Trial Title:
Pneumonitis in Older Lung Cancer Patients After Radiotherapy
NCT ID:
NCT06480734
Condition:
Lung Cancer
Conditions: Official terms:
Pneumonia
Lung Neoplasms
Conditions: Keywords:
Lung cancer
Radiotherapy
Pneumonitis
Scoring system
Study type:
Interventional
Study phase:
N/A
Overall status:
Not yet recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Intervention model description:
multi-center prospective study
Primary purpose:
Diagnostic
Masking:
None (Open Label)
Intervention:
Intervention type:
Other
Intervention name:
symptom-based scoring system (symptom-questionnaire, paper version)
Description:
The patients are asked to complete a paper-based questionnaire (symptom-based scoring
system, paper version) once a week during and up to 24 weeks following radiotherapy. The
patients state and score symptoms potentially associated with pneumonitis, namely cough,
shortness of breath and fever. Scoring points are assigned to severity of the symptoms,
and sum scores are used to identify pneumonitis. During the radiotherapy course, patients
complete the questionnaire prior to regular appointments with a physician. Following
radiotherapy, they are contacted by phone (to minimize the number of hospital visits)
once a week for completion of the questionnaire. In case of an increase of the total
score when compared to baseline, patients receive a follow-up phone call after 3 days,
are asked to come to the hospital as outpatients or are admitted to hospital.
Arm group label:
Elderly patients with lung cancer and risk of pneumonitis
Summary:
The main goal of this trial is to establish the performance characteristics and to
develop a decision-algorithm of a new symptom-based scoring system with respect to the
identification of elderly lung cancer patients developing pneumonitis after radiotherapy.
To assess the performance characteristics of the symptom-based scoring system for
detection of radiation pneumonitis the receiver operating characteristic (ROC) curve is
used to show the connection between sensitivity and specificity for every possible
cut-off for the symptom-based scoring system and to select the optimal scoring point for
detection of radiation pneumonitis. The area under the ROC curve (AUC) is calculated to
prove the diagnostic ability of the scoring system.
Secondary aims include patient satisfaction with the symptom-based scoring system
(symptom-questionnaire, paper version).
Detailed description:
The present prospective study investigates, whether the results of the previous
prospective trial can be generalized to elderly patients aged ≥65 years. Its major goal
is the identification of the optimal cut-off score to correctly diagnose pneumonitis and
discriminate it from other lung diseases in elderly patients irradiated for lung cancer.
In addition, the diagnostic value of an increase of the scoring points from baseline
scores is evaluated. This study is a prerequisite for the development of a mobile
application, which can be used by the patients at home to rate their symptoms possibly
related to pneumonitis. This information will contribute to the decision whether
pneumonitis is possible or likely and whether any action (e.g. consulting a pulmonologist
or visiting a hospital) is required.
The main goal of this trial is to establish the performance characteristics and to
develop a decision-algorithm of a new symptom-based scoring system with respect to the
identification of elderly patients developing pneumonitis after radiotherapy for lung
cancer. To assess the performance characteristics of the symptom-based scoring system for
detection of radiation pneumonitis in elderly lung cancer patients, the receiver
operating characteristic (ROC) curve is used to show the connection between sensitivity
and specificity for every possible cut-off for the scoring system and to select the
optimal scoring point for detection of radiation pneumonitis. The area under the ROC
curve (AUC) is calculated to assess the diagnostic ability of the scoring system.
Secondary aims include patient satisfaction with the symptom-based scoring system
(symptom-questionnaire, paper version), assessed at the end of radiotherapy.
In case of suspected pneumonitis, patients undergo lung function tests. The suspected
diagnosis of pneumonitis is considered substantiated in case of a decrease in forced
expiratory volume in 1 second (FEV1) and diffusing capacity of the lung for carbon
monoxide (DLCO) to less than 75% from baseline values. In this situation, patients
receive a chest x-ray (which may be supplemented by a computed tomography) in accordance
with the current standard procedures at the corresponding participating center. Radiation
pneumonitis is considered confirmed, if opacities confined to the irradiation fields are
seen on chest x-ray and/or ground-glass opacities (focal or nodular), consolidation or
both are seen on computed tomography [19, 20]. If the diagnosis symptomatic radiation
pneumonitis (grade ≥2) has been confirmed, patients receive medical intervention. The
vast majority of the patients receive prednisolone, which is considered the mainstay of
the treatment for radiation pneumonitis. If pneumonitis is not confirmed and symptoms are
caused by other (e.g. underlying) disease, the patients receive treatment for this
situation.
The symptom-based sum score is correlated to pneumonitis (yes vs. no). At the end of
radiotherapy, patients are asked to complete a questionnaire regarding their satisfaction
with the score. In case of a dissatisfaction rate >20%, the score needs modifications
before it can be used in future studies. In case of a dissatisfaction rate >40%, the
symptom-based scoring system will be considered not useful.
Based on samplesize calculations, 59 subjects (18 with radiation pneumonitis and 41
without radiation pneumonitis) are required within the Full Analysis Set. Assuming that
5% of subjects will not qualify for Full Analysis Set, a total of 62 subjects should be
enrolled.
The Full Analysis Set includes all subjects who started radiotherapy for lung cancer.
The primary aim of the study is to assess the performance characteristics of the
symptom-based scoring system for detection of radiation pneumonitis. The evaluation will
be performed in those subjects, who are available for assessment of the primary endpoint
and have completed at least 10 questionnaires (paper version) regarding the symptom-based
scoring system.
In order to allow for patient-based analyses, the multiple score values documented for
each patient over time will be reduced to one clinically relevant, patient-specific value
only. The following pragmatic and clinically persuasive approach is foreseen:
- For subjects without radiation pneumonitis during study, the maximum score value
documented throughout study will be selected.
- For subjects experiencing radiation pneumonitis, the value documented at the time of
diagnosis will be selected.
These patient-specific values represent the fundamental units for all further statistical
analyses. First of all, sensitivity and specificity will be estimated for every possible
cut-off value of the symptom-based scoring system.
The ROC curve is used to show in a graphical way the connection between sensitivity and
specificity. The term ROC stands for Receiver Operating Characteristic and is defined as
the plot of sensitivity versus 1-Specificity (false-positive rate) across varying
cut-offs. A ROC curve corresponding to greater discriminant capacity of the symptom-based
scoring system is located closer to the upper-left-hand corner. A ROC curve lying on the
diagonal line reflects the performance of a diagnostic test that is no better than chance
level.
The area under the curve (AUC) summarizes the entire location of the ROC curve. The AUC
is an effective and combined measure of the sensitivity and specificity that describes
the inherent validity of the usefulness of the test in general, where a greater area
means a more useful test. If AUC=1 the symptom-based scoring system is perfect in the
differentiation between subjects with and without radiation pneumonitis. This happens
when the distribution of the score values for the subjects with and without events do not
overlap. In contrast, AUC=0.5 means that the scoring system is performing no better than
chance. Therefore, the AUC can be considered as a valuable quantitative measure to prove
the diagnostic ability of the symptom-based scoring system. A rough guide for classifying
the accuracy of a diagnostic test is the traditional academic point system (AUCs of 0.5 -
0.6 = fail; 0.6-0.7 poor; 0.7-0.8 = fair, 0.8-0.9 = good and 0.9-1 = excellent).
Therefore, any symptom-based score leading to an AUC of at most 0.7 will be rated
insufficiently useful and is not considered worth pursuing.
Based on this definition, the following hypothesis system will be subjected to
statistical analysis:
H0: AUC=0.7 versus H1: AUC ≠0.7 Non-parametric methods for AUC estimation and testing
using the normal approximation of the asymptotic properties of the AUC with standard
errors derived by the method of DeLong, DeLong and Clarke-Pearson will be applied [25].
Technically, the SAS (SAS Institute Inc.) LOGISTIC procedure with the ROCCONTRAST
statement can be used to estimate the AUC and its 95% confidence limit and to provide the
p-value for the test mentioned above. A significance level of two-sided 5% is
prespecified.
If statistical significance of the AUC is reached, the most-informative (optimal) scoring
point to predict radiation pneumonitis will be established. Based on discussions with
various experts, optimality is defined as a score cut-off value with at least 90% and the
specificity at least 80%. In addition to this visual selection of a suitable cut-off
value, the Youden index (sensitivity + specificity - 1) will be applied to propose an
optimal cut-off value for further consideration.
Due to the limited sample size which could be realistically achieved in this multi-center
trial within the given study duration, it is not considered feasible to develop and
validate the optimal cut-off value identified within this single study at the same time
by dividing the study population into training and validation cohorts. Therefore, the
derived cut-off value should be considered as a preliminary suggestion which has to be
validated in subsequent studies.
As a further sensitivity analysis, the relationship between tertiles of the symptom-based
scores and the incidence of radiation pneumonitis will be statistically tested using the
Jonckheere-Terpstra test which is a nonparametric test for ordered differences among
groups of score values. It tests the global null hypothesis that the distribution of the
response variable does not differ among tertiles. The test is designed to detect
alternatives of ordered differences, meaning that the incidence of pneumonitis increases
with the tertiles of score values.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Histologically proven lung cancer
2. Indication for radiotherapy or chemoradiation
3. Mean radiation dose to ipsilateral lung >13 Gy
4. Age ≥65 years
5. Written informed consent
6. Capacity of the patient to contract
Exclusion Criteria:
1. Expected Non-Compliance
2. Baseline score of >4 points
Gender:
All
Minimum age:
65 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Vejle Hospital, University Hospital of Southern Denmark
Address:
City:
Vejle
Zip:
7100
Country:
Denmark
Contact:
Last name:
Charlotte Kristiansen, MD
Phone:
0045-7940
Phone ext:
6094
Email:
charlotte.kristiansen@rsyd.dk
Facility:
Name:
Medical Practice for Radiotherapy and Radiation Oncology
Address:
City:
Hannover
Zip:
30161
Country:
Germany
Contact:
Last name:
Stefan Janssen, MD
Phone:
0049-511-220
Phone ext:
60420
Email:
stefan.janssen@uksh.de
Facility:
Name:
Medical School Hamburg, Schwerin Campus
Address:
City:
Schwerin
Zip:
19055
Country:
Germany
Contact:
Last name:
Marciana N Duma, MD
Phone:
0049-385-520
Phone ext:
5070
Email:
Marciana.Duma@helios-gesundheit.de
Contact backup:
Last name:
Tobias Bartscht, MD
Phone:
0049-385-520
Phone ext:
3500
Email:
Tobias.Bartscht@helios-gesundheit.de
Facility:
Name:
Malteser Hospital St. Franziskus
Address:
City:
Flensburg
Zip:
24939
Country:
Germany
Contact:
Last name:
Carmen Timke, MD
Phone:
0049-461-816
Phone ext:
2518
Email:
carmen.timke@malteser.org
Facility:
Name:
Department of Radiation Oncology, University of Lübeck and University Medical Center Schleswig-Holstein
Address:
City:
Lubeck
Zip:
23562
Country:
Germany
Contact:
Last name:
Dirk Rades, MD, FASTRO
Phone:
+49-451-500
Phone ext:
45400
Email:
dirk.rades@uksh.de
Contact backup:
Last name:
Elisa M Werner, MD
Phone:
+49-451-500
Phone ext:
45420
Email:
ElisaMarie.Werner@uksh.de
Contact backup:
Last name:
Dirk Rades, Prof. Dr.
Contact backup:
Last name:
Elisa M Werner, Dr.
Contact backup:
Last name:
Inga Zwaan
Contact backup:
Last name:
Cansu Delikanli
Contact backup:
Last name:
Daphne Schepers-von Ohlen, Dr.
Contact backup:
Last name:
Sabine Bohnet, Dr.
Start date:
November 1, 2024
Completion date:
June 30, 2026
Lead sponsor:
Agency:
University Hospital Schleswig-Holstein
Agency class:
Other
Collaborator:
Agency:
University of Southern Denmark
Agency class:
Other
Collaborator:
Agency:
Medical School Hamburg
Agency class:
Other
Source:
University Hospital Schleswig-Holstein
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06480734
