Inl. J. Radrarron Oncology Em/. Phys, Vol. 23, pp. 215-216 Printed in the U.S.A. All rights reserved.
Copyright
0360.3016/92 $5.00 + .oO 0 1992 Pergamon Press Ltd
??Special Feature
BONE
METASTASIS
T. BATES, J. R. YARNOLD,
CONSENSUS
P. BLITZER,
0. S. NELSON, P. RUBIN AND J. MAHER better than average prognosis, more studies are needed to examine the effect of radiotherapy dose response duration in this group. In the meantime, patients with a short life expectation may be treated safely with a single fraction of 8 Gy (3, 9). There is a common perception that a minority of patients require a higher dose of fractionated radiotherapy, particularly those where the main aim of treatment is to restore or maintain the structural integrity of bone. This apparently straightforward issue is complicated by a possibly increased risk of pathological fracture, as shown by an 18% fracture rate in long bones of patients receiving a higher dose in the RTOG trial (2, 15). Studies are needed to identify the relationship between radiotherapy dose and the process of bone healing. In practice, radiotherapy is often prescribed with the combined aims of inducing pain relief and bone healing and many radiation oncologists believe that higher dose radiotherapy is indicated under these circumstances (1, 2). As previously discussed, the relationships between radiotherapy dose and response duration in terms of pain relief and bone healing are poorly defined and require further investigation. Alternative approaches to managing patients with multiple painful bone metastases include wide field radiotherapy and systemic treatment with radioactive isotopes. RTOG studies on wide field irradiation have clearly defined the feasibility and effectiveness of this approach ( 12). An increasing number of studies have also reported on the use of isotopes, especially the bone-seeking isotope 89-Sr, but the present data do not allow any final conclusion on their effectiveness (6, 11, 13, 14). Finally, the biological basis of pain relief by radiotherapy is not fully understood. The rapid onset of pain relief after hemi-body radiotherapy (5, 12), and the apparent lack of association between the onset of pain relief and tumour histology (1,9), argue against tumor shrinkage as a component of the initial response. Even the need for tumor cell kill can be questioned, and highlights the need for studies examining the biological basis of radiotherapy action.
Traditional notions concerning the aims and means of delivering radiotherapy to patients with metastatic bone pain are being questioned by prospective trials of local (2, 3, 5, 7, 8, 9) and wide-field (5, 12) radiotherapy conducted in Europe and the United States over the last decade. Even so, recent and current trials are limited either by the use of unreliable measures of response (e.g. physician assessment without including patient self-assessment) or by trials with only a few hundred patients and limited statistical power. For example, a large multicenter RTOG study accruing 10 16 patients from 39 institutions over 6 years, using physician assessment of pain relief, suggested initially that there was no statistically significant relationship between total dose/fraction number and the probability of complete pain relief (15). A reanalysis of this data by Blitzer (2) using different end points, including the need for retreatment and analgesic requirements, concluded the opposite, and found a dose response relationship. On the other hand, a one-center study from the United Kingdom accruing 288 patients over 4 years, using patient self-assessment of pain relief, failed to reveal a dose-response relationship for either incidence or duration of pain relief, at least over a 3-month period (9). Uncertainty as to the relationship between radiotherapy dose and the incidence/duration of pain relief (1, 2, 4, 8, 9, lo), highlights the need for large prospective trials using validated patient questionnaires as well as physician assessment of pain, which will address the benefits of low dose palliation in patients with only a few months to live. The results of the UK study (9) suggest that a single fraction of 8 Gy may be as effective as 30 Gy in 10 fractions, at least over a 3-month period, and possibly longer. In addition, the data so far fail to support a close relationship between the probability of pain relief and tumor histology, and point to the need for trials containing a large number of patients with different types of tumor histology. There are insufficient data to support a clear statement concerning radiotherapy dose and response duration beyond 3 months. Because the question of a relationship between radiotherapy dose and response duration is so important, particularly for patients perceived to have a Reprint requests to: P. Rubin, Division of Radiation ogy, Strong Memorial NY 14642.
Hospital,
60 1 Elmwood
STATEMENT
Accepted
OncolAve., Rochester, 215
for publication
14 November
199 1.
216
1.J.
Radiation Oncology 0 Biology??Physics
Volume 23, Number 1, 1992
REFERENCES 1. Arcangeli, G.; Micheli, A.; Arcangeli, G.; Giannarelli, D.; La Pasta, 0.; Tollis, A.; Uitullo, A.; Ghera, S.; Benassi, M. The responsiveness of bone metastases to radiotherapy: the effect if site, histology and radiation dose on pain relief. Radiother. Oncol. 14: 95-101; 1989. 2. Blitzer, P. H. Reanalysis of the RTOG study of the palliation of symptomatic osseous metastases. Cancer 5 5: 1468- 1472; 1985. 3. Cole, D. J. A randomised trial of a single treatment versus conventional fractionation in the palliative radiotherapy of painful bone metastases. Clin. Oncol. 1: 56-62; 1989. 4. Horwich, A. The role of radiotherapy in locally advanced and metastatic breast cancer. In: Coombes, R. C., Powles, T. J., Ford, H. T., Gaze& J.-C., eds. Breast cancer management. London: Academic; 1983: 227-266. 5. Hoskin, P. J.; Ford, H. T.; Harmer, C. L. Hemibody irradiation (HBl) for metastatic bone pain in two histocogically distinct groups of patients. Clin. Oncol. 1: 67-69; 1989. 6. Hoskin, P. J. Scientific and clinical aspects of radiotherapy in the relief of bone pain. Cancer Surveys 7: 69-86; 1988. 1. Madsen, E. L. Painful bone metastases: Efficacy of radiotherapy assessed by the patients: a randomnised trial comparing 4 Gy X 6 versus 10 Gy X 2. Int. J. Radiat. Oncol. Biol. Phys. 9: 1775-1779; 1983. 8. Okawa, T.; Kita, M.; Goto, M. Randomised prospective clinical study of small, large and three-a-day fraction radiotherapy for painful bone metastases. Radiother. Oncol. 13: 99-104; 1988.
9.Price, P.; Hoskin, P. J.; Easton, D.; Austin, A.; Palmer,
10.
11.
12.
13. 14.
15.
S. G.; Yarnold, J. R. Prospective randomised trial of single and multifraction radiotherapy schedules in the treatment of painful bone metastases. Radiother. Oncol. 6: 247-255; 1986. Price, P.; Hoskins, P. J.; Easton, D.; Austin, A.; Palmer, S. G.; Yarnold, J. R. Low dose single fraction radiotherapy in the treatment of metastatic bone pain: a pilot study. Radiother. Oncol. 12: 297-300; 1988. Robinson, R. G.; Blake, G. M.; Preston, D. F. Strontium89: treatment results and kinetics in patients with painful metastatic prostatic and breast cancer in bone. Radiographits 9: 271-281; 1989. Salazar, 0. M.; Rubin, P.; Hendrickson, F. R.; Komaki, R.; Poulter, C.; Newell, J. Single dose half-body irradiation for palliation of multiple bone metastases from solid tumors. Cancer 58: 29-36; 1986. Silberstein, E. B.; Williams, C. Strontium-89 therapy for the pain of osseous metastases. J. Nucl. Med. 26: 345-348; 1985. Tennvall, J.; Darte, L.; Lundgren, R.; El Hassan, A. M. Palliation of multiple bone metastases from prostate carcinoma with Strontium-89. Acta Oncol. 27(4): 365-369; 1988. Tong, D.; Gillick, L.; Hendrickson, F. R. The palliation of symptomatic osseous metastases. Final results of the Radiation Therapy Oncology Group. Cancer 50: 893-899; 1982.
Copyright
0360.3016/92 $5.00 + .oO 0 1992 Pergamon Press Ltd
??Special Feature
BONE
METASTASIS
T. BATES, J. R. YARNOLD,
CONSENSUS
P. BLITZER,
0. S. NELSON, P. RUBIN AND J. MAHER better than average prognosis, more studies are needed to examine the effect of radiotherapy dose response duration in this group. In the meantime, patients with a short life expectation may be treated safely with a single fraction of 8 Gy (3, 9). There is a common perception that a minority of patients require a higher dose of fractionated radiotherapy, particularly those where the main aim of treatment is to restore or maintain the structural integrity of bone. This apparently straightforward issue is complicated by a possibly increased risk of pathological fracture, as shown by an 18% fracture rate in long bones of patients receiving a higher dose in the RTOG trial (2, 15). Studies are needed to identify the relationship between radiotherapy dose and the process of bone healing. In practice, radiotherapy is often prescribed with the combined aims of inducing pain relief and bone healing and many radiation oncologists believe that higher dose radiotherapy is indicated under these circumstances (1, 2). As previously discussed, the relationships between radiotherapy dose and response duration in terms of pain relief and bone healing are poorly defined and require further investigation. Alternative approaches to managing patients with multiple painful bone metastases include wide field radiotherapy and systemic treatment with radioactive isotopes. RTOG studies on wide field irradiation have clearly defined the feasibility and effectiveness of this approach ( 12). An increasing number of studies have also reported on the use of isotopes, especially the bone-seeking isotope 89-Sr, but the present data do not allow any final conclusion on their effectiveness (6, 11, 13, 14). Finally, the biological basis of pain relief by radiotherapy is not fully understood. The rapid onset of pain relief after hemi-body radiotherapy (5, 12), and the apparent lack of association between the onset of pain relief and tumour histology (1,9), argue against tumor shrinkage as a component of the initial response. Even the need for tumor cell kill can be questioned, and highlights the need for studies examining the biological basis of radiotherapy action.
Traditional notions concerning the aims and means of delivering radiotherapy to patients with metastatic bone pain are being questioned by prospective trials of local (2, 3, 5, 7, 8, 9) and wide-field (5, 12) radiotherapy conducted in Europe and the United States over the last decade. Even so, recent and current trials are limited either by the use of unreliable measures of response (e.g. physician assessment without including patient self-assessment) or by trials with only a few hundred patients and limited statistical power. For example, a large multicenter RTOG study accruing 10 16 patients from 39 institutions over 6 years, using physician assessment of pain relief, suggested initially that there was no statistically significant relationship between total dose/fraction number and the probability of complete pain relief (15). A reanalysis of this data by Blitzer (2) using different end points, including the need for retreatment and analgesic requirements, concluded the opposite, and found a dose response relationship. On the other hand, a one-center study from the United Kingdom accruing 288 patients over 4 years, using patient self-assessment of pain relief, failed to reveal a dose-response relationship for either incidence or duration of pain relief, at least over a 3-month period (9). Uncertainty as to the relationship between radiotherapy dose and the incidence/duration of pain relief (1, 2, 4, 8, 9, lo), highlights the need for large prospective trials using validated patient questionnaires as well as physician assessment of pain, which will address the benefits of low dose palliation in patients with only a few months to live. The results of the UK study (9) suggest that a single fraction of 8 Gy may be as effective as 30 Gy in 10 fractions, at least over a 3-month period, and possibly longer. In addition, the data so far fail to support a close relationship between the probability of pain relief and tumor histology, and point to the need for trials containing a large number of patients with different types of tumor histology. There are insufficient data to support a clear statement concerning radiotherapy dose and response duration beyond 3 months. Because the question of a relationship between radiotherapy dose and response duration is so important, particularly for patients perceived to have a Reprint requests to: P. Rubin, Division of Radiation ogy, Strong Memorial NY 14642.
Hospital,
60 1 Elmwood
STATEMENT
Accepted
OncolAve., Rochester, 215
for publication
14 November
199 1.
216
1.J.
Radiation Oncology 0 Biology??Physics
Volume 23, Number 1, 1992
REFERENCES 1. Arcangeli, G.; Micheli, A.; Arcangeli, G.; Giannarelli, D.; La Pasta, 0.; Tollis, A.; Uitullo, A.; Ghera, S.; Benassi, M. The responsiveness of bone metastases to radiotherapy: the effect if site, histology and radiation dose on pain relief. Radiother. Oncol. 14: 95-101; 1989. 2. Blitzer, P. H. Reanalysis of the RTOG study of the palliation of symptomatic osseous metastases. Cancer 5 5: 1468- 1472; 1985. 3. Cole, D. J. A randomised trial of a single treatment versus conventional fractionation in the palliative radiotherapy of painful bone metastases. Clin. Oncol. 1: 56-62; 1989. 4. Horwich, A. The role of radiotherapy in locally advanced and metastatic breast cancer. In: Coombes, R. C., Powles, T. J., Ford, H. T., Gaze& J.-C., eds. Breast cancer management. London: Academic; 1983: 227-266. 5. Hoskin, P. J.; Ford, H. T.; Harmer, C. L. Hemibody irradiation (HBl) for metastatic bone pain in two histocogically distinct groups of patients. Clin. Oncol. 1: 67-69; 1989. 6. Hoskin, P. J. Scientific and clinical aspects of radiotherapy in the relief of bone pain. Cancer Surveys 7: 69-86; 1988. 1. Madsen, E. L. Painful bone metastases: Efficacy of radiotherapy assessed by the patients: a randomnised trial comparing 4 Gy X 6 versus 10 Gy X 2. Int. J. Radiat. Oncol. Biol. Phys. 9: 1775-1779; 1983. 8. Okawa, T.; Kita, M.; Goto, M. Randomised prospective clinical study of small, large and three-a-day fraction radiotherapy for painful bone metastases. Radiother. Oncol. 13: 99-104; 1988.
9.Price, P.; Hoskin, P. J.; Easton, D.; Austin, A.; Palmer,
10.
11.
12.
13. 14.
15.
S. G.; Yarnold, J. R. Prospective randomised trial of single and multifraction radiotherapy schedules in the treatment of painful bone metastases. Radiother. Oncol. 6: 247-255; 1986. Price, P.; Hoskins, P. J.; Easton, D.; Austin, A.; Palmer, S. G.; Yarnold, J. R. Low dose single fraction radiotherapy in the treatment of metastatic bone pain: a pilot study. Radiother. Oncol. 12: 297-300; 1988. Robinson, R. G.; Blake, G. M.; Preston, D. F. Strontium89: treatment results and kinetics in patients with painful metastatic prostatic and breast cancer in bone. Radiographits 9: 271-281; 1989. Salazar, 0. M.; Rubin, P.; Hendrickson, F. R.; Komaki, R.; Poulter, C.; Newell, J. Single dose half-body irradiation for palliation of multiple bone metastases from solid tumors. Cancer 58: 29-36; 1986. Silberstein, E. B.; Williams, C. Strontium-89 therapy for the pain of osseous metastases. J. Nucl. Med. 26: 345-348; 1985. Tennvall, J.; Darte, L.; Lundgren, R.; El Hassan, A. M. Palliation of multiple bone metastases from prostate carcinoma with Strontium-89. Acta Oncol. 27(4): 365-369; 1988. Tong, D.; Gillick, L.; Hendrickson, F. R. The palliation of symptomatic osseous metastases. Final results of the Radiation Therapy Oncology Group. Cancer 50: 893-899; 1982.
