PET/CT-guided dose-painting versus CT-based intensity modulated radiation therapy in locoregional advanced nasopharyngeal carcinoma

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Abstract

Background

The effect of ¹⁸F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT)-guided dose-painting intensity-modulated radiation therapy (IMRT) in locoregionally advanced nasopharyngeal carcinoma (NPC) is unclear. This study aimed to assess the efficacy and toxicity of such combination.

Methods

From 2012 to 2014, 213 patients with stage III-IVB NPC received chemoradiotherapy by PET/CT-guided DP-IMRT (group A, n = 101) or CT-based IMRT (group B, n = 112). In group A, subvolume GTVnx- _PET (gross tumor volume of nasopharynx in PET images) was defined within GTVnx (gross tumor volume of nasopharynx) as the SUV50%max isocontour; the dose to GTVnx- _PET was escalated to DT 75.2 Gy/32 and 77.55 Gy/33 Fx, respectively, for patients with T1-2 and T3-4 disease, respectively. In group B, PGTVnx was irradiated at DT 70.4–72.6 Gy/32–33 Fx in 2.2 Gy per fraction.

Results

Complete response rates were 99.0% (100/101) and 92.9% (104/112) in groups A and B, respectively ( P = 0.037). Compared with CT-based IMRT, FDG-PET/CT guided DP-IMRT significantly improved 3-year local failure-free survival (LFFS, 98.8% vs. 91.3%; P = 0.032), locoregional failure-free survival (LRFFS, 97.2 vs. 91.2%; P = 0.049), distant metastasis-free survival (DMFS, 92.9% vs. 87.4%; P = 0.041), disease free survival (DFS, 87.9% vs. 82.4%; P = 0.02), and overall survival (OS, 91.8% vs. 82.6%; P = 0.049). No statistically significant differences in acute and late toxic effects were observed. Multivariate analysis showed that dose painting (PET/CT-guided DP-IMRT vs CT-based IMRT without DP) was a significant independent prognostic factor for LFFS and DFS.

Conclusion

FDG-PET/CT guided DP-IMRT plus chemotherapy is associated with a considerable survival benefit, without increasing toxicity in patients with locoregional advanced NPC. Further randomized trials are needed to fully assess the role of PET/CT-guided DP-IMRT.

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Most cited references 27

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Addition of bevacizumab to standard chemoradiation for locoregionally advanced nasopharyngeal carcinoma (RTOG 0615): a phase 2 multi-institutional trial.

Nancy Lee, Qiang Zhang, David Pfister … (2012)

We aimed to improve the outcomes for locoregionally advanced nasopharyngeal carcinoma by testing the feasibility and safety of the addition of bevacizumab to chemoradiotherapy. We enrolled patients older than 18 years with stage IIB-IVB nasopharyngeal carcinoma from 19 centres in North America and Hong Kong. Treatment consisted of three cycles of bevacizumab (15 mg/kg) and cisplatin (100 mg/m(2)) both given on days 1, 22, and 43 of radiation (70 Gy) with intensity-modulated radiation therapy delivered over 33 days on a daily basis, Monday through Friday. Patients then received three cycles of bevacizumab (15 mg/kg) and cisplatin (80 mg/m(2)), both given on days 64, 85, and 106 after radiation, and three cycles of fluorouracil (1000 mg/m(2) per day), given on days 64-67, 85-88, and 106-109 after radiation. The primary endpoint was the occurrence of treatment-related grade 4 haemorrhage or any grade 5 adverse event in the first year. Analyses were done with all eligible patients who started protocol treatment. The trial is registered at ClinicalTrials.gov, number NCT00408694. From Dec 13, 2006, to Feb 5, 2009, we enrolled 46 patients, of whom 44 were eligible for analysis. We recorded no grade 3-4 haemorrhages or grade 5 adverse events; nine patients (20%) had a treatment-related grade 1-2 haemorrhage. Nine patients had one or more grade 4 blood or bone marrow-related complication (grade 4 leucopenia was noted in six patients, grade 4 lymphopenia in five, grade 4 neutrophils in five, and grade 4 anaemia in one). One patient had two grade 4 infections with grade 3-4 neutrophils. One patient reported grade 4 tinnitus, one patient reported grade 4 thrombosis, one reported grade 4 radiation mucositis, and two reported grade 4 pharyngolaryngeal pain. With a median follow-up of 2·5 years (IQR 2·1-2·9), the estimated 2 year locoregional progression-free interval was 83·7% (95% CI 72·6-94·9), the 2 year distant metastasis-free interval was 90·8% (82·2-99·5), the 2 year progression-free survival was 74·7% (61·8-87·6), and 2 year overall survival was 90·9% (82·3-99·4). The addition of bevacizumab to standard chemoradiation treatment for patients with nasopharyngeal carcinoma is feasible, and might delay the progression of subclinical distant disease. National Cancer Institute, USA. Copyright © 2012 Elsevier Ltd. All rights reserved.

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Plasma Epstein-Barr viral deoxyribonucleic acid quantitation complements tumor-node-metastasis staging prognostication in nasopharyngeal carcinoma.

Kwok Chan, Po Leung, Pauline Kwan … (2006)

To evaluate the effect of combining circulating Epstein-Barr viral (EBV) DNA load data with TNM staging data in pretherapy prognostication of nasopharyngeal carcinoma (NPC). Three hundred seventy-six patients with all stages of NPC were studied. Pretreatment plasma/serum EBV DNA concentrations were quantified by a polymerase chain reaction assay. Determinants of overall survival were assessed by multivariate analysis. Survival probabilities of patient groups, segregated by clinical stage (I, II, III, or IV) alone and also according to EBV DNA load (low or high), were compared. Pretherapy circulating EBV DNA load is an independent prognostic factor for overall survival in NPC. Patients with early-stage disease were segregated by EBV DNA levels into a poor-risk subgroup with survival similar to that of stage III disease and a good-risk subgroup with survival similar to stage I disease. Pretherapy circulating EBV DNA load is an independent prognostic factor to International Union Against Cancer (UICC) staging in NPC. Combined interpretation of EBV DNA data with UICC staging data leads to alteration of risk definition of patient subsets, with improved risk discrimination in early-stage disease. Validation studies are awaited.

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Prospective study of tailoring whole-body dual-modality [18F]fluorodeoxyglucose positron emission tomography/computed tomography with plasma Epstein-Barr virus DNA for detecting distant metastasis in endemic nasopharyngeal carcinoma at initial staging.

Chong Zhao, Qiu Chen, Xiang Guo … (2013)

To evaluate which patients with nasopharyngeal carcinoma (NPC) obtained the greatest benefits from the detection of distant metastasis with [(18)F]fluorodeoxyglucose positron emission tomography and computed tomography (PET/CT) combined with plasma Epstein-Barr virus (EBV) DNA levels. Consecutive patients with NPC were prospectively enrolled. PET/CT, conventional work-up (CWU), and quantification of plasma EBV DNA were performed before treatment. The accuracy of these strategies for distant metastases was assessed. The costs of the diagnostic strategies were compared. Eighty-six (14.8%) of the 583 eligible patients were found to have distant metastases; 71 patients (82.6%) by PET/CT and 31 patients (36.0%) by CWU. In the multivariable analysis, advanced N stage (odds ratio, 2.689; 95% CI, 1.894 to 3.818) and pretreatment EBV DNA level (odds ratio, 3.344; 95% CI, 1.825 to 6.126) were significant risk factors for distant metastases. PET/CT was not superior to CWU for detecting distant metastases in very low-risk patients (N0-1 with EBV DNA < 4,000 copies/mL; P = .062), but was superior for the low-risk patients (N0-1 with EBV DNA ≥ 4,000 copies/mL and N2-3 with EBV DNA < 4,000 copies/mL; P = .039) and intermediate-risk patients (N2-3 disease with EBV DNA ≥ 4,000 copies/mL; P < .001). The corresponding patient management changes based on PET/CT were 2.9%, 6.3%, and 16.5%, respectively. The costs per true-positive case detected by PET/CT among these groups were ¥324,138 (≈$47,458), ¥96,907 (≈$14,188), and ¥34,182 (≈$5,005), respectively. PET/CT detects more distant metastases than conventional staging in patients with NPC. The largest benefit in terms of cost and patient management was observed in the subgroup with N2-3 disease and EBV DNA ≥ 4,000 copies/mL.

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Author and article information

Contributors

Feng Liu: liufeng820111@163.com

Xu-ping Xi: xixuping2010@126.com

Hui Wang: wanghui710327@163.com

Ya-qian Han: hanyaqian@hnszlyy.com

Feng Xiao: xiaofeng0023@hnszlyy.com

Ying Hu: huying@hnszlyy.com

Qian He: heqian1162@hnszlyy.com

Lin Zhang: zhanglin1286@hnszlyy.com

Qin Xiao: xiaoqin2501@hnszlyy.com

Lin Liu: liulin@hnszlyy.com

Le Luo: luole@hnszlyy.com

Yun Li: liyun520@hnszlyy.com

Yi Mo: moyi201010@126.com

Hong-zhi Ma: mahongzhi@hnszlyy.com

Journal

Journal ID (nlm-ta): Radiat Oncol

Journal ID (iso-abbrev): Radiat Oncol

Title: Radiation Oncology (London, England)

Publisher: BioMed Central (London )

ISSN (Electronic): 1748-717X

Publication date (Electronic): 13 January 2017

Publication date PMC-release: 13 January 2017

Publication date Collection: 2017

Volume: 12

Electronic Location Identifier: 15

Affiliations

[1 ]ISNI 0000 0001 0379 7164, GRID grid.216417.7, Department of Radiation Oncology, , Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, ; Changsha, Hunan China

[2 ]ISNI 0000 0001 0379 7164, GRID grid.216417.7, Key Laboratory of Translational Radiation Oncology, Hunan Province Department of Radiation Oncology, , Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, ; Changsha, Hunan China

Article

Publisher ID: 739

DOI: 10.1186/s13014-016-0739-y

PMC ID: 5461636

PubMed ID: 28587681

SO-VID: 9d8b4d90-bb61-4e30-8fc9-9bbcf82702bc

License:

Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

History

Date received : 31 August 2016

Date accepted : 6 December 2016

Funding

Funded by: FundRef http://dx.doi.org/10.13039/501100002767, Hunan Provincial Science and Technology Department;

Award ID: 2016JJ6088

Award Recipient : Feng Liu

Funded by: Health and Family Planning Commission of Hunan Province

Award ID: B2016048

Award Recipient : Feng Liu

Custom metadata

ScienceOpen disciplines: Oncology & Radiotherapy

Keywords: nasopharyngeal carcinoma,fdg-pet/ct,dose painting,intensity-modulated radiation therapy,toxicity

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ScienceOpen disciplines: Oncology & Radiotherapy

Keywords: nasopharyngeal carcinoma, fdg-pet/ct, dose painting, intensity-modulated radiation therapy, toxicity

PET/CT-guided dose-painting versus CT-based intensity modulated radiation therapy in locoregional advanced nasopharyngeal carcinoma

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Abstract

Background

Methods

Results

Conclusion

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Karger: Oncology

Most cited references 27

Addition of bevacizumab to standard chemoradiation for locoregionally advanced nasopharyngeal carcinoma (RTOG 0615): a phase 2 multi-institutional trial.

Plasma Epstein-Barr viral deoxyribonucleic acid quantitation complements tumor-node-metastasis staging prognostication in nasopharyngeal carcinoma.

Prospective study of tailoring whole-body dual-modality [18F]fluorodeoxyglucose positron emission tomography/computed tomography with plasma Epstein-Barr virus DNA for detecting distant metastasis in endemic nasopharyngeal carcinoma at initial staging.

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