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Year : 2002  |  Volume : 12  |  Issue : 2  |  Page : 281-284
Multiple and single fraction palliative radiotherapy in bone secondaries a prospective study

Department of Radiotherapy, Medical College, 88, College Street, Calcutta-700073, West Bengal, India

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Objective: This prospective study was done to compare the role of the multi fraction (MF) and single fraction (SF) radiotherapy in the management of bone secondaries as regards potency for pain relief and resultant early toxicities. Materials and Methods: Seventy three out of eight five patients with bone metastases, who fulfilled the inclusion criteria were randomly divided into two groups to be treated by External radiation either by 3000 cGy over 2 weeks in 10 Fractions i.e. multiple fraction (MF) or by 8000 cGy in single fraction (SF). Pre and Post radiation pain relief potential and early toxicities due to the treatment were compared. Results: No significant difference (P>0.50) was observed as regards pain relief which was 84% in Gr-I (MF) and 76% in Gr - II (SF). Similarly incidence of complete pain relief, (42% VS - 35%) no response (16% VS 24%) and early toxicities also show marginal difference. Conclusion: Though both the radiation schedules resulted in considerable reduction of Bone pain in majority of the patients, no significant difference was observed as regards pain relief and early toxicities.

Keywords: Radiotherapy (RT), Multiple Fraction (MF), Single Fraction (SF), Pain Relief, Early Toxicity.

How to cite this article:
Sarkar S K, Sarkar S, Pahari B, Majumdar D. Multiple and single fraction palliative radiotherapy in bone secondaries a prospective study. Indian J Radiol Imaging 2002;12:281-4

How to cite this URL:
Sarkar S K, Sarkar S, Pahari B, Majumdar D. Multiple and single fraction palliative radiotherapy in bone secondaries a prospective study. Indian J Radiol Imaging [serial online] 2002 [cited 2020 Dec 3];12:281-4. Available from:

   Introduction Top

Osseous metastases are a major cause of pain and morbidity in cancer. Because of the long clinical course of the disease even after bone metastases especially in Breast and Prostate Cancer, bone secondaries present a major challenge for health care system. Though optimum management of bone metastases comprises a multidisciplinary team effort, radiation therapy is frequently utilized for palliation and pain relief. In a large prospective randomized United States study, the Radiation therapy Oncology group treated more than one thousand patients with metastatic bone pain. The complete response rate was 35% after 40.5 Gy in 15 fractions compared with only 28% after 25 Gy in 5 fractions (P=0.003) [1],[2]. However two other prospective randomized studies have shown no significant difference in response rate between single or short course radiation therapy and fractionated (conventional) courses given over two to three weeks [3],[4]. Against this background, the present prospective randomized trial was initiated in our department to compare the efficacy of pain relief and early toxicities in single fraction (SF) versus multiple fraction (MF) schedule of radiation in bone secondaries.

   Materials and methods Top

Out of the 3502 Cancer patients treated between Sept. '97 to August '98 in our Radio therapy dept, 85 (2.5%) presented with bone metastases. There were 54 men and 31 women. The age of the patients ranged from 21 to 76 years, majority being 40 to 70 years of age. In 25%, the primary site of malignancy could not be identified. Breast (25%) and lung (20%) are the two commonest sites of primary malignancy [Table I]. 74% patients had solitary site involvement whereas 26% patients had multiple bone metastases. Radiological study revealed lytic nature of the involved site in 85% of cases and only 15% being sclerotic, 8 patients (9%) presented with pathological fractures. The spine was involved in 55% of patients, whereas extremity bones were involved in 31% of cases [Table I].

Out of 85 patients who presented with painful bone metastases in our department, 73 patients, who fulfilled the inclusion criterias were randomly allocated in two different treatment groups - Group I and Group II.

Inclusion Criterias were -

  1. Cytologically or histologically proven malignant disease with painful bone metastases in single or multiple sites without pathological fracture.
  2. No history of previous radiotherapy on the treatment site.
  3. No history of concurrent chemotherapy or Hormone therapy.
  4. No history of Chemotherapy within the last 4 weeks or Hormone therapy within the last 8 weeks.
  5. Patient able to determine subjectively the amount of pain.

It is to be noted that in comparison to chemotherapy, hormonal response is delayed. 2 months gap also excludes any rebound effect due to hormonal manipulation.

The radiation was given a Telecobalt machine (Theratron 780C Telecobalt Sr. No. 241, International Theratronics Canada Ltd. Canada, Otawa). Group I (multi fraction group - 38 patients) received 30 Gy tumour dose in 10 daily fractions over two weeks whereas in Group II (single fraction group - 35 patients) - a single fraction of 8 Gy tumour dose was advised.

Pain assessment in this study was done by the Radiation Oncologist. A pre-irradiation pain assessment was done followed by pain assessment performed weekly i.e. 1, 2, 3, 4, weeks after completion of radiation and again on eighth week after radiation.

Pain was measured by a 4 point scale with numbers from 1 to 4.

Response was defined by a relief of pain at least by one category e.g. severe to moderate (4 to 3) or moderate to mild (3 to 2). Complete pain relief indicates absence of pain in treatment site. Signs of early toxicities like nausea, vomiting, diarrhea and skin reactions were noted during treatment and on each follow up.

In this study Chi-square (x2) test was employed as the method of testing the statistical significance between two groups (MF vs SF) regarding both response rates and early toxicities. It is done by setting up 'Null hypothesis' first, then calculating the difference between observed value and expected value and then setting up degree of freedom. From Probability table, the level of significance was P<0.05.

   Results Top

Out of 73, sixty patients [29 in Gr. I (MF) and 31 in Gr. II (SF)] could complete our irradiation schedule and attend our follow up clinic for pain assessment weekly for the first 4 weeks i.e. 1, 2, 3, 4 weeks after completion of radiation. However, 36 patients attended the follow up clinic 8 weeks after completion of irradiation [9 in Gr. I - multiple fraction (MF) and 17 in Gr. II - single fraction (SF)]. Cause of drop-out was mainly economical constraints

No significant difference (P<0.50) was observed in the speed of onset of Pain relief for the two treatment arms (Table II) which was 76% in Gr. I (MF) and 68% in Gr. II (SF) 4 weeks after completion of irradiation. Pain relief both complete and partial though marginally better with multiple fraction regime (Gr. I) were however not significantly better (P<0.50) than single fraction regime (Table III).

The incidence of complete pain relief as defined in this study protocol is shown in Table V. Here also no significant difference (P>0.50) between the two treatment arms could be noted (42%) vs. 35% 8 weeks after radiation). Similarly incidence of no response and progressive diseases also showed (Table IV) no significant difference

Mild nausea (Grade I) was the main early toxicity (35% in Group I vs. 29% in Group II) in both the treatment groups [Table VI]. Mild (Grade I) diarrhea was noticed in two patients in multiple fraction and three patients with single fraction regime. Skin reaction like mild (Grade I) erythema was also observed in some patients (6 in Group I and in Group II). These treatment related early toxicities were never severe enough to cause interruption in treatment procedure.

   Discussion Top

Radiation therapy has been shown to be an effective modality of treatment in cases with painful bone secondaries with incidence of pain relief ranging from 50-90%. Approximately 80% of patients receiving irradiation will achieve some relief of pain with nearly 50% achieving complete relief of pain at a given location. Moreover almost 90% of the patients who do experience pain relief do so within the first four weeks of therapy [5].

Shortly after the discovery of X-ray by Roentgen in 1985, radiation therapy was tried as an empiric form of treatment for bone metastases and relief of bone pain was observed [6]. Response rates ranging from 65% to 96% were reported on some retrospective studies using different radiation schedules. However they failed to demonstrate any dose response curves of pain relief [7],[8],[10],[11]

As regards time of onset of pain relief analysis of results of our study revealed no significant difference between single fraction of 8 Gy and multiple fraction of 30 Gy in 10 fractions over 2 weeks. The picture is more or less same in overall pain relief i.e. both complete and partial i.e. 84% in Gr. I (MF) vs. 76% in Gr. II (SF) 8 weeks after completion of irradiation.

In this present trial radiation oncologists have analysed the results on the basis of a numerical pain scale. A simultaneous assessment of pain relief by scoring the consumption of analgesic before and after treatment is expected to improve the sensitivity of the measurement. However patient's self assessment of pain using a visual analogue scale should remain our ultimate goal.

The present study also showed no significant difference in the percentage of patients not responding to irradiation therapy in the two protocol groups. (16% in multiple fraction vs 24% in single fraction).

It is to be noted that inspite of large treatment fields in some patients no significant early toxicity was observed in both groups and side effects were generally mild in nature and well tolerated.

Reports of various studies and results of the present prospective study indicate that there is no significant difference between speed of onset and overall incidence of pain relief following single or multiple fractions of irradiation in metastatic bone pain.

In fact, Hoegler. D in a recent article in 1997 had advocated that a single dose of 800 cGy may provide pain control in nearly 90% of patients which is comparable to a more protracted treatment at a higher dose of radiation [12].

However the American College of Radiology appointed a working group of experts to formulate appropriate criteria for irradiation of bone metastases. They, in their report in 1998 have given more emphasis and importance on the life expectancy of the patients. Short lasting schedules are acceptable in patients with short life expectancy i.e. less than 3 months. But further research is needed to establish this hypothesis. [13].

   Conclusion Top

To conclude both single fraction and multiple fraction radiation protocol are very effective in relieving bone pain following bone secondaries without any significant difference in response rate and early toxicities. In the above scenario, single fraction regime has some obvious advantages. Beside saving precious machine time in a busy center, one can also avoid repeated visits to the centers which is often troublesome, expensive and time consuming.

   References Top

1.Blitzer P. H, Reanalysis of the RTOG study of palliation of symptomatic osseous metastases; Cancer 1985: 55: 1468.  Back to cited text no. 1    
2.Teng. D, Gillick. L, Hendrickson. F; The palliation of symptomatic osseous metastases; Final results of the study by the radiation therapy oncology group. Cancer 1982; 50;893.  Back to cited text no. 2    
3.Price. P, Hoskin. P.J, Easton. D. etal: Prospective randomized trial of single and multifraction radiotherapy schedules in the treatment of painful bony metastases Radiother. Oncol. 1986; 6; 247.  Back to cited text no. 3    
4.Madsen. E.L, Painful bone metastases: Efficacy of Radiotherapy assessed by the patients; a rendomised trial comprising 4Gy X 6 versus 10 Gy X 2. Int. J. Radiat. Oncol. Biol. Phys. 1983; 9; 1775.  Back to cited text no. 4    
5.Addy. M. Levin - Bone metastases in Moosa. A.R, Schimoff. S. C, Robson, L.M. eds. Comprehensive Text Book of oncology - 2nd ed. - New York; Williams and Wilkins 1991; 1643.  Back to cited text no. 5    
6.Leddt. E.T.: Roentgen treatment of metastases to the vertebrae and bones of the pelvis from carcinoma of the breast. 1930; A. J.R. 231.  Back to cited text no. 6    
7.Bouchard. J, Skeletal metastases in cancer of the breast. Am. J. Roentgenol 1941;54;156 - 171.  Back to cited text no. 7    
8.Garmatis. C. J. Chu. F.C.H,: The effectiveness of radiation therapy in the treatment of bone metastases from breast cancer, Radiology 1978; 126; 235 - 237  Back to cited text no. 8    
9.Vargha Z. O, Glicksman A. S. and Boland J.; Single dose radiation therapy in the palliation of metastatic disease, Raidiology, 1969; 93; 1181 - 1184.  Back to cited text no. 9    
10.Gilberd H.A, Kogan, A.R, Nussbann, H, Rao. A.R, Evaluation of radiation therapy of bone metastases; pain relief and quality of life. Am J. Roentgenol 1977; 129 1095 - 1096.  Back to cited text no. 10    
11.Le Bourgeois, J. P, Cosset J. M, Irradiation Cancertredes metastases Osseous. J. Radiol Electrol. Med. Nucl. 1977; 58; 737 - 738.  Back to cited text no. 11    
12.Hoegler. D, Radiotherapy for palliation of symptoms in incurable cancer. Carr Probl. Cancer (US) May - June '97 21(3); 129 - 183.  Back to cited text no. 12    
13.Rose. C.M, Kagar, A.R, The final report of the expert panel for Radiation Oncology Bone metastases work group of the American College of Radiology. Int. J. Radiat. Oncol. Biol. Phys. (US) March15. 1998; 40(5) 1117-1124  Back to cited text no. 13    

Correspondence Address:
S K Sarkar
80/IE, Kanukilia Road, Calcutta-700029, West Bengal
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Source of Support: None, Conflict of Interest: None

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[Table - 1], [Table - 2], [Table - 3], [Table - 4], [Table - 5], [Table - 6]

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