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Gastrointestinal cancer
Combined High-Dose Radiotherapy with Sequential Gemcitabine-Cisplatin Based Chemotherapy Increase the Resectability and Survival in Locally Advanced Unresectable Intrahepatic Cholangiocarcinoma: A Multi-institutional Cohort Study
Jung Ho Im, Jeong Il Yu, Tae Hyun Kim, Tae Gyu Kim, Jun Won Kim, Jinsil Seong
Cancer Res Treat. 2024;56(3):838-846.   Published online January 2, 2024
DOI: https://doi.org/10.4143/crt.2023.886
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
The locally advanced unresectable intrahepatic cholangiocarcinoma (ICC) has detrimental oncological outcomes. In this study, we aimed to investigate the efficacy of radiotherapy in patients with locally advanced unresectable ICC.
Materials and Methods
Between 2001 and 2021, 116 patients were identified through medical record who underwent radiotherapy for locally advanced unresectable ICC. The resectability of ICC is determined by the multidisciplinary team at each institution. Overall survival (OS) were analyzed using the Kaplan-Meier method, and prognostic factors were analyzed using the Cox proportional hazards model.
Results
The median equivalent radiotherapy dose in 2 Gy fractions (EQD2) was 52 Gy (range, 30 to 110 Gy). Forty-seven patients (40.5%) received sequential gemcitabine-cisplatin based chemotherapy (GEM-CIS CTx). Multivariate analysis identified two risk factors, EQD2 of ≥ 60 Gy and application of sequential GEM-CIS CTx for OS. Patients were grouped by these two risk factors: group 1, EQD2 ≥ 60 Gy with sequential GEM-CIS CTx (n=25); group 2, EQD2 < 60 Gy with sequential GEM-CIS CTx or fluoropyrimidine-based concurrent chemoradiotherapy (n=70); and group 3, radiotherapy alone (n=21). Curative resection was more frequently undergone in group 1 than in groups 2 or 3 (28% vs. 8.6% vs. 0%, respectively). Consequently, OS was significantly better in group 1 than in groups 2 and 3 (p < 0.05).
Conclusion
Combined high-dose radiotherapy with sequential GEM-CIS CTx improved oncologic outcomes in patients with locally advanced unresectable ICC. Further prospective studies are required to validate these findings.
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Genitourinary Cancer
Neoadjuvant Chemotherapy–Guided Bladder-Sparing Treatment for Muscle-Invasive Bladder Cancer: Results of a Pilot Phase II Study
Hongzhe Shi, Wen Zhang, Xingang Bi, Dong Wang, Zejun Xiao, Youyan Guan, Kaopeng Guan, Jun Tian, Hongsong Bai, Linjun Hu, Chuanzhen Cao, Weixing Jiang, Zhilong Hu, Jin Zhang, Yan Chen, Shan Zheng, Xiaoli Feng, Changling Li, Yexiong Li, Jianhui Ma, Yueping Liu, Aiping Zhou, Jianzhong Shou
Cancer Res Treat. 2021;53(4):1156-1165.   Published online February 10, 2021
DOI: https://doi.org/10.4143/crt.2020.1356
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
Reduced quality of life after cystectomy has made bladder preservation a popular research topic for muscle-invasive bladder cancer (MIBC). Previous research has indicated significant tumor downstaging after neoadjuvant chemotherapy (NAC). However, maximal transurethral resection of bladder tumor (TURBT) was performed before NAC to define the pathology, impacting the real evaluation of NAC. This research aimed to assess real NAC efficacy without interference from TURBT and apply combined modality therapies guided by NAC efficacy.
Materials and Methods
Patients with cT2-4aN0M0 MIBC were confirmed by cystoscopic biopsy and imaging. NAC efficacy was assessed by imaging, urine cytology, and cystoscopy with multidisciplinary team discussion. Definite responders (≤ T1) underwent TURBT plus concurrent chemoradiotherapy. Incomplete responders underwent radical cystectomy or partial cystectomy if feasible. The primary endpoint was the bladder preservation rate.
Results
Fifty-nine patients were enrolled, and the median age was 63 years. Patients with cT3-4 accounted for 75%. The median number of NAC cycles was three. Definite responders were 52.5%. The complete response (CR) was 10.2%, and 59.3% of patients received bladder-sparing treatments. With a median follow-up of 44.6 months, the 3-year overall survival (OS) was 72.8%. Three-year OS and relapse-free survival were 88.4% and 60.0% in the bladder-sparing group but only 74.3% and 37.5% in the cystectomy group. The evaluations of preserved bladder function were satisfactory.
Conclusion
After stratifying MIBC patients by NAC efficacy, definite responders achieved a satisfactory bladder-sparing rate, prognosis, and bladder function. The CR rate reflected the real NAC efficacy for MIBC. This therapy is worth verifying through multicenter research.

Citations

Citations to this article as recorded by  
  • Concomitant chemotherapy in trimodal treatment of patients with muscle invasive bladder cancer: A systematic review of prospective trials
    Camille Baudelin, Paul Sargos, Derek Dinart, Christophe Hennequin, Diego Teyssonneau, Lucie Meynard, Nam-Son Vuong, Félix Lefort, Michael Baboudjian, Guilhem Roubaud
    Critical Reviews in Oncology/Hematology.2025; 205: 104557.     CrossRef
  • Does Bladder Cancer Subtype Influence Pathologic Complete Response (pCR) and Pelvic Diffusion-Weighted Magnetic Resonance Imaging (DW-MRI) Response Evaluation After Neoadjuvant Chemotherapy? Pathological Perspective
    Ji Min Kim, Euno Choi, Sun Hee Sung, Jungmin Jo, Dong-Hyeon Lee, Sanghui Park
    Clinical Genitourinary Cancer.2024; 22(2): 224.     CrossRef
  • A comparative analysis of radical cystectomy with perioperative chemotherapy, chemoradiation therapy, or systemic therapy in patients with clinically advanced node-positive bladder cancer (cN2/N3)
    Harshit Garg, Mukund Bhandari, Furkan Dursun, Michael A. Liss, Dharam Kaushik, Robert S. Svatek, Ahmed M. Mansour
    Frontiers in Oncology.2024;[Epub]     CrossRef
  • Clinical efficacy analysis of partial cystectomy and radical cystectomy in the treatment of muscle-invasive sarcomatoid carcinoma of the urinary bladder
    Jiansheng Xiao, Hua Chen, Jiaqi Ge, Tairong Liu
    Frontiers in Oncology.2024;[Epub]     CrossRef
  • Downstaging guided neoadjuvant strategy shift and bladder preservation in locally advanced bladder cancer: A case report
    Gan Du, Zhichao Jiang, Wang Qu, Jin Zhang, Shan Zheng, Yueping Liu, Aiping Zhou, Hongzhe Shi, Jianzhong Shou
    Heliyon.2024; 10(6): e27685.     CrossRef
  • Editorial: Organ-sparing surgery for genitourinary cancers
    Gongwei Long, Xingyuan Xiao, Haoran Liu, Yucong Zhang, Chunguang Yang
    Frontiers in Oncology.2024;[Epub]     CrossRef
  • News and prospects on radiotherapy for bladder cancer: Is trimodal therapy becoming the gold standard?
    Olivier Riou, Christophe Hennequin, Jonathan Khalifa, Paul Sargos
    Cancer/Radiothérapie.2024; 28(6-7): 623.     CrossRef
  • Health-related quality of life after curative treatment for muscle-invasive bladder cancer
    Elisabeth Grobet-Jeandin, Ugo Pinar, Jérôme Parra, Morgan Rouprêt, Thomas Seisen
    Nature Reviews Urology.2023; 20(5): 279.     CrossRef
  • Combined Modality Bladder-Sparing Therapy for Muscle-Invasive Bladder Cancer: How (Should) We Do It? A Narrative Review
    Artur Lemiński, Wojciech Michalski, Bartłomiej Masojć, Krystian Kaczmarek, Bartosz Małkiewicz, Jakub Kienitz, Barbara Zawisza-Lemińska, Michał Falco, Marcin Słojewski
    Journal of Clinical Medicine.2023; 12(4): 1560.     CrossRef
  • Survival after sequential neoadjuvant chemotherapy followed by trimodal treatment or radical cystectomy for muscle-invasive bladder cancer
    Pierre-Louis Reignier, Hélène Gauthier, Christophe Hennequin, Quiterie Aussedat, Evanguelos Xylinas, François Desgrandchamps, Stéphane Culine, Alexandra Masson-Lecomte, Clément Dumont
    World Journal of Urology.2023; 41(11): 3249.     CrossRef
  • Neoadjuvant chemotherapy with gemcitabine and cisplatin followed by selective bladder preservation chemoradiotherapy in muscle-invasive urothelial carcinoma of bladder
    Hyun Hwan Sung, Hana Kim, Ryul Kim, Chan Kyo Kim, Ghee Young Kwon, Won Park, Wan Song, Byong Chang Jeong, Se Hoon Park
    Investigative and Clinical Urology.2022; 63(2): 168.     CrossRef
  • Disease Management of Clinical Complete Responders to Neoadjuvant Chemotherapy of Muscle-Invasive Bladder Cancer: A Review of Literature
    Jie Wu, Rui-Yang Xie, Chuan-Zhen Cao, Bing-Qing Shang, Hong-Zhe Shi, Jian-Zhong Shou
    Frontiers in Oncology.2022;[Epub]     CrossRef
  • Contemporary Staging for Muscle-Invasive Bladder Cancer: Accuracy and Limitations
    Patrick J. Hensley, Valeria Panebianco, Eugene Pietzak, Alexander Kutikov, Raghu Vikram, Matthew D. Galsky, Shahrokh F. Shariat, Morgan Roupret, Ashish M. Kamat
    European Urology Oncology.2022; 5(4): 403.     CrossRef
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The Prognostic Impact of the Number of Metastatic Lymph Nodes and a New Prognostic Scoring System for Recurrence in Early-Stage Cervical Cancer with High Risk Factors: A Multicenter Cohort Study (KROG 15-04)
Jeanny Kwon, Keun-Young Eom, Young Seok Kim, Won Park, Mison Chun, Jihae Lee, Yong Bae Kim, Won Sup Yoon, Jin Hee Kim, Jin Hwa Choi, Sei Kyung Chang, Bae Kwon Jeong, Seok Ho Lee, Jihye Cha
Cancer Res Treat. 2018;50(3):964-974.   Published online October 24, 2017
DOI: https://doi.org/10.4143/crt.2017.346
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
We aimed to assess prognostic value of metastatic pelvic lymph node (mPLN) in early-stage cervical cancer treated with radical surgery followed by postoperative chemoradiotherapy. Also, we sought to define a high-risk group using prognosticators for recurrence.
Materials and Methods
A multicenter retrospective study was conducted using the data from 13 Korean institutions from 2000 to 2010. A total of 249 IB-IIA patients with high-risk factors were included. We evaluated distant metastasis-free survival (DMFS) and disease-free survival (DFS) in relation to clinicopathologic factors including pNstage, number of mPLN, lymph node (LN)ratio (number of positive LN/number of harvested LN), and log odds of mPLNs (log(number of positive LN+0.5/number of negative LN+0.5)).
Results
In univariate analysis, histology (squamous cell carcinoma [SqCC] vs. others), lymphovascular invasion (LVI), number of mPLNs (≤ 3 vs. > 3), LN ratio (≤ 17% vs. > 17%), and log odds of mPLNs (≤ ‒0.58 vs. > ‒0.58) were significant prognosticators for DMFS and DFS. Resection margin involvement only affected DFS. No significant survival difference was observed between pN0 patients and patients with 1-3 mPLNs. Multivariate analysis revealed that mPLN > 3, LVI, and non-SqCC were unfavorable index for both DMFS (p < 0.001, p=0.020, and p=0.031, respectively) and DFS (p < 0.001, p=0.017, and p=0.001, respectively). A scoring system using these three factors predicts risk of recurrence with relatively high concordance index (DMFS, 0.69; DFS, 0.71).
Conclusion
mPLN > 3 in early-stage cervical cancer affects DMFS and DFS. A scoring system using mPLNs > 3, LVI, and non-SqCC could stratify risk groups of recurrence in surgically resected early-stage cervix cancer with high-risk factors.

Citations

Citations to this article as recorded by  
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    Yang Wang, Xingyu Liu, Jing Liu, Liying Liu, Yue Ma
    Archives of Gynecology and Obstetrics.2025; 311(1): 123.     CrossRef
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    Elki Sze-Nga Cheung, Philip Yuguang Wu
    Cancers.2025; 17(2): 202.     CrossRef
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    Zheng Zeng, Yining Chen, Yuliang Sun, Bing Zhou, Haoran Xu, Lei He, Ke Hu, Jie Qiu, Fuquan Zhang, Junfang Yan
    Clinical & Experimental Metastasis.2025;[Epub]     CrossRef
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    Michihide Maeda, Seiji Mabuchi, Mina Sakata, Satoki Deguchi, Reisa Kakubari, Shinya Matsuzaki, Tsuyoshi Hisa, Shoji Kamiura
    Japanese Journal of Clinical Oncology.2024; 54(2): 146.     CrossRef
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    Jorge Cea García, Francisco Márquez Maraver, M. Carmen Rubio Rodríguez, Laura Ríos-Pena, Inmaculada Rodríguez Jiménez
    Indian Journal of Gynecologic Oncology.2024;[Epub]     CrossRef
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    Gui-Fen Ma, Gen-Lai Lin, Si-Tong Wang, Ya-Yu Huang, Chun-Li Xiao, Jing Sun, Ting-Yan Shi, Li-Bing Xiang
    BMC Women's Health.2024;[Epub]     CrossRef
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    Shuang Dong, Yan-Qing Peng, Ya-Nan Feng, Xiao-Ying Li, Li-Ping Gong, Shuang Zhang, Xiao-Shan Du, Li-Tao Sun
    BMC Women's Health.2024;[Epub]     CrossRef
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    BMC Cancer.2024;[Epub]     CrossRef
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    Syed S Abrar, Seoparjoo Azmel Mohd Isa, Suhaily Mohd Hairon, Najib M Yaacob, Mohd Pazudin Ismail
    Cureus.2024;[Epub]     CrossRef
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    Marina Senchukova
    American Journal of Clinical and Experimental Medicine.2024; 12(5): 61.     CrossRef
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    Journal of Obstetrics and Gynaecology.2023;[Epub]     CrossRef
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    Xingtao Long, Misi He, Lingling Yang, Dongling Zou, Dong Wang, Yuemei Chen, Qi Zhou
    Clinical Medicine Insights: Oncology.2023;[Epub]     CrossRef
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    Frontiers in Oncology.2022;[Epub]     CrossRef
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Review Article
Personalized Combined Modality Therapy for Locally Advanced Non-small Cell Lung Cancer
D. Nathan Kim, Taek-Keun Nam, Kevin S. Choe, Hak Choy
Cancer Res Treat. 2012;44(2):74-84.   Published online June 30, 2012
DOI: https://doi.org/10.4143/crt.2012.44.2.74
AbstractAbstract PDFPubReaderePub
Locally advanced non-small cell lung cancer (NSCLC) is a heterogeneous disease, and we have embarked on an era where patients will benefit from individualized therapeutic strategies based on identifiable molecular characteristics of the tumor. The landmark studies demonstrating the importance of molecular characterization of tumors for NSCLC patients, the promising molecular pathways, and the potential molecular targets/agents for treatment of this disease will be reviewed. Understanding these issues will aid in the development of rationally designed clinical trials, so as to determine best means of appropriately incorporating these molecular strategies, to the current standard of radiation and chemotherapy regimens, for the treatment of locally advanced NSCLC.

Citations

Citations to this article as recorded by  
  • The Correlation between Hemostatic Parameters and Mortality Rate in Patients with Non-Small Cell Lung Cancer
    Noni Novisari Soeroso, Fannie Rizki Ananda, Ganda Samosir, Herman Hariman, Putri Chairani Eyanoer
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    Rodney J. Landreneau, Daniel P. Normolle, Neil A. Christie, Omar Awais, Joseph J. Wizorek, Ghulam Abbas, Arjun Pennathur, Manisha Shende, Benny Weksler, James D. Luketich, Matthew J. Schuchert
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    Ping‐Li Sun, Yan Jin, Hyojin Kim, Choon‐Taek Lee, Sanghoon Jheon, Jin‐Haeng Chung
    Cancer Cytopathology.2013; 121(6): 311.     CrossRef
  • Thrombocytosis and immunohistochemical expression of connexin 43 at diagnosis predict survival in advanced non-small-cell lung cancer treated with cisplatin-based chemotherapy
    Gangjun Du, Yingming Yang, Yaping Zhang, Ting Sun, Weijie Liu, Yingying Wang, Jiahuan Li, Houyun Zhang
    Cancer Chemotherapy and Pharmacology.2013; 71(4): 893.     CrossRef
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  • 5 Crossref
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Editorial
New Step of Joint Publication with the Korean Association for Clinical Oncology
Il Han Kim
Cancer Res Treat. 2012;44(2):73-73.   Published online June 30, 2012
DOI: https://doi.org/10.4143/crt.2012.44.2.73
AbstractAbstract PDFPubReaderePub
No abstract available.
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Case Report
A Case of Non-Hodgkin's Lymphoma in Patient with Coombs' Negative Hemolytic Anemia and Idiopathic Thrombocytopenic Purpura
So Yeon Park, Soyon Kim, Eun Sil Kim, Soon Uk Choi, Hee Jae Hyun, Ju Young Ahn, Ju Hyoung Lee, Seo Hee Ryu, Jae Hyun Park, Gyeong In Lee, Hyo Jin Lee
Cancer Res Treat. 2012;44(1):69-72.   Published online March 31, 2012
DOI: https://doi.org/10.4143/crt.2012.44.1.69
AbstractAbstract PDFPubReaderePub
Coombs' negative autoimmune hemolytic anemia (AIHA) is a rare disease which shares similar clinical and hematological features with Coombs' positive AIHA, but its exact frequency remains unknown. There have been few reports of idiopathic thrombocytopenic purpura (ITP) and Coombs' negative AIHA associated with other lymphoproliferative disorders (LPDs). Since there is a well known association between LPDs and autoimmune phenomena, it is important to investigate the possibility of an underlying malignancy. We report a case of ITP and Coombs' negative AIHA associated with diffuse large B-cell lymphoma.

Citations

Citations to this article as recorded by  
  • Treatment of Secondary Immune Thrombocytopenia with Non-Hodgkin Lymphoma: A Case Report and Literature Review
    Yuya Kurihara, Kazuki Taoka, Eri Takagi, Kazuhiro Toyama, Kumi Nakazaki, Mineo Kurokawa
    Internal Medicine.2021; 60(10): 1583.     CrossRef
  • Primary, secondary or less frequent causes of immune thrombocytopenia: A case report
    Minodora Onisâi, Ana-Maria Vlădăreanu, Iuliana Iordan, Horia Bumbea, Mihaela Găman, Cristina Ciufu, Irina Voican, Diana Cîșleanu, Daniela Vasile, Cristina Marinescu, Anca Nicolescu, Andreea Spînu, Raluca Nistor, Adrian Alexandru
    Experimental and Therapeutic Medicine.2021;[Epub]     CrossRef
  • Successful Treatment of Aggressive Mature B-cell Lymphoma Mimicking Immune Thrombocytopenic Purpura
    Koya Ono, Yasushi Onishi, Masahiro Kobayashi, Satoshi Ichikawa, Shunsuke Hatta, Shotaro Watanabe, Yoko Okitsu, Noriko Fukuhara, Ryo Ichinohasama, Hideo Harigae
    Internal Medicine.2018; 57(17): 2573.     CrossRef
  • Efficacy of bendamustine on thrombocytopenia and hemolytic anemia secondary to CD5-positive B-cell lymphoma with massive splenomegaly in a patient with rheumatoid arthritis
    Yuzuru Hosoda, Hiroshi Hagino, Norihiko Hino, Toru Motokura
    Molecular and Clinical Oncology.2017; 7(5): 855.     CrossRef
  • Synchronous Occurrence of Diffuse Large B-cell Lymphoma of the Duodenum and Gastrointestinal Stromal Tumor of the Ileum in a Patient with Immune Thrombocytopenic Purpura
    Tohru Takahashi, Yumiko Maruyama, Mayuko Saitoh, Hideto Itoh, Mitsuru Yoshimoto, Masayuki Tsujisaki, Masato Nakayama
    Internal Medicine.2016; 55(20): 2951.     CrossRef
  • Clinical and reference lab characteristics of patients with suspected direct antiglobulin test (DAT)-negative immune hemolytic anemia
    M.S. Karafin, G.A. Denomme, M. Schanen, J.L. Gottschall
    Immunohematology.2015; 31(3): 108.     CrossRef
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Original Articles
Optimal Timing for the Administration of Capecitabine with Preoperative Chemoradiation for Locally Advanced Rectal Cancer
Young Ju Noh, Won Sik Choi, Jong Hoon Kim, Jin Cheon Kim, Chang Sik Yu, Hee Cheol Kim, Tae Won Kim, Heung Moon Chang, Min Hee Ryu, Seung Do Ahn, Sang-wook Lee, Seong Soo Shin, Jung Eun Lee, Eun Kyung Choi
Cancer Res Treat. 2006;38(1):30-34.   Published online February 28, 2006
DOI: https://doi.org/10.4143/crt.2006.38.1.30
AbstractAbstract PDFPubReaderePub
Purpose

Capecitabine is an oral fluoropyrimidine carbamate and it is known as an effective radiosensitizer. Capecitabine and its metabolite reach their peak concentration in the plasma at 1~2 hours after a single oral administration of capecitabine and the levels fall rapidly thereafter. To verify the radiosensitizing effect of capecitabine that is based on such pharmacokinetic characteristics, we performed a retrospective analysis on the optimal timing of capecitabine administration with performing preoperative chemoradiation for locally advanced rectal cancer.

Materials and Methods

Among 171 patients who were treated with preoperative radiotherapy and concurrent capecitabine administration for rectal cancer, 56 patients were administered capecitabine at 1~2 hours before radiotherapy (group A), and at other time in the other 115 patients (group B). Total mesorectal excision was done at 4 to 6 weeks after the completion of chemoradiation. The radiosensitizing effect of capecitabine was evaluated on the basis of the pathological response.

Results

Complete pathological regression of the primary tumor was observed in 12 patients (21.4%) for group A and in 11 patients (9.6%) for group B (p=0.031). Residual disease less than 0.5 cm (a good response) was observed in 19 patients (33.9%) for group A and in 23 patients (20.0%) for group B (p=0.038). On multivariate analysis, the capecitabine ingestion time showed marginal significance.

Conclusion

When performing preoperative chemoradiation for locally advanced rectal cancer, the radiosensitizing effect of capecitabine was enhanced when it was administered 1 hour before radiotherapy.

Citations

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  • Systematic review of treatment intensification using novel agents for chemoradiotherapy in rectal cancer
    R Clifford, N Govindarajah, J L Parsons, S Gollins, N P West, D Vimalachandran
    British Journal of Surgery.2018; 105(12): 1553.     CrossRef
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Combination Chemotherapy with 5-Fluorouracil and Carboplatin for Advanced Head and Neck Cancer
Eun Kyung Cho, Won Sup Lee, Chul Won Jung, Keun Seok Lee, Won Seog Kim, Ki Hyeong Lee, Dae Seog Heo, Yung Jue Bang, Kwang Hyun Kim, Charn II Park, Noe Kyeong Kim
J Korean Cancer Assoc. 1996;28(1):94-104.
AbstractAbstract PDF
Twenty-nine patients with previously untreated, locally advanced head and neck cancer were treated with two or three cycles of combination chemotherapy consisting of 5- fluorouracil infusion and carboplatin, followed by surgery and/or curative radiotherapy. Nine patients with recurrent head and neck cancer were treated with the same combination chemotherapy. The results were as follows; 1) Among 28 evaluable patients, response rate was 71.4%(partial response) after neoadjuvant chemotherapy. Following local modality(surgery and/or radiotherapy), response rate was 79%(complete response 51.4%, and partial response 25%). 2) One year survival rate in neoadjuvant group was 83% and one year progression-free survival rate, 68.8%. The progression-free survival of responders was significantly prolonged in comparison with that of non-responders(p<0.05). 3) In palliative treatment group, one partial response(11%) was observed among nine patients. Median time to progression was 6.8 weeks and median survival was 17.7 weeks; there was no significant difference between responders and non-responders. 4) Nausea and vomiting were frequently observed but easily controlled. Hematologic toxicities-leukopenia and thrombocytopenia were observed but were reversible. In conclusion, combination chemotherapy with carboplatin and 5-FU was effective for locally advanced head and neck cancer in neoadjuvant setting, but it had limited benefits for recurrent diseases. Toxicities were tolerable and neurotoxicity, ototoxicity, and nephrotoxicity were not observed.
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