Grid Radiation Therapy Based on Multileaf Collimator for Neoadjuvant Treatment of Large-Volume Intrahepatic Cholangiocarcinoma: A Case Report

Introduction

Intrahepatic cholangiocarcinoma (ICC) incidence has risen globally in recent years. It has a high mortality rate and poor prognosis due to its insidious onset. Surgical resection remains the cornerstone for long-term survival. However, some patients initially diagnosed with large-volume tumors often fail to meet the criteria for resection due to tumor size and major vessel invasion. Therefore, it is imperative to move beyond traditional single-modality treatments and develop effective therapies through multidisciplinary collaboration.

Spatially fractionated radiation therapy (SFRT) involves an uneven dose distribution within the tumor, with alternating dose peaks and valleys.¹ High-dose regions are distributed across different parts of the tumor, while surrounding normal tissues receive a lower dose. Its core mechanism lies in achieving therapeutic gain through spatial rather than temporal fractionation, as in traditional radiation therapy. The prescription for SFRT requires additional parameters, including peak dose, valley dose, beam size (or vertex size), beam spacing (ie, the distance between vertices), and peak-to-valley dose ratio.² Grid radiation therapy is a specific implementation of SFRT. It delivers a relatively high yet heterogeneous radiation dose to the tumor via a grid structure. Lattice radiation therapy is another type of SFRT, derived from Grid radiation therapy. It aims to construct 3-dimensional high-dose vertices within the tumor target area, forming an alternating “peak-valley” dose distribution relative to the surrounding low-dose areas. The typical dosimetric parameters for Grid radiation therapy are as follows: peak dose of 15 to 20 Gy, beam size of 1 to 2 cm, beam interval of 1 to 4 cm, and peak-to-valley dose ratio of 3 to 7.² For most tissue types, conventional radiation therapy administered after a single SFRT session is typically prescribed at 20 Gy in 5 fractions. For radioresistant tumors, the dose is usually increased to 30 to 50 Gy in 10 fractions.³ Based on current evidence, it is recommended that conventional fractionated external beam radiation therapy commence within 72 hours of SFRT.⁴

This case presents a patient diagnosed with stage IIIB ICC who met the criteria for surgical resection after receiving translational therapy, with significant tumor control postoperatively. The results indicate that Grid radiation therapy is a beneficial adjuvant in the management of unresectable ICC.

Case Presentation

The patient is a 60-year-old man. In September 2024, he presented to the Department of Hepatobiliary and Pancreatic Medicine at our hospital with a 1-year history of reduced appetite. Magnetic resonance imaging (MRI) revealed a 10.3 cm × 6.5 cm mass in the left and right anterior lobes of the liver. In October 2024, a percutaneous needle biopsy of the lesion was performed, and pathologic examination confirmed the presence of adenocarcinoma infiltration (Fig. 1). Based on the findings, the clinical diagnosis was cT1bN1M0 with multiple peritoneal lymph node metastases (in the hepatic hilum and paraortic region), corresponding to stage IIIB ICC.

Figure 1.

Pathological results of preoperative puncture tissue biopsy at (A) ×40 magnification and (B) ×100 magnification.

Due to the large tumor volume and vascular invasion, we administered translational therapy consisting of chemoimmunotherapy combined with concurrent local radiation therapy. On October 12, 2024, the patient commenced chemoimmunotherapy, consisting of capecitabine plus tislelizumab, supplemented by local radiation therapy targeting the tumor. First, the patient’s position was fixed using a body immobilization technique with a thermoplastic film that conformed to the patient’s body shape. The patient was instructed to breathe freely during the simulation and treatment. A small abdominal pressure bag was fixed and connected within the thermoplastic film and pressurized to 15 to 20 kPa to reduce liver motion. The Varian Eclipse version 15.6 treatment planning system was used. According to clinical guidelines and experience, the radiation therapy plan was divided into 2 courses: plan 1 (P1) and plan 2 (P2), both with the same target volume. The patient received 15 Gy in 1 fraction on the first day, followed by P2 (4 Gy × 5 fractions) 1 day later. Due to the high prescribed dose, the patient underwent cone beam computed tomography before each treatment to correct setup errors and ensure accurate delivery. P1 was delivered using Grid radiation therapy via a multileaf collimator (MLC). The MLC was configured with 1-cm apertures and a center-to-center spacing of 2 cm, resulting in a rod-like high-dose distribution within the tumor, with the maximum dose at 110.6% of the prescribed dose. The x-ray energy was 10 MV in flattening-filter mode, with a treatment dose rate of 600 MU/min and a delivery time of 252 seconds. P2 was delivered via volumetric modulated arc therapy using 6 MV flattening-filter-free x-rays at 600 MU/min and 3 arcs. The average delivery time for each fraction was 206 seconds. Treatment was delivered using a VitalBeam clinical linear accelerator (Varian). Target volume parameters were as follows: gross tumor volume = 334.47 cm³; planning tumor volume = 528.39 cm³. The peak-to-valley dose ratio was 4.883. For P2, the heterogeneity index was 0.0498, the conformity index was 0.97, and the gradient index was 3.149. The cumulative organ-at-risk doses of P1 and P2 were converted to equivalent dose in 2 Gy fractions (EQD2). The combined EQD2 doses were as follows: spinal cord Dmax = 26.29 Gy, stomach D0.5 cm³ = 40.29 Gy, small bowel D0.5 cm³ = 22.35 Gy, and liver Dmean = 8.07 Gy. These doses met the EQD2-based organ-at-risk constraints of spinal cord Dmax <57 Gy,⁵ stomach D0.5 cm³ <98 Gy,⁶ small bowel D0.5 cm³ <70 Gy,⁷ and liver Dmean <30 Gy.⁸ The target area design and dose-volume histogram for the 2-phase plan are shown in Fig. 2.

Figure 2.

Grid radiation therapy for large-volume intrahepatic cholangiocarcinoma based on a multileaf collimator. (A and D) Axial views of plan 1 (P1) and plan 2 (P2); (B and E) coronal views of P1 and P2; (C and F) BEV (Beam's Eye View) of P1 and P2; (G) dose-volume histogram of P1 and P2.

During the treatment interval, the patient developed pruritic, erythematous maculopapules that covered about 30% of the body surface area and impaired the patient’s ability to perform daily activities. This was classified as a grade 3 tislelizumab-induced skin reaction, leading to the discontinuation of tislelizumab. From December 10, 2024, to March 24, 2025, the treatment regimen was adjusted to chemotherapy plus targeted therapy consisting of gemcitabine, cisplatin, and lenvatinib, with a total of 4 cycles. On January 9, 2025, an interim abdominal MRI revealed further tumor shrinkage, with the mass measuring 8.3 cm × 5.5 cm. After completing all 4 cycles, a follow-up abdominal MRI showed that the primary tumor had decreased to 7.1 cm × 4.5 cm, representing a 52.3% volume reduction compared with the baseline measurement at diagnosis (Fig. 3). On May 13, 2025, an abdominal computed tomography scan showed that the maximum cross-section of the lesion was 6.4 cm × 3.9 cm. Slightly enlarged lymph nodes were noted in the hepatic hilum and periaortic regions, with short-axis diameters of 0.4 to 1.1 cm. Vascular assessment revealed no arterial anomalies, a patent portal vein without thrombus, unobstructed hepatic veins and inferior vena cava, and a large accessory hepatic vein in the right hepatic lobe. Surgical evaluation confirmed that the patient was eligible for curative resection.

Figure 3.

Changes in tumor volume before and after Grid radiation therapy combined with conventional radiation therapy and systemic treatment. (A, B, and C) Magnetic resonance images of the tumor at the time of diagnosis. (D, E, and F) Magnetic resonance images of the tumor after Grid radiation therapy combined with conventional radiation therapy and systemic treatment.

On May 23, 2025, postoperative pathological examination confirmed moderately to poorly differentiated ICC, with extensive tumor infarction and hyaline degeneration (affecting approximately 70% of the tumor). Peripheral tissue morphology corresponded to G1S1 to 2. The interstitial spaces of the gallbladder tissue showed abundant infiltration by lymphocytes and plasma cells. Negative surgical margins were achieved, indicating a complete (R0) resection (Fig. 4). On June 26, 2025, follow-up abdominal MRI, along with liver function tests and (Carbohydrate Antigen 19-9) levels, confirmed a significant therapeutic response. The patient’s diagnosis and treatment process are summarized in Fig. 5. The patient is currently recovering well and remains under close surveillance.

Figure 4.

(A) The surgically resected liver tumor. Pathological results of the postoperative resection margin at (B) ×40 magnification and (C) ×100 magnification.

Figure 5.

Changes in CA19-9 (Carbohydrate Antigen 19-9) levels and in aspartate aminotransferase (AST; blue), alanine aminotransferase (ALT; orange), gamma-glutamyl transpeptidase (GGT; gray), and albumin (ALB; yellow) during the entire diagnosis and treatment process. The image at the bottom shows the patient’s diagnosis and treatment processes.

Abbreviations: GRID = Grid radiation therapy; ICC = intrahepatic cholangiocarcinoma.

Discussion

To date, no published literature has reported the use of SFRT as a neoadjuvant treatment for large-volume ICC. The favorable prognosis in this case demonstrates efficacy and safety, providing a valuable reference for clinical treatment.

Accumulating clinical evidence supports Grid radiation therapy for large-volume tumors. One study demonstrated that it safely enables dose escalation when combined with conventional full-dose radiation therapy, thereby improving local control.⁹ Importantly, this approach, which combines SFRT with conventional irradiation, remains compatible with subsequent surgical procedures and postoperative healing.

Currently, Grid radiation therapy for large-volume ICC faces several clinical limitations. First, there are no standardized protocols or target dose-volume criteria. While relevant clinical cases serve as references, more standardized dose specifications are needed in practice to ensure the safety and efficacy of radiation therapy. Second, the alternating high-dose and low-dose distribution of Grid radiation therapy—delivering high doses to specific regions of the primary tumor—inevitably damages normal liver tissue in the radiation path. In our patient, a 5-month posttreatment liver MRI showed transient injury to normal hepatic tissue traversed by the radiation beam. The advantage of lattice radiation therapy is that it can adjust the lattice density according to the 3-dimensional morphology of the target volume, adapt to the irregular boundaries of the target area, and minimize damage to surrounding normal tissues.

Conclusions

This case report demonstrates that MLC-based Grid radiation therapy is a reliable alternative approach for large-volume ICC. Up to now, the patient remains in good condition at follow-up, with no radiation therapy-related adverse events observed. As a neoadjuvant strategy, SFRT can offer clinical benefits to patients with large-volume ICC.