Long-term patient reported outcomes following radiation therapy for oropharyngeal cancer: cross-sectional assessment of a prospective symptom survey in patients ≥65 years old
Eraj et al. Radiation Oncology
Long-term patient reported outcomes following radiation therapy for oropharyngeal cancer: cross-sectional assessment of a prospective symptom survey in patients ≥65 years old
Neck Cancer Symptom Working Group
Salman A. Eraj 0
Mona K. Jomaa 0
Crosby D. Rock 0
Abdallah S. R. Mohamed 0
Blaine D. Smith 0
Joshua B. Smith 0
Theodora Browne 0
Luke C. Cooksey 0
Bowman Williams 0
Brandi Temple 0
Kathryn E. Preston 0
Jeremy M. Aymar 0
Neil D. Gross
Randal S. Weber
Amy C. Hessel
Jack Phan 0
Erich M. Sturgis
Ehab Y. Hanna 1
Steven J. Frank 0
William H. Morrison 0
Ryan P. Goepfert
Stephen Y. Lai
David I. Rosenthal 0
Tito R. Mendoza
Charles S. Cleeland
Kate A. Hutcheson
Clifton D. Fuller 0
Adam S. Garden 0
G. Brandon Gunn 0 1
0 Department of Radiation Oncology, Unit 97, The University of Texas MD Anderson Cancer Center , 1515 Holcombe Boulevard, Houston, TX 77030 , USA
1 Department of Neurosurgery, Division of Surgery, The University of Texas MD Anderson Cancer Center , Houston, TX , USA
Background: Given the potential for older patients to experience exaggerated toxicity and symptoms, this study was performed to characterize patient reported outcomes in older patients following definitive radiation therapy (RT) for oropharyngeal cancer (OPC). Methods: Cancer-free head and neck cancer survivors (>6 months since treatment completion) were eligible for participation in a questionnaire-based study. Participants completed the MD Anderson Symptom Inventory-Head and Neck module (MDASI-HN). Those patients ≥65 years old at treatment for OPC with definitive RT were included. Individual and overall symptom severity and clinical variables were analyzed. Results: Of the 79 participants analyzed, 82% were male, 95% white, 41% T3/4 disease, 39% RT alone, 27% induction chemotherapy, 52% concurrent, and 18% both, and 96% IMRT. Median age at RT was 71 yrs. (range: 65-85); median time from RT to MDASI-HN was 46 mos. (2/3 > 24 mos.). The top 5 MDASI-HN items rated most severe in terms of mean (±SD) ratings (0-10 scale) were dry mouth (3.48 ± 2.95), taste (2.81 ± 3.29), swallowing (2.59 ± 2.96), mucus in mouth/throat (2.04 ± 2.68), and choking (1.30 ± 2.38) reported at moderate-severe levels (≥5) by 35, 29, 29, 18, and 13%, respectively. Thirty-nine % reported none (0) or no more than mild (1-4) symptoms across all 22 MDASI-HN symptoms items, and 38% had at least one item rated as severe (≥7). Hierarchical cluster analysis resulted in 3 patient groups: 1) ~65% with ranging from none to moderate symptom burden, 2) ~35% with moderate-severe ratings for a subset of classically RT-related symptoms (e.g. dry mouth, mucus, swallowing) and 3) 2 pts. with severe ratings of most items. (Continued on next page)
(Continued from previous page)
Conclusions: The overall long-term symptom burden seen in this older OPC cohort treated with modern standard
therapy was largely favorable, yet a higher symptom group (~35%) with a distinct pattern of mostly local and classically
RT-related symptoms was identified.
Radiation therapy (RT) (+/− concurrent systemic therapy)
is a well-accepted treatment for oropharyngeal carcinoma
(OPC). However, the optimal treatment for older patients
is not well defined [
]. In a large-scale meta-analysis, the
survival benefit of adding chemotherapy to local regional
therapy for OPC was shown to diminish with increasing
]. The lack of observed benefit in older patients
could be due to increased treatment-related toxicity,
poorer treatment tolerance, or confounding comorbid
conditions, all potentially offsetting any survival benefit.
Late sequelae of therapy remain concerning for older
populations due to the potential of irreversible functional
decline due to limited physical reserves or poor
compensatory mechanisms [
]. Additionally, symptoms may be
experienced synergistically along with age-related
functional decline, thus compounding morbidity from
There is now clinical research emphasis on treatment
de-escalation and toxicity reduction strategies in OPC,
particularly for those with more favorable/human
papillomavirus(HPV)-related disease, as the impact of late
toxicities associated with current standard therapies in
survivors is now recognized [
]. While HPV-related
OPC skews younger, most OPCs in older patients are
also HPV-related and incidence in this subset of patients
is increasing. With highly curable disease, the
importance of long-term toxicity reduction in older patients
with OPC should be emphasized [
Patients with OPC are increasingly being considered for
primary surgical management using transoral and robotic
surgery or de-escalation strategies with the goal of
maintaining cure rates and reducing toxicity compared to
current RT-based approaches [
]. At present, few
prospectively collected late toxicity assessment series of OPC
survivors treated with modern RT techniques (e.g. intensity
modulated radiation therapy(IMRT)) exist to serve as
benchmarks for estimation of symptom differentials for patients
treated with alternate modalities (e.g. surgery) or advanced
RT techniques (e.g. intensity modulated proton therapy).
To help define optimal treatment for older patients in
the setting of continually evolving and potentially
competing treatment modalities, OPC site-, treatment-, and
agespecific patient reported outcomes (PROs) are needed to
inform patients, clinicians, and investigators. Thus, we
analyzed results of a validated multi-symptom PRO
instrument in older OPC survivors in order to
characterize the post-therapy symptom experience in
patients treated at a tertiary academic medical center.
Consequently, the specific aims of the current study
Characterize the late patient reported symptom
profile of patients ≥65 years old
Identify potential demographic, disease,
treatment-related, and comorbidity-related factors
associated with long-term symptom severity
Explore symptom burden differences by selected
patient/treatment subgroups, including by tumor
sub-site and receipt of systemic therapy
Generate testable hypotheses for future clinical
As part of a large-scale Institutional Review
Boardapproved programmatic prospective symptom survey,
adults (≥18 years old) previously treated for head and
neck cancer without evidence of active disease and
who completed initial therapy more than 6 months
previous were eligible for this symptom assessment.
Study-specific informed consent was provided by all
participants, who then completed the MD Anderson
Symptom Inventory-Head and Neck module
(MDASIHN.) Patient demographic, tumor, and treatment
characteristics were extracted from medical records,
and patient performance status (PS) and comorbidity
burden was estimated at the time of treatment
according to the ECOG scale and age-adjusted Charlson
comorbidity index (CCI), respectively. The CCI
assesses 19 comorbid conditions weighted by potential
to influence mortality and is used to evaluate the
impact of comorbidity on survival and toxicity [
Patients targeted for this analysis included those
≥65 years old at the time of definitive RT for OPC. At least
6 months from completion of therapy to MDASI-HN
completion was specified in order to allow for stabilization/
resolution of acute effects of therapy, allowing focused
reporting on more late sequelae [
]. Patients who received
RT for recurrence or second primary were excluded.
Patients that underwent definitive or salvage surgery at the
site of primary disease at any point prior to questionnaire
completion were also excluded, excepting patients with a
neck dissection (either planned, or as a function of our
standardized surveillance protocol) or pre-therapy
Patient reported outcomes were detailed by the
MDASI-HN, a previously validated, brief,
patientreported outcome assessment tool [
]. It contains
28-items consisting of three subscales: 13 core items
rating the severity of general symptoms common to
all cancers, nine items specific to the MDASI-HN
questionnaire, and 6 items concerning how severely
symptoms interfere with activities of daily living. The
core and head and neck cancer specific items are
rated on a 0–10 (“not present” to “as bad as you can
imagine”) numeric scale indicating the presence and
severity of the symptom. The interference items are
rated on a 0–10 numeric scale from “did not
interfere” to “interfered completely.”
Cumulative symptom burden was characterized by
aggregate MDASI-HN symptom score with secondary
analysis of specific symptom items. A previously utilized
method of patient grouping was used: symptom free (all
ratings 0), no more than mild (all ratings <5), no more
than moderate (all ratings <7), and severe (at least one
item with rating ≥ 7) [
]. Individual item severity was
rated using a similar scheme: none (rating 0), mild
(rating 1–4), moderate (5–6), and severe (≥7). Grouped and
individual MDASI-HN items were tabulated and the
proportions of patients reporting each level of symptom
severity were presented graphically as heat maps for the
entire cohort, as well as for clinical subgroups of
interest, hypothesized to have different levels of symptom
severity (tumor subsite, T-category, and receipt of
concurrent systemic therapy).
The item severity rating means were compared using
Wilcoxon rank-sum tests and the proportions of the item
severity ratings were compared by Pearson’s chi-squared
test, or Fischer’s exact test. Univariate and multivariate
regression analysis were performed with the aggregate
MDASI-HN symptom items and with composite of the
top 5 symptom items as continuous variables against the
following variables: sex, race, cancer subsite, receipt of
systemic therapy, RT dose, T stage 1–2 vs. 3–4, N stage 0–1
vs. 2+, unilateral radiotherapy, neck dissection, smoking
status, and CCI. Variables with a p-value <0.3 on
univariate analysis were included in multivariate analysis and a
non-Bonferonni corrected p-value of 0.05 was used as the
cutoff for significance, owing to the hypothesis-generating
nature of this dataset. Patient clusters were defined by
hierarchal cluster analysis and each patient’s individual
item ratings are displayed via heat map.
Patient demographic, disease and treatment-related
characteristics for the 79 participants are shown in
Table 1. Sixty-seven percent completed the MDASI-HN
≥2 years since treatment completion and 89% ≥1 year.
Based on the AJCC 7th edition stage grouping, the
number of patients falling into stage I, II, III, IVA, and IVB
were 9 (11%), 5 (6%), 7 (9%), 57 (72%), and 1 (1%),
]. Of the 39 tumors tested, 87% were
considered HPV-positive, either by p16 or HPV DNA
detection. Pretreatment ECOG PS, was available for 68%
of the cohort, and 52% were ECOG 0, 39% ECOG 1, and
9% ECOG 2–3.
Twelve patients (15%) in the cohort underwent a neck
dissection as part of their therapy. Of these, 3 were prior
to and 9 were after RT. Seventy-six (96%) received IMRT
and 11 (14%) received unilateral neck RT for lateralized
primaries of the tonsillar fossa. All of the 21 (27%)
patients that received induction chemotherapy received
combinations of platinum and taxane-based therapies.
Of those who received CCRT (concurrent
chemoradiotherapy) (41 patients, 52%), the most utilized single
agents were cisplatin in 39%, followed by carboplatin in
29%, and cetuximab in 22%.
The comorbidity burden at time of treatment was
measured by age-adjusted CCI and had a median of ~3
(IQR 2–4) with 82% of the quantified comorbidity
burden coming from age adjustment. The most common
non-age-related comorbidity was diabetes mellitus type
II in 13 patients (16%), followed by cerebrovascular
disease in 7 patients (9%) and chronic pulmonary disease in
6 (8%). Beyond CCI measures, 37 patients (47%) had
hypertension and 43 (54%) had general cardiac
comorbidity (defined as the presence or history of
hypertension, coronary artery disease, myocardial infarction, or
congestive heart failure).
The mean individual, subscale, and composite
MDASIHN item ratings for the entire cohort are shown in Table 2.
A heat map of the proportion of the entire cohort
experiencing each level of symptom severity for the 22
MDASIHN symptom items is shown in Fig. 1. Overall, the five
most highly rated items by mean ± SD were dry mouth
(3.48 ± 2.95), problems tasting food (2.81 ± 3.29), difficulty
swallowing/chewing (2.59 ± 2.96), problem with mucus in
mouth/throat (2.04 ± 2.68), and choking/coughing
(1.30 ± 2.38), reported at moderate-severe levels (≥5) by
35, 29, 29, 18, and 13% of patients, respectively. Of the
entire cohort, 9% were symptom free (all 22 symptom items
rated zero), 30% had no more than mild symptoms (<5),
and 38% had at least one item rating that was severe (≥7).
For the 30 patients rating at least one item as severe,
the median number of items that were rated severe was
2 (IQR 1–4). In this subgroup, the five most highly rated
items mean ± SD were dry mouth (5.83 ± 3.00),
problems with taste (5.73 ± 3.34), difficulty
swallowing/chewing (4.33 ± 3.42), problem with mucus in mouth/throat
(3.37 ± 3.41), and problem with voice (2.43 ± 3.18), a
result similar to that of the entire cohort. This indicates
the presence of low overall item scoring with individual
items rated severe driving the mean. Notably, difficulty
swallowing/chewing, choking/coughing, and fatigue were
reported at severe levels (≥7), in 11%, 5%, and 3%,
respectively. Overall, only 2 patients had a feeding tube
present at the time of MDASI-HN.
The proportion of patients experiencing each level of
symptom severity for the 22 individual MDASI-HN
symptom items comparing clinical subgroups of interest
(primary site, T-category, and receipt of concurrent
chemotherapy) are shown as heat maps in Fig. 2 and the
proportions reporting these at moderate-severe levels
are compared in Additional file 1: Table S1. Likewise,
the proportions reporting severe levels are compared in
Additional file 2: Table S2. Statistically significant
differences in the proportions of patients reporting
moderatesevere levels were identified for a limited number of
symptoms in subgroup comparisons (difficulty with
voice and problems with teeth/gums were worse for T3/
4 and distress, problem tasting food, and difficulty with
voice were worse for those receiving concurrent
chemotherapy), and no differences were noted in tumor subsite
comparisons. Statistically significant differences in the
proportions of patients reporting severe levels were also
identified for a limited number of symptoms in subgroup
comparisons (problem tasting food, difficulty with voice,
problem with teeth/gums were worse for T3/4 and
problem tasting food and constipation were worse for those
receiving concurrent chemotherapy), and again no
differences were noted in by tumor subsite comparisons. To
explore symptom differentials by age, we compared the
proportions of patients reporting moderate-severe level
symptoms (≥5), comparing those ≥75 versus <75 years
old, and using this cut-point, there were no statistically
significant differences detected.
Hierarchical cluster analysis results are presented in
Fig. 3. Cluster A comprised the majority (64%), with a
subset symptom free and the majority with no more
than moderate ratings for a limited number of items.
The distribution of these items fell into two sub-clusters,
one centered around more general, constitutional
symptoms of fatigue, memory, drowsiness, and sadness, and
another centered around more classical RT-related
toxicities, such as choking/coughing, dry mouth, problem
with mucus in mouth/throat, difficulty
swallowing/chewing, and problem tasting food. Cluster B (33%) patients
had a more moderate-severe symptom burden with a
heterogeneous distribution of several severely rated
items. There again was a sub-cluster centered around
moderate global symptoms, yet more broadly spread
than cluster A. Similar to cluster A were distinct bands,
yet more severely rated, for the same classic RT-related
toxicities observed in cluster A. Cluster C formed the
small minority (~2%), with essentially severe ratings for
the majority of all 22 items.
Clinical correlates of symptom severity
On univariate analysis, none of the interrogated variables
were shown to be associated with increased composite
symptom scores at the p < 0.05 level (all 22 items). On
univariate analysis with a composite score of the top 5
symptoms, RT dose (p < 0.03) and T-category (p < 0.04)
were significantly associated, but on multivariate
analysis, neither of these were found to retain statistical
significance. Full results of univariate and multivariate
analysis are provided in Additional file 3: Table S3.
This prospective survivorship assessment study of older
patients treated with (chemo)RT for OPC using
contemporary standard approaches demonstrates a symptom
profile which is generally favorably with identifiable subsets of
patients with distinct post-therapy symptom
constellations. While no one item or items had moderate-severe
intensity recorded by a majority of respondents, items for
dry mouth, difficulty swallowing/chewing, and taste
received notable pluralities, with 35%, 29% and 29% of
survivors reporting moderate-severe levels, respectively
(Additional file 1: Table S1). Overall, these highest
intensity symptom items reported were consistent with “classic”
RT-related normal tissue late toxicities, namely
xerostomia and dysphagia.
The majority of respondents were free from
moderatesevere xerostomia, attributable to the well-characterized,
more conformal, treatment offered by IMRT, yet even
so, a detectable minority of 16% of the cohort reported
severe ratings for dry mouth [
approximately 10% of survivors reported severe late problems
with dysphagia-related symptoms. The correspondingly
lower proportion of patients with PEG tube at time of
MDASI-HN suggest that the use of objective clinical
endpoints alone do not capture the nuanced toxicity
burden of this cohort. Additionally, previous studies
have shown that even mild late dysphagia, which was
present in our cohort, is strongly correlated with overall
health related quality of life (HRQOL) (24). Thus,
further efforts to improve xerostomia and swallowing
dysfunction are likely to yield impactful gain and should
be pursued aggressively [
Notably, in this older patient cohort, T-category and
chemotherapy (either induction and/or concurrent) did
not predict strikingly different toxicity profiles. However,
individual item-level differences were associated with
concurrent chemotherapy and T-category. Specifically,
problem tasting food and voice symptoms were more
severe in the subgroup of patients with T3-T4 disease
which is in line with locally advanced disease infiltrating
a larger area of normal structures and resultant larger
RT volumes. Cancer subsites (i.e. base of tongue versus
tonsil) did not differentially impact the mean item
ratings or their distributions, suggesting that this factor
alone does not determine the late toxicities experienced
by older OPC patients.
Receipt of CCRT was not found to have an association
with PROs in univariate analysis. The survival benefit of
CCRT versus RT alone in older patients is not generally
supported but recent studies have shown that CCRT
should not be denied solely based on age [
further study is necessary, the survival benefit and
equivalent late toxicity suggested by our findings points
towards expansion of CCRT into more aged populations.
In a study using SEER-Medicare data regarding OPC in
the elderly, as age increased from 70 to 81, treatment
shifted toward surgery alone or no treatment [
the low symptom burden observed within our cohort, it
seems subsets of older patients should be considered for
standard therapies, as it appears that comorbidity and
age did not have a detectable effect upon reported late
symptom frequency nor severity.
Hierarchical cluster analysis was also informative with
consistent representation of xerostomia at some level in
the far majority of patients. While 64% of the cohort
presented with generally no to moderate symptom
burden, a dismaying ~33% of the cohort still reported
moderate-severe ratings for two subsets of symptoms:
one centered around classically RT-related symptoms
(e.g. dry mouth, problems with mucus, swallowing/
chewing, and taste) at moderate-severe ratings, and
another around general symptoms (e.g. fatigue, memory,
drowsiness) at more moderate ratings. This visualization
technique reinforces the continued presence of these
two categories of late toxicities and affirms that they
tend to co-occur in symptomatic patients, rather than
homogenously among the entire cohort.
One of these possible determinants was age-adjusted
comorbidity status pre-RT, which has already been
shown to have a negative association with overall
survival (OS) [
]. Our analysis showed that cohort
comorbidity, at least as measured by the age-adjusted CCI in our
specific cohort, did not have an association with PROs.
This finding may be due to the healthy, homogenous group
of older patients that made up our cohort, evidenced by
the median age-adjusted CCI of 3, which corresponds to
older patients with few comorbidities, and low comorbidity
burden outside of age-adjustment [
]. Our study shows
that for these older patients judged fit enough to receive
curative therapy, PROs remained favorable to a median
follow-up period of nearly 4 years (46 months), suggesting
that these patients, broadly, maintain global functionality
after completion of therapy, as revealed in the low mean
symptom interference reports observed here.
Inherent limitations of this analysis include data
collected from a large-scale, tertiary, academic cancer
institution, acknowledging that, patient self-selection and the
patient profile of our specific patient population may not
mirror the general OPC population. The patients in our
study had comparatively high performance status, low
comorbidity burden, and most received standard IMRT.
Additionally, survey timing varied widely, 6–117 months,
and while previous work has shown that most patients’
toxicity has stabilized 6 months after therapy, it is possible
that the varying follow-up periods may not precisely
capture late toxicity in this cohort and misrepresent true late
]. However, given the low symptom burden
observed overall, it is reasonable to presume that toxicity
could only have been better with a narrower and later
survey acquisition time range. Treatment strategies and
expected toxicities differ between AJCC stages and the
inhomogeneity of the cohort in this respect is a limitation
for external validity. Due to the unbalanced distribution of
AJCC stages within our cohort, T1/2 versus T3/4 was use
for comparisons as a proxy for locally confined versus
locally advanced disease. Baseline symptom data was
unavailable, so it is difficult to ascertain what
proportion of the symptoms reported were present
pretherapy and potentially persistent versus those that
were in fact an actionable secondary side-effect from
RT. The standard caveats from any cross-sectional
analysis apply in that longitudinal follow-up or the toxicity
deltas over time are lacking. Therefore, we recommend
the pursuit of studies examining the specific dosimetric
effects on normal structures, incorporating tumor HPV
status, as well as, analyzing symptom item scores
longitudinally with pretreatment baselines, which are already
underway at our institution.
Nonetheless our data represents, a large single-site
prospective cross-sectional interrogation of late
survivorship in older OPC patients who received definitive
radiotherapy. It provides a characterized multi-symptom
profile for these older patients treated with
contemporary techniques, using a standardized approach [
These data provide a reference/benchmark dataset
against which approaches leveraging alternate modalities
(e.g. advanced surgical techniques), or advanced
radiation therapy techniques such as proton therapy, may be
In conclusion, older OPC patients with a median of
nearly 4 years from completion of therapy exhibited a
broad freedom from global symptoms, with a majority
showing no more than mild-to-moderate intensity for
experienced symptoms. However, 38% reported at least
one severe symptom item. Moderate-severe xerostomia,
difficulty tasting food, and dysphagia related symptoms
were experienced by a plurality of patients
(approximately 1/3 each), but efforts should be made to increase
the currently small fraction (9%) of patients who are
symptom free survivors.
Additional file 1: Table S1. Proportions of patients reporting moderate
to severe (≥5) rating for the 22 MDASI-HN symptom items by clinical
subgroups of interest. (DOCX 20 kb)
Additional file 2: Table S2. Proportions of patients reporting severe
(≥7) rating for the 22 MDASI-HN symptom items by clinical subgroups of
interest. (DOCX 17 kb)
Additional file 3: Table S3. Results of univariate and multivariate
analysis comparing MDASI-HN symptom item composite and Top 5
MDASI-HN items by mean composite with clinical variables of interest.
(DOCX 16 kb)
CCI: Charlson comorbidity index; CCRT: Concurrent chemoradiotherapy;
ECOG: Eastern Cooperative Oncology Group; HPV: Human papillomavirus;
IMRT: Intensity modulated radiation therapy; MDASI-HN: MD Anderson
Symptom Inventory-Head and Neck module; OPC: Oropharyngeal cancer;
PRO: Patient reported outcome; PS: Performance status; RT: Radiation therapy
The authors would like to thank Ms. Barbara Habal, our senior research nurse,
for her data collection and project oversight.
Collective research efforts of the MD Anderson Head and Neck Cancer
Symptom Working Group† are accomplished with infrastructure support of
the multidisciplinary Stiefel Oropharyngeal Research Fund of the University
of Texas MD Anderson Cancer Center Charles and Daneen Stiefel Center for
Head and Neck Cancer. This study is supported by donations made by the
Family of Paul W. Beach to Dr. Gunn for the execution of symptom research
efforts, providing direct salary support for Dr. Jomaa. Drs. Lai, Hutcheson,
Mohamed and Fuller received funding support from the National Institutes
of Health (NIH)/National Institute for Dental and Craniofacial Research
(1R01DE025248–01/R56DE025248–01). Dr. Hutcheson also receives support
from the NIH/National Cancer Institute (NCI) Small Grants Program for
Cancer Research (R03 CA188162). Dr. Fuller received/(s) additional concurrent
grant and/or salary support during the interval of study execution from: the
National Science Foundation (NSF), Division of Mathematical Sciences, Joint
NIH/NSF Initiative on Quantitative Approaches to Biomedical Big Data
(QuBBD) Grant (NSF 1557679); NCI support from an Early Stage
Development of Technologies in Biomedical Computing, Informatics, and
Big Data Science (R01CA214825–01), Head and Neck Specialized Programs
of Research Excellence (SPORE) Developmental Research Program
(P50CA097007–10), and Paul Calabresi Clinical Oncology Program Awards
(K12 CA088084–06); an Elekta AB/MD Anderson Department of Radiation
Oncology Seed Grant; the Center for Radiation Oncology Research (CROR)
at MD Anderson Cancer Center; and the MD Anderson Institutional
Research Grant (IRG) Program. Dr. Fuller is an MD Anderson Cancer Center
Andrew Sabin Family Fellow, and received project support in this role from
the Andrew Sabin Family Foundation.
Availability of data and materials
The datasets used and/or analyzed during the current study are available
from the corresponding author on reasonable request.
All listed co-authors performed the following: 1. Substantial contributions to
the conception or design of the work; or the acquisition, analysis, or
interpretation of data for the work; 2. Drafting the work or revising it critically
for important intellectual content; 3. Final approval of the version to be
published; 4. Agreement to be accountable for all aspects of the work in
ensuring that questions related to the accuracy or integrity of any part of
the work are appropriately investigated and resolved. Specific additional
individual cooperative effort contributions to study/manuscript design/
execution/interpretation, in addition to all criteria above are listed as follows:
SAE- Drafted initial manuscript, undertook supervised collection, analysis and
interpretation of data. MK- Provided direct statistical support and data
interpretation assistance. Provided oversight of trainees (SE, CDR).
CDRAssisted with data collection, analysis and interpretation. ASRM- Provided
direct oversight and supervision of trainees (MJ, SAE, CDR). Contributed to
project conception. Responsible for oversight of trainee data acquisition
(BDS, JBS, LC, BW, BKG and KEP). BDS, JBS, LC, BW, BKG and KEP- Contacted
project participants and gathered questionnaire data. ASG, KAH, RSW, SYL,
AH, RF, JP, - Provision of direct patient care; programmatic participation via
Stiefel program oversight and contribution; editorial support. DIR, KH, TRM,
CSC- Programmatic oversight for MDASI development and global symptom
assessment implementation support; oversight of trainees (ASRM) and direct
project mentorship (CDF, GBG). CDF, GBG- Co-primary investigators.
Conceived and coordinated efforts related to the investigation. Assisted with
manuscript drafting and responsible for manuscript content and editorial
oversight. Ensured project integrity. Provided direct support and oversight
for trainees (SAE, MJ, CDR, BDS, JBS, LC, BW, BKG, KEP) and staff (ASRM) as
well as general project oversight. All authors read and approved the final
Ethics approval and consent to participate
MDACC Protocol ID #: DR09–0891.
Protocol Title: Prospective Data Collection of Symptom Burden in Patients
Previously Treated for Head and Neck Cancer.
Official IRB Approval Date: 04/23/2010.
Official Activation Date: 07/15/2010.
It was noted that the protocol, informed consent documents (ICDs) and/or
the Waivers of ICD and Authorization are satisfactory and in compliance with
federal and institutional guidelines. It was also noted that risks to human
subjects are minimal and that confidentiality of records will be maintained.
Consent for publication
Dr. Fuller has received direct industry grant funding and speaker travel from
Elekta AB for unrelated technical projects.
Springer Nature remains neutral with regard to jurisdictional claims in
published maps and institutional affiliations.
1Department of Radiation Oncology, Unit 97, The University of Texas MD
Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030,
USA. 2School of Medicine, The University of Texas Health Science Center at
Houston, McGovern School of Medicine, Houston, TX, USA. 3School of
Medicine, Texas Tech University Health Sciences Center, Paul L. Foster School
of Medicine, El Paso, TX, USA. 4Department of Clinical Oncology and Nuclear
Medicine, Faculty of Medicine, University of Alexandria, Alexandria, Egypt.
5Abilene Christian University, Abilene, TX, USA. 6Department of Head and
Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston,
TX, USA. 7Department of Medical Oncology, The University of Texas MD
Anderson Cancer Center, Houston, TX, USA. 8Department of Epidemiology,
Division of OVP, Cancer Prevention and Population Sciences, The University
of Texas MD Anderson Cancer Center, Houston, TX, USA. 9Department of
Neurosurgery, Division of Surgery, The University of Texas MD Anderson
Cancer Center, Houston, TX, USA. 10Department of Symptom Research,
Division of Internal Medicine, The University of Texas MD Anderson Cancer
Center, Houston, TX, USA. 11Medical Physics Program, The University of Texas
Graduate School of Biomedical Sciences, Houston, TX, USA.
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