A prospective randomized study to compare the efficacy of three different dose fractionation regimens in palliative radiotherapy for patients with painful bone metastasis.

AIM

 To compare the efficacy of three different fractionation regimens like 8GY / single fraction , 20GY/ 5 fractions, 30GY/10 fractions with palliative radiotherapy for patients with symptomatic bone metastases

OBJECTIVES

PRIMARY OBECTIVE

1.     To determine the duration of pain relief by using pain score

SECONDARY OBJECTIVE

1.      To determine the analgesic requirement by using narcotic score

2.      To determine the improvement in performance status by using ECOG

3.      To determine improvement in quality of life by using BOMET-QOL questionnaire

MATERIALS AND METHODS:

 **TYPE OF STUDY:**A prospective randomized control study

INCLUSION CRITERIA :

1.      Radiologically  evident  bone metastases from any primary tumor site.

2.      Patients with pain due to bone metastasis

3.      Patients with uncomplicated bone pain

4.      ECOG performance status 0-3

5.      Patients who have given informed consent

6.      Patients of age 18yrs or older

EXCLUSION CRITERIA:

1.      Previous history of radioisotope treatment

2.      Previous surgical intervention to same location

3.      Patients with pathological fracture

4.      Pregnant and lactating women

SELECTION OF PATIENT:

The study will be conducted on patients with bone metastasis who is satisfying inclusion criteria presenting to radiation oncology OPD at SVIMS  Tirupati

STUDY PERIOD :

18 months from the date of IEC approval.

SAMPLE SIZE

The number of subjects required in ARM A, ARM B & ARM C was calculated to be 65 in each group . Hence total sample size is 195 subjects .

But the patients who satisfy inclusion criteria during the specified time period will only be included or atleast 30 patients in each arm as appropriate .

REGULATORY APPROVALS

The study has been approved by Institutional Thesis Protocol Approval Committee 9 roc No. AS/12/TPAC/SVIMS/2017)(TPAC No. 822, dated 25.04.24) and Institutional Ethics committee ( Roc No. AS /11/IEC/SVIMS/2017) dated 24.06.24. The study will be registered at Clinical Trial Registry India (CTRI)

INFORMED CONSENT:

A written informed consent will be obtained from all patients participating in the study.

RADIOTHERAPY TECHNIQUE:

After randomization patient immobilization will be done based on the location of bone metastasis.

Patients  will undergo simulation on a SEIMENS CT (somatom definition AS, 80 cm bore size, Berlin, Munich-Germany) machine dedicated to radiotherapy treatment simulation in our institute.

CT images will be acquired in 3mm slice thickness and will be transferred to treatment planning system [Varian/Oncentra 4.3]

Planning will be done by 3DCRT technique

GTV, CTV, PTVand OARS will be contoured as per

GTV – clinically and radiologically identifiable bone lesions

CTV – GTV and areas harboring microscopic disease

PTV – CTV and a margin for set up errors and normal physiological movement of organs

Planning will be done on Oncentra/Eclipse treatment planning system such that PTV should get 95 -107% of total prescribed dose and normal tissue doses tolerance being respected.

Based on the randomization patients will receive 8Gy in single fraction or 20 Gy in 5 fractions or 30Gy in 10 fractions

EVALUATION OF PATIENT:

Patients will be evaluated for pain severity and frequency with pain score

Patients will also be evaluated for analgesic use before and after treatment

Pain assessmentand  evaluation of analgesic usage will be done on the day of treatment, followed by daily during the course of treatment and then monthly after completion of RT for 3 months.

PAIN SCALE

Visual analogue scales (VAS)

The VAS is an unmarked line with extremes marked as no pain and worst pain.

Patients are asked to mark the point in the line that describes their pain.

Categorical verbal rating scales (VRS) -- 4 point scale

A VRS involves a sequence of words describing different intensity levels of pain

such as:

0-None

1-3  Mild

4-7 Moderate

8-10 Severe.

 Evaluation of analgesic usage

Analgesic requirement was graded according to type of analgesic needed for pain relief, as:

0 = not requiring any analgesics;

1 = simple analgesics such as non-steroidal anti-inflammatory drugs (NSAIDS);

2 = mild narcotics (codeine, tramadol);

3 = strong narcotics (morphine, fentanyl);

4 = high dose narcotics inadequate.

Improvement in performance status was defined as a decrease in ECOG functional outcome score by at least one grade with respect to pre-treatment value.

STATISTICAL ANALYSIS

Study parameters data will be recorded on a predesigned study proforma and then entered in Microsoft office Excel and data studied by SPSS (26.0 V) version. Data will be summarised using number and percentage for qualitative +/- standard deviation.

• Association between any two categorical variables will be analysed using Chi square test.
• P value less than 0.05 indicates that there is an association between the two groups & the categorical variable.
• Statistically significant difference among the two groups with respect to any continuous variable will be analysed using sample T test.

·         P value less than 0.05 indicates that there is a significant difference between the mean values among the two groups with respect to that variable