Australas Radio1 1990; 34: 317-319
Half Body Irradiation for the Palliation of Bone Metastases B.H. BURMEISTER, M.B., Ch.B., F..E Rad (T), S.A., F.R.A.C.R. Acting Tutor Specialist in Oncology J.C. PROBERT,M.A.,B.M., F.R.C.R.,F.R.A.C.R. Associate Professor and Head of Department Department of Clinical Oncology, Auckland Hospital, Park Road, Auckland, New Zealand.
INTRODUCTION Disseminated malignant disease with bone metastases frequently causes severe pain and disability. Since half body irradiation (HBI) for the palliation of bone metastases was first described by Fitzpatrick and Rider in 1976, the technique has been employed by a variety of centres with variable results (Bartelink et a1 1980; Fitzpatrick and Rider 1976; Keen 1980; Nag and Shah 1986; Pene et a1 1981; Rowland 1979; Rowland et a1 1981; Salazar et al 1986). The original intent was to achieve a subjective response in pain involving either the upper or lower halfbody. It was particularly applicable where the use of small field fractionated irradiation was impractical due to poor patient performance status, thus limiting multiple fractions (Barak eb a1 1987; Bartelink et a1 1980; Salazar et a1 1986). In addition, some patients with extensive deposits have pain which is difficult to localise and palliation is thus unreliable with the use of small fields (Fitzpatrick and Rider 1976). Biologically, it has been shown that a single dose of 510 Gy may be associated with a cell kill of between 1-3 logs, thus potentially resulting in a more than 90% reduction in tumour cell mass (Rowland 1979). At Auckland Hospital since 1982, 16 patients with disseminated bone metastases have been treated with HBI and were evaluable for response and toxicity. This paper reports on the use of HBI in patients with advanced malignancy and poor performance status as well as a lesser group in whom conventional fractionated small field radiotherapy was not suitable due to difficulty with pain localisation. A third group of patients with breast carcinoma was also treated with HBI, as an alternative to cytotoxic chemotherapy where poor tolerance, patient refusal and geographic reasons had precluded the latter modality. Because many patients were taking analgesics, subjective responses regarding resolution of pain were difficult to assess and were based on a reduction of analgesic intake. Improvement in mobility and performance status was sometimes more reliable as an indicator of response. METHODS AND MATERIALS Of the 16 patients evaluable, 10 were female and 6
Key Words: Half body irradiation Bone Metastases Palliative Radiotherapy
Address for Correspondence: Dr. B. H. Burmeister Radiation Oncologist Queensland Radium Institute, P.O. Herston, Brisbane 4029 Australia
Australasian Radiology. Val. XXXIV, No. 4 , November. 1990
male, with a mean age of 55.4 years. The distribution of primary site is shown in Table 1. TABLE 1 Evaluabk Patients Treated With HBI 1982-1988 Diamosis
Breast Ca Prostate Ca Lymphoma Melanoma Total
No. 10 4
1 1
16
All patients had extensive, metastatic bone disease on x-ray or bone scintigraphy. At the time of treatment, radiation was administered to the half of the body which was more symptomatic. Megavoltage x-rays were used for all treatments. The first 11 patients were treated on the treatment floor at approximately 200 cm FSD using 8 MV photons. The next 5 patients were treated on the treatment couch at approximately 140 cm FSD with the posterior field administered from below, using 6 MV photons. Doses were calculated to the mid-plane. For 13 patients who received lower HBI,the usual dose was 8 Gy, but 3 patients received 5 , 6 and 7 Gy due to pre-existing myelosuppression, concurrent chemotherapy and poor general condition respectively. The lower half-body fields extended from the top of the iliac crest to the level of the knees. The variation of dose over this volume was on average k5%. The mean dose rate used for the lower half body was 0.27 Gylmin. For 4 patients who received upper HBI the mid-plane dose was 6 Gy in one and 5 Gy in three because they had received prior irradiation to the chest wall and thoracic spine. The upper half body field extended from the base of skull to the top of the iliac crest. Prior to therapy, patients were admitted and given suitable premedication with intravenous fluids, corticosteroids and antiemetics, After treatment the patients remained in hospital for at least 24 hours o r until mobilised and able to be discharged. All patients had routine full blood counts as we11 as a biochemical screen including serum calcium and alkaline phosphatase, Regular assessments of pain relief and changes in haematological or biochemical parameters were made as inpatients and at subsequent outpatient visits. Improvement in mobility was assessed according to changes in performance status. The pre and post treatment distribution of patients as described by the ECOG scale is shown in Table 2. Careful observation for possible complications was carried out. Submitted for publication an: 12th February, 1990 Resubmitted for publication on: 17th May, 1990 Accepted for publication on: 15th August. 1990
317
B.H. BURMEISTER AND J.C. PROBERT TABLE 2
Performance Status (ECOG)
Performance Status ot Patients 'Ikated With HBI pre
Post Treatment
Treatment
Bedridden (4) In bed > 5048 (3)
8 7
In bed < 5046 (2)
0 1
Mobile, symptomatic(1 )
RESULTS Fifteen patients experienced a subjective improvement in their pain. This was assessed according to whether a reduction in the regular analgesic intake of the patient was achieved. The mean time to response was 7 days with a range of 2 to 30 days. Improvement in mobility and performance status was noted in 11 out of 13 patients who received lower HBI and who were either bedridden or severely incapacitated by pain. Only 3 patients did not improve their performance status. Of 5 patients who had a raised serum calcium at the time of treatment, 2 showed a return of the calcium to normal levels for several months. Alkaline phosphatase levels were raised in all patients and did not change appreciably following treatment. Median survival for all patients following HBI was approximately 4 months. All patients who died within 3 months had life-threatening metastatic disease involving liver or lungs. Most patients relapsed with progressive disease in previously unirradiated bones. Only one patient developed recurrence of pain within the previously irradiated lower half body. Complications are detailed in Table 3. None were severe enough to be life threatening. Of the patients who showed myelosuppression, 3 had previously been irradiated or had been given previous myelosuppressive chemotherapy. In no patients did the TABLE 3 Complications of HaIfBcdy Irradiation No. of Pts. 6
Complication Nausea or Vomiting
Diarrhoea,
SUMMARY Half body irradiation using single large doses of photons has been reported as an effective modality for the palliation of symptoms due to widespread metastatic bone malignancy. Over a 7 year period (1982-1988) sixteen patients with disseminated malignancy were given half body irradiation at Auckland Hospital. Treatment consisted of a single dose of radiation of between 5 and 8 Gray. Either 6 or 8 MV photon beams were used. Twelve patients received treatment to the lower half body, three patients to the upper half body and one patient to both upper and lower half body. Significant pain relief occured in fifteen patients and two patients experienced improvement with hypercalcaemia. All patients tolerated the treatment well and toxicity was minimal.
I
Leucopema (< 3.0 x 10'/mm3) Anaemia Urinary tract inf&m/n%entim hxia
5* 1 2 1
*3 patients with previous chemotherapy.
total white cell count drop below 2.0 x 10-'/mm3,or result in any septicaemic complications. Clinical or radiological evidence of radiation pneumonitis was not observed in the 3 patients who received upper HBI. DISCUSSION
This report demonstrates that HBI is highly effective in improving pain and quality of life in patients with bone metastases. As with other studies, treatment-related toxicity was very limited, although patients who had prior radiotherapy or chemotherapy may drop their total white cell count (Bartelink et a1 1980; Keen 1980; Nag and Shah 1986; Pene et a1 1981; Rowland 1979; Rowland et a1 1981; Salazar ef a1 1986; Salazar et a1 1978). Survival following HBI is probably unaffected by the therapy, with most studies reporting a median survival of between 5 and 318
9 months (Fitzpatrick and Rider 1976; Keen 1980; Nag and Shah 1986; Pene et a1 1981). Some other advantages concerning HBI that have become apparent in this and other studies are: 1. The treatment is simple, relatively short, cost-effective and ideal for out-of-town patients (Keen 1980; Pene eta1 1981; Rowland et a1 1981). 2. The subjective response to single fractions, typically 8 Gy is probably equal to that of fractionated regimes of therapy as far as the onset and duration of pain relief is concerned (Barak et a1 1987; Price et a1 1986; Rubin and Heilmann 1988; Salazar et aE 1986). The lower half body is a region with few highly radiosensitive vital organs where the use of large fractions does not usually cause undue toxicity. 3. Bone marrow regeneration following the use of large fields appears to be more efficient than with small fields, possibly because the stimulus is greater (Sacks et a1 1978). This finding may be of importance if future chemotherapy is contemplated. It is a future necessity to define more accurately the criteria which make a patient suitable for HBI (Rubin and Heilmann 1988; Salazar et a1 1986). It may be that HBI will prove to be the modality of choice in those patients with widespread metastatic bone disease for the palliation of pain and disability.
REFERENCES Bar& F, Werner A, Walach N and Horn Y, The Palliative Efficacy of a Single High Dose of Radiation in the Treatment of Symptomatic Osseous Metastases. Int J Radiat 0 x 0 1 Biol Phys 1987; 13: 1233-1235. Bartelink H, Battermann J, and Hart G, Haif Body Irradiation. Int J Radiat Oncol Biol. Phys 1980; 6: 87-90. Fitzpatrick PI and Rider WD, Half-Body Radiotherapy of Advanced Cancer. J Canad Ass% Radio1 1976; 27: 75-79. Keen CW, Half Body Radiotherapy in the Management of Metastatic Carcinoma of the Prostate. J Urol 1980; 123: 713-715. Nag S and Shah V, Once-a-week Lower Hemibody Irradiation (HBI) for Metastatic Cancers. Int J Radiat Oncol. Biol Phys 1986; 12: 1003-1005. Pene F, Schlienger M Schmitt T, Izrael V, Kinay M, Aget H and Laugier A, Half-Body Irradiation for Pain Relief. Eur J Cancer Clin Oncol 1981; 17: 753-758. Price P, Hoskin PI, Easton D, Austin D. Palmer SG and Yarnold JR, Prospective Randomised Trial of Single and Multifraction Radiotherapy Schedules in the Treatment of Painful Bony Metastases. Radiother Oncol 1986 6 247-255. Rowland CG, Single Fraction Half Body Radiation Therapy. Clin Radio1 1979; 3 0 1-3. Rowland CG, Bullimore JA, Smith PJB and Roberts JBM, Half-Body Irradiation in the Treatment of Metastatic Prostatic Carcinoma. Br J Urol 1981; 53: 628-629.
Australasian Radiology, Vol. X X X N , No. 4, November. 1990
HALF BODY IRRADIATION FOR THE PALLIATION OF BONE METASTASES Rubin P and Heilmann H-P, Large Field Trials. Int J Radiat Oncol Biol PhyS 1988; 1 4 S65-S76. Sacks E, Gons MZ, Glatstein E, Gilbert E and Kaplan HS, Bone Marrow Regeneration following Large Field Irradiation. Cancer 1978; 42: 1057-1065. Salazar OM, Rubin P, Hendrickson FR, Komaki R, Poulter C, Newall J, Asbell SO, Mohiuddin M and Van Ess J, Single-Dose Half-Body
Awtrolasian Radiology, Vol.XXXW. No.4 . November. 1990
Irradiation for Palliation of Multiple Bone Metastases from Solid Turnours. Cancer 1986; 58: 29-36. Salazar OM, Rubin P,Keller B and Scarantino C, Systemic (Half-Body) Radiation Therapy: Response and Toxicity. Int J Radiat Oncol Biol F'hys 1978; 4 937-950.
319
Half Body Irradiation for the Palliation of Bone Metastases B.H. BURMEISTER, M.B., Ch.B., F..E Rad (T), S.A., F.R.A.C.R. Acting Tutor Specialist in Oncology J.C. PROBERT,M.A.,B.M., F.R.C.R.,F.R.A.C.R. Associate Professor and Head of Department Department of Clinical Oncology, Auckland Hospital, Park Road, Auckland, New Zealand.
INTRODUCTION Disseminated malignant disease with bone metastases frequently causes severe pain and disability. Since half body irradiation (HBI) for the palliation of bone metastases was first described by Fitzpatrick and Rider in 1976, the technique has been employed by a variety of centres with variable results (Bartelink et a1 1980; Fitzpatrick and Rider 1976; Keen 1980; Nag and Shah 1986; Pene et a1 1981; Rowland 1979; Rowland et a1 1981; Salazar et al 1986). The original intent was to achieve a subjective response in pain involving either the upper or lower halfbody. It was particularly applicable where the use of small field fractionated irradiation was impractical due to poor patient performance status, thus limiting multiple fractions (Barak eb a1 1987; Bartelink et a1 1980; Salazar et a1 1986). In addition, some patients with extensive deposits have pain which is difficult to localise and palliation is thus unreliable with the use of small fields (Fitzpatrick and Rider 1976). Biologically, it has been shown that a single dose of 510 Gy may be associated with a cell kill of between 1-3 logs, thus potentially resulting in a more than 90% reduction in tumour cell mass (Rowland 1979). At Auckland Hospital since 1982, 16 patients with disseminated bone metastases have been treated with HBI and were evaluable for response and toxicity. This paper reports on the use of HBI in patients with advanced malignancy and poor performance status as well as a lesser group in whom conventional fractionated small field radiotherapy was not suitable due to difficulty with pain localisation. A third group of patients with breast carcinoma was also treated with HBI, as an alternative to cytotoxic chemotherapy where poor tolerance, patient refusal and geographic reasons had precluded the latter modality. Because many patients were taking analgesics, subjective responses regarding resolution of pain were difficult to assess and were based on a reduction of analgesic intake. Improvement in mobility and performance status was sometimes more reliable as an indicator of response. METHODS AND MATERIALS Of the 16 patients evaluable, 10 were female and 6
Key Words: Half body irradiation Bone Metastases Palliative Radiotherapy
Address for Correspondence: Dr. B. H. Burmeister Radiation Oncologist Queensland Radium Institute, P.O. Herston, Brisbane 4029 Australia
Australasian Radiology. Val. XXXIV, No. 4 , November. 1990
male, with a mean age of 55.4 years. The distribution of primary site is shown in Table 1. TABLE 1 Evaluabk Patients Treated With HBI 1982-1988 Diamosis
Breast Ca Prostate Ca Lymphoma Melanoma Total
No. 10 4
1 1
16
All patients had extensive, metastatic bone disease on x-ray or bone scintigraphy. At the time of treatment, radiation was administered to the half of the body which was more symptomatic. Megavoltage x-rays were used for all treatments. The first 11 patients were treated on the treatment floor at approximately 200 cm FSD using 8 MV photons. The next 5 patients were treated on the treatment couch at approximately 140 cm FSD with the posterior field administered from below, using 6 MV photons. Doses were calculated to the mid-plane. For 13 patients who received lower HBI,the usual dose was 8 Gy, but 3 patients received 5 , 6 and 7 Gy due to pre-existing myelosuppression, concurrent chemotherapy and poor general condition respectively. The lower half-body fields extended from the top of the iliac crest to the level of the knees. The variation of dose over this volume was on average k5%. The mean dose rate used for the lower half body was 0.27 Gylmin. For 4 patients who received upper HBI the mid-plane dose was 6 Gy in one and 5 Gy in three because they had received prior irradiation to the chest wall and thoracic spine. The upper half body field extended from the base of skull to the top of the iliac crest. Prior to therapy, patients were admitted and given suitable premedication with intravenous fluids, corticosteroids and antiemetics, After treatment the patients remained in hospital for at least 24 hours o r until mobilised and able to be discharged. All patients had routine full blood counts as we11 as a biochemical screen including serum calcium and alkaline phosphatase, Regular assessments of pain relief and changes in haematological or biochemical parameters were made as inpatients and at subsequent outpatient visits. Improvement in mobility was assessed according to changes in performance status. The pre and post treatment distribution of patients as described by the ECOG scale is shown in Table 2. Careful observation for possible complications was carried out. Submitted for publication an: 12th February, 1990 Resubmitted for publication on: 17th May, 1990 Accepted for publication on: 15th August. 1990
317
B.H. BURMEISTER AND J.C. PROBERT TABLE 2
Performance Status (ECOG)
Performance Status ot Patients 'Ikated With HBI pre
Post Treatment
Treatment
Bedridden (4) In bed > 5048 (3)
8 7
In bed < 5046 (2)
0 1
Mobile, symptomatic(1 )
RESULTS Fifteen patients experienced a subjective improvement in their pain. This was assessed according to whether a reduction in the regular analgesic intake of the patient was achieved. The mean time to response was 7 days with a range of 2 to 30 days. Improvement in mobility and performance status was noted in 11 out of 13 patients who received lower HBI and who were either bedridden or severely incapacitated by pain. Only 3 patients did not improve their performance status. Of 5 patients who had a raised serum calcium at the time of treatment, 2 showed a return of the calcium to normal levels for several months. Alkaline phosphatase levels were raised in all patients and did not change appreciably following treatment. Median survival for all patients following HBI was approximately 4 months. All patients who died within 3 months had life-threatening metastatic disease involving liver or lungs. Most patients relapsed with progressive disease in previously unirradiated bones. Only one patient developed recurrence of pain within the previously irradiated lower half body. Complications are detailed in Table 3. None were severe enough to be life threatening. Of the patients who showed myelosuppression, 3 had previously been irradiated or had been given previous myelosuppressive chemotherapy. In no patients did the TABLE 3 Complications of HaIfBcdy Irradiation No. of Pts. 6
Complication Nausea or Vomiting
Diarrhoea,
SUMMARY Half body irradiation using single large doses of photons has been reported as an effective modality for the palliation of symptoms due to widespread metastatic bone malignancy. Over a 7 year period (1982-1988) sixteen patients with disseminated malignancy were given half body irradiation at Auckland Hospital. Treatment consisted of a single dose of radiation of between 5 and 8 Gray. Either 6 or 8 MV photon beams were used. Twelve patients received treatment to the lower half body, three patients to the upper half body and one patient to both upper and lower half body. Significant pain relief occured in fifteen patients and two patients experienced improvement with hypercalcaemia. All patients tolerated the treatment well and toxicity was minimal.
I
Leucopema (< 3.0 x 10'/mm3) Anaemia Urinary tract inf&m/n%entim hxia
5* 1 2 1
*3 patients with previous chemotherapy.
total white cell count drop below 2.0 x 10-'/mm3,or result in any septicaemic complications. Clinical or radiological evidence of radiation pneumonitis was not observed in the 3 patients who received upper HBI. DISCUSSION
This report demonstrates that HBI is highly effective in improving pain and quality of life in patients with bone metastases. As with other studies, treatment-related toxicity was very limited, although patients who had prior radiotherapy or chemotherapy may drop their total white cell count (Bartelink et a1 1980; Keen 1980; Nag and Shah 1986; Pene et a1 1981; Rowland 1979; Rowland et a1 1981; Salazar ef a1 1986; Salazar et a1 1978). Survival following HBI is probably unaffected by the therapy, with most studies reporting a median survival of between 5 and 318
9 months (Fitzpatrick and Rider 1976; Keen 1980; Nag and Shah 1986; Pene et a1 1981). Some other advantages concerning HBI that have become apparent in this and other studies are: 1. The treatment is simple, relatively short, cost-effective and ideal for out-of-town patients (Keen 1980; Pene eta1 1981; Rowland et a1 1981). 2. The subjective response to single fractions, typically 8 Gy is probably equal to that of fractionated regimes of therapy as far as the onset and duration of pain relief is concerned (Barak et a1 1987; Price et a1 1986; Rubin and Heilmann 1988; Salazar et aE 1986). The lower half body is a region with few highly radiosensitive vital organs where the use of large fractions does not usually cause undue toxicity. 3. Bone marrow regeneration following the use of large fields appears to be more efficient than with small fields, possibly because the stimulus is greater (Sacks et a1 1978). This finding may be of importance if future chemotherapy is contemplated. It is a future necessity to define more accurately the criteria which make a patient suitable for HBI (Rubin and Heilmann 1988; Salazar et a1 1986). It may be that HBI will prove to be the modality of choice in those patients with widespread metastatic bone disease for the palliation of pain and disability.
REFERENCES Bar& F, Werner A, Walach N and Horn Y, The Palliative Efficacy of a Single High Dose of Radiation in the Treatment of Symptomatic Osseous Metastases. Int J Radiat 0 x 0 1 Biol Phys 1987; 13: 1233-1235. Bartelink H, Battermann J, and Hart G, Haif Body Irradiation. Int J Radiat Oncol Biol. Phys 1980; 6: 87-90. Fitzpatrick PI and Rider WD, Half-Body Radiotherapy of Advanced Cancer. J Canad Ass% Radio1 1976; 27: 75-79. Keen CW, Half Body Radiotherapy in the Management of Metastatic Carcinoma of the Prostate. J Urol 1980; 123: 713-715. Nag S and Shah V, Once-a-week Lower Hemibody Irradiation (HBI) for Metastatic Cancers. Int J Radiat Oncol. Biol Phys 1986; 12: 1003-1005. Pene F, Schlienger M Schmitt T, Izrael V, Kinay M, Aget H and Laugier A, Half-Body Irradiation for Pain Relief. Eur J Cancer Clin Oncol 1981; 17: 753-758. Price P, Hoskin PI, Easton D, Austin D. Palmer SG and Yarnold JR, Prospective Randomised Trial of Single and Multifraction Radiotherapy Schedules in the Treatment of Painful Bony Metastases. Radiother Oncol 1986 6 247-255. Rowland CG, Single Fraction Half Body Radiation Therapy. Clin Radio1 1979; 3 0 1-3. Rowland CG, Bullimore JA, Smith PJB and Roberts JBM, Half-Body Irradiation in the Treatment of Metastatic Prostatic Carcinoma. Br J Urol 1981; 53: 628-629.
Australasian Radiology, Vol. X X X N , No. 4, November. 1990
HALF BODY IRRADIATION FOR THE PALLIATION OF BONE METASTASES Rubin P and Heilmann H-P, Large Field Trials. Int J Radiat Oncol Biol PhyS 1988; 1 4 S65-S76. Sacks E, Gons MZ, Glatstein E, Gilbert E and Kaplan HS, Bone Marrow Regeneration following Large Field Irradiation. Cancer 1978; 42: 1057-1065. Salazar OM, Rubin P, Hendrickson FR, Komaki R, Poulter C, Newall J, Asbell SO, Mohiuddin M and Van Ess J, Single-Dose Half-Body
Awtrolasian Radiology, Vol.XXXW. No.4 . November. 1990
Irradiation for Palliation of Multiple Bone Metastases from Solid Turnours. Cancer 1986; 58: 29-36. Salazar OM, Rubin P,Keller B and Scarantino C, Systemic (Half-Body) Radiation Therapy: Response and Toxicity. Int J Radiat Oncol Biol F'hys 1978; 4 937-950.
319
