Satumomab Pendetide (OncoScint, CYT-103)
A retrospective study was performed to determine the diagnostic value of OncoScint CR/OV immunoscintigraphy in patients with suspected recurrence of carcinoma of the colon or ovary (Pinkas et al., 1999). (3) Surgical and histopathological findings of 31 patients were compared to scintigraphic exams. The combined sensitivity and accuracy of immunoscintigraphy was significantly higher than that of cross sectional radiological imaging in detecting extra-hepatic disease. OncoScint scintigraphy is a sensitive method for detecting local recurrence and extra-hepatic metastases in colorectal and ovarian carcinoma. A multi-center clinical trial was conducted on 103 colorectal cancer patients (Doerr et al., 1991). (4) 111In-CYT-103 immunoscintigraphic findings were consistent with the pathologic diagnoses for 70% of patients with colorectal cancer and 90% of disease-free patients. Antibody imaging contributed to surgical decision-making by detecting occult disease (12% of patients) and confirming localized, potentially resectable disease without regional or metastatic spread. The researchers conclude that 111In-CYT-103 is a useful diagnostic tool for presurgical evaluation of colorectal cancer patients. In another multi-center clinical trial, 111In-CYT-103 immunoscintigraphy correctly identified surgically confirmed tumor in 68% of 103 patients with ovarian adenocarcinoma (Surwit et al., 1993). (5) Overall sensitivity of 111In-CYT-103 immunoscintigraphy was greater than that of CT imaging. The authors conclude that the results of this trial support 111In-CYT-103 immunoscintigraphy as a valuable addition to the presurgical evaluation of patients with suspected persistent or recurrent ovarian cancer.
TC 99m-arcitumomab (CEA Scan)
Comparison studies with CT scan have shown that this agent provides a 40% increase (66% vs. 47%) in detection of patients with respectable disease, a 143% increase (47% vs. 19%) in detection of patients with non-resectable disease, a 60% decrease (23% vs. 59%) in the false-negative (FN) rate, and a positive-predictive value of 97%.
Indium-111 pentetreotide (Octreoscan®)
OctreoScan® was studied in nine unblinded clinical studies in a total of 365 patients. Of these patients, 174 were male and 191 were female. Eligible patients had a demonstrated or high clinical suspicion of a neuroendocrine tumor. The most common tumors were carcinoids (132 of 309 evaluable patients). Scintigraphic results were compared to results of conventional localization procedures (CT, ultrasound, MRI, angiography, surgery and/or biopsy). OctreoScan® results were consistent with the final diagnosis (success) in 267 of 309 evaluable patients (86.4%). Compared with carcinoids and gastrinomas, lower success rates were noted for localization of insulinomas, neuroblastomas, pituitary adenomas and medullary thyroid carcinomas. OctreoScan® success was observed in 27 of 32 patients (84.4%) with clinically nonfunctioning neuroendocrine tumors (i.e., no symptom of a clinical syndrome mediated by abnormally elevated hormones). OctreoScan® localized previously unidentified tumors in 57/204 patients. In 55/195 patients, indium In-111 pentetreotide uptake occurred in lesions not thought to have somatostatin receptors. In a small subgroup of 39 patients who had tissue confirmation, the sensitivity rate for OctreoScan® scintigraphy was 85.7%; for CT/MRI the rate was 68%. The specificity rate for OctreoScan® scintigraphy was 50%, the rate for CT/MRI was 12%. Overall, including all tumor types with or without the presence of somatostatin receptors, there were 3/508 false positives and 104/508 false negatives. Of the 309 patients, 87 had received octreotide for therapeutic purposes within 72 hours of OctreoScan® administration. These patients had an overall 95% success rate. (6)
Capromab Pentetide (ProstaScint)
In one of the original studies, ProstaScint imaging was performed in 152 patients undergoing radical prostatectomy to evaluate pelvic lymph node status. The results of these ProstaScint scans were compared to the lymph node pathology obtained from pelvic lymphoadenectomy PLND. This study reported that ProstaScint was approximately 70% accurate. Of note, this study revealed that 14 of 25 men (56%) with negative lymph nodes on pathology but positive ProstaScint scans experienced PSA progression following radical prostatectomy. This suggested that the true accuracy of ProstaScint imaging may actually be higher than reported.
Because the value of a diagnostic imaging modality is measured in its potential impact on patient management and health outcomes, it is noteworthy that ProstaScint was found to be the best single predictor of positive lymph nodes in a study population at high risk for nodal metastasis. Gleason score, PSA, and ProstaScint results were all fairly good predictive factors when considered separately, but only ProstaScint demonstrated statistically significant, independent evidence for lymph node metastases if used alone. ProstaScint imaging detected lymph node lesions that were not identified by other diagnostic tests and were confirmed to be malignant in 38 patients in addition to revealing malignancy in 12 patients in areas outside the field of surgery.
In a multi-center study comparing ProstaScint imaging to PLND in 51 prostate carcinoma patients at high risk for lymph node metastases, ProstaScint surpassed the combined diagnostic performance of CT, MRI and US with an overall accuracy of 81%. Additional data from this study provided evidence of the potential beneficial impact of ProstaScint imaging on health outcomes. Two patients were found to have histologically proven “skip metastases” near the level of the aortic bifurcation, which is outside the conventional location of standard pelvic exploration. Both patients had had previous pelvic lymph node dissections that were pathologically negative, but ProstaScint scans that were abnormal. The investigators noted that because patients who have skip metastases and negative pelvic lymph nodes have been found to later develop distant metastases, ProstaScint imaging was instrumental in detecting metastatic disease early and prompting further investigation.
A study was conducted to evaluate the role of radioimmunoscintigraphy (RIS) directed against prostate-specific membrane antigen (PSMA) in influencing decision-making about radiotherapy (RT) following radical retropubic prostatectomy (RRP) (Jani et al., 2004).(7) The study evaluated RT treatment decisions based on knowledge gained from radioimmunoscintigraphy and compared them with those made before the radioimmunoscintigraphy. Knowledge of radioimmunoscintigraphy results led to withdrawal of the decision to offer RT for four of 54 patients (7.4%) and changes to the general treatment volume for six of 54 patients (11.1%). In total, radioimmunoscintigraphy altered the RT decision in 10 of 54 patients (18.5%).
In 2007, the National Comprehensive Cancer Network (NCCN) updated their Prostate Cancer Clinical Practice Guideline (v.2.2007) to include ProstaScint scan as an option under ‘Salvage Workup and Primary Salvage Therapy, Postsurgery Patients’ and under ‘Postradiation Recurrence’ (NCCN, 2007). On the NCCN’s patient information site, the NCCN states that “the advantage of this test is that it has the potential to detect spread of prostate cancer to bone, lymph nodes, and other organs and can distinguish prostate cancer from other cancers and benign disorders. The disadvantage is the lack of specificity, meaning that it often suggests spread when there is none. The ProstaScint scan is usually not used to stage the cancer before initial treatment. It may prove to be more useful after treatment, in cases where it is thought that the cancer has come back (recurred). Although mostly retrospective studies, evidence in the published, peer-reviewed scientific literature indicates that the use of ProstaScint® (Indium-111 labeled capromab pendetide) may aid in the diagnosis of prostate cancer. (11, 12, 13)
Imciromab Pentetate (MyoScint®)
MyoScint is highly specific (specificity of 97%), since normal myocytes do not take up MyoScint, and heavy chain myosin is not found free in the circulation. Thus the FAB fragments localize to sites of necrotic myocardium. The extent of cardiac uptake correlates with prognosis (e.g., risk of subsequent cardiac death), and sensitivity ranges from 84% acutely to 72% at two months post myocardial infarction. The agent can be injected immediately after the onset of chest pain. It may have diagnostic value when the EKG and cardiac enzyme studies are equivocal.
Monoclonal antibodies, though more commonly used in immunotherapy than in diagnosis, have been shown to be effective when used in scintigraphy to aid in detecting and diagnosing numerous cancers. Clinical trials and research will continue to expand both the number of monoclonal antibodies used as imaging agents and their potential indications for use.
A search of peer reviewed literature conducted through December 2012 identified the following scientific information specific to RIS imaging. Other than what’s addressed below, no additional scientific information or publications were found that would alter the current coverage position of this medical policy for RIS imaging (4)
OncoScint for Ovarian Cancer
In regards to ovarian cancer, serum CA-125 levels have been shown to be useful in predicting the presence of ovarian cancer, but negative titers do not preclude malignancy. In clinical trials, OncoScint has a sensitivity of 70 % versus 44 % for CT, and a specificity of 55 % (79 % for CT) in patients with ovarian cancer. Carcinomatosis was detectable by antibody imaging in 71 % of patients, but in only 45 % by CT.
ProstaScint for Prostate Cancer
In Version 1:2011 of the National Comprehensive Cancer Network (NCCN) Guidelines for prostate cancer ProstaScint was removed as a recommendation in the workup of a patient with recurrence after prostatectomy and with a recurrence after RT. No rationale listed. (14) In Version 1:2013 no mention or comments were found in the guidelines when searching for the term ProstaScint. (15)
I-131 meta-Iodobenzylguanidine (MIBG)
According to the NCI PDQ Database, CT and MRI scans are about equally sensitive (98 to 100 %) for pheochromocytoma, while MIBG scanning has a sensitivity of only 80 %. However, MIBG scanning has a specificity of 100 %, compared to specificity of 70 % for CT and MRI. Thus, I-131 MIBG imaging provides a method for confirming that a tumor is a pheochromocytoma and rules out metastatic disease. Currently, I-131 MIBG is approved as an adjunctive diagnostic agent in the localization of primary or metastatic pheochromocytoma and neuroblastoma. According to the National Cancer Institute’s PDQ Database, for staging of neuroblastoma, bone should be assessed by MIBG scan (applicable to all sites of disease) and by technetium-99 scan if the results of the MIBG imaging are negative or unavailable.(16)
Iobenguane I-123 injection (AdreView®)
The safety and effectiveness of iobenguane I-123 were assessed in a single-arm clinical study of patients with known or suspected neuroblastoma or pheochromocytoma. Diagnostic effectiveness was determined for 211 patients by comparison of focal increased radionuclide uptake on planar scintigraphy at 24 ± 6 hours post-administration of iobenguane I-123 injection against the definitive diagnosis (standard of truth). The standard of truth was a diagnosis of presence or absence of pheochromocytoma in 127 patients and neuroblastoma in 84 patients. The diagnosis was determined by histopathology or, when histopathology was unavailable, a composite of imaging, plasma/urine catecholamine and/or catecholamine metabolite measurements and clinical follow-up. In the detection of either neuroblastoma or pheochromocytoma, the iobenguane I-123's sensitivity and specificity were determined independently based upon results of 3 image-readers who were fully masked to clinical information. The sensitivity ranged from 77 % to 80 % and the specificity ranged from 69 % to 77 %. Performance characteristics were similar between the groups of patients who had either a pheochromocytoma or neuroblastoma truth standard. (17, 18)
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Procedure and diagnosis codes on Medical Policy documents are included only as a general reference tool for each policy. They may not be all-inclusive.
The presence or absence of procedure, service, supply, device or diagnosis codes in a Medical Policy document has no relevance for determination of benefit coverage for members or reimbursement for providers. Only the written coverage position in a medical policy should be used for such determinations.
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