly standardized adaptation criteria, and, frequently, mixed histological populations. Within this context, ART should currently be regarded as an emerging precision-treatment strategy rather than an established standard of care for LS-SCLC.

DOSIMETRIC CONSEQUENCES, CLINICAL TRANSLATION, AND PATIENT SELECTION FOR ART IN LS-SCLC

One of the principal arguments supporting ART is its ability to better align treatment delivery with evolving anatomy rather than relying exclusively on baseline simulation throughout the RT course. This concept is particularly relevant in LS-SCLC, where rapid tumor regression, mediastinal shifts, resolution of atelectasis, pleural fluid changes, and alterations in respiratory geometry may progressively modify the relationship between planned and delivered dose distributions. Across available studies, repeated imaging-guided replanning has been associated with reductions in GTV, PTV, MLD, lung dose-volume parameters, and reduced exposure of critical organs such as the heart, esophagus, and spinal cord while preserving target conformity[16,32-36]. However, these dosimetric improvements should be distinguished from demonstrated clinical benefit. Although reduced OAR exposure is biologically attractive, yet there is lack of high level evidence to support routinization of adaptive workflows and accumulation and maturization of data on improved toxicity, disease control, or survival are needed. In LS-SCLC, the greatest clinical value of ART may lie in preserving treatment feasibility. Adaptive replanning may enable continuation of curative-intent treatment in patients whose evolving anatomy would otherwise compromise target coverage or exceed OAR constraints, thereby maintaining treatment deliverability under changing anatomical conditions[16]. Triggers for adaptation may include loss of target coverage, violation of OAR constraints, major atelectatic changes, pleural-effusion alterations, infiltrative changes (i.e., pneumonia resolution), unexpected alterations in respiratory motion or body contour, clinically meaningful tumor regression or progression[16,32-36]. From a clinical perspective, patient selection may be particularly important because ART is unlikely to provide equivalent benefit for all patients with LS-SCLC. Patients with large initial tumor or target volumes, bulky mediastinal disease, tumors located close to dose-limiting organs, substantial baseline atelectasis, pleural fluid abnormalities, marked early tumor regression, or borderline baseline OAR constraints may be more likely to develop clinically meaningful changes during treatment and therefore represent potential candidates for adaptive reassessment. Conversely, patients with relatively small target volumes, stable thoracic anatomy, and favorable baseline dosimetry may have a lower likelihood of deriving sufficient benefit to justify the additional resources associated with adaptive workflows. These characteristics should be regarded as potential selection factors rather than validated eligibility criteria, because no prospective study has yet established a standardized clinical prediction model for identifying patients most likely to benefit from ART. However, no universally accepted thresholds currently exist for volumetric regression, anatomical displacement, pleural fluid variation, or deterioration of OAR dosimetry that should trigger replanning. Similarly, the optimal timing and frequency of repeated imaging have yet to be defined, although available evidence suggests that clinically meaningful anatomical changes often occur early during concurrent chemoradiotherapy[16,32-36]. In this context, triggers should initiate comprehensive evaluation of their potential dosimetric and clinical consequences before adaptive intervention is undertaken. Reduction in visible tumor volume should not be considered as compelling evidence for eradication of microscopic disease, and adaptive replanning should avoid unnecessary contraction of treatment volumes. Preservation of oncologic intent must remain central to adaptive decision-making. Future progress will depend on both recognizing treatment related anatomical changes and identifying which changes warrant intervention, when adaptation should occur, and which patients are most likely to benefit.

IMAGING-GUIDED ADAPTATION IN LS-SCLC: FROM ANATOMICAL OBSERVATION TO TREATMENT DECISION

Imaging is the fundamental enabling component of ART. Although adaptive treatment is often considered a planning strategy, its implementation depends on the ability to detect, interpret, and respond to anatomical changes during the course of RT. This is particularly important in LS-SCLC, where concurrent chemoradiotherapy may produce substantial anatomical changes over relatively short intervals. Historically, imaging in thoracic RT was used primarily for treatment planning and positional verification. Within adaptive workflows, however, repeated imaging serves a broader role by determining whether baseline treatment assumptions remain valid throughout therapy, thereby transforming imaging from a verification tool into a decision-support mechanism. Imaging platforms supporting ART and their current translational roles are summarized in Table 2.

Table 2 Imaging platforms supporting adaptive radiation therapy: Practical roles and translational positioning in limited-stage small cell lung cancer.

Imaging platform	Primary adaptive function	Major strength	Comment
Planning CT	Baseline geometry and dose calculation	Standardized anatomical definition	Standard for treatment simulation
Repeat CT Simulation	Offline adaptive replanning	High anatomical fidelity	Used for offline ART
4D-CT	Motion reassessment	Respiratory characterization	Used for motion assessment
Cone-beam CT	Longitudinal anatomical surveillance	Integrated into routine delivery	Used for IGRT and trigger detection/surveillance

CT: Computed tomography; 4D-CT: Four-dimensional computed tomography; ART: Adaptive radiation therapy; IGRT: Image guided radiation therapy.

CT simulation remains standard for RT planning by defining target volumes, OARs, and dose calculation parameters. In adaptive workflows, however, baseline CT should be regarded as the initial anatomical reference rather than a permanent representation of treatment anatomy. Accordingly, repeat CT simulation remains the most established method for offline adaptive replanning because it permits reassessment of target geometry and dose recalculation using updated anatomy.

Respiratory motion adds further complexity to thoracic RT. 4D-CT incorporates temporal assessment of respiratory motion and may be valuable in selected patients when evolving respiratory mechanics or changes in motion envelopes are likely to influence target coverage. Cone-beam CT (CBCT) is a practical platform for adaptive implementation because it is already integrated into routine IGRT workflows. Serial CBCT permits longitudinal assessment of tumor regression, mediastinal repositioning, pleural fluid variation, atelectatic change, body contour alteration, and changes in target-organ relationships without substantially disrupting treatment delivery. Consequently, its role extends beyond patient positioning to identifying anatomical changes that may justify adaptive replanning.

Clinical implementation of ART requires a structured transition from imaging observation to treatment decision. When interval imaging identifies potentially relevant anatomical changes, the findings should first be reviewed in the clinical context by the treating radiation oncologist and treatment team on a multidisciplinary basis. Relevant structures are then reassessed and contours modified on the updated imaging dataset, followed by evaluation of target coverage and OAR dose using the updated anatomy. If the observed changes result in clinically meaningful deterioration of target coverage, violation or anticipated violation of OAR constraints, or a substantial change in the relationship between the target and adjacent critical structures, adaptive replanning may be considered. The revised plan should undergo the institutional quality-assurance procedures required for clinical implementation before treatment is resumed with the adapted plan. Importantly, not every anatomical change identified on repeated imaging requires replanning; adaptation should be undertaken only when the anticipated dosimetric or clinical benefit justifies the additional resources and potential uncertainties associated with adaptive treatment.

Imaging challenges and emerging quantitative biomarkers

Several technical factors influence the reliability of imaging-guided adaptation. Although repeated imaging can identify anatomical evolution during treatment, adaptive decision-making depends on image quality, contour delineation, image registration, and dose assessment. CBCT, despite its practical advantages, is limited by reduced soft tissue contrast, image noise, scatter artifacts, and variability in Hounsfield unit accuracy, while repeated CT- and magnetic resonance imaging (MRI)-based assessments remain susceptible to interobserver variability, particularly when treatment response or inflammatory changes obscure anatomical boundaries. These uncertainties may affect both identification of adaptive indications and estimation of delivered dose.

Additional challenges arise during deformable image registration (DIR) and cumulative dose reconstruction. Although these techniques enable estimation of delivered rather than planned dose, registration uncertainty and methodological variability continue to limit standardization. Consequently, interpretation of adaptive imaging findings should consider both observed anatomical changes and the technical limitations of image acquisition and processing. An additional consideration is the estimation of cumulative delivered dose over the course of treatment. Although DIR enables longitudinal mapping of anatomical changes and accumulated dose distributions, its accuracy depends on the quality of image acquisition, registration algorithms, and contour consistency across serial imaging studies. Uncertainties may arise in regions of substantial tumor regression, atelectatic resolution, pleural fluid variation, or complex tissue deformation, where anatomical correspondence between sequential images becomes increasingly difficult. Consequently, cumulative dose estimates derived from DIR should be interpreted cautiously and regarded as approximations rather than exact representations of the delivered dose. Continued methodological refinement and prospective validation are needed before cumulative dose assessment can be considered sufficiently validated for routine clinical implementation in LS-SCLC.

FUTURE DIRECTIONS

Imaging alone does not constitute adaptation. The clinical value of repeated imaging depends on converting observed anatomical changes into appropriate treatment decisions. Current adaptive workflows remain largely based on visible anatomical findings, such as tumor regression and geometric alteration, although future strategies may increasingly incorporate quantitative imaging metrics capable of identifying clinically relevant response before macroscopic anatomical changes become apparent.

Volumetric changes remain the most established imaging-derived indicator supporting adaptive consideration. However, adaptation is generally prompted not by predefined numerical thresholds but by clinically meaningful anatomical changes, including substantial tumor regression, atelectatic evolution, pleural fluid alteration, mediastinal displacement, unexpected changes in respiratory motion, or deterioration of OAR relationships. These findings become clinically relevant only when they compromise target coverage, alter dose delivery, or threaten treatment intent. Accordingly, future progress will depend less on increasing imaging frequency than on reliably identifying which anatomical changes warrant intervention and implementing those decisions consistently across clinical practice.

A major barrier to widespread ART implementation remains operational complexity. Repeated imaging, contour reassessment, replanning, quality assurance, and workflow coordination require substantial institutional resources. Artificial intelligence (AI) has therefore emerged primarily as a supportive technology, facilitating contour generation, DIR, treatment planning, and workflow efficiency. However, current evidence does not support AI as an autonomous driver of adaptive decision-making. Adaptive treatment continues to depend on clinical interpretation, preservation of oncologic principles, and multidisciplinary oversight.

Future development of ART in LS-SCLC will require a transition from retrospective feasibility studies toward prospective clinical validation. Priority should be given to standardized adaptive workflows, cumulative dose assessment, clinically meaningful and patient-reported outcomes, and reproducible imaging strategies that facilitate comparison across institutions. Integration of functional imaging, quantitative image analysis, and longitudinal assessment of delivered dose may further refine adaptive implementation. Ultimately, the success of ART will depend not on generating additional imaging data, but on accurately identifying when adaptation is warranted and demonstrating that intervention improves patient outcomes.

CONCLUSION

LS-SCLC is a uniquely dynamic thoracic malignancy in which rapid treatment response is frequently accompanied by substantial anatomical changes during concurrent chemoradiotherapy. These characteristics provide a strong biological rationale for imaging-guided ART and position LS-SCLC as an important clinical model for response-adaptive treatment strategies.

Current evidence demonstrates that treatment related anatomical changes are common, repeated imaging can identify alterations with potential dosimetric consequences, and adaptive replanning is technically feasible in selected patients. However, the available literature remains dominated by retrospective and dosimetric studies, with limited evidence that adaptive interventions improve toxicity, disease control, survival, or patient-reported outcomes. Accordingly, ART should currently be regarded as an emerging precision-treatment strategy rather than an established standard of care for LS-SCLC.