Longitudinal Assessment of Quality of Life among Stage IV Non Small Cell Lung Cancer Patients in India

Methods

The study will be conducted as a prospective observationalstudy across a multiple centers in India. Initially thestudy will start at TMH and subsequently other centers will be included.  The eligibility criteria for inclusion in thestudy are as follows: a clinical diagnosis of NSCLC with advanced (stage IV),the ability to read, write and speak in one of the following Indian languages(Hindi, Marathi, Gujarati, or Indian English)and provide a written informedconsent to participate in the study; and no major disabling medical orpsychiatric conditions that would substantially impair cognitive functioning .Patients will be instructed to complete the questionnaires themselves beforethe start of their treatment, before start of 4th cycle ofchemotherapy and 3-4 weeks after 6th cycle of their chemotherapyduring their clinic visits with the treating oncologist. In patients receivingoral TKI QOL will be evaluated at every 2 months, which is the regular followup period. Patients who demonstrate difficulty in completing the questionnairescan seek assistance from pharmEDGE interviewers who are fluent in all Indianlanguages at any time during the study by dialing the help-line numbers thatwill be provided at the bottom of the study questionnaires. The interviewerswill then assist the patient’s by conducting the interview with themtelephonically and recording their responses. Given that the objective of thestudy is to evaluate longitudinal changes in QOL within individual patients, webelieve that a minimum sample size of 200 patients will be sufficient toevaluate meaningful differences in quality of life over the study time period.We expect that we will be able to recruit this number of patients in 1 year.This is an observational study where the main objective is to monitor changesin QOL within an individual patient, a sample size calculation is notwarranted.

3.1.0 Clinical Variables

Data will beabstracted on tumor characteristics, such as date of diagnosis, histology,tumor type, stage, and treatment, and patient characteristics like gender, dateof birth and co-morbidity at the time of diagnosis. We will only include thosecases with histology being categorized as NSCLC. Tumor type will be categorizedas squamous cell carcinoma, large cell carcinoma, adenocarcinoma, andundifferentiated carcinoma.  Patients whohave been newly diagnosed with stage IV NSCLC will be included in the HRQOLassessment. As most of thepatients will be receiving palliative care, treatment can be classifiedas chemotherapy and oral TKI.  Cancerduration will be derived by calculating the difference between the date ofentry and date of diagnosis, using month as the unit.

3.2.0****HRQOL Assessment

HRQOL will be measured using EORTC QLQC-30/LC-13 which is validated and used commonly in variousstudies including randomized controlled trials and observational studies tomeasure quality of life. The questionnaire will be administered in an electronicformat and will completed by patients during their clinic visit. The EORTC QOLCore Questionnaire (EORTC QLQ-C30) is a cancer-speciï¬c 30-item questionnaire usedfor assessing HRQOL and has been widely used in clinical trials. The scaleincludes 24 questions from nine multi item scales presenting various aspects ofHRQOL, whereas the remaining six scales are single-item scales describing differentcancer-relevant symptoms. The ï¬ve functional scales include questions thatassess physical functioning, role functioning; emotional functioning, cognitivefunctioning, and social functioning. The nine symptoms scales assess fatigue,nausea and vomiting, pain, dyspnea, insomnia, appetite loss, constipation,diarrhea, and ï¬nancial difficulties and a global health status scale. Inaddition, EORTC features a speciï¬c lung cancer module (LC13) that includes 10scales that address various symptoms such as dyspnea, coughing, hemoptysis,sore mouth, dysphagia, peripheral neuropathy, alopecia, pain in chest, pain inarm or shoulder, and pain in other parts. These instruments aretranslated and validated in 11 Indian languages (Bengali, English, Gujarati,Hindi, Kannada, Malayalam, Marathi, Punjabi, Tamil, Telugu, and Urdu).13-16

Data Analyses

Patient characteristics will be summarizedusing descriptive statistics such as mean, median, or mode. Changes in HRQOLscores during the study will be calculated as the difference between baselineand last follow-up value and compared using the paired t test.Effectsizes will be calculated by dividing the changes in each HRQOL score by the standarddeviation (SD) of that score estimated at baseline on the entire sample. Toaccount for the hierarchical nature of the data (repeated measurements withinpatients) and to control simultaneously for the possible confounding effects ofthe different variables, multivariate multilevel linear models will beutilized. In this longitudinal analyses, which will evaluate factors associatedwith a decline in HRQOL measures, multilevel methods will allow toappropriately model within- and between-patient variability. Results from thesemultivariate models will be expressed in terms of standardized β parameterswith the relative P value. Standardized β parameters indicate thechanges over time in QoL measures with respect to baseline for patients. Forthe second objective Cox proportional hazards model will be used to assess therelative risk of survival in terms of the HRQOL instrument. The QLQ C-30 andLC-13 will be categorized according to their tertiles. The single-item symptomscales will be dichotomized. We will then evaluate the crude risk of survivalseparately for each scale, and then with variables such as age, gender, stagesof cancer, treatment type, and duration of cancer. Continuous variables of theQLQ C-30

 and LC-13 scales will be used to testlinear trends. All analyses will be conducted using SAS, version 9.1 (SASInstitute Inc. Cary NC).