Dominant trajectory framework tracks priorities in multiple ground-glass nodules

A 2026 narrative opinion article proposes “dominant trajectory” as a way for clinicians to document which pulmonary ground-glass nodule deserves priority at each stage of follow-up and to record why that priority changes. The framework combines lesion-specific imaging, the status of the remaining nodules, available treatment capacity and patient goals. It is not a validated cancer-risk score, a measure of a nodule’s biological natural history or an independent indication for treatment. Although existing guidelines already call for longitudinal assessment of multiple ground-glass and part-solid nodules, the authors argue that an explicit record of shifting clinical priorities could improve continuity between visits and clinicians. The concept remains unvalidated, and the review emphasizes that the presence of a ground-glass nodule does not itself establish cancer.

The proposal responds to a practical difficulty in managing multiple ground-glass nodules, also called subsolid nodules. Clinical teams must consider not only which lesion appears most concerning, but also whether changes in that lesion are real, how other nodules are evolving, whether the patient can tolerate treatment and what matters to the patient. Existing guidance from the American Association for Thoracic Surgery and European thoracic surgery organizations already integrates serial change, solid-component size, morphology and fitness for surgery, while a Chinese multidisciplinary consensus addresses multiple GGN-like lung cancers. A dominant-trajectory record would therefore formalize reasoning already expected in longitudinal care rather than introduce an entirely new treatment rule. Its proposed novelty lies in making the hierarchy of concern and the reasons behind it visible over time.

Evidence for periodic reassessment comes partly from surgical cohorts, although these selected populations cannot show that re-ranking lesions improves survival. In a series of 67 patients reported by Shimada and colleagues, 39 had 118 unresected ground-glass opacities after surgery for the main cancer. Eight percent of the residual nodules grew, and new ground-glass opacities appeared in 15 patients, or 23%. Survival was associated with characteristics of the main cancer, not with residual growth or the appearance of new lesions. A separate report by Bongiolatti and colleagues described favorable outcomes after surgery for the dominant lesion, with observation and selective treatment of other lesions. Together, these observational findings support current management approaches but do not establish that a structured priority record produces better decisions or outcomes than guideline-concordant care.

Natural-history data nevertheless show why repeated characterization matters. In a prospective multicenter study of 795 patients with 1,229 subsolid nodules, 56 of 1,046 nodules that were initially pure ground-glass became part-solid during a mean follow-up of 4.3 years, a change observed in 5.4%. Particular attention is warranted when a pure ground-glass nodule develops a solid component or when the solid portion of a part-solid nodule enlarges. Diameter and attenuation changes in a persistent pure ground-glass nodule must be interpreted together with morphology and the technical comparability of CT scans. In the retrospective multicenter GORDON study, Catelli and colleagues found that greater preoperative diameter and higher CT attenuation were associated with invasive histology in resected pure ground-glass adenocarcinomas. Because the study involved a selected surgical population, these associations neither define treatment thresholds nor clarify how serial attenuation changes should be interpreted.

The proposed framework is intended to organize four domains: evidence about the individual lesion, the condition of the other nodules, future treatment capacity and patient priorities. Imagine a patient with a 15-mm pure ground-glass nodule and a separate 9-mm pure ground-glass nodule. If technically comparable follow-up scans show that the larger lesion remains stable while the smaller lesion develops a solid component that reproducibly enlarges, the smaller lesion might become the priority after the team evaluates imaging reliability, the remaining nodules and the available treatment options. Two lesions may be co-dominant when they generate similar concern and require parallel assessment. New diffuse or rapidly changing opacities would instead prompt consideration of inflammation or other diagnoses, within established diagnostic and treatment criteria. Even when priority changes, immediate management may remain unchanged. The record would capture what changed, what stayed stable, how confident the clinicians are and what factors influenced the decision, allowing the rationale to be reviewed rather than reconstructed from memory.

Dominant trajectory is intended to complement, not replace, quantitative growth assessment. Volume, volume doubling time and, where appropriate, mass change can help characterize a lesion when serial segmentation is reliable. One observational study reported median volume doubling times of approximately 1,832 days for growing pure ground-glass nodules, 1,229 days for part-solid nodules with solid components no larger than 5 mm and 759 days for those with solid components larger than 5 mm. These values describe an observed group, not intervention cutoffs, and thresholds derived mainly from solid nodules should not automatically be applied to ground-glass lesions. Technical uncertainty also needs to remain visible. In a same-day repeat-CT study of 69 subsolid nodules, longest-diameter measurements varied by plus or minus 1.3 mm with the same reader and plus or minus 2.2 mm with different readers. Solid-component measurements were especially variable between readers. Consistent acquisition, reconstruction, segmentation and reading are therefore important before small changes are treated as meaningful progression. A long estimated volume doubling time should not overrule convincing solid-component evolution, because increasing solid tissue may matter despite little change in overall diameter or volume.

Longitudinal assessment does not automatically require more CT examinations. Fleischner guidance for eligible adults with incidentally detected multiple subsolid nodules recommends initial CT at three to six months, with subsequent management based on persistence, size and the most suspicious nodule. Selected persistent nodules warrant surveillance extending to five years, but those recommendations are not screening protocols and do not directly apply to people with known cancer. After lung-cancer treatment, surveillance must instead reflect the relevant oncologic and residual-nodule context. Low-dose thin-section CT and coordinated examinations can reduce unnecessary exposure. Follow-up intensity and duration should balance lesion evolution, life expectancy, competing illness, ability to undergo treatment and informed preferences, while accounting for cumulative radiation, visits, incidental findings and financial burden. Reassessment may instead consist of reviewing existing imaging, and the framework should make these trade-offs explicit rather than assume that more surveillance is always better.

Preserving lung tissue is another central consideration when several lesions may eventually require treatment, but parenchymal-sparing surgery must remain oncologically appropriate. In the randomized JCOG0802/WJOG4607L trial involving 1,106 patients with peripheral non-small-cell lung cancer no larger than 2 cm and a consolidation-to-tumor ratio above 0.5, five-year overall survival was 94.3% after segmentectomy and 91.1% after lobectomy, while local relapse was more frequent with segmentectomy, at 10.5% versus 5.4%. The median one-year difference in forced expiratory volume in one second was only 3.5 percentage points. The randomized CALGB 140503 trial, with 697 patients with peripheral tumors no larger than 2 cm and intraoperatively confirmed node-negative disease, found that sublobar resection was noninferior for disease-free survival, with a hazard ratio of 1.01 and 90% confidence interval of 0.83 to 1.24. These trials support considering future treatment capacity, but they do not demonstrate the superiority of repeated sublobar resections for multifocal ground-glass disease or establish that large functional benefits should be expected.

For patients with a treatment-requiring lesion who are unsuitable for surgery, stereotactic body radiotherapy or thermal ablation may be considered after multidisciplinary review. Their ability to avoid anatomical resection must be weighed against lesion location, diagnostic certainty, local control, toxicity and the possibility of retreatment. Neither approach should be used simply to eliminate stable ground-glass nodules, and the framework cannot establish equivalence to surgery or prescribe an optimal sequence of local therapies. Patient preferences are also relevant to the burden of surveillance and treatment. In a nonrandomized cohort of 200 patients with multiple pulmonary nodules, Yuan and colleagues associated multidisciplinary care with better health knowledge, coping, quality of life and satisfaction at six months. The study did not show improved cancer detection or oncologic outcomes and was not restricted to multifocal ground-glass disease. Anxiety should be addressed with clear explanations, a written follow-up plan and access to support, but it should not be interpreted as biological progression.

The central limitation is that dominant trajectory has not been shown to offer clinical benefit beyond existing guidance. Qualitative prioritization may differ among clinicians, amplify measurement noise, add work or prompt unnecessary intervention if it is mistaken for a validated risk estimate. Evidence drawn from selected surgical cohorts and individual-nodule studies also may not generalize to everyone with multiple ground-glass nodules. Prospective evaluation should compare structured documentation with usual guideline-concordant multidisciplinary care and examine agreement on the priority lesion, reproducibility of priority changes, decision concordance and added workload. Patient-level outcomes would include stage at intervention, cancer-specific survival, pulmonary function, cumulative procedures, treatment morbidity, CT exposure, anxiety and quality of life. Analyses would also need to account for baseline nodule burden, prior cancer, comorbidity and competing mortality. The authors present dominant trajectory as a hypothesis-generating framework for longitudinal care, not a new staging system or validated decision rule. Its value will depend on whether explicit documentation improves decisions and patient outcomes while preserving appropriate care of the lesion that matters at each visit.

Subject of Research: Longitudinal clinical prioritization of multiple pulmonary ground-glass nodules

Article Title: Dominant trajectory as a longitudinal framework for multiple ground-glass nodules

Article References: Cheng, H., Zhang, Z., Ye, Y., & Lu, F. (2026). Dominant trajectory as a longitudinal framework for multiple ground-glass nodules. Frontiers in Medicine, 13, Article 1979153. https://doi.org/10.3389/fmed.2026.1979153

Image Credits: AI Generated

DOI: 10.3389/fmed.2026.1979153

Keywords: ground-glass nodules, subsolid nodules, lung cancer, CT surveillance, nodule prioritization, solid component, volume doubling time, multidisciplinary care, lung preservation, patient preferences, Dominant, trajectory