Quality of life assessment with different radiotherapy schedules in palliative management of advanced carcinoma esophagus: A prospective randomized study
Correspondence Address: Source of Support: None, Conflict of Interest: None DOI: 10.4103/0973-1075.45452
Source of Support: None, Conflict of Interest: None
Aim: To investigate the quality of life (QOL) of patients with advanced carcinoma esophagus treated with different palliative radiation schedules.
Keywords: Advanced carcinoma of the esophagus, brachytherapy, external radiotherapy, palliation, quality of life
Esophageal cancer is an aggressive malignancy usually associated with a poor prognosis because of locoregional failure and distal metastasis.  Unfortunately, about 60-70% of the patients are undernourished and in advanced stages of disease at presentation.  In a majority of these patients, quality of life (QOL) takes precedence over long-term prognosis. The major goal of therapy is restoring and/or maintaining the ability to swallow with minimum morbidity and with reasonable QOL.
Various methods of palliation have been used in an attempt to improve the patient's QOL and to provide near-normal swallowing till death. Radiotherapy is one of the most commonly used modalities for symptom relief, especially in developing countries like India with limited resources and financial constraints. External beam radiotherapy with or without intraluminal brachytherapy is widely used for palliation. , As there is no optimised radiation schedule, the three commonly used regimens of palliative radiotherapy are worth considering for comparison in view of QOL endpoint. Our study was designed to prospectively evaluate the QOL of patients receiving these three commonly used palliative radiotherapy schedules. QOL was assessed using the validated European Organization for Research and Treatment of Cancer (EORTC) questionnaire. ,
Between July 2003 and December 2004, 62 patients with previously untreated, inoperable, locally advanced carcinoma esophagus were enrolled in this trial with palliative intent at the Department of Radiotherapy, Post Graduate Institute of Medical Education and Research, Chandigarh, India.
The institutional ethics committee approved the study. Informed written consent was obtained from all patients before participation in the study. Tippet's random number table was used for randomisation of patients to the three arms, with at least 20 patients in each arm. The treatment arms compared were:
The patients were planned on a simulator and following barium swallow examination, fields were marked and checked under fluoroscopic vision or on plain radiographs. The fields used were a pair of parallel-opposed AP-PA fields so as to cover the tumor adequately along with a safety margin of 5 cm proximally and distally and 2-3 cm laterally. External radiation was delivered with megavoltage photon beams of Co-60 or a 6-MV Linear accelerator.
All the patients in Arm-A were given intraluminal brachytherapy 2 weeks after external beam radiotherapy. It was performed as an outpatient procedure. Endoscopy was performed to define the location and the extent of disease. With the help of a guide wire, an esophageal bougie was placed at least 2-3 cm beyond the distal end of the disease. In lesions where it was difficult to define the distal end, the esophageal bougie was placed to such an extent that it would facilitate a generous margin of treatment. The position of the bougie was verified under fluoroscopy using dummy sources. The entire length of the tumor with a 2-3 cm margin on both sides was treated. Treatment planning was carried out with the help of a Nucletron® PLATO treatment planning system using orthogonal films. A Nucletron HDR Microselectron® with an Ir-192 source was used for treatment. A step size of 5 mm was used. Dose was prescribed as 1 cm from the central axis of the source.
QOL assessment was performed using the validated questionnaire developed by the EORTC. The questionnaire modules used were EORTC QLQ-C30 and EORTC QLQ-OES 18. , Permission was obtained from the EORTC for using their questionnaire for this study. In case of illiterate patients, social workers helped the patients in completion of the questionnaires. QOL was assessed before starting radiation, at the end of radiation and 3 months after completion of treatment. All analysis was carried out using MS Excel 2000 Microsoft® and statistical software SPSS® version 10.
A total of 62 patients of locally advanced carcinoma of the esophagus were included in the study. The patient characteristics are shown in [Table 1]. No significant differences were found between Arms A, B and C with respect to age, sex, histology, location of disease and baseline blood results [Table 1]. Mean age was 56 years (30-70). Male to female ratio was 1.06:1. The most common location was the middle 1/3 rd (in 54.8%) and the most common histology (48.3%) was squamous cell carcinoma not otherwise specified. The endoscope was not negotiable in 77% of the patients at the time of presentation.
(A) General scores (QLQ C-30)
a) Global health status
The mean global health status score was 38 before treatment in arm-A, which improved to 52 after completion of treatment, further improving to 56 at the 3 months interval. In arm-B, it was 30 before treatment, became 44 after completion of treatment and 55 at 3 months. In arm C, it improved from 24 to 40 after treatment, but again decreased to 37 at 3 months [Figure 1].
b) Functional scores
The mean physical functioning score in arm-A was 68 before treatment, became 69 after treatment and 70 at the 3 months interval. In arm-B, it was 59 before treatment, decreased to 57 after treatment and improved to 64 at 3 months. In arm-C, it was 55 before treatment improved to 57 after treatment and decreased to 50 at the 3 months interval.
The mean role functioning score was 67 before and after treatment in arm-A, which improved to 69 at 3 months. In arm B, it improved from 58 pre-treatment to 62 after treatment to 65 at 3 months. In arm C, it was 55 before treatment, 57 after treatment and 43 at the 3 months interval.
The mean emotional functioning score improved from a 53 pre-treatment score to 71 at 3 months in arm-A, while in arm B it was 55 before treatment and became 66 at the 3 months interval. In arm C, it improved from 47 to 61, respectively.
There was not much change in the mean cognitive functional score in all the three arms after treatment and at the 3 months interval.
The mean social functioning score improved from 43 before treatment to 54 at 3 months in arm-A. In arm-B, it changed from 42 to 46 at 3 months and in arm-C, from 29 to 41, respectively.
c) Symptom scores
On symptom scale valuation, the mean fatigue score had decreased from 62 pre-treatment to 54 after treatment and 44 at 3 months in arm-A. In arm B, the scores were 64, 60 and 49, respectively. In arm-C, it decreased from 74 pre-treatment to 65 at 3 months.
The mean nausea/vomiting score was decreased from 31 to 9 at 3 months in arm-A, from 42 to 24 in arm-B and 44 to 25 in arm-C, respectively.
The mean pain score decreased from 55 to 51 after treatment in arm-A, which further decreased to 41 at 3 months. In arm-B, it decreased from 57 to 45 at 3 months after treatment. In arm-C, it was 68 before treatment and 62 after treatment and at 3 months.
Results of single-item scores like dyspnoea, insomnia, appetite loss, constipation and financial difficulties were also improved in all the three arms after treatment. None of the patients had diarrhea in all three arms before treatment while 1 patient in arms B and C developed diarrhea at 3 months, which was not related to treatment. The mean scores are as shown in [Table 2].
(B) Esophageal scores (QLQ OES-18)
The esophageal mean symptom scores were analysed using an OES-18 questionnaire, as shown in [Table 3]. The symptom scores showed marked improvement in all the arms after radiotherapy.
Maximum improvement in dysphagia scores was seen in arm-A (57.6%). In arm B, it was 54.4% and minimum (24%) in arm-C at 3 months after radiotherapy [Figure 2].
Improvement in the eating problems score at 3 months was maximum in arm-A (43.1%) while it was 31.3% in arm-B and 20.0% in arm-C.
Reflux symptom scores, in fact, deteriorated with treatment. In arm-A, there was early deterioration at first follow-up after treatment and then improvement at 3 months while in arms B and arm C, a deterioration in reflux scores was seen later in the time course at 3 months.
Pain scores improvement in arms A and B was similar (27% vs 30%) while in arm-C, only 17 % of the patients showed improvement.
The single-item symptom scores also showed improvement, as shown in [Table 4].
Acute radiation morbidity was assessed using the EORTC/RTOG criteria.  Esophagitis at 1 month was seen in 14 patients in arm-A, 10 in arm-B and eight patients in arm-C. All of the patients had only grade 1/grade 2 esophagitis. No stricture formation was seen. Dysphagia at follow-up was due to progression of disease rather than stenosis. Tracheo-esophageal fistula developed in one patient in arm-C at 3 months and one patient in arm-B at 6 months. None of the patients in arm-A developed tracheo-esophageal fistula.
Additional procedures to restore feeding (in the form of nasogastric tube insertion, endoscopic dilatation/stenting or feeding jejunostomy) were required in four patients at 3 months and six patients at 6 months in arm-A. In arm-B, six patients at 3 months and eight patients at 6 months needed additional procedures. In arm-C, eight patients at 3 months and six patients at 6 months needed alternative procedures for relief of dysphagia.
Palliation of symptoms in locally advanced carcinoma of the esophagus is a very important objective of treatment, given the poor prognosis of patients and short life expectancy. Various methods of palliation for carcinoma of the esophagus have been used in an attempt to improve the patient's QOL and to provide near-normal swallowing till death. These include surgical (bypass/resection), laser, dilatation, intubation, chemotherapy and radiotherapy. None of these modalities have changed the median survival, which ranges from 2.5 to 9.9 months for advanced inoperable cases.  Radiotherapy remains the mainstay in palliation of carcinoma of the esophagus, especially in the developing world as it is cost-effective, produces fewer complications, can be given on an outpatient basis and is readily acceptable to most of the patients. Various modalities of radiotherapy, including external radiation, brachytherapy or both in combination have been used with success.
Many studies have demonstrated efficacy and safety of external radiotherapy and brachytherapy for palliation of carcinoma of the esophagus. ,, Very few studies have assessed QOL in these patients with limited lifespan. We have taken QOL of the patients as an important factor for optimisation of treatment schedule to be used for palliation and analysed the same using QLQ C-30 and QLQ OES-18 questionnaires. QOL assessments in patients with esophageal cancer should provide clinically meaningful data that can assist management decisionmaking.
Blazeby et al. ,  in a study, defined measurement properties and clinical validity of the EORTC questionnaire module to assess QOL in esophageal cancer. The esophageal module, the QLQ-OES24 and core questionnaire and the QOL-Core 30 questionnaire (QLQ-C30) were administered in patients undergoing treatment with curative ( n = 267) or palliative intent ( n = 224) and second assessments performed 3 months or 3 weeks later, respectively. Psychometric tests examined scales and measurement properties of the module. Questionnaires were well accepted, compliance rates were high and less than 2% of the items had missing data. It was recommended for use with the core questionnaire, the QLQ-C30, to assess QOL in patients with esophageal cancer.
QLQ OES-24 was under phase-3 trial at the time of start of the study and was thus used for data collection. However, in July 2003, the EORTC issued QLQ OES-18 as the validated questionnaire in which six questions have been eliminated. The analysis was therefore carried out using the QLQ OES 18. The QLQ-C30 (version3.0) was used, which is composed of both multi-item scales and single-item measures. This questionnaire includes a global health status/QOL, five functional scales (physical functioning, role functioning, emotional functioning, cognitive functioning and social functioning), three symptom scales (fatigue, nausea/vomiting and pain) and different single-item scales. The QLQ-OES 18 contains symptom scales like dysphagia, eating trouble, reflux symptoms and pain. Each of the multi-item scales includes a different set of items. No item occurs in more than one scale.
All of the scales and single items range in score from 0 to 100. A high scale score represents a higher response level. The high score of functional scale represents high/healthy level of functioning, a high score for global health status represents a high QOL but high score for symptom scale represents high level of symptomatology or problems.
In our experiences, the questionnaire was well accepted and compliance rates were high among patients of carcinoma esophagus. Our study has shown that QOL in terms of global health status, functioning scale and symptom scales improved considerably after different radiotherapy schedules. According to the EORTC scoring manual, changes in score over time and differences between groups may be more difficult to interpret than absolute scores. There is no universally accepted method for analysing the difference between the groups. The fact that change is statistically significant does not necessarily imply that it also has clinical significance. Thus, interpretation of these scores should be on a clinical basis.
Given the limited number of patients in this study, the comparison between schedules is underpowered. However, the results of this trial indicate that a combination of external beam radiotherapy with intraluminal brachytherapy results in a more prolonged symptom palliation and a better overall improvement in the QOL as compared with the external radiotherapy alone. Yet, in the developing world with financial constraints and very limited resources, only 20 Gy/five fractions regimen could provide an equivalent benefit in symptom relief, especially in patients with poor performance status and limited survival thus qualifying to be a cost-effective method of palliation.
There is a trend toward better QOL with a combined radiotherapy regimen. Intraluminal brachytherapy should be considered along with external radiation as it provides consistent symptom relief with good QOL, thereby giving better palliation in advanced inoperable carcinoma of the esophagus.
These results warrant further prospective studies on a larger number of patients to determine the impact of the palliative radiotherapy regimen on QOL of patients in carcinoma of the esophagus.
We are grateful to our Medical Physicists Mr Arun S. Oinam and Mr. Dev Raj Goyal, for radiation planning and technical help.
[Figure 1], [Figure 2]
[Table 1], [Table 2], [Table 3], [Table 4]