Endoscopic ultrasound-guided tissue acquisition for focal liver lesions in patients with a history of multiple primary malignant neoplasms.

Objective: This study aimed to investigate the usefulness of endoscopic ultrasound-guided tissue acquisition (EUS-TA) for diagnosing focal liver lesions in patients with a history of multiple primary malignant neoplasms. Methods: Among patients who underwent EUS-TA for focal liver lesions between 2016 and 2022, those with a history of multiple malignant neoplasms were included. A histologically confirmed malignant tumor within the past 5 years before EUS-TA was defined as a history of malignant neoplasm. The primary outcomes were diagnostic ability and adverse events of EUS-TA. Results: This study included 16 patients (median age, 73 [33-90] years), the median tumor size was 32 (6-51) mm, 14 had a history of double malignant neoplasms, whereas two had triple malignant neoplasms. Malignant neoplasms were detected histologically or cytologically in all cases. Immunohistochemistry was performed in 75% (12/16), and the final diagnosis of EUS-TA was metastatic liver tumor in 12 patients, and primary malignant liver tumor in four patients. The primary site could be identified in 11 of 12 metastatic tumor cases. The diagnostic yield of EUS-TA was 100% (16/16) for differentiating benign and malignant tumors and 94% (15/16) for confirming the histological type including the primary site of metastatic lesions. No adverse events were associated with the procedure. Conclusion: EUS-TA is a useful diagnostic modality for focal liver lesions in patients with a history of multiple malignant neoplasms, allowing for the differential diagnosis of primary and metastatic tumors and identification of the primary site of metastatic lesions.

A flexible deep learning framework for liver tumor diagnosis using variable multi-phase contrast-enhanced CT scans.

BACKGROUND: Liver cancer is a significant cause of cancer-related mortality worldwide and requires tailored treatment strategies for different types. However, preoperative accurate diagnosis of the type presents a challenge. This study aims to develop an automatic diagnostic model based on multi-phase contrast-enhanced CT (CECT) images to distinguish between hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (ICC), and normal individuals. METHODS: We designed a Hierarchical Long Short-Term Memory (H-LSTM) model, whose core components consist of a shared image feature extractor across phases, an internal LSTM for each phase, and an external LSTM across phases. The internal LSTM aggregates features from different layers of 2D CECT images, while the external LSTM aggregates features across different phases. H-LSTM can handle incomplete phases and varying numbers of CECT image layers, making it suitable for real-world decision support scenarios. Additionally, we applied phase augmentation techniques to process multi-phase CECT images, improving the model's robustness. RESULTS: The H-LSTM model achieved an overall average AUROC of 0.93 (0.90, 1.00) on the test dataset, with AUROC for HCC classification reaching 0.97 (0.93, 1.00) and for ICC classification reaching 0.90 (0.78, 1.00). Comprehensive validation in scenarios with incomplete phases was performed, with the H-LSTM model consistently achieving AUROC values over 0.9. CONCLUSION: The proposed H-LSTM model can be employed for classification tasks involving incomplete phases of CECT images in real-world scenarios, demonstrating high performance. This highlights the potential of AI-assisted systems in achieving accurate diagnosis and treatment of liver cancer. H-LSTM offers an effective solution for processing multi-phase data and provides practical value for clinical diagnostics.

Glut-1-Negative Choroidal Malignant Melanoma with Liver Metastasis Recurrence 12 Years after Surgery without FDG Accumulation in a Recurrent Lesion on FDG-PET/CT: a Case Report.

Choroidal malignant melanoma is a rare malignant tumor that develops in adult eyeballs. It causes early lymph node and distant metastasis. Fluorodeoxyglucose (FDG)-positron emission tomography/computed tomography (CT) is widely used for screening malignant melanoma metastases. We encountered a 58-year-old man with choroidal malignant melanoma in whom liver metastasis recurred 12 years after surgery, without any observable FDG accumulation. Immunostaining revealed the absence of glucose transporter type 1 (GLUT-1) expression, crucial for intracellular FDG uptake. The lack of FDG accumulation in the lesion could be attributed to the diminished cellular FDG uptake due to the absence of GLUT-1 expression.

The Paradox of Modern Technology in Standardizing Thermal Liver Ablation: Fostering Uniformity or Diversity?

PURPOSE: Currently, significant medical practice variation exists in thermal ablation (TA) of malignant liver tumors with associated differences in outcomes. The IMaging and Advanced Guidance for workflow optimization in Interventional Oncology (IMAGIO) consortium aims to integrate interventional oncology into the standard clinical pathway for cancer treatment in Europe by 2030, by development of a standardized low-complex-high-precision workflow for TA of malignant liver tumors. This study was conducted at the start of the IMAGIO project with the aim to explore the current state and future role of modern technology in TA of malignant liver tumors. MATERIALS AND METHODS: A cross-sectional questionnaire was conducted followed by an expert focus group discussion with core members and collaborating partners of the consortium. RESULTS: Of the 13 participants, 10 respondents filled in the questionnaire. During the focus group discussion, there was consensus on the need for international standardization in TA and several aspects of the procedure, such as planning based on cross-sectional images, the adoption of different techniques for needle placement and the importance of needle position- and post-ablative margin confirmation scans. Yet, also considerable heterogeneity was reported in the adoption of modern technology, particularly in navigational systems and computer-assisted margin assessment. CONCLUSION: This study mirrored the current diversity in workflow of thermal liver ablation. To obtain comparable outcomes worldwide, standardization is needed. While advancements in tools and software hold the potential to homogenize outcome measurement and minimize operator-dependent variability, the rapid increase in availability also contributes to enhanced workflow variation.

A Case of Spontaneous Regression of Adult Multi-system Langerhans Cell Histiocytosis Presenting as Liver Tumor Rupture.

Adult multisystem Langerhans cell histiocytosis (MS-LCH) is rare and has a poor prognosis. A 67-year-old man with MS-LCH presented with a hepatic tumor rupture and multiple masses in the lungs, liver, and pancreas. Despite the initial aggressive disease course and involvement of organs at risk, the patient experienced spontaneous regression and lesion disappearance following smoking cessation without chemotherapy. A literature review revealed a distinct subset of MS-LCH that can be managed by smoking cessation and careful observation through follow-up imaging. This suggests that careful observation through follow-up imaging may be a reasonable alternative to chemotherapy in select adult cases of MS-LCH.

Magnetic resonance imaging and clinicopathological findings of primary hepatic angiosarcoma.

PURPOSE: To investigate the magnetic resonance imaging (MRI) and clinicopathological features of primary hepatic angiosarcoma (PHA) and enhance preoperative diagnosis. METHODS: MRI and clinicopathological information of 12 cases proved PHA were reviewed. Summarize the MRI characteristics of PHA combined with literature reviews. RESULTS: Among 12 cases (6 males and 6 females; age range, 23-70 years; mean, 53.3 years), one presented as a large mass, two as a diffuse infiltrating tumor, and nine as a mixed pattern of large masses with multiple nodules, all involving both lobes of the liver and ranging from 0.1 cm to 11 cm in diameter. A total of 63 lesions were analyzed, including 21 masses and 42 nodules. 13 masses (61.9%) demonstrated intratumoral hemorrhage. 18 masses (85.7%) demonstrated heterogeneous patchy, ring-shaped, septate, or irregular shaped enhancing foci on late arterial phase (LAP). On dynamic contrast-enhanced MRI (DCE-MRI), 14 masses (66.7%) showed a centripetal or centrifugal pattern of incomplete progressive enhancement. 6 nodules (14.3%) appeared intratumoral hemorrhage. 31 nodules (73.8%) showed no enhancing foci on LAP images and 27 nodules (64.3%) showed enhancement pattern of complete filling, either centripetal or centrifugal pattern. Moreover, 12 cases (100%) exhibited prominent vessels within or adjacent to at least one lesion. CONCLUSION: PHA exhibits diverse appearances on MRI. Typical MRI signs include multifoci with intratumoral hemorrhage, prominent vessels within or adjacent to the foci, as well as varied degrees of progressive enhancement with incomplete filling in dominant masses of PHA.

Mcl-1 expression is a predictive marker of response to gemcitabine plus nab-paclitaxel for metastatic pancreatic cancer.

Antiapoptotic protein, including Mcl-1, expression is frequently observed in pancreatic cancer. Gemcitabine plus nabpaclitaxel (GnP) is the standard chemotherapy for metastatic pancreatic cancer (MPC); however, predictive markers for its efficacy remain unestablished. This study evaluated the association between GnP's therapeutic effects and Mcl-1 expression in tissue samples obtained using endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) for pancreatic tumor or percutaneous ultrasound-guided biopsy for metastatic liver tumor. We retrospectively reviewed 38 patients with histologically diagnosed MPC who received GnP as the first-line chemotherapy at our institute between December 2014 and July 2018. Post-immunohistochemistry analysis for Mcl-1 expression detection, patients were divided to into two groups based on the cell proportion showing Mcl-1 immunoreactivity: positive (> 20%; 23 [60.5%] patients) and negative (≤ 20%; 15 [39.5%] patients) groups. Clinical characteristics did not differ between the two groups. The Mcl-1 positive group showed a significantly higher disease control rate (95.7% vs. 73.3%; P = 0.046), longer progressionfree survival (PFS) (7.2 months vs. 4.9 months; P = 0.018) and longer overall survival (OS) (14.9 months vs. 9.2 months; P = 0.008) than the Mcl-1 negative group. Multivariate analysis showed that Mcl-1 expression was an independent predictive marker for PFS and OS. Mcl-1 expression could be a predictive marker for favorable response to GnP.

Imaging features of hepatic angiosarcoma: retrospective analysis of two centers.

PURPOSE: Identifying primary hepatic angiosarcoma (PHA) preoperatively is challenging, often relying on postoperative pathology. Invasive biopsy increases bleeding risk, emphasizing the importance of early PHA diagnosis through imaging. However, comprehensive summaries of ultrasound, abdominal computed tomography (CT), magnetic resonance imaging (MRI), and whole- body positron emission tomography-CT (PET-CT) in this context are lacking. This study aimed to investigate the comprehensive imaging characteristics of PHA. PATIENTS AND METHODS: Imaging data were collected from 7 patients diagnosed with PHA via pathology between January 2000 and December 2019 in two provincial grade III hospitals. All patients underwent routine color ultrasound examinations before surgery, with 3 patients receiving contrast-enhanced ultrasound (CEUS).CT scans, both plain and enhanced, were performed on 5 patients, and whole-body PET-CT examinations were conducted on 2 patients. RESULTS: Among the 7 patients with PHA, 4 presented with a single solid intrahepatic mass (2 of which were large), 1 with a single exophytic macroblock type, 1 with a mixed type featuring multiple masses and nodules, and 1 with a multiple nodule type. Conventional ultrasound of PHA showed uneven echoes within the tumor, potentially accompanied by septal zone echoes, and a blood flow grade of 0-I. CEUS displayed early-stage circular high enhancement, a central non-enhancement area, and a "vascular sign" around the tumor. CT scans revealed low-density shadows in the plain scan stage, high peripheral ring enhancement, and punctate nodular enhancement in the arterial phase, with varying intensities and the presence of a "vascular sign." During the portal vein stage, the interior of the tumor was consistently unfilled and exhibited structural disorder. PET-CT showed low-density lesions in the liver and low fluorodeoxyglucose metabolism. CONCLUSIONS: Imaging diagnosis plays a crucial role in PHA diagnosis. When liver tumor imaging matches the above characteristics, consider PHA.

Angiographic Aspects of Transarterial Radioembolization: A Comparison of Technical Options to Avoid Extrahepatic Microsphere Depositions.

The influence of the interventional treatment approach for transarterial radioembolization (TARE) on the incidence of extrahepatic microsphere depositions and to angiographic complications was evaluated. In total, 398 TARE cycles were analyzed. Interventional treatment approaches were classified as single treatment position (TP) with interventional occlusion (IO), multiple TPs without IO, and multiple TPs with IO. Correlations with extrahepatic microsphere depositions, angiographic complications, and periprocedural clinical events were performed. Alternative treatment strategies were evaluated. Applications from multiple TPs could have ensured the safe application of microspheres in 48.2% of cases that were originally performed from a single TP after IO. Extrahepatic microsphere accumulations were detected after 5.2%, 5.3%, and 1.5% of TARE procedures from a single TP without IO, a single TP with IO, and multiple TPs without IO, respectively. Applications from multiple TPs did not increase angiographic complications. During the 30-day follow-up, nausea/vomiting and upper abdominal discomfort were observed more frequently in the group with IO than in the group without IO (7.9%/4.6% and 9.2%/5.9%, respectively). In many TARE procedures, the same target liver can be treated from multiple TPs instead of a single TP, reducing the need for the interventional occlusion of aberrant arteries and potential extrahepatic microsphere depositions.

Simultaneously Detected Liver and Lung Metastases from Colorectal Carcinoma: A Potential Treatment Strategy.

BACKGROUND/AIM: No clear treatment strategy for simultaneously detected liver and lung metastases (SLLM) of colorectal carcinoma has been established, to date. We aimed to identify the prognostic factors for SLLM and propose an appropriate treatment option. PATIENTS AND METHODS: This retrospective study included 64 patients with SLLM: 32 underwent pulmonary resection after hepatectomy in 32, while the other 32 underwent hepatectomy alone in 32. Poor prognostic factors and a suitable strategy for SLLM were assessed. RESULTS: Multivariate analysis showed that preoperative carcinoembryonic antigen (CEA) level ≥20 ng/ml (p=0.001) and unresected lung metastases (p=0.001) were independent prognostic factors for poor overall survival. Compared with the non-pulmonary resection group, the rate of R1 resection of liver tumors (46.8% vs. 15.6%; p=0.007), incidence of complications after hepatectomy (Clavien-Dindo grade ≥III: 21.8% vs. 0%; p=0.005) and having four or more metastatic lung nodules (40.6% vs. 3.2%; p=0.001) were significantly higher in the group that underwent hepatectomy only. CONCLUSION: Preoperative CEA ≥20 ng/ml and unresectable pulmonary nodules were prognostic factors for poor survival of patients with SLLM. Furthermore, the presence of more than four pulmonary nodules was a preoperative predictive factor for unresectable pulmonary nodules. R1 resection and the occurrence of complications after hepatectomy should be avoided; a smooth transition from hepatectomy to pulmonary resection is important.

Ultrasomics in liver cancer: Developing a radiomics model for differentiating intrahepatic cholangiocarcinoma from hepatocellular carcinoma using contrast-enhanced ultrasound.

BACKGROUND: Hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) represent the predominant histological types of primary liver cancer, comprising over 99% of cases. Given their differing biological behaviors, prognoses, and treatment strategies, accurately differentiating between HCC and ICC is crucial for effective clinical management. Radiomics, an emerging image processing technology, can automatically extract various quantitative image features that may elude the human eye. Reports on the application of ultrasound (US)-based radiomics methods in distinguishing HCC from ICC are limited. AIM: To develop and validate an ultrasomics model to accurately differentiate between HCC and ICC. METHODS: In our retrospective study, we included a total of 280 patients who were diagnosed with ICC (n = 140) and HCC (n = 140) between 1999 and 2019. These patients were divided into training (n = 224) and testing (n = 56) groups for analysis. US images and relevant clinical characteristics were collected. We utilized the XGBoost method to extract and select radiomics features and further employed a random forest algorithm to establish ultrasomics models. We compared the diagnostic performances of these ultrasomics models with that of radiologists. RESULTS: Four distinct ultrasomics models were constructed, with the number of selected features varying between models: 13 features for the US model; 15 for the contrast-enhanced ultrasound (CEUS) model; 13 for the combined US + CEUS model; and 21 for the US + CEUS + clinical data model. The US + CEUS + clinical data model yielded the highest area under the receiver operating characteristic curve (AUC) among all models, achieving an AUC of 0.973 in the validation cohort and 0.971 in the test cohort. This performance exceeded even the most experienced radiologist (AUC = 0.964). The AUC for the US + CEUS model (training cohort AUC = 0.964, test cohort AUC = 0.955) was significantly higher than that of the US model alone (training cohort AUC = 0.822, test cohort AUC = 0.816). This finding underscored the significant benefit of incorporating CEUS information in accurately distinguishing ICC from HCC. CONCLUSION: We developed a radiomics diagnostic model based on CEUS images capable of quickly distinguishing HCC from ICC, which outperformed experienced radiologists.

Pay attention to the application of indocyanine green fluorescence imaging technology in laparoscopic liver cancer resection.

Traditional laparoscopic liver cancer resection faces challenges, such as difficulties in tumor localization and accurate marking of liver segments, as well as the inability to provide real-time intraoperative navigation. This approach falls short of meeting the demands for precise and anatomical liver resection. The introduction of fluorescence imaging technology, particularly indocyanine green, has demonstrated significant advantages in visualizing bile ducts, tumor localization, segment staining, microscopic lesion display, margin examination, and lymph node visualization. This technology addresses the inherent limitations of traditional laparoscopy, which lacks direct tactile feedback, and is increasingly becoming the standard in laparoscopic procedures. Guided by fluorescence imaging technology, laparoscopic liver cancer resection is poised to become the predominant technique for liver tumor removal, enhancing the accuracy, safety and efficiency of the procedure.

Comparison of laparoscopic liver resection for the ventral versus the dorsal areas of segment 8.

PURPOSE: The technical difficulties of laparoscopic liver resection (LLR) are greatly associated with the location of liver tumors. Since segment 8 (S8) contains a wide area, the difficulty of LLR for S8 tumors may vary depending on the location within the segment, such as the ventral (S8v) and dorsal (S8d) area, but the difference is unclear. METHODS: We retrospectively investigated 30 patients who underwent primary laparoscopic partial liver resection for liver tumors in S8 at Kobe University Hospital between January 2018 and June 2023. RESULTS: Thirteen and 17 patients underwent LLR for S8v and S8d, respectively. The operation time was significantly longer (S8v 203[135-259] vs. S8d 261[186-415] min, P = 0.002) and the amount of blood loss was significantly higher (10[10-150] vs. 10[10-200] mL, P = 0.034) in the S8d group than in the S8v group. No significant differences were observed in postoperative complications or postoperative length of hospital stay. Additionally, intraoperative findings revealed that the rate at which the case performed partial liver mobilization in the S8d group was higher (2[15.4%] vs. 8[47.1%], P = 0.060) and the median parenchymal transection time of the S8d group was longer (102[27-148] vs. 129[37-175] min, P = 0.097) than those in the S8v group, but there were no significant differences. CONCLUSION: The safety of LLR for the S8d was comparable to that of LLR for S8v, although LLR for S8d resulted in longer operative time and more blood loss. THE TRIAL REGISTRATION NUMBER: B230165 (approved at December 26, 2023).

Clinical Characteristics and Outcomes of Neonatal Hepatoblastoma: A Single Center Study.

OBJECTIVE: Hepatoblastoma (HB) diagnosed within one month following birth qualifies for a diagnosis of neonatal HB, whose prognosis is reportedly controversial, and its treatment is challenging. This study discussed the diagnosis, treatment, and outcomes of neonatal HB at a single center so as to enhance its overall management in the future. METHODS: The clinical information of babies diagnosed with neonatal HB at our center from August 2009 to September 2023 were retrospectively analyzed for demographics, clinical features, therapy, and outcomes. The outcomes were estimated by the Kaplan-Meier analysis method. RESULTS: The study comprised 79 patients aged less than one year old, among which 14 had neonatal HB whereas 65 were non-neonatal HB patients. No differences were found between groups regarding gender, birth weight, delivery details, parental age, clinical signs, or treatment strategies. Neonatal HB patients were more likely to have PRETEXT I-II, smaller tumor size, congenital diseases, and lower risk tumor grade (p < 0.05). Additionally, the AFP levels of all neonatal HB patients were greater than 10,000 ng/ml (p = 0.009) and they had higher levels of ferritin (p = 0.003) and hemoglobin (p = 0.021), but lower levels of serum total proteins (p = 0.001). The three-year survival rate (100% vs 90.8%) and three-year event-free survival rate (100% vs 86.2%) in the neonatal HB group were higher than the non-neonatal HB group. CONCLUSION: Neonatal HB patients have unique clinical features and can achieve an excellent prognosis following combined treatment with surgery and chemotherapy. Tumor resection, when carefully performed, was safe even in babies younger than one months old. Further and long-term studies are needed from a larger neonatal HB population. LEVEL OF EVIDENCE: Level III.

Laparoscopic right upper transversal hepatectomy: Strategies for right hepatic vein resection and reconstruction.

OBJECTIVE: The right upper transversal hepatectomy (RUTH) is considered a complex technique of parenchymal-sparing hepatectomies. The intraoperative management of the right hepatic vein (RHV) is still controversial because it may cause obstruction of outflow in the remnant hepatic segment. The aim of this study is to present our experience of laparoscopic RUTH and the strategy of RHV resection and reconstruction in different settings. METHODS: Five patients who underwent laparoscopic RUTH for liver tumor were enrolled retrospectively. Clinical and pathological features of the patients, peri-operative treatment, as well as short- and long-term outcomes were collected for analysis. RESULTS: Laparoscopic RUTH was successfully performed in all five patients. Two individuals underwent RUTH while preserving RHV. Among the remaining patients who underwent RUTH with RHV resection, one patient underwent RHV reconstruction but the others did not. Immediate or long-term venous related complications did not occurred in a median follow-up period of nine months. CONCLUSIONS: Laparoscopic RUTH surgery for tumors in the right upper region of the liver is safe and feasible. The strategic workflow we proposed for the resection and reconstruction of the RHV offers a reliable method for preserving liver parenchyma and reducing the risk of postoperative liver failure.

Hepatitis B virus X protein differentially regulates the angiogenesis of Hepatocellular Carcinoma through p53-VEGF axis according to glucose levels.

INTRODUCTION AND OBJECTIVES: Blood glucose fluctuates severely in the diabetes (DM) and tumor microenvironment. Our previous works have found Hepatitis B virus X protein (HBx) differentially regulated metastasis and apoptosis of hepatoma cells depending on glucose concentration. We here aimed to explore whether HBx played dual roles in the angiogenesis of hepatocellular carcinoma varying on different glucose levels. MATERIALS AND METHODS: We collected conditioned medium from HBx-overexpressing cells cultured with two solubilities of glucose, and then applied to EA.hy926 cells. Alternatively, a co-culture cell system was established with hepatoma cells and EA.hy926 cells. We analyzed the angiogenesis of EA.hy926 cells with CCK8, wound-healing, transwell-migartion and tube formation experiment. ELISA was conducted to detect the secretion levels of angiogenesis-related factors. siRNAs were used to detect the P53-VEGF axis. RESULTS: HBx expressed in hepatoma cells suppressed VEGF secretion, and subsequently inhibited the proliferation, migration and tube formation of EA.hy926 cells in a high glucose condition, while attenuating these in the lower glucose condition. Furthermore, the p53-VEGF axis was required for the dual role of HBx in angiogenesis. Additionally, HBx mainly regulated the nuclear p53. CONCLUSIONS: These data suggest that the dual roles of HBx confer hepatoma cells to remain in a glucose-rich environment and escape from the glucose-low milieu through tumor vessels, promoting liver tumor progression overall. We exclusively revealed the dual role of HBx on the angiogenesis of liver tumors, which may shed new light on the mechanism and management strategy of HBV- and DM-related hepatocellular carcinoma.

CT-Guided Fiducial Marker Implantation with Ultra-fine 25-Gauge Needle Prior to Proton Therapy for Liver Malignancies.

PURPOSE: Proton therapy is highly effective for liver malignancies, and to increase its accuracy, placement of fiducial markers in the liver is preferred. We retrospectively evaluated the safety and feasibility of CT-guided fiducial marker implantation using ultra-fine 25-gauge needles before proton therapy for liver malignancies. MATERIALS AND METHODS: Between May 2016 and April 2021, 334 cases were investigated. All of procedures were performed without anesthesia. Technical success was defined as the completion of implantation at the intended site. Tumor-marker distance and possibility of synchronization between tumors and markers were evaluated and compared with Mann-Whitney U test. Complications were evaluated using the Common Terminology Criteria for Adverse Events, version 4.0. RESULTS: Technical success rate was 97.3%. Tumor-marker distance was 19.1 mm (median, range 0-96) in the group in which the implanted marker was synchronized with tumor (n = 315), while it was 34.5 mm (median, range 6-94) in the group in which the implanted marker was not synchronized (n = 13) (p value = 0.011 < 0.05). The complication rate was 2.4%, 2 were classified as grade 4 and 5 as grade 1, and 1 as grade 2. There were no grade 3 or higher complications that seemed to be related to the procedure. CONCLUSION: CT-guided marker implantation using a 25-gauge needle achieved a satisfactory success rate with few complications and was useful for the image-guided and respiratory-synchronized proton therapy. LEVEL OF EVIDENCE 3: Local non-random sample.