Download Using In-111 Satumomab Pendetide - FirstCarolinaCare Insurance

MP 6.01.25
Radioimmunoscintigraphy Imaging (Monoclonal Antibody Imaging) Using
In-111 Satumomab Pendetide (OncoScint) or Tc-99m Arcitumomab (IMMU4, CEA-Scan)
Medical Policy
Original Policy Date
12:2013
Section
Radiology
Issue
12:2013
Last Review Status/Date
Reviewed with literature
search/12:2013
Return to Medical Policy Index
Disclaimer
Our medical policies are designed for informational purposes only and are not an authorization,
or an explanation of benefits, or a contract. Receipt of benefits is subject to satisfaction of all
terms and conditions of the coverage. Medical technology is constantly changing, and we
reserve the right to review and update our policies periodically.
Description
Radioimmunoscintigraphy (RIS) involves the administration of radiolabeled monoclonal
antibodies (MAbs), which are directed against specific molecular targets, followed by imaging
with an external gamma camera. MAbs that react with specific cellular antigens are conjugated
with a radiolabeled isotope. The labeled antibody-isotope conjugate is then injected into the
patient and allowed to localize to the target over a 2- to 7-day period. The patient then
undergoes imaging with a nuclear medicine gamma camera, and radioisotope counts are
analyzed. Imaging can be performed with planar techniques or by using single-photon emission
computed tomography (SPECT).

Indium-111 satumomab pendetide (CYT-103, OncoScint CR/OV®) has been approved
by the U.S. Food and Drug Administration (FDA) for imaging of colorectal and ovarian
carcinomas.

Technetium-99m arcitumomab (IMMU-4, CEA-Scan®) has been approved by the FDA
for use in colorectal and ovarian carcinoma.
These RIS agents have also been used in an off-label use to evaluate other malignancies
including, but not limited to, breast cancer, lung cancer, and thyroid cancer.
OncoScint is no longer commercially available.
Policy
Radioimmunoscintigraphy using satumomab pendetide or arcitumomab as the monoclonal
antibody may be considered medically necessary in patients with known or suspected recurrent
colorectal carcinoma under the following conditions:
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
in patients with an elevated carcinoembryonic antigen level, who have no evidence of
disease with other imaging modalities (i.e., CT), in whom a second-look laparotomy is
under consideration; or

in patients with an isolated, potentially resectable recurrence identified with conventional
imaging modalities (i.e., CT), for whom the detection of additional occult lesions would
alter the surgical plan.
Other applications of radioimmunoscintigraphy using In-111 satumomab pendetide (OncoScint)
or Tc-99m-arcitumomab (IMMU-4, CEA-Scan) are considered investigational, including, but not
limited to ovarian cancer, breast cancer, medullary thyroid cancer, and lung cancer.
Policy Guidelines
PET scanning has largely replaced radioimmunoscintigraphy using satumomab pendetide or
aricutmomab as the as the imaging technique of choice to evaluate for suspected recurrent
colorectal carcinoma.
Rationale
Colon Cancer
The policy statement regarding RIS in patients with colorectal cancer is based on a 1994 TEC
Assessment (1) that concluded that the evidence was adequate to conclude that
radioimmunoscintigraphy improved health outcomes in certain patients with colorectal cancer.
Specifically, positive findings on radioimmunoscintigraphy can affect the surgical management
of patients with suspected occult cancer who would otherwise undergo second-look laparotomy
due to a rising carcinoembryonic antigen (CEA) level, or resection of a metastasis that was
incorrectly assumed to be an isolated lesion.
Additional review of the literature does not change the conclusions of the prior assessment.
However, further reports have illustrated that RIS findings may yield false-positive findings such
that biopsy or surgical confirmation of RIS findings may still be necessary to ensure appropriate
patient management. (2-6) Furthermore, Dominguez et al. (7) reported in 15 patients with
colorectal cancer that In-111 satumomab pendetide imaging had no effect on surgical
management in 67%, a beneficial effect in 13%, and a negative effect in 20% of cases.
Moffat et al. (8) reported a review of the literature using various RIS agents in colorectal cancer.
In a multicenter trial also by Moffat et al. (9) using Tc-99m-arcitumomab, RIS results were
associated with “potential clinical benefit” in 49 of 88 patients (56%) with suspected occult
colorectal cancer recurrence. In a larger analysis from this same study, RIS results provided
information that could have changed treatment planning in 89 of 210 (42%) patients.
Ovarian Cancer
The policy statement regarding RIS in patients with ovarian cancer is also based on a 1994 TEC
Assessment (1) that concluded that the evidence was inadequate to determine whether its use
was associated with beneficial health outcomes. Specifically, RIS has been investigated as a
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technique to select patients for second-look laparotomy after initial treatment for ovarian
carcinoma. However, the assessment concluded that the positive predictive value of RIS was
not fully reported in the available studies, and therefore it was not possible to determine whether
the use of RIS was a reliable basis for making patient management decisions.
Additional review of the literature does not provide sufficient evidence to demonstrate the
clinical effectiveness of RIS in ovarian cancer. (10-13) One study reviewed in the prior TEC
Assessment, Surwit et al. (14), reports sensitivity of RIS with In-111 satumomab pendetide to be
68% in 103 subjects who had suspected or proven ovarian cancer before surgical management.
However, when analysis was restricted to only patients with recurrent disease, sensitivity was
only 59%. In the overall population, specificity was only 50%. Blend et al. (12) included 29
subjects with suspected recurrent ovarian cancer in a retrospective analysis of the impact of RIS
using In-111 satumomab pendetide on management. In this study, clinical management was
influenced in 19 of 299 cases (65.5%). Surgery was initiated in 3 cases, cancelled in 1 case,
and limited exploration was elected in 2 cases. Chemotherapy was started in 8 cases. Several
smaller studies combine reporting for results with colorectal cancer and ovarian cancer, yet the
actual number of patients with ovarian cancer is very small, with only 2 in each study. (11,15)
Two studies evaluated the use of RIS prior to second-look laparotomy. (13,16) Method et al.
(13) reported a prospective, blinded study in 20 subjects with ovarian cancer who had “normal
CA 125 levels and no clinical evidence of disease after primary cytoreductive surgery and
cytotoxic chemotherapy.” All but 2 patients underwent reassessment laparotomy. Twelve
patients had true-positive findings on RIS that were confirmed on laparotomy, and RIS
sensitivity was calculated to be 100%, although specificity was relatively low at 16.7%. CT
scanning showed relatively poor sensitivity (16.7%) but higher specificity (66.7%). Hempling et
al. (16) studied 15 patients and found that RIS had a sensitivity of 62.5% and specificity of
57.1%. In patients with macroscopically visible tumor, disease location was correctly predicted
by RIS in only 57% of cases.
These preliminary results suggest that RIS may possibly be useful in detecting additional sites
of ovarian tumor in some cases, although reported sensitivity is variable. Specificity may be
relatively low, and confirmation of positive findings may be necessary. Despite some evidence
that RIS may be helpful in some cases where occult recurrence is suspected but cannot be
localized, the relatively small size of most studies and the retrospective nature of the analyses
without prospectively designed confirmation studies limits the conclusions that can be made
from the available data.
Breast Cancer
Gopalan et al. (17) review various nuclear medicine techniques in breast cancer imaging and
summarize findings using In-111 satumomab pendetide from a Phase I study by Lamki et al.
(18) in 16 patients with primary breast cancer. While RIS detected all primary cancers (ranging
in size from 1.2–2.5 cm), diagnostic accuracy in evaluating axillary lymph nodes was more
limited with both false negative and false positive findings observed. Goldenberg (19) also
mentions the use of anti-CEA RIS in evaluating breast cancer, but little empirical data was
identified.
Medullary Thyroid Cancer
Medullary thyroid cancer may express carcinoembryonic antigen (CEA), and CEA levels are
42 Memorial Drive  Suite 1  Pinehurst, N.C. 28374 Phone (910) 715-8100  Fax (910) 715-8101
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one method used to monitor disease for recurrence. Radiolabeled anti-CEA monoclonal
antibodies have been applied as an adjunct to evaluate patients with medullary thyroid cancer,
however, most of the identified studies (20-24) used indium- or iodine-labeled monoclonal
antibodies, which are not the same as the FDA-approved technetium-labeled product. One
study of 26 subjects included 1 subject who received the FDA-approved Tc-99m arcitumomab
(IMMU-4; CEA-scan). In that case, RIS showed uptake in the 3 lesions that were also visible on
CT.
Lung Cancer
The 1997 TEC Assessment (25) on radioimmunoscintigraphy for lung cancer reviews 2 studies
and 1 abstract using Tc-99m arcitumomab (IMMU-4; CEA-Scan®, Immunomedics, Inc.) for
evaluation of non-small cell lung cancer (NSCLC). These reports included relatively small
samples, and some studies did not provide reporting of sensitivity and specificity. One study of
17 subjects found that RIS had 67% sensitivity in demonstrating 39 malignant lesions that were
known to express CEA and that had been detected on conventional imaging techniques. It is not
clear from these results how RIS would be useful in improving management and health
outcomes.
Other Cancers
Bombardieri et al. (26) note that anti-CEA RIS has been used in evaluating other malignancies
including pancreatic, gastric, and esophageal cancers, but there appears to be little evidence on
this use.
References:
1. 1994 TEC Assessments; Tab 5.
2. Su WT, Brachman M, O’Connell TX. Use of OncoScint scan to assess resectability of
hepatic metastases from colorectal cancer. Am Surg 2001; 67(12):1200-3.
3. Bhatia M, Baron PL, Alderman DF et al. False-positive imaging of In-111 labeled
monoclonal antibody conjugate CYT-103 in a patient with metastatic colorectal
carcinoma. Clin Nucl Med 1995; 20(11):979-80.
4. Muxi A, Pons F, Vidal-Sicart A et al. Radioimmunoguided surgery of colorectal
carcinoma with a 111In-labelled anti-TAG72 monoclonal antibody. Nucl Med Commun
1999; 20(2):123-30.
5. Volpe CM, Abdel-Nabi HH, Kulaylat MN et al. Results of immunoscintigraphy using a
cocktail of radiolabeled monoclonal antibodies in the detection of colorectal cancer. Ann
Surg Oncol 1998; 5(6):489-94.
6. Wegener WA, Petrelli N, Serafini A et al. Safety and efficacy of arcitumomab imaging in
colorectal cancer after repeated administration. J Nucl Med 2000; 41(6):1016-20.
7. Dominguez JM, Wolff BG, Nelson H et al. 111In-CYT-103 scanning in recurrent
colorectal cancer – does it affect standard management? Dis Colon Rectum 1996;
39(5):514-9.
42 Memorial Drive  Suite 1  Pinehurst, N.C. 28374 Phone (910) 715-8100  Fax (910) 715-8101
FirstCarolinaCare Insurance Company, Inc. is a wholly-owned subsidiary of
8. Moffat FL, Gulec SA, Serafini AN et al. A thousand points of light or just dim bulbs?
Radiolabeled antibodies and colorectal cancer imaging. Cancer Invest 1999; 17(5):32234.
9. Moffat FL, Pinsky CM, Hammershaimb L et al. Clinical utility of external
immunoscintigraphy with the IMMU-4 technetium-99m Fab’ antibody fragment in patients
undergoing surgery for carcinoma of the colon and rectum: results of a pivotal phase III
trial. J Clin Oncol 1996; 14(8):2295-305.
10. Kalofonos HP, Karamouzis MV, Epenetos AA. Radioimmunoscintigraphy in patients with
ovarian cancer. Acta Oncol 2001; 40(5):549-57.
11. Pinkas L, Robins PD, Forstrom LA et al. Clinical experience with radiolabelled
monoclonal antibodies in the detection of colorectal and ovarian carcinoma recurrence
and review of the literature. Nucl Med Commun 1999; 20(8):689-96.
12. Blend MJ, Bhadkamkar VA. Impact of radioimmunoscintigraphy on the management of
colorectal and ovarian cancer patients: a retrospective study. Cancer Invest 1998;
16(7):431-41.
13. Method MW, Serafini AN, Averette HE et al. The role of radioimmunoscintigraphy and
computed tomography scan prior to reassessment laparotomy of patients with ovarian
carcinoma. A preliminary report. Cancer 1996; 77(11):2286-93.
14. Surwit EA, Childers JM, Krag DN et al. Clinical assessment of 111In-CYT-103
immunoscintigraphy in ovarian cancer. Gynecol Oncol 1993; 48(3):285-92.
15. Bohdiewicz PJ, Scott GC, Juni JE et al. Indium-111 OncoScint CR/OV and F-18 FDG in
colorectal and ovarian carcinoma recurrences. Early observations. Clin Nucl Med 1995;
20(3):230-6.
16. Hempling RE, Piver MS, Baker TR et al. Immunoscintigraphy using 111InCyt103 prior to
second look laparotomy in ovarian cancer. A pilot study. Am J Clin Oncol 1994;
17(4):331-4.
17. Gopalan D, Bomanji JB, Costa DC et al. Nuclear medicine in primary breast cancer
imaging. Clin Radiol 2002; 57(7):565-74.
18. Lamki LM, Buzdar AU, Singletary SE et al. Indium-111-labeled B72.3 monoclonal
antibody in the detection and staging of breast cancer: a phase I study. J Nucl Med
1991; 32(7):1326-32.
19. Goldenberg DM. Perspectives on oncologic imaging with radiolabeled antibodies.
Cancer 1997; 80(12 Suppl):2431-5
20. Barbet J, Peltier P, Bardet S et al. Radioimmunodetection of medullary thyroid
carcinoma using indium-111 bivalent hapten and anti-CEA x anti-DTPA-indium bispecific
antibody. J Nucl Med 1998; 39(7):1172-8.
21. Vuillez JP, Peltier P, Caravel JP et al. Immunoscintigraphy using 111-In-labeled F(ab’)2
fragments of anticarcinoembryonic antigen monoclonal antibody for detecting
recurrences of medullary thyroid carcinoma. J Clin Endocrinol Metab 1992; 74(1):15763.
42 Memorial Drive  Suite 1  Pinehurst, N.C. 28374 Phone (910) 715-8100  Fax (910) 715-8101
FirstCarolinaCare Insurance Company, Inc. is a wholly-owned subsidiary of
22. Zanin DEA, van Dongen A, Hoefnagel CA et al. Radioimmunoscintigraphy using iodine131 anti-CEA monoclonal antibodies and thallium-201 scintigraphy in medullary thyroid
carcinoma: a case report. J Nucl Med 1990; 31(11):1854-5.
23. Riva P, Moscatelli G, Paganelli G et al. Antibody-guided diagnosis: an Italian experience
on CEA-expressing tumours. Int J Cancer Suppl 1988; 2:114-20.
24. Juweid M, Sharkey RM, Behr T et al. Improved detection of medullary thyroid cancer
with radiolabeled antibodies to carcinoembryonic antigen. J Clin Oncol 1996;
14(4):1209-17.
25. 1997 TEC Assessments; Tab 17.
26. Bombardieri E, Aliberti G, de Graaf C et al. Positron emission tomography (PET) and
other nuclear medicine modalities in staging gastrointestinal cancer. Semin Surg Oncol
2001; 20(2):134-46.
Codes
Number
CPT
Description
Radiopharmaceutical localization of tumor or
distribution of radiopharmaceutical agent(s);
limited area
Radiopharmaceutical localization of tumor or
78801
distribution of radiopharmaceutical agent(s);
multiple areas
Radiopharmaceutical localization of tumor or
78802
distribution of radiopharmaceutical agent(s);
whole body, single day imaging
Radiopharmaceutical localization of tumor or
78803
distribution of radiopharmaceutical agent(s);
tomographic (SPECT)
Radiopharmaceutical localization of tumor or
distribution of radiopharmaceutical agent(s);
78804
whole body, requiring two or more days
imaging
Generation of automated data; interactive
process involving nuclear physician and/or
78890-78891
allied health professional personnel; simple
manipulations and interpretation, code range
92.16
Scan of lymphatic system
92.18
Total body scan, radioisotope
92.19
Scan, other sites
(Codes given for medically necessary indications only)
154.0
Malignant neoplasm, colon with rectum
Malignant neoplasm, ovary and other uterine
183.0–183.9
adnexa, code range
78800
ICD-9 Procedure
ICD-9 Diagnosis
42 Memorial Drive  Suite 1  Pinehurst, N.C. 28374 Phone (910) 715-8100  Fax (910) 715-8101
FirstCarolinaCare Insurance Company, Inc. is a wholly-owned subsidiary of
235.20
V10.04
V10.06
HCPCS
A4641
A4642
Type of Service
Place of Service
Neoplasm of uncertain behavior, intestine and
rectum
Personal history malignant neoplasm, ovary
Personal history malignant neoplasm,
rectosigmoid
Supply of radiopharmaceutical diagnostic
imaging agent, not otherwise classified
Supply of satumomab pendetide,
radiopharmaceutical diagnostic imaging agent,
per dose
Radiology
Outpatient
Index
Acitumomab
CEA-Scan
CYT-103
IMMU-4
OncoScint
Radioimmunoscintigraphy
Satumomab pendetide
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FirstCarolinaCare Insurance Company, Inc. is a wholly-owned subsidiary of