Real-World Study on Efficacy and Influencing Factors of Immunotherapy for Pan-Cancer Lymph Node Metastases.

Real-World Study on the Efficacy of Immunotherapy for Pan-Cancer Lymph Node Metastatic Tumors and Its Influencing Factors

Lymph node metastasis is a key stage of malignant tumor progression and a core factor affecting the efficacy of immunotherapy. The therapeutic response of lymph node metastases to immune checkpoint inhibitors (ICIs) varies significantly among different cancer types, and the underlying regulatory mechanisms remain unclear. This single-center, retrospective observational study was approved by the Ethics Committee of Sun Yat-sen Memorial Hospital of Sun Yat-sen University (Approval No.: SYSKY-2026-278-01). We plan to enroll no less than 5000 patients with pan-cancer lymph node metastasis who received ICI therapy in our hospital. The efficacy of primary tumors (T) and metastatic lymph nodes (N) before and after immunotherapy will be evaluated based on TNM staging changes, and the objective response rate (ORR) at both levels will be calculated. Patients will be divided into two groups according to the use of β-blockers during immunotherapy to compare the ORR differences, and explore the clinical factors affecting the efficacy of immunotherapy for pan-cancer lymph node metastases. This study aims to provide evidence-based medical basis for formulating individualized immunotherapy strategies for pan-cancer lymph node metastasis.

Study Overview

• Status: Not yet recruiting
• Conditions: Malignant Solid Tumors With Lymph Node Metastasis

Detailed Description

This is a single-center, retrospective observational study conducted at Sun Yat-sen Memorial Hospital of Sun Yat-sen University, approved by the hospital's Ethics Committee (Approval No.: SYSKY-2026-278-01). The study aims to systematically evaluate the efficacy of immune checkpoint inhibitor (ICI) immunotherapy in patients with pan-cancer lymph node metastases, and to explore the influencing factors of efficacy, especially the regulatory effect of β-blocker use on the response of metastatic lymph nodes to immunotherapy.

1. Study Background Lymph node metastasis is a critical stage in the progression of various malignant solid tumors, and is an independent risk factor for poor prognosis in patients. In recent years, immune checkpoint inhibitors (ICIs) represented by PD-1/PD-L1 inhibitors have significantly improved the survival of patients with multiple advanced cancers, becoming a core treatment modality for malignant tumors. However, the response of metastatic lymph nodes to immunotherapy is often inconsistent with that of primary tumors, and the efficacy varies greatly among different cancer types. At present, most relevant studies focus on the efficacy of primary tumors, and there is a lack of systematic pan-cancer analysis focusing on the response of metastatic lymph nodes to immunotherapy. In addition, preclinical and clinical studies have shown that β-blockers can regulate the tumor immune microenvironment, enhance the anti-tumor effect of immunotherapy, and improve the prognosis of patients. However, whether β-blockers can improve the response of metastatic lymph nodes to immunotherapy in pan-cancer populations has not been systematically verified. This study fills this gap by conducting a real-world retrospective analysis of a large sample of pan-cancer patients with lymph node metastasis who received immunotherapy.

2. Study Objectives Primary Objectives To evaluate the objective response rate (ORR) of metastatic lymph nodes (N stage) and primary tumors (T stage) in patients with pan-cancer lymph node metastasis after ICI immunotherapy.

   To compare the difference in ORR of metastatic lymph nodes between patients who received β-blockers during immunotherapy and those who did not.

   Secondary Objectives To analyze the consistency of therapeutic response between primary tumors and metastatic lymph nodes in the same patient.

   To calculate the downstaging rate of T stage, N stage and overall TNM stage after immunotherapy, and the disease control rate (DCR) at T and N levels.

   To explore the clinical factors (including cancer type, baseline stage, treatment line, combined therapy, local treatment, baseline laboratory indicators, etc.) associated with the ORR of metastatic lymph nodes.

   Exploratory Objectives To analyze the correlation between the timing and duration of β-blocker use and the ORR of metastatic lymph nodes.

   To conduct subgroup analysis of the effect of β-blockers on the ORR of metastatic lymph nodes in different cancer types (such as bladder cancer, lung cancer, colorectal cancer, etc.).

   To evaluate the long-term clinical outcomes of patients, including progression-free survival (PFS), overall survival (OS) and time to lymph node progression.

3. Study Design This study adopts a retrospective cohort study design. We will retrospectively collect the clinical data of patients who received ICI immunotherapy at Sun Yat-sen Memorial Hospital of Sun Yat-sen University from January 2018 to December 2025, and screen eligible patients according to the inclusion and exclusion criteria. The estimated sample size is no less than 5000 cases. Patients will be divided into two groups according to whether they used β-blockers during immunotherapy: the β-blocker combined with immunotherapy group and the immunotherapy alone control group. All data will be collected from the hospital's electronic medical record system, imaging system and follow-up system, and will be desensitized to protect patient privacy in accordance with ethical requirements.

4. Study Population Inclusion Criteria Histopathologically or cytologically confirmed malignant solid tumors (including non-small cell lung cancer, small cell lung cancer, gastric cancer, colorectal cancer, bladder cancer, breast cancer, esophageal cancer, liver cancer, pancreatic cancer, melanoma, etc.).

   Confirmed regional or distant lymph node metastasis by enhanced CT, MRI, PET-CT or pathological examination.

   Received at least 1 cycle of ICI immunotherapy (monotherapy or combined therapy), with clear treatment initiation time and regimen records.

   Complete clinical diagnosis, treatment, efficacy evaluation and follow-up records, with available baseline imaging before immunotherapy and at least one imaging reexamination after immunotherapy for T and N stage assessment.

   Evaluable tumor lesions according to RECIST 1.1 criteria. Clear records of β-blocker use in medical records. Aged ≥18 years, regardless of gender. Exclusion Criteria Less than 1 cycle of ICI therapy, unevaluable efficacy, or missing medication time/regimen information.

   Incomplete clinical records with missing key data required for analysis. Complicated with other synchronous or metachronous malignant tumors. Received other anti-tumor immunotherapy (such as adoptive cell therapy, tumor vaccine, etc.) before ICI therapy.

   Unclear diagnosis of lymph node metastasis or unlocatable/evaluable lymph node metastatic lesions.

   Pregnant women, or patients whose data cannot be desensitized or meet ethical and data compliance requirements.

   Imaging cannot distinguish the changes of primary tumors and lymph node lesions.

5. Data Collection and Follow-up

   We will collect the following data from the electronic medical record system:

   Basic patient information: age, gender, smoking history, comorbidities, etc. Tumor-related information: cancer type, baseline TNM stage, primary tumor site, lymph node metastasis site, etc.

   Treatment-related information: ICI regimen, treatment line, combined therapy (chemotherapy, targeted therapy, etc.), local treatment (surgery, radiotherapy, etc.), β-blocker use (type, dosage, duration, timing of use relative to immunotherapy), etc.

   Efficacy evaluation data: baseline and post-immunotherapy imaging reports, T and N stage changes, ORR, DCR, etc.

   Follow-up data: PFS, OS, time to lymph node progression, adverse events, etc. All patients will be followed up until December 2026, and the follow-up data will be obtained from outpatient reexamination records, inpatient records and telephone follow-up.

6. Statistical Analysis All statistical analyses will be performed using R software (version 4.3.1) and SPSS (version 26.0). Categorical variables will be expressed as frequency and percentage, and compared using the chi-square test or Fisher's exact test. Continuous variables will be expressed as mean ± standard deviation or median (interquartile range), and compared using the t-test or Mann-Whitney U test. The ORR and DCR of T and N stages will be calculated, and the difference between the β-blocker group and the control group will be compared. The consistency of T and N efficacy will be evaluated using the Kappa coefficient. Univariate and multivariate logistic regression analyses will be used to explore the independent influencing factors of ORR of metastatic lymph nodes. Survival analysis will be performed using the Kaplan-Meier method, and the difference between groups will be compared using the log-rank test. Subgroup analysis will be conducted according to cancer type, β-blocker type, etc. A two-sided P value < 0.05 will be considered statistically significant.
7. Ethical Considerations This study has been approved by the Ethics Committee of Sun Yat-sen Memorial Hospital of Sun Yat-sen University (Approval No.: SYSKY-2026-278-01). As a retrospective observational study, the requirement for informed consent has been waived by the ethics committee. All patient data will be strictly desensitized, encrypted and stored, and only the research team can access the data, ensuring the protection of patient privacy and compliance with the Declaration of Helsinki and relevant ethical guidelines.

• Study Type: Observational
• Enrollment (Estimated): 5000

Contacts and Locations

• Study Contact: Name: Tianxin Lin, MD, PhD, Professor; Phone Number: +86-13724008338; Email: ltxgcp2017@163.com
• Study Contact Backup: Name: Wenlong Zhong, MD, PhD, Associate Professor; Phone Number: 020-81332402; Email: zhongwlong3@mail.sysu.edu.cn

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510120
      • Sun Yat-sen Memorial Hospital of Sun Yat-sen University
      • Contact: Wenlong Zhong, MD, PhD, Associate Professor; Phone Number: 020-81332402; Email: zhongwlong3@mail.sysu.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

This study enrolls adult patients (aged ≥18 years) with histopathologically confirmed malignant solid tumors and lymph node metastasis, who received at least 1 cycle of immune checkpoint inhibitor (ICI) immunotherapy at Sun Yat-sen Memorial Hospital of Sun Yat-sen University, with complete clinical, imaging and follow-up records.

Description

Inclusion Criteria:

- Histopathologically or cytologically confirmed malignant solid tumors (including non-small cell lung cancer, small cell lung cancer, gastric cancer, colorectal cancer, bladder cancer, breast cancer, esophageal cancer, liver cancer, pancreatic cancer, melanoma, etc.) Confirmed regional or distant lymph node metastasis by imaging (enhanced CT/MRI/PET-CT) or pathological examination Received at least 1 cycle of ICI therapy (monotherapy or combined therapy) with clear treatment initiation time and regimen records Complete clinical diagnosis, treatment, efficacy evaluation and follow-up records, with available baseline and post-immunotherapy imaging for T/N stage assessment Evaluable tumor lesions according to the RECIST 1.1 criteria Clear β-blocker use records in medical records Aged ≥18 years, regardless of gende

Exclusion Criteria:

• Less than 1 cycle of ICI therapy, unevaluable efficacy, or missing medication time/regimen information Incomplete clinical records with missing key data for analysis Complicated with other synchronous or metachronous malignant tumors Received other anti-tumor immunotherapy before ICI therapy (e.g., adoptive cell therapy, tumor vaccine) Unclear diagnosis of lymph node metastasis or unlocatable/evaluable lymph node metastatic lesions Pregnant women, or patients whose data cannot be desensitized or meet ethical/data compliance requirements Imaging cannot distinguish the changes of primary tumors and lymph node lesions

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
β-blocker combined with immunotherapy group; Patients who received β-blocker administration during immune checkpoint inhibitor (ICI) immunotherapy
Immunotherapy alone group (control group); Patients who received ICI immunotherapy without β-blocker administration

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR) at the primary tumor (T) level	Proportion of patients with decreased T stage after immunotherapy (downstaging = response; stable/elevated T stage = non-response/progression)	6-12 weeks after the initiation of immunotherapy
Objective Response Rate (ORR) at the metastatic lymph node (N) level	Proportion of patients with decreased N stage after immunotherapy (downstaging = response; stable/elevated N stage = non-response/progression)	6-12 weeks after the initiation of immunotherapy
Effect of β-blocker administration on N-level ORR	Comparison of metastatic lymph node ORR between the β-blocker combined group and the immunotherapy alone control group	6-12 weeks after the initiation of immunotherapy

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Consistency of T and N efficacy	Consistency/inconsistency rate of therapeutic response between primary tumors and metastatic lymph nodes in the same patient	6-12 weeks after the initiation of immunotherapy
Outcome Measure:	Proportion of overall TNM/T/N downstaging after immunotherapy, including separate T and N downstaging rates	6-12 weeks after the initiation of immunotherapy

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Relationship between β-blocker exposure intensity/timing and N-level ORR	Association between β-blocker use time (before/concurrent with immunotherapy) and duration with N-level ORR	6-12 weeks after the initiation of immunotherapy
Subgroup analysis of different cancer types	Consistency/heterogeneity of the association between β-blocker and N-level ORR in bladder cancer, lung cancer, colorectal cancer, etc.	6-12 weeks after the initiation of immunotherapy

Collaborators and Investigators

• Sponsor: Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University

Study record dates

Study Major Dates

• Study Start (Estimated): March 30, 2026
• Primary Completion (Estimated): April 15, 2027
• Study Completion (Estimated): May 1, 2027

Study Registration Dates

• First Submitted: April 13, 2026
• First Submitted That Met QC Criteria: April 13, 2026
• First Posted (Actual): April 20, 2026

Study Record Updates

• Last Update Posted (Actual): April 20, 2026
• Last Update Submitted That Met QC Criteria: April 13, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Immunotherapy; Immune checkpoint inhibitor; ICI; Lymph node metastasis; Objective response rate; Pan-cancer; Real-world study; β-blocker; Retrospective cohort study
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Neoplastic Processes; Neoplasm Metastasis; Pathological Conditions, Signs and Symptoms; Lymphatic Metastasis
• Other Study ID Numbers: SYSKY-2026-278-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: The individual participant data (IPD) will not be shared, due to the protection of patient privacy and confidentiality, as well as the restrictions of the hospital's data management policy. This is a single-center retrospective observational study, and the data involves sensitive clinical information of patients, which cannot be disclosed to external researchers without explicit ethical approval and patient consent.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No