Effect of Radiotherapy Alone vs Radiotherapy With Concurrent Chemoradiotherapy on Survival Without Disease Relapse in Patients With Low-risk Nasopharyngeal Carcinoma A Randomized Clinical Trial

Concurrent chemoradiotherapy has been the standard treatment for stage II nasopharyngeal carcinoma (NPC) based on data using 2-dimensional conventional radiotherapy. There is limited evidence for the role of chemotherapy with use of intensity-modulated radiation therapy (IMRT). To assess whether con...

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Published inJAMA : the journal of the American Medical Association Vol. 328; no. 8; pp. 728 - 736
Main Authors Tang, Ling-Long, Guo, Rui, Zhang, Ning, Deng, Bin, Chen, Lei, Cheng, Zhi-Bin, Huang, Jing, Hu, Wei-Han, Huang, Shao Hui, Luo, Wei-Jun, Liang, Jin-Hui, Zheng, Yu-Ming, Zhang, Fan, Mao, Yan-Ping, Li, Wen-Fei, Zhou, Guan-Qun, Liu, Xu, Chen, Yu-Pei, Xu, Cheng, Lin, Li, Liu, Qing, Du, Xiao-Jing, Zhang, Yuan, Sun, Ying, Ma, Jun
Format Journal Article
LanguageEnglish
Published United States American Medical Association 23.08.2022
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Online AccessGet full text
ISSN0098-7484
1538-3598
1538-3598
DOI10.1001/jama.2022.13997

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Abstract Concurrent chemoradiotherapy has been the standard treatment for stage II nasopharyngeal carcinoma (NPC) based on data using 2-dimensional conventional radiotherapy. There is limited evidence for the role of chemotherapy with use of intensity-modulated radiation therapy (IMRT). To assess whether concurrent chemotherapy can be safely omitted for patients with low-risk stage II/T3N0 NPC treated with IMRT. This multicenter, open-label, randomized, phase 3, noninferiority clinical trial was conducted at 5 Chinese hospitals, including 341 adult patients with low-risk NPC, defined as stage II/T3N0M0 without adverse features (all nodes <3 cm, no level IV/Vb nodes; no extranodal extension; Epstein-Barr virus DNA <4000 copies/mL), with enrollment between November 2015 and August 2020. The final date of follow-up was March 15, 2022. Patients were randomly assigned to receive IMRT alone (n = 172) or concurrent chemoradiotherapy (IMRT with cisplatin, 100 mg/m2 every 3 weeks for 3 cycles [n = 169]). The primary end point was 3-year failure-free survival (time from randomization to any disease relapse or death), with a noninferiority margin of 10%. Secondary end points comprised overall survival, locoregional relapse-free survival, distant metastasis-free survival, adverse events, and health-related quality of life (QOL) measured by the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (QLQ-C30; range, 0-100 points; minimum clinically important difference ≥10 for physical function, symptom control, or health-related QOL; higher score indicates better functioning and global health status or worse symptoms). Among 341 randomized patients (mean [SD] age, 48 [10] years; 30% women), 334 (98.0%) completed the trial. Median follow-up was 46 months (IQR, 34-58). Three-year failure-free survival was 90.5% for the IMRT-alone group vs 91.9% for the concurrent chemoradiotherapy group (difference, -1.4%; 1-sided 95% CI, -7.4% to ∞; P value for noninferiority, <.001). No significant differences were observed between groups in overall survival, locoregional relapse, or distant metastasis. The IMRT-alone group experienced a significantly lower incidence of grade 3 to 4 adverse events (17% vs 46%; difference, -29% [95% CI, -39% to -20%]), including hematologic toxicities (leukopenia, neutropenia) and nonhematologic toxicities (nausea, vomiting, anorexia, weight loss, mucositis). The IMRT-alone group had significantly better QOL scores during radiotherapy including the domains of global health status, social functioning, fatigue, nausea and vomiting, pain, insomnia, appetite loss, and constipation. Among patients with low-risk NPC, treatment with IMRT alone resulted in 3-year failure-free survival that was not inferior to concurrent chemoradiotherapy. ClinicalTrials.gov Identifier: NCT02633202.
AbstractList Concurrent chemoradiotherapy has been the standard treatment for stage II nasopharyngeal carcinoma (NPC) based on data using 2-dimensional conventional radiotherapy. There is limited evidence for the role of chemotherapy with use of intensity-modulated radiation therapy (IMRT). To assess whether concurrent chemotherapy can be safely omitted for patients with low-risk stage II/T3N0 NPC treated with IMRT. This multicenter, open-label, randomized, phase 3, noninferiority clinical trial was conducted at 5 Chinese hospitals, including 341 adult patients with low-risk NPC, defined as stage II/T3N0M0 without adverse features (all nodes <3 cm, no level IV/Vb nodes; no extranodal extension; Epstein-Barr virus DNA <4000 copies/mL), with enrollment between November 2015 and August 2020. The final date of follow-up was March 15, 2022. Patients were randomly assigned to receive IMRT alone (n = 172) or concurrent chemoradiotherapy (IMRT with cisplatin, 100 mg/m2 every 3 weeks for 3 cycles [n = 169]). The primary end point was 3-year failure-free survival (time from randomization to any disease relapse or death), with a noninferiority margin of 10%. Secondary end points comprised overall survival, locoregional relapse-free survival, distant metastasis-free survival, adverse events, and health-related quality of life (QOL) measured by the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (QLQ-C30; range, 0-100 points; minimum clinically important difference ≥10 for physical function, symptom control, or health-related QOL; higher score indicates better functioning and global health status or worse symptoms). Among 341 randomized patients (mean [SD] age, 48 [10] years; 30% women), 334 (98.0%) completed the trial. Median follow-up was 46 months (IQR, 34-58). Three-year failure-free survival was 90.5% for the IMRT-alone group vs 91.9% for the concurrent chemoradiotherapy group (difference, -1.4%; 1-sided 95% CI, -7.4% to ∞; P value for noninferiority, <.001). No significant differences were observed between groups in overall survival, locoregional relapse, or distant metastasis. The IMRT-alone group experienced a significantly lower incidence of grade 3 to 4 adverse events (17% vs 46%; difference, -29% [95% CI, -39% to -20%]), including hematologic toxicities (leukopenia, neutropenia) and nonhematologic toxicities (nausea, vomiting, anorexia, weight loss, mucositis). The IMRT-alone group had significantly better QOL scores during radiotherapy including the domains of global health status, social functioning, fatigue, nausea and vomiting, pain, insomnia, appetite loss, and constipation. Among patients with low-risk NPC, treatment with IMRT alone resulted in 3-year failure-free survival that was not inferior to concurrent chemoradiotherapy. ClinicalTrials.gov Identifier: NCT02633202.
Importance Concurrent chemoradiotherapy has been the standard treatment for stage II nasopharyngeal carcinoma (NPC) based on data using 2-dimensional conventional radiotherapy. There is limited evidence for the role of chemotherapy with use of intensity-modulated radiation therapy (IMRT). Objective To assess whether concurrent chemotherapy can be safely omitted for patients with low-risk stage II/T3N0 NPC treated with IMRT. Design, Setting, and Participants This multicenter, open-label, randomized, phase 3, noninferiority clinical trial was conducted at 5 Chinese hospitals, including 341 adult patients with low-risk NPC, defined as stage II/T3N0M0 without adverse features (all nodes <3 cm, no level IV/Vb nodes; no extranodal extension; Epstein-Barr virus DNA <4000 copies/mL), with enrollment between November 2015 and August 2020. The final date of follow-up was March 15, 2022. Interventions Patients were randomly assigned to receive IMRT alone (n = 172) or concurrent chemoradiotherapy (IMRT with cisplatin, 100 mg/m2 every 3 weeks for 3 cycles [n = 169]). Main Outcomes and Measures The primary end point was 3-year failure-free survival (time from randomization to any disease relapse or death), with a noninferiority margin of 10%. Secondary end points comprised overall survival, locoregional relapse-free survival, distant metastasis-free survival, adverse events, and health-related quality of life (QOL) measured by the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (QLQ-C30; range, 0-100 points; minimum clinically important difference ≥10 for physical function, symptom control, or health-related QOL; higher score indicates better functioning and global health status or worse symptoms). Results Among 341 randomized patients (mean [SD] age, 48 [10] years; 30% women), 334 (98.0%) completed the trial. Median follow-up was 46 months (IQR, 34-58). Three-year failure-free survival was 90.5% for the IMRT-alone group vs 91.9% for the concurrent chemoradiotherapy group (difference, −1.4%; 1-sided 95% CI, −7.4% to ∞; P value for noninferiority, <.001). No significant differences were observed between groups in overall survival, locoregional relapse, or distant metastasis. The IMRT-alone group experienced a significantly lower incidence of grade 3 to 4 adverse events (17% vs 46%; difference, −29% [95% CI, −39% to −20%]), including hematologic toxicities (leukopenia, neutropenia) and nonhematologic toxicities (nausea, vomiting, anorexia, weight loss, mucositis). The IMRT-alone group had significantly better QOL scores during radiotherapy including the domains of global health status, social functioning, fatigue, nausea and vomiting, pain, insomnia, appetite loss, and constipation. Conclusions and Relevance Among patients with low-risk NPC, treatment with IMRT alone resulted in 3-year failure-free survival that was not inferior to concurrent chemoradiotherapy.
This randomized clinical trial compares the rate of 3-year survival without disease relapse among adult patients with low-risk nasopharyngeal carcinoma who were treated with intensity-modulated radiation therapy alone vs with concurrent chemoradiotherapy.
Concurrent chemoradiotherapy has been the standard treatment for stage II nasopharyngeal carcinoma (NPC) based on data using 2-dimensional conventional radiotherapy. There is limited evidence for the role of chemotherapy with use of intensity-modulated radiation therapy (IMRT).ImportanceConcurrent chemoradiotherapy has been the standard treatment for stage II nasopharyngeal carcinoma (NPC) based on data using 2-dimensional conventional radiotherapy. There is limited evidence for the role of chemotherapy with use of intensity-modulated radiation therapy (IMRT).To assess whether concurrent chemotherapy can be safely omitted for patients with low-risk stage II/T3N0 NPC treated with IMRT.ObjectiveTo assess whether concurrent chemotherapy can be safely omitted for patients with low-risk stage II/T3N0 NPC treated with IMRT.This multicenter, open-label, randomized, phase 3, noninferiority clinical trial was conducted at 5 Chinese hospitals, including 341 adult patients with low-risk NPC, defined as stage II/T3N0M0 without adverse features (all nodes <3 cm, no level IV/Vb nodes; no extranodal extension; Epstein-Barr virus DNA <4000 copies/mL), with enrollment between November 2015 and August 2020. The final date of follow-up was March 15, 2022.Design, Setting, and ParticipantsThis multicenter, open-label, randomized, phase 3, noninferiority clinical trial was conducted at 5 Chinese hospitals, including 341 adult patients with low-risk NPC, defined as stage II/T3N0M0 without adverse features (all nodes <3 cm, no level IV/Vb nodes; no extranodal extension; Epstein-Barr virus DNA <4000 copies/mL), with enrollment between November 2015 and August 2020. The final date of follow-up was March 15, 2022.Patients were randomly assigned to receive IMRT alone (n = 172) or concurrent chemoradiotherapy (IMRT with cisplatin, 100 mg/m2 every 3 weeks for 3 cycles [n = 169]).InterventionsPatients were randomly assigned to receive IMRT alone (n = 172) or concurrent chemoradiotherapy (IMRT with cisplatin, 100 mg/m2 every 3 weeks for 3 cycles [n = 169]).The primary end point was 3-year failure-free survival (time from randomization to any disease relapse or death), with a noninferiority margin of 10%. Secondary end points comprised overall survival, locoregional relapse-free survival, distant metastasis-free survival, adverse events, and health-related quality of life (QOL) measured by the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (QLQ-C30; range, 0-100 points; minimum clinically important difference ≥10 for physical function, symptom control, or health-related QOL; higher score indicates better functioning and global health status or worse symptoms).Main Outcomes and MeasuresThe primary end point was 3-year failure-free survival (time from randomization to any disease relapse or death), with a noninferiority margin of 10%. Secondary end points comprised overall survival, locoregional relapse-free survival, distant metastasis-free survival, adverse events, and health-related quality of life (QOL) measured by the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (QLQ-C30; range, 0-100 points; minimum clinically important difference ≥10 for physical function, symptom control, or health-related QOL; higher score indicates better functioning and global health status or worse symptoms).Among 341 randomized patients (mean [SD] age, 48 [10] years; 30% women), 334 (98.0%) completed the trial. Median follow-up was 46 months (IQR, 34-58). Three-year failure-free survival was 90.5% for the IMRT-alone group vs 91.9% for the concurrent chemoradiotherapy group (difference, -1.4%; 1-sided 95% CI, -7.4% to ∞; P value for noninferiority, <.001). No significant differences were observed between groups in overall survival, locoregional relapse, or distant metastasis. The IMRT-alone group experienced a significantly lower incidence of grade 3 to 4 adverse events (17% vs 46%; difference, -29% [95% CI, -39% to -20%]), including hematologic toxicities (leukopenia, neutropenia) and nonhematologic toxicities (nausea, vomiting, anorexia, weight loss, mucositis). The IMRT-alone group had significantly better QOL scores during radiotherapy including the domains of global health status, social functioning, fatigue, nausea and vomiting, pain, insomnia, appetite loss, and constipation.ResultsAmong 341 randomized patients (mean [SD] age, 48 [10] years; 30% women), 334 (98.0%) completed the trial. Median follow-up was 46 months (IQR, 34-58). Three-year failure-free survival was 90.5% for the IMRT-alone group vs 91.9% for the concurrent chemoradiotherapy group (difference, -1.4%; 1-sided 95% CI, -7.4% to ∞; P value for noninferiority, <.001). No significant differences were observed between groups in overall survival, locoregional relapse, or distant metastasis. The IMRT-alone group experienced a significantly lower incidence of grade 3 to 4 adverse events (17% vs 46%; difference, -29% [95% CI, -39% to -20%]), including hematologic toxicities (leukopenia, neutropenia) and nonhematologic toxicities (nausea, vomiting, anorexia, weight loss, mucositis). The IMRT-alone group had significantly better QOL scores during radiotherapy including the domains of global health status, social functioning, fatigue, nausea and vomiting, pain, insomnia, appetite loss, and constipation.Among patients with low-risk NPC, treatment with IMRT alone resulted in 3-year failure-free survival that was not inferior to concurrent chemoradiotherapy.Conclusions and RelevanceAmong patients with low-risk NPC, treatment with IMRT alone resulted in 3-year failure-free survival that was not inferior to concurrent chemoradiotherapy.ClinicalTrials.gov Identifier: NCT02633202.Trial RegistrationClinicalTrials.gov Identifier: NCT02633202.
Author Sun, Ying
Mao, Yan-Ping
Du, Xiao-Jing
Liu, Xu
Zhou, Guan-Qun
Li, Wen-Fei
Luo, Wei-Jun
Huang, Shao Hui
Zhang, Ning
Hu, Wei-Han
Guo, Rui
Chen, Lei
Deng, Bin
Lin, Li
Chen, Yu-Pei
Zhang, Fan
Liang, Jin-Hui
Cheng, Zhi-Bin
Xu, Cheng
Huang, Jing
Zheng, Yu-Ming
Liu, Qing
Zhang, Yuan
Ma, Jun
Tang, Ling-Long
AuthorAffiliation 3 Department of Radiation Oncology, the Wuzhou Red Cross Hospital, Wuzhou, Guangxi, China
2 Department of Radiation Oncology, First People’s Hospital of Foshan, Foshan Guangdong, China
5 Department of Oncology, Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People’s China
4 Department of Radiation Oncology, the Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, Guangdong, China
6 Department of Radiation Oncology, Princess Margaret Cancer Centre/University of Toronto, Ontario, Canada
7 Clinical Trials Centre, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Centre for Cancer Medicine, Guangzhou, Guangdong, China
8 Center for Precision Medicine, Sun Yat-sen University, Guangzhou, Guangdong, China
1 Department of Radiation Oncology, Sun Yat-sen University Cancer Center, the State Key Laboratory of Oncology in South China, Collaborative Innovation Center fo
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  givenname: Wei-Jun
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  organization: Department of Radiation Oncology, First People’s Hospital of Foshan, Foshan Guangdong, China
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– sequence: 16
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  surname: Zhou
  fullname: Zhou, Guan-Qun
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  organization: Department of Radiation Oncology, Sun Yat-sen University Cancer Center, the State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangzhou, Guangdong, China
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  givenname: Xiao-Jing
  surname: Du
  fullname: Du, Xiao-Jing
  organization: Department of Radiation Oncology, Sun Yat-sen University Cancer Center, the State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangzhou, Guangdong, China
– sequence: 23
  givenname: Yuan
  surname: Zhang
  fullname: Zhang, Yuan
  organization: Department of Radiation Oncology, Sun Yat-sen University Cancer Center, the State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangzhou, Guangdong, China
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  givenname: Ying
  surname: Sun
  fullname: Sun, Ying
  organization: Department of Radiation Oncology, Sun Yat-sen University Cancer Center, the State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangzhou, Guangdong, China
– sequence: 25
  givenname: Jun
  surname: Ma
  fullname: Ma, Jun
  organization: Department of Radiation Oncology, Sun Yat-sen University Cancer Center, the State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangzhou, Guangdong, China, Center for Precision Medicine, Sun Yat-sen University, Guangzhou, Guangdong, China
BackLink https://www.ncbi.nlm.nih.gov/pubmed/35997729$$D View this record in MEDLINE/PubMed
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SSID ssj0000137
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Snippet Concurrent chemoradiotherapy has been the standard treatment for stage II nasopharyngeal carcinoma (NPC) based on data using 2-dimensional conventional...
Importance Concurrent chemoradiotherapy has been the standard treatment for stage II nasopharyngeal carcinoma (NPC) based on data using 2-dimensional...
This randomized clinical trial compares the rate of 3-year survival without disease relapse among adult patients with low-risk nasopharyngeal carcinoma who...
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SubjectTerms Adult
Adverse events
Anorexia
Antineoplastic Combined Chemotherapy Protocols - adverse effects
Antineoplastic Combined Chemotherapy Protocols - therapeutic use
Appetite loss
Body weight loss
Cancer
Chemoradiotherapy
Chemoradiotherapy - adverse effects
Chemoradiotherapy - methods
Chemotherapy
Cisplatin
Cisplatin - administration & dosage
Cisplatin - adverse effects
Clinical trials
Constipation
DNA viruses
Epstein-Barr virus
Epstein-Barr Virus Infections - complications
Female
Global health
Health services
Herpesvirus 4, Human
Humans
Insomnia
Leukopenia
Male
Metastases
Metastasis
Middle Aged
Mucositis
Nasopharyngeal carcinoma
Nasopharyngeal Carcinoma - drug therapy
Nasopharyngeal Carcinoma - etiology
Nasopharyngeal Carcinoma - pathology
Nasopharyngeal Carcinoma - radiotherapy
Nasopharyngeal Neoplasms - drug therapy
Nasopharyngeal Neoplasms - etiology
Nasopharyngeal Neoplasms - pathology
Nasopharyngeal Neoplasms - radiotherapy
Nausea
Neutropenia
Nodes
Original Investigation
Pain
Patients
Public health
Quality of Life
Radiation
Radiation therapy
Radiotherapy, Intensity-Modulated - adverse effects
Radiotherapy, Intensity-Modulated - methods
Randomization
Risk
Signs and symptoms
Sleep disorders
Survival
Throat cancer
Toxicity
Vomiting
Weight loss
Subtitle A Randomized Clinical Trial
Title Effect of Radiotherapy Alone vs Radiotherapy With Concurrent Chemoradiotherapy on Survival Without Disease Relapse in Patients With Low-risk Nasopharyngeal Carcinoma
URI https://www.ncbi.nlm.nih.gov/pubmed/35997729
https://www.proquest.com/docview/2712888679
https://www.proquest.com/docview/2705751291
https://pubmed.ncbi.nlm.nih.gov/PMC9399866
Volume 328
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