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Concurrent and Adjuvant Temozolomide for Newly Diagnosed Grade III Gliomas without 1p/19q Co-deletion: A Randomized, Open-Label, Phase 2 Study (KNOG-1101 Study)
Kihwan Hwang, Tae Min Kim, Chul-Kee Park, Jong Hee Chang, Tae-Young Jung, Jin Hee Kim, Do-Hyun Nam, Se-Hyuk Kim, Heon Yoo, Yong-Kil Hong, Eun-Young Kim, Dong-Eun Lee, Jungnam Joo, Yu Jung Kim, Gheeyoung Choe, Byung Se Choi, Seok-Gu Kang, Jeong Hoon Kim, Chae-Yong Kim
Cancer Res Treat. 2020;52(2):505-515.   Published online October 28, 2019
DOI: https://doi.org/10.4143/crt.2019.421
AbstractAbstract PDFPubReaderePub
Purpose
We investigated the efficacy of temozolomide during and after radiotherapy in Korean adults with anaplastic gliomas without 1p/19q co-deletion.
Materials and Methods
This was a randomized, open-label, phase 2 study and notably the first multicenter trial for Korean grade III glioma patients. Eligible patients were aged 18 years or older and had newly diagnosed non-co-deleted anaplastic glioma with an Eastern Cooperative Oncology Group performance status of 0-2. Patients were randomized 1:1 to receive radiotherapy alone (60 Gy in 30 fractions of 2 Gy) (control group, n=44) or to receive radiotherapy with concurrent temozolomide (75 mg/m2/day) followed by adjuvant temozolomide (150-200 mg/m2/day for 5 days during six 28-day cycles) (treatment group, n=40). The primary end-point was 2-year progression-free survival (PFS). Seventy patients (83.3%) were available for the analysis of the isocitrate dehydrogenase 1 gene (IDH1) mutation status.
Results
The two-year PFS was 42.2% in the treatment group and 37.2% in the control group. Overall survival (OS) did not reach to significant difference between the groups. In multivariable analysis, age was a significant risk factor for PFS (hazard ratio [HR], 2.08; 95% confidence interval [CI], 1.04 to 4.16). The IDH1 mutation was the only significant prognostic factor for PFS (HR, 0.28; 95% CI, 0.13 to 0.59) and OS (HR, 0.19; 95% CI, 0.07 to 0.50). Adverse events over grade 3 were seen in 16 patients (40.0%) in the treatment group and were reversible.
Conclusion
Concurrent and adjuvant temozolomide in Korean adults with newly diagnosed non-co- deleted anaplastic gliomas showed improved 2-year PFS. The survival benefit of this regimen needs further analysis with long-term follow-up at least more than 10 years.

Citations

Citations to this article as recorded by  
  • Impact of upfront adjuvant chemoradiation on survival in patients with molecularly defined oligodendroglioma: the benefits of PCV over TMZ
    Jordina Rincon-Torroella, Maureen Rakovec, Anita L. Kalluri, Kelly Jiang, Carly Weber-Levine, Megan Parker, Divyaansh Raj, Josh Materi, Sadra Sepehri, Abel Ferres, Karisa C. Schreck, Iban Aldecoa, Calixto-Hope G. Lucas, Haris I. Sair, Kristin J. Redmond,
    Journal of Neuro-Oncology.2025; 171(1): 35.     CrossRef
  • Multidisciplinary Management of Isocitrate Dehydrogenase–Mutated Gliomas in a Contemporary Molecularly Defined Era
    Rupesh Kotecha, David Schiff, Arnab Chakravarti, Jessica L. Fleming, Paul D. Brown, Vinay K. Puduvalli, Michael A. Vogelbaum, Vinai Gondi, Marco Gallus, Hideho Okada, Minesh P. Mehta
    Journal of Clinical Oncology.2024; 42(21): 2588.     CrossRef
  • The IDH paradox: Meta-analysis of alkylating chemotherapy in IDH-wild type and -mutant lower grade gliomas
    Connor J Kinslow, Soumyajit Roy, Fabio M Iwamoto, Paul D Brown, David M DeStephano, Peter D Canoll, Summer S Qureshi, Matthew Gallito, Michael B Sisti, Jeffrey N Bruce, David P Horowitz, Lisa A Kachnic, Alfred I Neugut, James B Yu, Minesh P Mehta, Simon K
    Neuro-Oncology.2024; 26(10): 1839.     CrossRef
  • The Role of Systemic Therapies in the Treatment of Grades 1-4 Gliomas
    Jan Stepka, Mariusz Dotka, Maciej Kosiński, Piotr Suchecki, Maciej Hobot, Igor Piotrowski
    Cureus.2024;[Epub]     CrossRef
  • Therapy for Diffuse Astrocytic and Oligodendroglial Tumors in Adults: ASCO-SNO Guideline
    Nimish A. Mohile, Hans Messersmith, Na Tosha Gatson, Andreas F. Hottinger, Andrew Lassman, Jordan Morton, Douglas Ney, Phioanh Leia Nghiemphu, Adriana Olar, Jeffery Olson, James Perry, Jana Portnow, David Schiff, Anne Shannon, Helen A. Shih, Roy Strowd, M
    Journal of Clinical Oncology.2022; 40(4): 403.     CrossRef
  • Therapy for Diffuse Astrocytic and Oligodendroglial Tumors in Adults: ASCO-SNO Guideline
    Nimish A Mohile, Hans Messersmith, Na Tosha N Gatson, Andreas F Hottinger, Andrew B Lassman, Jordan Morton, Douglas Ney, Phioanh Leia Nghiemphu, Adriana Olar, Jeffery Olson, James Perry, Jana Portnow, David Schiff, Anne Shannon, Helen A Shih, Roy Strowd,
    Neuro-Oncology.2022; 24(3): 358.     CrossRef
  • Executive summary of American Radium Society’s appropriate use criteria for the postoperative management of lower grade gliomas
    Martin C. Tom, Michael T. Milano, Samuel T. Chao, Scott G. Soltys, Jonathan P.S. Knisely, Arjun Sahgal, Seema Nagpal, Simon S. Lo, Siavash Jabbari, Tony J.C. Wang, Manmeet S. Ahluwalia, Marian Simonson, Joshua D. Palmer, Melanie Hayden Gephart, Lia M. Hal
    Radiotherapy and Oncology.2022; 170: 79.     CrossRef
  • Influence of Concurrent and Adjuvant Temozolomide on Health-Related Quality of Life of Patients with Grade III Gliomas: A Secondary Analysis of a Randomized Clinical Trial (KNOG-1101 Study)
    Grace S. Ahn, Kihwan Hwang, Tae Min Kim, Chul Kee Park, Jong Hee Chang, Tae-Young Jung, Jin Hee Kim, Do-Hyun Nam, Se-Hyuk Kim, Heon Yoo, Yong-Kil Hong, Eun-Young Kim, Dong-Eun Lee, Jungnam Joo, Yu Jung Kim, Gheeyoung Choe, Byung Se Choi, Seok-Gu Kang, Jeo
    Cancer Research and Treatment.2022; 54(2): 396.     CrossRef
  • The Risk of Heart Disease-Related Death Among Anaplastic Astrocytoma Patients After Chemotherapy: A SEER Population-Based Analysis
    Qi Lin, Jia-Hao Bao, Fei Xue, Jia-Jun Qin, Zhen Chen, Zhong-Rong Chen, Chao Li, Yi-Xuan Yan, Jin Fu, Zhao-Li Shen, Xian-Zhen Chen
    Frontiers in Oncology.2022;[Epub]     CrossRef
  • Association between a prior cancer history and prognosis in adult patients with high‑grade glioma
    Dongjie He, Peiwen Wu, Gaiyan Li, Siying Zhu, Qiming Wang, Qiuju Shao, Hao Chang
    Journal of Clinical Neuroscience.2022; 106: 20.     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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    Archives of Gynecology and Obstetrics.2025; 311(1): 123.     CrossRef
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    Cancers.2025; 17(2): 202.     CrossRef
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    Clinical & Experimental Metastasis.2025;[Epub]     CrossRef
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    Mingke Tian, Fengying Qin, Xinyan Sun, Huiting Pang, Tao Yu, Yue Dong
    Journal of Imaging Informatics in Medicine.2025;[Epub]     CrossRef
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    Shuang-Zheng Jia, Duan Yang, Xue-Jiao Yang, Rui Wang, Xi Yang, Man-Ni Huang, Ju-Sheng An
    Radiation Oncology.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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    Yanna Ye, Rui Lian, Zhiqiang Li, Xiaolin Chen, Yahong Huang, Jilong Yao, Anwei Lu, Jinghe Lang, Ping Liu, Chunlin Chen
    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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    Yiping Hao, Qingqing Liu, Ruowen Li, Zhonghao Mao, Nan Jiang, Bingyu Wang, Wenjing Zhang, Baoxia Cui
    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
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    Keisuke Kodama, Chuya Tateishi, Tsuyoshi Oda, Lin Cui, Kazutaka Kuramoto, Hideaki Yahata, Kaoru Okugawa, Shoji Maenohara, Hiroshi Yagi, Masafumi Yasunaga, Ichiro Onoyama, Kazuo Asanoma, Takeshi Mori, Yoshiki Katayama, Kiyoko Kato
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    Jia Li, Hao Zhou, Xiaofei Lu, Yiren Wang, Haowen Pang, Daniel Cesar, Aiai Liu, Ping Zhou
    BMC Medical Imaging.2023;[Epub]     CrossRef
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    Clinical and Experimental Obstetrics & Gynecology.2023;[Epub]     CrossRef
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    Maki Matoda, Nobuhiro Takeshima, Hirofumi Michimae, Takashi Iwata, Harushige Yokota, Yutaka Torii, Yorito Yamamoto, Kazuhiro Takehara, Shin Nishio, Hirokuni Takano, Mika Mizuno, Yoshiyuki Takahashi, Yuji Takei, Tetsuya Hasegawa, Mikio Mikami, Takayuki Eno
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Impact of the New AJCC Staging System and Adjuvant Treatment in Rectal Cancer
Shin Ae Lee, Hyuk-Chan Kwon, Min Ah Park, Chang Kil Jung, Sung-Hyun Kim, Ki-Jae Park, Hong-Jo Choi, Hyung-Sik Lee, Mee Sook Roh, Jae-Seok Kim, Hyo-Jin Kim
Cancer Res Treat. 2004;36(2):121-127.   Published online April 30, 2004
DOI: https://doi.org/10.4143/crt.2004.36.2.121
AbstractAbstract PDFPubReaderePub
Purpose

The combination of chemoradiation and fluorouracil based chemotherapy has been the standard adjuvant treatment for colorectal cancer patients. The aim of this study was to evaluate treatment outcome of patients classified by the new AJCC staging system and to compare treatment outcome of oral doxifluridine and the standard Mayo Clinic regimen after chemoradiation in advanced rectal cancer patients.

Materials and Methods

One hundred nine patients underwent curative surgical resection and chemoradiation followed by chemotherapy. 45 Gy pelvic irradiation was given to the entire pelvis and the boost radiation with 50.4 to 54 Gy, and simultaneously 5-fluorouracil (5-FU) 375 mg/m2/day was given on day 1~3 and 26~28. After the completion of chemoradiation, patients were given either 6 cycles of the Mayo Clinic regimen (5-FU 425 mg/m2 plus leucovorin 20 mg/m2 intravenous bolus infusion on day 1~5, every 4 weeks) or oral doxifluridine (600 mg/m2/day) for 1 year.

Results

The median follow-up duration was 30 months. Among 102 evaluable patients, 38 patients (37.3%) relapsed: the locoregional recurrence in 10 patients (9.8%) and systemic relapse in 28 patients (27.5%). The systemic relapse rate was 15.6% in the stage IIA, 25.0% in the stage IIIB , and 59.1% in the stage IIIC (p=0.048). The 5-year disease-free survival (DFS) rate was significantly higher in the IIA and IIIA patients than the IIIB and IIIC patients (72% and 100% vs 48.1% and 11.2%, respectively. p<0.001). The 5-year overall survival (OS) rate was also significantly different between in the IIA/IIIA patients and the IIIB/IIIC (67.3%/100% vs 48.4%/22.3%. p<0.001). However, the difference in DFS or OS between the oral doxifluridine group and the Mayo Clinic regimen group was not significant. Cox regression multivariate analyses showed that the new AJCC stage and tumor differentiation were significant independent prognostic factors in DFS and OS.

Conclusion

These results support that the new AJCC staging system is superior to Dukes' staging system in the prognostic stratification. Regarding DFS and OS, oral doxifluridine is comparable to the standard Mayo Clinic regimen in rectal cancer patients when combined with postoperative chemoradiation. Stage IIIC patients should be selected for aggressive therapy as they have a dismal prognosis.

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