PDF(2593 KB)
Exploratory study of the MRI reassessment interval after neoadjuvant chemoradiotherapy followed by immunotherapy in pMMR/MSS rectal cancer
ZHANG Hua-qing, SUN Zhen, LI Ke-xuan, LIN Guo-le, WU Bin, LU Jun-yang, XU Lai, ZHANG Guan-nan, NIU Bei-zhan, XIAO Yi
Chinese Journal of Practical Surgery ›› 2026, Vol. 46 ›› Issue (9) : 1267-1274.
PDF(2593 KB)
PDF(2593 KB)
Exploratory study of the MRI reassessment interval after neoadjuvant chemoradiotherapy followed by immunotherapy in pMMR/MSS rectal cancer
Objective To determine whether, beyond the conventional radiotherapy-based time anchor, the interval from the last immunotherapy administration to MRI reassessment also constitutes a key time anchor influencing assessment accuracy in patients with proficient mismatch repair/microsatellite-stable (pMMR/MSS) mid-to-low locally advanced rectal cancer treated with neoadjuvant chemoradiotherapy followed by immunotherapy (inCRT). Methods This retrospective study included 406 patients who underwent radical surgery after neoadjuvant therapy at Peking Union Medical College Hospital between June 2022 and April 2026. The inCRT cohort (n=136) was the primary analysis cohort, and the neoadjuvant chemoradiotherapy (nCRT) cohort (n=270) served as the reference. Pathologic suitability for organ preservation was defined as ypT0-1N0, and MRI suitability as MRI tumor regression grade (mrTRG) 1-2 with no suspicious residual lymph nodes (ymrN0). Concordance between MRI and pathology was considered an accurate assessment and served as the primary endpoint. The MRI reassessment interval was defined as the time from completion of the last relevant antitumor treatment to MRI reassessment; the interval from completion of radiotherapy to MRI was examined in sensitivity analyses. Multivariable Logistic regression and restricted cubic spline (RCS) models were used to evaluate time-effect associations of diagnostic performance. Results In the inCRT cohort, the median age was 60 years (Q1, 52; Q3, 67), 89 patients (65.4%) were male, 29 (21.3%) had baseline mrT4 disease, 83 (61.0%) had mrN2 disease, 63 (46.3%) had mesorectal fascia involvement, and 76 (55.9%) had extramural vascular invasion; 107 patients (78.7%) received long-course radiotherapy. 35 patients (25.7%) met the MRI criteria for suitability for organ preservation, whereas 66 patients (48.5%) met the pathologic criterion. The accuracy, sensitivity, and specificity of MRI assessment were 65.4%, 40.9%, and 88.6%, respectively. The interval from the last immunotherapy administration to MRI was longer in patients with accurate than inaccurate assessments [26 (17, 36) vs. 18 (9.5, 33) days, P=0.017]. Each 7-day increase in the interval was associated with greater odds of an accurate MRI assessment (adjusted OR, 1.273; 95%CI 1.025-1.600; P=0.029). RCS analysis showed a significant overall association between the interval and assessment accuracy (overall P=0.034), without evidence of nonlinearity (P for nonlinearity=0.158). Mean adjusted predicted accuracies during weeks 1-2, 3-4, and 5-6 after the last immunotherapy administration were 50.1%, 69.7%, and 72.6%, respectively. Accuracy during weeks 3-4 was 19.7 percentage points higher than during weeks 1-2 (95%CI 3.0-36.9 percentage points; P=0.046), whereas no further significant improvement was observed during weeks 5-6 (P=1.000). When the interval was anchored to completion of radiotherapy, no significant time-dependent associations were observed for accuracy, sensitivity, or specificity in the inCRT cohort. In the nCRT cohort, the interval was shorter in patients with accurate assessments [15.5 (5, 25) vs. 21 (10, 28.75) days, P=0.018], but neither Logistic regression nor the overall RCS test showed improved diagnostic performance with increasing interval. Conclusion In patients with pMMR/MSS locally advanced rectal cancer treated with neoadjuvant chemoradiotherapy followed by immunotherapy, an appropriate delay in MRI reassessment after the last immunotherapy administration may improve identification of patients pathologically suitable for organ preservation. Reassessment at 3-4 weeks may provide a reasonable balance between assessment reliability and timely subsequent decision-making and warrants further prospective validation.
rectal neoplasms / neoadjuvant therapy / immunotherapy / magnetic resonance imaging / organ preservation
| [1] |
|
| [2] |
|
| [3] |
中华医学会外科学分会结直肠外科学组, 中国研究型医院学会结直肠肛门外科专业委员会, 中华医学会消化内镜学分会超级微创协作组. 直肠癌新辅助治疗达临床完全缓解或近临床完全缓解后局部切除策略专家共识(2026版)[J]. 中华胃肠外科杂志, 2026, 29(3): 258-274. DOI:10.3760/cma.j.cn441530-20260113-00031.
|
| [4] |
李心翔, 翁俊勇. 新辅助治疗后临床完全缓解或近临床完全缓解直肠癌病人临床治疗策略[J]. 中国实用外科杂志, 2024, 44(7): 751-756. DOI:10.19538/j.cjps.issn1005-2208.2024.07.07.
|
| [5] |
中国直肠癌新辅助治疗后等待观察数据库研究协作组, 中华医学会外科学分会结直肠外科学组, 中国医师协会结直肠肿瘤医师专业委员会, 等. 直肠癌新辅助治疗后等待观察策略中国专家共识(2024版)[J]. 中华胃肠外科杂志, 2024, 27(4): 301-315. DOI:10.3760/cma.j.cn441530-20240227-00075.
|
| [6] |
杨正阳, 张忠涛. 从精准解剖性根治手术到精准功能保全:直肠癌治疗理念变迁与未来展望[J]. 中国实用外科杂志, 2026, 46(2): 180-183. DOI:10.19538/j.cjps.issn1005-2208.2026.02.04.
|
| [7] |
The optimal timing of surgery after preoperative radiotherapy in rectal cancer is unknown. The aim of this trial was to evaluate the role of the interval between preoperative radiotherapy and surgery.Patients with rectal carcinoma accessible to rectal digital examination, staged T2 to T3, NX, M0, were randomized before radiotherapy (39 Gy in 13 fractions) into two groups: in the short interval (SI) group, surgery had to be performed within 2 weeks after completion of radiation therapy, compared with 6 to 8 weeks in the long interval (LI) group. Between 1991 and 1995, 201 patients were enrolled onto the study.A long interval between preoperative radiotherapy and surgery was associated with a significantly better clinical tumor response (53. 1% in the SI group v 71.7% in the LI group, P =.007) and pathologic downstaging (10.3% in the SI group v 26% in the LI group, P =.005). At a median follow-up of 33 months, there were no differences in morbidity, local relapse, and short-term survival between the two groups. Sphincter-preserving surgery was performed in 76% of cases in the LI group versus 68% in the SI group (P = 0.27).A long interval between preoperative irradiation and surgery provides increased tumor downstaging with no detrimental effect on toxicity and early clinical results. When sphincter preservation is questionable, a long interval may increase the chance of a successful sphincter-saving surgery.
|
| [8] |
|
| [9] |
|
| [10] |
|
| [11] |
|
| [12] |
|
| [13] |
|
| [14] |
|
| [15] |
|
| [16] |
|
| [17] |
|
| [18] |
|
| [19] |
中国医师协会内镜医师分会腹腔镜外科专业委员会, 中国医师协会结直肠肿瘤专业委员会腹腔镜专业委员会, 中华医学会外科学分会结直肠外科学组, 等. 中国直肠癌侧方淋巴结转移诊疗专家共识(2024版)[J]. 中华胃肠外科杂志, 2024, 27(1): 1-14. DOI:10.3760/cma.j.cn441530-20231212-00211.
|
| [20] |
|
| [21] |
|
| [22] |
National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology(NCCN Guidelines):Rectal Cancer, Version 1.2026[EB/OL]. 2026-03-05 [2026-05-24]. https://www.nccn.org/professionals/physician_gls/pdf/rectal.pdf.
|
| [23] |
T-cell exhaustion was originally identified during chronic infection in mice, and was subsequently observed in humans with cancer. The exhausted T cells in the tumor microenvironment show overexpressed inhibitory receptors, decreased effector cytokine production and cytolytic activity, leading to the failure of cancer elimination. Restoring exhausted T cells represents an inspiring strategy for cancer treatment, which has yielded promising results and become a significant breakthrough in the cancer immunotherapy. In this review, we overview the updated understanding on the exhausted T cells in cancer and their potential regulatory mechanisms and discuss current therapeutic interventions targeting exhausted T cells in clinical trials.
|
| [24] |
|
| [25] |
|
| [26] |
|
| [27] |
Background: Immune checkpoint inhibitor (ICI) treatment in patients with microsatellite instability-high/mismatch repair deficient (MSI-H/dMMR) tumors holds promise in reshaping organ preservation in rectal cancer. However, the benefits are accompanied by distinctive patterns of response, introducing a dilemma in the response evaluation for clinical decision-making. Patients and Methods: Patients with locally advanced rectal cancer with MSI-H/dMMR tumors receiving neoadjuvant ICI (nICI) treatment (n=13) and matched patients receiving neoadjuvant chemoradiotherapy (nCRT; n=13) were included to compare clinical response and histopathologic features. Results: Among the 13 patients receiving nICI treatment, in the final radiologic evaluation prior to surgery (at a median of 103 days after initiation of therapy), progressive disease (n=3), stable disease (n=1), partial response (n=7), and complete response (n=2) were observed. However, these patients were later confirmed as having pathologic complete response, resulting in pseudoprogression and pseudoresidue with incidences of 23.1% (n=3) and 76.9% (n=10), respectively, whereas no pseudoprogression was found in the 13 patients receiving nCRT. We further revealed the histopathologic basis underlying the pseudoprogression and pseudoresidue by discovering the distinctive immune-related regression features after nICI treatment, including fibrogenesis, dense lymphocytes, and plasma cell infiltration. Conclusions: Pseudoprogression and pseudoresidue were unique and prevalent response patterns in MSI-H/dMMR rectal cancer after nICI treatment. Our findings highlight the importance of developing specific strategies for response evaluation in neoadjuvant immunotherapy to identify patients with a good response in whom sphincter/organ-preserving or watch-and-wait strategies may be considered.
|
| [28] |
|
| [29] |
Tumours respond differently to immunotherapies compared with chemotherapeutic drugs, raising questions about the assessment of changes in tumour burden-a mainstay of evaluation of cancer therapeutics that provides key information about objective response and disease progression. A consensus guideline-iRECIST-was developed by the RECIST working group for the use of modified Response Evaluation Criteria in Solid Tumours (RECIST version 1.1) in cancer immunotherapy trials, to ensure consistent design and data collection, facilitate the ongoing collection of trial data, and ultimate validation of the guideline. This guideline describes a standard approach to solid tumour measurements and definitions for objective change in tumour size for use in trials in which an immunotherapy is used. Additionally, it defines the minimum datapoints required from future trials and those currently in development to facilitate the compilation of a data warehouse to use to later validate iRECIST. An unprecedented number of trials have been done, initiated, or are planned to test new immune modulators for cancer therapy using a variety of modified response criteria. This guideline will allow consistent conduct, interpretation, and analysis of trials of immunotherapies.Copyright © 2017 Elsevier Ltd. All rights reserved.
|
| [30] |
Immunotherapy, specifically the introduction of immune checkpoint inhibitors, has transformed the treatment of cancer, enabling long-term tumour control even in individuals with advanced-stage disease. Unfortunately, only a small subset of patients show a response to currently available immunotherapies. Despite a growing consensus that combining immune checkpoint inhibitors with radiotherapy can increase response rates, this approach might be limited by the development of persistent radiation-induced immunosuppression. The ultimate goal of combining immunotherapy with radiotherapy is to induce a shift from an ineffective, pre-existing immune response to a long-lasting, therapy-induced immune response at all sites of disease. To achieve this goal and enable the adaptation and monitoring of individualized treatment approaches, assessment of the dynamic changes in the immune system at the patient level is essential. In this Review, we summarize the available clinical data, including forthcoming methods to assess the immune response to radiotherapy at the patient level, ranging from serum biomarkers to imaging techniques that enable investigation of immune cell dynamics in patients. Furthermore, we discuss modelling approaches that have been developed to predict the interaction of immunotherapy with radiotherapy, and highlight how they could be combined with biomarkers of antitumour immunity to optimize radiotherapy regimens and maximize their synergy with immunotherapy.
|
利益冲突 所有作者均声明不存在利益冲突
/
| 〈 |
|
〉 |