Bone is one of the most common sites of metastases in more than half of the patients with advanced malignancy. It is the third most common site of involvement after the lung and liver. The incidence of bone metastasis from population-based studies is limited and mostly they are based on autopsy data and may not reflect current treatment patterns. The most common primary malignancies which metastasize to bone are breast in women and prostate in men but secondary lesions from lung cancer have risen in both sexes in the last two decades [1]. The most common site of involvement is the vertebral spine followed by the pelvis and long bones. Bone metastases cause a considerable amount of morbidity and affect one’s Quality of Life even more than the disease process. Metastatic spinal cord compression is an Oncological emergency. Key elements in the prognosis are early diagnosis, early initiation of high dose steroids followed by spine stabilization via surgery or radiotherapy. Radiation treatment found to be effective in the treatment of skeletal metastases [2]. Studies have demonstrated its efficacy in relieving pain, with more than 50% experiencing complete response irrespective of fractionation schedule being used.  Quality of life is a multidimensional model that attempts to capture the physical, social and psychological wellbeing of the patient. Many components influence quality of life including physical symptoms of the disease, side effects of treatment, social and family support. The treatment goal in the advanced cancer is palliative than curative in intent thereby managing symptoms as opposed to prolonging life. There is lacking data on the effect of palliative radiotherapy on symptomatology and various domains of quality of life in bone metastases patients in our population. Hence the study aims to find the improvement in symptoms like pain relief, locomotor function, etc. and various domains (physical, social, emotional, financial) of quality of life in patients with bone metastases from any primary in South Indian population and to identify the socio-demographic and clinical factors associated with the effect of palliative radiotherapy on symptoms and quality of life.

This study was conducted in the Palliative Care Unit, Department of Radiation Oncology. The design of the study was a prospective observational study with a before and after comparison at 3 different time intervals. Data from 171 patients were used for statistical analysis in the study.

• Age < 65 years
• Eastern Cooperative Oncology Group Performance status -2, 3, 4
• All cancer patients with newly diagnosed bone metastases (axial and appendicular) -AJCC stage IV, any nodal status with distant metastases
• Previously not received any form of radiation to bony regions.
• All patients registered in the JIPMER RCC Palliative care unit, Radiation Oncology OPD with the above following criteria 1,2,3,4.

Exclusion Criteria

• Previous associated existing neurological diseases
• Previous associated existing orthopaedic diseases
• Patients with poor compliance
• Any psychiatric illness / Any form of cognitive impairment

Sampling

• The sample size was estimated with an expected proportion of patients with relief in symptoms in patients with bone metastases as an impact of Palliative Radiotherapy as 50% and the sample size was estimated at a 5% level of significance and 15% relative precision. Convenience sampling technique was used.

Study Procedure

• All Cancer patients with newly diagnosed bone metastases attending the RCC Radiation Oncology OPD who met the inclusion criteria and registered in JIPMER palliative care unit, Radiation Oncology OPD were given initial Pre-RT counselling and health education and pre-treatment symptom assessment was done using EORTC QLQ-C30, QLQ-BM22, Brief Pain Inventory questionnaires (BPI) and pre-treatment symptom scores were calculated.
• Socio-demographic data like age, sex, address, marital status, income, education, occupation, addictions were also obtained from patients and recorded.
• Clinical data regarding diagnosis and stage, history of illness, symptoms, comorbidities, prior anticancer treatment received, and prior analgesic usage was also recorded for each patient.
• They were subjected to the proposed treatment plan.
• They were subsequently assessed for the symptom improvement on follow-up
• 2 weeks, 4weeks, 8 weeks after receiving radiation treatment in OPD using the EORTC QLQ-C30, QLQ-BM22, and BPI questionnaires. This follow-up was done as per departmental protocol and the improvement in scores was assessed.
• Patients who could not be assessed at 2 weeks, 4 weeks, 8 weeks post RT at the hospital were given home care visit /telephonically communicated whichever was feasible. This was done as per the routine home care visit given by JIPMER Palliative care unit on every Wednesday.
• The data collected were subjected to statistical analysis.

The distribution of data on categorical variables such as gender, the primary site of cancer, socio-demographic characters, comorbidities, performance status, site of bone involvement, radiation fractionation schedule, and the primary site of cancer was expressed as frequency and percentage. The continuous data such as age, the QLQC30 and QLQBM22 scores for QOL, BPI score for pain, etc. were expressed as mean with standard deviation or median with range. All statistical analysis was carried out at 5% level of significance. The final analysis was done using SPSS software version 19.

After the approval from the hospital ethics committee, 171 patients fulfilling eligibility criteria after proper informed consent were enrolled in the study.

Patient Characteristics

• Mean age of the patients was 57.6 years
• Age of the patients ranged from 25 -78 years
• 101 (59.3%) were males
• 70 (40.7%) were Females
• 2% had some family history of malignancy in our study
• 169 (98.8%) were Uneducated
• Most were engaged in Unskilled Occupations
• Median Income in our study was INR 2000/- per month
• Most of our patients (46.2%) were Eastern Cooperative Oncology Group Performance Score 3.
• Most of the patients (84.5%) received 30Gy/10# Palliative RT to the involved bony site.

Physical Functioning Scale from EORTC QLQC30 showed a significant rising trend in median scores post-Radiation Therapy, which was found to have statistical differences when assessed at different time points.

Table 1: Distribution of patients by primary malignancy site.

Table 2: Distribution of Patients based on histology.

Table 3: Change in functioning scores with respect to time.

Table 4: Change in symptoms scores with respect to time.

Table 5: Change in symptoms score with respect to time.

After we analysed the results of 171 patients who had bone metastases and have received Palliative Radiation Therapy with different fractionation schedule from July 2017 to December 2019, the overall trend shows that with palliative radiation therapy, the symptoms, and QOL parameters, as assessed by EORTC QLQ C30, EORTC QLQ BM 22, BPI, have improved among all domains comparing pre and post-radiation therapy. This has been shown by previous studies3.

Our study assesses the symptoms and QOL parameters at baseline and posts 2, 4 and 8weeks post-radiation therapy, whereas the previous studies have compared only baseline with immediately or after 4 weeks post-radiation therapy. This helps us to find out if there is an earlier response in the symptoms and Quality of Life parameters. Our study showed that a better response is noted in most domains post 4 weeks.

In our study, the most common primary malignancy presented with bone metastasis to our department was Carcinoma Breast followed by Carcinoma Prostate. A similar distribution was seen with a previous study4 which showed that the incidence of bone metastasis was higher in metastatic breast carcinoma (65-75%) followed by metastatic prostate carcinoma (65-75%).

This study shows most of the patients had more than one site of bone metastasis, which is seen more commonly with breast, prostate, and lung primary malignancies. The most common site of bone involvement in our study was vertebral spine which is similar when compared with the reports from previous studies. In our study, the most common histology that presented with bone metastasis was Adenocarcinoma.

In our study, the most common palliative fractionation used for pain management of bone metastasis was 30Gy/10#, which is widely followed and is shown to have no significant differences in symptom control when compared with other various fractionation schedules in multiple retrospective studies.

In our study, we noticed an increasing trend in the functioning scales at different time intervals post RT. No similar such studies conducted before have shown any trends in the functional and symptom domains of the EORTC QLQ C30, QLQ BM22, BPI Questionnaire pre and post-radiation therapy at different time points post radiation therapy.

Physical Functioning, Emotional Functioning, Role Functioning, Social Functioning, Cognitive Functioning, Global Functioning, and Psychological Aspects Scores showed a general increasing trend pre radiation treatment for bone metastasis, when compared with the scores post radiation therapy. They showed a general improvement from baseline scores pre radiation therapy and post-radiation therapy. Scores such as Physical Functioning, Role Functioning showed a clear increasing trend noted from 2 weeks of post-radiation therapy. This may be explained by the role of radiation therapy in decreasing pain in the patients of bone metastasis. Global Functioning and Cognitive Functioning showed an increasing trend from 4 weeks of post-radiation therapy. Scores such as Emotional Functioning, Psychological Aspects, Emotional Functioning showed variable trends immediately post radiation therapy, however, at 8 weeks post-radiation therapy, these scores showed a statistically significant improvement from baseline scores. This may be due to the effect of radiation therapy on control of symptoms like pain and indirectly influencing fatigue, insomnia. Psychological aspects showed a poorer score immediately post Radiation therapy, which then slowly increased later. This probably shows the need for more psychological support for the patients of bone metastasis during and after the course of treatment.

Among the symptom scales, Appetite Loss, Dyspnoea, Fatigue, Financial Difficulty, Insomnia, Pain, Painful sites, Pain characteristics, Pain Severity, Pain Interference scores showed a significant decrease in post-radiation therapy. Diarrhoea, Nausea and Vomiting scores remained stable after decreasing from baseline at 2 weeks post-radiation therapy. Appetite Loss, Dyspnoea, Fatigue, Financial Difficulty, Insomnia, Pain scores showed a decreasing trend 4 weeks after Radiation Therapy. The change in Financial Difficulty score may be explained by the decrease in symptoms such as pain, fatigue, insomnia, appetite loss, they were able to do their occupation or job.  Pain severity and pain interference scores showed a steady decreasing trend of post-radiation therapy.

Constipation did not show a clear trend throughout the course of follow up post-radiation therapy, however, at 8 weeks post Radiation therapy, symptoms had worsened. This may be explained by probably increased intake of analgesics like morphine or other organic causes. Therefore, we may expect a worsening of symptoms of constipation and consider starting laxatives in case of distressing symptoms.

Functional Interference scores were noted to increase suggesting worsening scores. This could be because of the presence of visceral metastases like liver and lung metastasis, which adds to the disease burden and symptom burden of the patient.

Zeng et al3 study compared the improvement at baseline and 1-month post-Radiation Therapy in 76 patients using EORTC QLQ C30 and EORTC QLQ BM22 in pain responders and found that at 1 month follow up, 3 out of 4 EORTC QLQ BM 22 scales and 3 of 15 EORTC QLQ C30 scales were improved. Painful sites (Mean change -22.7; p < 0.0001), Painful Characteristics (Mean change -36.4; p<0.0001), Pain (Mean change -40.9; p<0.0001) were significantly lower 1 month post RT, whereas physical functioning (Mean change 16.7; p=0.006), role functioning (Mean change 20.5; p=0.0026) were improved. Functional Interference (Mean change -30.9; p<0.0001) had decreased significantly. Other parameters that improved in the study were Constipation (Mean change -24.2), Psychological aspects and global health status. Our study, however, showed statistically significant changes in all scores. This may be explained by the larger sample size in our study and multiple time points of assessment in our study as compared to Zeng et al (2012).

Another study5 also showed improvement in Pain site, Pain characteristics and Functional interference scores with patients of bone metastasis post-RT when they were evaluated with QLQ C30 and BM22 questionnaire at baseline and 2 months post-RT. None of the domains of QLQ C30 showed any significant improvement with radiation treatment.

Using BPI Questionnaire, a study6 showed that Radiation Therapy improved the symptoms of pain in bone metastasis at baseline and 1, 2, 3 months post-RT. Our study showed there was a statistically significant decrease in the pain severity and the pain interference scores with the addition of RT post 8 weeks after radiation therapy.

In our study, all domains of the EORTC QLQ BM22 showed a statistically significant improvement with RT till post 8 weeks except functional interference which initially worsened post 4 weeks after RT. This could be explained by the primary disease per se which affects the overall performance of the patient.

All patients were followed up for at least 2 months post radiation therapy. The study reveals that the symptom control and Quality of Life score improvements were detected at 2 weeks and most showed an improving trend till 2 months post radiation therapy.

Palliative Radiation therapy to bone metastases improves the Quality of Life across all functional domains like physical, social, emotional, role and cognitive functioning when the baseline scores were compared with post Radiation therapy which was statistically significant. Palliative Radiation therapy to bone metastases improves the symptoms like appetite loss, nausea and vomiting, fatigue, insomnia, diarrhoea, dyspnoea, financial difficulty, pain which was all found to be statistically significant, except changes in Constipation score, which showed a worsening trend. Palliative RT decreases pain severity and pain interference in bone metastasis patients as assessed by using the Brief Pain inventory. Pelvic bone metastasis was found to be associated with poorer QOL scores at baseline. The presence or absence of femur metastasis showed a significant change in scores in insomnia and appetite loss scales. The presence or absence of Pelvic bone metastasis showed a poorer score in Physical Functioning, appetite loss and insomnia scales which was statistically significant. The presence of the absence of humerus bone metastasis had a statistically significant change in scores of Pain interference, Pain severity, and Physical Functioning among the groups. Females were associated with worsening of dyspnoea and financial difficulties at baseline assessment. Financial difficulties improved in younger age (<50 years) after radiation treatment when compared to baseline. The change in the mean score of the global functioning scale was higher in patients with an ECOG performance score of 3 or 4. Thus, the addition of palliative radiation to bony metastatic sites, there is a statistically significant improvement in overall QOL and better symptom control.

Acknowledgments: Nil

Funding Sources: Nil

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