The 2024 Annual Progress Conference on Clinical Oncology in China (BOC) and Best of ASCO 2024 China (BOC/BOA 2024) was held in Guangzhou. Since 2015, the highly anticipated Annual Progress in Clinical Oncology Research in China report has been released during this event, focusing on research with distinct Chinese characteristics. This year was no exception. Dr. Jianwei Zhang from the Sixth Affiliated Hospital, Sun Yat-sen University presented the 10 most significant research advancements in the field of colorectal cancer for 2023, alongside a ranking of the top 20 authors and research institutions based on publication volume. Below is a summary of the highlights for industry professionals to reference and learn from.Background of Research Selection and Recommendations
Under the guidance of the Chinese Society of Clinical Oncology (CSCO), Peking University Library retrieved 6,435 publications on colorectal cancer from the SCI database. Among these, 5,195 articles were eligible for data analysis. The Colorectal Cancer Expert Group of the CSCO Youth Committee ultimately selected 10 landmark scientific research advancements from over 5,000 articles. These studies, spanning basic and translational research, surgical treatment, perioperative treatment, and treatment for metastatic colorectal cancer, were included in the Annual Progress in Clinical Oncology Research in China for Colorectal Cancer. Additionally, the committee compiled rankings of the top 20 authors and institutions based on publication volume in the field in 2023.
Top 10 Advances in Clinical Oncology for Colorectal Cancer in 2023
1. Single-Cell Exploration of PD-1 Antibodies in Immune and Stromal Remodeling of dMMR Colorectal Cancer Institution: Sixth Affiliated Hospital of Sun Yat-sen University Journal: Cancer Cell (Impact Factor: 50.3) Key Findings: This study utilized single-cell sequencing and multiplex immunofluorescence to explore the dynamic remodeling of the tumor microenvironment in dMMR/MSI-H colorectal cancer treated with the PD-1 antibody toripalimab as neoadjuvant therapy. The research highlighted the immune and stromal characteristics distinguishing complete responders from non-responders, emphasizing the role of the inflammatory microenvironment in balancing immune clearance and immune evasion. The study involved 40 tumor and normal tissue samples from 19 patients in the PICC trial. Findings included increased CD8+ T-cell cytotoxicity, reduced proliferation and exhaustion programs, decreased CD4+ Treg cells, and enhanced CD40LG-CD40 signaling among CD4- B cells in complete responders. In contrast, pro-inflammatory cytokine-secreting cells, such as IL1B+ monocytes and CCL2+ fibroblasts, were reduced, with T and B cells shifting toward an inflammation-resolving phenotype. The study also identified potential therapeutic targets, such as IL-1β and Treg cells in non-pCR-enriched populations, and revealed the critical roles of HLA-DRA+ endothelial cells and CXCL12+ fibroblast subpopulations in lymphocyte recruitment and activation.
2. Gut Microbiota-Mediated Nucleotide Synthesis and Its Impact on Rectal Cancer Response to Neoadjuvant Chemoradiotherapy Institution: Peking University Cancer Hospital Journal: Cancer Cell (Impact Factor: 50.3) Key Findings: The study demonstrated reduced gut microbiota diversity following neoadjuvant chemoradiotherapy in rectal cancer patients. Among patients with locally advanced rectal cancer who did not respond to treatment, nucleotide synthesis and DNA repair functions were enriched, driven by Bacteroides-mediated nucleotide synthesis. This suggests that uric acid could serve as a prognostic marker for rectal cancer patients undergoing neoadjuvant chemoradiotherapy, particularly for those considering a watch-and-wait strategy.
3. Short-Term Outcomes of Transanal vs. Laparoscopic Total Mesorectal Excision for Rectal Cancer: Multicenter Randomized Controlled Trial Institution: Sixth Affiliated Hospital of Sun Yat-sen University Journal: Annals of Surgery (Impact Factor: 10.1) Key Findings: The study compared transanal total mesorectal excision (taTME) with laparoscopic total mesorectal excision (laTME) in terms of short-term survival, pathological outcomes, and complications. The trial enrolled 1,115 patients, randomly assigned in a 1:1 ratio to receive either taTME or laTME. Results showed no significant differences between the two groups in intraoperative complications (4.8% vs. 6.1%, 95% CI: -4.2% to 1.7%, P=0.42), postoperative complications (13.4% vs. 12.1%, 95% CI: -2.8% to 5.2%, P=0.53), or mortality (0.2% in both groups). Long-term results, presented at ASCO 2024, revealed a 3-year disease-free survival (DFS) rate of 83.42% for the taTME group and 82.86% for the laTME group. The marginal difference of 0.56% (97.5% CI: -4.83 to 5.95) and non-inferiority P<0.0001 demonstrated equivalent outcomes, providing evidence supporting the clinical efficacy of taTME in rectal cancer treatment.
4. Robotic vs. Open Synchronous Resection for Rectal Cancer with Liver Metastases: A Randomized Controlled Trial Institution: Zhongshan Hospital, Fudan University Journal: International Journal of Surgery (Impact Factor: 15.3) Key Findings: This study aimed to compare the short- and long-term outcomes of robotic-assisted versus open synchronous surgery for rectal cancer with liver metastases. A total of 171 patients participated, with 86 in the robotic group and 85 in the open group. The results demonstrated that within 30 days post-surgery, the robotic group had significantly fewer complications compared to the open group (31.4% vs. 57.6%, P=0.014), with no deaths reported in either group. The robotic group experienced less blood loss (125.5±38.3 ml vs. 211.6±68.7 ml, P<0.001), faster recovery of bowel function (63.7±27.4 hours vs. 93.8±33.5 hours, P<0.001), and shorter hospital stays (mean ± SD, 8.0 vs. 10.7 days, P<0.001). Additionally, bladder and sexual function recovery within three months post-surgery was faster in the robotic group. There were no significant differences between the groups in three-year recurrence-free survival (39.5% vs. 35.3%, P=0.739) or three-year overall survival (76.7% vs. 72.9%, P=0.712).
5. Phase II Study of PD-1 Inhibitor Neoadjuvant Therapy for Locally Advanced dMMR/MSI-H Rectal Cancer Institution: Sun Yat-sen University Cancer Center Journal: Lancet Gastroenterology & Hepatology (Impact Factor: 35.7) Key Findings: This study included 17 patients with dMMR/MSI-H locally advanced rectal cancer, of whom 13 completed eight cycles of sintilimab therapy. One patient was lost to follow-up after one cycle, one discontinued treatment due to tumor progression, and one due to severe adverse events, while one declined further treatment. None of the patients received radiotherapy or chemotherapy. Among 16 evaluable patients, tumor shrinkage was observed in 15 (94%) during the first evaluation after treatment. Three patients (19%) underwent radical surgery with a pathological complete response (pCR), nine (56%) achieved clinical complete response (cCR) and opted for a watch-and-wait strategy, and three (19%) who did not achieve cCR underwent surgery, with residual tumors detected in pathology. One patient (6%) discontinued treatment due to grade 3 encephalitis, did not achieve cCR, and refused surgery. The study reported an overall complete response rate of 75% (95% CI: 47–92), with a median time to cCR of 5.2 months.
6. Pseudoprogression and Residual Lesions in Neoadjuvant Immunotherapy for Rectal Cancer Institution: Sixth Affiliated Hospital of Sun Yat-sen University Journal: Journal of the National Comprehensive Cancer Network (Impact Factor: 13.4) Key Findings: This study involved 13 patients with MSI-H/dMMR locally advanced rectal cancer who underwent a median of 103 days of neoadjuvant immunotherapy. Imaging evaluations revealed three cases of progressive disease (PD), one stable disease (SD), seven partial responses (PR), and two complete responses (CR). Pathological evaluations confirmed complete response in all cases, including three cases of pseudoprogression and ten cases of pseudoresidual lesions. Pathological analysis showed that pseudoprogression and pseudoresidual lesions in the immunotherapy group were characterized by fibrosis and dense infiltration of lymphocytes and plasma cells, which were not observed in the chemotherapy group. This study underscores the importance of using multiple techniques to comprehensively evaluate treatment efficacy and avoid unnecessary organ resection.
7. Neoadjuvant Immunotherapy for Locally Advanced dMMR Colorectal Cancer Yields Remarkable Efficacy and Low Recurrence Rates Institution: Sun Yat-sen University Cancer Center Journal: Journal of the National Comprehensive Cancer Network (Impact Factor: 13.4) Key Findings: This retrospective study analyzed 73 patients with dMMR/MSI-H colorectal cancer treated with PD-1 antibodies. The overall response rate (ORR) was 84.9%, with a CR rate of 23.3% and a PR rate of 61.6%. The median time to response was 9.6 weeks. The response rate for cT4a/4b tumors was comparable to that for cT2-3 tumors (85.4% vs. 84.0%), with an objective response rate of 93.1% for cT4b. However, cT2-3 tumors were more likely to achieve CR than cT4a/4b (52% vs. 8.3%). Among surgical patients, the pCR rate was nearly 60%. After a mean follow-up of 17.2 months, neither median disease-free survival (DFS) nor median overall survival (OS) was reached. For patients who underwent surgery or achieved CR, the two-year tumor-specific DFS and OS rates were both 100%. Eight patients experienced grade 3–4 adverse events during neoadjuvant treatment, with four requiring urgent intervention and three requiring additional surgeries for severe postoperative complications.
8. Postoperative Stratification of Stage I–III Colorectal Cancer Using ctDNA Methylation Institution: Fudan University Cancer Hospital Journal: JAMA Oncology (Impact Factor: 28.4) Key Findings: This study evaluated six DNA methylation markers to detect ctDNA and assess its association with prognosis. A total of 299 stage I–III colorectal cancer patients undergoing curative surgery were included. Blood samples were collected at pre-surgery, one month post-surgery, during adjuvant therapy, and every three months after adjuvant chemotherapy for dynamic ctDNA monitoring. Of the 296 patients with pre-surgery specimens, 78.4% were ctDNA-positive, with positivity rates of 65.1%, 82.7%, and 81.5% for stages I, II, and III, respectively. Among 54 recurrence cases, 94.4% were ctDNA-positive pre-surgery. One month post-surgery, ctDNA-positive patients were 17.5 times more likely to relapse compared to ctDNA-negative patients. Combining ctDNA with CEA marginally improved relapse prediction (AUC=0.849). After adjuvant chemotherapy, ctDNA-positive patients had significantly shorter recurrence-free survival compared to ctDNA-negative patients (HR 13.8, P<0.001). Dynamic ctDNA methylation monitoring was shown to significantly aid in early relapse detection, offering a potential strategy to optimize postoperative stratification and treatment in colorectal cancer.
9. BBCAPX: Progress in Immunotherapy for RAS-Mutated/MSS mCRC Institution: Second Affiliated Hospital of Zhejiang University Journal: EClinicalMedicine (Impact Factor: 15.1) Key Findings: The BBCAPX study was a phase II, single-arm, open-label, single-center trial involving 25 patients with KRAS-mutated, MSS advanced colorectal cancer. Following multidisciplinary discussion, patients with unresectable metastases received sintilimab, bevacizumab, and CapeOx as first-line treatment. All 25 patients showed varying degrees of tumor shrinkage. The median PFS was 18.2 months (for first analysis) and 9.9 months (for progression-free survival).
10. Multicenter Phase II Trial of Pertuzumab for dMMR/MSI-H Solid Tumors Institution: Cancer Hospital, Chinese Academy of Medical Sciences Journal: Cell Reports Medicine (Impact Factor: 14.3) Key Findings: This study enrolled 100 patients (71 colorectal cancer, 10 gastric cancer, and 19 other cancers), including 43 previously treated with first-line therapies and 28 with second-line therapies. The primary endpoint was independently assessed ORR, which was 50.0%. Treatment-related adverse events occurred in 85% of patients, with grade 3–4 adverse events in 18% and one grade 5 case (myocarditis). The KMT2D mutation was identified as a predictive biomarker, with mutated patients achieving an ORR of 69.8%, compared to 15% in wild-type patients.
