Scarantino et al. (1996)

Scarantino et al. (1996)
Design: Phase II study (prognosis), evidence level: 3
Country: United States
Inclusion criteria:
Single or multiple bone metastases secondary to prostate or breast cancer
Painful sites (1–2) confined to one hemi body field (upper, middle or lower)
Pain score of ≥ 2 and narcotic score of ≥ 2 according to the RTOG Pain and Narcotic Scale
Karnofsky performance scale ≥ 60
Defined haematological and laboratory criteria
Previous endocrine therapy and RT acceptable
Written informed consent.
Exclusion criteria:
Number of patients = 142.
Five doses of RT at a daily dose of 2.5 Gy:
10 Gy (x 4 fractions) n = 37 (incl. 1 ineligible)
12.5 Gy x 6 fractions n = 23
15 Gy (x 6 fractions) n = 18
17.5 Gy (x 7 fractions) n = 40 (incl. 1 ineligible)
20 Gy (x 8 fractions) n = 26
Shielding reduced the exposure of the lungs to not more than 6 Gy or 15 Gy to the liver/kidneys
Time to progression
Overall survival
Follow up:
Blood counts were repeated weekly (or until normal) following HBI then every 3 months. Bone scans, KPS assessments, history, pain and narcotic scores were recorded every 3 months for the first year and then 6-monthly.

125/142 patients died by the study end. Median follow-up = 9.4 months (range: 0.6–60 months).
Treatment arms were similar in most respects except for KPS.

Adverse events (10 Gy/12 Gy/15 Gy/17.5 Gy/20 Gy):
31/120 patients who completed their treatment experienced grade 3/4 adverse events:
Anaemia: (4/0/1/3/3)
Leukopenia: (5/2/3/6/5)
Thromboleukopenia: (3/2/1/5/5)
GI: (2/2/0/2/2)
Lung: 0/0/0/0/0 (1 patient had a grade 5 (fatal) pulmonary toxicity)
There were no dose-limiting, non-haematological toxicities at any dose.

Time to new disease in the HB field:
There was no difference in failure % after 17.5 Gy (19%) compared to 10 Gy (19%) at 12 months and after 18 months the rate is slightly better (19% versus 25%) but not significant.

Time to new treatment (RT) in the HB field:
The percentage failure increases with decreasing doses of HBRT, as would be expected. At 1 year, for example, the time to RT for patients after 10 Gy HBRT is 36% compared with 19% for patients that had received 20 Gy HBRT. At 18 months these figures are, respectively, 42% versus 30%.

This was not an endpoint in the study but was partially reported. At 12 months, 41% patients who had received 10 Gy and 12.5 Gy fractionated HBRT were alive, compared with 44% after 15 Gy or 17.5 Gy. Initially survival was better for those patients having received 20 Gy than lower doses, but by 2yrs this advantage had been lost.
General comments:
This paper is primarily reporting results of a multi-centre, dose searching phase I trial of fractionated hemi-body irradiation but also reports some of the resultant haematological and other toxicities, time to progression and some survival data. The study spans 1989–1993 and the data were analysed in 1995.

41/142 (29%) patients were female. It is not stated whether any of the males had breast cancer.

Eligibility was confirmed by telephone call whereupon patients were assigned to treatment sequentially to one of five different dose regimes.

According to previously established criteria, the authors concluded the maximum tolerable dose of HBRT, with the least toxicity, was 17.5 Gy delivered in 2.5 Gy fractions.

From: Chapter 6, Management of specific problems

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Advanced Breast Cancer: Diagnosis and Treatment.
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