The Role of Radiotherapy in Management of Metastatic Bone Disease P. Pradeep Kumar, MD, Feraydoon Bahrassa, MD and Maria C. Espinoza, MD Washington, DC
Pain relief from bone metastases is achieved in 80 percent of patients by local irradiation. Response to local irradiation is much faster in metastases from breast and lung than in prostate bone metastases. Local irradiation is also very effective in preventing pathological fractures in lytic bone lesions, and healing of the pathological fractures by new bone formation. Although much attention is given to treatment of primary cancers, less is said about management of the metastatic cancers from which most cancer patients die ultimately. Seventy percent of patients with cancer have metastasis to bone at autopsy. ' Primary sites of cancer which metastasize to bone in decending order of frequency are breast, prostate, lung, thyroid, kidney, pancreas, cervix, stomach, colorectum, ovary, and esophagus.2 In descending order of frequency, bones that are most commonly involved with metastatic cancer are the spine, pelvis, femur, ribs, skull, and humerus. Metastases to bones of the forearm, wrist, and hand and to bones of the leg, ankle, and foot occur infrequently. However, bone metastasis can occur anywhere from head to toe.3 Therefore, while doing a bone survey for metastatic disease, extremities
Requests for reprints should be addressed to P. Pradeep Kumar, MD, Associate Professor, Department of Radiotherapy, Howard University Hospital, 2041 Georgia Avenue, NW, Washington, DC 20060.
should not be excluded from the study. Procedures that are most valuable in the diagnosis of metastatic bone disease are, in order of diminishing accuracy, bone marrow biopsy, bone marrow aspiration, bone scan, and x-rays. Bones are not the number one site for metastatic disease in all cancer patients. Most cancer patients treated for metastatic disease in this Department of Radiotherapy have bone metastases. The earliest symptom of metastatic bone disease is pain. Patients with metastatic disease in the lymph nodes, lungs, and liver can remain asymptomatic for long periods of time before metastases are detected. With the exception of carcinoma of the prostate, where metastasis usually gives rise to a condensation of bone, areas of skeletal invasion by malignant neoplasms are characteristically destructive. In individual cases, however, the opposite effect may be noted, and a carcinoma of the breast or stomach occasionally may give rise to formative or osteoblastic metastases, whereas carcinoma of the prostate sometimes induces destructive or osteolytic lesions.
JOURNAL OF THE NATIONAL MEDICAL ASSOCIATION, VOL. 70, NO. 12, 1978
Disability from pain is a prominent feature of metastatic bone cancer. However, occasionally pathologic fracture may be the first indication that metastasis to bone has taken place. Less often, a metastasis may be the first evidence of primary disease. Both bone pain and pathological fractures from metastatic bone disease can cause a cancer patient to be bedridden, leading to further complications such as decubitus ulcers and hypercalcemia (Figure 1). Pathologic fractures of the spine can also cause permanent neurological deficit. Therefore, it is extremely important to diagnose and treat metastatic bone disease before the development of complications, which make management of a cancer patient much more difficult and the prognosis worse.
Materials and Methods Over five years, 112 cancer patients with metastatic bone disease were treated in the Department of Radiotherapy at Howard University Hospital. The sites of the primary and metastatic bone disease are given in Table 1. Three common primary carcinomas with metastatic bone disease are breast, lung, and prostate. In these three primary tumors, the sites of bone metastases in the order of descending frequency are vertebrae, pelvis, long bones of the thighs and arms, ribs, and skull. All patients with bone metastases referred for radiotherapy received a 909
3,000 rad tumor dose in 15 fractions over a three-week period. Relief of pain is achieved in almost 80 percent of patients. However, in patients with metastatic breast and lung carcinomas, pain relief was achieved much earlier than in metastatic prostatic cancer (Table 2). This slower response of pain to radiation in metastatic prostate cancer is consistent with the hypothesis that slowly growing tumors, such as those in the prostate, respond more slowly.
Patients with metastatic bone disease, admitted in wheelchairs or stretchers *and requiring hospitalization due to severe pain, become ambulatory as soon as the pain is relieved. Early ambulation is not only important in preventing complications like decubitus ulcers and hypercalcemia; it also reduces hospitalization costs and relieves pressure on relatives attending these patients at home (Figure 1). Local bone irradiation is not only
RT Pain
Pathological fractures
it
With
RT
or
without
neurological deficits
External or internal fixation + RT Bed Ridden
1~
Decubitus ulcers, Hypercalcemia Figure 1. Complications of bone metastases and their prevention. RTRadiotherapy
very effective in relieving pain from metastatic bone disease but it also helps in new bone formation by destroying tumor cells. New bone formation is important in preventing pathological fractures which require external or internal immobilization and long convalescence. However, large lytic lesions in vulnerable weightbearing bony parts like the neck of the femur and vertebral bodies should be stabilized prior to irradiation (internally in the former and externally in the latter) in order to prevent pathological fracture (Figures 2 and 3). Once a pathological fracture develops from metastatic bone disease, either external or internal immobilization becomes mandatory. This should be followed by local irradiation. The fractured fragments should be properly proximated and totally immobilized so that new bone formation can occur. Once this is achieved, local irradiation is very effective in healing of the fractures (Figures 4-6).
Summary and Conclusions Table 1. Bone Metastases
Primary Site Breast Lung Prostate Colon Cervix Thyroid Head and Neck Eosophagus Pancreas Total
Number of Patients 40 30 25 7 3 3 2 1 1
112
Vertebrae
Location of Metastases Pelvis Long Bones Ribs
29 18 14 5 1
19 10 9 3 2
2 1 1
1 72
13 6 4
Skull
6 4 7
4
1 1
-
2 1
important. 43
25
18
6
Table 2. Pain Status with Time and Primary Tumor Site Following Local Irradiation Time
No Change
1 2 3
15% 12% 10%
1 2 3
20% 15% 15%
1 2 3
45% 30% 15%
(Weeks)
910
Metastatic bone disease can cause cancer patients to become bedridden from pain and/or develop pathological fractures with or without neurological deficit. It is extremely important to keep a cancer patient ambulatory as long as possible to avoid further complications such as decubitus ulcers and hypercalcemia which will further complicate management. Therefore, the early diagnosis and effective treatment of metastatic bone disease is extremely
Improved Breast (40 pts) 25% 30% 20% Lung (30 pts) 15% 20% 10% Prostate (25 pts) 5% 10% 5%
Relieved
Worse
55% 53% 60%
5% 5% 10%
65% 65% 75%
0% 0% 0%
50% 60% 80%
0% 0% 0%
The role of surgery in the management of metastatic bone disease is intramedullary fixation for pathological fractures of long bones and laminectomy for cord compression from pathological fractures of vertebral bodies. However, these procedures do not control the pathological process, so the tumor continues to grow and further destroy bone, rendering the surgical procedure useless. Therefore, following intramedullary fixation or laminectomy for metastatic bone cancer, definitive treatment to destroy the tumor should be given. While hormone therapy in the management of metastatic bone disease from prostate4 and breast5 cancer has been proved useful, the percentage of response is very low. No chemotherapeutic agent has been proved to be useful for the treatment of metastatic bone
JOURNAL OF THE NATIONAL MEDICAL ASSOCIATION, VOL. 70, NO. 12, 1978
Figure 4. X-ray of the right humerus showing pathological fracture in the lower part. The patient had breast cancer.
Figure 2. X-ray showing lytic bone metastases in the n-eck of the right femur and subtrochantic region of the left femur.
.
.:~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~.~ . ~.
I~~~~~~~~~
Figure 5. X-ray shows external immobilization of the pathological fracture shown in Figure 4 and irradliation field.
Figure 3. Pelvic x-ray of the patient shown in Figure 2 following radiotherapy. There is good new bone formation on the left side. The patient developed a pathological fracture on the right side and required a prosthesis. cancer. The most effective modality of treatment of the metastatic bone cancer is radiotherapy. Local irradiation of the bone metastasis not only relieves pain in most paients by reducing tumor volume, it also helps new bone formation by destroying the tumor. New bone formation can only take place when at least a part of the periosteum is present. If the outline of the bone with metastatic cancer cannot be seen on x-ray, new bone formation cannot take place even if the entire tumor is completely destroyed by irradiation. In this situation, bone fragments should be proximated for new bone formation.
ato.
Therefore, early diagnosis and immediate local irradiation are essential in the management of metastatic bone cancer. Literature Cited 1. Jaffee HL: Tumors and Tumorous Conditions of the Bones and Joints. Philadelphia, Lea and Febiger, 1958, pp 154-165 2. Abrams HL, Spiro R, Goldstein N: Metastases in carcinoma: Analysis of 1,000 autopsied cases. Cancer 3:74-85, 1950 3. Kumar PP: Metastases to the bones of the hand. J Natl Med Assoc 67:275-276, 1975 4. Huggines C, Hodges CV: Studies on prostate cancer: Effects of castration, estrogen and androgen injection on serum phosphatases in metastatic carcinoma of the prostate. Cancer Res 1:293-297, 1941 5. Kennedy BJ: Hormone therapy for advanced breast cancer. Cancer 18:1551-1557, 1965
JOURNAL OF THE NATIONAL MEDICAL ASSOCIATION, VOL. 70, NO. 12, 1978
911
Pain relief from bone metastases is achieved in 80 percent of patients by local irradiation. Response to local irradiation is much faster in metastases from breast and lung than in prostate bone metastases. Local irradiation is also very effective in preventing pathological fractures in lytic bone lesions, and healing of the pathological fractures by new bone formation. Although much attention is given to treatment of primary cancers, less is said about management of the metastatic cancers from which most cancer patients die ultimately. Seventy percent of patients with cancer have metastasis to bone at autopsy. ' Primary sites of cancer which metastasize to bone in decending order of frequency are breast, prostate, lung, thyroid, kidney, pancreas, cervix, stomach, colorectum, ovary, and esophagus.2 In descending order of frequency, bones that are most commonly involved with metastatic cancer are the spine, pelvis, femur, ribs, skull, and humerus. Metastases to bones of the forearm, wrist, and hand and to bones of the leg, ankle, and foot occur infrequently. However, bone metastasis can occur anywhere from head to toe.3 Therefore, while doing a bone survey for metastatic disease, extremities
Requests for reprints should be addressed to P. Pradeep Kumar, MD, Associate Professor, Department of Radiotherapy, Howard University Hospital, 2041 Georgia Avenue, NW, Washington, DC 20060.
should not be excluded from the study. Procedures that are most valuable in the diagnosis of metastatic bone disease are, in order of diminishing accuracy, bone marrow biopsy, bone marrow aspiration, bone scan, and x-rays. Bones are not the number one site for metastatic disease in all cancer patients. Most cancer patients treated for metastatic disease in this Department of Radiotherapy have bone metastases. The earliest symptom of metastatic bone disease is pain. Patients with metastatic disease in the lymph nodes, lungs, and liver can remain asymptomatic for long periods of time before metastases are detected. With the exception of carcinoma of the prostate, where metastasis usually gives rise to a condensation of bone, areas of skeletal invasion by malignant neoplasms are characteristically destructive. In individual cases, however, the opposite effect may be noted, and a carcinoma of the breast or stomach occasionally may give rise to formative or osteoblastic metastases, whereas carcinoma of the prostate sometimes induces destructive or osteolytic lesions.
JOURNAL OF THE NATIONAL MEDICAL ASSOCIATION, VOL. 70, NO. 12, 1978
Disability from pain is a prominent feature of metastatic bone cancer. However, occasionally pathologic fracture may be the first indication that metastasis to bone has taken place. Less often, a metastasis may be the first evidence of primary disease. Both bone pain and pathological fractures from metastatic bone disease can cause a cancer patient to be bedridden, leading to further complications such as decubitus ulcers and hypercalcemia (Figure 1). Pathologic fractures of the spine can also cause permanent neurological deficit. Therefore, it is extremely important to diagnose and treat metastatic bone disease before the development of complications, which make management of a cancer patient much more difficult and the prognosis worse.
Materials and Methods Over five years, 112 cancer patients with metastatic bone disease were treated in the Department of Radiotherapy at Howard University Hospital. The sites of the primary and metastatic bone disease are given in Table 1. Three common primary carcinomas with metastatic bone disease are breast, lung, and prostate. In these three primary tumors, the sites of bone metastases in the order of descending frequency are vertebrae, pelvis, long bones of the thighs and arms, ribs, and skull. All patients with bone metastases referred for radiotherapy received a 909
3,000 rad tumor dose in 15 fractions over a three-week period. Relief of pain is achieved in almost 80 percent of patients. However, in patients with metastatic breast and lung carcinomas, pain relief was achieved much earlier than in metastatic prostatic cancer (Table 2). This slower response of pain to radiation in metastatic prostate cancer is consistent with the hypothesis that slowly growing tumors, such as those in the prostate, respond more slowly.
Patients with metastatic bone disease, admitted in wheelchairs or stretchers *and requiring hospitalization due to severe pain, become ambulatory as soon as the pain is relieved. Early ambulation is not only important in preventing complications like decubitus ulcers and hypercalcemia; it also reduces hospitalization costs and relieves pressure on relatives attending these patients at home (Figure 1). Local bone irradiation is not only
RT Pain
Pathological fractures
it
With
RT
or
without
neurological deficits
External or internal fixation + RT Bed Ridden
1~
Decubitus ulcers, Hypercalcemia Figure 1. Complications of bone metastases and their prevention. RTRadiotherapy
very effective in relieving pain from metastatic bone disease but it also helps in new bone formation by destroying tumor cells. New bone formation is important in preventing pathological fractures which require external or internal immobilization and long convalescence. However, large lytic lesions in vulnerable weightbearing bony parts like the neck of the femur and vertebral bodies should be stabilized prior to irradiation (internally in the former and externally in the latter) in order to prevent pathological fracture (Figures 2 and 3). Once a pathological fracture develops from metastatic bone disease, either external or internal immobilization becomes mandatory. This should be followed by local irradiation. The fractured fragments should be properly proximated and totally immobilized so that new bone formation can occur. Once this is achieved, local irradiation is very effective in healing of the fractures (Figures 4-6).
Summary and Conclusions Table 1. Bone Metastases
Primary Site Breast Lung Prostate Colon Cervix Thyroid Head and Neck Eosophagus Pancreas Total
Number of Patients 40 30 25 7 3 3 2 1 1
112
Vertebrae
Location of Metastases Pelvis Long Bones Ribs
29 18 14 5 1
19 10 9 3 2
2 1 1
1 72
13 6 4
Skull
6 4 7
4
1 1
-
2 1
important. 43
25
18
6
Table 2. Pain Status with Time and Primary Tumor Site Following Local Irradiation Time
No Change
1 2 3
15% 12% 10%
1 2 3
20% 15% 15%
1 2 3
45% 30% 15%
(Weeks)
910
Metastatic bone disease can cause cancer patients to become bedridden from pain and/or develop pathological fractures with or without neurological deficit. It is extremely important to keep a cancer patient ambulatory as long as possible to avoid further complications such as decubitus ulcers and hypercalcemia which will further complicate management. Therefore, the early diagnosis and effective treatment of metastatic bone disease is extremely
Improved Breast (40 pts) 25% 30% 20% Lung (30 pts) 15% 20% 10% Prostate (25 pts) 5% 10% 5%
Relieved
Worse
55% 53% 60%
5% 5% 10%
65% 65% 75%
0% 0% 0%
50% 60% 80%
0% 0% 0%
The role of surgery in the management of metastatic bone disease is intramedullary fixation for pathological fractures of long bones and laminectomy for cord compression from pathological fractures of vertebral bodies. However, these procedures do not control the pathological process, so the tumor continues to grow and further destroy bone, rendering the surgical procedure useless. Therefore, following intramedullary fixation or laminectomy for metastatic bone cancer, definitive treatment to destroy the tumor should be given. While hormone therapy in the management of metastatic bone disease from prostate4 and breast5 cancer has been proved useful, the percentage of response is very low. No chemotherapeutic agent has been proved to be useful for the treatment of metastatic bone
JOURNAL OF THE NATIONAL MEDICAL ASSOCIATION, VOL. 70, NO. 12, 1978
Figure 4. X-ray of the right humerus showing pathological fracture in the lower part. The patient had breast cancer.
Figure 2. X-ray showing lytic bone metastases in the n-eck of the right femur and subtrochantic region of the left femur.
.
.:~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~.~ . ~.
I~~~~~~~~~
Figure 5. X-ray shows external immobilization of the pathological fracture shown in Figure 4 and irradliation field.
Figure 3. Pelvic x-ray of the patient shown in Figure 2 following radiotherapy. There is good new bone formation on the left side. The patient developed a pathological fracture on the right side and required a prosthesis. cancer. The most effective modality of treatment of the metastatic bone cancer is radiotherapy. Local irradiation of the bone metastasis not only relieves pain in most paients by reducing tumor volume, it also helps new bone formation by destroying the tumor. New bone formation can only take place when at least a part of the periosteum is present. If the outline of the bone with metastatic cancer cannot be seen on x-ray, new bone formation cannot take place even if the entire tumor is completely destroyed by irradiation. In this situation, bone fragments should be proximated for new bone formation.
ato.
Therefore, early diagnosis and immediate local irradiation are essential in the management of metastatic bone cancer. Literature Cited 1. Jaffee HL: Tumors and Tumorous Conditions of the Bones and Joints. Philadelphia, Lea and Febiger, 1958, pp 154-165 2. Abrams HL, Spiro R, Goldstein N: Metastases in carcinoma: Analysis of 1,000 autopsied cases. Cancer 3:74-85, 1950 3. Kumar PP: Metastases to the bones of the hand. J Natl Med Assoc 67:275-276, 1975 4. Huggines C, Hodges CV: Studies on prostate cancer: Effects of castration, estrogen and androgen injection on serum phosphatases in metastatic carcinoma of the prostate. Cancer Res 1:293-297, 1941 5. Kennedy BJ: Hormone therapy for advanced breast cancer. Cancer 18:1551-1557, 1965
JOURNAL OF THE NATIONAL MEDICAL ASSOCIATION, VOL. 70, NO. 12, 1978
911
