Study Design and Participants
This was a prospective longitudinal cohort study, using repeated measures on a convenience sample of newly diagnosed patients with SCLC from [removed for blind review]. The study was approved by the [removed for blind review] ethics committee prior to commencement (HREC approval: [removed for blind review]) and all participants provided written informed consent prior to participation.
Patients with newly diagnosed limited-stage SCLC were recruited prior to receiving chemoradiotherapy at one of [removed for blind review]’s three radiotherapy sites across [city, country; removed for blind review]. Patients were eligible for inclusion if they were: over 18 years of age; had limited stage disease (defined as no known distant metastatic disease and appropriate for radical chemoradiotherapy); able to read English; no previous radiotherapy to the head or neck; and no previous conditions or treatment that could cause swallowing or voice impairment.
Chemotherapy consisted of either carboplatin and etoposide or cisplatin and etoposide, given every 3 weeks for 4 cycles. Radiotherapy commenced with the second cycle of chemotherapy and was delivered using one of the following established protocols: 40 Gy in 15 fractions over 3 weeks (1 fraction per day); 45 Gy in 30 fractions over 3 weeks (2 fractions per day); or 50 Gy in 25 fractions over 5 weeks (1 fraction per day).
Data Collection
Data were collected on patients at four time points: prior to commencement of radiotherapy; 1 month post-completion of radiotherapy; 3 months post-completion of radiotherapy; and 6 months post-completion of radiotherapy.
At each time point data were collected on: swallowing function, limitations to oral intake, patient-reported swallowing and voice problems, health-related quality of life (QOL) and nutritional outcomes. Study data were entered into and managed using the REDCap electronic data capture tool hosted at [removed for blind review]16,17.
Videofluoroscopic swallowing studies (VFSS; also referred to as the modified barium swallow) were used to analyse swallowing function. Swallowing images were recorded using the Philips Allura FD20 X-ray system and converted to .avi format for later analysis. During the VFSS participants completed the following with the patient seated in the lateral position: three swallows of 5 ml and one swallow of 10 ml liquid, three swallows of 5 ml semi-solid (pureed fruit), and a piece of solid food (½ cracker). All boluses were mixed or coated with barium to allow clear visualisation of the bolus through the oral cavity, pharynx and upper oesophagus. An anterior-posterior view was also taken while the participant swallowed 5 ml bolus of semi-solid, to allow observation of the presence of oesophageal motility disorder(s). Measures taken from the VFSS images were: (i) aspiration of liquids, using the Penetration-Aspiration Scale18, an 8-point scale ranging from 1 (material does not enter the airway) to 8 (material enters the airway, passes below the vocal folds, and no effort is made to eject), (ii) overall swallow function of liquids, semi-solids and solids, using the Swallowing Performance Status Scale (SPSS)19, a 7-point rating scale which takes a number of different swallowing features into account, including how safely and effectively the bolus moves through the oral cavity and pharynx, and (iii) oesophageal motility disorder(s), rated as present or absent.
Oral intake was measured using the Functional Oral Intake Scale (FOIS) which rates the degree to which a person needs to modify the consistency/texture of food they eat and/or requires tube feeding. The scale ranges from 7 (total oral intake with no restrictions) to 1 (nothing by mouth) and has demonstrated validity and reliability20.
Patient-reported swallowing and voice problems were measured using the Dysphagia Handicap Index (DHI)21 and the Voice Handicap Index (VHI)22 respectively. These are questionnaires which, for the DHI, comprise 25 items with three response options (never; sometimes; always) and one global item, and for the VHI, comprises 30 items rated on a 5-point Likert-type scale.
The University of Washington QOL questionnaire (UW-QOL)23 was used to measure health-related QOL. It includes 16 questions regarding pain, appearance, activity, recreation, swallowing, chewing, speech, shoulder, taste, saliva, mood and anxiety.
Demographic and treatment-related data were collected from the medical records. Data of interest included: gender, age, nutritional status (using the Patient-Generated Subjective Global Assessment [PG-SGA]24,25), radiotherapy regimen, chemotherapy agent, mean radiation dose to the oesophagus, maximum radiation dose to the oesophagus, oesophagitis (worst CTCAE score recorded and duration of worst CTCAE score recorded) and required admission for neutropenia.
Statistical Analysis
Descriptive statistics were used to summarise the demographic and clinical characteristics of the participants. These included counts and percentages for nominal valued variables; and means and standard deviations or medians, interquartile ranges and ranges for continuous valued variables.
For the purposes of analysis, the global item scores of the DHI were rated as normal (score of 1), mild (score of 2 or 3), moderate (score of 4 or 5) or severe (score of 6 or 7)26.