Medical Policy

 

Subject: Selective Internal Radiation Therapy (SIRT) of Primary or Metastatic Liver Tumors
Document #: THER-RAD.00006 Publish Date:    02/28/2018
Status: Reviewed Last Review Date:    01/25/2018

Description/Scope

This document addresses the use of Selective Internal Radiation Therapy (SIRT).  At the time of diagnosis, most liver tumors, whether primary or from metastases, are unresectable and chemotherapy is generally only palliative.  Various locoregional therapies have been investigated for potential palliation or even cure of unresectable liver tumors.  Some examples of such treatments include cryosurgery, radiofrequency ablation (RFA), and transcatheter arterial chemoembolization (TACE).  One of these therapies, SIRT, also known as radioembolization, targets the delivery of small beads or microspheres containing yttrium-90 (90Y) to the tumor since liver tissue is radiation-sensitive.

Note: Please see the following related documents for additional information:

Position Statement

Medically Necessary:

A.  Palliative Treatment

Selective internal radiation therapy (SIRT) is considered medically necessary as palliative treatment for individuals with any of the following:

  1. Neuroendocrine tumors (for example, carcinoid tumors, pancreatic islet cell tumors, parathyroid adenomas, pituitary adenomas) with hepatic metastases, when systemic therapy has failed to control symptoms such as carcinoid syndrome (for example, debilitating flushing, wheezing, and diarrhea); or
  2. Symptoms from non-carcinoid neuroendocrine tumors with hepatic metastases (for example, hypoglycemia, severe diabetes, Zollinger-Ellison Syndrome); or
  3. Specific liver-related symptoms due to tumor bulk (for example, pain) from any primary or metastatic hepatic tumor.

B.  Hepatocellular Carcinoma or Bridge to Liver Transplantation

SIRT is considered medically necessary as a primary treatment for surgically unresectable primary hepatocellular carcinoma (HCC) or, as a bridge to liver transplantation, when all of the following criteria are met for either indication:

  1. Preserved liver function defined as Childs-Turcotte-Pugh Class A or B; and
  2. Three or fewer encapsulated nodules and each nodule is less than or equal to 5 centimeters in diameter; and
  3. No evidence of extra-hepatic metastases; and
  4. No evidence of severe renal function impairment; and
  5. No evidence of portal vein occlusion.

C.  Hepatocellular Carcinoma in Individuals Who May Become Eligible for Liver Transplantation

SIRT is considered medically necessary for the treatment of individuals with hepatocellular carcinoma who:

  1. May become eligible for liver transplantation except that the hepatic lesion(s) is greater than 5 centimeters in maximal diameter; and
  2. It can be reasonably expected that treatment with SIRT will result in tumor size reduction to less than or equal to 5 centimeters in maximal diameter.

Investigational and Not Medically Necessary:

SIRT is considered investigational and not medically necessary when the above criteria are not met.

Rationale

Two commercial forms of 90Y have received approval by the United States (U.S.) Food and Drug Administration (FDA).  TheraSphere® (MDS NordianTM Inc., Ottawa, Ontario) received premarket approval (PMA) in 1997 and SIR-Spheres® (Sirtex Medical Inc., Lake Forest, IL) received approval in 2002 under an FDA Humanitarian Device Exemption (HDE).  The uses of both technologies are additionally regulated by the U.S. Nuclear Regulatory Commission (NRC).

There is extensive published literature regarding technical issues and clinical outcomes of SIRT and other locally ablative treatments for liver tumors.  Current evidence presents favorable effects of SIRT on locoregional control of liver cancer; yet most lack long-term follow-up data to document the duration of responses or survival after SIRT.  At present, no large randomized controlled trial has been published on the safety and efficacy of SIRT, though a growing body of lower level evidence has led to expert consensus support for a limited number of indications.  Larger Phase III trials are underway.

Liver-Related Symptoms Due to Tumor Bulk

Most studies addressing the use of SIRT for hepatic tumors are uncontrolled and have relatively short-term follow-up.  However, there is sufficient data to demonstrate palliative benefit from SIRT for hepatic tumors related to a wide variety of primary cancers.  The published data supports the ability of SIRT to provide, at minimum, short-term symptom control by decreasing tumor bulk and reducing the neuroendocrine and endocrine effects of hepatic metastases.  SIRT has become widely accepted as a treatment of specific liver-related symptoms due to tumor bulk (for example, pain) from primary or metastatic hepatic tumors.

SIRT for Hepatocellular Carcinoma (HCC)

In 2009, Salem and colleagues published the findings of a large prospective case series.  This study included 291 participants with unresectable HCC.  Using World Health Organization (WHO) and European Association for the Study of the Liver (EASL) guidelines, response rates were reported to be 42% and 57% respectively.  Survival times differed significantly between individuals with Child-Pugh A and Child-Pugh B classifications, with the former surviving a mean of 17.2 months and the latter 7.7 months.  Furthermore, individuals with Child-Pugh B class disease with portal vein thrombosis (PVT) survived a mean of only 5.6 months.  Similar findings regarding the impact of PVT on SIRT outcomes were reported by Woodall (2009).

Vente and colleagues (2009) conducted a meta-analysis of the literature addressing SIRT for unresectable liver metastases.  The authors included all forms of SIRT, including SIR-Spheres and TheraSpheres, analyzing 30 articles that included 1217 subjects.  For individuals with colorectal cancer (CRC) metastases, a total of 19 eligible studies, which included 792 subjects, were included in the analysis.  Of these, 195 had received SIRT as a first-line treatment and 486 received SIRT as salvage therapy.  There was a significant difference in response when used for first-line therapy versus salvage, with the response rates reported as 91% and 79% respectively (p=0.07).  The median survival time varied between 6.7 to 17 months, irrespective of microsphere type, chemotherapy regimen, disease stage, or salvage versus first-line therapy.  Median survival from time of diagnosis ranged from 10.8 to 29.4 months.  For individuals with HCC, the authors included 14 studies in their analysis.  These studies included 425 subjects who underwent SIRT therapy.  Of these studies, only 12 reported on tumor response, leaving 318 subjects.  The authors noted that treatment with resin microspheres (e.g., SIR-Spheres) was associated with a significantly higher response rate when compared to glass microspheres (e.g., TheraSpheres) (89% vs. 78%, p=0.02).  Median survival was reported in only seven studies.  Median survival from time of SIRT treatment varied between 7.1 to 21 months.  Median survival from time of diagnosis or recurrence was reported to be between 9.4 to 24 months.

Four meta-analyses have been published comparing the safety and efficacy of TACE compared to SIRT in the treatment of unresectable HCC by Lobo (2016), Facciorusso (2016), Zhang (2015) and Ludwig (2016) which included 4, 10, 8 and 14 studies, respectively.  The published literature chosen for inclusion in the analyses varied on SIRT’s utility as primary versus salvage treatment and on outcomes of interest, some of which included tumor response, survival and quality of life measures.  Other variations between studies included subjects with PVT or minimal extra-hepatic disease while others excluded for any evidence of PVT or extra-hepatic disease.  Two of the four meta-analyses concluded that outcomes, including survival, appear comparable between SIRT and TACE for unresectable HCC, but SIRT resulted in fewer complications and less hospitalization when compared to TACE.  Zhang (2015), reported that only three of the eight studies chosen for inclusion in their analysis reported on OS but among them, SIRT was found to have a statistically significant survival advantage over TACE (hazard ratio [HR]=0.74, 95% Confidence Interval [CI], 0.61-0.90; p=0.002).  Although OS appeared to be improved in those who received SIRT versus TACE, Zhang (2015) also reported that no beneficial effect was seen in SIRT recipients in the outcomes of complications (other than abdominal pain), tumor response or over-all tumor control.  Ludwig (2016) similarly found a survival benefit with SIRT but no significant difference in tumor response.  Given the seemingly contradictory findings amongst and within the meta-analyses, further investigation is warranted in the form of large randomized controlled trials (RCTs) to more definitely describe the safety and efficacy of SIRT versus TACE in individuals with unresectable HCC.

Ragnoni (2016) conducted a systematic review and meta-analyses to evaluate the efficacy and safety of SIRT in intermediate-advanced HCC.  A total of 21 studies were chosen for inclusion in the analysis.  Only three comparative studies were identified (SIRT vs. TACE or sorafenib), two of which were RCTs, the rest were observational cohorts; all were deemed to be of low to medium methodological quality.  Authors concluded that evidence supporting the use of SIRT in HCC is largely based on retrospective and cohort studies and that SIRT appears to be a valid treatment option for intermediate-advanced stage HCC. 

A Cochrane review (Abdel-Rahman, 2016) which similarly identified two RCTs concluded the following:

There was insufficient evidence to assess the beneficial and harmful effects of yttrium-90 microsphere radioembolisation for people with unresectable hepatocellular carcinoma. Further randomised clinical trials are mandatory to better assess the potential beneficial and harmful outcomes of yttrium-90 microsphere trans-arterial radioembolisation either as a monotherapy or in combination with other systemic or locoregional therapies [such as Sorafenib] versus placebo, no treatment, or other systemic or locoregional therapies for people with unresectable hepatocellular carcinoma.

The National Comprehensive Cancer Network® (NCCN) Clinical Practice Guidelines in Oncology® for HCC (2017) states the following with Category 2A recommendations in the Principles of Locoregional Therapy section:

Bridge to Transplantation

SIRT has also been proposed as a treatment for subjects who have exhausted other treatment options, but continue to be viable candidates for orthotopic liver transplantation (OLT). 

A case series study by Kulik and colleagues details the use of TheraSpheres in 150 subjects with unresectable HCC (2006).  Of the 34 initially staged as UNOS T3, 19 (56%) were downgraded to stage T2 following treatment with 90Y.  A total of 8 were successfully downgraded and received orthotopic liver transplants following treatment.  The authors report survival to be 84%, 54% and 27% at 1, 2 and 3 years, respectively.

In 2009, Lewandowski and colleagues published the results of a nonrandomized controlled study that compared TACE (n=43) to SIRT with Theraspheres (n=43) as a method of downstaging subjects with T3 HCC as a bridge to transplantation.  The authors reported that successful downstaging to T2 was observed in 31% (11/35) of TACE subjects and 58% (25/42) of SIRT subjects (p=0.023).  This trend was noted in all lesion sizes.  The median time to UNOS downstaging was not reached in the TACE group, but was reported as 3.1 months in the SIRT group (p=0.027).  There was no significant difference in the number of subjects downstaged to resection, but 8 TACE and 18 SIRT subjects were downstaged to RFA treatment.  The median WHO time to progressive disease was 19.6 months in the TACE group vs. 48.6 months in the SIRT group (p=0.008).  The 1-year progression rates according to EASL criteria were 4% in the TACE group and 8% in the SIRT group (p=0.01).  Using the UNOS criteria, time to progression (TTP) was 18.2 months for the TACE group and 33.3 months in the SIRT group.  For TACE, OS without censoring to radical therapies (for example, transplantation/resection) at 1, 2 and 3 years was 75%, 42% and 19%, and 81%, 69% and 59%, respectively, for the SIRT group (p=0.008).  When censored to radical therapies, OS at 1, 2 and 3 years was 73%, 28% and 19% for the TACE group and 77%, 59% and 45%, respectively, for the SIRT group (p=0.18).  A total of 2 out of 11 of the TACE subjects had relapsed following transplantation with a 1-year relapse-free survival of 73%, 2 out of the 9 SIRT subjects relapsed following transplantation with a 1-year relapse-free survival of 89%.  This difference was not found to be statistically significant.

A systematic review conducted by Braat and colleagues (2016) included 43 original studies and case reports (including the two described in detail above) evaluating SIRT as a therapy option for bridge to liver transplant.  Authors caution that although SIRT has shown promise as a tool for down-staging to liver transplant, more research is warranted in quantifying dose-response relationships to mitigate both the potential for insufficient tumor response (if an inadequate amount of radiation is delivered) and the potential for liver failure (from damage to non-tumorous parenchyma if radiation quantities exceed the balance of efficacy and overall benefit).

SIRT for Treatment of Metastatic Tumors to the Liver

Based on panel consensus, the NCCN Clinical Practice Guidelines in Oncology® for Colon and Rectal Cancer (2017) have assigned a Category 2A recommendation for the use of SIRT in the treatment of unresectable liver-dominant metastases that are refractory to chemotherapy.  NCCN states, “Whereas very little data show any impact on patient survival and data supporting its efficacy are limited, toxicity with radioembolization is relatively low.” NCCN cautions, “Reported complications include cholecystitis/bilirubin toxicity, gastrointestinal ulceration, radiation-induced liver disease, and abscess formation.”

Two reports were published from a single randomized trial of individuals with unresectable metastases from CRC treated with hepatic artery infusion (HAI) of 5-fluorodeoxyuridine (5-FUDR) alone (n=34) or HAI of 5-FUDR with SIRT (n=36).  The first published report by Moroz and colleagues (2001) reported on changes in normal liver and spleen volume following HAI+SIRT, but did not provide data on long-term treatment outcomes.  The second report, the main report of this study, describes how it was initially designed to enroll 95 subjects (Gray, 2001).  However, when investigators detected a 30% increase in median survival for those in the experimental arm compared with controls, with 90% power and 95% confidence, the investigators closed the study after entering only 74 subjects (n=70 eligible for randomization).  Reasons cited for the early closure included: (1) increasing individual and physician reluctance to participate; (2) decision by the FDA to accept intermediate endpoints to support applications for premarket application approval; and (3) lack of funding to complete the study.  The smaller study population was adequate to detect increases in response rate (from 20% to 55%) and median TTP (by 32% from 4.5 months) with 80% power and 95% confidence, but lacked sufficient statistical power to detect changes in survival.

To monitor responses to therapy, investigators serially measured serum levels of carcinoembryonic antigen (CEA) and estimated tumor cross-sectional area and volume from repeated computerized tomographic (CT) scans read by blinded physicians.  They reported increased overall responses (complete plus partial) measured by area (44% versus 18%, p=0.01; HAI+SIRT vs. HAI, respectively) and volume (50% versus 24%, p=0.03), or by serum CEA levels (72% versus 47%, p=0.004).  They also reported increased TTP detected by increased area (9.7 versus 15.9 months, p=0.001) or volume (7.6 versus 12.0 months, p=0.04).  However, there were no significant differences between treatment arms in actuarial survival rates (p=0.18 by log rank test) or in 11 quality of life measures.  Treatment-related complications (grades 3-4) included 23 events in each arm (primarily changes in liver function tests).  Nevertheless, investigators concluded that a “single injection of SIR-Spheres plus HAI is substantially more effective” than the same HAI regimen delivered alone.  Limitations to this study include: (1) accrual was halted early, leaving the study underpowered; (2) early closure was at the sole discretion of the principal investigator without independent review or prospectively designed data monitoring procedures and stopping rules; (3) results for the SIRT+HAI group are within the range reported by other randomized trials of HAI in comparable subjects (Kemeny, 2002; Meta-Analysis Group, 1996); (4) results of this study may reflect use of a shorter-than-standard duration of HAI therapy, and are confounded by administration of non-protocol chemotherapy before and after SIRT; and (5) they did not report on survival.

In 2005, Lim and colleagues reported on a study of 32 subjects to prospectively evaluate the efficacy and safety of SIRT in individuals with inoperable liver metastases from CRC who have failed 5-FU based chemotherapy.  A total of 30 subjects were treated between January 2002 and March 2004.  In July 2004, the median follow-up was 18.3 months.  Median participant age was 61.7 years (range 36-77 years).  The authors concluded that: “In patients with metastatic CRC that have previously received treatment with 5-FU based chemotherapy, treatment with SIR-spheres has demonstrated encouraging activity.  Further studies are required to better define the subsets of patients most likely to respond.”

A retrospective case series study was published by Kennedy and colleagues in 2008.  This study included 148 subjects with hepatic metastases from neuroendocrine tumors including pancreas, lung, colon, ovary, kidney and small intestine.  The mean follow-up period was 42 months at the time of publication.  The authors report that there were no acute or delayed toxicity-related adverse events in 67% of the subjects.  Fatigue was reported by 6.5% and nausea and pain reported by 3.2% and 2.7% respectively.  Response to treatment, judged by imaging response, was reported to be 90%, with stable disease in 22.7%, partial response in 60.5%, complete response in 2.7%, and progressive disease in 4.9%.  The authors indicate there were some participants lost to follow-up, but no details are provided.  The report concludes by noting that compared to data from other studies, SIRT for the treatment of neuroendocrine tumors demonstrated a similar safety profile, improvement in debulking of tumor and survival similar to other local treatment methods, and that controlled prospective studies are warranted to further investigate these potential benefits.

In 2009, Mulcahy and others reported on a case series study involving 72 subjects with hepatic tumors from metastatic CRC.  The tumor response rate was reported to be 40.3%.  Median time to hepatic progression was 15.4 months and median duration of response was 15 months.  The positron emission tomography (PET) response rate was 77%.  OS from time of first treatment with SIRT was 14.5 months.  The authors noted that survival was significantly impacted by tumor volume, with individuals with less than or equal to 25% tumor replacement volume having a mean survival rate of 18.7 months vs. 5.2 months for those with greater than or equal to 25% tumor replacement volume.  Additionally, the presence of extra-hepatic disease had a significantly adverse impact on survival.  Subjects with extra-hepatic disease had an OS of 7.9 months vs. 21 months for those without.

A retrospective case series study involving 51 subjects with progressive chemotherapy-refractory metastatic CRC treated with SIRT was published in 2011 by Nace and colleagues.  CEA response was available in 41 subjects (80.4%), 17 (41%) showed a response to therapy.  A total of 31 subjects (60.8%) had imaging available for review, and none demonstrated a complete response.  Partial response was noted in 4 subjects (13%), stable disease in 20 (64%), and progressive disease in 7 (23%).  A total of 38 subjects (74.5%) died during the 3 year follow-up period.  OS was 10.2 months.  Notably, subjects who had previously received cetuximab therapy had a significantly decreased median survival (5.1 months, p=0.001).  The significant loss to follow-up (n=20; 39%), lack of a control group and other methodological concerns impact the generalizability of this study.

A retrospective, nonrandomized controlled study evaluating the use of SIRT as a salvage treatment for individuals with hepatic metastases was described by Bester and colleagues in 2012.  The study involved 390 subjects, 339 who were treated with SIRT and 51 who either declined SIRT or were ineligible due to variant hepatic arterial anatomy or extensive hepatopulmonary shunting and who were subsequently used as controls.  Of the SIRT treated subjects, 224 had metastatic CRC, and the remainder had an assortment of other metastatic cancers, including neuroendocrine (n=40), breast (n=16), unknown primary (n=10), pancreatic (n=8), gastric (n=8), and others (for example, melanoma; n=33).  No significant differences were noted between the treatment and control groups at baseline, including the presence of extra-hepatic disease and hepatic tumor burden.  At the time of final follow-up, 59% (201/390) of the SIRT subjects had died, while 76% (39/51) of the control group had died.  OS was reported to be 12 months for the SIRT group and 6.3 months for the control group (p<0.001).  In a subgroup analysis, OS was reported as 11.9 months for the CRC group (p<0.001 vs. control) and 12.7 months in the non CRC SIRT group (p<0.024 vs. control).  SIRT treatment was a significant predictor of OS (p<0.002), with a 43% reduction in the hazard of death vs. control subjects.  An important finding is that the site of primary tumor was not a significant predictor of outcomes.  No SIRT-related deaths were reported within the 3 month follow-up period.  However, several significant complications were noted, including Grade 1 abdominal pain in the immediate postoperative period as well as within 1 month of treatment.  The authors comment that this study was limited due to lack of randomization, and its retrospective nature. 

In 2013, Benson and colleagues described the results of a case series study of 151 subjects with a variety of liver metastases (CRC, n=61; neuroendocrine, n=43; and other tumor types, n=47) that were refractory to other therapies subsequently treated with TheraSpheres.  Disease control rates were 59%, 93% and 63% for CRC, neuroendocrine and other primaries, respectively.  Median progression-free survival (PFS) was 2.9 and 2.8 months for CRC and other primaries, respectively.  PFS was not achieved in the neuroendocrine group.  The median reported survival from SIRT was 8.8 months for CRC and 10.4 months for other primaries.  The authors stated that the median survival for subjects with neuroendocrine tumors has not been reached.  Grade 3/4 adverse events included pain (12.8%), elevated alkaline phosphatase (8.1%), hyperbilirubinemia (5.3%), lymphopenia (4.1%), ascites (3.4%) and vomiting (3.4%).  The authors concluded that individuals with liver metastases can be safely treated with SIRT.

In 2014, Saxena and colleagues conducted a systematic review assessing the safety and efficacy of SIRT in chemorefractory CRC metastases to the liver.  A total of 20 studies comprising 979 subjects were chosen for inclusion.  Following treatment, the percentage of participants with a radiological response, partial response and stable disease was 0%, 31% and 40.5%, respectively.  The median TTP and OS were 9 and 12 months, respectively, and the overall acute toxicity rate ranged from 11 to 100%.  Zero percent of 979 participants achieved a complete response; only 2 studies enrolled more than 100 participants.  Some of the studies used resin-based microspheres while others used glass-based microspheres and negative prognostic indicators were variable as was the use of concomitant chemotherapy.  This may account, in part, for the range of outcomes reported across the studies.  Authors conclude that, “There exists a need, however, to conduct prospective, adequately powered studies to further evaluate this treatment modality.”

Cianni and colleagues reported the use of an unspecified 90Y microsphere product on 110 subjects with liver metastases from a wide variety of primary cancers, including: CRC, breast, gastric, pancreatic, pulmonary, esophageal, pharyngeal, cholangiocarcinoma and melanoma (2010).  The authors reported complete or partial response in 45 subjects, stable disease in 42 subjects and progressive disease in 23 subjects.  While the results in this study are promising for cancers beyond the previously discussed and well-studied indications (HCC, CRC, etc.), the data presented for others such as esophageal, breast, etc. are hampered by small sample sizes.  Further studies with larger sample sizes are needed.  The authors themselves state that “Further phase III clinical trials should clearly determine the real and effective impact of radioembolization with Y-90 on survival rates, experimenting with the combination of SIRT, chemotherapy and modern biological agents as a first-line treatment.”

A study by Sato and colleagues (2008) included 147 subjects with chemorefractory metastatic hepatic tumors from a variety of primary tumors including colon, breast, neuroendocrine, cholangiocarcinoma and others (2008).  Clinical toxicities reported include fatigue (56%), pain (26%) and nausea (23%).  Imaging response was 42.8% (2.1% complete, 40.7% partial) and biological tumor response was 87%.  The 1-year survival was 47%, 2-year survival was 30.9% and median OS was 300 days.  Median survival according to primary tumor site was: 457 days for CRC, 776 days for neuroendocrine tumors, and 207 days for non-CRC and non-neuroendocrine tumors.  The authors note that the majority of subjects in this study were treated prior to the availability of growth factor inhibitors, which makes the impact of such treatment in conjunction with SIRT impossible to assess.  They also note the heterogeneous population and open-label study methodology makes the findings difficult to generalize to other populations.

Systematic reviews have been conducted evaluating SIRT’s safety and effectiveness in other primary cancers that have metastasized to the liver.  Conclusions demonstrate that although SIRT has activity in reducing tumor size, RCTs have shown that this treatment approach has not been shown to prolong survival or quality of life (Kuei, 2015; Zacharias, 2015).

Background/Overview

Hepatic (liver) tumors can arise either as primary liver cancer or by metastasis to the liver from other tissues or organs.  Local therapy for hepatic metastasis is indicated only when there is no extra-hepatic disease, which rarely occurs for individuals with primary cancers other than CRC or certain neuroendocrine malignancies.  At present, surgical resection with tumor-free margins and liver transplantation are the only potentially curative treatments.  For liver metastases from CRC, randomized trials have reported that post-surgical adjuvant chemotherapy (administered systemically or via the hepatic artery) decreases recurrence rates and increases time to recurrence.  Important prognostic factors for survival include site and extent of primary tumor, hepatic tumor burden, and performance status.

Unfortunately, most hepatic tumors are unresectable at diagnosis, due either to their anatomic location, size, number of lesions, concurrent nonmalignant liver disease, or insufficient hepatic reserve.  Palliative chemotherapy by combined systemic and HAI may increase disease-free intervals for individuals with unresectable hepatic metastases from CRC. However, durable responses to chemotherapy are less likely for those with unresectable primary HCC.

Various non-surgical ablative techniques have been investigated that seek to cure or palliate unresectable hepatic tumors by improving loco-regional control.  These techniques rely on extreme temperature changes, particle and wave physics (microwave or laser ablation), or pharmacologic/biochemical interventions.  Another of these, SIRT, relies on targeted delivery of small beads (microspheres) impregnated with radioactive 90Y.  The rationale for SIRT is based on the following: (1) the liver parenchyma is sensitive to radiation; (2) the hepatic circulation is uniquely organized, whereby tumors greater than 0.5 cm rely on the hepatic artery for blood supply while normal liver is primarily perfused via the portal vein; and (3) 90Y is a pure beta emitter with a relatively limited effective range and short half-life that helps focus the radiation and minimize its spread.  Candidates for SIRT are initially examined by liver angiography and technetium (99mTm) lung scan to rule out aberrant hepatic vasculature or significant lung shunting that would permit diffusion of injected microspheres.

Heckman (2008) noted the incidence of disease progression while listed for transplant was 10-23%.  Various technologies have been explored to maintain transplant eligibility by controlling disease progression, of which TACE and RFA were the most frequently studied.  A “bridge” to liver transplant involves ablative techniques to minimize and control disease progression to allow individuals with limited HCC to remain eligible on the OLT waitlist.  The goal of bridging is to prevent drop-off from the waiting list and to improve post-transplant survival (DuBay, 2011).

The current Organ Procurement and Transplantation Network (OPTN) and United Network for Organ Sharing (UNOS) allocation policy (2016) encourages the use of loco-regional therapies to downsize (downstage) tumors to T2 status and to prevent progression while on the transplant wait list.  In addition, the OPTN/UNOS policy appears to implicitly recognize the role of loco-regional therapy in the pre-transplant setting.  These indications are in part related to the current OPTN/UNOS liver allocation scoring system referred to as the Model for End-stage Liver Disease (MELD), for adults ages 12 and older, and the Pediatric End-stage Liver Disease (PELD) scoring system for candidates younger than 12 years of age.  The MELD score is a continuous disease severity scale incorporating serum bilirubin, prothrombin time (i.e., international normalized ratio-INR), and serum creatinine into an equation, producing a number ranging from 6 (less ill) to 40 (gravely ill).  The MELD score estimates how urgently the individual needs a liver transplant within the next 3 months.  PELD is similar to MELD but uses additional factors to recognize the specific growth and development needs of children.  PELD scores may also range higher or lower than the range of MELD scores.  The PELD scoring system includes measures of serum bilirubin, INR, albumin, growth failure, and whether the child is less than 1 year old.  Candidates that meet the staging and imaging criteria specified in the OPTN/UNOS Allocation of Livers and Liver-Intestines Policy: Candidates with Hepatocellular Carcinoma (HCC) sections 9.3.G.iv-v may receive extra priority on the "Waiting List."  A candidate with an HCC tumor that is stage T2 may be registered at a MELD/PELD score equivalent to a 15% risk of candidate death within 3 months if additional criteria are also met.  OPTN/UNOS defines stage T2 lesions as including any of the following:

The largest dimension of each tumor is used to report the size of HCC lesions.  Nodules < 1 cm are indeterminate and cannot be considered for additional priority.  Past loco-regional treatment for HCC (OPTN Class 5 [T2] lesion or biopsy proven prior to ablation) are eligible for automatic priority.

Currently, two commercial forms of 90Y microspheres are available: TheraSpheres, which are glass beads bound to 90Y, and SIR-Sphere, in which 90Y is bound to resin beads. Non-commercial forms are used mostly outside the U.S. While the commercial products use the same radioisotope (90Y) and have the same target dose (100 Gy), they differ in microsphere size profile, base material (i.e., glass versus resin, respectively) and size of commercially available doses. These physical characteristics of the active and inactive ingredients affect the flow of microspheres during injection, their retention at the tumor site, spread outside the therapeutic target region, and dosimetry calculations. Note also that the U.S. FDA granted PMA of SIR-Sphere, for use in combination with 5-floxuridine (5-FUDR) chemotherapy by HAI, to treat unresectable hepatic metastases from CRC cancer. In contrast, TheraSpheres is approved by HDE for use as monotherapy to treat unresectable HCC. For these reasons, results obtained with one product do not necessarily apply to other commercial (or non-commercial) products.

The FDA labeling for TheraSpheres (2014) and Sir-Spheres (2014) state that the following tests are recommended before treatment:

Planar nuclear medicine scans (for example, scintigraphy) are the most widely used imaging approach to evaluate SIRT candidates for inappropriate shunting. Although the use of 3-D scans are becoming increasingly widespread, their utility over planar imaging continues to be investigated.

Definitions

Metastatic tumor: A cancerous tumor that has spread beyond the boundaries of the primary organ to other organs and/or lymph nodes.

Palliative care: Medical treatments that are intended to alleviate pain and suffering.

Coding

The following codes for treatments and procedures applicable to this document are included below for informational purposes. Inclusion or exclusion of a procedure, diagnosis or device code(s) does not constitute or imply member coverage or provider reimbursement policy. Please refer to the member's contract benefits in effect at the time of service to determine coverage or non-coverage of these services as it applies to an individual member.

When services may be Medically Necessary when criteria are met:

CPT

 

37243

Vascular embolization or occlusion, inclusive of all radiological supervision and interpretation, intraprocedural roadmapping, and imaging guidance necessary to complete the intervention; for tumors, organ ischemia, or infarction [when specified as radioembolization using yttrium-90 microspheres]

79445

Radiopharmaceutical therapy, by intra-arterial particulate administration [when specified as transcatheter tumor destruction procedure using yttrium-90 microspheres]

 

 

HCPCS

 

C2616

Brachytherapy source, nonstranded, yttrium-90, per source [when specified as yttrium-90 microspheres]

S2095

Transcatheter occlusion or embolization for tumor destruction, percutaneous, any method, using yttrium-90 microspheres

 

 

ICD-10 Procedure

 

3E053HZ

Introduction of radioactive substance into peripheral artery, percutaneous approach [when specified as SIRT using yttrium-90 microspheres]

 

 

ICD-10 Diagnosis

 

 

For the diagnosis codes listed below for treatment of primary liver tumors:

C22.0-C22.9

Malignant neoplasm of liver and intrahepatic bile ducts

D01.5

Carcinoma in situ of liver, gallbladder and bile ducts

Z76.82

Awaiting organ transplant status

 

For the following diagnosis code ranges for palliation of liver metastases:

C00.0-C80.2

Malignant neoplasms

E16.0-E16.2

Drug-induced, other and unspecified hypoglycemia

E16.4

Increased secretion of gastrin (Zollinger-Ellison syndrome)

E34.0

Carcinoid syndrome

When services are Investigational and Not Medically Necessary:
For the procedure and diagnosis codes listed above when criteria are not met or when the code describes a procedure indicated in the Position Statement section as investigational and not medically necessary.

References

Peer Reviewed Publications:

  1. Al-Adra DP, Gill RS, Axford SJ, et al. Treatment of unresectable intrahepatic cholangiocarcinoma with yttrium-90 radioembolization: a systematic review and pooled analysis. Eur J Surg Oncol. 2015; 41(1):120-127.
  2. Bangash AK, Atassi B, Kaklamani V, et al. 90Y radioembolization of metastatic breast cancer to the liver: toxicity, imaging response, survival. J Vasc Interv Radiol. 2007; 18(5):621-628.
  3. Benson AB 3rd, Geschwind JF, Mulcahy MF, et al. Radioembolisation for liver metastases: results from a prospective 151 patient multi-institutional phase II study. Eur J Cancer. 2013; 49(15):3122-3130.
  4. Bester L, Meteling B, Pocock N, et al. Radioembolization versus standard care of hepatic metastases: comparative retrospective cohort study of survival outcomes and adverse events in salvage patients. J Vasc Interv Radiol. 2012; 23(1):96-105.
  5. Boehm LM, Jayakrishnan TT, Miura JT, et al. Comparative effectiveness of hepatic artery based therapies for unresectable intrahepatic cholangiocarcinoma. J Surg Oncol. 2015; 111(2):213-220.
  6. Braat MN, Samim M, van den Bosch MA, Lam MG. The role of (90)Y-radioembolization in downstaging primary and secondary hepatic malignancies: a systematic review. Clin Transl Imaging. 2016; 4:283-295.
  7. Cao CQ, Yan TD, Bester L, et al. Radioembolization with yttrium microspheres for neuroendocrine tumour liver metastases. Br J Surg. 2010; 97(4):537-543.   
  8. Cao X, He N, Sun J, et al. Hepatic radioembolization with Yttrium-90 glass microspheres for treatment of primary liver cancer. Chin Med J. (Engl) 1999; 112(5):430-432.
  9. Cianni R, Urigo C, Notarianni E, et al. Radioembolisation using yttrium 90 (Y-90) in patients affected by unresectable hepatic metastases. Radiol Med. 2010; 115(4):619-633.
  10. Devcic Z, Rosenberg J, Braat AJ, et al. The efficacy of hepatic 90Y resin radioembolization for metastatic neuroendocrine tumors: a meta-analysis. J Nucl Med. 2014; 55(9):1404-1410.
  11. DuBay D, Sandroussi C, Kachura JR, et al. Radiofrequency ablation of hepatocellular carcinoma as a bridge to liver transplantation. HPB (Oxford). 2011; 13(1):24-32.
  12. Dunfee BL, Riaz A, Lewandowski RJ, et al. Yttrium-90 radioembolization for liver malignancies: prognostic factors associated with survival. J Vasc Interv Radiol. 2010; 21(1):90-95.
  13. El Fouly A, Ertle J, El Dorry A, et al. In intermediate stage hepatocellular carcinoma: radioembolization with yttrium 90 or chemoembolization? Liver Int. 2015; 35(2):627-635.
  14. Facciorusso A, Serviddio G, Muscatiello N. Transarterial radioembolization vs chemoembolization for hepatocarcinoma patients: a systematic review and meta-analysis. World J Hepatol. 2016; 8(18):770-778.
  15. Garin E, Rolland Y, Edeline J, et al. Personalized dosimetry with intensification using 90Y-loaded glass microsphere radioembolization induces prolonged overall survival in hepatocellular carcinoma patients with portal vein thrombosis. J Nucl Med. 2015; 56(3):339-346.
  16. Georgiades CS, Ramsey DE, Solomon S, et al. New non-surgical therapies in the treatment of hepatocellular carcinomas. Tech Vasc Intervent Radiol. 2001; 4(3):193-199.
  17. Gramenzi A, Golfieri R, Mosconi C, et al. Yttrium-90 radioembolization vs sorafenib for intermediate-locally advanced hepatocellular carcinoma: a cohort study with propensity score analysis. Liver Int. 2015; 35(3):1036-1047.
  18. Gray B, Van Hazel G, Hope M, et al. Randomized trial of SIR-Spheres® plus chemotherapy vs. chemotherapy alone for treating patients with liver metastases from primary large bowel cancer. Ann Oncol. 2001; 12(12):1711-1720. 
  19. Gulec SA, Pennington K, Wheeler J, et al. Yttrium-90 microsphere-selective internal radiation therapy with chemotherapy (chemo-SIRT) for colorectal cancer liver metastases: an in vivo double-arm-controlled phase II trial. Am J Clin Oncol. 2013; 36(5):455-460.
  20. Heckman J, Devera M, Marsh J, et al. Bridging locoregional therapy for hepatocellular carcinoma prior to liver transplantation. Ann Surg Oncol. 2008; 15(11):3169-3177.
  21. Hendlisz A, Van den Eynde M, et al. Phase III trial comparing protracted intravenous fluorouracil infusion alone or with yttrium-90 resin microspheres radioembolization for liver-limited metastatic colorectal cancer refractory to standard chemotherapy. J Clin Oncol. 2010; 28(23):3687-3694.
  22. Herba MJ, Thirlwell MP. Radioembolization for hepatic metastases. Semin Oncol. 2002; 29(2):152-159.
  23. Ho S, Lau WY, Leung TW, et al. Internal radiation therapy for patients with primary or metastatic hepatic cancer. Cancer. 1998; 83(9):1894-1907.
  24. Jakobs TF, Hoffmann RT, Fischer T, et al. Radioembolization in patients with hepatic metastases from breast cancer. J Vasc Interv Radiol. 2008; 19(5):683-690.
  25. Kemeny MM, Adak S, Gray B, et al. Combined-modality treatment for resectable colorectal carcinoma to the liver: surgical resection of hepatic metastases in combination with continuous infusion of chemotherapy – an intergroup study. J Clin Oncol. 2002; 20(6):1499-1505.
  26. Kennedy AS, Dezarn WA, McNeillie P, et al. Radioembolization for unresectable neuroendocrine hepatic metastases using resin 90Y-microspheres: early results in 148 patients. Am J Clin Oncol. 2008; 31(3):271-279. 
  27. Kim DY, Park BJ, Kim YH, Radioembolization with yttrium-90 resin microspheres in hepatocellular carcinoma: a multicenter prospective study. Am J Clin Oncol. 2015; 38(5):495-501.
  28. King J, Quinn R, Glenn DM, et al. Radioembolization with selective internal radiation microspheres for neuroendocrine liver metastases. Cancer. 2008; 113(5):921-929. 
  29. Kolligs FT, Bilbao JI, Jakobs T, et al. Pilot randomized trial of selective internal radiation therapy vs. chemoembolization in unresectable hepatocellular carcinoma. Liver Int. 2015; 35(6):1715-1721.
  30. Kuei A, Saab S, Cho SK, et al. Effects of yttrium-90 selective internal radiation therapy on non-conventional liver tumors. World J Gastroenterol. 2015; 21(27):8271-8283.
  31. Kulik LM, Atassi B, van Holsbeeck L, et al. Yttrium-90 microspheres (TheraSphere) treatment of unresectable hepatocellular carcinoma: downstaging to resection, RFA and bridge to transplantation. J Surg Oncol. 2006; 94(7):572-586.
  32. Kwok PC, Leung KC, Cheung MT, et al. Survival benefit of radioembolization for inoperable hepatocellular carcinoma using yttrium-90 microspheres. J Gastroenterol Hepatol. 2014; 29(11):1897-1904.
  33. Lance C, McLennan G, Obuchowski N, et al. Comparative analysis of the safety and efficacy of transcatheter arterial chemoembolization and yttrium-90 radioembolization in patients with unresectable hepatocellular carcinoma. J Vasc Interv Radiol. 2011; 22(12):1697-1705.
  34. Lewandowski RJ, Kulik LM, Riaz A, et al. A comparative analysis of transarterial downstaging for hepatocellular carcinoma: chemoembolization versus radioembolization. Am J Transplant. 2009; 9(8):1920-1928.
  35. Lewandowski RJ, Memon K, Mulcahy MF, et al. Twelve-year experience of radioembolization for colorectal hepatic metastases in 214 patients: survival by era and chemotherapy. Eur J Nucl Med Mol Imaging. 2014; 41(10):1861-1869.
  36. Lim L, Gibbs P, Yip D, et al. Prospective study of treatment with selective internal radiation therapy spheres in patients with unresectable primary or secondary hepatic malignancies. Intern Med J. 2005; 35(4):222-227.
  37. Lobo L, Yakoub D, Picado O, et al.  Unresectable hepatocellular carcinoma: radioembolization versus chemoembolization: a systematic review and meta-analysis. Cardiovasc Intervent Radiol. 2016; 39(11):1580-1588.
  38. Ludwig JM, Zhang D, Xing M, Kim HS. Meta-analysis: adjusted indirect comparison of drug-eluting bead transarterial chemoembolization versus (90)Y-radioembolization for hepatocellular carcinoma. Eur Radiol. 2017; 27(5):2031-2041.Kallini JR, Gabr A, Thorlund K et al. Comparison of the adverse event profile of TheraSphere(®) with SIR-Spheres(®) for the treatment of unresectable hepatocellular carcinoma: a systematic review. Cardiovasc Intervent Radiol. 2017; 40(7):1033-1043.
  39. Meta-Analysis Group in Cancer. Reappraisal of hepatic arterial infusion in the treatment of nonresectable liver metastases from colorectal cancer. J Natl Cancer Inst. 1996; 88(5):252-258.
  40. Moreno-Luna LE, Yang JD, Sanchez W, et al. Efficacy and safety of transarterial radioembolization versus chemoembolization in patients with hepatocellular carcinoma. Cardiovasc Intervent Radiol. 2013; 36(3):714-723.
  41. Moroz P, Anderson JE, Van Hazel G, et al. Effect of selective internal radiation therapy and hepatic arterial chemotherapy on normal liver volume and spleen volume. J Surg Oncol. 2001; 78(4):248-252.
  42. Mulcahy MF, Lewandowski RJ, Ibrahim SM, et al. Radioembolization of colorectal hepatic metastases using yttrium-90 microspheres. Cancer. 2009; 115(9):1849-1858.
  43. Nace GW, Steel JL, Amesur N, et al. Yttrium-90 radioembolization for colorectal cancer liver metastases: a single institution experience. Int J Surg Oncol. 2011; 2011:571261.
  44. Ramsey DE, Geschwind JF. New interventions for liver tumors. Semin Roentgenol. 2002; 37(4):303-311.
  45. Rhee TK, Lewandowski RJ, Liu DM, et al. 90Y Radioembolization for metastatic neuroendocrine liver tumors: preliminary results from a multi-institutional experience. Ann Surg. 2008; 247(6):1029-1035.
  46. Rognoni C, Ciani O, Sommariva S, et al. Trans-arterial radioembolization in intermediate-advanced hepatocellular carcinoma: systematic review and meta-analyses. Oncotarget.  2016; 7(44):72343-72355.
  47. Salem R, Lewandowski RJ, Kulik L, et al. Radioembolization results in longer time-to-progression and reduced toxicity compared with chemoembolization in patients with hepatocellular carcinoma. Gastroenterology. 2011; 140(2):497-507.
  48. Salem R, Lewandowski RJ, Mulcahy MF, et al. Radioembolization for hepatocellular carcinoma using Yttrium-90 microspheres: a comprehensive report of long-term outcomes. Gastroenterology. 2010; 138(1):52-64. 
  49. Sangro B, Carpanese L, Cianni R, et al.; European Network on Radioembolization with Yttrium-90 Resin Microspheres (ENRY). Survival after yttrium-90 resin microsphere radioembolization of hepatocellular carcinoma across Barcelona clinic liver cancer stages: a European evaluation. Hepatology. 2011; 54(3):868-878.
  50. Sangro B, Martínez-Urbistondo D, Bester L, et al. Prevention and treatment of complications of selective internal radiation therapy: Expert guidance and systematic review. Hepatology. 2017; 66(3):969-982.
  51. Sato KT, Lewandowski RJ, Mulcahy MF, et al. Unresectable chemorefractory liver metastases: radioembolization with 90Y microspheres--safety, efficacy, and survival. Radiology, 2008; 247(2):507-515.
  52. Saxena A, Bester L, Shan L, et al. A systematic review on the safety and efficacy of yttrium-90 radioembolization for unresectable, chemorefractory colorectal cancer liver metastases. J Cancer Res Clin Oncol. 2014; 140(4):537-547.
  53. Saxena A, Chua TC, Bester L, et al. Factors predicting response and survival after yttrium-90 radioembolization of unresectable neuroendocrine tumor liver metastases: a critical appraisal of 48 cases. Ann Surg. 2010; 251(5):910-916.
  54. Saxena A, Meteling B, Kapoor J, et al. Yttrium-90 radioembolization is a safe and effective treatment for unresectable hepatocellular carcinoma: a single centre experience of 45 consecutive patients. Int J Surg. 2014; 12(12):1403-1408.  
  55. Steel J, Baum A, Carr B. Quality of life in patients diagnosed with primary hepatocellular carcinoma: hepatic arterial infusion of cisplatin versus 90-yttrium microspheres (Therasphere) Psycho-oncology. 2004; 13(2):73-79.
  56. Tian JH, Xu BX, Zhang JM, et al. Ultrasound-guided internal radiotherapy using yttrium-90-glass microspheres for liver malignancy. J Nucl Med. 1996; 37(6):958-963.
  57. Trinchet JC, Ganne-Carrie N, Beaugrand M. Review article: intra-arterial treatments in patients with hepatocellular carcinoma. Aliment Pharmacol Ther. 2003; 17(Suppl 2):111-118.
  58. Van Hazel G, Pavlakis N, Goldstein D, et al. Treatment of fluorouracil-refractory patients with liver metastases from colorectal cancer by using Yttrium-90 resin microspheres plus concomitant systemic irinotecan chemotherapy. J Clin Oncol. 2009; 27(25):4089-4095.
  59. Vente MA, Wondergem M, van der Tweel I, et al. Yttrium-90 microsphere radioembolization for the treatment of liver malignancies: a structured meta-analysis. Eur Radiol. 2009; 19(4):951-959.
  60. Vouche M, Habib A, Ward TJ, et al. Unresectable solitary hepatocellular carcinoma not amenable to radiofrequency ablation: multicenter radiology-pathology correlation and survival of radiation segmentectomy. Hepatology. 2014; 60(1):192-201.
  61. Woodall EC, Scoggins CR, Ellis SF, et al. Is selective internal radioembolization safe and effective for patients with inoperable hepatocellular carcinoma and venous thrombosis? J Am Coll Surg. 2009; 208(3):375-382.
  62. Young JY, Rhee TK, Atassi B, et al. Radiation dose limits and liver toxicities resulting from multiple yttrium-90 radioembolization treatments for hepatocellular carcinoma. J Vasc Interv Radiol. 2007; 18(11):1375-1382.
  63. Zacharias AJ, Jayakrishnan TT, Rajeev R, et al. Comparative effectiveness of hepatic artery based therapies for unresectable colorectal liver metastases: a meta-analysis. PLoS One. 2015;10(10).
  64. Zhang Y, Li Y, Ji H, et al. Transarterial Y90 radioembolization versus chemoembolization for patients with hepatocellular carcinoma: A meta-analysis. Biosci Trends. 2015; 9(5):289-298.

Government Agency, Medical Society, and Other Authoritative Publications:

  1. Abdel-Rahman OM, Elsayed Z. Yttrium-90 microsphere radioembolisation for unresectable hepatocellular carcinoma. Cochrane Database Syst Rev. 2016;(2):CD011313.
  2. American College of Radiology (ACR) Practice Guideline for Radioembolization with Microsphere Brachytherapy Device (RMBD) for Treatment of Liver Malignancies. 2014. Available at: https://www.acr.org/-/media/ACR/Files/Practice-Parameters/RMBD.pdf. Accessed on September 24, 2017.
  3. National Comprehensive Cancer Network® (NCCN) Clinical Practice Guidelines in Oncology®. © 2016 National Comprehensive Cancer Network, Inc. For additional information visit the NCCN website: http://www.nccn.org/index.asp. Accessed on September 09, 2016.
    • Colon Cancer (V.2.2016). Revised November 24, 2015.
    • Rectal Cancer (V.2.2016). Revised April 06, 2016.
    • Heptaobilliary Cancer (V.2.2016). Revised June 27, 2016.
  4. Organ Procurement and Transplantation Network. United Network for Organ Sharing (UNOS). Policies. Policy 9–Liver-intestine allocation. Effective September 09, 2017. Available at: https://optn.transplant.hrsa.gov/media/1200/optn_policies.pdf#nameddest=Policy_09. . Accessed on September 24, 2017.
  5. SIR-Spheres Product Information [PI] Label. Woburn, MA. Sirtex Medical Inc., 2014. Available at: http://www.sirtex.com/media/29845/ssl-us-10.pdf. Accessed on September 24, 2017.
  6. TheraSphere. PI Label. Surrey, UK. Biocompatibles UJNK Ltd.  2014. Available at: http://pbadupws.nrc.gov/docs/ML1427/ML14279A535.pdf. Accessed on September 25, 2017.
  7. Townsend A, Price T, Karapetis C. Selective internal radiation therapy for liver metastases from colorectal cancer. Cochrane Database Syst Rev. 2009;(4):CD007045.
  8. United States Nuclear Regulatory Commission (U.S. NRC). Microsphere Brachytherapy Sources and Devices. Licensing Guidance: ThereSphere® and SIR-Spheres® Yttrium-90 Microspheres. Revised June 2012. Available at: http://pbadupws.nrc.gov/docs/ML1217/ML12179A353.pdf. Accessed on September 24, 2017.
Index

Colorectal Cancer
Hepatic Metastases
Hepatocellular Carcinoma
Liver Tumors
Metastatic Liver Tumors
Radioembolization
Selective Internal Radiation Therapy
Selective Internal Radiation Treatment
SIR-Spheres
SIRT
TheraSphere
yttrium-90 Microspheres

The use of specific product names is illustrative only.  It is not intended to be a recommendation of one product over another, and is not intended to represent a complete listing of all products available. 

Document History

Status

Date

Action

Reviewed 01/25/2018 Medical Policy & Technology Assessment Committee (MPTAC) review.
Reviewed 01/17/2018 Hematology/Oncology Subcommittee review.

Reviewed

11/02/2017

MPTAC review.

Reviewed

11/01/2017

Hematology/Oncology Subcommittee review. Updated header language from “Current Effective Date” to “Publish Date.” Updated Rationale, Background/Overview and References sections.

Reviewed

11/03/2016

MPTAC review.

Reviewed

11/02/2016

Hematology/Oncology Subcommittee review. Updated Rationale, Background/Overview and References sections.

Reviewed

11/05/2015

MPTAC review.

Reviewed

11/04/2015

Hematology/Oncology Subcommittee review. Updated Rationale and Reference sections. Changed document number from RAD.00033 to THER-RAD.00006. Removed ICD-9 codes from Coding section.

Revised

05/07/2015

MPTAC review.

Revised

05/06/2015

Hematology/Oncology Subcommittee review. Clarified criteria, and updated Scope, Rationale, Background/Overview, Coding and References sections.

Revised

07/08/2014

MPTAC review.

Revised

06/20/2014

Hematology/Oncology Subcommittee review. Clarified bridge to transplant criteria.

Revised

05/15/2014

MPTAC review.

Revised

05/14/2014

Hematology/Oncology Subcommittee review. Clarified medically necessary criteria regarding bridge to transplantation tumor size and number. Updated Rationale and References sections.

 

01/01/2014

Updated Coding section with 01/01/2014 CPT changes; removed 37204 deleted 12/31/2013, and 75894.

Revised

05/09/2013

MPTAC review.

Revised

05/08/2013

Hematology/Oncology Subcommittee review. Updated title by removing specific product names. Revised medically necessary position statement to include treatment of liver-related symptoms due to any primary or metastatic tumors. Added medically necessary position statements for SIRT as a bridge to transplantation for individuals with HCC when criteria are met, or for those who may meet transplant criteria with SIRT as a result of decreased tumor size. Updated Rationale, Coding and References sections.

Reviewed

11/08/2012

MPTAC review.

Reviewed

11/07/2012  

Hematology/Oncology Subcommittee review. Wording clarification made to medically necessary criterion for neuroendocrine tumors. Updated Websites.

Reviewed

11/17/2011

MPTAC review.

Reviewed

11/16/2011  

Hematology/Oncology Subcommittee review.

Reviewed

11/18/2010

MPTAC review.

Reviewed

11/17/2010  

Hematology/Oncology Subcommittee review. Updated Coding and References sections.

Revised

11/19/2009

MPTAC review.

Revised

11/18/2009  

Hematology/Oncology Subcommittee review. Updated position statement to consider SIRT medically necessary for the treatment of hepatocellular carcinoma, primary or metastatic hepatic carcinoid tumors, hepatic metastases of colorectal cancer or islet cell tumors. Updated Rationale, Coding and References sections

Reviewed

11/20/2008

MPTAC review.

Reviewed  

11/19/2008  

Hematology/Oncology Subcommittee review. No change to position statement. Updated Rationale and References sections

Reviewed

11/29/2007

MPTAC review. No change to position statement.

Reviewed  

11/28/2007  

Hematology/Oncology Subcommittee review. The phrase “investigational/not medically necessary” was clarified to read “investigational and not medically necessary.” Updated references.

Reviewed

12/07/2006

MPTAC review.

Reviewed

12/06/2006

Hematology/Oncology Subcommittee review. No change to position statement. Updated Rationale and References sections.

Reviewed

06/08/2006

MPTAC review. References updated, 2005 small study added to the rationale section. No change to position statement.

Revised

07/14/2005

MPTAC review.  Revision based on Pre-merger Anthem and Pre-merger WellPoint Harmonization.

Pre-Merger Organizations

Last Review Date

Document Number

Title

 

Anthem, Inc.

 

01/29/2004

RAD.00033

Selective Internal Radiation Therapy (SIRT, i.e. SIR-Spheres and TheraSpheres) Brachytherapy

WellPoint Health Networks, Inc.

12/02/2004

4.11.11

Selective Internal Radiation Therapy of Primary or Metastatic Liver Tumors