EuropeanJournalof
Nuclear Medicine
Original article
Assessment of anthracycline-induced myocardial damage by quantitative indium 111 myosin-specific monoclonal antibody studies* Ignasi Carri61, Montserrat Estorch 1, Lluis Berne. 1, Josep R. Germ& 2, Carmen Alonso 2, Belen Ojeda, Luis de Andr6s 2, Antonio Lopez-Pousa 2, Carlos Martinez-Duncker 1, and Gustavo Tortes 1 Departments of 1 Nuclear Medicine and 20ncology, Hospital de Sant Pau, Pare Claret 167, E-08025 Barcelona, Spain Received 6 April and in revised form 15 May 1991
Abstract. To assess chemotherapeutically induced myocardial damage, myosin-specific antibody scans and ejection fraction measurements were performed in 32 patients with breast cancer and in 9 patients with other tumours. All patients had received chemotherapy including anthracyclines. The ejection fraction decreased by > 10% in 14 of 41 (34%) patients after chemotherapy. Antimyosin uptake in the myocardium was observed in 38 of 41 (92%) patients after chemotherapy. Antimyosin uptake was quantified by means of a heart-to-lung ratio, revealing a correlation between the degree of antimyosin uptake in the myocardium and the cumulative dose of anthracycline. Patients with a decreased ejection fraction showed more intense antimyosin uptake, indicating more severe myocardial damage. A higher degree of antimyosin uptake was found in 17 breast cancer patients treated with doxorubicin compared with 15 patients treated with mitoxantrone. We conclude that antimyosin studies provide a sensitive, non-invasive method to monitor myocardial damage in patients treated with anthracyclines. Antimyosin uptake in the myocardium precedes ejection fraction deterioration. This technique may be helpful in the early identification of patients at risk of congestive heart failure during chemotherapy including anthracyclines. Key words." Myosin-specific monoclonal antibody stu-
dies - Cardiotoxicity - Anthracycline toxicity Eur J Nucl Med (1991) 18:806-812
Introduction
Anthracyclines are effective chemotherapeutic agents used alone or in combination chemotherapy. They are employed in the treatment of breast cancer, lymphomas * This work has been supported by grant DGICYT PM89-0125 and by a research grant from Amersham Ib6rica Offprint requests to: I. Carri6
and various solid turnouts. Their efficacy, however, depends upon high cumulative doses, and it is limited by the appearance of toxicity. Acute toxicity includes haematologic and non-haematologic reactions (nausea and vomiting, alopecia and fatigue), but the most serious toxic effect is the appearance of cardiomyopathy (Schwartz et al. 1987). This type of delayed toxicity is related to the cumulative dose administered. It has been shown that after reaching a cumulative dose of 500 mg/m 2, additional treatment produces an increasing incidence of clinically significant, and often fatal, cardiomyopathy (Piver et al. 1985). Therefore, cancer patients under anthracycline therapy require cardiac monitoring to assess cardiotoxicity. Patients at risk of congestive heart failure benefit from early identification, because they can still receive high cumulative doses if the schedule of administration is modified to avoid heart failure and appropriate guidelines are used in their management (Schwartz et al. 1987; Hortobagyi et al. 1989). Detection of anthracycline cardiotoxicity is performed by serial ejection fraction measurements or sequential endomyocardial biopsies. It has been shown that the single measurement of ejection fraction at rest is an insensitive method to detect patients at risk of congestive heart failure (Billingham and Bristow 1984). The performance of rest/exercise ejection fraction measurements results in an increase in sensitivity with a loss of specificity (McKillop et al. 1983). In addition, many cancer patients are not able to exercise adequately. Endomyocardial biopsy with electron microscopy of the specimens is more sensitive than functional assessment but is invasive, of high cost and not widely available. Cardiac monitoring with serial ejection fraction measurements provides effective guideline criteria to reduce the incidence and severity of congestive heart failure in anthracycline therapy (Schwartz et al. 1987; Choi et al. 1983). However, a noninvasive test capable of identifying patients at risk of heart failure before the ejection fraction deteriorates would have clinical utility. © Springer-Verlag 1991
807 I n d i u m 111 m y o s i n - s p e c i f i c a n t i b o d y studies a l l o w in vivo n o n - i n v a s i v e d e t e c t i o n o f m y o c a r d i a l d a m a g e . B i n d i n g o f this a n t i b o d y to i n t r a c e l l u l a r m y o s i n t a k e s p l a c e o n l y w h e n s a r c o l e m m a l d i s r u p t i o n o c c u r s a n d the cell is i r r e v e r s i b l y d a m a g e d ( K h a w et al. 1986). A n t i m y o sin studies h a v e b e e n s h o w n to be sensitive in the detect i o n o f i n f a r c t ( K h a w et at. 1986), m y o c a r d i t i s ( Y a s u d a et al. 1987; O b r a d o r et al. 1989) a n d c a r d i a c r e j e c t i o n (Ballester et al. 1988). We h a v e r e c e n t l y s h o w n t h a t the m o r p h o l o g i c a l d a m a g e in the m y o c y t e s p r e s e n t in d o x o r u b i c i n t o x i c i t y c a n be d e t e c t e d b y a n t i m y o s i n scans (Est o r c h et al. 1990). This s t u d y w a s u n d e r t a k e n to assess the r e l a t i o n s h i p b e t w e e n the c u m u l a t i v e d o s e o f a n t h r a c y c l i n e s a n d the i n t e n s i t y o f a n t i m y o s i n u p t a k e in c a n c e r p a t i e n t s , to assess the r e l a t i o n s h i p b e t w e e n a n t i m y o s i n u p t a k e a n d the decrease in ejection f r a c t i o n d u r i n g c h e m o t h e r a p y a n d to c o m p a r e t w o different a n t h r a c y c l i n e derivatives.
Patients and methods Breast cancer. We studied 32 consecutive women (mean age 49
years, range 27-68 years) with the histological diagnosis of breast cancer (T3b-T, ~ and/or metastatic disease, American Joint Commission in Cancer Staging) eligible for chemotherapy including anthracyclines (doxorubicin or mitoxantrone). Patients had oestrogen receptor-negative tumours, had not responded to hormonal treatment, or presented with life-threatening disease requiring immediate chemotherapy. None had a history of hypertension, previous cardiac disease or previous chemotherapy or mediastinal radiotherapy. All patients had adequate hepatic and renal function; none of them had evidence of central nervous system, mediastinal or cardiac metastases. Informed consent was obtained from all patients. In 17 patients chemotherapy was administered in 10 cycles of cyclophosphamide (600 mg/m2), doxorubicin (50 mg/m 2) and 5fluorouracil (600 mg/m2). Doxorubicin and 5-fluorouracil were administered by direct intravenous injection; cyclophosphamide was injected over 30 min diluted in 250 ml physiological saline. Courses were repeated every 3 weeks after haematologic testing. In 15 patients chemotherapy was administered in 10 cycles of cyclophosphamide (600 mg/m2), mitoxantrone (12 mg/m 2) and 5fluorouracil (600 mg/m2). 5-Fluorouracil was administered by direct intravenous injection; cyclophosphamide and mitoxantrone were injected dyer 30 rain, diluted in 250 ml of physiological saline. Courses were repeated every 3 weeks after haematologic testing. Patients received chemotherapy including doxorubicin or mitoxantrone at random, as part of a continuing trial to compare the efficacy of both drugs. Other tumours. We studied 9 patients with sarcoma (5 patients),
oat cell carcinoma (2 patients) and non-Hodgkin's lymphoma (2 patients). Regimens utilizing doxorubicin were based on chemotherapeutic protocol and disease status. None of the patients had received mediastinal radiotherapy. Doxorubicin was administered every 3 4 weeks at a dose of 50-100 mg/m 2. The total cumulative dose of doxorubicin in this group oscillated between 600 and 1090 mg/m 2. Congestive heart failure was defined according to the New York Heart Association (class III-IV). Clinical follow-up after chemotherapy covered 4-15 months.
Ejection fraction measurements. Left ventricular ejection fraction
was measured in the group of patients with breast cancer before and after 10 cycles of chemotherapy (cumulative dose of doxorubicin 500 mg/m 2 or mitoxantrone 120 mg/m2). Eight patients were studied at an intermediate cumulative dose of doxorubicin (200300 rag/m2). Left ventricular ejection fraction was measured in patients with other turnouts at their maximal cumulative dose of doxorubicin (600-1090 mg/m2). After in vivo red blood cell labelling with 25 mCi of 99myc and with the patients lying supine, gated blood pool scans were acquired with a large field-of-view camera (Siemens Orbiter ZLC with a high resolution collimator linked to a Siemens Microdelta computer) in the left anterior oblique (LAO) 30°-50 ° projection and 5°-10 ° caudal tilt to provide the best separation between both ventricles and atria. The cardiac cycle was separated into 30 frames of 64 x 64, with a minimum of 300000 counts collected in each frame. Data were stored on a magnetic disk for subsequent analysis. Left ventricular ejection fraction was measured using a semiautomatic edge detection and counts technique with a varying region of interest. Fourier phase and amplitude images were generated to help trace regions of interest. Antimyosin studies. Antimyosin studies were performed within the
week of left ventricular ejection fraction measurements after chemotherapy was completed. Eight patients with breast cancer underwent antimyosin studies before chemotherapy and at an intermediate cumulative dose of doxorubicin (200-300 mg/m2). A dose of 0.5 mg of R11-D10-Fab-diethylenetriamine pentaacetic acid (Centocor Europe, Leiden) labelled with 2 mCi of 111In was administered by slow intravenous injection. Planar scans were obtained 48 h later using a medium energy collimator with a 20% window centred on both peaks of 111In at a preset time of 10 min. Scans were stored in 128 x 128 frames. The presence of antimyosin uptake in the heart was assessed using a four-step score (Carri6 et al. 1988); 0, no uptake; 1, mild or faint uptake; 2, clear but moderate uptake; and 3, intense myocardial uptake. A quantitative method was then applied (Carri6 et al. 1988). This consisted of drawing a region of interest on the heart and regions on the lungs on the anterior view of the thorax (Fig. 1). A heart-to-lung ratio was obtained by dividing average counts per pixel in the heart by average counts per pixel in the lungs. A cutoff point of > 1.58 (normal value 1.46 + 0.4+ 3 standard deviations) was used to define abnormal studies (Carri6 et al. 1988; Obrador et al. 1989). Statistical analysis. Results are expressed as mean_+ SD with nonparametric analysis of groups using the Mann-Whitney and Wilcoxon tests and one-way ANOVA. Regression analysis was used to assess correlation between variables. ~2 analysis was used when appropriate. The statistical package for social sciences (SPSS/PC) was used.
Results B r e a s t cancer
In p a t i e n t s with b r e a s t cancer, the left v e n t r i c u l a r eject i o n f r a c t i o n b e f o r e c h e m o t h e r a p y was 59.8% _+ 7 % a n d after c h e m o t h e r a p y was 5 3 . 8 % _ + 9 % (NS) (Table 1). E i g h t o f 32 p a t i e n t s p r e s e n t e d w i t h a decrease in left v e n t r i c u l a r ejection f r a c t i o n > 10% in a b s o l u t e ejection f r a c t i o n units. T h e ejection f r a c t i o n b e f o r e c h e m o t h e r a -
8O8 Table 1. Results of antimyosin studies and left ventricular ejection fraction measurements in patients with breast cancer Patients
Left ventricular ejection fraction
Antimyosin studies (heart-tolung ratio)
Before treatment
After treatment
All patients (n = 32)
59.8%+7%
53.8%_+9%
1.94_+0.25
_>10% decrease
60.3%_+8%
45%_+9%
2.15_+0.25
58.3%+7%
56.3%_+7%
1.83_+0.26
A
B
(n = 8) < 1 0 % decrease or no decrease (n=24)
py in this group was 60.3% _+8% and after chemotherapy was 45%_+9% (P 1.58 as the cutoff point, antimyosin studies were abnormal in the same 90% of patients. In the 8 patients with a decrease in ejection fraction > 10%, the heart-to-lung ratios were higher: 2.15_+0.25 (range 1.92 2.31)versus 1.83_+0.26 (range 1.4~2.2) ( P = 0.005). Seven patients had a heartto-lung ratio _>2.10. Three of them presented with symptoms of congestive heart failure. Doxorubicin. In the 17 patients treated with doxorubicin, the ejection fraction before chemotherapy was 60.6% _+ 7% and after chemotherapy was 50.5% -+ 9% ( P = 0.001) (Table 2). Seven of 17 patients exhibited a decrease in ejection fraction > 10%. Three of these patients presented with symptoms of congestive heart failure, two of them during chemotherapy and one patient 1 month after chemotherapy. Antimyosin uptake in the myocardium was observed in all patients after chemotherapy. The heart-to-lung ratio in antimyosin studies was 2.03 -+ 0.26 (range 1.62-2.70) (Fig. 2). In the group of 8 patients who underwent antimyosin studies before chemotherapy, none of the patients presented with antimyosin uptake in the myocardium before chemotherapy. The heart-to-lung ratio was 1.45_+0.04 (NS compared with normal subjects) (Fig. 2). The left ventricular ejection fraction at that time was 60.3% _+8%. When these patients were studied at an intermediate cumulative dose of 200-300 mg/m 2, antimyosin uptake in the myocar-
C
Fig. 1 A-F. Antimyosin studies in patients treated with anthracyclines. A Antirnyosin scan in a patient studied before chemotherapy; note the absence of myocardial antimyosin uptake. B Scan of a patient studied at a cumulative dose of 300 mg/m 2 of doxorubicin. C Scan of a patient studied at 500 mg/m 2 of doxorubicin. D, E Scans of patients studied at > 500 mg/m 2 of doxorubicin. F Regions of interest used to calculate the heart-to-lung ratio of patient in E
dium was observed in 6 of 8 patients. The heart-to-lung ratio was 1.64_+0.12 (range 1.52-1.85) (P 1 0 % (P
Nuclear Medicine
Original article
Assessment of anthracycline-induced myocardial damage by quantitative indium 111 myosin-specific monoclonal antibody studies* Ignasi Carri61, Montserrat Estorch 1, Lluis Berne. 1, Josep R. Germ& 2, Carmen Alonso 2, Belen Ojeda, Luis de Andr6s 2, Antonio Lopez-Pousa 2, Carlos Martinez-Duncker 1, and Gustavo Tortes 1 Departments of 1 Nuclear Medicine and 20ncology, Hospital de Sant Pau, Pare Claret 167, E-08025 Barcelona, Spain Received 6 April and in revised form 15 May 1991
Abstract. To assess chemotherapeutically induced myocardial damage, myosin-specific antibody scans and ejection fraction measurements were performed in 32 patients with breast cancer and in 9 patients with other tumours. All patients had received chemotherapy including anthracyclines. The ejection fraction decreased by > 10% in 14 of 41 (34%) patients after chemotherapy. Antimyosin uptake in the myocardium was observed in 38 of 41 (92%) patients after chemotherapy. Antimyosin uptake was quantified by means of a heart-to-lung ratio, revealing a correlation between the degree of antimyosin uptake in the myocardium and the cumulative dose of anthracycline. Patients with a decreased ejection fraction showed more intense antimyosin uptake, indicating more severe myocardial damage. A higher degree of antimyosin uptake was found in 17 breast cancer patients treated with doxorubicin compared with 15 patients treated with mitoxantrone. We conclude that antimyosin studies provide a sensitive, non-invasive method to monitor myocardial damage in patients treated with anthracyclines. Antimyosin uptake in the myocardium precedes ejection fraction deterioration. This technique may be helpful in the early identification of patients at risk of congestive heart failure during chemotherapy including anthracyclines. Key words." Myosin-specific monoclonal antibody stu-
dies - Cardiotoxicity - Anthracycline toxicity Eur J Nucl Med (1991) 18:806-812
Introduction
Anthracyclines are effective chemotherapeutic agents used alone or in combination chemotherapy. They are employed in the treatment of breast cancer, lymphomas * This work has been supported by grant DGICYT PM89-0125 and by a research grant from Amersham Ib6rica Offprint requests to: I. Carri6
and various solid turnouts. Their efficacy, however, depends upon high cumulative doses, and it is limited by the appearance of toxicity. Acute toxicity includes haematologic and non-haematologic reactions (nausea and vomiting, alopecia and fatigue), but the most serious toxic effect is the appearance of cardiomyopathy (Schwartz et al. 1987). This type of delayed toxicity is related to the cumulative dose administered. It has been shown that after reaching a cumulative dose of 500 mg/m 2, additional treatment produces an increasing incidence of clinically significant, and often fatal, cardiomyopathy (Piver et al. 1985). Therefore, cancer patients under anthracycline therapy require cardiac monitoring to assess cardiotoxicity. Patients at risk of congestive heart failure benefit from early identification, because they can still receive high cumulative doses if the schedule of administration is modified to avoid heart failure and appropriate guidelines are used in their management (Schwartz et al. 1987; Hortobagyi et al. 1989). Detection of anthracycline cardiotoxicity is performed by serial ejection fraction measurements or sequential endomyocardial biopsies. It has been shown that the single measurement of ejection fraction at rest is an insensitive method to detect patients at risk of congestive heart failure (Billingham and Bristow 1984). The performance of rest/exercise ejection fraction measurements results in an increase in sensitivity with a loss of specificity (McKillop et al. 1983). In addition, many cancer patients are not able to exercise adequately. Endomyocardial biopsy with electron microscopy of the specimens is more sensitive than functional assessment but is invasive, of high cost and not widely available. Cardiac monitoring with serial ejection fraction measurements provides effective guideline criteria to reduce the incidence and severity of congestive heart failure in anthracycline therapy (Schwartz et al. 1987; Choi et al. 1983). However, a noninvasive test capable of identifying patients at risk of heart failure before the ejection fraction deteriorates would have clinical utility. © Springer-Verlag 1991
807 I n d i u m 111 m y o s i n - s p e c i f i c a n t i b o d y studies a l l o w in vivo n o n - i n v a s i v e d e t e c t i o n o f m y o c a r d i a l d a m a g e . B i n d i n g o f this a n t i b o d y to i n t r a c e l l u l a r m y o s i n t a k e s p l a c e o n l y w h e n s a r c o l e m m a l d i s r u p t i o n o c c u r s a n d the cell is i r r e v e r s i b l y d a m a g e d ( K h a w et al. 1986). A n t i m y o sin studies h a v e b e e n s h o w n to be sensitive in the detect i o n o f i n f a r c t ( K h a w et at. 1986), m y o c a r d i t i s ( Y a s u d a et al. 1987; O b r a d o r et al. 1989) a n d c a r d i a c r e j e c t i o n (Ballester et al. 1988). We h a v e r e c e n t l y s h o w n t h a t the m o r p h o l o g i c a l d a m a g e in the m y o c y t e s p r e s e n t in d o x o r u b i c i n t o x i c i t y c a n be d e t e c t e d b y a n t i m y o s i n scans (Est o r c h et al. 1990). This s t u d y w a s u n d e r t a k e n to assess the r e l a t i o n s h i p b e t w e e n the c u m u l a t i v e d o s e o f a n t h r a c y c l i n e s a n d the i n t e n s i t y o f a n t i m y o s i n u p t a k e in c a n c e r p a t i e n t s , to assess the r e l a t i o n s h i p b e t w e e n a n t i m y o s i n u p t a k e a n d the decrease in ejection f r a c t i o n d u r i n g c h e m o t h e r a p y a n d to c o m p a r e t w o different a n t h r a c y c l i n e derivatives.
Patients and methods Breast cancer. We studied 32 consecutive women (mean age 49
years, range 27-68 years) with the histological diagnosis of breast cancer (T3b-T, ~ and/or metastatic disease, American Joint Commission in Cancer Staging) eligible for chemotherapy including anthracyclines (doxorubicin or mitoxantrone). Patients had oestrogen receptor-negative tumours, had not responded to hormonal treatment, or presented with life-threatening disease requiring immediate chemotherapy. None had a history of hypertension, previous cardiac disease or previous chemotherapy or mediastinal radiotherapy. All patients had adequate hepatic and renal function; none of them had evidence of central nervous system, mediastinal or cardiac metastases. Informed consent was obtained from all patients. In 17 patients chemotherapy was administered in 10 cycles of cyclophosphamide (600 mg/m2), doxorubicin (50 mg/m 2) and 5fluorouracil (600 mg/m2). Doxorubicin and 5-fluorouracil were administered by direct intravenous injection; cyclophosphamide was injected over 30 min diluted in 250 ml physiological saline. Courses were repeated every 3 weeks after haematologic testing. In 15 patients chemotherapy was administered in 10 cycles of cyclophosphamide (600 mg/m2), mitoxantrone (12 mg/m 2) and 5fluorouracil (600 mg/m2). 5-Fluorouracil was administered by direct intravenous injection; cyclophosphamide and mitoxantrone were injected dyer 30 rain, diluted in 250 ml of physiological saline. Courses were repeated every 3 weeks after haematologic testing. Patients received chemotherapy including doxorubicin or mitoxantrone at random, as part of a continuing trial to compare the efficacy of both drugs. Other tumours. We studied 9 patients with sarcoma (5 patients),
oat cell carcinoma (2 patients) and non-Hodgkin's lymphoma (2 patients). Regimens utilizing doxorubicin were based on chemotherapeutic protocol and disease status. None of the patients had received mediastinal radiotherapy. Doxorubicin was administered every 3 4 weeks at a dose of 50-100 mg/m 2. The total cumulative dose of doxorubicin in this group oscillated between 600 and 1090 mg/m 2. Congestive heart failure was defined according to the New York Heart Association (class III-IV). Clinical follow-up after chemotherapy covered 4-15 months.
Ejection fraction measurements. Left ventricular ejection fraction
was measured in the group of patients with breast cancer before and after 10 cycles of chemotherapy (cumulative dose of doxorubicin 500 mg/m 2 or mitoxantrone 120 mg/m2). Eight patients were studied at an intermediate cumulative dose of doxorubicin (200300 rag/m2). Left ventricular ejection fraction was measured in patients with other turnouts at their maximal cumulative dose of doxorubicin (600-1090 mg/m2). After in vivo red blood cell labelling with 25 mCi of 99myc and with the patients lying supine, gated blood pool scans were acquired with a large field-of-view camera (Siemens Orbiter ZLC with a high resolution collimator linked to a Siemens Microdelta computer) in the left anterior oblique (LAO) 30°-50 ° projection and 5°-10 ° caudal tilt to provide the best separation between both ventricles and atria. The cardiac cycle was separated into 30 frames of 64 x 64, with a minimum of 300000 counts collected in each frame. Data were stored on a magnetic disk for subsequent analysis. Left ventricular ejection fraction was measured using a semiautomatic edge detection and counts technique with a varying region of interest. Fourier phase and amplitude images were generated to help trace regions of interest. Antimyosin studies. Antimyosin studies were performed within the
week of left ventricular ejection fraction measurements after chemotherapy was completed. Eight patients with breast cancer underwent antimyosin studies before chemotherapy and at an intermediate cumulative dose of doxorubicin (200-300 mg/m2). A dose of 0.5 mg of R11-D10-Fab-diethylenetriamine pentaacetic acid (Centocor Europe, Leiden) labelled with 2 mCi of 111In was administered by slow intravenous injection. Planar scans were obtained 48 h later using a medium energy collimator with a 20% window centred on both peaks of 111In at a preset time of 10 min. Scans were stored in 128 x 128 frames. The presence of antimyosin uptake in the heart was assessed using a four-step score (Carri6 et al. 1988); 0, no uptake; 1, mild or faint uptake; 2, clear but moderate uptake; and 3, intense myocardial uptake. A quantitative method was then applied (Carri6 et al. 1988). This consisted of drawing a region of interest on the heart and regions on the lungs on the anterior view of the thorax (Fig. 1). A heart-to-lung ratio was obtained by dividing average counts per pixel in the heart by average counts per pixel in the lungs. A cutoff point of > 1.58 (normal value 1.46 + 0.4+ 3 standard deviations) was used to define abnormal studies (Carri6 et al. 1988; Obrador et al. 1989). Statistical analysis. Results are expressed as mean_+ SD with nonparametric analysis of groups using the Mann-Whitney and Wilcoxon tests and one-way ANOVA. Regression analysis was used to assess correlation between variables. ~2 analysis was used when appropriate. The statistical package for social sciences (SPSS/PC) was used.
Results B r e a s t cancer
In p a t i e n t s with b r e a s t cancer, the left v e n t r i c u l a r eject i o n f r a c t i o n b e f o r e c h e m o t h e r a p y was 59.8% _+ 7 % a n d after c h e m o t h e r a p y was 5 3 . 8 % _ + 9 % (NS) (Table 1). E i g h t o f 32 p a t i e n t s p r e s e n t e d w i t h a decrease in left v e n t r i c u l a r ejection f r a c t i o n > 10% in a b s o l u t e ejection f r a c t i o n units. T h e ejection f r a c t i o n b e f o r e c h e m o t h e r a -
8O8 Table 1. Results of antimyosin studies and left ventricular ejection fraction measurements in patients with breast cancer Patients
Left ventricular ejection fraction
Antimyosin studies (heart-tolung ratio)
Before treatment
After treatment
All patients (n = 32)
59.8%+7%
53.8%_+9%
1.94_+0.25
_>10% decrease
60.3%_+8%
45%_+9%
2.15_+0.25
58.3%+7%
56.3%_+7%
1.83_+0.26
A
B
(n = 8) < 1 0 % decrease or no decrease (n=24)
py in this group was 60.3% _+8% and after chemotherapy was 45%_+9% (P 1.58 as the cutoff point, antimyosin studies were abnormal in the same 90% of patients. In the 8 patients with a decrease in ejection fraction > 10%, the heart-to-lung ratios were higher: 2.15_+0.25 (range 1.92 2.31)versus 1.83_+0.26 (range 1.4~2.2) ( P = 0.005). Seven patients had a heartto-lung ratio _>2.10. Three of them presented with symptoms of congestive heart failure. Doxorubicin. In the 17 patients treated with doxorubicin, the ejection fraction before chemotherapy was 60.6% _+ 7% and after chemotherapy was 50.5% -+ 9% ( P = 0.001) (Table 2). Seven of 17 patients exhibited a decrease in ejection fraction > 10%. Three of these patients presented with symptoms of congestive heart failure, two of them during chemotherapy and one patient 1 month after chemotherapy. Antimyosin uptake in the myocardium was observed in all patients after chemotherapy. The heart-to-lung ratio in antimyosin studies was 2.03 -+ 0.26 (range 1.62-2.70) (Fig. 2). In the group of 8 patients who underwent antimyosin studies before chemotherapy, none of the patients presented with antimyosin uptake in the myocardium before chemotherapy. The heart-to-lung ratio was 1.45_+0.04 (NS compared with normal subjects) (Fig. 2). The left ventricular ejection fraction at that time was 60.3% _+8%. When these patients were studied at an intermediate cumulative dose of 200-300 mg/m 2, antimyosin uptake in the myocar-
C
Fig. 1 A-F. Antimyosin studies in patients treated with anthracyclines. A Antirnyosin scan in a patient studied before chemotherapy; note the absence of myocardial antimyosin uptake. B Scan of a patient studied at a cumulative dose of 300 mg/m 2 of doxorubicin. C Scan of a patient studied at 500 mg/m 2 of doxorubicin. D, E Scans of patients studied at > 500 mg/m 2 of doxorubicin. F Regions of interest used to calculate the heart-to-lung ratio of patient in E
dium was observed in 6 of 8 patients. The heart-to-lung ratio was 1.64_+0.12 (range 1.52-1.85) (P 1 0 % (P
