scholarly journals Neoadjuvant Treatment Response As an Early Response Indicator for Patients With Rectal Cancer

2012 ◽  
Vol 30 (15) ◽  
pp. 1770-1776 ◽  
Author(s):  
In Ja Park ◽  
Y. Nancy You ◽  
Atin Agarwal ◽  
John M. Skibber ◽  
Miguel A. Rodriguez-Bigas ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Treatment Response ◽  
Tumor Response ◽  
Locally Advanced ◽  
Neoadjuvant Treatment ◽  
Neoadjuvant Chemoradiotherapy ◽  
Treatment Strategies ◽  
Surrogate Marker ◽  
Radical Resection ◽  
Oncologic Outcomes

Purpose Neoadjuvant chemoradiotherapy for rectal cancer is associated with improved local control and may result in complete tumor response. Associations between tumor response and disease control following radical resection should be established before tumor response is used to evaluate treatment strategies. The purpose of this study was to assess and compare oncologic outcomes associated with the degree of pathologic response after chemoradiotherapy. Patients and Methods All patients with locally advanced (cT3-4 or cN+ by endorectal ultrasonography, computed tomography, or magnetic resonance imaging) rectal carcinoma diagnosed from 1993 to 2008 at our institution and treated with preoperative chemoradiotherapy and radical resection were identified, and their records were retrospectively reviewed. The median radiation dose was 50.4 Gy with concurrent chemotherapy. Recurrence-free survival (RFS), distant metastasis (DM), and local recurrence (LR) rates were compared among patients with complete (ypT0N0), intermediate (ypT1-2N0), or poor (ypT3-4 or N+) response by using Kaplan-Meier survival analysis and multivariate Cox proportional hazards regression. Results In all, 725 patients were classified by tumor response: complete (131; 18.1%), intermediate (210; 29.0%), and poor (384; 53.0%). Age, sex, cN stage, and tumor location were not related to tumor response. Tumor response (complete v intermediate v poor) was associated with 5-year RFS (90.5% v 78.7% v 58.5%; P < .001), 5-year DM rates (7.0% v 10.1% v 26.5%; P < .001), and 5-year LR only rates (0% v 1.4% v 4.4%; P = .002). Conclusion Treatment response to neoadjuvant chemoradiotherapy among patients with locally advanced rectal cancer undergoing radical resection is an early surrogate marker and correlate to oncologic outcomes. These data provide guidance with response-stratified oncologic benchmarks for comparisons of novel treatment strategies.

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.

The effect of mistletoe extract on tumor response in neoadjuvant chemoradiotherapy for rectal cancer

2021 ◽  
Author(s):  
Jeong-Heum Baek ◽  
Youngbae Jeon ◽  
Kyoung-Won Han ◽  
Kyung-Ok Kim
Keyword(s):  
Rectal Cancer ◽  
Cancer Patients ◽  
Tumor Response ◽  
Anal Verge ◽  
Locally Advanced ◽  
Pathologic Complete Response ◽  
Neoadjuvant Chemoradiotherapy ◽  
Oncologic Outcomes ◽  
Tumor Regression Grade ◽  
Mistletoe Extract

Abstract Background Mistletoe extract, which is usually used as a complementary agent for cancer patients, provides an anticancer effect on various malignancies. The present study aimed to evaluate the effect of mistletoe extract (Abnoba Viscum Q®) on tumor responses in neoadjuvant chemoradiotherapy for locally advanced rectal cancer. Methods The rectal cancer patients who underwent neoadjuvant chemoradiotherapy were analyzed from Jan 2018 to Jul 2020. In the mistletoe group (MG), the patients were administered Abnoba Viscum Q® subcutaneously during chemoradiotherapy, and it was maintained just before surgery. Patients' demographics, clinical outcomes, and histopathological outcomes were compared between chemoradiation with the MG and nonmistletoe group (NMG). Results A total of 52 patients were included. There were MG of 15 patients and NMG of 37 patients. Baseline demographics were statistically similar between the two groups except the CA19-9 and tumor location levels from anal verge. There was no difference in the clinical stage for both groups. We also observed better tumor response in MG in terms of TRG, T stage, and overall TNM stage. Tumor response was significantly better in MG comparing NMG in terms of pathologic complete response rate (53.3% vs 21.6%, p = 0.044), good responder of tumor regression grade (66.7% vs 32.4%, p = 0.024), T downstaging (86.7% vs 43.2%, p = 0.004), and overall downstaging (86.7% vs 56.8%, p = 0.040). The toxicities during NCRT in both groups were minimal. Conclusion MG treated with chemoradiation combined with mistletoe extract showed better outcomes than NMG in terms of tumor responses. This diversity in treatment may elevate the method to hope for better oncologic outcomes. Prospective and randomized studies with long-term follow-up are warranted to confirm and extend this study.

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.

scholarly journals MRI-based clinical-radiomics model predicts tumor response before treatment in locally advanced rectal cancer

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Andrea Delli Pizzi ◽  
Antonio Maria Chiarelli ◽  
Piero Chiacchiaretta ◽  
Martina d’Annibale ◽  
Pierpaolo Croce ◽  
...  
Keyword(s):  
Machine Learning ◽  
Rectal Cancer ◽  
Treatment Response ◽  
Randomized Clinical Trials ◽  
Locally Advanced ◽  
Neoadjuvant Treatment ◽  
Learning Model ◽  
Partial Least Square ◽  
Machine Learning Model ◽  
Pre Treatment

AbstractNeoadjuvant chemo-radiotherapy (CRT) followed by total mesorectal excision (TME) represents the standard treatment for patients with locally advanced (≥ T3 or N+) rectal cancer (LARC). Approximately 15% of patients with LARC shows a complete response after CRT. The use of pre-treatment MRI as predictive biomarker could help to increase the chance of organ preservation by tailoring the neoadjuvant treatment. We present a novel machine learning model combining pre-treatment MRI-based clinical and radiomic features for the early prediction of treatment response in LARC patients. MRI scans (3.0 T, T2-weighted) of 72 patients with LARC were included. Two readers independently segmented each tumor. Radiomic features were extracted from both the “tumor core” (TC) and the “tumor border” (TB). Partial least square (PLS) regression was used as the multivariate, machine learning, algorithm of choice and leave-one-out nested cross-validation was used to optimize hyperparameters of the PLS. The MRI-Based “clinical-radiomic” machine learning model properly predicted the treatment response (AUC = 0.793, p = 5.6 × 10–5). Importantly, the prediction improved when combining MRI-based clinical features and radiomic features, the latter extracted from both TC and TB. Prospective validation studies in randomized clinical trials are warranted to better define the role of radiomics in the development of rectal cancer precision medicine.

scholarly journals Pathological Complete Response Following Different Neoadjuvant Treatment Strategies for Locally Advanced Rectal Cancer: A Systematic Review and Meta-analysis

2020 ◽  
Vol 27 (11) ◽  
pp. 4319-4336 ◽  
Author(s):  
S. Hoendervangers ◽  
J. P. M. Burbach ◽  
M. M. Lacle ◽  
M. Koopman ◽  
W. M. U. van Grevenstein ◽  
...  
Keyword(s):  
Systematic Review ◽  
Rectal Cancer ◽  
Pathological Complete Response ◽  
Meta Analysis ◽  
Locally Advanced ◽  
Neoadjuvant Treatment ◽  
Treatment Strategies ◽  
Complete Response ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer

Abstract Background Pathological complete response (pCR) following neoadjuvant treatment for locally advanced rectal cancer (LARC) is associated with better survival, less local recurrence, and less distant failure. Furthermore, pCR indicates that the rectum may have been preserved. This meta-analysis gives an overview of available neoadjuvant treatment strategies for LARC and analyzes how these perform in achieving pCR as compared with the standard of care. Methods Pubmed, Embase, and Cochrane Central bibliographic databases were searched. Randomized controlled trials in which patients received neoadjuvant treatment for MRI-staged nonmetastatic resectable LARC were included. The primary outcome was pCR, defined as ypT0N0. A meta-analysis of studies comparing an intervention with standard fluoropyrimidine-based chemoradiation (CRT) was performed. Results Of the 17 articles included in the systematic review, 11 were used for the meta-analysis. Addition of oxaliplatin to fluoropyrimidine-based CRT resulted in significantly more pCR compared with fluoropyrimidine-based CRT only (OR 1.46), but at the expense of more ≥ grade 3 toxicity. Other treatment strategies, including consolidation/induction chemotherapy and short-course radiotherapy (SCRT), did not improve pCR rates. None of the included trials reported a benefit in local control or OS. Five-year DFS was significantly worse after SCRT-delay compared with CRT (59% vs. 75.1%, HR 1.93). Conclusions All included trials fail to deliver high-level evidence to show an improvement in pCR compared with standard fluoropyrimidine-based CRT. The addition of oxaliplatin might result in more pCR but at the expense of more toxicity. Furthermore, this benefit does not translate into less local recurrence or improved survival.

Prognostic value of neoadjuvant treatment response in locally advanced rectal cancer

2018 ◽  
Vol 226 ◽  
pp. 15-23 ◽  
Author(s):  
Yvonne H. Sada ◽  
Hop S. Tran Cao ◽  
George J. Chang ◽  
Avo Artinyan ◽  
Benjamin L. Musher ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Treatment Response ◽  
Prognostic Value ◽  
Locally Advanced ◽  
Neoadjuvant Treatment ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer

scholarly journals Local environment in biopsy better predict the pathological response to neoadjuvant chemoradiotherapy in rectal cancer

2019 ◽  
Vol 39 (3) ◽  
Author(s):  
Yan Huang ◽  
Xiao-ying Lou ◽  
Ya-xi Zhu ◽  
Yu-chen Wang ◽  
Lei Zhang ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Tumor Response ◽  
Tumor Regression ◽  
Locally Advanced ◽  
Neoadjuvant Chemoradiotherapy ◽  
Pathological Response ◽  
Local Tumor ◽  
Independent Predictive Factor ◽  
Tumor Environment ◽  
The Impact

Abstract Neoadjuvant chemoradiotherapy (nCRT) followed by surgery is the standard treatment for locally advanced rectal cancer. Here, we analyzed the impact of local and systemic environments on the tumor response to preoperative chemoradiotherapy in rectal cancer. We recruited 141 patients with rectal cancer treated with nCRT. We evaluated the local tumor environment, including tumor-infiltrating lymphocytes (TILs), intratumor budding (ITB), and the systemic inflammatory environment, including the neutrophil-to-lymphocyte ratio (NLR) and C-reactive protein (CRP) level. Our finding revealed that tumor regression was significantly associated with the density of CD8+ TILs in the intraepithelial, the presence of ITB, the combination of NLR and CRP (NLR-CRP) value, and the combination of CD8+ intraepithelial TIL (iTIL) density and ITB presence. Moreover, multivariate analysis showed that only the combination of CD8+ iTILs and ITB was an independent predictive factor for the pathological response to nCRT in rectal cancer. Our finding demonstrate that the local tumor environment was a better predictor of the tumor response than the systemic environment and thus provided new insight into screening for patients who are more likely to benefit from cancer treatment.

What determines adjuvant chemotherapy use after neoadjuvant chemoradiotherapy for rectal cancer?

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 546-546 ◽  
Author(s):  
George J. Chang ◽  
Chung-Yuan Hu ◽  
Y. Nancy You ◽  
Cathy Eng ◽  
Miguel A. Rodriguez-Bigas ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Adjuvant Chemotherapy ◽  
Treatment Guidelines ◽  
Locally Advanced ◽  
Neoadjuvant Chemoradiotherapy ◽  
Radical Resection ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
Clinicopathologic Characteristics ◽  
Treatment Standard

546 Background: The treatment standard for rectal cancer patients after neoadjuvant chemoradiotherapy (CXRT) and radical resection includes adjuvant chemotherapy (CT). The purpose of this study was to evaluate patient demographic and clinicopathologic characteristics in relation to adjuvant CT use. Methods: A retrospective cohort study of patients ≥ 65 years old with rectal cancer treated by neoadjuvant CXRT and radical resection in the Surveillance, Epidemiology, and End Results-linked Medicare database (1998-2007, Medicare Part A/B only) was performed. Multivariate logistic regression was used to assess CT utilization in relation to patient, tumor and treatment response characteristics. Results: Among 1344 patients who met study criteria, 748 (55.6%) received adjuvant CT with 5-fluorouracil (FU) including 189 (25.3%) who also received oxaliplatin (Ox). ypStage was the strongest determinant of both any post-operative CT (43.1% stage I, 51.3% stage II, 73.4% stage III). Other associated factors included age, comorbidity, marital status and surgery type. In addition, age, socioeconomic status, and grade were associated with Ox use. These effects persisted even after exclusion of patients with comorbidities. Conclusions: Although standard treatment guidelines for locally advanced rectal cancer include postoperative CT for all patients after neoadjuvant CXRT and radical resection, nearly 1 in 2 patients failed to receive adjuvant CT. Despite the absence of established evidence, treatment decisions appear to be influenced by the findings at surgical pathology. [Table: see text]

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