The relationship between Pim-3 expression and chemoradiotherapy resistance in locally advanced rectal cancer patients.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e15112-e15112
Author(s):  
Rong-xin Zhang ◽  
Zhongguo Zhou ◽  
Shi-xun Lu ◽  
Zhen-hai LU ◽  
Desen Wan ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Multivariate Analysis ◽  
Cancer Patients ◽  
Rectal Cancer Patient ◽  
Locally Advanced ◽  
Neoadjuvant Treatment ◽  
Neoadjuvant Chemoradiotherapy ◽  
Tissue Bank ◽  
Disease Free Survival ◽  
Significant Factors

e15112 Background: It is difficult for clinical oncologists to predict which types of rectal cancer patient would respond to neoadjuvant chemoradiotherapy. About 30% of rectal cancer patients who could not benefit from chemoradiotherapy, and about 10% of patients even suffered from disease progression. It is of considerable importance to identify a bio-marker to identify patients who would benefit from neoadjuvant treatment. Methods: This study enrolled 175 rectal cancer patients who underwent neoadjuvant treatment. Tissue samples from all the patients were deposited in the tissue bank of Sun Yat-sen University Cancer Center prior to neoadjuvant treatment. We compared the expression of Pim-3 in rectal tumors and investigated correlations with the response to chemoradiotherapy and with survival. Results: The Pim-3-negative patients were more likely to achieve a pathological complete response to chemoradiotherapy (P = 0.001, RR = 5.132, 95% CI: 2.442–10.787). Cox multivariate analysis in 137 patients with at least 24 months follow-up showed that the expression of Pim-3 (P = 0.041, RR = 1.209, 95% CI = 1.007–1.452) and cycles of neoadjuvant chemotherapy cycles (P = 0.006, RR = 0.557, 95% CI = 0.367–0.845) were significant factors affecting the survival status of patients. Cox multivariate analysis of disease-free survival showed that Pim-3 expression (P = 0.012, RR = 1.180, 95% CI: 1.037–1.344) and adjuvant chemotherapy cycles (P = 0.003, RR = 0.745, 95% CI: 0.615–0.902) were statistically significant factors. Conclusions: Pim-3 could be a potential predictive bio-marker of the response to chemoradiotherapy.

scholarly journals Molecular and Dynamic Evaluation of Proteins Related to Resistance to Neoadjuvant Treatment with Chemoradiotherapy in Circulating Tumor Cells of Patients with Locally Advanced Rectal Cancer

Cells ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 1539
Author(s):  
Virgílio Souza e Silva ◽  
Emne Ali Abdallah ◽  
Bianca de Cássia Troncarelli Flores ◽  
Alexcia Camila Braun ◽  
Daniela de Jesus Ferreira Costa ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Transforming Growth Factor ◽  
Locally Advanced ◽  
Neoadjuvant Treatment ◽  
Neoadjuvant Chemoradiotherapy ◽  
Disease Free Survival ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer

The heterogeneity of response to neoadjuvant chemoradiotherapy (NCRT) is still a challenge in locally advanced rectal cancer (LARC). The evaluation of thymidylate synthase (TYMS) and RAD23 homolog B (RAD23B) expression in circulating tumor cells (CTCs) provides complementary clinical information. CTCs were prospectively evaluated in 166 blood samples (63 patients) with LARC undergoing NCRT. The primary objective was to verify if the absence of RAD23B/TYMS in CTCs would correlate with pathological complete response (pCR). Secondary objectives were to correlate CTC kinetics before (C1)/after NCRT (C2), in addition to the expression of transforming growth factor-β receptor I (TGF-βRI) with survival rates. CTCs were isolated by ISET and evaluated by immunocytochemistry (protein expression). At C1, RAD23B was detected in 54.1% of patients with no pCR and its absence in 91.7% of patients with pCR (p = 0.014); TYMS− was observed in 90% of patients with pCR and TYMS+ in 51.7% without pCR (p = 0.057). Patients with CTC2 > CTC1 had worse disease-free survival (DFS) (p = 0.00025) and overall survival (OS) (p = 0.0036) compared with those with CTC2 ≤ CTC1. TGF-βRI expression in any time correlated with worse DFS (p = 0.059). To conclude, RAD23B/TYMS and CTC kinetics may facilitate the personalized treatment of LARC.

Neoadjuvant treatment response as a tumor necrosis grade for patients with rectal cancer.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e14563-e14563
Author(s):  
Byoungyong Shim ◽  
Ji Han Jung ◽  
Hyun Min Cho ◽  
Hyung Jin Kim ◽  
Ji Hyung Hong ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Cancer Patients ◽  
Tumor Cells ◽  
Tumor Necrosis ◽  
Locally Advanced ◽  
Neoadjuvant Treatment ◽  
Neoadjuvant Chemoradiotherapy ◽  
Surrogate Marker ◽  
Oncologic Outcomes ◽  
Adjuvant Chemoradiotherapy

e14563 Background: Neoadjuvant chemoradiotherapy for rectal cancer results in prevention of local recurrence and may achieve sphincter conserving surgery. Association between pathologic response evaluated after radical tumor resection and patient prognosis was well established. The object of this study was to assess the association between the degree of tumor necrosis after chemoradiotherapy and oncologic outcomes. Methods: In all, 225 patients with locally advanced rectal cancer (stage II and III by endorectal ultrasonography, CT and MRI) had 50.4 Gy over 5.5 weeks, plus 5-fluorouracil and leucovorin and surgery was performed at 7 to 10 weeks after completion of all therapies. Pathologic tissue necrosis after chemoradiotherapy was reviewed and scored as follows: Grade 0, no response; Grade 1, necrosis or disappearance of tumor cells less than 2/3; Grade 2, necrosis or disappearance of tumor cells more than 2/3; and Grade 3, no viable cells (ypCR). Correlation analysis was performed using Pearson’s Chi square or Fisher’s exact test, as appropriate. Recurrence-free survival and overall survival were calculated using the Kaplan-Meier method. Results: This study included cStage II (101 patients) and cStage III (124 patients) rectal cancer patients, and down stage rate was 57.3% and pCR was 16.9%. The pathologic tumor response ( pStage 0 v I v II v III) was associated with 5-year RFS (97.4 % v 81.5% v 76.6% v 50.0%; p<0.001). The tumor necrosis (Grade 0 & 1 v 2 v 3) was associated with 5-year RFS (64.4% v 76.8 v 97.4%; p=.002). Conclusions: The tumor necrosis to neoadjuvant chemoradiotherapy is a surrogate marker for recurrence and oncologic outcomes in rectal cancer patients treated with 5 flurouracil and leucovorin neo-adjuvant chemoradiotherapy.

Watch and wait approach following neoadjuvant chemoradiotherapy for rectal cancer patients: A single-centre experience.

2019 ◽  
Vol 37 (4_suppl) ◽  
pp. 681-681
Author(s):  
Ji Zhu ◽  
Jingwen Wang
Keyword(s):  
Rectal Cancer ◽  
Cancer Patients ◽  
Locally Advanced ◽  
Neoadjuvant Chemoradiotherapy ◽  
Disease Free Survival ◽  
Complete Response ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
Preoperative Treatment ◽  
Watch And Wait

681 Background: A watch-and-wait approach for patients with clinical complete response to neoadjuvant chemoradiation could avoid the morbidity of conventional surgery for rectal cancer. Here, we report the survival outcome of patients with this strategy in our center. Methods: We retrospectively analyzed the rectal cancer patients who received neoadjuvant chemoradiotherapy since 2015 in our center. Preoperative regimen included long-course radiotherapy (50 Gy / 25 Fx) combined fluoropyrimidin–based chemotherapy concurrently. MRI and endoscopic evaluation were performed after preoperative treatment. Patients with complete tumor response were referred to the “watch-and-wait” approach and omitted the surgery. Four to six cycles of consolidation chemotherapy were performed. Patients were followed up clinically, endoscopically, and radiologically to assess for local recurrence or disease progression. Results: From January 2015 to March 2018, a total of 47 patients with rectal cancer in our center received conservative treatment following neoadjuvant therapy. The median age of the patients is 58 (53-66). The proportions of stages I to IV are 4.3%, 12.8%, 70.2%, 8.5%, respectively. After a median follow-up of 20 month, tumor regrowth occurred in five out of 47 (10.6%) patients. All local regrowth was diagnosed in the first two years, and four out of five (80%) of local regrowth was located in the bowel wall. All patients underwent salvage surgery. Distant metastasis was diagnosed in four of 47 patients (8.5%). two-year overall survival was 89.9%, and two-year disease-free survival was 76.5%. Conclusions: Organ preservation for locally advanced rectal cancer is feasible for selected patients who achieve a complete response to individualized neoadjuvant CRT. The survival of patients is not impaired with “watch-and-wait” strategy.

scholarly journals Elevated Platelet Count as Predictor of Recurrence in Rectal Cancer Patients Undergoing Preoperative Chemoradiotherapy Followed by Surgery

2015 ◽  
Vol 100 (2) ◽  
pp. 199-207 ◽  
Author(s):  
Yuji Toiyama ◽  
Yasuhiro Inoue ◽  
Mikio Kawamura ◽  
Aya Kawamoto ◽  
Yoshinaga Okugawa ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Cancer Patients ◽  
Locally Advanced ◽  
Neoadjuvant Chemoradiotherapy ◽  
Disease Free Survival ◽  
Advanced Rectal Cancer ◽  
Poor Overall Survival ◽  
Neutrophil Lymphocyte Ratio ◽  
Lymphocyte Ratio ◽  
The Impact

The impact of systemic inflammatory response (SIR) on prognostic and predictive outcome in rectal cancer after neoadjuvant chemoradiotherapy (CRT) has not been fully investigated. This retrospective study enrolled 89 patients with locally advanced rectal cancer who underwent neoadjuvant CRT and for whom platelet (PLT) counts and SIR status [neutrophil/lymphocyte ratio (NLR) and platelet/lymphocyte ratio (PLR)] were available. Both clinical values of PLT and SIR status in rectal cancer patients were investigated. Elevated PLT, NLR, PLR, and pathologic TNM stage III [ypN(+)] were associated with significantly poor overall survival (OS). Elevated PLT, NLR, and ypN(+) were shown to independently predict OS. Elevated PLT and ypN(+) significantly predicted poor disease-free survival (DFS). Elevated PLT was identified as the only independent predictor of DFS. PLT counts are a promising pre-CRT biomarker for predicting recurrence and poor prognosis in rectal cancer.

scholarly journals CANCER-EMBRYONIC ANTIGEN IN PREDICTING THERAPEUTIC TUMOR PATHOMORPHISM AFTER NEOADJUVANT CHEMORADIOTHERAPY IN PATIENTS WITH RECTAL CANCER

2018 ◽  
Vol 5 (2) ◽  
pp. 36-47
Author(s):  
D. V. Erygin ◽  
N. G. Minaeva ◽  
S. A. Ivanov ◽  
N. Yu. Dvinskikh ◽  
N. Yu. Novikov ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Rectal Cancer ◽  
Clinical Stage ◽  
Combined Treatment ◽  
Locally Advanced ◽  
Neoadjuvant Treatment ◽  
Prognostic Significance ◽  
Neoadjuvant Chemoradiotherapy ◽  
Disease Free Survival ◽  
Advanced Rectal Cancer

The purpose of the study was to evaluate the prognostic significance of carcinoerembryonic antigen in patients with rectal cancer and correlate its baseline with the degree of therapeutic pathomorphosis after neoadjuvant chemoradiotherapy.Materials and methods. An estimate of the informative value of carcinoerembryonic antigen (CEA) indices in 179 patients with colorectal cancer determined before and after preoperative chemoradiotherapy (CRT) in SOD 50 Gy.Results. Analysis of the results presented in the study showed that in all patients, CRT caused a significant decrease in the level of CEA (–71%) 10 weeks after its end (p < 0.001). In the course of the pathomorphological study, after the neoadjuvant treatment, the first degree of tumor pathomorphism was recorded in 4.5% of patients, II – 38.5%, III – 45%, IV – 12% (the degree of pathomorphosis is not related to the clinical stage and the degree of differentiation of colorectal cancer). It was revealed that patients with III and IV degrees of therapeutic pathomorphosis initially had a CEA level lower, in comparison with patients with grade I-II. Clinical progression of the disease is diagnosed in 24% of cases (43/179). It was noted that in patients with the IV degree of therapeutic pathomorphism of the tumor, no recurrence of the rectal cancer was detected in either case.Conclusion. The results of the study showed that the problem of individual prediction of the effectiveness of combined treatment of the rectal cancer remains very relevant, rather complicated and yet not completely solved. However, it can be assumed that the use of such an indicator as CEA in monitoring patients after the treatment, can serve as a criterion for the sensitivity of colorectal cancer to CRT. Initially low antigen level can be considered as a positive factor of tumor response to ongoing treatment and disease-free survival of patients with locally advanced rectal cancer.

The consensus Immunoscore adapted to biopsies in patients with locally advanced rectal cancer: Potential clinical significance for a “Watch and Wait” strategy.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 2628-2628
Author(s):  
Carine El Sissy ◽  
Amos Kirilovsky ◽  
Marc Van Den Eynde ◽  
Alfredo Romero ◽  
Florence Marliot ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Locally Advanced ◽  
Neoadjuvant Treatment ◽  
Neoadjuvant Chemoradiotherapy ◽  
Disease Free Survival ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
Reliable Estimate ◽  
Watch And Wait ◽  
Significant Difference

2628 Background: We investigated whether an adaptation to rectal biopsies of the recently validated consensus Immunoscore, could predict the response to neoadjuvant treatment and delineate clinical responders that could benefit from a “Watch and Wait” (W&W) strategy with acceptable outcomes. Methods: Initial biopsies from 273 patients with locally advanced rectal cancer (LARC) treated by neoadjuvant chemoradiotherapy (nCRT) followed by Total Mesorectal Excision (TME), were immunostained for CD3+ and cytotoxic CD8+ T cells and quantified by digital pathology to determine the Immunoscore within pre-treatment Biopsy (ISB). Expression level of 44 immune related genes post-neoadjuvant treatment was investigated by Nanostring technology (n = 64 patients). Results were correlated with response to neoadjuvant treatment, disease free survival (DFS) and time to recurrence (TTR). Prognostic performance of ISB was finally assessed in 73 LARC treated by W&W strategy. Results: ISB Low, Intermediate and High were respectively observed in 23.3, 50.4 and 26.3 % of the cohort. ISB was positively and significantly correlated with the response to nCRT, as evaluated by Dworak classification (P = .0034), ypTNM (P = .0003), down-staging (P = .0014), and neoadjuvant rectal (NAR) score, (P < .0001). ISB status was also positively associated with the degree of local immune activation post-neoadjuvant treatment. ISB High patients were at low risk of relapse, with 5-year DFS rates of 81.1 % (CI, 71.3-92.1 %) as compared to 57.8 % (CI, 45.9-72.9 %) in ISB low patients. In multivariate analysis, ISB was the only significant parameter at presentation associated with DFS (High vs Low: P = .001). Among W&W patients, significant difference was observed for TTR according to ISB status (High vs Low: P = .025). Conclusions: ISB could provide a reliable estimate of the response to nCRT and risk of recurrence in LARC patients' treated by TME or W&W strategy.

scholarly journals Neoadjuvant chemoradiotherapy followed by surgery benefits patients aged 75 years or older with locally advanced rectal cancer

2019 ◽  
Author(s):  
Xiaoliang Liu ◽  
Ke Hu ◽  
Fuquan Zhang ◽  
Xiaorong Hou ◽  
Yi Xiao ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Elderly Patients ◽  
Locally Advanced ◽  
Neoadjuvant Treatment ◽  
Neoadjuvant Chemoradiotherapy ◽  
Disease Free Survival ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
Significant Prognostic Factor ◽  
Clinical Records

Abstract Background: To evaluate the efficacy and treatment related morbidity of neoadjuvant chemoradiotherapy and surgery in elderly patients (aged 75 years or older) with locally advanced rectal cancer (LARC). Methods: We reviewed clinical records of elderly patients with LARC treated with neoadjuvant chemoradiotherapy from January 2008 to June 2017 at our institute. A dose of 45-50Gy in 25 fractions was delivered to pelvis. The primary tumor received a dose of 55Gy concomitantly. The concurrent chemotherapy included capecitabine alone and capecitabine plus oxaliplatin (Xelox). Surgery was performed for suitable patients at least 6 weeks after neoadjuvant treatment. Overall survival (OS), disease specific survival (DSS), disease free survival (DFS) and local control (LC) were calculated with Kaplan-Meier method. Univariate and multivariate analyses were performed with cox proportional hazards model. A two-side value of P<0.05 was defined as statistical significance. Results: A total of 85 patients were enrolled in this study, the median age was 80 years old (range: 75-90 years). After neoadjuvant treatment, surgery was performed in 56 patients (65.9%). Twelve patients (21.4%) obtained pathological complete response (pCR). The incidence of grade 3 or greater acute hematological, gastrointestinal and genitourinary toxicities were 10.7%, 5.2% and 1.8%, respectively. Seven patients (12.5%) experienced postoperative complications. The median follow-up duration was 35.7 months (range: 4.3-100.3 months), The 3-year OS, DSS, DFS and LC were 68.9%, 75.8%, 68.2% and 83.9%, respectively. Surgery was a significant prognostic factor for OS (HR: 10.092, 95%CI: 2.082-36.351, P<0.001), DSS (HR: 4.681, 95%CI: 1.971-11.113, P<0.001), DFS (HR: 5.509, 95%CI: 1.964-15.454, P=0.001) and LC (HR: 3.089, 95%CI: 1.244-11.669, P=0.019). Clinical T downstaging after neoadjuvant treatment was significantly associated with better DFS (HR: 4.554, 95%CI: 1.601-12.958, P=0.004). Conclusion: In patients aged 75 years or older with LARC, neoadjuvant chemoradiotherapy followed by surgery was well tolerated with promising survival outcomes, which should be strongly suggested if medically suitable.

Role of 18F-PET-CT to Predict Pathological Response After Neoadjuvant Treatment of Rectal Cancer

2021 ◽  
Author(s):  
Riccardo Caruso ◽  
Emilio Vicente ◽  
Yolanda Quijano ◽  
Hipolito Duran ◽  
Isabel Fabra ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Fdg Pet ◽  
Locally Advanced ◽  
Neoadjuvant Treatment ◽  
Standardized Uptake Value ◽  
Disease Free Survival ◽  
Pet Ct ◽  
Significant Difference ◽  
18F Fdg ◽  
Fdg Pet Ct

Abstract Objectives: Neoadjuvant radiochemotherapy (nCRT) is universally considered to be a valid treatment to achieve downstaging, improve local disease control and obtain better resectability in locally advanced rectal cancer (LARC). The aim of this study is to correlate the change in tumor 18F -FDG PET-CT standardized uptake value (SUV) before and after nCRT, in order to obtain an early prediction of pathologic response (pR) achieved in patients with LARC.Data description: We performed a retrospective analysis of patients with LARC diagnosis who underwent curative resection. All patients received nCRT and surgical treatment was carried after 8/12th. All patients underwent a baseline 18F -FDG PET-CT scan within the week prior to the initiation of the treatment (PET-CT SUV1) and a second scan (PET-C T SUV2) within six weeks of the completion of nCRT. Furthermore, we evaluated the prognostic value of 18F -FDG PET-CT in terms of disease free survival (DFS) and overall survival (OS) in patients with LARC.A total of 133 patients with LARC were included in the study. Patients were divided in two groups according to the TRG (tumor regression grade): 107 (80%) as Responders group (TRG0-TRG1) and 26 (25%) as the No-Responders group (TRG2-TRG3). We obtained a significant difference in Δ%SUV between the two different groups responders vs no responders (p<0.012).The results of this analysis have shown that 18F-FDG PET-CT may be an indicator in order to evaluate the pR to nCRT in patients with LARC. The decrease in 18F-FDG PET-CT uptake in the primary tumor may offer primary information in order to early identify those patients more likely to obtain a pCR to nCRT and predict those unlikely to regress significantly.

scholarly journals Association of mismatch repair status with survival and response to neoadjuvant chemo(radio)therapy in rectal cancer

2020 ◽  
Vol 4 (1) ◽  
Author(s):  
Shu-Biao Ye ◽  
Yi-Kan Cheng ◽  
Lin Zhang ◽  
Yi-Feng Zou ◽  
Ping Chen ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Cancer Patients ◽  
Mismatch Repair ◽  
Neoadjuvant Chemoradiotherapy ◽  
Disease Free Survival ◽  
Stage Iii ◽  
Neoadjuvant Radiotherapy ◽  
Radio Therapy ◽  
Colorectal Cancer Patients ◽  
The Impact

Abstract Prior reports have indicated that defective mismatch repair (MMR) has a favorable impact on outcome in colorectal cancer patients treated with surgery, immunotherapy, or adjuvant chemotherapy. However, the impact of MMR status on response to neoadjuvant radiotherapy in rectal cancer is not well understood. Here we report that dMMR was associated with improved disease-free survival (DFS) (P = 0.034) in patients receiving neoadjuvant chemotherapy (NCT). Patients with dMMR tumors who received neoadjuvant chemoradiotherapy (NCRT) achieved significantly worse DFS (P = 0.026) than those treated with NCT. Conversely, NCRT improved DFS (P = 0.043) in patients with pMMR tumors, especially for stage III disease with improved DFS (P = 0.02). The presence of dMMR was associated with better prognosis in rectal cancer patients treated with NCT. NCT benefited patients with dMMR tumors; while NCRT benefited patients with stage III disease and pMMR tumors. Patients stratified by MMR status may provide a more tailored approach to rectal cancer neoadjuvant therapy.

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