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Severe late dysphagia and cause of death after concurrent
chemoradiation for larynx cancer in patients eligible for RTOG 91-11 q
Matthew C. Ward a,⇑, David J. Adelstein b, Priyanka Bhateja c, Tobenna I. Nwizu b, Joseph Scharpf d,
Narcissa Houston a, Eric D. Lamarre d, Robert Lorenz d, Brian B. Burkey d , John F. Greskovich a,
Shlomo A. Koyfman a
a Department of Radiation Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH, United States
b Department of Hematology and Medical Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH, United States
cDepartment of Hematology & Oncology, University Hospitals Seidman Cancer Center, Case Western Reserve University, Cleveland, OH, United States
d Department of Otolaryngology, Head and Neck Institute, Cleveland Clinic, Cleveland, OH, United States
a r t i c l e i n f o
Article history:
Received 16 February 2016
Received in revised form 14 March 2016
Accepted 15 March 2016
Available online 1 April 2016
Keywords:
Late toxicity
Larynx cancer
Chemoradiation
Dysphagia
Larynx preservation
s u m m a r y
Purpose: The long-term results of RTOG 91-11 suggested increased deaths not attributed to larynx cancer
after concomitant chemoradiotherapy (CRT) despite no apparent increase in late effects. Because the tim-
ing of events was not reported by RTOG 91-11, one possibility is that severe late dysphagia (SLD) devel-
ops beyond five years and leads to unreported treatment-related deaths. Here we explore the timing of
SLD after CRT.
Methods: Patients who would have met eligibility criteria for RTOG 91-11 and were treated with CRT
between 1993 and 2013 were identified. Events occurring beyond 3 months after treatment and sugges-
tive of SLD were recorded including esophageal stricture dilations, hospital admissions for aspiration
pneumonia or feeding-tube insertion. Feeding-tube dependence beyond one year was also considered
SLD. The cumulative incidence of SLD and its components was quantified using Gray’s competing risk
analysis with recurrence or death considered competing risks.
Results: Eighty-four patients were included with a median follow-up of 43 months. The 5-year overall
survival was 70% (95% CI 58–80%). No death was directly a result of treatment-induced late dysphagia.
The 5-year incidence of SLD was 26.5%. While 15 of 18 (83%) first stricture dilations occurred within
5 years after CRT, 3 of 5 (60%) aspiration admissions and 5 of 8 late feeding tube insertions occurred
beyond five years from CRT.
Conclusions: SLD is common after CRT for larynx cancer and can occur beyond 5 years from the end of
treatment, emphasizing the importance of survivorship follow-up. Despite the incidence of SLD, death
related to dysphagia is uncommon.
2016 Elsevier Ltd. All rights reserved.
Introduction
After the landmark Veterans Affairs Laryngeal Cancer Study
Group (VALSG) larynx-preservation trial reported in 1991,
induction chemotherapy and radiation became a viable
organ-preservation strategy for the treatment of locoregionally-
advanced larynx cancer [1] . Building on this trial, Radiation
Therapy Oncology Group (RTOG) 91-11 compared three strategies
for non-operative organ-preservation treatment: radiotherapy
alone, radiotherapy with concurrent cisplatin and the VALSCG
regimen of induction cisplatin and 5-fluorouracil followed by
radiotherapy. The long-term report of this trial confirmed the
continued efficacy of the two combined-modality arms and
encouraged the adoption of larynx-preservation strategies in daily
practice [2].
Although the concurrent cisplatin arm of RTOG 91-11 demon-
strated a clear advantage with regards to locoregional control, this
did not translate to an overall survival benefit when compared to
the other arms. In the final update, there was a trend toward infe-
rior overall survival in the concurrent arm when compared to
induction chemotherapy (HR 1.25, p = 0.08) with an increase in
non-cancer related deaths with concurrent chemotherapy but no
1368-8375/ 2016 Elsevier Ltd. All rights reserved.
q Presented at the 2015 ASTRO Annual Meeting, San Antonio, TX, United States.
⇑ Corresponding author at: Department of Radiation Oncology, Taussig Cancer
Institute, Cleveland Clinic, 9500 Euclid Avenue, T28, Cleveland, OH 44195, United
States. Tel.:+1 (216) 444 5571 ; fax:+1 (216) 445 1068 .
E-mail address: (M.C. Ward).
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Reprinted by permission of Oral Oncol. 2016; 57:21-26.
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