Supplementary data
Study population
For the retrospective cohort, all patients with locally advanced NSCLC consecutively referred to the department of radiotherapy of the Maastricht University Medical Centre + (MAASTRO clinic) from the 1st of January 2006 till the 31st of December 2008 for sequential or concurrent CT-RT with curative intent were enrolled (n=282). A consort diagram is depicted in Figure 1. Clinical data was obtained by reviewing the clinical charts. Patients visited the outpatient clinic weekly during radiation treatment, where body weight and toxicity of treatment was recorded by a radiation oncologist. A schematic representation of the study points in the retrospective cohort is depicted in Figure 2A.
For prospective data collection, patients with locally advanced NSCLC consecutively referred to the department of Respiratory Medicine of the Maastricht University Medical Centre + (MAASTRO clinic) from the 1st of October 2010 till the 30th of September 2011 were eligible for inclusion. A total of 21 were included. As can be observed in the consort diagram in figure 1, body weight and toxicity scoring of a proportion of the group was missing at some time points (due to toxicity and/or physical fatigue). Therefore, only data of the 9 patients of which data on body weight was present at all study points are presented here. Data analysis was also performed on all patients of whom at least 3 points were present (n=15) and this revealed the same results (data not shown).
Due to the non-interfering design of the study, evaluation of a medical ethical committee and trial registration was not required. However, the study was nonetheless submitted to review by the local medical ethics committee and it was confirmed that the study followed all standard medical ethical guidelines. In addition, all patients signed informed consent. A schematic representation of study points in the prospective can be observed in Figure 2B.
Tumor stage was recorded in accordance with the 7th tumor-node-metastasis (TNM) International Staging System for Lung Cancer [2]. Comorbidity of all patients was scored using the Charlson Comorbidity Index [1]. Patients were classified as never, former or current smoker. Never smokers were defined as those having used less than 100 cigarettes in their life-time, former smokers as those who did not smoke at the time of initiation of radiotherapy, and current smokers as those individuals who kept on smoking at the start of treatment.
Radiotherapy
In short, in all patients a treatment planning 18F-deoxyglucose (FDG)-PET-CT scan was performed in radiotherapy position on a dedicated PET-CT-simulator. The CT scan performed was a spiral CT scan of the whole thorax, with intravenous contrast. Subsequently, a 4D-CT scan was performed. Gross Tumor Volumes (GTV) were delineated on a mid-ventilation CT scan.
The GTV was defined as the primary tumor on CT and lymph nodes positive on PET scan or proven to be positive on mediastinoscopy or transesophageal/transbronchial biopsy. If the patient received induction chemotherapy the pre-chemotherapy PET scan was used to decide which nodal regions needed to be included in the GTV. No elective hilar of mediastinal irradiation was carried out. The Clinical Target Volume (CTV) was defined as the GTV with a margin of 5 mm, whereas an individual non-isotropic margin (Amplitudo/4) with an extra 2 mm for set-up margins was added to define the Planning Target Volume (PTV).
For the calculation of the mean lung dose (MLD), the volume of both lungs minus the GTV was considered. The outer contour of the esophagus was contoured from the cricoid to the esophago-gastric junction.
Muscle strength
For hand muscle strength assessment, patients sat upright on a chair with the shoulder placed in 0° abduction and the elbow in 90° flexion. The lower arm was placed on the table for support. Patients were instructed to press the hand grip meter (Jamer, Sammons Preston INC, Maastricht) as hard as possible for 5 seconds. The hand grip strength was calculated as the mean of three measurements (kg).
For quadriceps muscle strength, subjects were seated on the Biodex dynamometer (Biodex system version 3.3) chair with belts attached at the level the thigh and ankle for stability. Isometric muscle strength was assessed by 3 maximal voluntary contractions (MVCs) at an angle of 60°. Muscle strength was defined as the highest muscular force output (peak torque) in Newton meters (Nm).
References
[1] Charlson M, Szatrowski TP, Peterson J Gold J. Validation of a combined comorbidity index. J Clin Epidemiol 1994;47:1245-1251.
[2] Mirsadraee S, Oswal D, Alizadeh Y, Caulo A van Beek E, Jr. The 7th lung cancer TNM classification and staging system: Review of the changes and implications. World J Radiol 2012;4:128-134.