European ~ h It',l~,-ar Journalof I ~1~,!%~1~;C1,/
Eur. J. Nucl. Med. 4, 207-210 (1979)
Medicine © by Springer-Verlag 1979
The Value of Whole Body Bone Scan in the Pre-Operative Assessment in Carcinoma of the Breast P. Hahn 1, K.J. Vikterl6f z, H. Rydman 3, K.W. Beckman z, and O. Blom 3 1 Department of Oncology 2 Department of Radiation Physics 3 Department of Diagnostic Radiology, Orebro Regional Hospital, 0rebro, Sweden
Abstract. In 126 patients with primary breast cancer a patient moving whole body bone scan was performed when they first presented. None of the patients in stage I had an evidence of skeletal metastases. Two patients (3%) of 62 in stage II and 4 patients (17%) in stage III had evidence of skeletal metastases. It appears that whole body scanning is the most accurate, sensitive and convenient method of detecting osseous metastases and of staging breast cancer. This investigation should be carried out pre-operatively. Detection of early asymptomatic bony metastases will provide a better planning of treatment with rational approach.
Introduction Carcinoma of the breast is the most common malignancy in woman in Sweden. About 7% develop the disease and about 40-50% of those die within 10 years. It accounts for 25% of all female patients with cancer and is the leading cause of death in women. In spite o f better techniques of radiotherapy and surgery, there has been no significant change noted in the past 50 years. The treatment of breast cancer depends on the stage of the disease and if the disease is disseminated at the time of their primary treatment, local therapy with surgery and radiation cannot improve the prognosis. The skeleton is the commonest site of distant metastases from breast cancer and is frequently the first organ in which metastases are detected. Since the prognosis depends on whether the cancer has already disseminated when the patient is first presented, it is important to detect the metastases at the time of their primary treatment. Send offprint requests to : P. Hahn, M.D., Department of Oncology, Orebro Regional Hospital, S-701 85 Orebro, Sweden
This prospective study was undertaken to assess the value of pre-operative whole body scan in a group of unselected patients with cancer of the breast from a 250,000 population area.
Patients and Methods During 1977 a total of 126 female patients with carcinoma of the breast were seen at our Department of Oncology, 0rebro Regional Hospital. All patients had pre-operative routine whole body scans regardless of the stage of the disease. All the patients had a careful clinical examination, electrocardiography and bone radiography. Bone radiography consist of antero-posterior and lateral views of the thoracic, dorsal and lumbar spine, a posterior-anterior X-ray of the chest and a anterior-posterior film of the pelvis. Bone radiography of the skull and cervical vertebrae were not taken regularly as a routine. The bone radiography and the scintigraphy were examined independently by different observers and the findings recorded and compared. Interpretation of whole body scan were reported as negative (normal) and positive (increased uptake of radionuclide). Positive scans were subdivided into (a) probably normal (changes due to benign cause), (b) suspicious (either metastatic disease or benign condition), (c) metastasis. In suspicious cases additional examination with tomography of the region of interest and hydroxyproline excretion in urine were measured [7] to support the interpretation of bone scan. The mean age of the patients was 65.
Controls. 100 patients with no malignant disease were used as a control. Apparatus. We have deviced our own patient moving whole body scan which consist of two General Electric Maxicameras (Fig. 2). These cameras offer high resolution in combination with high sensitivity and are specially suitable for registering the 140 KeV radiation from 99TCm. A multihole parallel diverging collimator, specially designed for whole body scan was used. The electric unit controls a moving band where the patient lies in a prone position as shown in Figure 1. The patient moves comfortably for a whole body registration. The band moves discountinously with a speed normaly about 10 cm/40 s and the band transports the patient in a step of 1 cm. Scanning time for one patient (188 cm) is about 15 min and approximately 1 million counts are recorded. During this time both posterior and anterior polaroid picture a n d X-ray
0340-6997/79/0004/0207/$01.00
208
P. H a h n et al. : The Value of Whole Body Bone Scan
Fig. 1. Patient moving whole body bone scan
Results
Fig. 2. Two opposing g a m m a cameras
film with the size of 18 x 24 cm are obtained. All patients received 15mCi 99Tcm ethylenehydroxydiphosphonate (EHDP) intravenously and pictures were taken 4 h later of the whole body skeleton. Since October 1977 we have used 12 mCi 99Tcm of methylenediphosphonate (MDP) and pictures were taken 3 h after intravenously administration.
The distribution of whole body scan interpretations according to the clinical stage is shown in Table 1. None of the 36 patients with stage I had evidence of skeletal metastases. Two patients (3%) of 62 in stage II and 4 patients of 23 (17%) in stage III had evidence of skeletal metastases. Twenty nine patients (23%) had completely normal appearing bone scans and 83 patients (66%) had probably normal (benign changes) appearing bone scans. Thus, 112 (89%) of 126 patients had no malignant lesions in initial whole body scanning. Eight patients (6%) had suspicious bone scans. Eleven patients of 36 in stage I had a 6 month routine bone scan control and none of them had conversion from initial bone scan. Twenty two patients in stage II had a 6 month control and of these one patient had evidence of skeletal metastases which were not seen on the initial bone scan. Seven patients in stage III had a 6 month control and of these one patient showed progress of skeletal metastases and one patient had a suspicious bone scan. All 6 patients with metastases on the bone scan had no symptoms of pain. Bone radiography was normal in 5 of 6 patients who had evidence of skeletal metastases. Only one patient showed skeletal metastases on initial bone radiography. In 45 patients (36%) an apparent increased diffuse uptake of radionuclide was noted in the skeletal extremities and 38 patients (30%) had diffuse increased uptake of radionuclide in the thoracic, lumbar vertebrae and hip bone regions. An apparent increased diffuse uptake of radionuclide was most frequently seen in the skeletal extremity and cervical vertebrae.
P. Hahn et al. : The Value of Whole Body Bone Scan
209
Table 1. Distribution of 126 initial whole body scans according to interpretation
Clinical stage I Clinical stage II Clinical stage III >Age50 < Age 50
(36) (62) (23) (111) (15)
Negative
Positive
Normal (29)
Probably normal (83)
Suspicious (8)
Metastasis (6)
13 12 4 22 7
21 49 13 77 6
2 4 2 7 1
0 2 4 5 1
Probably normal = changes due to benign cause; Suspicious = either metastatic disease or benign conditions
Discussion
Conventional radiography was found to be a relatively insensitive technique for detection of occult bony metastases. Skeletal metastases are often not demonstrable in the roentgenogram until bone destruction is present. A comparison between roentgen and postmortem findings, as well as experimental studies by Babaiantz, have shown that bone decalcification must reach about 50% before it is evident in the roentgen film [1, 3]. Bone radiography is still used widely in Sweden as a routine preoperative examination of skeleton and bone scanning has been used as a supplement to X-ray radiologic examinations. We feel that this situation should be reversed as the results of our study and other studies have shown that osseous metastases can be detected more early and accurately by radionuclide than by roentgenological examinations. Skeletal metastases are recognized in the bone scan as " h o t spots", due to increased local uptake of the administrated 99Tcm E H D H or M D P as illustrated in Figure 3. A localized or diffuse increased concentration of bone-seeking isotopes is not specific f o r skeletal metastases and any condition which is associated with new bone formation will show as an area of increased uptake of isotope. Increased uptake of isotope can be seen, for example, in arthrosis deformans, arthritis, Paget's disease of bone, fracture etc., and benign causes for this uptake can be seen on bone radiography and thus, can easily be excluded from malignant lesions. According to our present study, we could exclude benign disease without the help of bone radiography in 112 patients (89%) of 126 patients. Only 8 patients (8%) needed bone radiography, laboratory test (serum calcium, alkaline phosphatase and excretion of hydroxyproline in urine) and anamnesis (for instance, old multiple rib-fractures after traffic accident) to eliminate from malignant lesions. C. Hoffman et al.
Fig. 3. A 58 year-old woman with clinical stage II carcinoma of the breast demonstrated metastases in the thoracic, and lumbar spine, rib X D X and skull. Detected by initial pre-operative whole body scan. The patient was asymptomatic and the first roentgenogram was negative
found 19 of 47 patients (40%) with positive bone scans in early breast cancer [4]. Our result show none of the patients in stage I had evidence of skeletal metastases. Two patients of 62 clinical stage II and 4 patients of 23 in stage III had evidence of skeletal metastases. Galasko et al. found 72% positive scans in advanced mammary cancer [2]. Hoffman and Galasko's study did not made reference to the stage of the disease. Thus, these results do not represent the true involvment of patients with breast cancer. We had only 6 patients who had evidence of skeletal metastases at the time of their first presentation, but these number will probably increase as the time goes on. Our retrospective study of breast cancer from 1963 to 1972 showed that most metastases develop within 3 years and bone is the most frequent site of metastases [6]. There are authors who have doubts on the value of bone scanning in the initial assessment of patients with breast cancer as few patients have evidence of skeletal metastases at their first presentation and they believe that it is an expensive
210
examination. We do not think it is so. Whole body scanning is an inexpensive and convenient examination to confirm skeletal metastases. We know that patients with positive scans have a poor prognosis. Our present study showed that we can exclude malignant lesions in bone scans without help of roentgenogram in 89%. This means that a negative whole body scan alone essentially preclude radiographically evident metastases, and thus extensive radiographic skeletal surveys can be eliminated in many cases, preventing needless radiation exposure and saving the patient both time and money. Is it necessary to do bone scanning for pre-operative evaluation with clinical stage I patient? We think it is. The T N M clinical classification system does have a practical value, but it does not take into full account the nature of the tumour itself. Clinical staging provides a guide to the obvious extent of a tumour, but it fails to indicate the likelihood of occult lymphatic and blood-born metastases being present in what appears to be an early cancer, nor does it indicate the speed with which such metastases may develop. Thus, clinical stage I patients with histological malignancy grade III have a poor prognosis and can develop metastases earlier. We also feel that all patients should have a bone scan pre-operatively as a criterion of inoperability and to reclassify clinical stages. What is the use of radical mastectomy when the disease is already disseminated? What must be done with patients who have a suspicious bone scan? As we mentioned before we do tomography and take urinary hydroxyproline [7]. We do not do bone biopsy if tomography is normal. How then must patients be managed who showed no other evidence of metastatic desease except for a suspicious bone scan? We believe that these patients should be classified as a risk group and adjuvant chemotherapy together with post-operative irradiation should be given following simple mastectomy [5]. Follow-up scan should be done every 3 months
P. Hahn et al. : The Value of Whole Body Bone Scan
in suspicious cases to see if the initial bone scan changes. In conclusion, patient moving whole body bone scans seem to be a more sensitive, accurate and convenient method of detecting metastatic disease than radiography. Initial whole body scans should be done for all patients with primary breast cancer at their first presentation to determine the presence of asymptomatic occult bone metastases before the planning of treatment and also as a criterion of inoperability since in cases of dissemination, surgery becomes irrational. Radiography should be used only in suspicious cases to exclude benign lesions. If the bone scan shows metastases, the patient should be placed in stage IV.
Acknowledgements. The authors gratefully acknowledge secretarial work of Eva Litsander and Karin Millg~trdh.
References 1. Babaiantz, L. : Les ost~opathics arthrophiques. J. Radiol. Electrol. 29, 333 (1949) 2. Galasko, C.S.B.: Skeletal metastases and mammary cancer. Ann. Roy. Coll. Surg. Engl. 50 (1972) 3. Gynning; I., Langeland, P., Lindberg, S., Walderskog, B.: Localization with Sr s5 of spinal metastases in mammary cancer and changes in uptake after hormone and roentgen therapy. Acta Radiol. 55, 119-129 (1961) 4. Hoffman, C.H., Marty, R.: Bone Scanning: Its value in the preoperative evaluation of patients with suspicious breast masses. Am. J. Surgery 124 (1972) 5. Hahn, P., Hallberg, O., Vikterl6f, K.J.: Acute skin reactions of postoperative breast cancer patients receiving radiotherapy plus adjuvant chemotherapy. Am. J. Roentgenology, 130, 137 I41 (1978) 6. Hahn, P., Hallberg, O., Vikterl6f, K.J.: The efficiency of postoperative radiotherapy in carcinoma of the breast and comparison between two methods. (To be published) (1979) 7. Powels, T.J., Rosset, G., Lesse, C.L., Bondy, P.K.: Early morning hydroxyproline excretion in patients with breast cancer. Cancer 38, 25645566 (1976) Received April 18, 1978
Eur. J. Nucl. Med. 4, 207-210 (1979)
Medicine © by Springer-Verlag 1979
The Value of Whole Body Bone Scan in the Pre-Operative Assessment in Carcinoma of the Breast P. Hahn 1, K.J. Vikterl6f z, H. Rydman 3, K.W. Beckman z, and O. Blom 3 1 Department of Oncology 2 Department of Radiation Physics 3 Department of Diagnostic Radiology, Orebro Regional Hospital, 0rebro, Sweden
Abstract. In 126 patients with primary breast cancer a patient moving whole body bone scan was performed when they first presented. None of the patients in stage I had an evidence of skeletal metastases. Two patients (3%) of 62 in stage II and 4 patients (17%) in stage III had evidence of skeletal metastases. It appears that whole body scanning is the most accurate, sensitive and convenient method of detecting osseous metastases and of staging breast cancer. This investigation should be carried out pre-operatively. Detection of early asymptomatic bony metastases will provide a better planning of treatment with rational approach.
Introduction Carcinoma of the breast is the most common malignancy in woman in Sweden. About 7% develop the disease and about 40-50% of those die within 10 years. It accounts for 25% of all female patients with cancer and is the leading cause of death in women. In spite o f better techniques of radiotherapy and surgery, there has been no significant change noted in the past 50 years. The treatment of breast cancer depends on the stage of the disease and if the disease is disseminated at the time of their primary treatment, local therapy with surgery and radiation cannot improve the prognosis. The skeleton is the commonest site of distant metastases from breast cancer and is frequently the first organ in which metastases are detected. Since the prognosis depends on whether the cancer has already disseminated when the patient is first presented, it is important to detect the metastases at the time of their primary treatment. Send offprint requests to : P. Hahn, M.D., Department of Oncology, Orebro Regional Hospital, S-701 85 Orebro, Sweden
This prospective study was undertaken to assess the value of pre-operative whole body scan in a group of unselected patients with cancer of the breast from a 250,000 population area.
Patients and Methods During 1977 a total of 126 female patients with carcinoma of the breast were seen at our Department of Oncology, 0rebro Regional Hospital. All patients had pre-operative routine whole body scans regardless of the stage of the disease. All the patients had a careful clinical examination, electrocardiography and bone radiography. Bone radiography consist of antero-posterior and lateral views of the thoracic, dorsal and lumbar spine, a posterior-anterior X-ray of the chest and a anterior-posterior film of the pelvis. Bone radiography of the skull and cervical vertebrae were not taken regularly as a routine. The bone radiography and the scintigraphy were examined independently by different observers and the findings recorded and compared. Interpretation of whole body scan were reported as negative (normal) and positive (increased uptake of radionuclide). Positive scans were subdivided into (a) probably normal (changes due to benign cause), (b) suspicious (either metastatic disease or benign condition), (c) metastasis. In suspicious cases additional examination with tomography of the region of interest and hydroxyproline excretion in urine were measured [7] to support the interpretation of bone scan. The mean age of the patients was 65.
Controls. 100 patients with no malignant disease were used as a control. Apparatus. We have deviced our own patient moving whole body scan which consist of two General Electric Maxicameras (Fig. 2). These cameras offer high resolution in combination with high sensitivity and are specially suitable for registering the 140 KeV radiation from 99TCm. A multihole parallel diverging collimator, specially designed for whole body scan was used. The electric unit controls a moving band where the patient lies in a prone position as shown in Figure 1. The patient moves comfortably for a whole body registration. The band moves discountinously with a speed normaly about 10 cm/40 s and the band transports the patient in a step of 1 cm. Scanning time for one patient (188 cm) is about 15 min and approximately 1 million counts are recorded. During this time both posterior and anterior polaroid picture a n d X-ray
0340-6997/79/0004/0207/$01.00
208
P. H a h n et al. : The Value of Whole Body Bone Scan
Fig. 1. Patient moving whole body bone scan
Results
Fig. 2. Two opposing g a m m a cameras
film with the size of 18 x 24 cm are obtained. All patients received 15mCi 99Tcm ethylenehydroxydiphosphonate (EHDP) intravenously and pictures were taken 4 h later of the whole body skeleton. Since October 1977 we have used 12 mCi 99Tcm of methylenediphosphonate (MDP) and pictures were taken 3 h after intravenously administration.
The distribution of whole body scan interpretations according to the clinical stage is shown in Table 1. None of the 36 patients with stage I had evidence of skeletal metastases. Two patients (3%) of 62 in stage II and 4 patients of 23 (17%) in stage III had evidence of skeletal metastases. Twenty nine patients (23%) had completely normal appearing bone scans and 83 patients (66%) had probably normal (benign changes) appearing bone scans. Thus, 112 (89%) of 126 patients had no malignant lesions in initial whole body scanning. Eight patients (6%) had suspicious bone scans. Eleven patients of 36 in stage I had a 6 month routine bone scan control and none of them had conversion from initial bone scan. Twenty two patients in stage II had a 6 month control and of these one patient had evidence of skeletal metastases which were not seen on the initial bone scan. Seven patients in stage III had a 6 month control and of these one patient showed progress of skeletal metastases and one patient had a suspicious bone scan. All 6 patients with metastases on the bone scan had no symptoms of pain. Bone radiography was normal in 5 of 6 patients who had evidence of skeletal metastases. Only one patient showed skeletal metastases on initial bone radiography. In 45 patients (36%) an apparent increased diffuse uptake of radionuclide was noted in the skeletal extremities and 38 patients (30%) had diffuse increased uptake of radionuclide in the thoracic, lumbar vertebrae and hip bone regions. An apparent increased diffuse uptake of radionuclide was most frequently seen in the skeletal extremity and cervical vertebrae.
P. Hahn et al. : The Value of Whole Body Bone Scan
209
Table 1. Distribution of 126 initial whole body scans according to interpretation
Clinical stage I Clinical stage II Clinical stage III >Age50 < Age 50
(36) (62) (23) (111) (15)
Negative
Positive
Normal (29)
Probably normal (83)
Suspicious (8)
Metastasis (6)
13 12 4 22 7
21 49 13 77 6
2 4 2 7 1
0 2 4 5 1
Probably normal = changes due to benign cause; Suspicious = either metastatic disease or benign conditions
Discussion
Conventional radiography was found to be a relatively insensitive technique for detection of occult bony metastases. Skeletal metastases are often not demonstrable in the roentgenogram until bone destruction is present. A comparison between roentgen and postmortem findings, as well as experimental studies by Babaiantz, have shown that bone decalcification must reach about 50% before it is evident in the roentgen film [1, 3]. Bone radiography is still used widely in Sweden as a routine preoperative examination of skeleton and bone scanning has been used as a supplement to X-ray radiologic examinations. We feel that this situation should be reversed as the results of our study and other studies have shown that osseous metastases can be detected more early and accurately by radionuclide than by roentgenological examinations. Skeletal metastases are recognized in the bone scan as " h o t spots", due to increased local uptake of the administrated 99Tcm E H D H or M D P as illustrated in Figure 3. A localized or diffuse increased concentration of bone-seeking isotopes is not specific f o r skeletal metastases and any condition which is associated with new bone formation will show as an area of increased uptake of isotope. Increased uptake of isotope can be seen, for example, in arthrosis deformans, arthritis, Paget's disease of bone, fracture etc., and benign causes for this uptake can be seen on bone radiography and thus, can easily be excluded from malignant lesions. According to our present study, we could exclude benign disease without the help of bone radiography in 112 patients (89%) of 126 patients. Only 8 patients (8%) needed bone radiography, laboratory test (serum calcium, alkaline phosphatase and excretion of hydroxyproline in urine) and anamnesis (for instance, old multiple rib-fractures after traffic accident) to eliminate from malignant lesions. C. Hoffman et al.
Fig. 3. A 58 year-old woman with clinical stage II carcinoma of the breast demonstrated metastases in the thoracic, and lumbar spine, rib X D X and skull. Detected by initial pre-operative whole body scan. The patient was asymptomatic and the first roentgenogram was negative
found 19 of 47 patients (40%) with positive bone scans in early breast cancer [4]. Our result show none of the patients in stage I had evidence of skeletal metastases. Two patients of 62 clinical stage II and 4 patients of 23 in stage III had evidence of skeletal metastases. Galasko et al. found 72% positive scans in advanced mammary cancer [2]. Hoffman and Galasko's study did not made reference to the stage of the disease. Thus, these results do not represent the true involvment of patients with breast cancer. We had only 6 patients who had evidence of skeletal metastases at the time of their first presentation, but these number will probably increase as the time goes on. Our retrospective study of breast cancer from 1963 to 1972 showed that most metastases develop within 3 years and bone is the most frequent site of metastases [6]. There are authors who have doubts on the value of bone scanning in the initial assessment of patients with breast cancer as few patients have evidence of skeletal metastases at their first presentation and they believe that it is an expensive
210
examination. We do not think it is so. Whole body scanning is an inexpensive and convenient examination to confirm skeletal metastases. We know that patients with positive scans have a poor prognosis. Our present study showed that we can exclude malignant lesions in bone scans without help of roentgenogram in 89%. This means that a negative whole body scan alone essentially preclude radiographically evident metastases, and thus extensive radiographic skeletal surveys can be eliminated in many cases, preventing needless radiation exposure and saving the patient both time and money. Is it necessary to do bone scanning for pre-operative evaluation with clinical stage I patient? We think it is. The T N M clinical classification system does have a practical value, but it does not take into full account the nature of the tumour itself. Clinical staging provides a guide to the obvious extent of a tumour, but it fails to indicate the likelihood of occult lymphatic and blood-born metastases being present in what appears to be an early cancer, nor does it indicate the speed with which such metastases may develop. Thus, clinical stage I patients with histological malignancy grade III have a poor prognosis and can develop metastases earlier. We also feel that all patients should have a bone scan pre-operatively as a criterion of inoperability and to reclassify clinical stages. What is the use of radical mastectomy when the disease is already disseminated? What must be done with patients who have a suspicious bone scan? As we mentioned before we do tomography and take urinary hydroxyproline [7]. We do not do bone biopsy if tomography is normal. How then must patients be managed who showed no other evidence of metastatic desease except for a suspicious bone scan? We believe that these patients should be classified as a risk group and adjuvant chemotherapy together with post-operative irradiation should be given following simple mastectomy [5]. Follow-up scan should be done every 3 months
P. Hahn et al. : The Value of Whole Body Bone Scan
in suspicious cases to see if the initial bone scan changes. In conclusion, patient moving whole body bone scans seem to be a more sensitive, accurate and convenient method of detecting metastatic disease than radiography. Initial whole body scans should be done for all patients with primary breast cancer at their first presentation to determine the presence of asymptomatic occult bone metastases before the planning of treatment and also as a criterion of inoperability since in cases of dissemination, surgery becomes irrational. Radiography should be used only in suspicious cases to exclude benign lesions. If the bone scan shows metastases, the patient should be placed in stage IV.
Acknowledgements. The authors gratefully acknowledge secretarial work of Eva Litsander and Karin Millg~trdh.
References 1. Babaiantz, L. : Les ost~opathics arthrophiques. J. Radiol. Electrol. 29, 333 (1949) 2. Galasko, C.S.B.: Skeletal metastases and mammary cancer. Ann. Roy. Coll. Surg. Engl. 50 (1972) 3. Gynning; I., Langeland, P., Lindberg, S., Walderskog, B.: Localization with Sr s5 of spinal metastases in mammary cancer and changes in uptake after hormone and roentgen therapy. Acta Radiol. 55, 119-129 (1961) 4. Hoffman, C.H., Marty, R.: Bone Scanning: Its value in the preoperative evaluation of patients with suspicious breast masses. Am. J. Surgery 124 (1972) 5. Hahn, P., Hallberg, O., Vikterl6f, K.J.: Acute skin reactions of postoperative breast cancer patients receiving radiotherapy plus adjuvant chemotherapy. Am. J. Roentgenology, 130, 137 I41 (1978) 6. Hahn, P., Hallberg, O., Vikterl6f, K.J.: The efficiency of postoperative radiotherapy in carcinoma of the breast and comparison between two methods. (To be published) (1979) 7. Powels, T.J., Rosset, G., Lesse, C.L., Bondy, P.K.: Early morning hydroxyproline excretion in patients with breast cancer. Cancer 38, 25645566 (1976) Received April 18, 1978
