Patterns of utilization and comparative efficacy of altered fractionation and concurrent chemoradiation for treatment for T2N0M0 glottic carcinoma
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To study radiotherapeutic treatment approaches in larynx-preservation for T2N0M0 glottic carcinoma at free-standing centers in the USA.
We retrospectively audited fractionation and chemoradiation at 59 centers in 5 geographic regions from 2000 to 2015. Chi-squared test and Fisher’s exact test were used to compare frequencies, the Cox proportional hazards model and Kaplan-Meier procedure were used for survival analyses, and log-rank test to compare survival curves.
Among 180 patients, chemoradiation, accelerated hypofractionation (2.25 Gy/fraction), and hyperfractionation was given to 14.4%, 13.3%, and 13.3%, respectively. Hypofractionation rates varied by geographic location: western/southern 33%, northeast 18.6%, Florida 5.6%, and Michigan 0% (p < 0.001). Conversely, hyperfractionation rates were as follows: Florida 23.6%, Michigan 14%, southern 9.5%, northeast and western 0% (p < 0.001). Hypofractionation increased from 6.3% in 2000–2004 to 25.0% in 2010–2015 (p < 0.001) and steadily declined for hyperfractionation. Chemoradiation did not vary by region but increased over time: 0% in 2000–2004, 17.6% in 2010–2015(p = 0.029).
At mean follow-up at 32.3 months, 36 months survivals were as follows: accelerated fractionation 85%, hyperfractionation 81%, and standard fractionation 66%, (p = 0.01); treatment duration < 50 days 82%, > 50 days 59% (p = 0.03). There was no difference in overall survival, progression-free survival, or locoregional-recurrence-free survival between chemoradiation and radiotherapy-only (all fractionations). Accelerated fractionation, (the fractionation with the highest survival) gave similar 36 months survivals as chemoradiation: 85% and 68%, respectively (p = 0.69). Chemoradiation worsened acute grades 2–4 toxicity rate versus radiotherapy-only: 80.8% and 54.5%, respectively (p = 0.01, univariate and multivariate).
Hypofractionation gave superior survival than standard fractionation for glottic T2N0M0 tumors. Its use varies among treatment centers but is increasing with time. Chemoradiation gave a lower therapeutic ratio: more than 30% greater acute toxicity without improvement of survival; yet, its use is growing over time. More explicit guidelines are needed.
KeywordsT2 glottic Early larynx cancer Accelerated hypofractionation Head and neck squamous cell carcinoma Chemoradiation Patterns of care
We wish to thank the patients who were the subjects of this study and the staff who provided care, 21st Century Oncology, FL, USA.
All authors contributed to the study conception and design.
Conceptualization and methodology were performed by Anesa Ahamad, Sharon Salenius, and Eduardo Fernandez.
Material preparation and data collection were performed by Rudi Ross.
Analyses were performed by Sharon Salenius.
Interpretation of the results was performed by Anesa Ahamad, Sharon Salenius, and Eduardo Fernandez.
Radiobiological calculations were performed by Raj Selvaraj.
Writing was performed by Anesa Ahamad.
Review and editing were performed by Anesa Ahamad, Sharon Salenius, and Eduardo Fernandez.
The first draft of the manuscript was written by Anesa Ahamad and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.
Compliance with ethical standards
No funding was received for this study.
Conflict of interest
The authors declare that they have no conflict of interest.
All procedures performed in studies involving human participants were in accordance with the ethical standards of The Office for Human Research Protections of the U.S. Department of Health and Human Services and with the 1964 Helsinki declaration and with the Helsinki Declaration of 1975, as revised in 2008, and its later amendments or comparable ethical standards. This was a retrospective study and was approved by an appropriate ethics committee: an institutional Review Board.
Statement of informed consent was not applicable since the manuscript does not contain any patient data. This was a retrospective study. Prior to embarking on this study, an Institutional Review Board (IRB) reviewed the proposal and study description and granted a waiver of the requirement for individuals to provide signed consent for retrospective review of case files that was the procedure involved in this study.
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