Special Care Patterns for Elderly HNSCC Patients Undergoing Radiotherapy
Conditions: HNSCC, Oral Cavity Cancer, Oropharynx Cancer, Hypopharynx Cancer, Larynx Cancer
Sponsor: University Hospital Freiburg

Study Protocol SENIOR Study 
 
Version 4.2, July 26, 2024 
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1. Title, Protocol ID, IRB number 
English: Special Care Patterns for Elderly HNSCC Patients Undergoing Radiotherapy (SENIOR) 
German: Klinisches Ansprechen und Verträglichkeit von Radio(chemo)therapie bei älteren Patienten 
mit Kopf-Hals-Tumoren 
Protocol ID: FRKS003723 and NCT05337631 
IRB number of the Local Ethics Committee Freiburg: 551/18 
Version 4.2 (last update at July 26, 2024) 
2. Synopsis 
PIs 
Prof. Dr. Dr. Nils H. Nicolay, M.D., Ph.D. 
Department of Radiation Oncology, University Medical Center Freiburg 
Robert-Koch-Str. 3, 79106 Freiburg, Germany 
Tel: +49 (0) 761 270-95200 
Fax: +49 (0) 761 270-94720 
Mail: nils.nicolay@uniklinik-freiburg.de 
(Since 2022: Head of Department of Radiation Oncology, University 
Medical Center Leipzig; nils.nicolay@medizin.uni-leipzig.de) 
and 
PD Dr. Alexander Rühle, M.D. 
Department of Radiation Oncology, University Medical Center Freiburg 
Robert-Koch-Str. 3, 79106 Freiburg, Germany 
Tel: +49 (0) 761 270-94520 
Fax: +49 (0) 761 270-94720 
Mail: alexander.ruehle@uniklinik-freiburg.de 
Title 
English:  
Special Care Patterns for Elderly HNSCC Patients Undergoing 
Radiotherapy (SENIOR) 
German: 
Klinisches Ansprechen und Verträglichkeit von Radio(chemo)therapie bei 
älteren Patienten mit Kopf-Hals-Tumoren 
Patient Population 
Elderly (≥65 years) patients with head-and-neck squamous cell carcinoma 
undergoing definitive (chemo)radiotherapy with curative intention 
Aim 
To determine the value of concomitant chemotherapy of concomitant 
chemotherapy in elderly patients with locally advanced head-and-neck 
squamous 
cell 
carcinoma 
(HNSCC) 
undergoing 
definitive 
(chemo)radiotherapy 
Intervention 
No intervention 
Inclusion and Exclusion 
Criteria 
Inclusion Criteria: 
• 
definitive (chemo-)radiotherapy with curative intention of a 
locally advanced (cT3-4 and/or cN+) head-and-neck squamous 
cell carcinoma (HNSCC) of the oral cavity, oropharynx, 
hypopharynx or larynx 
• 
(chemo-)radiotherapy between 2005 and 2019 
• 
age ≥65 years at the time of (chemo-)radiotherapy 
 
 

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Exclusion Criteria: 
• 
adjuvant (chemo-)radiotherapy 
• 
induction chemotherapy 
• 
history of previous head-and-neck cancer 
• 
distant metastases at (chemo-)radiotherapy initiation (M1) 
• 
HNSCCs of the nasopharynx, salivary glands, skin or with 
unknown primary 
Outcome Measure 
Primary: 
• 
Overall survival (OS) 
Secondary: 
• 
Progression-free survival (PFS) 
• 
Type of concomitant chemotherapy 
• 
Cumulative cisplatin dose 
• 
Radiotherapy completion rate 
• 
Chemotherapy completion rate 
Study Design 
Multinational, multicenter, retrospective, observational study 
Statistics 
Patient demographics and treatment parameter will be described using 
descriptive statistics. Overall survival (OS) will be calculated from the 
beginning of (chemo)radiotherapy until death, while progression-free 
survival (PFS) is defined as time interval between start of 
(chemo)radiotherapy 
until 
death, 
local/locoregional 
or 
distant 
progression. The Kaplan-Meier method will be used to calculate OS and 
PFS, and groups will be compared using log-rank tests. Both uni- and 
multivariate Cox proportional hazard regression analyses will be 
performed to analyze the prognostic role of several patient- und 
treatment-related parameters including chemotherapy administration on 
survival. In order to control for potential confounder variables, both 
propensity score matching and inverse probability weighting approaches 
are aimed to conduct. 
Enrollment 
1400 anticipated 
Study Completion 
March 2025 
 
3. PIs – Funding 
Senior-PI: Prof. Dr. Dr. Nils H. Nicolay, M.D., Ph.D. 
Junior-PI: Dr. Alexander Rühle, M.D., MHBA 
Funding: No external funding 
 
4. Brief Summary 
The number of elderly head-and-neck squamous cell carcinoma (HNSCC) patients is increasing (1); 
however, the evidence regarding the ideal treatment for this often vulnerable and frail patient 
cohort is limited (2, 3). Although the benefit of concomitant chemotherapy has been reported to 
decrease in elderly HNSCC patients based on the MACH-NC meta-analysis (4), it remains unknown 
whether state-of-the art radiotherapy techniques such as intensity-modulated radiotherapy (IMRT), 
modern supportive treatments and alternative chemotherapy fractionation (e.g., cisplatin weekly) 
may have altered this observation (5-7). The objective of this retrospective multinational multicenter 
study is to determine the oncological outcomes of elderly patients (≥65 years) with locally advanced 
HNSCCs undergoing definitive (chemo-)radiation and to investigate the influence of concomitant 

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chemotherapy on overall survival and progression-free survival after adjusting for potential 
confounder variables such as age, performance status and comorbidity burden. 
5. Aim 
Multinational multicenter retrospective analysis to reveal the role of concomitant chemotherapy in 
elderly patients with locally advanced head-and-neck squamous cell carcinoma (HNSCC) undergoing 
definitive (chemo)radiotherapy  
6. Outcome Measures: 
Primary Outcome Measure: 
• 
Overall survival (OS) 
 
Secondary Outcome Measures: 
• 
Progression-free survival (PFS) 
• 
Locoregional control (LRC) 
• 
Patterns-of-care regarding chemotherapy administration and radiotherapy 
 
7. Study Population and Methods 
All Elderly (≥65 years) head-and-neck squamous cell carcinoma (HNSCC) patients undergoing 
definitive (chemo)radiotherapy with curative intention between 2005 and 2019 at a tertiary cancer 
center will be included and analyzed in terms of overall survival and the potential benefit of 
concomitant chemotherapy administration. 
Methods 
The SENIOR study is an investigator-initiated multinational multicenter retrospective observational 
study aiming to elucidate the value of concomitant chemotherapy in elderly patients with locally 
advanced HNSCCs undergoing definitive (chemo)radiotherapy with curative intention. About 1000 
patients that received a definitive (chemo)radiotherapy between 2005 and 2019 at 13 tertiary cancer 
centers in Germany, Switzerland, Cyprus, and the USA will be included. 
Patient and treatment data will be collected retrospectively using patient charts. The following 
criteria will be collected: 
• 
Date of radiotherapy initation 
• 
Patient age at start of radiation 
• 
Gender 
• 
Site of cancer 
• 
T Stage 
• 
N Stage 
• 
HPV status 
• 
Grading 
• 
Tobacco History 
• 
Pack Year history 
• 
Active Smoking During Radiation 

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• 
ECOG 
• 
Age-adjusted Charlson Comorbidiity Index 
• 
Hemoglobin at start 
• 
Leukocytes at start 
• 
CRP at start 
• 
Creatinine at start 
• 
GFR at start 
• 
Weight at start 
• 
Planned total radiotherapy dose 
• 
Planned radiotherapy dose per fraction 
• 
Planned number of fractions 
• 
Planned total radiotherapy dose, EQD2 
• 
Applied total radiotherapy dose 
• 
Applied number of fractions 
• 
Applied radiotherapy dose per fraction 
• 
Applied total radiotherapy dose, EQD2 
• 
Radiotherapy completed 
• 
Chemotherapy received 
• 
If chemotherapy, which type 
• 
Cumulative cisplatin dose 
• 
Chemotherapy completed 
• 
Status locoregional control 
• 
Locoregional control (months) 
• 
Status progression-free survival  
• 
Progression-free survival (months) 
• 
Status overall survival 
• 
Overall survival (months) 
 
8. Statistics 
Patient demographics and treatment parameter will be described using descriptive statistics. Overall 
survival (OS) will be calculated from the beginning of (chemo)radiotherapy until death, while 
progression-free survival (PFS) is defined as time interval between start of (chemo)radiotherapy until 
death, local/locoregional or distant progression. The Kaplan-Meier method will be used to calculate 
OS and PFS. Groups will be compared using log-rank tests. Both uni- and multivariate Cox 
proportional hazard regression analyses will be performed to analyze the prognostic role of several 
patient- und treatment-related parameters including chemotherapy administration on survival. In 
order to control for potential confounder variables, propensity score matching and inverse 
probability weighting approaches are aimed to conduct. The statistical analyses will be performed in 
collaboration with the Institute of Medical Biometry and Statistics (IMBI) Freiburg. 
9. Publication and Authorship Rules 
Results of the study will be published in peer-reviewed journals. Decisions regarding the inclusion of 
co-authors and determination of the author order will be performed by the PIs following the 
Guidelines for Good Scientific Practice of the DFG (German Research Foundation). 

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10. Data Management and Data Protection 
Data collection will be conducted at the respective center. Prior to data transfer to the primary 
center Freiburg, patient data will be pseudonymized (e.g., FR-001). Patient-related data such as name 
and date of birth will not be shared with the primary center. The list with the assignment between 
patient name and pseudonymization-code (e.g., FR-001) will be securely stored at the participating 
center. Due to the number of patients per center (approximately 100 per center), backtracking of 
individual patients is not possible for the leading center Freiburg.  
We have created a Data Protection Concept for our study. 
Following the rules of good scientific practice, analyzed data sets will be stored for at least 10 years 
in institutional databases. There is no disclosure of personal data to third parties. 
11. Participating Centers 
• 
Department of Radiation Oncology, University Medical Center Freiburg, Freiburg, Germany 
• 
Department of Radiooncology, Charité - Universitätsmedizin Berlin, Berlin, Germany 
• 
Department of Radiotherapy and Oncology, J. W. Goethe University, Frankfurt am Main, 
Germany 
• 
Department of Radiation Oncology, University of Würzburg, Würzburg, Germany 
• 
Department of Radiation Oncology, University Hospital Schleswig-Holstein, Kiel, Germany 
• 
Department of Radiation Oncology, University Medical Center, Johannes Gutenberg 
University, Mainz, Germany 
• 
Department of Radiation Oncology, University Hospital LMU Munich, Munich, Germany 
• 
Department of Radiation Oncology, Friedrich-Alexander-Universität Erlangen-Nürnberg, 
Erlangen, Germany 
• 
Department of Radiation Oncology, University Hospital Zurich, Zurich, Switzerland 
• 
Department of Radiation Oncology, German Oncology Center, Limassol, Cyprus 
• 
Department of Radiation Oncology, Case Western Reserve University, Cleveland, USA 
• 
Department of Radiation Oncology, Icahn School of Medicine at Mount Sinai, New York, USA 
• 
Division of Radiation Oncology, The Ohio State University Wexner, Columbus, USA 
• 
Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins 
University School of Medicine, Baltimore, USA 
• 
Department of Radiation Oncology, University Medical Center Leipzig, Leipzig, Germany 
• 
Department of Radiotherapy and Radiation Oncology, Jena University Hospital, Jena, 
Germany 
• 
Department of Radiation Oncology, Giessen-Marburg University Hospital, Giessen, Germany 
• 
Department of Radiation Oncology, Masaryk Memorial Cancer Institute, Brno, Czechia 
• 
Department of Radiation Oncology, University Hospital Halle (Saale), Halle (Saale), Germany 
 
 
12. References 
1. Smith BD, Smith GL, Hurria A, Hortobagyi GN, Buchholz TA. Future of cancer incidence in the 
United States: burdens upon an aging, changing nation. J Clin Oncol. 2009;27(17):2758-65. 

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2. Dickstein DR, Lehrer EJ, Hsieh K, Hotca A, Jones BM, Powers A, et al. Management of Older 
Adults with Locally Advanced Head and Neck Cancer. Cancers (Basel). 2022;14(11). 
3. VanderWalde NA, Fleming M, Weiss J, Chera BS. Treatment of older patients with head and 
neck cancer: a review. Oncologist. 2013;18(5):568-78. 
4. Lacas B, Carmel A, Landais C, Wong SJ, Licitra L, Tobias JS, et al. Meta-analysis of 
chemotherapy in head and neck cancer (MACH-NC): An update on 107 randomized trials and 
19805 patients, on behalf of MACH-NC group. Radiother Oncol. 2021. 
5. Szturz P, Wouters K, Kiyota N, Tahara M, Prabhash K, Noronha V, et al. Low-Dose vs. High-
Dose Cisplatin: Lessons Learned From 59 Chemoradiotherapy Trials in Head and Neck Cancer. 
Frontiers in oncology. 2019;9:86-. 
6. VanderWalde NA, Meyer AM, Deal AM, Layton JB, Liu H, Carpenter WR, et al. Effectiveness of 
chemoradiation for head and neck cancer in an older patient population. Int J Radiat Oncol Biol 
Phys. 2014;89(1):30-7. 
7. Amini A, Jones BL, McDermott JD, Serracino HS, Jimeno A, Raben D, et al. Survival outcomes 
with concurrent chemoradiation for elderly patients with locally advanced head and neck cancer 
according to the National Cancer Data Base. Cancer. 2016;122(10):1533-43. 
 
13. Signatures 
    
 
 
Prof. Dr. Dr. Nils Nicolay 
 
 
PD Dr. Alexander Rühle