Clinical characteristics and treatment outcomes of neuroblastoma with pulmonary metastases

Abstract

Objective

To describe the clinical characteristics, treatment processes, and prognosis of primary neuroblastoma (NB) with concurrent pulmonary metastases.

Methods

Clinical data were collected retrospectively from 10 patients with primary NB and concurrent pulmonary metastases in our institution from March 2019 to October 2025. We collected and analyzed clinical and pathological features, imaging characteristics, and therapeutic responses.

Results

This cohort comprised seven boys and three girls, with a median age of 45.5 months (range 29–200 months). All patients were classified as stage M and high-risk group. N-myc proto-oncogene (MYCN) amplification was seen in four cases and gain in three cases. Heterogeneous responses to induction chemotherapy were observed. The primary tumor and bone marrow metastases showed favorable responses, whereas pulmonary metastases exhibited low sensitivity to chemotherapy. Nine patients died with a median survival of 17 months (range 5–64 months); one patient survived for 62 months. In the later stages of treatment, tumor progression or recurrence occurred in 9 patients, with bone (n=4), liver (n=4), lung (n=4), primary tumor site (n=3), distant lymph nodes (n=2), brain (n=2), and bone marrow (n=1) being the sites of first progression or recurrence.

Conclusions

Primary NB with pulmonary metastases is uncommon, frequently associated with MYCN amplification and multiple non-pulmonary metastases; prognosis is poor. Current clinical management predominantly involves systemic therapy, with limited local interventions for pulmonary metastases. Treatment responses vary across primary tumors and different metastatic sites.

WHAT IS ALREADY KNOWN ON THIS TOPIC.

• Pulmonary metastases at initial diagnosis of neuroblastoma are rare and associated with high-risk disease and poor prognosis.

• Their clinical characteristics, treatment responses, and optimal management remain poorly defined.

WHAT THIS STUDY ADDS

• This study adds to the limited evidence for neuroblastoma by reporting 10 newly diagnosed cases with concurrent pulmonary metastases.

• We add a comprehensive description of their clinical characteristics, molecular features, treatment responses, and prognosis.

• This study confirms that patients with pulmonary metastases frequently exhibited MYCN amplification, adrenal primary tumors, multiple metastatic sites, and extremely poor survival.

• We provide a detailed radiographic description of pulmonary metastatic neuroblastoma lesions that are of value in informing future diagnostic frameworks.

• We demonstrate heterogeneous responses to induction therapy across metastatic sites, with pulmonary metastases showing substantially lower sensitivity than primary tumors and bone marrow lesions; this highlights the limitations of current treatment strategies.

HOW THIS STUDY MIGHT AFFECT RESEARCH, PRACTICE OR POLICY

• These findings improve the understanding of this rare metastatic pattern and may facilitate earlier risk assessment.

• The marked heterogeneity in treatment response supports the development of site-specific therapeutic strategies and prospective multicenter studies to improve patient outcomes.

Introduction

Neuroblastoma (NB) is the most common extracranial solid malignant tumor in children, originating from the adrenal medulla or paravertebral sympathetic ganglia. It accounts for 8%–10% of childhood cancers^1–4 and contributes to at least 15% of tumor-related deaths in children.² Over 50% of patients present with metastases at diagnosis, with common sites including bones, bone marrow, and lymph nodes.^3–5 Pulmonary metastases are comparatively rare, with a reported incidence at initial diagnosis ranging from 0.2% to 3.7%.³ Pulmonary metastases are considered an adverse event, significantly increasing the risk of early mortality.^5–7 However, owing to its rarity, clinical understanding of primary NB with concurrent pulmonary metastases is poor; imaging characteristics, treatment response, and clinical outcomes of pulmonary metastases are also poorly defined. In this study, we summarize the clinical characteristics, treatment processes, and prognosis of patients with primary NB and concurrent pulmonary metastases treated at a single tertiary pediatric center in China. Our objective is to enhance clinical awareness and explore potential strategies to improve poor outcomes.

Methods

This study received approval from the local institutional review board. A waiver of consent was granted for the analyses performed in this study. Clinical data of 653 children with NB admitted to the same institution from March 2019 to October 2025 were retrospectively collected. Among these, 10 patients were diagnosed with primary NB with concurrent pulmonary metastases. Although a proportion of these patients were derived from our previously published cohorts,^8–10 the present study addresses a unique clinical question and employs a different set of inclusion criteria. Clinical characteristics, imaging findings, chemotherapy regimens, surgical details, along with pathological and molecular outcomes were obtained from medical records. Initial diagnosis of NB was made according to the International Neuroblastoma Staging System criteria.¹¹ Patients were staged according to the International Neuroblastoma Risk Group Staging System¹² and then grouped by the International Neuroblastoma Risk Group (INRG) classification system.¹³ Pulmonary metastases were identified via chest computed tomography (CT) and iodine-123 metaiodobenzylguanidine (¹²³I-MIBG) scintigraphy or 18F-fluorodeoxyglucose (¹⁸F-FDG) positron emission tomography-computed tomography (PET-CT). Consistent with previous studies, nodules in patients with NB with pulmonary metastases typically measured 5–10 mm in diameter,^{3 14} frequently presenting as multiple pulmonary nodules and often corresponding to areas of abnormal MIBG or PET-CT uptake.^{15 16} Patients received multimodal therapy adhering to the Chinese guideline for NB treatment (2019).^{8 9} All treatment planning and care was conducted in accordance with relevant guidelines and regulations. Oncological prognosis was obtained through outpatient records and telephone follow-up, with follow-up dates extending to June 2026 or the date of the patient’s death.

Results

Patient characteristics

This cohort comprised seven boys and three girls, with a median age of 45.5 months (range 29–200 months). In nine cases, the primary lesions originated from the adrenal glands, and in one case, it was located in the posterior mediastinum. The median diameter of the primary tumor was 12.75 cm (range 5.3–16.6 cm). Initial presenting symptoms included fever (n=5), abdominal pain (n=3), abdominal mass (n=3), bone pain (n=3), and cough (n=4). In addition to pulmonary metastases, bone and bone marrow (n=6), distant lymph node (n=5), and liver (n=5) were other metastatic sites. All patients were classified as stage M and high-risk according to the INRG criteria. Pathology findings indicate that, apart from case 7 presenting as a differentiated NB and case 10 as an undifferentiated NB, all other patients were diagnosed with poorly differentiated NB. Laboratory investigations revealed that tumor markers including neuron-specific enolase, lactate dehydrogenase (LDH), urinary vanillylmandelic acid/creatinine, and urinary homovanillic acid/creatinine were significantly elevated above the normal range in all 10 patients. Molecular biological characteristics revealed four cases of N-myc proto-oncogene (MYCN) amplification and three cases of MYCN gain. In addition, four cases exhibited 1p deletion, three cases demonstrated 1p imbalance, and two cases showed 11q deletion (table 1).

Table 1.

Clinical characteristics of 10 patients with neuroblastoma

Case	Age group	Primary lesion and pathology	Metastatic site	NSE (ng/mL)	LDH (U/L)	VMA/Crn and HVA/Crn (μmol/mmol)	MYCN	1 p and 11q
1	Early childhood	R adrenal/poorly differentiated NB	Lung/bone marrow/bone	430	1271	/	Normal	Imbalance/normal
2	Early childhood	R adrenal/poorly differentiated NB	Lung/bone marrow/bone/distant lymph node/liver	1115	2812	/	Amplification	Imbalance/deletion
3*	Early adolescence	L adrenal/poorly differentiated NB	Lung/distant lymph node/liver	176	378	349.207/27.402	Normal	Imbalance/normal
4*	Early childhood	R adrenal/poorly differentiated NB	Lung	805	1381	/	Gain	Normal/normal
5	Early childhood	L adrenal/poorly differentiated NB	Lung/bone marrow/bone	750	2339	1.792/750.336	Amplification	Deletion/normal
6	Middle childhood	L adrenal/poorly differentiated NB	Lung/bone marrow/bone	694.5	1019	109.457/23.194	Gain	Deletion/normal
7	Early childhood	R adrenal/differentiated NB	Lung/bone marrow/bone/distant lymph node/liver	475.5	2059	27.617/3.980	Amplification	Deletion/gain
8	Early childhood	Posterior mediastinum/poorly differentiated NB	Lung/bone marrow/bone/distant lymph node/liver	685	1599	1386/98.276	Gain	Normal/deletion
9	Middle childhood	L Adrenal/poorly differentiated NB	Lung/liver	910	1123	/	Normal	Normal/normal
10	Early childhood	R adrenal/undifferentiated NB	Lung/distant lymph node	1030	4214	/	Amplification	Deletion/normal

Normal range: NSE (≤25 ng/mL); LDH (110–295 U/L); VMA/Crn (0.954–9.348 μmol/mmol); HVA/Crn (1.081–9.740 μmol/mmol).

*ALK status: Case 3: no ALK variation. Case 4: ALK mutation (Exon 23). The other 8 patients were not assessed for ALK status.

ALK, anaplastic lymphoma kinase; Crn, creatinine; HVA, homovanillic acid; L, left; LDH, lactate dehydrogenase; MYCN, N-myc proto-oncogene; NB, neuroblastoma; NSE, neuron-specific enolase; 1p/11q, chromosomal 1p and 11q alterations; R, right; VMA, vanillylmandelic acid.

Response to treatment

All patients were treated with the chemotherapy regimen for high-risk cases following diagnosis. The treatment responses for each lesion were assessed at two time points according to the International Neuroblastoma Response Criteria:¹⁷ (1)during the induction phase, and (2) at the time of first progression or relapse or last follow-up with stable condition (table 2).

Table 2.

Evaluation of treatment response for 10 patients with neuroblastoma

Tumor lesion		Case 1	Case 2	Case 3	Case 4	Case 5	Case 6	Case 7	Case 8	Case 9	Case10
Primary tumor site	Initial diagnosis	Positive	Positive	Positive	Positive	Positive	Positive	Positive	Positive	Positive	Positive
	After induction therapy	CR	CR	CR	PR	CR	CR	CR	PR	PD	PR
	First progression or recurrence	CR*	CR	CR	CR	PD	CR	CR	PD	PD	PR
Lung	Initial diagnosis	Positive	Positive	Positive	Positive	Positive	Positive	Positive	Positive	Positive	Positive
	After induction therapy	CR	PD	SD	SD	SD	PR	PR	PR	PD	PD
	First progression or recurrence	CR	PD	SD	PR	PR	CR	CR	PD	PD	PD
Bone marrow	Initial diagnosis	Positive	Positive	Negative	Negative	Positive	Positive	Positive	Positive	Negative	Negative
	After induction therapy	CR	MD	Negative	Negative	CR	MD	MD	MD	Negative	Negative
	First progression or recurrence	CR	PD	Negative	Negative	MD	MD	MD	MD	Negative	Negative
Bone	Initial diagnosis	Positive	Positive	Negative	Negative	Positive	Positive	Positive	Positive	Negative	Negative
	First progression or recurrence	CR	PD	Negative	Negative	PD	Unknown	PD	PD	Negative	Negative
Distant lymph node	Initial diagnosis	Negative	Positive	Positive	Negative	Negative	Negative	Positive	Positive	Negative	Positive
	After induction therapy	Negative	PR	SD	Negative	Negative	Negative	SD	PR	Negative	PR
	First progression or recurrence	Negative	PD	PR	Negative	Negative	Negative	PD	SD	Negative	PR
Liver	Initial diagnosis	Negative	Positive	Positive	Negative	Negative	Negative	Positive	Positive	Positive	Negative
	After induction therapy	Negative	CR	SD	Negative	Negative	Negative	SD	PR	PD	Negative
	First progression or recurrence	Negative	PD	PD	PD	Negative	Negative	CR	SD	PD	Negative

*Case 1 has not experienced a recurrence or progression of the disease.

CR, complete response; MD, minimal disease; PD, progressive disease; PR, partial response; SD, stable disease.

During induction therapy, six patients showed a complete response (CR) of the primary lesion, three exhibited partial response (PR), while case 9 experienced progressive disease (PD) before surgery. These response patterns indicate that chemotherapy combined with surgery was associated with control of disease progression at the primary site. Bone marrow metastases demonstrated relative sensitivity to induction therapy, with four of six patients achieving minimal disease (MD) and two of six achieving CR. Regarding distant lymph node responses, two of five patients showed stable disease (SD), and three of five achieved PR. Among patients presenting with liver metastases at initial diagnosis, five patients demonstrated the following responses: PD (n=1), SD (n=2), PR (n=1), and CR (n=1). As for the pulmonary metastases, three experienced PD, three showed SD, three achieved PR, and one advanced CR (figures 1 and 2 depict imaging of case 6 and case 8 who achieved PR of pulmonary metastases during the induction therapy phase). This demonstrates that different lesions exhibit heterogeneous responses to induction therapy.

Figure 1.

Imaging characteristics of case 6 before and after treatment. (A) PET-CT scan pretreatment; (B) Chest CT scan pretreatment; (C) Chest CT scan after induction therapy (PR); (D) Chest CT scan of last assessment (CR); (E) ¹²³I-MIBG scan after induction therapy. The arrows in the picture indicate a typical lung metastatic lesion. CR, complete response; PR, partial response; PET-CT, positron emission tomography-computed tomography; ¹²³I-MIBG, iodine-123 metaiodobenzylguanidine.

Figure 2.

Imaging characteristics of case 8 before and after treatment. (A) Chest CT scan pretreatment; (B) Chest CT scan after induction therapy (PR); (C) Chest CT scan of last assessment (PD). The arrows in the picture indicate a typical lung metastatic lesion. PD, progressive disease; PR, partial response.

Efficacy at the last follow-up with stable condition or first progression or relapse is described below. Case 1 survived without tumor recurrence (achieving CR in all lesions). The other nine patients all progressed or relapsed. Their therapeutic responses were as follows. For five patients with bone marrow metastases, one showed PD and four MD. For bone metastases there was an unknown response in case 6; all other patients exhibited varying degrees of worsening bone destruction or new bone metastases (PD=4). Two patients with distant lymph node lesions exhibited PD, one with SD, and two with PR. For liver metastases, one patient achieved CR following surgical resection of the liver metastases, while the remaining four patients showed PD and one patient with SD (characterized by tumor enlargement that had not yet met the criteria of PD). Treatment outcomes for pulmonary metastases showed that four patients showed PD (figure 2), one SD, two PR, and two CR (figure 1).

Prognosis

Case 1 is currently tumor-free at 62 months. The remaining nine patients all died of their illnesses (table 3). Cases 2–10 all experienced tumor progression or recurrence, with the median survival time of 17 months (range 5–64 months). The sites of first progression or recurrence of these nine patients included bone (n=4), lung (n=4), liver (n=4), primary tumor site (n=3), distant lymph nodes (n=2), brain (n=2), and bone marrow (n=1).

Table 3.

Prognosis of 10 patients with neuroblastoma

Case	Conventional treatment*	Time to first progression or recurrence	Site of first progression or recurrence	Postprogression or recurrence treatment	Prognosis	Survival period (months)
1	Chemotherapy-surgery-chemotherapy	/	/	/	Tumor-free survival	62
2	Chemotherapy-surgery	5 months after treatment initiation	Brain, lung, bone marrow, bone, distant lymph nodes, liver	Chemotherapy-surgery†	Death	17
3	Chemotherapy-surgery-chemotherapy	15 months after treatment initiation	Liver	Chemotherapy	Death	17
4	Chemotherapy-surgery-chemotherapy-surgery‡-radiotherapy-chemotherapy	16 months after treatment initiation	Liver	Chemotherapy	Death	28
5	Chemotherapy-surgery-chemotherapy	7 months after treatment initiation	Primary site, bone	Chemotherapy	Death	12
6	Emergency surgery§-chemotherapy-surgery-chemotherapy	34 months after treatment initiation	Brain	Chemotherapy	Death	36
7	Chemotherapy-surgery-chemotherapy-GD2 immunotherapy	44 months after treatment initiation	Bone, distant lymph nodes	Chemotherapy-DFMO	Death	64
8	Chemotherapy-surgery-chemotherapy-surgery¶-radiotherapy	9 months after treatment initiation	Primary site, lung, bone	Chemotherapy	Death	19
9	Chemotherapy	1 month after treatment initiation	Primary site, lung, liver	Chemotherapy-surgery	Death	6
10	Chemotherapy	1 month after treatment initiation	Lung	Chemotherapy-surgery-surgery**	Death	5

*Unless otherwise specified, ‘surgery’ refers to resection of the primary tumor.

†Wedge resection of the right middle lobe of the lung.

‡Resection of residual retroperitoneal tumor.

§Microsurgical resection of extradural tumor.

¶Resection of residual retroperitoneal and mediastinal tumors plus dissection of distant lymph nodes.

**Resection of the primary tumor and tumors in the right mediastinum and chest wall.

DFMO, difluoromethylornithine.

Four patients with progressive pulmonary metastases had shorter survival times: 17 months, 19 months, 6 months, and 5 months, respectively. Among these, case 2 and case 8 had uncontrolled pulmonary metastases and ultimately died from multisystem tumor progression and excessive disease burden. For case 9, pulmonary metastases continued to worsen, ultimately causing shortness of breath and cardiac arrest, thus leading to death (figure 3 depicts the progression of pulmonary metastases in case 9). Patient 10 died of severe infection and multiple organ failure following surgery (retroperitoneal and mediastinal). Case 3, the oldest at diagnosis at 200 months, developed severe bone marrow suppression during chemotherapy and died 2 months after liver progression, with a survival period of 17 months. Case 4 presented with just pulmonary metastases at initial diagnosis and harbored both ALK mutation and MYCN gain (table 1). This patient developed new liver metastases after induction therapy and died 1 year after recurrence, with a survival period of 28 months. Case 5 presented with the largest primary tumor diameter at initial diagnosis (16.6 cm). Following 7 months of standard treatment, recurrence of the primary tumor and progression of bone metastases led to death, with a survival period of only 12 months. Case 6 presented with multiple metastases at initial diagnosis and underwent emergency microsurgical resection of the extradural tumor; induction therapy provided symptomatic relief. However, the patient ultimately died from intracranial progression after 36 months. Case 7 demonstrated the longest survival at 64 months. Despite receiving multimodal, long-course, multiline comprehensive therapy, the development of multidrug resistance was ultimately inevitable, and the patient succumbed to multiple metastatic sites including brain, lung, and liver.

Figure 3.

Imaging characteristics of case 9 before and after treatment. (A) PET-CT scan pretreatment; (B) Chest CT pretreatment; (C) Chest CT scan after two cycles of chemotherapy (PD). PD, progressive disease; PET-CT, positron emission tomography-computed tomography.

Discussion

Pulmonary metastases are uncommon in NB. In contrast, Wilms tumor (WT) and osteosarcoma (OS) are the most common pediatric malignancies with pulmonary metastases. Pulmonary metastases of NB typically appear as multiple, bilateral, round, small, non-calcified solid nodules (median number, five nodules), with a random distribution, slight predominance in the lung bases, and smooth or spiculated margins, which is presumably related to the fact that NB mainly spreads through the bloodstream.^{3 14 18} Consistent with these findings, most patients in our cohort presented with multiple well-defined solid nodules randomly distributed in the peripheral and subpleural lung fields.

Pulmonary metastases from NB also exhibited atypical imaging features. Pleural metastases, cavitary changes, and ground-glass opacities are observed (figures 1–3). Although calcified foci can be seen in the primary tumors and lymph node metastases of most NB, calcified foci are rarely seen in the pulmonary metastases, also consistent with previous reports.^{3 14} In contrast, WT usually presents with larger, well-circumscribed pulmonary nodules, and OS more frequently exhibits calcified nodules, cavitation, the CT halo sign, and pleural metastases.^19–21

Currently, there are limited data on CT evaluation for pulmonary metastases in NB. Referencing the diagnostic standards used for other solid tumors may be a viable approach. Methods for assessing primary solid tumors include chest X-rays, ultrasound, MRI, and nuclear imaging, but CT scanning is more commonly used in evaluating pulmonary metastases. Relevant literature indicates that solitary nodules ≥10 mm or multiple nodules ≥5 mm is considered pulmonary metastases (e.g., European Ewing Tumor Working Initiative of National Groups–Ewing Tumor Studies 1999). Nodules smaller than 5 mm are defined as micro-metastases and are not counted as pulmonary metastases; they require only follow-up observation (e.g., European Pediatric Soft Tissue Sarcoma Study Group RMS 2005 Study).²² Other studies indicate that imaging assessments of metastatic lesions should only be used for reference, particularly with limitations in evaluating lesions <6 mm. Pathological examination remains the gold standard for definitive diagnosis.²³

Different metastatic sites exhibited marked heterogeneity in response to treatment. The curative effect on the primary lesion is remarkable; most patients showed CR or PR after induction therapy, apart from case 9 who experienced progression at the primary site prior to surgery. Bone marrow metastasis was also chemotherapy-sensitive, whereas bone and lung metastases showed relatively poorer outcomes. Liver metastases were sensitive to chemotherapy during the induction phase but were prone to recurrence or progression in later stages; three patients ultimately died from progression of liver metastases. Distant lymph node metastases exhibited significant individual variability.

Of note, pulmonary metastases were less sensitive to chemotherapy and frequently progressed. Four patients with progressive pulmonary metastases had short survival periods. Two of three patients who exhibited PR after induction therapy showed longer survival and later recurrence or progression compared with other patients, suggesting that pulmonary metastases might be closely associated with disease progression and poor prognosis. This finding is consistent with previous studies.^5–7

The mechanisms underlying treatment heterogeneity are not fully understood. One possible explanation is that pulmonary metastases are frequently associated with adverse biological features, including MYCN amplification, elevated LDH levels, and multiple metastatic sites; these factors may further reduce sensitivity to treatment and lead to a poor prognosis.^{5–7 24} Therefore, metastatic sites should be evaluated independently, particularly pulmonary lesions to facilitate timely therapeutic adjustment.

In a series of retrospective cohorts, the number of cases in which patients with NB received pulmonary nodule resection or whole-pulmonary radiotherapy was extremely small. Pulmonary surgery was only used to obtain histological confirmation, and no survival benefit was observed. Moreover, local surgery or radiotherapy did not markedly change the systemic disease status.^25–27 In this cohort, only case 2 underwent surgery for pulmonary metastases after induction treatment and tumor progression to determine pathological and molecular characteristics. This patient had multiple metastases at multiple sites, a large tumor burden, and the pulmonary lesions recurred repeatedly during treatment, with a relatively short overall survival. A previous case report showed that with repeated pulmonary and liver metastatic relapses, the patient’s condition could be alleviated after combined treatment with chemotherapy, radiotherapy, and resection of metastatic lesions, suggesting that pulmonary resection remains an option that can be considered under specific circumstances.²⁸

Prior studies indicate that pulmonary metastases are more common in patients with MYCN amplification, primary adrenal tumors, or elevated LDH levels.^{6 7 24} Additionally, some studies have indicated that the unfavorable pathological prognostic type is more prevalent among patients with lung metastases; however, its specificity cannot be established.¹⁴ In our cohort, all had varying LDH elevations. The primary lesions of nine patients were in the adrenal gland, and MYCN was abnormal in seven patients (four cases of MYCN amplification and three cases of MYCN gain). The MYCN result of case 1 with tumor-free survival was normal, which may be related to the good prognosis.

NB metastases tend to occur in the bone, bone marrow, liver, distant lymph nodes; pulmonary metastases are relatively rare. The current reason for its rarity is still unclear. Previous relevant studies have shown that the abnormally high expression of molecules such as MYCN, SRCIN1/p140Cap (SRC proto-oncogene (SRC) kinase signaling inhibitor 1/p130Cas-associated protein), and LIM domain only 1 (LMO1) enhances the invasive ability of tumor cells and increases the likelihood of pulmonary metastases.^{29 30} Some chemokines such as CXCR4/CXCR7/CXCL12 (C-X-C motif chemokine receptor 4/C-X-C motif chemokine receptor 7/C-X-C motif chemokine ligand 12) may be directly involved in determining the sites of distant metastases.³¹ In addition, the random distribution resulting from hematogenous dissemination cannot explain the metastasis pattern of NB; there is more likely a specific growth pattern or nutritional preference.³² A further study suggests that the characteristics of the pulmonary microenvironment, with low requirements for growth factors and high immune pressure, inhibit the possibility of pulmonary metastases in NB. However, the mechanism underlying pulmonary metastases in NB is unknown and requires further in-depth study.³³

Pulmonary metastasis often occurs in the late stage of disease progression and is associated with poor prognosis. Univariate analyses in relevant studies have consistently shown that pulmonary metastasis is related to a decrease in event-free survival. However, after adjustment for factors such as age, MYCN, LDH, and bone marrow involvement, pulmonary metastasis itself is not an independent poor prognostic factor.^{5 7} Comprehensive analysis of multiple clinical studies indicates that pulmonary metastasis rarely exists in isolation. Most cases are accompanied by bone, bone marrow, liver, or even central nervous system metastases, suggesting that it is a manifestation of advanced disease and one of the markers of high tumor burden. Therefore, the occurrence of pulmonary metastasis in NB is still associated with a poor clinical prognosis.6 14 24 34 Only a single patient in our cohort experienced disease-free survival, eight died of tumor progression or recurrence, and case 10 died as a result of poor general health following surgery. This demonstrates the possible poor prognosis of patients with newly diagnosed NB with pulmonary metastasis and suggests that for such patients, it may be necessary to adjust the treatment plan as early as possible and explore more powerful and effective treatment options.

Limitations

This is a single-center retrospective analysis of a small sample that underscores a need for larger, multicenter studies to validate these findings. The extended study period, coupled with constraints such as drug availability and cost, meant that not all patients received standardized autologous hematopoietic stem cell transplantation, disialoganglioside GD2 monoclonal antibody therapy, or difluoromethylornithine treatment. This precludes in-depth analysis of the relationship between treatment regimens and prognosis. Furthermore, this study exhibits high treatment heterogeneity, lacks a control group, and does not include multivariate analysis. Future large-scale, multicenter prospective studies are required.

Conclusion

In summary, NB with pulmonary metastases is uncommon in clinical practice. It is frequently associated with markedly elevated tumor markers, MYCN amplification, and adrenal primary tumors, often accompanied by distant metastases, indicating a poor prognosis. Current clinical management predominantly involves systemic therapy, and treatment responses vary across metastatic sites, with limited local interventions for pulmonary metastases.

Data availability statement

All data relevant to the study are included in the article or uploaded as supplementary information.

Ethics statements

Patient consent for publication

Not applicable.

Ethics approval

This study involves human participants. This retrospective study was approved by the Medical Ethics Committee of Beijing Children's Hospital (Approval no.:(2023)-E-029-Y-01). The requirement for individual informed consent was waived because this was a retrospective study using only anonymized patient data, where identifying information had been removed.