Nie TT, Li YX, Yang X, Liu T, Niu XH, Guo XF, Liu YL. Tumor-related imaging parameters predict response and survival after neoadjuvant chemoradiotherapy in rectal cancer. World J Gastrointest Oncol 2026; 18(6): 117694 [DOI: 10.4251/wjgo.v18.i6.117694]
Corresponding Author of This Article
Xiao-Fang Guo, MD, PhD, Department of Radiology, Hubei Cancer Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 116 Zhuodaoquan South Road, Hongshan District, Wuhan 430079, Hubei Province, China. guoxiaofang2001@163.com
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Nie TT, Li YX, Yang X, Liu T, Niu XH, Guo XF, Liu YL. Tumor-related imaging parameters predict response and survival after neoadjuvant chemoradiotherapy in rectal cancer. World J Gastrointest Oncol 2026; 18(6): 117694 [DOI: 10.4251/wjgo.v18.i6.117694]
Ting-Ting Nie, Tao Liu, Xiao-Fang Guo, Yu-Lin Liu, Department of Radiology, Hubei Cancer Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430079, Hubei Province, China
Yu-Xia Li, Xiao-Hui Niu, College of Informatics, Huazhong Agriculture University, Wuhan 430070, Hubei Province, China
Xuan Yang, Department of Radiology, Wuhan Children’s Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430014, Hubei Province, China
Co-corresponding authors: Xiao-Fang Guo and Yu-Lin Liu.
Author contributions: Nie TT and Li YX drafted the article or revised it critically for important intellectual content, approved the version to be published, have agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved as co-first authors; Li YX, Yang X, Liu T, and Niu XH have made a substantial contribution to the acquisition, analysis, or interpretation of data for the article; Guo XF and Liu YL have made a substantial contribution to the concept or design of the article as co-corresponding authors; all of the authors read and approved the final version of the manuscript to be published.
AI contribution statement: The use of ChatGPT in this study was strictly limited to language polishing of author-written content. The AI tool did not contribute to the intellectual content of the manuscript in any way.
Supported by Guiding Program of Natural Science Foundation of Hubei Province, No. 2024AFC050; Special Project of Biomedical Research Center of Hubei Cancer Hospital, No. 2022SWZX06; and Hubei Province “Chutian Talents Program” Medical and Health Personnel Project, No. CTYC001.
Institutional review board statement: This retrospective study was approved by the Institutional Review Board of Hubei Cancer Hospital in compliance with ethical principles derived from the Declaration of Helsinki and its subsequent amendments, No.[2020]KYLL(S05).
Informed consent statement: Informed consent was waived because the study was approved by the Ethics Committee with an exemption from obtaining individual informed consent. This study involved no direct contact with participants and collected only baseline clinical data from outpatient and inpatient medical records. All identifying information was removed prior to analysis to ensure confidentiality and protect personal privacy. Therefore, the study posed no more than minimal risk to the participants.
Conflict-of-interest statement: All authors declare no conflict of interest in publishing the manuscript.
Data sharing statement: The datasets used and/or analysed during the current study are available from the corresponding author upon reasonable request.
Corresponding author: Xiao-Fang Guo, MD, PhD, Department of Radiology, Hubei Cancer Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 116 Zhuodaoquan South Road, Hongshan District, Wuhan 430079, Hubei Province, China. guoxiaofang2001@163.com
Received: December 15, 2025 Revised: January 6, 2026 Accepted: February 5, 2026 Published online: June 15, 2026 Processing time: 178 Days and 2.8 Hours
Abstract
BACKGROUND
Response to neoadjuvant chemoradiotherapy (nCRT) varies substantially among patients with rectal cancer (RC). Identifying clinically accessible pretreatment predictors is essential for optimizing risk stratification and individualized treatment planning.
AIM
To investigate whether pretreatment sarcopenia and tumor-related imaging parameters assessed on magnetic resonance imaging can predict treatment response, tumor downstaging, and overall survival (OS) in patients with RC undergoing nCRT.
METHODS
This retrospective study included 137 patients with RC who underwent standard nCRT. Clinical characteristics, tumor-related imaging parameters derived from pretreatment magnetic resonance imaging, and pretreatment sarcopenia were analyzed as potential prognostic factors. Sarcopenia was assessed using the skeletal muscle index measured on computed tomography at the time of diagnosis. Univariate and multivariate logistic regression analyses were performed to identify predictors of treatment response and tumor downstaging. OS was analyzed using the Kaplan-Meier method and Cox proportional hazards regression.
RESULTS
Pretreatment sarcopenia was non-significantly associated with response to nCRT or OS. Conversely, tumor length [hazard ratio (HR) = 1.029, 95%CI: 1.011-1.056; P = 0.004] and mesorectal fascia (MRF) involvement (HR = 1.853, 95%CI: 0.873-3.970; P = 0.025) independently predicted treatment response. Clinical T stage (HR = 4.928, 95%CI: 2.170-12.340; P < 0.001) and MRF status (HR = 4.456, 95%CI: 1.881-11.532; P = 0.001) were significantly associated with tumor downstaging. Nodal status (HR = 2.655, 95%CI: 1.281-5.503; P = 0.009) and MRF status (HR = 2.149, 95%CI: 1.005-4.596; P = 0.049) were associated with OS in univariate analysis; however, they did not remain independent predictors in multivariate models.
CONCLUSION
Pretreatment sarcopenia is not an independent predictor of treatment response or survival in patients with RC undergoing nCRT. Conversely, tumor-related parameters – including tumor length, MRF involvement, and clinical staging – have greater prognostic value and may assist in pretreatment risk stratification and in the individualized management of RC.
Core Tip: This study evaluated the impact of pretreatment sarcopenia and tumor-related magnetic resonance imaging parameters on the response to neoadjuvant chemoradiotherapy and overall survival in rectal cancer patients. The results show that while sarcopenia was not an independent predictor of treatment response or survival, tumor-related factors such as tumor length, mesorectal fascia involvement, and clinical T/N stage were significant predictors. These findings highlight the value of tumor-related imaging parameters in pretreatment risk stratification and personalized management for rectal cancer patients undergoing neoadjuvant chemoradiotherapy.
Citation: Nie TT, Li YX, Yang X, Liu T, Niu XH, Guo XF, Liu YL. Tumor-related imaging parameters predict response and survival after neoadjuvant chemoradiotherapy in rectal cancer. World J Gastrointest Oncol 2026; 18(6): 117694
Colorectal cancer, particularly rectal cancer (RC), accounts for approximately 30% of all colorectal cancer cases. It is the third most commonly diagnosed malignancy worldwide and the second leading cause of cancer-related mortality[1]. Currently, the standard treatment strategy for patients with locally advanced RC is neoadjuvant chemoradiotherapy (nCRT) followed by total mesorectal excision[2]. However, responses to nCRT vary significantly among patients, ranging from pathological complete response (pCR) to minimal or no tumor regression, and in some cases, disease progression[3,4]. Notably, a favorable response to neoadjuvant therapy has been associated with improved oncologic outcomes[5,6]. Extending the interval between nCRT and surgery may further increase the likelihood of achieving pCR and organ preservation[7]. Conversely, patients who respond poorly to neoadjuvant therapy may experience limited benefit while being exposed to additional treatment-related toxicity[8,9]. Consequently, accurately predicting treatment responses before initiating therapy is crucial for optimizing treatment strategies and facilitating individualized management in RC.
Recently, there has been growing interest in the relationship between nutritional status and cancer outcomes. Among various nutritional indicators, sarcopenia – characterized by the progressive loss of skeletal muscle mass – has emerged as a potential prognostic marker in oncology[10,11]. Sarcopenia is commonly assessed using computed tomography (CT)-based measurements, particularly the skeletal muscle index (SMI) at the level of the third lumbar vertebra[12]. Accumulating evidence suggests that radiologically defined sarcopenia may be associated with an unfavorable prognosis in several malignancies, including gastrointestinal cancers in 7 articles[13-19]. However, the prognostic significance of pretreatment sarcopenia varies across different cancer types. Several studies have reported a non-significant association between sarcopenia and survival outcomes in urological, gynecological, and lung cancers treated with chemoradiotherapy or radiotherapy[20-23]. Similar inconsistencies have been observed in RC, where the association of sarcopenia with postoperative complications and long-term survival remains unclear[24-26]. These conflicting results suggest that the prognostic value of pretreatment sarcopenia in patients with RC undergoing nCRT remains controversial.
In addition to host-related factors, tumor-related characteristics assessed before treatment play a critical role in determining response to neoadjuvant therapy. Previous studies have demonstrated that baseline tumor extent and local invasion patterns, as assessed by magnetic resonance imaging (MRI), are closely associated with treatment response and prognosis in RC[27]. As MRI is routinely used for local staging and treatment planning in RC, tumor-related imaging parameters obtained from pretreatment MRI may provide valuable information for pretreatment risk stratification. Consequently, the present study aimed to investigate the prognostic value of pretreatment sarcopenia and tumor-related imaging parameters in predicting response to nCRT and overall survival (OS) in patients with RC.
MATERIALS AND METHODS
Patient characteristics
This retrospective study was approved by the Institutional Review Board of Hubei Cancer Hospital in compliance with the ethical principles outlined in the Declaration of Helsinki and its subsequent amendments. This study included 137 consecutive patients treated between July 2014 and October 2021. This study focused on patients with locally advanced rectal cancer who underwent nCRT, which is the standard of care for this patient group in our institution. The primary research question was to evaluate the impact of pre-treatment sarcopenia on nCRT response and survival outcomes. We selected this particular cohort specifically because nCRT itself can lead to nutritional deficits and muscle wasting, both of which are critical factors in treatment response and prognosis. We acknowledge that limiting our study to this group may reduce the generalizability of our findings. However, we intended to focus on patients who are routinely treated with nCRT and to better understand predictors of treatment efficacy and oncologic outcomes in this population. The criteria for patient enrollment were strict and included the following: (1) Confirmation of a solitary, primary RC through pathological examination; (2) Adherence to the standardized neoadjuvant therapy protocol established by Chinese colorectal diagnosis and treatment standards, without prior anticancer treatment received at any other medical facility; (3) Availability of a pelvic magnetic resonance (MR) scan with superior image quality before treatment; (4) Possession of abdominal CT images (including the L3 vertebral level) pretreatment for sarcopenia assessment; (5) Successful completion of total mesorectal excision surgery following neoadjuvant therapy; and (6) Comprehensive clinical and pathological data at the time of diagnosis. Conversely, patients were excluded if they met any of the following criteria: (1) The presence of concurrent malignancy elsewhere; (2) An incomplete MR study providing insufficient information for accurate tumor staging or exhibiting imaging artifacts that could compromise radiomic analysis; and (3) A history of pelvic radiotherapy.
Clinical features, such as age, sex, serum tumor markers (carcinoembryonic antigen and carbohydrate antigen 19-9), oncological information derived from pretreatment MRI, pretreatment body mass index, and sarcopenia, were analyzed as prognostic factors. The reassessment process was performed based on baseline MRI scans without access to any medical records and yielded consistent results. Additionally, rectal tumor reassessment was performed by two experienced gastrointestinal radiologists with 10 years and 15 years of expertise, respectively. The baseline tumor-related imaging parameters include the following: (1) Maximum diameter of the tumor [the long diameter of the major solid tumor on high resolution T2-weighted imaging (T2WI)]; (2) Tumor length (the distance from the inferior margin to the superior margin of the tumor); (3) Maximum diameter perpendicular to the intestinal wall on T2WI; (4) Maximum cross-sectional area of the tumor on T2WI; (5) Distance of the tumor from the anal verge; (6) Short diameter of the largest lymph node; (7) Extent of tumor involvement in the intestinal ring (circles, 1, 2, 3, and 4, respectively, indicate the extent of enterospheric invasion); (8) Tumor signal (homogeneous is defined as similar signals in more than 75% of tumors on the short axis); (9) Tumor spiculation (spiculation, a cord of soft tissue along the edge of a tumor similar to the signal of the tumor); (10) Cancerous node (an irregularly shaped tumor nodule in the peripheral mesangium that differs from a lymph node); (11) Mural stratification; (12) The status of mesorectal fascia (MRF) (positive indicates that the distance between the mesangial fascia around the rectum and any of the tumor itself, metastatic lymph nodes, cancer nodules, or vascular invasion lesions is less than 1 mm); (13) Extramural vascular invasion (positive findings indicate that either the tumor has infiltrated the rectal wall in a linear pattern or the adjacent vascular lumen exhibits a tumor-like medium signal with dilation or irregular vascular contour); (14) Extra-mesenteric lymph node (extraMRF, lymph nodes metastasizing beyond the mesangial area around the rectum); and (15) Baseline clinical T and N stages, American Joint Committee on Cancer 7th edition[28].
Pathological assessment
The resected specimens were independently evaluated by two blinded pathologists who were unaware of the clinical results of the patients. Detailed records were kept for all pathological stages and tumor regression grades (TRGs). The American Joint Committee on Cancer TNM staging system (7th edition) was utilized for assessment and considered the most reliable and standardized framework at that time[28].
The TRG was categorized as follows: TRG 0 and TRG 1 comprised the good response group, with the absence of residual viable malignant cells or the presence of only small cell clusters or isolated malignant cells. Conversely, TRG 2 and TRG 3 included the poor response group, with residual malignant cells accompanied by significant fibrosis, limited or no cancer cell death, or a significant residual tumor.
Based on the postoperative pathological T stage, patients with ypT0, ypT1, or ypT2 were grouped into the good response category (ypT0-2). The ‘y’ prefix indicated the staging classification after neoadjuvant treatment. A comparative analysis was conducted between the postoperative pathological T and T stages assessed from high-resolution baseline MR images. Patients who exhibited a reduced T stage postoperatively were considered to have undergone tumor downstaging.
Assessment of pretreatment sarcopenia
Before treatment, CT scans were utilized to delineate the significant landmarks of the left and right psoas, including the quadrate psoas, erectus, transverse abdominis, internal and external oblique abdominis, and rectus abdominis. Subsequently, skeletal muscle cross-sectional area was automatically computed using ImageJ software. For the analysis, two adjacent CT images were selected from the third lumbar spine plane. The tissue Hounsfield unit (HU) thresholds were defined as subcutaneous fat ranging from 190 HU to 30 HU, visceral fat from 150 HU to 50 HU, and muscles between 29 HU and 150 HU.
The subsequent step involved assessing the presence of sarcopenia on the CT scans before neoadjuvant therapy. Sarcopenia was defined as calculating the cumulative cross-sectional areas of all skeletal muscles in the two consecutive CT images of the third lumbar spine plane, averaging the values, and then dividing by the square of the individual’s height to obtain the SMI at the L3 level (L3SMI) (cm2/m2) (Figure 1). This calculation is represented as L3SMI (cm2/m2) = L3 skeletal muscle cross-sectional area/height2. According to Chinese standards, the diagnostic cut-offs for sarcopenia, based on the L3 skeletal index, are 40.8 cm2/m2 for males and 34.9 cm2/m2 for females[29].
Figure 1 Segmented computed tomography images indicating skeletal muscle and fat distribution at the L3 level.
Axial and sagittal computed tomography images at the L3 level displaying segmented skeletal muscle (red), visceral fat (green), subcutaneous fat (peach), and intramuscular fat (blue). Skeletal muscle index was calculated to assess sarcopenia. HU: Hounsfield unit.
Statistical analysis
R software (version 3.5.1; http://www.R-project.org) and Python (version 3.7.12) were used for statistical analyses. Categorical variables were analyzed using χ2 tests, while continuous variables with a normal distribution were evaluated through independent sample t-tests. For variables with non-normal distributions, the Mann-Whitney U test was performed. For short-term outcomes (TRG and downstaging), variables with P < 0.10 in univariate logistic regression or deemed clinically relevant were included in multivariate logistic regression. For OS, Kaplan-Meier analysis with log-rank test was used, and multivariate Cox proportional hazards regression identified independent prognostic factors. Variables were selected based on univariate P < 0.10 or clinical importance. OS was defined as the time elapsed from the initial date of nCRT to the date of death or the last follow-up. All statistical evaluations were conducted using a two-sided test, and a P < 0.05 was considered statistically significant.
RESULTS
Clinicopathologic characteristics
Table 1 comprehensively depicts the clinical data and MR image characteristics of 137 patients, along with a comparative analysis between the sarcopenia and non-sarcopenia groups. Using sarcopenia calculations and predefined cut-off values, it was determined that 35 patients (26.3%) exhibited sarcopenia, while 98 patients (73.7%) did not. Among the total patient population, 74.5% (n = 102) were classified as having downstaging, and a notable 35% (n = 48) achieved a good response characterized by a TRG of 0 or 1 after nCRT. The median follow-up time was 23 months (range: 3-102 months), and the median OS has not been reached due to a relatively low number of death events.
Table 1 Clinical and magnetic resonance image characteristics of non-sarcopenic and sarcopenic patients evaluated before neoadjuvant chemoradiotherapy for rectal cancer, n (%)/median (interquartile range).
Characteristics
Total (n = 133)
Non-sarcopenia (n = 98)
Sarcopenia (n = 35)
P value
Age (years)
56 (50, 64)
57 (50, 64)
56 (49, 66)
0.829
Maximum diameter of the tumor (mm)
37 (33, 45)
36 (33, 44)
40 (33.5, 46.5)
0.357
Length (mm)
56 (44, 68)
56 (44, 67.8)
57 (45, 69)
0.424
Short diameter of the largest lymph node (mm)
7 (5, 10)
7 (5, 10)
8 (5, 13)
0.718
Maximum diameter perpendicular to the intestinal wall on T2WI (mm2)
20 (15, 24)
20 (15, 24)
21 (15.5, 24.5)
0.272
Maximum cross-sectional area of the tumor on T2WI (mm2)
After completion of nCRT, post-treatment management and oncologic outcomes were further evaluated. All 137 patients included in the study subsequently underwent surgical resection, although detailed information regarding specific surgical procedures was unavailable due to incomplete operative records. The pCR was achieved in 23 patients (17%) based on postoperative pathological assessment. Additionally, 35 patients (25.5%) demonstrated a near-complete clinical response following nCRT. Regarding postoperative systemic therapy, 60 patients (43.8%) received adjuvant chemotherapy, while the remaining patients did not receive further systemic treatment due to clinical considerations or patient preference. Information regarding postoperative recurrence or metastatic status was not systematically available for all patients, primarily because long-term follow-up data were incomplete and some patients continued follow-up at external institutions. These data are presented descriptively to provide an overview of post-nCRT management in the study cohort.
Pretreatment sarcopenia did not demonstrate a significant association with either the response or OS after nCRT for RC. This was indicated by univariate (P = 0.062) and multivariate (P = 0.554) analyses (Table 2). These statistical approaches assessed the correlation between various predictive factors and tumor outcomes, specifically the response to nCRT (Tables 3 and 4) and OS (Table 5).
Table 2 Univariate analysis of sarcopenia for tumor regression grades, T downstaging, and overall survival.
In univariate analysis, baseline MRI features, specifically tumor length and MRF status, emerged as predictive factors for the response to neoadjuvant therapy in RC. Patients with shorter tumor lengths and negative MRF status were more likely to achieve a favorable treatment response. Conversely, among patients with longer tumor lengths, the likelihood of a poor response was 1.033 times greater than that of a good response (95%CI: 1.011-1.056, P = 0.004). Similarly, in patients with a positive MRF status, the probability of a poor response was significantly increased, 2.289 times that of a good response (95%CI: 1.119-4.777, P = 0.025). The multi-parameter analysis further confirmed the significance of tumor length as an independent predictor of treatment response (Table 3). Conversely, other factors did not exhibit a significant association with nCRT response. Additionally, ROC curve analyses were utilized to assess the predictive power of these factors, revealing an area under the curve of 0.657 for predicting a good response (Figure 2A).
Figure 2 The area under the curve.
A: The area under the curve of the longitudinal tumor diameter for predicting tumor regression grades following neoadjuvant therapy in rectal cancer was 0.657; B: The area under the curve for mesorectal fascia status in predicting tumor downstaging in patients with rectal cancer was 0.703.
In a univariate analysis, the clinical T stage and MRF status emerged as significant risk factors for downstaging in patients with RC undergoing nCRT. Notably, individuals with a lower clinical T stage and negative MRF status were more likely to achieve successful downstaging. Conversely, patients with a higher clinical T stage demonstrated a 4.928-fold increased risk of non-downstaging compared with those who achieved downstaging (95%CI: 2.170-12.340, P = 0.000). Similarly, in patients with a positive MRF status, the probability of non-downstaging was 4.556 times higher than that of downstaging (95%CI: 1.881-11.532, P = 0.001). Multivariate analysis further supported the independent predictive value of MRF status in determining downstaging outcomes (Table 4). Notably, the area under the curve of MRF in predicting downstaging in patients with RC was 0.703, indicating its relatively strong discriminatory power (Figure 2B).
Risk factors associated with OS
Logistic regression analysis revealed that node and MRF status were risk factors for OS following nCRT (Table 5). Patients without local lymph node metastasis and with MRF-negative status exhibited a higher likelihood of achieving a prolonged survival duration. Notably, node-positive patients demonstrated a 2.655-fold greater risk of mortality compared to node-negative patients (95%CI: 1.281-5.503, P = 0.009). Similarly, patients with a positive MRF status demonstrated a 2.149-fold increased risk of death compared to patients with a negative MRF status (95%CI: 1.005-4.596, P = 0.049). Figure 3 displays the survival curves for baseline lymph node and MRF status for predicting OS after nCRT in RC. However, in a multivariable analysis, neither node status nor MRF status emerged as independent predictors of OS.
Figure 3 The survival curves of baseline lymph node and mesorectal fascia status for predicting overall survival after neoadjuvant therapy in rectal.
MRF: Mesorectal fascia.
In the multivariate Cox regression model for OS, variables with P < 0.10 in univariate analysis – including node status, MRF status, signal heterogeneity, and clinical N stage – were entered. After adjustment, none of the variables remained statistically significant. Node positivity showed a borderline association with worse OS (hazard ratio = 2.199, 95%CI: 0.9645-5.014, P = 0.0609), while MRF positivity was non-significantly associated with OS (hazard ratio = 1.501, 95%CI: 0.636-3.543, P = 0.3537). Collectively, these findings indicate that although certain baseline imaging and clinical features may correlate with OS in univariate analysis, they do not independently predict long-term outcomes after adjustment for confounders.
DISCUSSION
This study aimed to evaluate whether pretreatment sarcopenia and tumor-related imaging parameters could predict treatment response and OS in patients with RC undergoing nCRT. Our results revealed that pretreatment sarcopenia was non-significantly associated with either treatment response or OS. Conversely, tumor length, MRF status, and clinical T/N stage emerged as significant predictors of both short-term and long-term outcomes. By integrating routinely available tumor-related imaging parameters and CT-based body composition assessment using population-specific sarcopenia criteria, this study provides clinically applicable information for pretreatment risk stratification in patients with RC.
Currently, prediction models for nCRT response in RC mainly rely on tumor burden, TNM stage, tumor markers, and imaging characteristics, including radiological and radiomics-based approaches. Among these factors, clinical T stage and positive MRF status have consistently been recognized as adverse prognostic indicators associated with lower pathological response rates and increased local recurrence. Sarcopenia, reflecting nutritional status and systemic inflammatory burden, has also been proposed as a potential biomarker for adverse oncologic outcomes across multiple malignancies. In RC, multiple studies have reported associations between sarcopenia and poor postoperative outcomes or inferior long-term survival, notably in elderly patients or those receiving intensive neoadjuvant regimens. However, the role of sarcopenia in predicting treatment response and survival in RC remains controversial. While some studies have identified sarcopenia as an independent predictor of poor response to nCRT and reduced survival[30-32], others, consistent with our findings, failed to exhibit a significant association between pretreatment sarcopenia and oncologic outcomes[26,33].
Several factors may explain the lack of prognostic significance of sarcopenia observed in our cohort. First, heterogeneity in the definition and diagnostic thresholds of sarcopenia across studies may contribute to inconsistent results. Although we applied Chinese-specific L3SMI cut-off values[33,34], which are considered appropriate for the local population, substantial variability in sarcopenia definitions persists internationally. For instance, Abe et al[26] used a different sarcopenia metric (psoas MSI) with cohort-specific cut-off values. They demonstrated that post nCRT sarcopenia, rather than pretreatment sarcopenia, is independently associated with worse long-term oncologic outcomes, including disease-free and OS. In contrast, our study primarily evaluated pretreatment sarcopenia and pretreatment MRI-derived tumor parameters in relation to treatment response and survival, which may partly explain the discrepant findings. Second, the modest prevalence of sarcopenia in our cohort (26.3%, compared with 25%-68% reported in other studies) may have limited the statistical power to detect significant associations. Although our cohort was larger than several studies reporting positive results[33,35], studies with even larger sample sizes have yielded mixed findings, suggesting that sample size alone does not fully account for the observed heterogeneity. Additionally, variations in CT acquisition parameters and the retrospective nature of the study may have introduced measurement variability, potentially affecting the assessment of skeletal muscle mass[36,37]. These technical factors, which are often underreported, underscore the need for standardized imaging protocols in sarcopenia research. Finally, sarcopenia in RC may exert a greater influence on long-term oncologic outcomes or post-treatment disease progression rather than on immediate tumor regression or short-term survival following nCRT. In this context, differences in follow-up duration and event rates between studies may further contribute to inconsistent conclusions. Taken together, the discrepancy between our findings and those of studies such as Abe et al[26] emphasizes the need for prospective investigations with larger cohorts, standardized sarcopenia definitions, and longitudinal assessment of muscle changes to better clarify the prognostic role of sarcopenia in RC.
In contrast to sarcopenia, tumor-related imaging parameters reflecting local tumor extent demonstrated more consistent prognostic relevance in our study. Previous research has demonstrated that MRI-based parameters, including tumor length, depth of invasion, and MRF involvement, are closely associated with pathological response and survival outcomes in RC[27,38]. Our findings are concordant with this evidence, reaffirming that patients with shorter tumor length and negative MRF status are more likely to achieve tumor downstaging and favorable TRGs[39,40]. Furthermore, clinical T stage and nodal status were associated with OS, consistent with earlier studies demonstrating that advanced stage and lymph node involvement predict poorer long-term survival[41,42]. These tumor-related parameters are particularly valuable because they are routinely available at diagnosis and can inform early risk stratification and treatment planning.
We acknowledge that the median OS of 23 months observed in our study is relatively short. This may be due to several factors, including the high recurrence risk in patients with locally advanced rectal cancer despite nCRT. A significant portion of our cohort displayed advanced-stage disease, which is associated with poorer prognosis, and many patients did not achieve a complete response to nCRT. Additionally, some patients experienced disease progression despite treatment. Notably, the median OS has not yet been reached, given the relatively low number of deaths, which could have influenced the survival calculation. The 23-month follow-up period may not fully capture long-term survival outcomes, as recurrences or metastases may occur beyond this time. In conclusion, the relatively short median OS is likely due to a combination of patient factors, advanced disease, incomplete nCRT response, and disease progression. Further studies with longer follow-up periods will be needed to fully understand the long-term survival outcomes.
This study has several limitations. The retrospective, single-center design may limit the generalizability of our findings. The cohort included only 137 patients, reducing statistical power to detect modest effects of sarcopenia on treatment response and survival. While the sample size is larger than that in previous studies linking sarcopenia to poor prognosis in RC[33,35], it remains small compared to multicenter or large-cohort studies, increasing the risk of type II errors. Granular post-nCRT treatment data, including detailed surgical procedures and metastasis status, were unavailable due to incomplete medical records and limitations in follow-up inherent to retrospective analyses. Although information on overall surgical management and adjuvant chemotherapy was available, missing data on surgical subtypes and metastatic outcomes may have limited more detailed post-treatment analyses. Additionally, variations in imaging protocols and potential interobserver variability may have influenced tumor-related imaging accuracy[36,37]. The L3SMI is widely used to assess muscle mass; however, it does not capture muscle function or quality, which are increasingly recognized as important components of sarcopenia[43,44]. Future multicenter studies with standardized imaging protocols and comprehensive outcome data are required to further clarify host- and tumor-related factors in RC[38,45].
CONCLUSION
This study finds that pretreatment sarcopenia is not an independent predictor of treatment response or OS in patients with RC undergoing nCRT. Conversely, tumor-related factors, including tumor length, MRF involvement, and clinical T/N stage, are stronger predictors of both short- and long-term outcomes. These findings underscore the value of tumor-related imaging parameters in pretreatment risk stratification and personalized treatment planning for RC.
Maas M, Nelemans PJ, Valentini V, Das P, Rödel C, Kuo LJ, Calvo FA, García-Aguilar J, Glynne-Jones R, Haustermans K, Mohiuddin M, Pucciarelli S, Small W Jr, Suárez J, Theodoropoulos G, Biondo S, Beets-Tan RG, Beets GL. Long-term outcome in patients with a pathological complete response after chemoradiation for rectal cancer: a pooled analysis of individual patient data.Lancet Oncol. 2010;11:835-844.
[RCA] [PubMed] [DOI] [Full Text][Cited by in Crossref: 1651][Cited by in RCA: 1504][Article Influence: 94.0][Reference Citation Analysis (4)]
Fearon K, Strasser F, Anker SD, Bosaeus I, Bruera E, Fainsinger RL, Jatoi A, Loprinzi C, MacDonald N, Mantovani G, Davis M, Muscaritoli M, Ottery F, Radbruch L, Ravasco P, Walsh D, Wilcock A, Kaasa S, Baracos VE. Definition and classification of cancer cachexia: an international consensus.Lancet Oncol. 2011;12:489-495.
[RCA] [PubMed] [DOI] [Full Text][Cited by in Crossref: 4755][Cited by in RCA: 4136][Article Influence: 275.7][Reference Citation Analysis (4)]
Miyake M, Morizawa Y, Hori S, Marugami N, Iida K, Ohnishi K, Gotoh D, Tatsumi Y, Nakai Y, Inoue T, Anai S, Torimoto K, Aoki K, Tanaka N, Shimada K, Konishi N, Fujimoto K. Integrative Assessment of Pretreatment Inflammation-, Nutrition-, and Muscle-Based Prognostic Markers in Patients with Muscle-Invasive Bladder Cancer Undergoing Radical Cystectomy.Oncology. 2017;93:259-269.
[RCA] [PubMed] [DOI] [Full Text][Cited by in Crossref: 39][Cited by in RCA: 61][Article Influence: 6.8][Reference Citation Analysis (0)]
Berkel AEM, Klaase JM, de Graaff F, Brusse-Keizer MGJ, Bongers BC, van Meeteren NLU. Patient's Skeletal Muscle Radiation Attenuation and Sarcopenic Obesity are Associated with Postoperative Morbidity after Neoadjuvant Chemoradiation and Resection for Rectal Cancer.Dig Surg. 2019;36:376-383.
[RCA] [PubMed] [DOI] [Full Text][Cited by in Crossref: 39][Cited by in RCA: 33][Article Influence: 4.1][Reference Citation Analysis (0)]
Takeda Y, Akiyoshi T, Matsueda K, Fukuoka H, Ogura A, Miki H, Hiyoshi Y, Nagasaki T, Konishi T, Fujimoto Y, Fukunaga Y, Ueno M. Skeletal muscle loss is an independent negative prognostic factor in patients with advanced lower rectal cancer treated with neoadjuvant chemoradiotherapy.PLoS One. 2018;13:e0195406.
[RCA] [PubMed] [DOI] [Full Text] [Full Text (PDF)][Cited by in Crossref: 65][Cited by in RCA: 63][Article Influence: 7.9][Reference Citation Analysis (0)]
Cruz-Jentoft AJ, Bahat G, Bauer J, Boirie Y, Bruyère O, Cederholm T, Cooper C, Landi F, Rolland Y, Sayer AA, Schneider SM, Sieber CC, Topinkova E, Vandewoude M, Visser M, Zamboni M; Writing Group for the European Working Group on Sarcopenia in Older People 2 (EWGSOP2), and the Extended Group for EWGSOP2. Sarcopenia: revised European consensus on definition and diagnosis.Age Ageing. 2019;48:601.
[RCA] [PubMed] [DOI] [Full Text] [Full Text (PDF)][Cited by in Crossref: 2270][Cited by in RCA: 1847][Article Influence: 263.9][Reference Citation Analysis (4)]
Chen LK, Woo J, Assantachai P, Auyeung TW, Chou MY, Iijima K, Jang HC, Kang L, Kim M, Kim S, Kojima T, Kuzuya M, Lee JSW, Lee SY, Lee WJ, Lee Y, Liang CK, Lim JY, Lim WS, Peng LN, Sugimoto K, Tanaka T, Won CW, Yamada M, Zhang T, Akishita M, Arai H. Asian Working Group for Sarcopenia: 2019 Consensus Update on Sarcopenia Diagnosis and Treatment.J Am Med Dir Assoc. 2020;21:300-307.e2.
[RCA] [PubMed] [DOI] [Full Text][Cited by in Crossref: 5704][Cited by in RCA: 4866][Article Influence: 811.0][Reference Citation Analysis (1)]
Qin P, Chen H, Wang Y, Huang L, Huang K, Xiao G, Han C, Hu J, Lin D, Wan X, Zheng Y, Liu Y, Li G, Yang H, Ye S, Luo M, Fu Y, Xu H, Wen L, Guo Z, Shen X, Li Z, Wang C, Chen X, Wang L, Sun L, Ren D, Wu L, Wang J, Liu S, Lin H. Cancer-associated fibroblasts undergoing neoadjuvant chemotherapy suppress rectal cancer revealed by single-cell and spatial transcriptomics.Cell Rep Med. 2023;4:101231.
[RCA] [PubMed] [DOI] [Full Text] [Full Text (PDF)][Cited by in Crossref: 52][Cited by in RCA: 45][Article Influence: 15.0][Reference Citation Analysis (0)]
Footnotes
Peer review: Externally peer reviewed.
Peer-review model: Single blind
Specialty type: Oncology
Country of origin: China
Peer-review report’s classification
Scientific quality: Grade B
Novelty: Grade B
Creativity or innovation: Grade B
Scientific significance: Grade C
P-Reviewer: Rajendran N, MD, Associate Professor, United Kingdom S-Editor: Luo ML L-Editor: A P-Editor: Zhao YQ
