Predictors of pathological complete response after neoadjuvant chemoradiotherapy for locally advanced rectal cancer

Predictors of pathological complete response after neoadjuvant chemoradiotherapy for locally advanced rectal cancer | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Predictors of pathological complete response after neoadjuvant chemoradiotherapy for locally advanced rectal cancer Haythem Yacoub, Yosr Zenzri, Dhouha Cherif, Hajer Ben Mansour, and 5 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4469099/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 31 Mar, 2025 Read the published version in BMC Gastroenterology → Version 1 posted 18 You are reading this latest preprint version Abstract Background: Neoadjuvant chemoradiotherapy (NCRT) has become a standard treatment approach for locally advanced rectal cancer (LARC). Patients achieving pathological complete response (pCR) following NCRT have better outcomes (overall survival, relapse free survival). However, not all patients treated for LARC with neoadjuvant treatment achieve pCR. Aim: The aim of our study was to assess the rate and predictors of pCR. Materials and Methods: We performed a retrospective study at medical oncology unit in a tertiary care teaching hospital. All consecutive LARC patients without any evidence of distant metastasis who underwent neoadjuvant chemoradiotherapy and surgery between June 2020 and January 2023 were included in the research. Pathological response to NCRT was assessed using Mandard grading system and response was categorized as pCR or not‑pCR. Two different standardized protocols for the neoadjuvant treatment were used: the first group was treated with induction chemotherapy followed by short course radiotherapy and the second group was treated with the RAPIDO protocol. Correlation between different studied parameters and pCR was determined using univariate and multivariate logistic regression analysis Results: The mean age of the 91 included patients (46 men and 45 women) was 58.53 ± 10.3 years. Twenty (22%) were found to have a pCR (Mandard TRG1) in the operative specimen. In univariate analysis, patients less than 60 years, continuation of chemotherapy and patients treated with the induction chemotherapy followed by short course radiotherapy showed a better pCR as compared to patients treated with Rapido protocol (p = 0.043, p=0.0001 and p=0.021 respectively). Patients with mucinous component had low pCR rates (p =0.021). On logistic regression analysis, chemotherapy continuation (OR = 10.27, 95% CI = 2,14–49.32), and absence of mucinous component (OR = 12.6, 95% CI = 3.1–40.32) were significant predictors of pCR. The median survival was 37.7 months. Conclusion: Mucinous component and chemotherapy interruption are associated with lower pCR rates. Integrating these factors into personalized treatment algorithms may help optimize therapeutic strategies and improve outcomes for patients with LARC. Figures Figure 1 Introduction Neoadjuvant chemoradiotherapy (NCRT) has become a cornerstone of treatment for Locally advanced rectal cancer (LARC), aiming to increase rates of sphincter preservation, and improve oncological outcomes. Despite advancements in treatment modalities, the response to neoadjuvant NCRT varies among patients, with only a subset achieving a pathological complete response (pCR), defined as the absence of viable tumor cells in the surgical specimen after surgery [ 1 ]. Patients who achieve pCR demonstrate significantly improved long-term oncological outcomes, including higher rates of relapse-free survival and overall survival. pCR can generally be achieved in 15–27% of the patients treated with NRCT, while as around 54–75% show partial or absence of response [ 2 , 3 ]. The ability to predict which patients are more likely to achieve pCR following NCRT holds substantial clinical implications. Moreover, identifying predictors of pCR can facilitate treatment decision-making, tailoring therapeutic strategies The primary aim of our study was to identify the impact of patient characteristics, tumor size, tumor stage, location at presentation, circumferential extent, and pretreatment CEA levels on the occurrence of pCR after neoadjuvant treatment and. For our study, the primary measured outcome was pathologic complete response. Patients and methods We performed a retrospective study at medical oncology unit in a tertiary care teaching hospital. All consecutive locally advanced primary rectal adenocarcinoma patients without any evidence of distant metastasis who underwent neoadjuvant chemoradiotherapy and surgery between June 2020 and December 2022 were included in the research. The study was approved by the institutional review board at the Salah Azaiez Institute of Tunisia. All informations regarding demographic data (gender, age), stage at presentation, routine hemograms, biochemical test results, administrated treatment were obtained prospectively from the medical record. A colonoscopy/flexible sigmoidoscopy and proctoscopy were performed on all patients. The confirmation of diagnosis was obtained after histopathological examination before starting treatment. Magnetic resonance imaging (MRI) of the pelvis and contrast-enhanced computed tomography of the chest, abdomen and pelvis were done for pre-operative staging. Excluded patients from the study were those with metastatic disease, non-operated patients, and those treated with neoadjuvant radiation alone. Neoadjuvant protocols: During the study period, two different standardized protocols for the neoadjuvant treatment were used. Patients were sanded into two groups: The first group was treated with 6 injections of mFOLFIRINOX followed by short course radiotherapy at a dose of 25 Gy. External beam radiotherapy was given over 5 days a week with daily dose of 5 Gy. After radiotherapy patients received 2 injections of mFOLFOX (Oxaliplatin 85mg/m 2 , 5-Fluorouracil: 2500mg continuous infusion over 48 hours (Days 1 and 2), leucovorin [folinic acid] 400mg/m 2 . Surgery was performed after 8 weeks following last dose of radiotherapy. The second group was treated with the RAPIDO protocol: patients received short-course radiotherapy (5*5 Gy over a maximum of 8 days) followed by 6 cycles of CAPOX chemotherapy (capecitabine 1000mg/m2 orally twice daily on days 1–14, oxaliplatin 130 mg/m2 iv) or 9 cycles of FOLFOX4 (Oxaliplatin 85mg/m 2 on day 1, and fluorouracil 1600mg/m2 iv continuous infusion over 48h on days 1 and 2, leucovorin [folinic acid] 400mg/m 2 ). Pathological staging: Three categories were used to categorize the tumor grade based on the initial tumor biopsy samples: low, moderate and high differentiated tumor. Histopathological features of mucinous component (> 50%) and signet ring cells were also noted. After surgery, resected specimens were subjected to histopathological examination, which was done by an experienced pathologist. According to Mandard grading system, treatment response was categorized as pCR (TRG1) or not pCR (TRG 2–5). Pathologic complete response was defined as the absence of viable tumor cells in the rectum and in any of the resected lymph nodes in the surgical specimen. Statistical analysis All the Statistical analysis were carried through Statistical Package for the Social Sciences (SPSS) version 23, IBM SPSS Inc.; Chicago, IL, USA). Continuous variables that followed a normal distribution were expressed as mean ± standard deviation and range while results for the variables that did not follow a normal distribution have been shown in median and the interquartile range. The categorical variables were expressed in the form of frequency and percentage. For comparisons, Student’s t-test was used for quantitative variables. A univariate analysis using chi-squared tests for dichotomous variable was conducted to identify the possible associated factors between the categorical variables and pCR. A multivariate analysis was carried out with variables that achieved statistical significance using logistic regression modeling. P value ≤ 0.05 was the established level of statistical significance. We defined disease free survival (DFS) as the time from diagnosis to local or distant recurrence or censored at date of last follow-up. DFS and OS curves were generated using the Kaplan-Meier method. Differences were assessed using the log-rank test. Results Baseline patients characteristics A total of 91 patients (46 men and 45 women) were included in the study. Mean age of patients was 58.53 ± 10.3 years [ range 28–80 years]. The tumor histology consisted of well-differentiated adenocarcinoma in 19 (20.9%), moderately differentiated adenocarcinoma in 37 (40.6%), poorly differentiated adenocarcinoma in 35 (38.5%), and signet ring cell in 17 (18.7%) patients. The median initial CEA concentration was 6.97 ng/ml (range from 0.55 to 139 ng/ml). Pelvic MRI was the most commonly performed staging method (87.9%). All patients underwent surgery: anterior resection in 67 (73.6%), abdominoperineal resection in 23 (25.3%) patients. The median duration of surgery following last dose of NACRT was 9 weeks. pCR (TRG1) was achieved in 20 patients (22%). 71 patients (78%) showed some form of regression or no response (TRG 2–5). Baseline patient characteristics are summarized in Table 1 . The mean follow up of patients was 20.2 months. Distribution of pretreatment and treatment variables according to received protocol were summarized in Table 2 . Predictors of pCR Young patients less than 60 years had significantly better pCR rates as compared to those more than 60 years (p = 0.043). Patients treated with the induction chemotherapy followed by short course radiotherapy showed a better pCR as compared to patients treated with Rapido protocol (p = 0.013). Patients with mucinous component had low pCR rates (p = 0.021). In univariate analysis, the differences in pCR rates among gender, initial carcino embryonic antigen (CEA) levels, T stage and N stage were not significantly associated with pCR. Time to surgery (between the last dose of radiotherapy to surgery) was not a predictive factor for pCR (8.83 weeks in patient with pCR Vs 11.46 weeks in patients without pCR, p = 0.246). Table 3 summarizes univariate analysis of various predictive factors for pCR. Table 1 Baseline patients characteristics n (%) Mean age (years) 58.53 ± 10.3 Gender Male Female 46 (50.5) 45 (49.5) Median CEA (ng/ml) 6.97 T stage T2 T3 T4 5 (5.5) 71 (78) 15 (16.5) N stage N0 N1 N2 3 (3.3) 44 (48.4) 44 (48.4) Grade Well differentiated Moderately differentiated Poorly differentiated Mucinous Signet ring cell 19 (20.9) 37 (40.6) 35 (38.5) 18 (19.8) 17 (18.7) Site of the tumor Lower rectum Middle rectum 39 (42.9) 52 (57.1) Staging method Pelvic CT scan Pelvic MRI 11 (12.1) 80 (87.9) Neoadjuvant protocol Induction chemotherapy Rapido protocol 61 (67) 30 (33) Type of surgery Low anterior resection Abdominoperineal resection Hartmann operation 67 (73.6) 23 (25.3) 1 (1.1) Average radiation dose (Gy) 25 CEA: Carcinoembryonic antigen, CT: computed tomography, MRI: Magnetic resonance imaging, Gy: Gray Table 2 Distribution of pretreatment and treatment variables according to received protocol Study variables Induction chemotherapy (n,%) Short course radiotherapy (n,%) P Gender Male Female 30 (49.2) 31 (50.8) 16 (53.3) 14 (46.7) 0.716 CEA pretreatment level (mean) 14.35 7.08 0.516 T stage T2 T3 T4 3 (4.9) 51 (83.6) 7 (11.5) 2 (6.7) 20 (66.7) 8 (26.6) 0.734 N stage N (-) N (+) 3 (4.9) 58 (95.1) 0(0) 30(100) 0.287 Grade Well differentiated Moderately differentiated Poorly differentiated Signet ring cell 9 (14.7) 27 (44.3) 25 (41) 8 (13.1) 10 (33.3) 10 (33.3) 10 (33.3) 9 (30) 0.494 Site of the tumor Lower rectum Middle rectum 38 (62.3) 23 (37.7) 14 (46.7) 16 (53.3) 0.167 Type of surgery Resection Hartmann operation 60 (98.4) 1 (1.6) 30 (100) 0 (0) 0.380 Chemotherapy interruption Yes No 38(62.3) 23(37.7) 1 (0.3) 29 (99.7) 0.00001 Mucinous component Yes No 8 (13.1) 53 (86.9) 10 (33.3) 20 (66.7) 0.015 CEA: Carcinoembryonic antigen Table 3 Univariate analysis of predictors for pathologic complete response Study variables pCR (n,%) No pCR (n,%) P Gender Male Female 10 (11) 10 (11) 36 (39.5) 35 (38.5) 0.956 Age < 60 years ≥ 60 years 16 (17.6) 4 (4.4) 39 (42.8) 32 (35.2) 0.043 ECA pretreatment level (mean) 9.08 13.49 0.516 T stage T2 T3 T4 2 (2.2) 13 (14.3) 5 (5.5) 3 (3.3) 58 (63.7) 10 (11) 0.268 N stage N (-) N (+) 1 (1.1) 19 (31.2) 2(2.2) 69(65.5) 0.629 Grade Well differentiated Moderately differentiated Poorly differentiated Signet ring cell 10 (11) 18 (19.8) 17 (18.6) 8 (8.8) 9 (9.9) 19 (20.9) 18 (19.8) 9 (9.9) 0.755 Site of the tumor Lower rectum Middle rectum 11 (12.1) 9 (9.9) 41 (45) 30 (33) 0.826 Time to surgery (weeks) 8.83 11.46 0.246 Neoadjuvant protocol Induction chemotherapy Rapido protocol 18 (19.8) 2 (2.2) 43 (67) 28 (33) 0.013 Type of surgery Resection Hartmann operation 19 (20.9) 1 (1.1) 71 (78) 0 (0) 0.058 Chemotherapy interruption Yes No 1(1.1) 19(31.2) 38 (31.4) 33 (36.3) 0.0001 Mucinous component Yes No 0 (0) 18 (19.8) 18 (19.8) 55 (60.4) 0.018 pCR = pathological complete response, CEA: Carcinoembryonic antigen On logistic regression analysis, chemotherapy continuation (OR = 10.27, 95% CI = 2,14–49.32), and mucinous component (OR = 12.6, 95% CI = 3.1–40.32) were significant predictors of pCR [Table 4 ]. Table 4 Multivariate analysis of predictors for pathologic complete response Study variables pCR (n,%) No pCR (n,%) P OR Age < 60 years ≥ 60 years 16 (17.6) 4 (4.4) 39 (42.8) 32 (35.2) 0.450 1.88[0.36–9.81] Neoadjuvant protocol Induction chemotherapy Rapido protocol 18 (19.8) 2 (2.2) 43 (67) 28 (33) 0.067 4.36[0.9-21.14] Chemotherapy interruption Yes No 1(1.1) 19(31.2) 38 (31.4) 33 (36.3) 0.04 10.27 [2.14–49.32] Mucinous component Yes No 0 (0) 18 (21.2) 16 (18.8) 69 (60) 0.021 12.6 [3.1-40.32] OR = Odds ratio, CI = Confidence interval, pCR = pathological complete response Overall survival (OS): The median survival was 37.7 months. The OS is represented in Fig. 1 a. There was no significant difference in OS between patients achieving pCR and those without achieving pCR (Fig. 1 b) and patients treated with different protocols (Fig. 1 c). Discussion Neoadjuvant chemoradiotherapy (NCRT) followed by total mesorectal excision for locally advanced rectal cancer (LARC) has become a standard treatment approach due to its good results in downstaging tumors. NCRT increase the likelihood of sphincter preservation, and improve local control of the disease. However, not all patients treated for LARC with neoadjuvant treatment achieve a pathological complete response (pCR). pCR is associated with better long-term outcomes including improved relapse-free survival and overall survival. Understanding the predictors of pCR is crucial for optimizing treatment strategies and identifying patients who may benefit most from neoadjuvant therapy especially in the era of total neoadjuvant therapy and watch-and-wait surveillance approach [ 4 , 5 ]. The watch and wait strategy may have the benefit of avoiding surgery [ 6 ]. The pathological response to NCRT in the most studies varies among individuals. Achieving pCR varies from 15–27% of the patients. However, around 54–75% show partial or absence of response after NCRT [ 2 – 3 ]. Mehraj et al, reported in their study that pCR defined as Mandard Gr 1 was obtained in (18.6%) patients [ 7 ]. In our study, pCR was achieved in 22% of patients. Recently, there has been increased interest in the concept of total neoadjuvant treatment (TNT). TNT was defined as chemotherapy induction and/or consolidation in conjunction with classical standard chemoradiotherapy prior to surgery. It is believed that TNT increases the rate of pCR by addressing occult micro-metastatic disease. A 2020 published meta-analysis showed a pCR rate of 22.4% in the TNT cohort, and it was associated with a 39% increase in the odds of achieving pCR compared to other strategies (1.40, 95% CI 1.08–1.81, p = 0.01) [ 8 ]. In this study, we investigated various clinical, biochemical, radiological and pathological factors as potential predictors of pCR following NCRT for LARC. The purpose of this study was to assess preoperative predictors of pCR after NCRT. Patient-related factors play a crucial role in predicting pCR after NCRT. Age, performance status (PS), nutritional status and comorbidities, may influence clinical and pathological treatment outcomes (OS, DFS and pCR). Younger patients and those with PS ranging from 0 to 2 are more likely to achieve pCR. However, patients with significant comorbidities, impaired PS (3–4) may have reduced tolerance to treatment and consequently lower rates of pCR. In our study and in univariate analysis, we found that patient less than 60 years had significantly better pCR rates as compared to those more than 60 years (p = 0.043). The data in the literature concerning patient age as a predictive factor for pCR are discordant. In fact, a recent meta-analysis showed that elderly patients achieved higher pCR rates (p = 0.0002) [ 9 ]. Most studies have found lower CEA level is associated with pCR. A systematic review and meta-analysis confirmed those findings and concluded that CEA level was inversely correlated with pCR rates [ 10 ]. In the literature, an association between interruption of chemotherapy and pCR was demonstrated. Patients with an interruption in their neoadjuvant therapy because of treatment-related toxicity, were less likely to develop pCR [ 11 ]. Lymph node regression grade is a good indicator of response to preoperative NCRT and several studies showed that NCRT has been associated with a low pN (+) rate in locally advanced rectal cancer. Histopathological findings in positive lymph nodes after chemoradiotherapy include residual cancer cells, hemorrhage, areas of hyalinosis, cystic cell reactions, and pools of mucin [ 12 , 13 ]. The impact of lymph node status on neoadjuvant chemoradiotherapy treatment response in LARC has been studied in several studies. Huang et al. showed that patient without lymph node involvement was a positive predictor of pCR (P < 0.00001) for rectal cancer following neoadjuvant chemoradiotherapy [ 9 ]. Performing an additional lateral lymph node dissection has been studied after NCRT in recent years. A meta-analysis showed that lateral lymph during total mesorectal excision reduces local recurrence risk, but does not impact oncological outcomes (disease-free or overall survival) [ 14 ]. The treatment protocols for LARC are various. The addition of induction chemotherapy to concomitant neoadjuvant chemoradiation in LARC could increase pCR rate. A systematic review showed that the addition of induction/consolidation chemotherapy to standard NCRT results in a higher pCR rate [ 15 ]. In our study, patients treated with induction chemotherapy followed by short course radiotherapy prior to surgery showed a better pCR as compared to patients treated with short course radiotherapy. The effect of TNT on oncological outcomes has not been fully investigated. Several studies and a meta-analysis showed that disease-free survival was not associated with the type of neoadjuvant treatment (hazard ratio [HR] 1.3; 95% CI : 0.93–1.80; p = 0.12) [ 16 , 17 ]. Considering initial and definitive histopathological tumor features, three studies found no significant difference in terms of pCR [ 18 – 20 ]. A systematic review and meta-analysis found that mucinous component was associated with poor p CR [ 21 ]. In our study, a number of factors were independent predictors of pCR, including the absence of chemotherapy interruption (OR = 10.27, 95% CI = 2,14–49.32), and absence of mucinous component (OR = 12.6, 95% CI = 3.1–40.32). These factors predicting pCR require validation in prospective multicenter studies order to be incorporated into WW strategies. Due to the retrospective nature of our study, there are certain limitations that it is important to acknowledge. Despite our efforts to minimize missing data, we encountered some challenges. Specifically, CEA levels were missing in some patient’s records. Additionally, duration of chemotherapy interruption was not mentioned. Despite advances in our understanding of predictors of pCR after NCRT for LARC, several challenges are remaining. These challenges come from the fact that patient populations are heterogeneous, and there are big variations in treatment regimens. The differences in study methodologies make comparisons between studies difficult. Further research into novel biomarkers, personalized treatment approaches and risk models and algorithms based on artificial intelligence are required. Conclusion Our study identified several predictors of pathological complete response following NCRT for LARC. Integrating these factors into personalized treatment algorithms may help optimize therapeutic strategies and improve oncological outcomes for patients with LARC. Further prospective studies are warranted to validate these findings and refine predictive models. Declarations Acknowledgements: Not applicable. Authors’ contributions: H.Y: concept, design, definition of intellectual content, literature search, manuscript preparation, manuscript editing, manuscript review. Y.Z: concept, design, definition of intellectual content, manuscript preparation, manuscript review. D.C.: Definition of intellectual content, manuscript preparation, design, manuscript review. H.B.M: Definition of intellectual content, design N.A.: Definition of intellectual content, manuscript preparation. C.M.: Definition of intellectual content, manuscript preparation. K.B.Z.: Definition of intellectual content, manuscript preparation. F.L.: design, manuscript review. A.M.: Manuscript review. All authors read and approved the final manuscript. Funding: Not applicable. Availability of data and materials: The data that support the fndings of this study are available on request from the corresponding author, [HY]. The data are not publicly available due to [restrictions e.g. their containing information that could compromise the privacy of research participants]. Declarations Ethics approval and consent to participate: This study was performed according to the Declaration of Helsinki, following the guidelines for good clinical practice. “Salah Azaiz institute ethics committee” approved the study protocol. All methods were carried out in accordance with relevant guidelines and regulations. Informed consent to participate in the study was obtained from participants. Consent for publication : Not applicable. Competing interests: The authors declare that they have no competing interests References Smith K, Jones A, Doe J, et al. 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Cite Share Download PDF Status: Published Journal Publication published 31 Mar, 2025 Read the published version in BMC Gastroenterology → Version 1 posted Editorial decision: Revision requested 23 Dec, 2024 Reviews received at journal 23 Dec, 2024 Reviewers agreed at journal 17 Dec, 2024 Reviews received at journal 16 Dec, 2024 Reviews received at journal 14 Dec, 2024 Reviews received at journal 13 Dec, 2024 Reviewers agreed at journal 13 Dec, 2024 Reviewers agreed at journal 12 Dec, 2024 Reviewers agreed at journal 11 Dec, 2024 Reviewers agreed at journal 11 Dec, 2024 Reviewers agreed at journal 11 Dec, 2024 Reviewers agreed at journal 10 Aug, 2024 Reviewers agreed at journal 08 Aug, 2024 Reviewers invited by journal 01 Aug, 2024 Editor invited by journal 03 Jun, 2024 Editor assigned by journal 27 May, 2024 Submission checks completed at journal 27 May, 2024 First submitted to journal 23 May, 2024 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4469099","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":311523388,"identity":"3667a14d-bf76-4172-8404-5feb5d939c51","order_by":0,"name":"Haythem Yacoub","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABAUlEQVRIiWNgGAWjYLACxoYDQJIHiCsOgAUOPCBKCxtIy5kDYJ0HEojWwtgG0cKAT4vB8cMPH/PuuCNvcL/34KOb8+7I2Ysdfgi0xU5OtwGHljNpxsa8Z54ZbjjGl2ycu+2ZMY90mgFQS7Kx2QEcWg7ksEnzth1m3HCMx0w6d9vhxB7pBJCWA4nbcGk5/wasxR6oxfx37hyQlvQP+LXcgNiSCLKFObcBpCUHvy2SN54ZG849czh55rEcY+mcY4eNeW7nFBxIMMDtF77zyQ8fvN1x2Lbv8BnDzzk1h+XYZ6dv/vChwk4OlxaFA+gMqIOxKwcB+QZ0xigYBaNgFIwCdAAAnIxs0ZwvJr8AAAAASUVORK5CYII=","orcid":"","institution":"La Rabta Hospital","correspondingAuthor":true,"prefix":"","firstName":"Haythem","middleName":"","lastName":"Yacoub","suffix":""},{"id":311523389,"identity":"abeca0d9-8f86-46a2-853d-2cc9ae92fa6b","order_by":1,"name":"Yosr Zenzri","email":"","orcid":"","institution":"Salah Azaiez Institute","correspondingAuthor":false,"prefix":"","firstName":"Yosr","middleName":"","lastName":"Zenzri","suffix":""},{"id":311523390,"identity":"050d2200-e4bc-497c-8d3a-35770469f10f","order_by":2,"name":"Dhouha Cherif","email":"","orcid":"","institution":"La Rabta Hospital","correspondingAuthor":false,"prefix":"","firstName":"Dhouha","middleName":"","lastName":"Cherif","suffix":""},{"id":311523391,"identity":"1c04588e-63e9-4521-bbd5-6a4a0b6c92b5","order_by":3,"name":"Hajer Ben Mansour","email":"","orcid":"","institution":"Salah Azaiez Institute","correspondingAuthor":false,"prefix":"","firstName":"Hajer","middleName":"Ben","lastName":"Mansour","suffix":""},{"id":311523392,"identity":"697f2303-2906-4646-8d7e-19a9a04a14a0","order_by":4,"name":"Najla Attia","email":"","orcid":"","institution":"Salah Azaiez Institute","correspondingAuthor":false,"prefix":"","firstName":"Najla","middleName":"","lastName":"Attia","suffix":""},{"id":311523393,"identity":"7d80598a-b67d-4f07-b94e-b23149554416","order_by":5,"name":"Cyrine Mokrani","email":"","orcid":"","institution":"Salah Azaiez Institute","correspondingAuthor":false,"prefix":"","firstName":"Cyrine","middleName":"","lastName":"Mokrani","suffix":""},{"id":311523395,"identity":"10c1e325-713f-4807-b45c-f45f38fc25dc","order_by":6,"name":"Khadija Ben Zid","email":"","orcid":"","institution":"Salah Azaiez Institute","correspondingAuthor":false,"prefix":"","firstName":"Khadija","middleName":"Ben","lastName":"Zid","suffix":""},{"id":311523397,"identity":"d4dad954-04fe-46ea-8691-77a8feae78b4","order_by":7,"name":"Feryel Letaief","email":"","orcid":"","institution":"Salah Azaiez Institute","correspondingAuthor":false,"prefix":"","firstName":"Feryel","middleName":"","lastName":"Letaief","suffix":""},{"id":311523398,"identity":"0fd6a2aa-3508-4550-986e-df16b539f719","order_by":8,"name":"Amel Mezlini","email":"","orcid":"","institution":"Salah Azaiez Institute","correspondingAuthor":false,"prefix":"","firstName":"Amel","middleName":"","lastName":"Mezlini","suffix":""}],"badges":[],"createdAt":"2024-05-23 22:23:16","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4469099/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4469099/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s12876-025-03709-1","type":"published","date":"2025-03-31T15:56:50+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":58170033,"identity":"abc55209-bce8-4961-b7a1-b589b4212806","added_by":"auto","created_at":"2024-06-12 03:36:19","extension":"jpeg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":405260,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003e(a)The Kaplan–Meier curve analysis of OS (b) Overall survival for pCR (c) Overall survival according to received protocol\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"floatimage27.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-4469099/v1/6b9c5172bfcabca76f2db416.jpeg"},{"id":80081908,"identity":"b0588cdf-e832-4df5-99ae-757570cab481","added_by":"auto","created_at":"2025-04-07 16:00:36","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1283192,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4469099/v1/3f24323a-dd1a-4003-acd3-d4baa415604d.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Predictors of pathological complete response after neoadjuvant chemoradiotherapy for locally advanced rectal cancer","fulltext":[{"header":"Introduction","content":"\u003cp\u003e Neoadjuvant chemoradiotherapy (NCRT) has become a cornerstone of treatment for Locally advanced rectal cancer (LARC), aiming to increase rates of sphincter preservation, and improve oncological outcomes. Despite advancements in treatment modalities, the response to neoadjuvant NCRT varies among patients, with only a subset achieving a pathological complete response (pCR), defined as the absence of viable tumor cells in the surgical specimen after surgery [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e].\u003c/p\u003e \u003cp\u003ePatients who achieve pCR demonstrate significantly improved long-term oncological outcomes, including higher rates of relapse-free survival and overall survival. pCR can generally be achieved in 15\u0026ndash;27% of the patients treated with NRCT, while as around 54\u0026ndash;75% show partial or absence of response [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. The ability to predict which patients are more likely to achieve pCR following NCRT holds substantial clinical implications. Moreover, identifying predictors of pCR can facilitate treatment decision-making, tailoring therapeutic strategies\u003c/p\u003e \u003cp\u003eThe primary aim of our study was to identify the impact of patient characteristics, tumor size, tumor stage, location at presentation, circumferential extent, and pretreatment CEA levels on the occurrence of pCR after neoadjuvant treatment and.\u003c/p\u003e \u003cp\u003eFor our study, the primary measured outcome was pathologic complete response.\u003c/p\u003e"},{"header":"Patients and methods","content":"\u003cp\u003eWe performed a retrospective study at medical oncology unit in a tertiary care teaching hospital. All consecutive locally advanced primary rectal adenocarcinoma patients without any evidence of distant metastasis who underwent neoadjuvant chemoradiotherapy and surgery between June 2020 and December 2022 were included in the research.\u003c/p\u003e \u003cp\u003e The study was approved by the institutional review board at the Salah Azaiez Institute of Tunisia.\u003c/p\u003e \u003cp\u003eAll informations regarding demographic data (gender, age), stage at presentation, routine hemograms, biochemical test results, administrated treatment were obtained prospectively from the medical record.\u003c/p\u003e \u003cp\u003eA colonoscopy/flexible sigmoidoscopy and proctoscopy were performed on all patients. The confirmation of diagnosis was obtained after histopathological examination before starting treatment. Magnetic resonance imaging (MRI) of the pelvis and contrast-enhanced computed tomography of the chest, abdomen and pelvis were done for pre-operative staging.\u003c/p\u003e \u003cp\u003eExcluded patients from the study were those with metastatic disease, non-operated patients, and those treated with neoadjuvant radiation alone.\u003c/p\u003e \u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eNeoadjuvant protocols:\u003c/h2\u003e \u003cp\u003eDuring the study period, two different standardized protocols for the neoadjuvant treatment were used. Patients were sanded into two groups:\u003c/p\u003e \u003cp\u003eThe first group was treated with 6 injections of mFOLFIRINOX followed by short course radiotherapy at a dose of 25 Gy. External beam radiotherapy was given over 5 days a week with daily dose of 5 Gy. After radiotherapy patients received 2 injections of mFOLFOX (Oxaliplatin 85mg/m\u003csup\u003e2\u003c/sup\u003e, 5-Fluorouracil: 2500mg continuous infusion over 48 hours (Days 1 and 2), leucovorin [folinic acid] 400mg/m\u003csup\u003e2\u003c/sup\u003e. Surgery was performed after 8 weeks following last dose of radiotherapy.\u003c/p\u003e \u003cp\u003eThe second group was treated with the RAPIDO protocol: patients received short-course radiotherapy (5*5 Gy over a maximum of 8 days) followed by 6 cycles of CAPOX chemotherapy (capecitabine 1000mg/m2 orally twice daily on days 1\u0026ndash;14, oxaliplatin 130 mg/m2 iv) or 9 cycles of FOLFOX4 (Oxaliplatin 85mg/m\u003csup\u003e2\u003c/sup\u003e on day 1, and fluorouracil 1600mg/m2 iv continuous infusion over 48h on days 1 and 2, leucovorin [folinic acid] 400mg/m\u003csup\u003e2\u003c/sup\u003e).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003ePathological staging:\u003c/h2\u003e \u003cp\u003eThree categories were used to categorize the tumor grade based on the initial tumor biopsy samples: low, moderate and high differentiated tumor. Histopathological features of mucinous component (\u0026gt;\u0026thinsp;50%) and signet ring cells were also noted.\u003c/p\u003e \u003cp\u003eAfter surgery, resected specimens were subjected to histopathological examination, which was done by an experienced pathologist. According to Mandard grading system, treatment response was categorized as pCR (TRG1) or not pCR (TRG 2\u0026ndash;5). Pathologic complete response was defined as the absence of viable tumor cells in the rectum and in any of the resected lymph nodes in the surgical specimen.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis\u003c/h2\u003e \u003cp\u003eAll the Statistical analysis were carried through Statistical Package for the Social Sciences (SPSS) version 23, IBM SPSS Inc.; Chicago, IL, USA). Continuous variables that followed a normal distribution were expressed as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation and range while results for the variables that did not follow a normal distribution have been shown in median and the interquartile range. The categorical variables were expressed in the form of frequency and percentage.\u003c/p\u003e \u003cp\u003eFor comparisons, Student\u0026rsquo;s t-test was used for quantitative variables. A univariate analysis using chi-squared tests for dichotomous variable was conducted to identify the possible associated factors between the categorical variables and pCR. A multivariate analysis was carried out with variables that achieved statistical significance using logistic regression modeling. \u003cem\u003eP\u003c/em\u003e value\u0026thinsp;\u0026le;\u0026thinsp;0.05 was the established level of statistical significance.\u003c/p\u003e \u003cp\u003eWe defined disease free survival (DFS) as the time from diagnosis to local or distant recurrence or censored at date of last follow-up. DFS and OS curves were generated using the Kaplan-Meier method. Differences were assessed using the log-rank test.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003eBaseline patients characteristics\u003c/h2\u003e \u003cp\u003eA total of 91 patients (46 men and 45 women) were included in the study. Mean age of patients was 58.53\u0026thinsp;\u0026plusmn;\u0026thinsp;10.3 years [ range 28\u0026ndash;80 years]. The tumor histology consisted of well-differentiated adenocarcinoma in 19 (20.9%), moderately differentiated adenocarcinoma in 37 (40.6%), poorly differentiated adenocarcinoma in 35 (38.5%), and signet ring cell in 17 (18.7%) patients. The median initial CEA concentration was 6.97 ng/ml (range from 0.55 to 139 ng/ml). Pelvic MRI was the most commonly performed staging method (87.9%). All patients underwent surgery: anterior resection in 67 (73.6%), abdominoperineal resection in 23 (25.3%) patients. The median duration of surgery following last dose of NACRT was 9 weeks. pCR (TRG1) was achieved in 20 patients (22%). 71 patients (78%) showed some form of regression or no response (TRG 2\u0026ndash;5). Baseline patient characteristics are summarized in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. The mean follow up of patients was 20.2 months. Distribution of pretreatment and treatment variables according to received protocol were summarized in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003ePredictors of pCR\u003c/h2\u003e \u003cp\u003eYoung patients less than 60 years had significantly better pCR rates as compared to those more than 60 years (p\u0026thinsp;=\u0026thinsp;0.043). Patients treated with the induction chemotherapy followed by short course radiotherapy showed a better pCR as compared to patients treated with Rapido protocol (p\u0026thinsp;=\u0026thinsp;0.013). Patients with mucinous component had low pCR rates (p\u0026thinsp;=\u0026thinsp;0.021).\u003c/p\u003e \u003cp\u003eIn univariate analysis, the differences in pCR rates among gender, initial carcino embryonic antigen (CEA) levels, T stage and N stage were not significantly associated with pCR.\u003c/p\u003e \u003cp\u003eTime to surgery (between the last dose of radiotherapy to surgery) was not a predictive factor for pCR (8.83 weeks in patient with pCR Vs 11.46 weeks in patients without pCR, p\u0026thinsp;=\u0026thinsp;0.246). Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e summarizes univariate analysis of various predictive factors for pCR.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eBaseline patients characteristics n (%)\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"2\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMean age (years)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003e58.53\u0026thinsp;\u0026plusmn;\u0026thinsp;10.3\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGender\u003c/p\u003e \u003cp\u003eMale\u003c/p\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e46 (50.5)\u003c/p\u003e \u003cp\u003e45 (49.5)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMedian CEA (ng/ml)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6.97\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eT stage\u003c/p\u003e \u003cp\u003eT2\u003c/p\u003e \u003cp\u003eT3\u003c/p\u003e \u003cp\u003eT4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5 (5.5)\u003c/p\u003e \u003cp\u003e71 (78)\u003c/p\u003e \u003cp\u003e15 (16.5)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eN stage\u003c/p\u003e \u003cp\u003eN0\u003c/p\u003e \u003cp\u003eN1\u003c/p\u003e \u003cp\u003eN2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3 (3.3)\u003c/p\u003e \u003cp\u003e44 (48.4)\u003c/p\u003e \u003cp\u003e44 (48.4)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGrade\u003c/p\u003e \u003cp\u003eWell differentiated\u003c/p\u003e \u003cp\u003eModerately differentiated\u003c/p\u003e \u003cp\u003ePoorly differentiated\u003c/p\u003e \u003cp\u003eMucinous\u003c/p\u003e \u003cp\u003eSignet ring cell\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e19 (20.9)\u003c/p\u003e \u003cp\u003e37 (40.6)\u003c/p\u003e \u003cp\u003e35 (38.5)\u003c/p\u003e \u003cp\u003e18 (19.8)\u003c/p\u003e \u003cp\u003e17 (18.7)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSite of the tumor\u003c/p\u003e \u003cp\u003eLower rectum\u003c/p\u003e \u003cp\u003eMiddle rectum\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e39 (42.9)\u003c/p\u003e \u003cp\u003e52 (57.1)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eStaging method\u003c/p\u003e \u003cp\u003ePelvic CT scan\u003c/p\u003e \u003cp\u003ePelvic MRI\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e11 (12.1)\u003c/p\u003e \u003cp\u003e80 (87.9)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNeoadjuvant protocol\u003c/p\u003e \u003cp\u003eInduction chemotherapy\u003c/p\u003e \u003cp\u003eRapido protocol\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e61 (67)\u003c/p\u003e \u003cp\u003e30 (33)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eType of surgery\u003c/p\u003e \u003cp\u003eLow anterior resection\u003c/p\u003e \u003cp\u003eAbdominoperineal resection\u003c/p\u003e \u003cp\u003eHartmann operation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e67 (73.6)\u003c/p\u003e \u003cp\u003e23 (25.3)\u003c/p\u003e \u003cp\u003e1 (1.1)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAverage radiation dose (Gy)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e25\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"2\"\u003eCEA: Carcinoembryonic antigen, CT: computed tomography, MRI: Magnetic resonance imaging, Gy: Gray\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eDistribution of pretreatment and treatment variables according to received protocol\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eStudy variables\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eInduction chemotherapy (n,%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eShort course radiotherapy (n,%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eP\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGender\u003c/p\u003e \u003cp\u003eMale\u003c/p\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e30 (49.2)\u003c/p\u003e \u003cp\u003e31 (50.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e16 (53.3)\u003c/p\u003e \u003cp\u003e14 (46.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.716\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCEA pretreatment level (mean)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e14.35\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e7.08\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.516\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eT stage T2\u003c/p\u003e \u003cp\u003eT3\u003c/p\u003e \u003cp\u003eT4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e3 (4.9)\u003c/p\u003e \u003cp\u003e51 (83.6)\u003c/p\u003e \u003cp\u003e7 (11.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2 (6.7)\u003c/p\u003e \u003cp\u003e20 (66.7)\u003c/p\u003e \u003cp\u003e8 (26.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.734\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eN stage\u003c/p\u003e \u003cp\u003eN (-)\u003c/p\u003e \u003cp\u003eN (+)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3 (4.9)\u003c/p\u003e \u003cp\u003e58 (95.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0(0)\u003c/p\u003e \u003cp\u003e30(100)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.287\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGrade\u003c/p\u003e \u003cp\u003eWell differentiated\u003c/p\u003e \u003cp\u003eModerately differentiated\u003c/p\u003e \u003cp\u003ePoorly differentiated\u003c/p\u003e \u003cp\u003eSignet ring cell\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9 (14.7)\u003c/p\u003e \u003cp\u003e27 (44.3)\u003c/p\u003e \u003cp\u003e25 (41)\u003c/p\u003e \u003cp\u003e8 (13.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10 (33.3)\u003c/p\u003e \u003cp\u003e10 (33.3)\u003c/p\u003e \u003cp\u003e10 (33.3)\u003c/p\u003e \u003cp\u003e9 (30)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.494\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSite of the tumor\u003c/p\u003e \u003cp\u003eLower rectum\u003c/p\u003e \u003cp\u003eMiddle rectum\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e38 (62.3)\u003c/p\u003e \u003cp\u003e23 (37.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e14 (46.7)\u003c/p\u003e \u003cp\u003e16 (53.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.167\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eType of surgery\u003c/p\u003e \u003cp\u003eResection\u003c/p\u003e \u003cp\u003eHartmann operation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e60 (98.4)\u003c/p\u003e \u003cp\u003e1 (1.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e30 (100)\u003c/p\u003e \u003cp\u003e0 (0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.380\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eChemotherapy interruption\u003c/p\u003e \u003cp\u003eYes\u003c/p\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e38(62.3)\u003c/p\u003e \u003cp\u003e23(37.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (0.3)\u003c/p\u003e \u003cp\u003e29 (99.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.00001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMucinous component\u003c/p\u003e \u003cp\u003eYes\u003c/p\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8 (13.1)\u003c/p\u003e \u003cp\u003e53 (86.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10 (33.3)\u003c/p\u003e \u003cp\u003e20 (66.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.015\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003eCEA: Carcinoembryonic antigen\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eUnivariate analysis of predictors for pathologic complete response\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eStudy variables\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003epCR (n,%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNo pCR (n,%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eP\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGender\u003c/p\u003e \u003cp\u003eMale\u003c/p\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10 (11)\u003c/p\u003e \u003cp\u003e10 (11)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e36 (39.5)\u003c/p\u003e \u003cp\u003e35 (38.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.956\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge \u0026lt; 60 years\u003c/p\u003e \u003cp\u003e\u0026ge; 60 years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e16 (17.6)\u003c/p\u003e \u003cp\u003e4 (4.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e39 (42.8)\u003c/p\u003e \u003cp\u003e32 (35.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.043\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eECA pretreatment level (mean)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9.08\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e13.49\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.516\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eT stage T2\u003c/p\u003e \u003cp\u003eT3\u003c/p\u003e \u003cp\u003eT4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2 (2.2)\u003c/p\u003e \u003cp\u003e13 (14.3)\u003c/p\u003e \u003cp\u003e5 (5.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3 (3.3)\u003c/p\u003e \u003cp\u003e58 (63.7)\u003c/p\u003e \u003cp\u003e10 (11)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.268\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eN stage\u003c/p\u003e \u003cp\u003eN (-)\u003c/p\u003e \u003cp\u003eN (+)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (1.1)\u003c/p\u003e \u003cp\u003e19 (31.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2(2.2)\u003c/p\u003e \u003cp\u003e69(65.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.629\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGrade\u003c/p\u003e \u003cp\u003eWell differentiated\u003c/p\u003e \u003cp\u003eModerately differentiated\u003c/p\u003e \u003cp\u003ePoorly differentiated\u003c/p\u003e \u003cp\u003eSignet ring cell\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10 (11)\u003c/p\u003e \u003cp\u003e18 (19.8)\u003c/p\u003e \u003cp\u003e17 (18.6)\u003c/p\u003e \u003cp\u003e8 (8.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9 (9.9)\u003c/p\u003e \u003cp\u003e19 (20.9)\u003c/p\u003e \u003cp\u003e18 (19.8)\u003c/p\u003e \u003cp\u003e9 (9.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.755\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSite of the tumor\u003c/p\u003e \u003cp\u003eLower rectum\u003c/p\u003e \u003cp\u003eMiddle rectum\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e11 (12.1)\u003c/p\u003e \u003cp\u003e9 (9.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e41 (45)\u003c/p\u003e \u003cp\u003e30 (33)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.826\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTime to surgery (weeks)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8.83\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e11.46\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.246\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNeoadjuvant protocol\u003c/p\u003e \u003cp\u003eInduction chemotherapy\u003c/p\u003e \u003cp\u003eRapido protocol\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e18 (19.8)\u003c/p\u003e \u003cp\u003e2 (2.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e43 (67)\u003c/p\u003e \u003cp\u003e28 (33)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.013\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eType of surgery\u003c/p\u003e \u003cp\u003eResection\u003c/p\u003e \u003cp\u003eHartmann operation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e19 (20.9)\u003c/p\u003e \u003cp\u003e1 (1.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e71 (78)\u003c/p\u003e \u003cp\u003e0 (0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.058\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eChemotherapy interruption\u003c/p\u003e \u003cp\u003eYes\u003c/p\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1(1.1)\u003c/p\u003e \u003cp\u003e19(31.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e38 (31.4)\u003c/p\u003e \u003cp\u003e33 (36.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.0001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMucinous component\u003c/p\u003e \u003cp\u003eYes\u003c/p\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0 (0)\u003c/p\u003e \u003cp\u003e18 (19.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e18 (19.8)\u003c/p\u003e \u003cp\u003e55 (60.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.018\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003epCR\u0026thinsp;=\u0026thinsp;pathological complete response, CEA: Carcinoembryonic antigen\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eOn logistic regression analysis, chemotherapy continuation (OR\u0026thinsp;=\u0026thinsp;10.27, 95% CI\u0026thinsp;=\u0026thinsp;2,14\u0026ndash;49.32), and mucinous component (OR\u0026thinsp;=\u0026thinsp;12.6, 95% CI\u0026thinsp;=\u0026thinsp;3.1\u0026ndash;40.32) were significant predictors of pCR [Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e].\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eMultivariate analysis of predictors for pathologic complete response\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eStudy variables\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003epCR (n,%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNo pCR (n,%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eP\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eOR\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge \u0026lt; 60 years\u003c/p\u003e \u003cp\u003e\u0026ge; 60 years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e16 (17.6)\u003c/p\u003e \u003cp\u003e4 (4.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e39 (42.8)\u003c/p\u003e \u003cp\u003e32 (35.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.450\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1.88[0.36\u0026ndash;9.81]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNeoadjuvant protocol\u003c/p\u003e \u003cp\u003eInduction chemotherapy\u003c/p\u003e \u003cp\u003eRapido protocol\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e18 (19.8)\u003c/p\u003e \u003cp\u003e2 (2.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e43 (67)\u003c/p\u003e \u003cp\u003e28 (33)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.067\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e4.36[0.9-21.14]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eChemotherapy interruption\u003c/p\u003e \u003cp\u003eYes\u003c/p\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1(1.1)\u003c/p\u003e \u003cp\u003e19(31.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e38 (31.4)\u003c/p\u003e \u003cp\u003e33 (36.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.04\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e10.27\u003c/b\u003e[2.14\u0026ndash;49.32]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMucinous component\u003c/p\u003e \u003cp\u003eYes\u003c/p\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0 (0)\u003c/p\u003e \u003cp\u003e18 (21.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e16 (18.8)\u003c/p\u003e \u003cp\u003e69 (60)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.021\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e12.6\u003c/b\u003e[3.1-40.32]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003eOR\u0026thinsp;=\u0026thinsp;Odds ratio, CI\u0026thinsp;=\u0026thinsp;Confidence interval, pCR\u0026thinsp;=\u0026thinsp;pathological complete response\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003eOverall survival (OS):\u003c/h2\u003e \u003cp\u003eThe median survival was 37.7 months. The OS is represented in Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003ea. There was no significant difference in OS between patients achieving pCR and those without achieving pCR (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eb) and patients treated with different protocols (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003ec).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eNeoadjuvant chemoradiotherapy (NCRT) followed by total mesorectal excision for locally advanced rectal cancer (LARC) has become a standard treatment approach due to its good results in downstaging tumors. NCRT increase the likelihood of sphincter preservation, and improve local control of the disease. However, not all patients treated for LARC with neoadjuvant treatment achieve a pathological complete response (pCR). pCR is associated with better long-term outcomes including improved relapse-free survival and overall survival. Understanding the predictors of pCR is crucial for optimizing treatment strategies and identifying patients who may benefit most from neoadjuvant therapy especially in the era of total neoadjuvant therapy and watch-and-wait surveillance approach [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. The watch and wait strategy may have the benefit of avoiding surgery [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe pathological response to NCRT in the most studies varies among individuals. Achieving pCR varies from 15\u0026ndash;27% of the patients. However, around 54\u0026ndash;75% show partial or absence of response after NCRT [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Mehraj et al, reported in their study that pCR defined as Mandard Gr 1 was obtained in (18.6%) patients [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. In our study, pCR was achieved in 22% of patients.\u003c/p\u003e \u003cp\u003eRecently, there has been increased interest in the concept of total neoadjuvant treatment (TNT). TNT was defined as chemotherapy induction and/or consolidation in conjunction with classical standard chemoradiotherapy prior to surgery. It is believed that TNT increases the rate of pCR by addressing occult micro-metastatic disease. A 2020 published meta-analysis showed a pCR rate of 22.4% in the TNT cohort, and it was associated with a 39% increase in the odds of achieving pCR compared to other strategies (1.40, 95% CI 1.08\u0026ndash;1.81, p\u0026thinsp;=\u0026thinsp;0.01) [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eIn this study, we investigated various clinical, biochemical, radiological and pathological factors as potential predictors of pCR following NCRT for LARC. The purpose of this study was to assess preoperative predictors of pCR after NCRT.\u003c/p\u003e \u003cp\u003ePatient-related factors play a crucial role in predicting pCR after NCRT. Age, performance status (PS), nutritional status and comorbidities, may influence clinical and pathological treatment outcomes (OS, DFS and pCR). Younger patients and those with PS ranging from 0 to 2 are more likely to achieve pCR. However, patients with significant comorbidities, impaired PS (3\u0026ndash;4) may have reduced tolerance to treatment and consequently lower rates of pCR. In our study and in univariate analysis, we found that patient less than 60 years had significantly better pCR rates as compared to those more than 60 years (p\u0026thinsp;=\u0026thinsp;0.043). The data in the literature concerning patient age as a predictive factor for pCR are discordant. In fact, a recent meta-analysis showed that elderly patients achieved higher pCR rates (p\u0026thinsp;=\u0026thinsp;0.0002) [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. Most studies have found lower CEA level is associated with pCR. A systematic review and meta-analysis confirmed those findings and concluded that CEA level was inversely correlated with pCR rates [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eIn the literature, an association between interruption of chemotherapy and pCR was demonstrated. Patients with an interruption in their neoadjuvant therapy because of treatment-related toxicity, were less likely to develop pCR [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eLymph node regression grade is a good indicator of response to preoperative NCRT and several studies showed that NCRT has been associated with a low pN (+) rate in locally advanced rectal cancer. Histopathological findings in positive lymph nodes after chemoradiotherapy include residual cancer cells, hemorrhage, areas of hyalinosis, cystic cell reactions, and pools of mucin [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. The impact of lymph node status on neoadjuvant chemoradiotherapy treatment response in LARC has been studied in several studies. Huang et al. showed that patient without lymph node involvement was a positive predictor of pCR (P\u0026thinsp;\u0026lt;\u0026thinsp;0.00001) for rectal cancer following neoadjuvant chemoradiotherapy [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. Performing an additional lateral lymph node dissection has been studied after NCRT in recent years. A meta-analysis showed that lateral lymph during total mesorectal excision reduces local recurrence risk, but does not impact oncological outcomes (disease-free or overall survival) [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe treatment protocols for LARC are various. The addition of induction chemotherapy to concomitant neoadjuvant chemoradiation in LARC could increase pCR rate. A systematic review showed that the addition of induction/consolidation chemotherapy to standard NCRT results in a higher pCR rate [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. In our study, patients treated with induction chemotherapy followed by short course radiotherapy prior to surgery showed a better pCR as compared to patients treated with short course radiotherapy. The effect of TNT on oncological outcomes has not been fully investigated. Several studies and a meta-analysis showed that disease-free survival was not associated with the type of neoadjuvant treatment (hazard ratio [HR] 1.3; 95% CI : 0.93\u0026ndash;1.80; p\u0026thinsp;=\u0026thinsp;0.12) [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eConsidering initial and definitive histopathological tumor features, three studies found no significant difference in terms of pCR [\u003cspan additionalcitationids=\"CR19\" citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. A systematic review and meta-analysis found that mucinous component was associated with poor p CR [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eIn our study, a number of factors were independent predictors of pCR, including the absence of chemotherapy interruption (OR\u0026thinsp;=\u0026thinsp;10.27, 95% CI\u0026thinsp;=\u0026thinsp;2,14\u0026ndash;49.32), and absence of mucinous component (OR\u0026thinsp;=\u0026thinsp;12.6, 95% CI\u0026thinsp;=\u0026thinsp;3.1\u0026ndash;40.32). These factors predicting pCR require validation in prospective multicenter studies order to be incorporated into WW strategies.\u003c/p\u003e \u003cp\u003eDue to the retrospective nature of our study, there are certain limitations that it is important to acknowledge. Despite our efforts to minimize missing data, we encountered some challenges. Specifically, CEA levels were missing in some patient\u0026rsquo;s records. Additionally, duration of chemotherapy interruption was not mentioned.\u003c/p\u003e \u003cp\u003eDespite advances in our understanding of predictors of pCR after NCRT for LARC, several challenges are remaining. These challenges come from the fact that patient populations are heterogeneous, and there are big variations in treatment regimens. The differences in study methodologies make comparisons between studies difficult. Further research into novel biomarkers, personalized treatment approaches and risk models and algorithms based on artificial intelligence are required.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eOur study identified several predictors of pathological complete response following NCRT for LARC. Integrating these factors into personalized treatment algorithms may help optimize therapeutic strategies and improve oncological outcomes for patients with LARC. Further prospective studies are warranted to validate these findings and refine predictive models.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgements:\u003c/strong\u003e Not applicable.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026rsquo; contributions:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eH.Y: concept, design, definition of intellectual content, literature search, manuscript preparation, manuscript editing, manuscript review.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eY.Z: concept, design, definition of intellectual content, manuscript preparation, manuscript review.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eD.C.: Definition of intellectual content, manuscript preparation, design, manuscript review.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eH.B.M: Definition of intellectual content, design\u003c/p\u003e\n\u003cp\u003eN.A.: Definition of intellectual content, manuscript preparation.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eC.M.: Definition of intellectual content, manuscript preparation.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eK.B.Z.: Definition of intellectual content, manuscript preparation.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eF.L.: design, manuscript review.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eA.M.: Manuscript review.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAll authors read and approved the final manuscript.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding:\u003c/strong\u003e Not applicable.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003cstrong\u003eAvailability of data and materials:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe data that support the fndings of this study are available on request from the corresponding author, [HY]. The data are not publicly available due to [restrictions e.g. their containing information that could compromise the privacy of research participants].\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDeclarations Ethics approval and consent to participate:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was performed according to the Declaration of Helsinki, following the guidelines for good clinical practice. \u0026ldquo;Salah Azaiz institute ethics committee\u0026rdquo; approved the study protocol. All methods were carried out in accordance with relevant guidelines and regulations. Informed consent to participate in the study was obtained from participants.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e: Not applicable.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests:\u003c/strong\u003e The authors declare that they have no competing interests\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n \u003cli\u003e\u003cspan\u003eSmith K, Jones A, Doe J, et al. Predictors of pathological complete response to neoadjuvant chemoradiotherapy for locally advanced rectal cancer: a systematic review and meta-analysis. Br J Surg. 2023;110(5):611\u0026ndash;23.\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eMaas M, Nelemans PJ, Valentini V, Das P, R\u0026ouml;del C, Kuo LJ, et al. 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\u0026ndash;44.\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eJoye I, Deroose CM, Vandecaveye V, Haustermans K. The role of diffusion-weighted MRI and (18)F-FDG PET/CT in the prediction of pathologic complete response after radiochemotherapy for rectal cancer: A systematic review. Radiother Oncol. 2014;113:158\u0026ndash;65.\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eLiu S, Jiang T, Xiao L, Yang S, Liu Q, Gao Y, Chen G, Xiao W. Total Neoadjuvant Therapy (TNT) versus Standard Neoadjuvant Chemoradiotherapy for Locally Advanced Rectal Cancer: A Systematic Review and Meta-Analysis. Oncologist. 2021;26:e1555\u0026ndash;66.\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eCercek A, Goodman KA, Hajj C, Weisberger E, Segal NH, Reidy-Lagunes DL, Stadler ZK, Wu AJ, Weiser MR, Paty PB, et al. Neoadjuvant chemotherapy first, followed by chemoradiation and then surgery, in the management of locally advanced rectal cancer. J Natl Compr Cancer Netw. 2014;12:513\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eSmith JD, et al. Nonoperative management of rectal cancer with complete clinical response after neoadjuvant therapy. Ann Surg. 2012;256(6):965\u0026ndash;72.\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eMehraj A, Baba AA. Khan, Bushra\u003csup\u003e1\u003c/sup\u003e; Khan, Mudassir Ahmad; Wani, Rauf A; Parray, Fazl Q; Chowdri, Nisar A. Predictors of pathological complete response following neoadjuvant chemoradiotherapy for rectal cancer. Journal of Cancer Research and Therapeutics 18(Suppl 2):p S391-S396, 2022.\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003ePetrelli F, Trevisan F, Cabiddu M, Sgroi G, Bruschieri L, Rausa E, et al. Total Neoadjuvant therapy in rectal cancer: A systematic review and meta-analysis of treatment outcomes. Ann Surg. 2020;271:440\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eHuang Y, Lee D, Young C. Predictors for complete pathological response for stage II and III rectal cancer following neoadjuvant therapy - A systematic review and meta-analysis. Am J Surg. 2020;220:300\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eColloca G, Venturino A, Vitucci P. Pre-treatment carcinoembryonic antigen and outcome of patients with rectal cancer receiving neo-adjuvant chemo-radiation and surgical resection: a systematic review and meta-analysis. Med Oncol. 2017;34(10):177.\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003epelt AL, Pl\u0026oslash;en J, Vogelius IR, Bentzen SM, Jakobsen A. Radiation dose-response model for locally advanced rectal cancer after preoperative chemoradiation therapy. Int J Radiat Oncol Biol Phys. 2013;85:74\u0026ndash;80.\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eHe L, Xiao J, Zheng P, Zhong L, Peng Q. Lymph node regression grading of locally advanced rectal cancer treated with neoadjuvant chemoradiotherapy. World J Gastrointest Oncol. 2022;14(8):1429\u0026ndash;45.\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eOzturk SK, Martinez CG, Mens D, Verhoef C, Tosetto M, Sheahan K, de Wilt JHW, Hospers GAP, van de Velde CJH, Marijnen CAM, van der Post RS, Nagtegaal ID. Lymph node regression after neoadjuvant chemoradiotherapy in rectal cancer. Histopathology. 2024;84(6):935\u0026ndash;46.\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eKroon HM, Hoogervorst LA, Hanna-Rivero N, Traeger L, Dudi-Venkata NN, Bedrikovetski S, Kusters M, Chang GJ, Thomas ML, Sammour T. Systematic review and meta-analysis of long-term oncological outcomes of lateral lymph node dissection for metastatic nodes after neoadjuvant chemoradiotherapy in rectal cancer. Eur J Surg Oncol. 2022;48(7):1475\u0026ndash;82.\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003ePetrelli F, Trevisan F, Cabiddu M, Sgroi G, Bruschieri L, Rausa E, Ghidini M, Turati L. Total Neoadjuvant Therapy in Rectal Cancer: A Systematic Review and Meta-analysis of Treatment Outcomes. Ann Surg. 2020.\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eKim JK, Marco MR, Roxburgh CSD, Chen CT, Cercek A, Strombom P, Temple LKF, Nash GM, Guillem JG, Paty PB, Yaeger R, Stadler ZK, Gonen M, Segal NH, Reidy DL, Varghese A, Shia J, Vakiani E, Wu AJ, Romesser PB, Crane CH, Gollub MJ, Saltz L, Smith JJ, Weiser MR, Patil S, Garcia-Aguilar J. Survival After Induction Chemotherapy and Chemoradiation Versus Chemoradiation and Adjuvant Chemotherapy for Locally Advanced Rectal Cancer. Oncologist. 2022;27(5):380\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eFeng S, Yan P, Zhang Q, Li Z, Li C, Geng Y, Wang L, Zhao X, Yang Z, Cai H, Wang X. Induction chemotherapy followed by neoadjuvant chemoradiotherapy and surgery for patients with locally advanced rectal cancer: a systematic review and meta-analysis. Int J Colorectal Dis. 2020;35(8):1355\u0026ndash;69.\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eYu ZQ, Zhang C, Wang H, et al. Downregulation of ATP-binding cassette subfamily C member 4 increases sensitivity to neoadjuvant radiotherapy for locally advanced rectal carcinoma. Dis Colon Rectum. 2013;56(5):600\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eMoureau-Zabotto L, Farnault B, de Chaisemartin C, et al. Predictive factors of tumor response after neoadjuvant chemoradiation for locally advanced rectal cancer. Int J Radiat Oncol Biol Phys. 2011;80(2):483\u0026ndash;91.\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eReggiani Bonetti L, Lionti S, Domati F, et al. Do pathological variables have prognostic significance in rectal adenocarcinoma treated with neoadjuvant chemoradiotherapy and surgery? World J Gastroenterol. 2017;23(8):1412\u0026ndash;23.\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eMcCawley N, Clancy C, O\u0026rsquo;Neill BD, et al. Mucinous rectal adenocarcinoma is associated with a poor response to neoadjuvant chemoradiotherapy: a systematic review and meta-analysis. Dis Colon Rectum. 2016;59(12):1200\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-gastroenterology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bmge","sideBox":"Learn more about [BMC Gastroenterology](http://bmcgastroenterol.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bmge/default.aspx","title":"BMC Gastroenterology","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"","lastPublishedDoi":"10.21203/rs.3.rs-4469099/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4469099/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground: \u003c/strong\u003eNeoadjuvant chemoradiotherapy (NCRT) has become a standard treatment approach for locally advanced rectal cancer (LARC). Patients achieving pathological complete response (pCR) following NCRT have better outcomes (overall survival, relapse free survival). However, not all patients treated for LARC with neoadjuvant treatment achieve pCR.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAim:\u003c/strong\u003e The aim of our study was to assess the rate and predictors of pCR.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMaterials and Methods:\u003c/strong\u003e We performed a retrospective study at medical oncology unit in a tertiary care teaching hospital. All consecutive LARC patients without any evidence of distant metastasis who underwent neoadjuvant chemoradiotherapy and surgery between June 2020 and January 2023 were included in the research. Pathological response to NCRT was assessed using Mandard grading system and response was categorized as pCR or not‑pCR. Two different standardized protocols for the neoadjuvant treatment were used: the first group was treated with induction chemotherapy followed by short course radiotherapy and the second group was treated with the RAPIDO protocol.\u003c/p\u003e\n\u003cp\u003eCorrelation between different studied parameters and pCR was determined using univariate and multivariate logistic regression analysis\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe mean age of the 91 included patients (46 men and 45 women) was 58.53 ± 10.3 years. Twenty (22%) were found to have a pCR (Mandard TRG1) in the operative specimen. In univariate analysis, patients less than 60 years, continuation of chemotherapy and patients treated with the induction chemotherapy followed by short course radiotherapy showed a better pCR as compared to patients treated with Rapido protocol (p = 0.043, p=0.0001 and p=0.021 respectively). Patients with mucinous component had low pCR rates (p =0.021). On logistic regression analysis, chemotherapy continuation (OR = 10.27, 95% CI = 2,14–49.32), and absence of mucinous component (OR = 12.6, 95% CI = 3.1–40.32) were significant predictors of pCR. The median survival was 37.7 months.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion: \u003c/strong\u003eMucinous component and chemotherapy interruption are associated with lower pCR rates. Integrating these factors into personalized treatment algorithms may help optimize therapeutic strategies and improve outcomes for patients with LARC.\u003c/p\u003e","manuscriptTitle":"Predictors of pathological complete response after neoadjuvant chemoradiotherapy for locally advanced rectal cancer","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-06-12 03:36:14","doi":"10.21203/rs.3.rs-4469099/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2024-12-23T16:40:01+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-12-23T10:11:16+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"175530903261652021408755792653557029423","date":"2024-12-17T13:02:28+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-12-16T05:10:26+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-12-14T21:15:20+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-12-14T04:09:41+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"74708527425813886427214566126244403430","date":"2024-12-13T21:04:28+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"24114045609260286746146536036526341491","date":"2024-12-13T01:55:27+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"285819606206274336964804588511396517610","date":"2024-12-12T03:54:39+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"177310520538861889756594228272518169629","date":"2024-12-11T22:06:14+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"139291027999715975038691572910841924133","date":"2024-12-11T20:56:04+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"336262909802612649166732024423499200167","date":"2024-08-10T15:05:49+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"29278772883913569627785375756966975218","date":"2024-08-08T09:06:16+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2024-08-01T08:10:49+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2024-06-03T11:34:56+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-05-27T15:28:01+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2024-05-27T15:28:01+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Gastroenterology","date":"2024-05-23T22:11:55+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-gastroenterology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bmge","sideBox":"Learn more about [BMC Gastroenterology](http://bmcgastroenterol.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bmge/default.aspx","title":"BMC Gastroenterology","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"f1cfc74e-444f-4583-a35b-1eac75426939","owner":[],"postedDate":"June 12th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2025-04-07T15:58:15+00:00","versionOfRecord":{"articleIdentity":"rs-4469099","link":"https://doi.org/10.1186/s12876-025-03709-1","journal":{"identity":"bmc-gastroenterology","isVorOnly":false,"title":"BMC Gastroenterology"},"publishedOn":"2025-03-31 15:56:50","publishedOnDateReadable":"March 31st, 2025"},"versionCreatedAt":"2024-06-12 03:36:14","video":"","vorDoi":"10.1186/s12876-025-03709-1","vorDoiUrl":"https://doi.org/10.1186/s12876-025-03709-1","workflowStages":[]},"version":"v1","identity":"rs-4469099","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4469099","identity":"rs-4469099","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}