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

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.

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.