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Efficacy and Feasibility of Adding Induction Chemotherapy to Neoadjuvant Chemoradiation in Locally Advanced Rectal Cancer: A Phase II Clinical Trial
Hamid Nasrolahi, Sepideh Mirzaei, Mohammad Mohammadianpanah, Ali Mohammad Bananzadeh, Maral Mokhtari, Mohammad Reza Sasani, Ahmad Mosalaei, Shapour Omidvari, Mansour Ansari, Niloofar Ahmadloo, Seyed Hasan Hamedi, Nezhat Khanjani
Ann Coloproctol. 2019;35(5):242-248.   Published online October 31, 2019
DOI: https://doi.org/10.3393/ac.2018.09.06
  • 4,761 View
  • 90 Download
  • 5 Web of Science
  • 5 Citations
AbstractAbstract PDF
Purpose
Currently, neoadjuvant chemoradiation (CRT) followed by total mesorectal resection is considered the standard of care for treating locally advanced rectal cancer. This study aimed to investigate the efficacy and feasibility of adding induction chemotherapy to neoadjuvant CRT in locally advanced rectal cancer.
Methods
This phase-II clinical trial included 54 patients with newly diagnosed, locally advanced (clinical T3–4 and/or N1–2, M0) rectal cancer. All patients were treated with 3 cycles of preoperative chemotherapy using the XELOX (capecitabine + oxaliplatin) regimen before and after a concurrent standard long course of CRT (45–50.4 Gy) followed by standard radical surgery. Pathologic complete response (PCR) rate and toxicity were the primary and secondary endpoints, respectively.
Results
The study participants included 37 males and 17 females, with a median age of 59 years (range, 20–80 years). Twenty-nine patients (54%) had clinical stage-II disease, and 25 patients (46%) had clinical stage-III disease. Larger tumor size (P = 0.006) and distal rectal location (P = 0.009) showed lower PCR compared to smaller tumor size and upper rectal location. Pathologic examinations showed significant tumor regression (6.1 ± 2.7 cm vs. 1.9 ± 1.8 cm, P < 0.001) with 10 PCRs (18.5%) compared to before the intervention. The surgical margin was free of cancer in 52 patients (96.3%). Treatment-related toxicities were easily tolerated, and all patients completed their planned treatment without interruption. Grade III and IV toxicities were infrequent.
Conclusion
The addition of induction chemotherapy to neoadjuvant CRT is an effective and well-tolerated treatment approach in patients with rectal cancer.

Citations

Citations to this article as recorded by  
  • Nanomedicine integrating the lipidic derivative of 5-fluorouracil, miriplatin and PD-L1 siRNA for enhancing tumor therapy
    An Lu, Yuhao Guo, Yi Yan, Lin Zhai, Xiangyu Wang, Weiran Cao, Zijie Li, Zhixia Zhao, Yujie Shi, Yuanjun Zhu, Xiaoyan Liu, Huining He, Zhiyu Wang, Jian-Cheng Wang
    Chinese Chemical Letters.2024; 35(6): 108928.     CrossRef
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    In Ja Park
    Precision and Future Medicine.2022; 6(2): 91.     CrossRef
  • Intensified Total Neoadjuvant Therapy in Patients With Locally Advanced Rectal Cancer: A Phase II Trial
    F. De Felice, G. D'Ambrosio, F. Iafrate, A. Gelibter, F.M. Magliocca, D. Musio, S. Caponetto, G. Casella, I. Clementi, A. Picchetto, G. Sirgiovani, M. Parisi, C. Orciuoli, G. Torrese, G. De Toma, V. Tombolini, E. Cortesi
    Clinical Oncology.2021; 33(12): 788.     CrossRef
  • Efficacy and safety of sequential neoadjuvant chemotherapy and short-course radiation therapy followed by delayed surgery in locally advanced rectal cancer: a single-arm phase II clinical trial with subgroup analysis between the older and young patients
    Alimohammad Bananzadeh, Ali Akbar Hafezi, NamPhong Nguyen, Shapour Omidvari, Ahmad Mosalaei, Niloofar Ahmadloo, Mansour Ansari, Mohammad Mohammadianpanah
    Radiation Oncology Journal.2021; 39(4): 270.     CrossRef
  • Induction Chemotherapy in Patients With Anal Canal Cancer: A Pilot Study
    Francesca De Felice, Daniela Musio, Vincenzo Tombolini
    Clinical Colorectal Cancer.2020; 19(3): e137.     CrossRef
Oncologic Outcomes in Patients Who Undergo Neoadjuvant Chemoradiotherapy and Total Mesorectal Excision for Locally Advanced Rectal Cancer: A 14-Year Experience in a Single Institution
Min Jung Kim, Seung-Yong Jeong, Ji Won Park, Seung-Bum Ryoo, Sang Sik Cho, Ki Young Lee, Kyu Joo Park
Ann Coloproctol. 2019;35(2):83-93.   Published online April 30, 2019
DOI: https://doi.org/10.3393/ac.2019.04.22.1
  • 5,131 View
  • 97 Download
  • 21 Web of Science
  • 19 Citations
AbstractAbstract PDF
Purpose
This study evaluated the oncologic outcomes of locally advanced rectal cancer patients who underwent preoperative neoadjuvant chemoradiotherapy (CRT) followed by surgery and determined the prognostic significance of pathologic complete response (pCR).
Methods
Between January 2002 and December 2015, 580 patients with rectal cancer who underwent surgery after neoadjuvant CRT were identified. Survival according to tumor response to CRT and pathologic stage was analyzed using the Kaplan-Meier method, and the Cox proportional hazard model was used to identify factors associated with survival outcomes.
Results
A total of 111 patients (23.7%) achieved pCR while the other 469 patients showed residual disease. Patients with pCR had a lower pretreatment carcinoembryonic antigen level and earlier cT classification than those with residual disease. With a median follow-up of 78 months, disease-free survival (DFS) and overall survival (OS) were significantly better in the pCR group than in the residual disease group. The 5-year DFS and 5-year OS for patients with ypStage 0, I, II, or III were 92.5%, 85.1%, 72.2%, 54.3% (P < 0.001) and 94.5%, 91.0%, 83.1%, 69.3%, respectively (P < 0.001). Pathologic AJCC stage after CRT was the most statistically significant independent predictor of OS (HR, 6.97 [95% confidence interval, 3.16–15.39] for stage III vs. stage 0) and DFS (HR, 7.30 [95% confidence interval, 3.63–14.67] for stage III vs. stage 0).
Conclusion
Rectal cancer patients who achieved pCR showed improved survival compared to those with residual disease after preoperative CRT. Moreover, pCR was an independent indicator of OS and DFS, and pathologic AJCC stage was correlated with survival after preoperative CRT.

Citations

Citations to this article as recorded by  
  • Analysis of clinical and pathological prognostic factors of survival in rectal adenocarcinoma treated with preoperative radiochemotherapy
    Sarhan Sydney Saad, Nora Forones, Gaspar Lopes Filho, Jaques Waisberg, Elesiario Caetano Júnior, Ricardo Artigiani-Neto, Delcio Matos
    Acta Cirúrgica Brasileira.2025;[Epub]     CrossRef
  • Lateral pelvic lymph node dissection based on nodal response to neoadjuvant chemoradiotherapy in mid/low rectal cancer: a retrospective comparative cohort study
    Tae-Gyun Lee, Duck-Woo Kim, Hong-min Ahn, Hye-Rim Shin, Mi Jeong Choi, Min Hyeong Jo, Heung-Kwon Oh, Sung-Bum Kang
    Annals of Surgical Treatment and Research.2025; 108(6): 333.     CrossRef
  • Predicting Positive Radial Margin on Restaging MRI of Patients with Low Rectal Cancer: Can We Do Better?
    Anurima Patra, Aisha Lakhani, Antony Augustine, Priyanka Mohapatra, Anu Eapen, Ashish Singh, Dipti Masih, Thomas S. Ram, Mark R. Jesudason, Rohin Mittal, Anuradha Chandramohan
    Indian Journal of Radiology and Imaging.2024; 34(01): 85.     CrossRef
  • A Review of Neoadjuvant Therapy and the Watch-and-Wait Protocol in Rectal Cancer: Current Evidence and Future Directions
    Iulian M Slavu, Octavian Munteanu, Florin Filipoiu, Raluca Tulin, Anca Monica Macovei Oprescu , Ileana Dima, Iulian A Dogaru, Adrian Tulin
    Cureus.2024;[Epub]     CrossRef
  • Significant Pathologic Response Following Neoadjuvant Therapy and Curative Resection in Patients With Rectal Cancer: Surgical and Oncological Outcomes From a Retrospective Cohort Study
    Fatemeh Shahabi, Majid Ansari, Khadijeh Najafi Ghobadi, Abolfazl Ghahramani, Amiresmaeil Parandeh, Maryam Saberi‐Karimian, Ala Orafaie, Abbas Abdollahi
    Cancer Reports.2024;[Epub]     CrossRef
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    In Ja Park
    The Ewha Medical Journal.2022; 45(1): 3.     CrossRef
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    Gyung Mo Son, In Young Lee, Sung Hwan Cho, Byung-Soo Park, Hyun Sung Kim, Su Bum Park, Hyung Wook Kim, Sang Bo Oh, Tae Un Kim, Dong Hoon Shin
    Precision and Future Medicine.2022; 6(1): 32.     CrossRef
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    In Ja Park
    Precision and Future Medicine.2022; 6(2): 91.     CrossRef
  • Patient Survival With ypT0N+ Following Neoadjuvant Therapy in Rectal Cancer
    Mohamedraed Elshami, Robert N. Goldstone, Lawrence S. Blaszkowsky, James C. Cusack, Theodore S. Hong, Jennifer Y. Wo, Motaz Qadan
    Diseases of the Colon & Rectum.2022; 65(10): 1224.     CrossRef
  • Neoadjuvant Radiotherapy Dose Escalation in Locally Advanced Rectal Cancer: a Systematic Review and Meta-analysis of Modern Treatment Approaches and Outcomes
    N. Hearn, D. Atwell, K. Cahill, J. Elks, D. Vignarajah, J. Lagopoulos, M. Min
    Clinical Oncology.2021; 33(1): e1.     CrossRef
  • Can normalized carcinoembryonic antigen following neoadjuvant chemoradiation predict tumour recurrence after curative resection for locally advanced rectal cancer?
    Youngki Hong, Amandeep Ghuman, Keat Seong Poh, Dimitri Krizzuk, Arun Nagarajan, Sudha Amarnath, Juan J. Nogueras, Steven D. Wexner, Giovanna DaSilva
    Colorectal Disease.2021; 23(6): 1346.     CrossRef
  • Omission of or Poor Response to Preoperative Chemoradiotherapy Impacts Radial Margin Positivity Rates in Locally Advanced Rectal Cancer
    Ana Sofia Ore, Gabrielle E. Dombek, Carlos A. Cordova-Cassia, Jeanne F. Quinn, Thomas E. Cataldo, Benjamin L. Schlechter, Matthew J. Abrams, Evangelos Messaris
    Diseases of the Colon & Rectum.2021; 64(6): 669.     CrossRef
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    Min-Young Park, In-Ja Park, Hyo-Seon Ryu, Jay Jung, Min-Sung Kim, Seok-Byung Lim, Chang-Sik Yu, Jin-Cheon Kim
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    Ye Won Jeon, In Ja Park, Jeong Eun Kim, Jin-Hong Park, Seok-Byung Lim, Chan Wook Kim, Yong Sik Yoon, Jong Lyul Lee, Chang Sik Yu, Jin Cheon Kim
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    Soo Young Oh, In Ja Park, Young IL Kim, Jong-Lyul Lee, Chan Wook Kim, Yong Sik Yoon, Seok-Byung Lim, Chang Sik Yu, Jin Cheon Kim
    Cancers.2021; 13(19): 4823.     CrossRef
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    Durim Delishaj, Ilaria Costanza Fumagalli, Stefano Ursino, Agostino Cristaudo, Francesco Colangelo, Antonio Stefanelli, Alessandro Alghisi, Giuseppe De Nobili, Romerai D’Amico, Alessandra Cocchi, Antonio Ardizzoia, Carlo Pietro Soatti
    World Journal of Clinical Cases.2021; 9(30): 9077.     CrossRef
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    Min Chul Kim, Jae Hwan Oh
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    Annals of Coloproctology.2019; 35(2): 51.     CrossRef
Review
How to Achieve a Higher Pathologic Complete Response in Patients With Locally Advanced Rectal Cancer Who Receive Preoperative Chemoradiation Therapy
Suk-Hwan Lee
Ann Coloproctol. 2019;35(1):3-8.   Published online February 28, 2019
DOI: https://doi.org/10.3393/ac.2019.02.17
  • 4,716 View
  • 109 Download
  • 3 Web of Science
  • 3 Citations
AbstractAbstract PDF
The current standard of care for treating patients with locally advanced rectal cancer includes preoperative chemoradiation therapy (PCRT) followed by a total mesorectal excision and postoperative adjuvant chemotherapy. A subset of these patients has achieved a pathologic complete response (pCR) and they have shown improved disease-free and overall survival compared to non-pCR patients. Thus, many efforts have been made to achieve a higher pCR through PCRT. In this review, results from various ongoing and recently completed clinical trials that are being or have been conducted with an aim to improve tumor response by modifying therapy will be discussed.

Citations

Citations to this article as recorded by  
  • Predictors of Pathologic Response After Total Neoadjuvant Therapy in Patients With Rectal Adenocarcinoma: A National Cancer Database Analysis
    David M McDermott, Sarah A Singh, Paul B Renz, Shaakir Hasan, Josh Weir
    Cureus.2021;[Epub]     CrossRef
  • Can Pretreatment Blood Biomarkers Predict Pathological Response to Neoadjuvant Chemoradiotherapy in Patients with Locally Advanced Rectal Cancer?
    Marina Morais, Telma Fonseca, Raquel Machado-Neves, Mrinalini Honavar, Ana Rita Coelho, Joanne Lopes, Elisabete Barbosa, Emanuel Guerreiro, Silvestre Carneiro
    Future Oncology.2021; 17(35): 4947.     CrossRef
  • Pretreatment Blood Biomarkers Predict Pathologic Responses to Neo-Crt in Patients with Locally Advanced Rectal Cancer
    Aijie Li, Kewen He, Dong Guo, Chao Liu, Duoying Wang, Xiangkui Mu, Jinming Yu
    Future Oncology.2019; 15(28): 3233.     CrossRef
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