Prevalence of respiratory complications in long-term survivors of childhood and adolescent cancer: a systematic review and meta-analysis

Introduction

With ongoing advances in therapeutic approaches, survival rates for childhood and adolescent cancers have significantly improved, exceeding 80% at 5 years in well-resourced settings (1,2). This progress has given rise to a growing population of long-term survivors. However, the achievement of cure is accompanied by a considerable risk of treatmentrelated late effects over subsequent decades, which together represent a significant burden of morbidity throughout survivorship (3,4). Studies confirm that, compared with their healthy peers, childhood cancer survivors face markedly elevated risks of chronic health problems, functional limitations, and premature non-cancer mortality (5-7).

While effective in eradicating malignancy, cancer treatments can also induce lasting injury to normal tissues. Among various long-term effects, respiratory complications warrant particular attention due to their direct impact on quality of life and survival (8). Therapeutic modalities such as thoracic radiotherapy, chemotherapeutic agents with recognized pulmonary toxicity (e.g., bleomycin, alkylating agents, nitrosoureas), thoracic surgery, and hematopoietic stem cell transplantation can all cause damage to pulmonary parenchyma and airways. Pathological outcomes may manifest as pulmonary fibrosis, restrictive or obstructive ventilatory dysfunction, impaired gas exchange capacity (diffusion impairment), and recurrent respiratory infections. These pathologies may emerge years or even decades after treatment concludes (9-11). Given the lifelong essential function of the lungs, respiratory complications constitute a key determinant of long-term health-related quality of life and nonneoplastic mortality in this population (12,13).

The mechanisms and patterns of pulmonary injury vary substantially by tumor type and treatment modality. Survivors of Hodgkin lymphoma treated with bleomycin-containing regimens are at risk for progressive pulmonary fibrosis from oxidative damage to alveolar epithelial cells (9,14), whereas restrictive lung disease following craniospinal irradiation for central nervous system tumors often results from impaired chest wall and spinal growth (15,16). Survivors who undergo hematopoietic stem cell transplantation for leukemia face compounded risks from conditioning regimens, graft-versus-host disease, and infectious complications (11,17). While these distinct pathophysiological pathways contribute to clinical heterogeneity, a comprehensive synthesis of the overall respiratory burden across diagnostic groups is needed to inform long-term follow-up guidelines and risk-stratified surveillance strategies (18).

Despite a considerable number of observational studies conducted on this topic, existing evidence remains significantly limited and fragmented. First, reported prevalence rates of respiratory complications vary widely across studies, ranging from less than 10% to over 50% (19,20). This heterogeneity likely reflects differences in study populations, follow-up durations, and the definitions and diagnostic criteria for complications. This wide variation in reported estimates, rather than precluding a meta-analysis, underscores the need for a quantitative synthesis that can provide an overall estimate while systematically exploring sources of heterogeneity. Second, there is currently no comprehensive, quantitative synthesis to accurately assess the overall burden of such complications. Furthermore, quantitative evidence linking specific treatment exposures to respiratory outcomes remains fragmented and inconclusive, limiting the ability to tailor follow-up based on individualized risk. Additionally, as treatment modalities evolve with advances in radiation therapy precision and the adoption of targeted therapies, the patterns of complication risk among long-term survivors of childhood and adolescent cancer may shift across diagnostic eras; systematic evaluations of these changes remain limited.

To address this gap, we conducted a systematic review and meta-analysis to synthesize fragmented evidence, quantify the overall prevalence of respiratory complications and explore factors associated with higher complication rates through pre-specified subgroup analyses. This study aims to provide critical data to inform evidence-based long-term follow-up guidelines, support risk-stratified surveillance strategies, and enhance patient education and counseling. We present this article in accordance with the PRISMA reporting checklist (available at https://tp.amegroups.com/article/view/10.21037/tp-2026-1-0139/rc).

Methods

Search strategy

To comprehensively identify relevant studies, we systematically searched the following electronic databases: PubMed, Embase, Web of Science Core Collection, Cochrane Central Register of Controlled Trials (CENTRAL), China National Knowledge Infrastructure (CNKI), Wanfang Data Knowledge Service Platform, and VIP Chinese Science and Technology Journal Database. We systematically searched electronic databases from their inception to December 30, 2025. In addition, we manually screened the reference lists of eligible studies and searched gray literature sources, including ClinicalTrials.gov and the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP). The search strategy combined subject headings (e.g., MeSH, Emtree) with free-text terms covering core concepts such as “childhood/adolescent malignancies”, “survivors”, “respiratory diseases/pulmonary diseases”, and “incidence/prevalence/risk”. The full search strategy is provided in Appendix 1.

To enhance transparency, this review was registered with the PROSPERO database (registration number: CRD420261306368).

Research selection and inclusion criteria

Two reviewers independently screened the literature. In the initial phase, titles and abstracts were assessed to exclude studies clearly irrelevant to the research question. Full texts of the remaining records were then retrieved and independently evaluated against predefined inclusion and exclusion criteria. Any discrepancies were resolved through discussion between the two researchers or, when necessary, by consultation with a third senior reviewer.

This review was conducted according to the following PICOS framework: (I) Population (P): long-term survivors (≥5 years post-diagnosis) of childhood or adolescent cancer (diagnosed at age <21 years); (II) Intervention/exposure (I): any antineoplastic therapy with potential pulmonary toxicity, including chemotherapy, radiotherapy, thoracic surgery, and hematopoietic stem cell transplantation; (III) Comparator (C): not applicable for prevalence estimates; where reported, comparisons to sibling controls or general population were noted; (IV) Outcomes (O): primary outcomes: prevalence of any respiratory complication (composite), reduced forced vital capacity (FVC), reduced forced expiratory volume in one second (FEV₁), impaired diffusing capacity of the lungs for carbon monoxide (DLCO), restrictive ventilatory dysfunction, and symptomatic respiratory disease. Secondary outcomes: complication-specific prevalence rates and associated risk factors; (V) Study design (S): observational studies (cohort, cross-sectional, case-control) and randomized controlled trials reporting long-term follow-up outcomes. However, only cohort studies were identified during screening; no cross-sectional, case-control studies or randomized controlled trials (RCTs) met the inclusion criteria.

Exclusion criteria include: (I) studies focusing solely on the acute treatment phase (5 years); (II) case reports, reviews, or commentary articles; (III) studies from which required data could not be extracted or derived.

Definition of time intervals

For the purposes of this review, two distinct time intervals were defined: (I) survival time: the interval from the date of initial cancer diagnosis to the date of respiratory outcome assessment. To capture late-onset pulmonary sequelae, the inclusion criteria required participants to have survived for at least five years following their initial cancer diagnosis; (II) follow-up time: the interval from the completion of primary cancer therapy to the date of respiratory outcome assessment. This measure is reported as the median or mean follow‑up duration in Table 1 and is used for subgroup analyses comparing studies with follow‑up <5 vs. ≥5 years. Accordingly, studies were eligible for inclusion if participants had a survival time ≥5 years, even when the reported follow‑up time (post‑treatment) was <5 years. For the primary analysis, the prevalence of each respiratory outcome was defined as the proportion of survivors reported to have the condition at the time of assessment.

Data extraction

Data extraction was performed independently by two reviewers using a standardized, pre-designed form, followed by cross-verification. The following information was extracted: (I) study characteristics: first author, publication year, country/region, study design, follow-up duration; (II) population characteristics: total sample size, age at diagnosis/median age, tumor type distribution; (III) exposure characteristics: detailed treatment regimens (specific chemotherapy agents and cumulative doses, radiotherapy sites and doses, presence of stem cell transplantation, etc.); (IV) outcome data: clearly defined respiratory complications, diagnostic methods, number of events, total participants, incidence/prevalence rates with 95% confidence intervals (CIs), adjusted effect sizes [e.g., relative risk (RR), odds ratio (OR), hazard ratio (HR)], and adjusted confounding factors. Where studies reported cumulative incidence, these data were extracted but are distinguished from prevalence in the reporting; (V) information required for risk of bias assessment.

Bias risk assessment

Two researchers independently assessed the methodological quality of included cohort and case-control studies using the Newcastle-Ottawa Scale (NOS) (21). The NOS assesses three domains: selection of study groups (maximum 4 stars), comparability of groups (maximum 2 stars), and ascertainment of outcome (maximum 3 stars), yielding a total maximum score of 9. Studies scoring ≥7 were considered at low risk of bias. For studies relying on self-reported outcomes without independent clinical verification, a point was deducted in the outcome assessment domain to reflect the potential for recall bias. Any assessment discrepancies were resolved through discussion.

Data synthesis and analysis

All statistical analyses were performed using Stata 18.0. The primary summary measure was the pooled prevalence of each respiratory complication. Prevalence was defined as the proportion of survivors reported to have the condition at the time of assessment. For studies reporting cumulative incidence, these data were treated as approximating prevalence when the follow-up window encompassed a substantial proportion of the survivorship period, but the distinction is noted as a limitation. For prevalence data, raw proportions were first transformed using the Freeman-Tukey double arcsine transformation. Pooled estimates were then calculated using the Der Simonian-Laird random‑effects model to account for anticipated between‑study heterogeneity. Summary estimates were back‑transformed to proportions and reported with 95% CIs.

Between‑study heterogeneity was assessed using Cochran’s Q test and the I² statistic, with I²>50% considered indicative of substantial heterogeneity.

Pulmonary‑toxic chemotherapy was defined as exposure to any agent with established pulmonary toxicity, including bleomycin, alkylating agents [cyclophosphamide, busulfan, carmustine (BCNU), lomustine (CCNU)], methotrexate, and other high‑risk drugs. Based on the treatment patterns reported in the included studies, exposure risk was categorized as follows: High risk: documented receipt of two or more agents from the high‑risk list; Moderate risk: documented receipt of exactly one agent from the high‑risk list; Low risk: no documented receipt of any high‑risk agent (may have received agents with lower or uncertain pulmonary toxicity, e.g., conventional‑dose methotrexate).

To explore potential sources of heterogeneity, we conducted pre-specified subgroup analyses according to primary tumor type (hematologic malignancies, solid tumors, central nervous system tumors), chemotherapy-induced pulmonary toxicity risk category (high risk, mediate risk, low risk), diagnostic era (before 2000 vs. after 2000), and median follow-up duration (<5 vs. ≥5 years). Subgroup analyses by tumor type and chemotherapy risk level was conducted to explore the sources of clinical heterogeneity resulting from the broad inclusion criteria. Sensitivity analysis was performed by sequentially omitting individual studies to assess the robustness of the pooled estimates. Potential publication bias was evaluated by visual inspection of funnel plots and formally tested using Egger’s linear regression test.

We acknowledge that the included studies employed varying diagnostic thresholds for pulmonary function abnormalities (e.g., DLCO <75% vs. <80% predicted, FVC <80% vs. <75% predicted). Owing to the lack of individual participant data, we were unable to apply a uniform diagnostic criterion across studies. Instead, we retained the outcome definitions as reported in the original studies. The impact of this heterogeneity in diagnostic criteria on the pooled estimates is recognized as an important source of clinical and methodological diversity and is reflected in the high statistical heterogeneity (I²) observed.

Results

Literature search and screening process

A total of 3,674 records were identified through systematic database searches and supplementary sources (3,647 from databases, 27 from other sources: citation searching, ClinicalTrials.gov, and WHO ICTRP)]. After removing duplicates, 2,058 records remained. Of these, 2,027 clearly irrelevant records were excluded. The full texts of the remaining 31 studies from databases and the 27 records from other sources were retrieved and assessed for eligibility. No eligible studies were identified from the other sources beyond those already captured by database searches. Ultimately, 11 studies met the predefined inclusion criteria and were included in this systematic review and meta-analysis (18,22-31). The detailed literature selection process and reasons for exclusion are illustrated in Figure 1.

Figure 1 Research screening flowchart. CNKI, China National Knowledge Infrastructure.

Characteristics of included studies

The 11 included studies encompassed a total of 128,509 long-term survivors of childhood and adolescent cancer, with individual sample sizes ranging from 39 to 65,173. All studies applied the same core inclusion criteria: age at diagnosis <21 years and survival ≥5 years post-diagnosis. Study characteristics are summarized in Table 1. Ten studies were retrospective cohort studies, and one was a prospective longitudinal study. The majority of studies were conducted in North America and Europe. Median follow-up duration ranged from 3.3 to 25 years. Tumor types included leukemia, lymphoma, central nervous system tumors, and a range of solid tumors. All studies reported prior exposure to antineoplastic therapies associated with pulmonary toxicity, most commonly bleomycin, cyclophosphamide, nitrosoureas, and thoracic radiotherapy. Definitions and diagnostic methods for respiratory outcomes varied across studies, as detailed in Table 2.

Risk of bias assessment

The methodological quality of the included cohort studies was evaluated using the NOS for cohort studies. The median score was 8 out of a maximum of 9 points (range, 7–9), indicating generally high methodological quality. Studies relying on self-reported outcomes without independent clinical verification received lower scores in the outcome assessment domain. The most common methodological limitations were reliance on self-reported pulmonary outcomes subject to recall bias and incomplete control of potential confounders such as smoking status. Domain-specific scores for each study are reported in Table S1.

Prevalence of respiratory complications

Any respiratory complications

Nine studies reported the prevalence of any respiratory complications as a composite outcome. The random-effects meta-analysis yielded a pooled prevalence of 35% (95% CI: 30–40%), with substantial heterogeneity observed across studies (I²=99.0%, P<0.001), as shown in Figure 2. Given the extreme heterogeneity (I²=99.0%), this pooled estimate should be interpreted with caution and serves primarily as a broad overview of disease burden rather than a clinically precise metric.

Figure 2 Forest plot of the prevalence of any respiratory complication in childhood and adolescent cancer survivors. CI, confidence interval.

Specific pulmonary function abnormalities

The pooled prevalence of FVC decline based on 3 studies was 19% (95% CI: 7–32%, I²=82.0%; Figure 3A). Similarly, the pooled prevalence of FEV₁ decline based on 3 studies was 19% (95% CI: 2–35%, I²=93.6%; Figure 3B). The pooled prevalence of diffusion impairment (commonly defined as DLCO below a certain percentage of predicted value, with thresholds ranging from <75% to <80% across studies) based on 4 studies was 39% (95% CI: 9–70%, I²=98.0%; Figure 3C). These estimates are based on four studies with small sample sizes (range, 39–180), and the wide CI reflects substantial uncertainty.

Figure 3 Forest plots for the prevalence of specific respiratory complications in childhood and adolescent cancer survivors. (A) FVC reduction. (B) FEV₁ reduction. (C) Impaired diffusing capacity (DLCO). (D) Restrictive ventilatory defects. CI, confidence interval; DLCO, diffusing capacity of the lungs for carbon monoxide; FEV₁, forced expiratory volume in one second; FVC, forced vital capacity.

Specific clinical diagnoses

The prevalence of restrictive ventilatory dysfunction based on six studies was 14% (95% CI: 6–22%, I²=98.3%; Figure 3D). The combined prevalence of symptomatic respiratory disease based on six studies was 14% (95% CI: 10–19%, I²=75.3%), as shown in Figure 4.

Figure 4 Forest plot for the prevalence of symptomatic respiratory disease in long-term childhood cancer survivors. CI, confidence interval.

Subgroup analyses and exploration of sources of heterogeneity

To explore sources of heterogeneity, we conducted pre-specified subgroup analyses (Figures S1-S9).

Tumor type

The prevalence of respiratory complications varied across tumor types, with solid tumor survivors exhibiting the highest prevalence (subgroup analyses shown in Figures S1,S5A,S6A,S7A,S8A,S9A).

Chemotherapy-induced pulmonary toxicity risk level

Survivors exposed to high-risk pulmonary toxicity chemotherapy regimens exhibited significantly higher prevalence rates for all types of complications compared to the low-risk group (see Figures S2,S5B,S6B,S7B,S8B,S9B).

Diagnostic era

The pooled prevalence was higher in the subgroup of studies where survivors were predominantly diagnosed before the year 2000, compared to the subgroup diagnosed later (see Figures S3,S8C,S9C).

Follow-up duration

Studies with a median follow-up duration of ≥5 years reported higher prevalence rates than those with shorter follow-up durations (see Figures S4,S5C,S6C,S7C,S8D,S9D).

Sensitivity analyses and publication bias

Sensitivity analysis involving the sequential exclusion of “any respiratory complication” prevalence showed that the pooled effect size remained stable within the range of 30% to 40% (Table S2), indicating robust results. The funnel plot for this outcome was visually symmetrical (Figure S10), and Egger’s test did not indicate significant publication bias (P=0.44).

Other important findings from large cohort studies

In addition to prevalence estimates, two large cohort studies provided critical data on healthcare utilization and temporal trends. A Nordic registry-based study (n=21,297 survivors) found that the incidence rate of hospitalization for respiratory diseases was 314 per 100,000 person-years, corresponding to a near two-fold increased risk compared to the general population (RR 1.94, 95% CI 1.91–1.97) (Table 3). Furthermore, an analysis from the Childhood Cancer Survivor Study suggested that the 15-year cumulative incidence of severe (grade 3–5) chronic respiratory conditions may be lower among survivors diagnosed in the 1990s (0.8%) compared to those diagnosed in the 1970s (1.2%), indicating a potential positive effect of evolving treatment protocols.

Discussion

This systematic review and meta-analysis, integrating data from over 120,000 childhood and adolescent cancer survivors, yielded several key findings. First, approximately one‑third (35%) of survivors experienced at least one identifiable respiratory complication, underscoring the substantial burden of long‑term pulmonary sequelae. Second, prevalence estimates varied considerably by complication type; impaired diffusion capacity—reflecting damage to the alveolar-capillary membrane—was the most common abnormality. Third, specific treatment exposures (e.g., high‑risk pulmonary‑toxic chemotherapy), earlier diagnostic era (pre‑2000), and longer follow‑up duration were significantly associated with increased risk of respiratory complications. Fourth, large-cohort data confirmed that survivors face approximately twice the risk of hospitalization for respiratory diseases compared with the general population, although cumulative incidence rates of severe complications have shown a declining trend in parallel with refinements in treatment regimens.

The pooled prevalence estimate of 35% established in this meta-analysis provides a critical benchmark for clinical practice. This substantial burden indicates that respiratory health should become an indispensable core component of long-term follow-up for childhood cancer survivors. Pulmonary function testing, particularly comprehensive panels including DLCO measurement, should be considered routine monitoring for high-risk survivors. Impaired diffusion capacity was observed in a substantial proportion of survivors (pooled estimate 39%), though this estimate is based on a small subset of studies with limited sample sizes; larger confirmatory studies are needed. The observed excess relative to ventilatory function indicators warrants further investigation. This observation may relate to the known sensitivity of the alveolar-capillary membrane to antineoplastic therapies, though the included studies do not directly elucidate cellular mechanisms. The finding that diffusion impairment appears to exceed ventilatory dysfunction is a hypothesis-generating observation that warrants prospective investigation (8,32,33). Thus, DLCO may serve as a more sensitive, earlier biomarker for monitoring pulmonary toxicity.

The observed difference in complication prevalence across diagnostic eras is notable. In our analysis, survivors diagnosed before the year 2000 faced a higher burden of respiratory complications. While this is an observational association derived from retrospective data and cannot establish direct causality, it strongly aligns with the temporal trend of major therapeutic advances. The decades around and after 2000 witnessed significant modifications in oncologic practice aimed at reducing late effects, such as the systematic reduction or omission of chest radiotherapy for many malignancies, the refinement of chemotherapy dosing (e.g., lower cumulative doses of bleomycin), the adoption of more targeted agents, and improvements in supportive care (32,34-36). The lower risk observed in the more contemporary cohort is plausibly a consequence of these cumulative refinements in treatment strategy. This observed temporal trend is consistent with data from Gibson et al. [2018], which reported a decline in the cumulative incidence of severe respiratory conditions across successive treatment eras. However, as this is an observational association derived from retrospective data, we cannot establish direct causality or fully exclude the influence of other temporal factors such as changes in diagnostic criteria, surveillance intensity, or lifestyle factors. However, the “diagnostic era” variable serves as a composite proxy for a multitude of concurrent changes. We cannot rule out the influence of other temporal factors, such as evolving diagnostic criteria for complications, increased awareness and surveillance in more recent cohorts, or changes in lifestyle factors (e.g., smoking). The non-randomized, retrospective nature of the included studies limits our ability to fully disentangle the specific contribution of treatment modulation from these potential confounders. Nonetheless, the consistent direction and magnitude of the era effect across multiple studies provide compelling circumstantial evidence that the evolution of treatment protocols has begun to successfully mitigate some long-term pulmonary risks.

Our findings are broadly consistent with qualitative descriptions from previous smaller reviews or single-cohort studies (37,38). However, this study offers the advantage of providing a more precise and comprehensive range of prevalence estimates through quantitative synthesis. While prior research has highlighted the risks associated with pulmonary toxicity treatment (37), this analysis quantifies differences between chemotherapy regimens with varying risk levels across subgroups and systematically evaluates the diagnostic era as a key variable—representing a significant addition to the existing evidence. The doubled risk of hospitalization identified in studies offers a health economics perspective on disease burden, underscoring that respiratory complications represent not only functional challenges but also a major driver of increased healthcare resource utilization (39,40).

The strengths of this study include strict adherence to the PRISMA guidelines, extensive literature searches (covering both Chinese and English databases), and the inclusion of a large sample size. We conducted comprehensive subgroup and sensitivity analyses, yielding robust results. However, several important limitations must be acknowledged. First, extremely high statistical heterogeneity existed among the included studies (I² values frequently exceeding 90%). Although this was accounted for using a random-effects model, it still indicates that the pooled estimates should be interpreted with caution. Heterogeneity primarily stemmed from substantial differences between studies in population characteristics, follow-up duration, and most critically—the definitions and diagnostic methods for respiratory complications. For instance, some studies relied on objective pulmonary function testing (using different cutoff values), while others were based on patient self-reports or hospital diagnosis codes. This inconsistency in definitions represents a fundamental challenge for evidence synthesis in this field and underscores the urgency for future studies to standardize outcome definitions. The high statistical heterogeneity observed reflects the clinical and methodological diversity across studies. Furthermore, the wide inclusion criteria may have introduced clinical heterogeneity. The mechanisms of pulmonary injury differ substantially across tumor types and treatment exposures, and the pooled estimates should be interpreted as an overall burden rather than precise estimates for any single diagnostic group. Future studies should focus on specific cancer diagnoses with standardized outcome definitions to permit more precise risk quantification. Second, while the majority of included studies reported point prevalence, Dietz et al. [2016] contributed cumulative incidence estimates from a longitudinal cohort. Although cumulative incidence over a follow-up period of 25 years approximates the proportion of survivors ever affected, the distinction between prevalence and incidence should be acknowledged. Relatedly, de Fine Licht et al. [2017] and Gibson et al. [2018] reported hospitalization incidence rates and temporal trends in cumulative incidence, respectively; these studies were summarized narratively rather than included in the pooled prevalence syntheses. Thirdly, a fundamental challenge in synthesizing evidence in this field is the lack of standardized definitions for respiratory outcomes. As detailed in Table 2, the included studies utilized diverse diagnostic criteria and cut-off values for defining pulmonary function abnormalities (e.g., DLCO <75% vs. <80% predicted) and clinical endpoints. This clinical heterogeneity in outcome measurement is a major contributor to the high statistical heterogeneity observed and means that our pooled prevalence estimates represent an average across varying definitions rather than a unified clinical endpoint. Future research must prioritize the adoption of consensus-based, standardized definitions (e.g., using GLI Z-scores for pulmonary function) to enable more valid and comparable evidence synthesis. In addition, the stratification of chemotherapy-induced pulmonary toxicity risk, while necessary for subgroup analysis, was limited by the variable and often incomplete reporting of treatment details in the original studies, particularly regarding cumulative doses. The “High/Moderate/Low” classification is therefore a simplified surrogate and may not capture the full gradient of individual risk. Finally, the included studies primarily originated from high-income countries, and their findings may not be directly generalizable to regions with different healthcare resources. The quality assessment in this review was constrained by the inherent limitations of the NOS, which, although widely used, does not capture all sources of bias with equal sensitivity. In particular, the NOS does not explicitly evaluate the validity of self-reported outcomes or the adequacy of pulmonary function testing protocols. To partially address this, we deducted points in the outcome domain for studies that relied on self-report without independent clinical confirmation. The resulting scores (range, 7–9) should be interpreted with this caveat. The development of risk of bias tools specifically designed for survivorship prevalence studies remains a methodological need.

Based on these findings and limitations, future research should promote the standardization of respiratory outcome assessment for childhood cancer survivors globally. This includes adopting consistent definitions of pulmonary function abnormalities (e.g., Z-scores based on the Global Lung Initiative), standardized imaging assessment tools, and validated patient-reported outcome measures. More prospective longitudinal studies are needed to elucidate the natural course of complications and establish clear risk prediction models. Concurrently, the role of biomarkers in early identification of subclinical lung injury should be explored.

All childhood cancer survivors, particularly those who received thoracic radiotherapy, highly pulmonary toxic chemotherapy, or hematopoietic stem cell transplantation, should undergo regular respiratory evaluations during long-term follow-up after treatment completion. Clinicians should recognize that survivors may exhibit significant pulmonary impairment even in the absence of symptoms. Risk-stratified follow-up strategies should be tailored based on individual treatment history, current symptoms, and baseline pulmonary function results. Patient education is also critical, emphasizing the importance of lung health, recognizing relevant symptoms, and strongly advising against additional lung injury risks such as smoking.

Conclusions

In summary, this meta-analysis confirms that respiratory complications represent a common and clinically significant late effect among long-term survivors of childhood and adolescent cancer. Although advances in treatment have reduced risk for more recently diagnosed cohorts, the overall burden remains substantial. These findings underscore the urgent need for treatment-based risk stratification and the implementation of systematic, lifelong pulmonary health surveillance. Future standardized studies and prospective cohorts are needed to further optimize risk management strategies, ultimately improving the long-term quality of life and health outcomes for this growing survivor population.

Acknowledgments

None.

Footnote

Reporting Checklist: The authors have completed the PRISMA reporting checklist. Available at https://tp.amegroups.com/article/view/10.21037/tp-2026-1-0139/rc

Peer Review File: Available at https://tp.amegroups.com/article/view/10.21037/tp-2026-1-0139/prf

Funding: None.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tp.amegroups.com/article/view/10.21037/tp-2026-1-0139/coif). The 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.

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/.

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