Accelerated vs. conventionally fractionated adjuvant radiotherapy in high-risk head and neck cancer: a meta-analysis

doi:10.1186/s13014-018-1133-8

Meta-Analysis

. 2018 Oct 4;13(1):195.

doi: 10.1186/s13014-018-1133-8.

Accelerated vs. conventionally fractionated adjuvant radiotherapy in high-risk head and neck cancer: a meta-analysis

Affiliations

¹ Department of Radiotherapy and Radiooncology, Medical Faculty, Heinrich Heine University, Moorenstr. 5, 40225, Dusseldorf, Germany.
² Department of Radiotherapy and Radiooncology, Medical Faculty, Heinrich Heine University, Moorenstr. 5, 40225, Dusseldorf, Germany. boelke@med.uni-duesseldorf.de.
³ Department of Oto-Rhino-Laryngology, Head and Neck Surgery, Ulm University Medical Center, Ulm, Germany.
⁴ Department of Dermatology, Medical Faculty Heinrich Heine University Dusseldorf, Dusseldorf, Germany.
⁵ Division of Biostatistics and Bioinformatics, Department of Oncology, The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
⁶ Department of Oto-Rhino-Laryngology, Head and Neck Surgery, Heinrich Heine University Dusseldorf, Dusseldorf, Germany.
⁷ Vincere Cancer Center, Scottsdale, AZ, USA.

PMID: 30286777
PMCID: PMC6172789
DOI: 10.1186/s13014-018-1133-8

Meta-Analysis

Accelerated vs. conventionally fractionated adjuvant radiotherapy in high-risk head and neck cancer: a meta-analysis

Christiane Matuschek et al. Radiat Oncol. 2018.

. 2018 Oct 4;13(1):195.

doi: 10.1186/s13014-018-1133-8.

Affiliations

¹ Department of Radiotherapy and Radiooncology, Medical Faculty, Heinrich Heine University, Moorenstr. 5, 40225, Dusseldorf, Germany.
² Department of Radiotherapy and Radiooncology, Medical Faculty, Heinrich Heine University, Moorenstr. 5, 40225, Dusseldorf, Germany. boelke@med.uni-duesseldorf.de.
³ Department of Oto-Rhino-Laryngology, Head and Neck Surgery, Ulm University Medical Center, Ulm, Germany.
⁴ Department of Dermatology, Medical Faculty Heinrich Heine University Dusseldorf, Dusseldorf, Germany.
⁵ Division of Biostatistics and Bioinformatics, Department of Oncology, The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
⁶ Department of Oto-Rhino-Laryngology, Head and Neck Surgery, Heinrich Heine University Dusseldorf, Dusseldorf, Germany.
⁷ Vincere Cancer Center, Scottsdale, AZ, USA.

PMID: 30286777
PMCID: PMC6172789
DOI: 10.1186/s13014-018-1133-8

Abstract

Background: Adjuvant radiotherapy in advanced head and neck squamous cell cancer (HNSCC) reduces the risk of local-regional failure and most likely increases the survival rate. Patients at high risk for tumor recurrence may benefit from more aggressive altered fractionation schedules in order to reduce the overall time from surgery to completion of radiotherapy. Here, we reviewed the results of six randomized trials addressing the above hypothesis.

Methods: In the six trials of interest, a total of 988 patients with locally advanced HNSCC were randomly assigned to receive either accelerated or conventionally fractionated adjuvant radiotherapy. Hazard ratios (HR) were extracted from available publications for local-regional control, distant metastasis as well as overall-, cancer specific- and disease-free survival. Meta-analysis of the effect sizes was performed using fixed and random effect models. Acute and late side effects were categorized and summarized for comparison.

Results: Accelerated radiotherapy did not improve the loco-regional control (n = 988, HR = 0.740, CI = 0.48-1.13, p = 0.162), progression-free survival (HR = 0.89, CI = 0.76-1.04, p = 0.132) or overall survival (HR = 0.88, CI = 0.75-1.04, p = 0.148) significantly. Acute confluent mucositis occurred with significant higher frequency with accelerated radiotherapy. Late side effects did not differ significantly in either group.

Conclusion: Accelerated radiotherapy does not result in a significant improvement of loco-regional control or overall survival in high-risk patients. Acute but not late radiation toxicity were more frequent with the accelerated RT technique. In clinical practice accelerated postoperative radiation therapy might be a suitable option only for a subset of patients.

Keywords: Accelerated fractionation; Adjuvant therapy; Conventional fractionation; Head and neck cancer; High risk; Radiation therapy.

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Conflict of interest statement

Ethics approval and consent to participate

There was no ethics approval necessary because in this meta-analysis we were pulling numbers from the published manuscripts and pooling results.

Consent for publication

Not applicable because in this meta-analysis we were pulling numbers from the published manuscripts and pooling results.

Competing interests

The authors declare that they have no competing interests.

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Figures

**Fig. 1**
Forest plot of comparison of locoregional failure between accelerated and conventional radiation using random effect model. Horizontal bars indicate the amount of variation (95% confidence intervals of the parameter estimates). Sizes of squares indicate weight in the pooled effect size

**Fig. 2**
Forest plot of comparison of local failure between accelerated and conventional radiation using fixed effect model

**Fig. 3**
Forest plot of comparison of regional failure between accelerated and conventional radiation using fixed effect model

**Fig. 4**
Forest plot of comparison of distant failure between accelerated and conventional radiation using fixed effect model

**Fig. 5**
Forest plot of comparison of progression-free survival between accelerated and conventional radiation using fixed effect model

**Fig. 6**
Forest plot of comparison of overall survival between accelerated and conventional radiation using fixed effect model

**Fig. 7**
Forest plot of comparison of cancer mortality between accelerated and conventional radiation using fixed effect model

**Fig. 8**
Forest plot of comparison of non-cancer mortality between accelerated and conventional radiation using fixed effect model

See this image and copyright information in PMC

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References

1. Tarnawski R, Fowler J, Skladowski K, et al. How fast is repopulation of tumor cells during the treatment gap? Int J Radiat Oncol Biol Phys. 2002;54:229–236. doi: 10.1016/S0360-3016(02)02936-X. - DOI - PubMed
1. Trott KR. Cell repopulation and overall treatment time. Int J Radiat Oncol Biol Phys. 1990;19:1071–1075. doi: 10.1016/0360-3016(90)90036-J. - DOI - PubMed
1. Maciejewski B, Withers HR, Taylor JM, Hliniak A. Dose fractionation and regeneration in radiotherapy for cancer of the oral cavity and oropharynx: tumor dose-response and repopulation. Int J Radiat Oncol Biol Phys. 1989;16:831–843. doi: 10.1016/0360-3016(89)90503-8. - DOI - PubMed
1. Withers HR, Maciejewski B, Taylor JM, Hliniak A. Accelerated repopulation in head and neck cancer. Front Radiat Ther Oncol. 1988;22:105–110. doi: 10.1159/000415101. - DOI - PubMed
1. Mehanna H, Wong WL, McConkey CC, et al. PET-CT surveillance versus neck dissection in advanced head and neck Cancer. N Engl J Med. 2016;374:1444–1454. doi: 10.1056/NEJMoa1514493. - DOI - PubMed

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[1] Tarnawski R, Fowler J, Skladowski K, et al. How fast is repopulation of tumor cells during the treatment gap? Int J Radiat Oncol Biol Phys. 2002;54:229–236. doi: 10.1016/S0360-3016(02)02936-X. - DOI - PubMed

[2] Tarnawski R, Fowler J, Skladowski K, et al. How fast is repopulation of tumor cells during the treatment gap? Int J Radiat Oncol Biol Phys. 2002;54:229–236. doi: 10.1016/S0360-3016(02)02936-X. - DOI - PubMed

[3] Trott KR. Cell repopulation and overall treatment time. Int J Radiat Oncol Biol Phys. 1990;19:1071–1075. doi: 10.1016/0360-3016(90)90036-J. - DOI - PubMed

[4] Trott KR. Cell repopulation and overall treatment time. Int J Radiat Oncol Biol Phys. 1990;19:1071–1075. doi: 10.1016/0360-3016(90)90036-J. - DOI - PubMed

[5] Maciejewski B, Withers HR, Taylor JM, Hliniak A. Dose fractionation and regeneration in radiotherapy for cancer of the oral cavity and oropharynx: tumor dose-response and repopulation. Int J Radiat Oncol Biol Phys. 1989;16:831–843. doi: 10.1016/0360-3016(89)90503-8. - DOI - PubMed

[6] Maciejewski B, Withers HR, Taylor JM, Hliniak A. Dose fractionation and regeneration in radiotherapy for cancer of the oral cavity and oropharynx: tumor dose-response and repopulation. Int J Radiat Oncol Biol Phys. 1989;16:831–843. doi: 10.1016/0360-3016(89)90503-8. - DOI - PubMed

[7] Withers HR, Maciejewski B, Taylor JM, Hliniak A. Accelerated repopulation in head and neck cancer. Front Radiat Ther Oncol. 1988;22:105–110. doi: 10.1159/000415101. - DOI - PubMed

[8] Withers HR, Maciejewski B, Taylor JM, Hliniak A. Accelerated repopulation in head and neck cancer. Front Radiat Ther Oncol. 1988;22:105–110. doi: 10.1159/000415101. - DOI - PubMed

[9] Mehanna H, Wong WL, McConkey CC, et al. PET-CT surveillance versus neck dissection in advanced head and neck Cancer. N Engl J Med. 2016;374:1444–1454. doi: 10.1056/NEJMoa1514493. - DOI - PubMed

[10] Mehanna H, Wong WL, McConkey CC, et al. PET-CT surveillance versus neck dissection in advanced head and neck Cancer. N Engl J Med. 2016;374:1444–1454. doi: 10.1056/NEJMoa1514493. - DOI - PubMed

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