Clinical Oncology (1992) 4:101-107 © 1992 The Royal College of Radiologists

Clinical Oncology

Original Article Palliation of Bone Metastases in Prostate Cancer. Hemibody Irradiation or Strontium-89? D. P. Dearnaley 1'2, R. J. Bayly 4, R. P. A'Hern 1, J. Gadd 1, M. M. Zivanovic 3 and V. J. Lewington 3 1Royal Marsden Hospital, London and Surrey, 2Institute of Cancer Research, Sutton, 3Southampton General Hospital,

Southampton and Amersham International, Buckinghamshire, UK

Abstract. The palliation of bone pain is a common clinical problem once metastatic prostate cancer has escaped from hormonal control. This retrospective study compares the results of treatment using hemibody irradiation (HBI) at the Royal Marsden Hospital (27 cases) with isotope therapy using the bone-seeking isotope strontium-89 (89Sr) at Southampton General Hospital (51 cases). Prior to analysis patients were matched for potential prognostic factors (performance status, bone scan extent of disease, age, histology and duration of hormone response) to minimize the effect of treatment selection bias. Pain control assessed at 3 months was similar for HBI and matched 89Sr cases, with 63% and 52% respectively showing some benefit. Median survival was similar for these groups at 20 and 21 weeks respectively. The unmatched 89Sr group, which had more favourable prognostic factors, had a better outcome with 96% showing improvement in pain and with a median survival of 59 weeks. Subsequent univariate analysis demonstrated that performance status and extent of disease on bone scan were of overriding importance in determining outcome. Transfusion requirements were higher for the HBI group than for the matched 89Sr group (50% and 25% respectively) but other bone marrow toxicity was similar. Despite routine anti-emetic therapy 37% of patients treated with HBI had some nausea or vomiting. Although expensive, 89Sr appears as effective a treatment option as HBI. Response is most likely with either approach when patients have a good performance status and a limited extent of disease. Keywords: Bone metastases; Hemibody radiotherapy; Prognostic factors; Prostate cancer; strontium89

Correspondence and offprint requests to: Dr D. P. Dearnaley, Department of Radiotherapy and Oncology, Royal Marsden Hospital, Downs Road, Sutton SM2 5PT, Surrey, UK.

INTRODUCTION

Hemibody irradiation (HBI) has an established place in the palliation of bone pain in prostate cancer patients who have developed recurrent disease after initial androgen deprivation. Pain relief is obtained in between 71% - 89% of patients [1-6] and is maintained until death in approximately two-thirds of patients. Although effective, normal tissue toxicity is not trivial [4] and many centres admit patients for treatment. The use of unsealed radioisotopes which localize to bone provide an alternative method of treatment. Recently, interest has centred on the use of strontium-89 (89Sr) which is a pure beta-emitting bone-seeking isotope (maximum beta energy 1.46 MeV, half life 50.6 days) which shows selective uptake in areas of osteoblastic activity [7,8]. Pain relief has been reported in between 50% - 90% of treated cases [9-13] and haematological toxicity is usually slight. One report [14] suggested that 89Sr therapy was associated with prolonged survival compared to a placebo controlled group. We were interested to compare the survival and response of patients treated with HBI or 89Sr and this report details the results of these treatment methods at the Royal Marsden Hospital [5] and Southampton General Hospital respectively. In order to minimize the effect of selection bias at the time of treatment the analysis was performed on pairs of patients who had been matched for potential prognostic factors.

PATIENTS AND METHODS

The case records of 27 patients treated with HBI at the Royal Marsden Hospital between October 1982 and February 1988, and a further 51 patients treated with SSSr at the Southampton General Hospital between November 1984 and May 1988, have been reviewed. Patient, disease and treatment related factors, together with follow-up details including

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Table 1. Patients treated with HBI or 89Sr No. of Median Extent of disease on bone scan Performance patients age status (WHO) years Slight Moderate Extensive Super-scan (range) 0/1 2 3

HBI

27

898r (all

51

patients) S9Sr (matched patients)

27

72 0 (40-86) 71 8 (55-84) 71 1 (55-84)

Time from HistologyGrade bone metastases 1 2 3 Unknown to treatment median (range) in months

1

22

4

3

12

12

12 (3-38)

11

22

10

28

17

6

2

18

6

8

13

6

response to treatment, toxicity, and survival, were recorded. All patients had developed symptomatic bone metastases having previously been treated with one or more h o r m o n e manoeuvres. The skeleton was the predominant site of metastatic disease in all cases. In order to compare the effects of either H B I or 89Sr in similar groups, patients were matched for potential prognostic factors [6,15-17] before analyzing the results of treatment. Performance status using the World Health Organization ( W H O ) scale was assessed from the records immediately prior to treatment and bone scans taken within six weeks of treatment were reviewed and graded as described by Soloway and co-workers [17]. The date of initial bone metastasis was taken from the first documentation of skeletal involvement on bone scans or skeletal radiographs (all patients had initially recurred in bone). Histological verification of prostate cancer was available in all cases and histological grading was available in 42 of the 78. All but 4 of the 78 patients were taking some form of regular analgesia. A variety of strong opiate drugs [18] were being taken by 38 (49%) of patients at a median dose of or equivalent to 70 mg oral morphine/24 hours (range 10-540 mg), 9 patients were taking weak opiate preparations and the remaining 27 used non-opiate analgesics. Patients details are shown in Table 1.

TREATMENT H B I was given using either a conventional cobalt unit, a purpose built twin headed cobalt unit or a 6MV linear accelerator. Prescribed doses were 6 Gy midplane dose (MPD) for upper half H B I , and 8 Gy M P D for lower half H B I or mid-third irradiation fields. The dose rate was 0.15-0.25 Gy/min, depending on the treatment unit. No bolus or shielding was used and lung corrections were not made. Seventeen patients were given lower half HBI, 1 had upper half HBI, 2 had mid-third, wide field irradiation and 7 had sequential lower and upper half HBI. Isotope treatment with S9Sr was given as a slow intravenous injection using activity ranging from 1.5-3.0 MBq/ Kg.

4

6

6

11

19 (4-110)

10 8

8

25

16 (6-83)

4 4

5

14

PATIENT MATCHING PROCEDURE

The 27 patients treated with H B I were matched with 27 men treated with 89Sr using the criteria outlined below. This matching process was made before the analysis of response or survival data, and subsequently these endpoints were studied in the matched populations of patients treated with H B I and 89Sr as well as the unmatched 89Sr cases. The initial step in the matching process was to define possible pairings on the basis of performance status ( W H O ) and bone scan (Soloway classification). An exact match or variation of + / - 1 in one of these parameters only was accepted. Patients were then matched for age, histology and time from development of bone metastases to treatment. Patients were divided into three age bands; 76 years and matching was accepted if a patient pair were in the same age band or within 6 years of each other. Similarly, for time of bone metastases prior to treatment, patients were divided into three groups; 24 months and matching was accepted if a patient pair were in the same band or within 6 months of each other. Histological match was accepted provided patients with well differentiated tumours were separate from those with poorly differentiated prostate cancer. The final patient pairings were accepted providing: (1) bone scan and performance status matched exactly (8 pairs) or there was a mismatch of 1 in either parameter (19 pairs), (2) there was an exact match for the remaining three parameters of age, time to bone metastases and histology (18 pairs) or a mismatch of one of these factors (9 pairs).

ASSESSMENT OF BONE PAIN, RESPONSE TO TREATMENT AND SURVIVAL

Patients' performance status ( W H O ) , and analgesic intake (quantity and type) prior to treatment were recorded, and a physician-based assessment made of sites of pain, types of pain (on movement only,

Palliation of Bone Metastases in Prostate Cancer. Hemibody Irradiation or Strontium-89?

intermittent, constant) and severity of pain (mild, moderate, severe, intractable). Response to HBI or 89Sr w a s judged 3 months after treatment. Patients were re-assessed for pain, analgesic intake, mobility and general condition. A composite score of these factors (Table 2) was used to produce the overall assessment.

Table 2. Assessment of response 3 months after treatment with HBI or 89Sr

Pain Score - 2 At least 1 point increase in type and/or severity of majority of affected sites - 1 About 1 point increase in type and/or severity in some sites 0 No change in most sites + 1 About 1 point decrease in type and/or severity in some sites +2 At least f point decrease in type and/or severity at the majority of affected sites Analgesic Score - 1 0 +1 +2 +3

intake Quantity increased Essentially unchanged Quantity decreased by 20%-49% Quantity decreased by 50%-80% Virtually discontinued

Mobility Score - 1 More restricted 0 Essentially unchanged +1 Less restricted General Condition S c o r e - 1 Deterioration 0 Unchanged + 1 Some improvement +2 Definitely better Overall Assessment Score negative - f/0+ 1 +2/+3 +4/+5/+6 +7/+8

Deterioration Unchanged Some improvement Substantial improvement Dramatic improvement

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RESULTS Patient and Tumour Variables at the Time of Treatment with HBI or S9Sr Fifty-eight of the 78 patients (74%) had bone scans showing extensive disease or super-scan appearances. Only 1 of the 27 HBI patients had slight or moderate involvement compared to 16 of 51 of the 89Sr group (P

Palliation of bone metastases in prostate cancer. Hemibody irradiation or strontium-89?

The palliation of bone pain is a common clinical problem once metastatic prostate cancer has escaped from hormonal control. This retrospective study c...
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