Setup errors in patients with head-neck cancer (HNC), treated using the Intensity Modulated Radiation Therapy (IMRT) technique: how it influences the customised immobilisation systems, patient’s pain and anxiety

This is a longitudinal, prospective study: data were collected before CT simulation and during all the treatment sessions. All the patients enrolled were identified by a numeric code to allow blind data analysis and ensure the patient’s privacy. Written informed consent was obtained during the first radiation therapy visit. The information was provided by the same radiation therapists for all the patients involved in the study, in order to ensure homogeneity. The local Ethics Committee approved the study.

In our department radiation therapy treatments can be performed using the TomoTherapy® Hi-Art® System 3.0 (Accuray Incorporated, Madison, WI), which involves a helical fan beam scan using 3.5MV photons and an arc-shaped xenon CT detector array mounted on the opposite side of the ring gantry Mega Volt Fan Beam Computed Tomography (MVFBCT).

All patients with head-neck tumour were immobilised using a 5-points mask: four fixing points for the neck and shoulders plus an additional one on the head (Acquaplast RT® Fibreplast ™ Thermoplastics, Avondale, PA, USA). The patient’s position was maintained by means of a standard rigid base made of carbon fibre, created specially to stabilise the patient’s head and neck during IMRT treatments. This supporting base of the patient is always fixed to the Computer Tomography and the Tomotherapy beds.

To maintain the patient’s position standard neck supports were used in different sizes (Large, Small size), connected to the base. In some cases, to improve patient comfort, an additional customised neck support was used (MOLDCARE® CUSHION For Head, Neck and Small Regions Rt -4492S, ALCARE Co., Ltd. Tokyo, Japan). All the patients enrolled were subjected to Virtual Simulation Computed Tomography (GE Medical System HiSPEED NX/I) using the same technical protocol (120 kV, 250 mA, Thickness of acquisition 3 mm, Pitch 3, Thickness of reconstruction 3 mm, Reconstruction interval 3 mm).

Before each treatment, patient positioning was obtained by means of alignment of the lasers of the room with 4 reference points positioned on the “mask” at the time of CT simulation.

In IGRT-IMRT treatments dispensed in Tomotherapy, the MVFBCT images were acquired daily before each treatment and matched with those obtained during the CT simulation. Alignment of the images was obtained by means of automatic software tools and, if necessary, also with manual adjustments [10‐12].

We considered the translational mediolateral (ML), craniocaudal (CC), and anteroposterior (AP) deviations; antero-posterior correction of 3.8 mm is applied for the systematic AP setup error caused by couch sag [13‐16] that occurs when the patient is moved to the treatment isocenter (inside the bore) from virtual isocenter located 70 cm outside. Rotational corrections like pitch, roll and yaw were not recorded.

We prospectively collected data for a sample of consecutive patients with head and neck cancer, treated with the IMRT technique by our department from September 2011 to August 2013.

The eligibility criteria were: female and male patients with head and neck cancer who underwent intensity modulated radiation therapy, ≥14 years old and ≤85 years old, without cognitive disfunctions, performance status score of 0–1 [17] and with written informed consent.

For all the patients, the thermoplastic mask and other custom immobilization devices were prepared before CT simulation, on the basis of the same internal operating protocol.

We created an ad-hoc report to record all the environmental and technical variables that might have a correlation with the setup error. On the baseline (BL) day of CT simulation we recorded: anxiety [18] and pain [19‐24], before starting the simulation procedure (more on the measurements scales below); patient’s weight and height [25, 26]; intent of radiation therapy; variable influencing patient positioning such as shoulders forced down, scoliosis or kyphosis; some patient and environment variables such as presence of mobile dental prosthesis, use of bite for locking of the jaw, tracheostomy, voluminous beard, voluminous hair, room temperature of the CT room and temperature of the water used for shaping the thermoplastic mask; type of standard neck supports used and the eventual addition of customized neck support; number of radiation therapy team members who worked together to shape the thermoplastic mask and temporary removal of the mask before the acquisition of CT simulation. On the first day of every week of treatment we measured the patient’s weight. Finally on each treatment day we recorded: Mediolateral (ML), craniocaudal (CC), and anteroposterior (AP) deviations; radiation therapists executing the procedure; anxiety and pain, before starting the treatment session; changes related to the presence of mobile dental prosthesis, use of dental bite, tracheostomy, beard or voluminous hair, temperature of the treatment room.

The anxiety was measured using the STAI Y form, a test validated worldwide [27] consisting of two scales: the TRATTO-A scale, which measures the predisposition for anxiety, and the STATE-A scale which evaluates the anxiety state, i.e. the emotional state at a given moment. Only STATE-A was used in the study, which consists of 20 items; the compilation, done directly by the patient, requires an average of 5–7 min. The test was administered to the patient in the waiting room.

Pain was measured using the Numeric Pain Rating Scale, [19‐24] a numeric scale that describes the intensity of pain, ranging from 0 (no pain) to 10 (max value of pain); the measurement was performed directly by the patients themselves in the waiting rooms.

In absence of a-priori hypothesis given the exploratory nature of the study, no formal sample sizing was performed. Nonetheless, a limited measurement period (recruiting: September 2011 to August 2013, data collection: first 6 weeks of treatment for each patient) was defined, in order to ensure general feasibility, homogeneity of the procedures and of the data collected.

Clinical and demographic data were expressed in terms of frequency and percentage for categorical variables, mean ± standard deviation for symmetric quantitative variables, median + IQR for skewed ones.

Overall mean error (M), systematic SD (∑) and random SD (σ) were calculated, both for full sample and by groups (determined according to site) of patients.

In order to explore the correlation between relevant variable and treatment setup errors, we adopted a single Euclidean distance measure. Setup error (in any of the three directions) can assume positive or negative values; regardless of the direction, the more the error deviates from value 0 the more unfavourable the it is. Therefore, to collapse all the three errors (cranial-caudal, medial-lateral and anterior-posterior) in one single measurement readily available for multivariate analysis, we considered each setup error as a vector and calculated 3-dimension modulus as an overall measure of error severity; accordingly, total error e _tot was simply calculated as Euclidean distance, as follows:

where e _ml is medial-lateral (ML), e _cc is cranial-caudal (CC) and e _ap is anterior-posterior (AP) error (to simplify notation we avoided patient and time subscripting; however e _tot has to be considered as overall setup error for patient i at time t). The total error, expressed in mm, was log-transformed (in order to mitigate the positive-skewness effects on the residuals normality) and then analysed using a linear mixed effects model (complete-case analysis). This method was choosed to accommodate non-independency of the observations sampled (eg. due to clustering within individuals): the method assumes that setup errors can be explained in terms of both fixed and random effects. Fixed effects represent the effects of factors of intrinsic interest (in our case those that can be associated to setup error) because of being repeatable in other populations (eg number of therapists, mask removal etc.); random effects represent random deviation (from the relation depicted by the fixed effects) associated to factors of no intrinsic interest (not strictly repeatable, eg the single patient) which are nonetheless considered in the estimation process [28].

The base group for the model reported is represented by patients without ‘Shoulders down’, ‘Scoliosis/kyphosis’ and ‘Mask removal’ at baseline setup; with ‘Large size standard plus customized neck support device’ (the most common); followed by 2 radiation therapists at baseline for mask and setup (the minimum/standard encountered); with no pain (pain = 0); with mid-point anxiety (anxiety = 50); patient who during the entire treatment cycle, was followed by 12 radiation therapists (minimum) during treatment weeks; with a mean BMI.

In order to ease interpretation of results, coefficients (and their confidence intervals) were transformed using (((exp(coefficient) – 1)*100)-100) and presented using a forestplot-like graph: this leads to an estimate of each factor contribution as percentage variation (compared to an otherwise identical patients without it).

Confidence intervals (considering a 0.95 confidence level) and models comparison were performed with bootstrap methods [29]; a confidence interval not including the threshold of no differences (0% for transformed coefficients) denoted the contribution of the factor analysed as statistically significant. Statistical analysis was carried out using R 3.3.2.