Effect of interrupted time during intensity modulated radiation therapy on survival outcomes in patients with nasopharyngeal cancer

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Abstract

Objective

To evaluate the influence of interrupted time (IT) during intensity-modulated radiotherapy (IMRT) on survival outcomes in patients with nasopharyngeal cancer (NPC).

Materials and methods

515 NPC patients receiving IMRT between January 2007 and December 2011 were retrospectively reviewed. The association of IT with loco-regional failure-free survival (LRFS), progression free survival (PFS) and overall survival (OS) was assessed by univariate and multivariate analysis. The Kaplan–Meier methodology was used for survival analyses and the differences among groups were assessed by the log-rank test. The Cox model was used for evaluating the prognostic factors for LRFS, PFS, and OS.

Results

The 3-year PFS and OS analysis revealed significant difference between patients with a IT >4 days and those with a IT ≤4 days (72.1% vs 81.9%, p <0.05; 80.8% vs 87.9%, p <0.05). Age (≥44 years vs <44 years), T classification, N classification, and IT (>4 days vs ≤4 days) were independent prognostic factors for PFS and OS, respectively ( p <0.05). Only N classification acted as the prognostic factor for LRFS ( p <0.05).

Conclusion

The IT of more than 4 days during IMRT may affect survival outcomes of NPC patients. We should minimize the interruption of radiotherapy caused by any reason as much as possible.

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Most cited references 9

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Phase III study of concurrent chemoradiotherapy versus radiotherapy alone for advanced nasopharyngeal carcinoma: positive effect on overall and progression-free survival.

Jin-Ching Lin, Jian-Sheng Jan, Chen-Yi Hsu … (2003)

Nasopharyngeal carcinoma (NPC) is a radiosensitive and chemosensitive tumor. This randomized phase III trial compared concurrent chemoradiotherapy (CCRT) versus radiotherapy (RT) alone in patients with advanced NPC. From December 1993 to April 1999, 284 patients with 1992 American Joint Committee on Cancer stage III to IV (M0) NPC were randomly allocated into two arms. Similar dosage and fractionation of RT was administered in both arms. The investigational arm received two cycles of concurrent chemotherapy with cisplatin 20 mg/m(2)/d plus fluorouracil 400 mg/m(2)/d by 96-hour continuous infusion during the weeks 1 and 5 of RT. Survival analysis was estimated by the Kaplan-Meier method and compared by the log-rank test. Baseline patient characteristics were comparable in both arms. After a median follow-up of 65 months, 26.2% (37 of 141) and 46.2% (66 of 143) of patients developed tumor relapse in the CCRT and RT-alone groups, respectively. The 5-year overall survival rates were 72.3% for the CCRT arm and 54.2% for the RT-only arm (P =.0022). The 5-year progression-free survival rates were 71.6% for the CCRT group compared with 53.0% for the RT-only group (P =.0012). Although significantly more toxicity was noted in the CCRT arm, including leukopenia and emesis, compliance with the combined treatment was good. The second cycle of concurrent chemotherapy was refused by nine patients and was delayed for > or = 1 week for another nine patients. There were no treatment-related deaths in either arm. We conclude that CCRT is superior to RT alone for patients with advanced NPC in endemic areas.

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Concurrent chemotherapy-radiotherapy compared with radiotherapy alone in locoregionally advanced nasopharyngeal carcinoma: progression-free survival analysis of a phase III randomized trial.

Savio K H Yu, Peter M L Teo, Eward D. Chan … (2002)

Nasopharyngeal carcinoma (NPC) is highly sensitive to both radiotherapy (RT) and chemotherapy. This randomized phase III trial compared concurrent cisplatin-RT (CRT) with RT alone in patients with locoregionally advanced NPC. Patients with Ho's N2 or N3 stage or N1 stage with nodal size > or = 4 cm were randomized to receive cisplatin 40 mg/m(2) weekly up to 8 weeks concurrently with radical RT (CRT) or RT alone. The primary end point was progression-free survival (PFS). Three hundred fifty eligible patients were randomized. Baseline patient characteristics were comparable in both arms. There were significantly more toxicities, including mucositis, myelosuppression, and weight loss in the CRT arm. There were no treatment-related deaths in the CRT arm, and one patient died during treatment in the RT-alone arm. At a median follow-up of 2.71 years, the 2-year PFS was 76% in the CRT arm and 69% in the RT-alone arm (P =.10) with a hazards ratio of 1.367 (95% confidence interval [CI], 0.93 to 2.00). The treatment effect had a significant covariate interaction with tumor stage, and a subgroup analysis demonstrated a highly significant difference in favor of the CRT arm in Ho's stage T3 (P =.0075) with a hazards ratio of 2.328 (95% CI, 1.26 to 4.28). For T3 stage, the time to first distant failure was statistically significantly different in favor of the CRT arm (P =.016). Concurrent CRT is well tolerated in patients with advanced NPC in endemic areas. Although PFS was not significantly different between the concurrent CRT arm and the RT-alone arm in the overall comparison, PFS was significantly prolonged in patients with advanced tumor and node stages.

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The effect of interruptions and prolonged treatment time in radiotherapy for nasopharyngeal carcinoma.

D Choy, D Chua, J Sham … (1997)

The effect of interruptions and prolonged overall treatment time in radiotherapy for nasopharyngeal carcinoma and the significance of timing of interruption was investigated. Treatment records of 229 patients treated with continuous course (CC) and 567 patients treated with split course (SC) radiotherapy for nonmetastatic NPC were reviewed. Overall treatment time without inclusion of time for boost was calculated. Treatment that extended 1 week beyond scheduled time was considered prolonged. Outcome in patients who completed treatment "per schedule" were compared with those who had "prolonged" treatment. Because of known patient selection bias between CC and SC, patients on the two schedules were analyzed separately. Multivariate analysis was performed for patients on SC. Total number of days of interruption, age, sex, T and N stage, and the use of boost were tested for the whole SC group. Analysis on the effect of timing of interruption was performed in a subgroup of 223 patients on SC who had a single unplanned interruption. Timing of interruption, either before or after the fourth week for the unplanned interruption, was tested in addition to the other variables in multivariate analysis for this subgroup of SC. Twenty-seven (11.8%) patients on CC and 96 (16.9%) patients on SC had prolonged treatment. Patients on SC who had prolonged treatment had significantly poorer loco-regional control rate and disease free survival when compared with those who completed radiotherapy per schedule (p = 0.0063 and 0.001, respectively, with adjustment for stage). For CC, the effect of prolonged treatment on outcome was not significant. The small number of events for patients on CC probably account for the insignificant finding. The number of days of interruption was confirmed as prognostic factor, independent of T and N stages, for loco-regional control and disease-free survival in multivariate analysis for SC. The hazard rate for loco-regional failure increased by 3.3% for each day of interruption. The timing of interruption, at the beginning or towards end of treatment, did not significantly alter outcome. Interruptions and prolonged treatment adversely affect outcome in radiotherapy for NPC and the effect of repopulation was confirmed. Every effort should be made to keep treatment on schedule and interruptions for whatever reasons should be minimized.

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Author and article information

Journal

Journal ID (nlm-ta): Oncotarget

Journal ID (iso-abbrev): Oncotarget

Journal ID (publisher-id): Oncotarget

Journal ID (publisher-id): ImpactJ

Title: Oncotarget

Publisher: Impact Journals LLC

ISSN (Electronic): 1949-2553

Publication date Collection: 6 June 2017

Publication date (Electronic): 30 November 2016

Volume: 8

Issue: 23

Pages: 37817-37825

Affiliations

¹ Department of Radiation Oncology, Cancer Hospital of Guangxi Medical University, Nanning, People's Republic of China

Author notes

Correspondence to: Xiao-Dong Zhu, zhuxdonggxmu@ 123456126.com

Article

Publisher ID: 13713

DOI: 10.18632/oncotarget.13713

PMC ID: 5514952

PubMed ID: 27911864

SO-VID: b0de64f7-b7e1-4452-8a1f-b49032306abc

License:

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC-BY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Effect of interrupted time during intensity modulated radiation therapy on survival outcomes in patients with nasopharyngeal cancer

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Abstract

Objective

Materials and methods

Results

Conclusion

Related collections

Karger: Oncology

Most cited references 9

Phase III study of concurrent chemoradiotherapy versus radiotherapy alone for advanced nasopharyngeal carcinoma: positive effect on overall and progression-free survival.

Concurrent chemotherapy-radiotherapy compared with radiotherapy alone in locoregionally advanced nasopharyngeal carcinoma: progression-free survival analysis of a phase III randomized trial.

The effect of interruptions and prolonged treatment time in radiotherapy for nasopharyngeal carcinoma.

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