---
title: "CT-guided intratumoral immunotherapy for advanced solid tumors: safety and systemic effects"
id: "frontiers-in-immunology-3-ct-guided-intratumoral-immunotherapy-for-advanced-solid-tumors-a-prospective"
canonical_url: "https://medichelpline.com/clinical-feed/frontiers-in-immunology-3-ct-guided-intratumoral-immunotherapy-for-advanced-solid-tumors-a-prospective"
content_type: "clinical_feed_article"
specialty: "Infectious Disease"
source_name: "Frontiers in Immunology"
source_url: "https://www.frontiersin.org/articles/10.3389/fimmu.2026.1869154"
published_at: "2026-07-24T00:00:00.000Z"
evidence_level: "Journal Feed"
license: "CC-BY-NC-4.0 / Informational Use"
---
# CT-guided intratumoral immunotherapy for advanced solid tumors: safety and systemic effects
## Provenance & Clinical Metadata
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- **Specialty:** [Infectious Disease](https://medichelpline.com/clinical-feed/infectious-disease.md)
- **Primary Source:** Frontiers in Immunology
- **Source URL:** [Original Journal Publication](https://www.frontiersin.org/articles/10.3389/fimmu.2026.1869154)
- **Published At:** 2026-07-24T00:00:00.000Z
- **Evidence Rating:** Journal Feed
## Executive GIST (TL;DR)
- This pooled prospective cohort combined several single-arm clinical trials to evaluate the safety and preliminary systemic efficacy of **CT-guided intratumoral** delivery of immunotherapeutic agents in patients with advanced, treatment-refractory solid tumors. - The cohort included 169 patients (median follow-up 8.4 months, range 1.0–38.0 months) who received CT-guided intratumoral injections of immune checkpoint inhibitors (PD-1, PD-L1, CTLA-4) or CAR-T cells. - Procedures: 878 CT-guided injection sessions were performed, targeting liver, abdominal cavity, lung, subcutaneous and other sites; most commonly used needles were 21G and 23G; drug leakage occurred in 12.07% of procedures and was usually limited and clinically insignificant. - Safety (primary endpoint): 15 patients (8.88%) experienced grade 3–4 adverse events (10 grade 3; 5 grade 4); no treatment-related deaths were reported. The most frequent any-grade AEs were fever (60.36%), local puncture-site pain (54.44%), chills (18.34%), and vomiting (14.79%). Most events were mild and transient. - Efficacy (descriptive): Best overall responses were 4 complete responses (2.37%), 15 partial responses (8.88%), 142 stable disease (84.02%), and 8 progressive disease (4.73%). The **objective response rate (ORR)** was 11.24% and the **disease control rate (DCR)** was 95.27%. Median **progression-free survival (PFS)** was 3.6 months (95% CI, 3.1–4.1) and median **overall survival (OS)** was 8.8 months (95% CI, 8.2–9.3). - Subgroup reporting: exploratory descriptive analyses were presented by tumor type (lung, liver, gastrointestinal, pancreatic) and by treatment regimen (PD-1/CTLA-4, PD-L1/CTLA-4, CAR-T), but no formal statistical comparisons were made owing to heterogeneity and single-arm design. - Procedural details: Intratumoral ICI doses were standardized at half the approved intravenous dose; CAR-T dose was 1 × 10^6 cells/kg intratumorally; contrast-dilution (iodine) was used to visualize intratumoral distribution during CT guidance. - Conclusion: The pooled data indicate that **CT-guided intratumoral injection** is feasible and has an acceptable safety profile with preliminary signals of systemic antitumor activity; authors note further research is needed to validate therapeutic efficacy and standardize procedures.
## Clinical Analysis & Structured Key Points
Frontiers | CT-guided intratumoral immunotherapy for advanced solid tumors: a prospective clinical study of safety and systemic antitumor effects CLINICAL TRIAL article Front. Immunol. , 24 July 2026 Sec. Cancer Immunity and Immunotherapy Volume 17 - 2026 | https://doi.org/10.3389/fimmu.2026.1869154 Published in Frontiers in Immunology Cancer Immunity and Immunotherapy 7 impact factor 11.3 citescore Editor & Reviewers Edited by S F Steven Fiering Reviewed by Y S Yangmeihui SONG H L Haonan Li Outline Figures and Tables Figure 1 View in article Figure 2 View in article Figure 3 View in article Table 1 Demographic and disease characteristics at baseline. View in article Table 2 Characteristics of intratumoral injection procedures. View in article Table 3 Treatment-related adverse events observed during follow-up. View in article CLINICAL TRIAL article Front. Immunol. , 24 July 2026 Sec. Cancer Immunity and Immunotherapy Volume 17 - 2026 | https://doi.org/10.3389/fimmu.2026.1869154 CT-guided intratumoral immunotherapy for advanced solid tumors: a prospective clinical study of safety and systemic antitumor effects Y O Yongqiong Ou 1 † J Z Jian Zhang 2 † H T Hongye Tan 1 † B H Binjia He 1 † T L Tianheng Li 1 † M L Manting Liu 1 C Z Cheng Zhi 3 J H Junhao Huang 1 M L Ming Li 1 S Z Shenghua Zuo 1 N U Noor Ul Huda Shah 1 Y C Yuning Chen 1 J H Junjian Huang 1 D C Dongni Chen 1 R Q Ruzhai Qin 4 X L Xufeng Li 1 H L Hui Lian 1 Q W Qingde Wu 5 * H Y Hainan Yang 1 * +11 more Z Z Zhenfeng Zhang 1 * 1. Department of Radiology; Translational Medicine Center; Guangzhou Key Laboratory for Research and Development of Nano-Biomedical Technology for Diagnosis and Therapy; Guangdong Provincial Education Department Key Laboratory of Nano-Immunoregulation Tumor Microenvironment; Central Laboratory, the Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China 2. Department of Radiology, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China 3. Department of Pathology, the Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China 4. Center for Clinical Trial, the Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China 5. Department of Radiology, Shunde Chinese Medicine Hospital, the Affiliated Hospital of Traditional Chinese Medicine University of Guangzhou, Foshan, China See more Article metrics View details https://clinicaltrials.gov https://clinicaltrials.gov , identifier NCT03198052, NCT03769129, NCT03755739, NCT03952065, and NCT05341492. Abstract Background: Systemic administration of immunotherapy via intravenous injection is frequently associated with off-target toxicity throughout the body. In contrast, intratumoral injection has emerged as a promising strategy to mitigate systemic adverse effects. However, data regarding the safety of CT-guided intratumoral immunotherapy remain limited. Methods: This pooled prospective cohort study included patients from several single-arm clinical trials. Eligible participants had histologically confirmed advanced solid tumors that were refractory or intolerant to standard therapies. Each participant had at least one measurable tumor lesion accessible for puncture under imaging guidance. All patients received CT-guided intratumoral injection of various ICIs (PD-1, PD-L1, and CTLA-4 inhibitors) either alone or in combination, or of CAR-T cells. The primary endpoint was safety of the treatment. Results: A total of 169 patients were included in the study cohort, with a median follow-up duration of 8.4 months (range, 1.0–38.0 months). Grade 3–4 adverse events occurred in 15 patients (8.88%), comprising 10 (5.92%) grade 3 and 5 (2.96%) grade 4 events; no treatment-related deaths were observed. Efficacy outcomes included 4 patients (2.37%) with complete response (CR), 15 (8.88%) with partial response (PR), 142 (84.02%) with stable disease (SD), and 8 (4.73%) with progressive disease (PD). The objective response rate (ORR) was 11.24%, and the disease control rate (DCR) was 95.27%. The median progression-free survival (PFS) was 3.6 months (95% CI, 3.1–4.1 months), and the median overall survival (OS) was 8.8 months (95% CI, 8.2–9.3 months). Conclusion: This study indicates the safety and preliminary therapeutic potential of intratumoral injection. Intratumoral injection may be a promising strategy for mitigating systemic toxicity; however, further research is necessary to validate its therapeutic efficacy. Clinical trial registration: https://clinicaltrials.gov , identifier NCT03198052, NCT03769129, NCT03755739, NCT03952065, and NCT05341492. Introduction Over the past decade, systemic immunotherapy has demonstrated significant clinical benefits as an adjuvant treatment for solid tumors ( 1 – 3 ). However, routine intravenous delivery may lead to systemic off-target toxicities affecting multiple organs, including pneumonitis, arthritis, and other immune-related adverse events ( 4 , 5 ). Consequently, increasing attention has been directed toward strategies that deliver immunoregulatory agents directly into tumor lesions using image-guided puncture techniques. Intratumoral immunotherapy enables a higher local concentration and improved bioavailability of immunotherapeutic agents within the tumor while minimizing systemic exposure and reducing the risk of treatment-related toxicity ( 6 , 7 ). Moreover, achieving a higher intratumoral drug concentration may reduce the total dose required to trigger effective immune activation, potentially lowering the treatment costs for patients with cancer ( 8 – 10 ). In addition, immunotherapeutic agents can modulate the immunosuppressive tumor microenvironment (TME), converting it into an immunostimulatory microenvironment that promotes tumor-specific immune responses and enhances tumor cell killing ( 11 – 13 ). Activated effector immune cells generated during this process may circulate through the bloodstream and exert antitumor activity at distant, uninjected tumor sites, a phenomenon known as the abscopal effect, or systemic effects following local therapy ( 14 – 16 ). In 2015, the U.S. Food and Drug Administration (FDA) approved talimogene laherparepvec (T-VEC), the first oncolytic virus-based immunotherapy, for the treatment of patients with unresectable metastatic melanoma ( 17 ). Since then, a variety of intratumoral immunotherapeutic agents have been investigated, including RNAs, cytokines, oncolytic viruses, bacteria, monoclonal antibodies, pattern recognition receptor agonists, and immune cells ( 18 – 23 ). Furthermore, early clinical studies of combination intratumoral immunotherapy strategies have demonstrated promising results, suggesting improved local and systemic antitumor efficacy ( 24 – 26 ). Collectively, these studies suggest that local delivery of immunotherapeutic agents into tumors may represent an effective strategy to overcome several limitations associated with systemic drug administration ( 27 – 29 ). Despite the growing interest in intratumoral immunotherapy, the safety, feasibility, and technical standardization of CT-guided intratumoral injection remain insufficiently studied, and there is currently no consensus regarding standardized procedural protocols. Therefore, in this study, we aimed to evaluate the safety and preliminary efficacy of CT-guided intratumoral delivery of immunotherapeutic agents in patients with advanced solid tumors and to provide clinical evidence that may help inform technical guidelines for intratumoral immunotherapy. Methods Ethics approval This study was designed as a pooled analysis of multiple prospective, single-arm, non-randomized, open-label clinical trials conducted at the Second Affiliated Hospital (Panyu Campus) of Guangzhou Medical University in Guangzhou, China. The Ethics Committee of the Second Affiliated Hospital of Guangzhou Medical University approved the study protocol. The clinical trials were registered with ClinicalTrials.gov, and the ClinicalTrials.gov identifiers (NCT number) are provided in Supplementary Table 1 . The pooled analysis encompasses data collected from March 1, 2018, to December 31, 2024. All participants in the constituent trials received comprehensive study information and provided written informed consent prior to enrollment. Study population Eligible participants were ≥18 years old and had histologically confirmed advanced solid tumors that were refractory to or intolerant of standard therapies. Each participant had at least one measurable tumor lesion that was accessible for puncture under imaging guidance. The estimated life expectancy was at least three months. The key exclusion criteria were severe organ failure, serious underlying diseases or critical medical conditions, prior treatment similar to the proposed intervention, inability to comply with treatment procedures or follow-up assessments, and a history of severe allergic reactions to any of the drugs used in this study. Endpoints The primary endpoint of this study was safety. Secondary endpoints were progression-free survival (PFS) and overall survival (OS). CT-guided intratumoral injection All procedures were performed by experienced interventional physicians. The puncture needle was selected based on the tumor size and the distance between the tumor center and the puncture entry site on the skin. Under CT guidance, the needle was inserted into the center of the lesion, and the immunotherapeutic agent was administered in accordance with the predetermined dose and injection volume. Successful intratumoral delivery was characterized by the administration of the planned total drug dose within the target tumor. For large lesions, multiple needles were employed to ensure adequate drug distribution. Decisions regarding treatment for each patient were determined by a multidisciplinary team utilizing pretreatment immunohistochemistry, genetic testing, and the patient’s previous use of immune agents as the basis for their evaluations. For example, patients who had previously received PD-1 antibodies with no clinical response may be treated with PD-L1 antibodies. All patients received CT-guided intratumoral injections of specific immunotherapeutic agents, which included PD-1 inhibitors (such as pembrolizumab, nivolumab, and sintilimab), PD-L1 inhibitors (such as atezolizumab and durvalumab), and CTLA-4 inhibitors (such as ipilimumab), either as monotherapy or in combination. The intratumoral dosage for each immune checkpoint inhibitor (ICI) was standardized to half of the approved intravenous dosage, as indicated in the drug label. For patients undergoing CAR-T cell therapy, a dose of 1 × 10 6 cells per kilogram was administered intratumorally. The injection volume was adjusted according to the size of the lesion. Treatments were scheduled every three weeks (Q3W) and continued until disease progression, the occurrence of unacceptable toxicity, or patient withdrawal. All procedures were performed under local anesthesia with 1% lidocaine to ensure appropriate analgesia. Patients’ vital signs were continuously monitored throughout the procedure. Preoperative planning, intraoperative needle placement, and postoperative evaluation of drug distribution were performed under CT guidance. To visualize intratumoral drug distribution, a 10-fold dilution of an iodine-containing contrast agent, such as ioversol or iodixanol, was combined with selected immunotherapy agents. Safety and clinical efficacy evaluation Safety evaluation involved monitoring adverse events (AEs) and grading them in accordance with the Common Terminology Criteria for Adverse Events (CTCAE), version 5.0. At each follow-up visit, all AEs were documented and assessed for their association with either the intratumoral injection procedure or the immunotherapeutic agent. The clinical data collected included physical examination findings, ECOG performance status, vital signs, and laboratory tests. Tumor evaluations were performed approximately every three weeks using the same imaging modality and measurement methods to ensure consistency. Treatment response was assessed according to the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Responses were classified as complete response (CR), partial response (PR), stable disease (SD), or progressive disease (PD). The objective response rate (ORR) was defined as the proportion of patients achieving CR or PR, while the disease control rate (DCR) was defined as the proportion achieving CR, PR, or SD as their best overall response. PFS was defined as the interval from the intratumoral injection to the first documented instance of radiographic disease progression or death from any cause, whichever occurred first. OS was defined as the time from intratumoral injection to death from any cause. Statistical analysis Statistical analyses and survival curves were generated using GraphPad Prism 10 (version 10.1.2). The median follow−up duration was estimated using the reverse Kaplan–Meier method. Continuous variables that did not follow a normal distribution were presented as medians (ranges) with 95% confidence intervals (CIs), whereas categorical variables were expressed as percentages. Given the single−arm, exploratory design and the heterogeneity of immunotherapeutic agents and tumor types across this pooled cohort, all analyses were descriptive, and no formal comparisons were made between trials or treatment subgroups. Results Participants and baseline characteristics A total of 202 patients were initially screened for eligibility. Of these, 33 patients underwent only puncture biopsy and were excluded from the final analysis. Ultimately, 169 patients were included in the pooled cohort. All data reported in this study were collected and analyzed prior to March 31, 2025. The demographic and baseline disease characteristics of the patients are summarized in Table 1 . At the data cutoff, 28 patients (16.6%) remained under active follow-up, whereas 141 patients (83.4%) had reached their endpoints. The median follow-up duration was 8.4 months, ranging from 1.0 to 38.0 months. Table 1 Characteristics Patients (N = 169) Age, years Mean 55 Range 20-87 Age category, n (%) <65 years 116 (68.64) ≥65 years 53 (31.36) Sex, n (%) Male 113 (66.86) Female 56 (33.14) ECOG performance status score, n (%) 0 68 (40.24) 1 51 (30.18) 2 34 (20.12) 3 16 (9.46) Cancer histological distribution, n (%) Lung cancer 45 (26.63) Liver cancer 41 (24.26) Gastrointestinal cancer 30 (17.75) Pancreatic cancer 16 (9.47) Urinary tract cancer 5 (2.96) Breast cancer 5 (2.96) Oral squamous cell cancer 4 (2.37) Ovarian cancer 4 (2.37) Malignant melanoma of the skin 3 (1.78) Vaginal cancer 2 (1.18) Others 14 (8.27) Metastasis, n (%) Yes 130 (76.92) No 39 (23.08) Number of intratumoral injections, n (%) 1 55 (32.54) 2 48 (28.40) 3 27 (15.98) 4 18 (10.65) ≥5 21 (12.43) Demographic and disease characteristics at baseline. ECOG, Eastern Cooperative Oncology Group. ECOG performance status scores range from 0 to 5, with 0 indicating no. symptoms and higher scores indicating increasing disability. The histological distribution of advanced solid tumors comprised 45 patients (26.63%) with lung cancer, 41 patients (24.26%) with liver cancer, and 30 patients (17.75%) with gastrointestinal cancer. Additionally, there were 16 patients (9.47%) with pancreatic cancer, 5 patients (2.96%) with urinary tract cancer, and 5 patients (2.96%) with breast cancer. Furthermore, 4 patients (2.37%) had oral squamous cell carcinoma, 4 patients (2.37%) had ovarian cancer, and 3 patients (1.78%) had cutaneous malignant melanoma. The cohort also included 2 patients (1.18%) with vaginal cancer and 14 patients (8.27%) with other types of tumors. To comprehensively evaluate the safety and efficacy of intratumoral injection therapy, exploratory subgroup analyses were stratified by tumor type and treatment regimen. A minimum reporting threshold of 10 cases per category was established for both stratification approaches. Four tumor-type subgroups met this threshold: lung cancer (n=45), liver cancer (n=41), gastrointestinal cancer (n=30), and pancreatic cancer (n=16). Similarly, three treatment regimens met this threshold: PD-1/CTLA-4 inhibitors (n=75), PD-L1/CTLA-4 inhibitors (n=53), and CAR-T cells (n=21). The remaining tumor types and treatment groups were excluded because of insufficient sample sizes. No formal statistical comparisons were conducted between the groups in either analysis, given the descriptive nature of these exploratory analyses and the disparity in sample sizes. Intratumoral injection procedures During the study period, 169 patients underwent 878 CT-guided intratumoral injection procedures. The key characteristics of these procedures are summarized in Table 2 . Some patients received multiple injections, and in certain treatment sessions, up to five different tumor sites were punctured within a single procedure. The most frequently used needle gauges were 21G and 23G. Table 2 Characteristics Procedures (N = 878) Target lesion length (cm) Mean 3.7 Range 1.0-31.5 Needle size, n (%) 17G, 18G, 19G and 20G 78 (8.88) 21G 359 (40.89) 22G 38 (4.33) 23G 403 (45.90) Sites of injection, n (%) Liver 264 (30.07) Abdominal cavity 115 (13.10) Lung 112 (12.76) Subcutaneous 86 (9.80) Retroperitoneal 84 (9.57) Osteoarticular and vertebral 68 (7.74) Head and neck 54 (6.15) Pelvic cavity 42 (4.78) Mediastinum and pleura 35 (3.99) Pancreas 18 (2.04) Lesion type, n (%) Metastatic 615 (70.05) Primary 263 (29.95) Drug leakage, n (%) Yes 106 (12.07) No 772 (87.93) Characteristics of intratumoral injection procedures. Among the 878 intratumoral injection procedures, the distribution of target lesions was as follows: liver lesions (264, 30.07%), abdominal cavity lesions (115, 13.10%), lung lesions (112, 12.76%), subcutaneous lesions (86, 9.80%), retroperitoneal lesions (84, 9.57%), osteoarticular and vertebral lesions (68, 7.74%), head and neck lesions (54, 6.15%), pelvic cavity lesions (42, 4.78%), mediastinal and pleural lesions (35, 3.99%), and pancreatic lesions (18, 2.04%). Drug leakage into the surrounding interstitial tissue was observed in 106 of the 878 intratumoral injection procedures (12.07%). In the majority of these cases, leakage was confined to the peritumoral area and did not necessitate any additional intervention. Furthermore, no severe complications, such as organ infarction or major bleeding, were directly attributed to the leakage. Safety Adverse events (AEs) were systematically monitored and documented throughout the follow-up period following each intratumoral injection, as detailed in Table 3 . Among the 169 patients, the most frequently reported events were fever (102, 60.36%), local pain at the puncture site (92, 54.44%), chills (31, 18.34%), and vomiting (25, 14.79%). The majority of these adverse events were mild and resolved spontaneously within 24 hours, without necessitating specific medical intervention. For patients who experienced intolerable symptoms, symptomatic treatment was sufficient to relieve the adverse effects. Table 3 Adverse events Patients (N = 169) Any grade, n (%) Grade 3–4, n (%) Fever 102 (60.36) 13 (7.69) Local pain at the puncture site 92 (54.44) 7 (4.14) Chills 31 (18.34) 4 (2.37) Vomiting 25 (14.79) 3 (1.78) Leukocytopenia 16 (9.47) 1 (0.59) Fatigue 13 (7.69) 2 (1.18) Nausea 13 (7.69) 2 (1.18) Alanine aminotransferase increased 13 (7.69) 0 Cough 8 (4.73) 1 (0.59) Dyspnea 7 (4.14) 2 (1.18) Hypotension 5 (2.96) 5 (2.96) Pruritus 4 (2.37) 0 Immune-related pneumonitis 4 (2.37) 4 (2.37) Dizziness 3 (1.78) 0 Immune-related rash 3 (1.78) 3 (1.78) Respiratory failure 3 (1.78) 3 (1.78) Diarrhea 2 (1.18) 0 Treatment-related adverse events observed during follow-up. All participants who received at least one trial treatment were included in the analyses. Adverse events attributed to the treatment were documented by the investigators on the case report form. According
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