Journal of gastrointestinal oncology最新文献

Background and objective: Magnetic resonance guided radiotherapy (MRgRT) is an emerging technological innovation with more and more institutions gaining clinical experience in this new field of radiation oncology. The ability to better visualize both tumors and healthy tissues due to excellent soft tissue contrast combined with new possibilities regarding motion management and the capability of online adaptive radiotherapy might increase tumor control rates while potentially reducing the risk of radiation-induced toxicities. As conventional computed tomography (CT)-based image guidance methods are insufficient for adaptive workflows in abdominal tumors, MRgRT appears to be an optimal method for this tumor site. The aim of this narrative review is to outline the opportunities and challenges in magnetic resonance guided radiation therapy in gastrointestinal cancers.

Methods: We searched for studies, reviews and conceptual articles, including the general technique of MRgRT and the specific utilization in gastrointestinal cancers, focusing on pancreatic cancer, liver metastases and primary liver cancer, rectal cancer and esophageal cancer.

Key content and findings: This review is highlighting the innovative approach of MRgRT in gastrointestinal cancer and gives an overview of the currently available literature with regard to clinical experiences and theoretical background.

Conclusions: MRgRT is a promising new tool in radiation oncology, which can play off several of its beneficial features in the specific field of gastrointestinal cancers. However, clinical data is still scarce. Nevertheless, the available literature points out large potential for improvements regarding dose coverage and escalation as well as the reduction of dose exposure to critical organs at risk (OAR). Further prospective studies are needed to demonstrate the role of this innovative technology in gastrointestinal cancer management, in particular trials that randomly compare MRgRT with conventional CT-based image-guided radiotherapy (IGRT) would be of high value.

Background: Single-agent immunotherapy is less effective in patients with DNA mismatch repair-proficient/microsatellite stable (pMMR/MSS) metastatic colorectal cancer (mCRC). Whether pMMR/MSS mCRC patients benefit from combination immunotherapy remains unclear. This study aimed to evaluate the efficacy and safety of anti-programmed cell death protein 1 (PD-1) therapy combined with chemotherapy and bevacizumab in pMMR/MSS colorectal liver metastases (CRLM) patients.

Methods: A total of 12 patients with pMMR/MSS CRLM treated at The Sixth Affiliated Hospital of Sun Yat-sen University were enrolled. All patients were treated with at least 4 doses of PD-1 monoclonal antibody combined with chemotherapy and bevacizumab as neoadjuvant/adjuvant therapy.

Results: A total of 10 of the 12 patients received the combined therapies before primary tumor resection; the disease control rate (DCR) was 100% (10/10), and the objective response rate (ORR) was 70% (7/10). The ORR of liver metastases was 75% (9/12). Pathological complete response (pCR) was achieved in 1 primary tumor patient and 2 patients with hepatic lesions. A total of 5 patients underwent simultaneous resection of the primary tumor and liver metastases; 9 patients underwent microwave ablation for liver metastases. A total of 7 patients were assessed as having no evidence of disease (NED) with a median progression-free survival (PFS) interval of 9.2 (1.5-15.8) months after multimodality treatments for both primary and metastatic lesions. No severe immune-related adverse events (irAEs) and operational complications were observed.

Conclusions: PD-1 blockade combined with chemotherapy and bevacizumab might be safe and effective for patients with pMMR/MSS CRLM. This treatment strategy might lead to better tumor regression and a higher chance of achieving NED.

Background: Few data are available on metastatic colorectal cancer (mCRC) treated with late-line regorafenib monotherapy or combined with other therapies. This study thus aimed to examine regorafenib combined with immune checkpoint inhibitors (ICIs) compared with regorafenib monotherapy in patients with advanced CRC.

Methods: This single-center retrospective cohort study included patients with advanced CRC who experienced recurrence and progression after standard first- and second-line treatments treatment from November 2018 to December 2021. The patients received regorafenib plus ICIs or regorafenib monotherapy. Treatment response was evaluated based on Response Evaluation Criteria in Solid Tumors (RECIST). Overall survival (OS) and progression-free survival (PFS) were analyzed via multivariate analysis.

Results: The combined group and the monotherapy group included 30 and 43 patients, respectively. The median OS (13.7 vs. 10.1 months; P=0.10) and PFS (4 vs. 3.6 months; P=0.32) were not significantly different between the two groups. In males, the median OS was significantly longer in the combined group compared with the monotherapy group (not reached vs. 8.03 months; P=0.02), but the median PFS showed no significant difference (7.23 vs. 3.90 months; P=0.16). There was no significant difference in OS (P=0.71) or PFS (P=0.89) in females. Eastern Cooperative Oncology Group performance status (ECOG PS) 1 [vs. 0; hazard ratio (HR) =3.13, 95% confidence interval (CI): 1.61-6.10; P<0.001] was independently associated with PFS. ECOG PS 1 (vs. 0; HR =3.63, 95% CI: 1.54-8.56; P=0.003) and combined therapy (vs. monotherapy; HR =0.47, 95% CI: 0.22-0.99; P=0.048) were associated with OS.

Conclusions: Regorafenib combined with ICIs led to numerically longer PFS and significantly prolonged OS in patients with mCRC compared to regorafenib monotherapy, especially in male patients.

Background: In oligometastatic colorectal cancer (CRC), stereotactic body radiation therapy (SBRT) represents a valid non-invasive local ablative treatment with high rates of local control (LC) and a low toxicity profile. This literature review was performed to evaluate the clinical benefit and toxicity of SBRT on non-liver metastases in CRC oligometastatic patients.

Methods: After searching PubMed, Medscape and Embase databases, 18 retrospective studies focused on body oligometastases excluding bone metastases were included in the analysis.

Results: A total of 1,450 patients with 3,227 lung metastases and 53 patients with 66 nodes lesions were analyzed. BED10 ranged from 76 to 180 Gy. In the lung group, the LC rate was 62-91%, 54-81% and 56-77% after 1, 3 and 5 years, respectively. In the nodes group, the 3-year LC rate was 65-75%. The 1-, 3- and 5-year OS rates were 73-100%, 51-64% and 34-43%, respectively for the lung group, and 63-81% at 3 years for the nodes group.

Conclusions: In CRC patients with non-liver oligometastases, the use of SBRT is effective and safe reaching high LC and survival, with few severe side effects. However, prospective randomized studies are needed to validate the results. These studies will also be useful for identifying any predictive factors that allow us to select the subgroup of patients who benefit from SBRT.

Background: Hepatocellular carcinoma (HCC) ranks prominently in cancer-related mortality globally. Surgery remains the main therapeutic option for the treatment of HCC, but high post-operative recurrence rate makes prognostic prediction challenging. The quest for a reliable model to predict HCC recurrence continues to enhance prognosis. We aim to develop a nomogram with multiple factors to accurately estimate the risk of post-operative recurrence in patients with HCC.

Methods: A single-center retrospective study on 262 patients who underwent partial hepatectomy for HCC at the Eastern Hepatobiliary Surgery Hospital from May 2010 to April 2013 was conducted where immunohistochemistry assessed Yes-associated protein (YAP) expression in HCC. In the training cohort, a nomogram that incorporated YAP expression and clinicopathological features was constructed to predict 2-, 3-, and 5-year recurrence-free survival (RFS). The performance of the nomogram was assessed with respect to discrimination calibration, and clinical usefulness with external validation.

Results: A total of 262 patients who underwent partial hepatectomy for HCC at the Eastern Hepatobiliary Surgery Hospital were included in our study. HCC patients with high YAP expression exhibited significantly higher recurrence and reduced overall survival (OS) rates compared to those with low YAP expression (P<0.001). YAP was significantly associated with alpha-fetoprotein (AFP) (P=0.03), microvascular invasion (MVI) (P<0.001), and tumor differentiation grade (P<0.001). In the training cohort, factors like YAP expression, hepatitis B surface antigen (HBsAg), hepatitis B virus deoxyribonucleic acid (HBV-DNA), Child-Pugh stage, tumor size, MVI, and tumor differentiation were identified as key elements for the predictive model. Two YAP-centric Nomograms were developed, with one focused on predicting postoperative OS and the other on RFS. The calibration curve further confirmed the model's accuracy in the training cohort. The validation cohort confirmed the model's predictive accuracy.

Conclusions: The proposed nomogram combining the YAP, a predictor of HCC progression, and clinical features achieved more-accurate prognostic prediction for patients with HCC after partial hepatectomy, which may help clinicians implement more appropriate interventions.

Background: Only a small percentage of patients with large hepatocellular carcinoma (HCC) can undergo surgical resection (SR) therapy while the prognosis of patients with large HCC is poor. However, innovations in surgical techniques have expanded the scope of surgical interventions accessible to patients with large HCC. Currently, most of the existing nomograms are focused on patients with large HCC, and research on patients who undergo surgery is limited. This study aimed to establish a nomogram to predict cancer-specific survival (CSS) in patients with large HCC who will undergo SR.

Methods: The study retrieved data from the Surveillance, Epidemiology, and End Results (SEER) database encompassing patients with HCC between 2010 and 2015. Patients with large HCC accepting SR were eligible participants. Patients were randomly divided into the training (70%) and internal validation (30%) groups. Patients from Air Force Medical Center between 2012 and 2019 who met the inclusion and exclusion criteria were used as external datasets. Demographic information such as sex, age, race, etc. and clinical characteristics such as chemotherapy, histological grade, fibrosis score, etc. were analyzed. CSS was the primary endpoint. All-subset regression and Cox regression were used to determine the relevant variables required for constructing the nomogram. Decision curve analysis (DCA) was used to evaluate the clinical utility of the nomogram. The area under the receiver operating characteristic curve (AUC) and calibration curve were used to validate the nomogram. The Kaplan-Meier curve was used to assess the CSS of patients with HCC in different risk groups.

Results: In total, 1,209 eligible patients from SEER database and 21 eligible patients from Air Force Medical Center were included. Most patients were male and accepted surgery to lymph node. The independent prognostic factors included sex, histological grade, T stage, chemotherapy, α-fetoprotein (AFP) level, and vascular invasion. The CSS rate for training cohort at 12, 24, and 36 months were 0.726, 0.731, and 0.725 respectively. The CSS rate for internal validation cohort at 12, 24, and 36 months were 0.785, 0.752, and 0.734 respectively. The CSS rate for external validation cohort at 12, 24, and 36 months were 0.937, 0.929, and 0.913 respectively. The calibration curve demonstrated good consistency between the newly established nomogram and real-world observations. The Kaplan-Meier curve showed significantly unfavorable CSS in the high-risk group (P<0.001). DCA demonstrated favorable clinical applicability of the nomogram.

Conclusions: The nomogram constructed based on sex, histological grade, T stage, chemotherapy and AFP levels can predict the CSS in patients with large HCC accepting SR, which may aid in clinical decision-making and treatment.

Background: The optimal timing to discontinue immune checkpoint inhibitor (ICI) therapy in hepatocellular carcinoma (HCC) patients with clinical benefits remains unclear. This study aimed to assess the outcomes of HCC patients after ICI discontinuation.

Methods: Patients with HCC were retrospectively screened and those discontinued ICI therapy in the absence of progressive disease (PD) were included. Responses at discontinuation were evaluated per response evaluation criteria in solid tumors (RECIST) version 1.1 and modified RECIST (mRECIST). Patients were classified into five subgroups according to the cause of discontinuation: complete response (CR), partial response (PR), stable disease (SD) per RESICT version 1.1, adverse event (AE), or others. Progression-free survival (PFS) and overall survival (OS) since ICI start or after ICI discontinuation were assessed.

Results: A total of 66 patients were included. The median follow-up was 29.33 months. The median PFS since ICI start was 30.83 months [95% confidence interval (CI): 24.93-36.72], and the median OS was not reached. The median PFS after discontinuation was 20.6 months (95% CI: 7.63-33.56), and the median OS after discontinuation was not reached. Univariate analysis showed that age, treatment after discontinuation, Response (RECIST version 1.1) at discontinuation and modified response (mResponse per mRECIST) at discontinuation were significantly associated with PFS after discontinuation, while age and mResponse at discontinuation were significantly associated with OS after discontinuation. Multivariate analysis further demonstrated that mResponse at discontinuation and treatment after discontinuation were independently associated with PFS after discontinuation, while age was independently associated with OS after discontinuation.

Conclusions: ICIs might be discontinued in HCC patients with a response of CR per mRECIST. Patients with a response of PR/SD per mRECIST or elder age could continue ICI therapy after achieving clinical benefits. Tyrosine kinase inhibitor (TKI) maintenance therapy might help to prevent progression after ICI discontinuation.