Liver Transplantation for Malignancies

April 27, 2012

Tamara Syrek Jensen, JD
Deputy Director, Coverage and Analysis Group
Centers for Medicare and Medicaid Services
7500 Security Boulevard
Baltimore, Maryland 21244-1850

Re: Proposed Decision Memo for Liver Transplantation for Malignancies (CAG-0091R)

Dear Ms Jensen:

Thank you for the opportunity to comment on the Proposed Decision Memo for Liver Transplantation for Malignancies (CAG-0091R). The proposal expands Medicare coverage of adult liver transplantations for beneficiaries with the following malignancies: 1) liver metastases due to a neuroendocrine tumor (NET); 2) hemangioendothelioma (HAE), and, in particular, 3) extrahepatic unresectable cholangiocarcinoma (CCA). Under NCD 260.1, National Coverage Determination for Adult Liver Transplantation, Medicare covers adult liver transplants for hepatocellular carcinoma (HCC) patients in certain circumstances. However, Medicare coverage of other malignancies for adult liver transplantation is currently non-covered.

Mayo Clinic urges CMS to expand Medicare coverage of NCD 260.1 to include all three malignancies for adult liver transplantation, in particular, coverage of CCA. For several years, Mayo Clinic has used neoadjuvant therapy following liver transplantation on patients with CCA. Treating patients with this protocol has been very effective in improving patient outcomes. The five-year survival rate with the use of neoadjuvant therapy is greater than 70%. Without the use of this therapy, the five-year survival rate for patients with CCA is less than 20%. Mayo Clinic, in collaboration with several other US transplant centers, published an article, “Efficacy of Neoadjuvant Chemoradiation followed by Liver Transplantation for Perihilar Cholangiocarcinoma at 12 US Centers”. The article is in regards to the effectiveness of liver transplant for extrahepatic unresectable cholangiocarcinoma and addresses the wide use and effectiveness of this protocol outside of Mayo. It has been attached for your reference. CMS has proposed that Medicare coverage of these malignancies for adult liver transplantation be at the discretion of the Medicare Administrative Contractors (MACs) acting within their jurisdictions. We strongly believe that coverage be given to selected patients who are treated at transplant centers with existing protocols approved by the Organ Procurement and Transplant Network (OPTN). This would save time, potentially avoid appeals should a coverage conflict arise, and, most importantly, give patients help and hope now.

If, however, CMS decides not to use the existing, approved protocols, then the local contractors should make the most appropriate determinations based on evidence-based outcomes, individual patient characteristics, and best practices used by the local medical community.

We appreciate the opportunity to comment on the proposed decision memo and urge CMS to cover all three malignancies for adult liver transplantation. If you have questions or would like to discuss further, please contact me at (507) 284-4627 or Teri Hills (480) 301-4885.

Sincerely,

Ron W. Grousky
Vice Chair, Revenue Cycle – Medicare Strategy Unit

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April 26, 2012

Tamara Syrek Jensen, JD
Deputy Director, Coverage and Analysis Group
Centers for Medicare and Medicaid Services
7500 Security Boulevard
Baltimore, Maryland 21244-1850

Re: Proposed Decision Memo for Liver Transplantation for Malignancies (CAG-0091R)

Dear Ms Jensen:

Thank you for the opportunity to comment on the Proposed Decision Memo for Liver Transplantation for Malignancies (CAG-0091R). I will restrict my comments specifically to the concerns regarding coverage for transplantation for hilar cholangiocarcinoma in the setting of neoadjuvant chemoradiotherapy. I will address the concerns your reviewers had raised in your analysis point by point.

1. Concern regarding lack of definition of unresectable disease in the publication by Heimbach et al: We regret if we have been unclear in our definition of unresectable disease. Patients are considered unresectable if they have disease occurring in the setting of advanced underlying liver disease, or if bilobar involvement of malignancy to the second order biliary radicals. As stated in our previous publications, we always include a consultation with an experienced hepatobiliary surgeon to be sure our interpretation of unresectable is accurate.

2. It is unclear if more than two transplant centers (Mayo Clinic/Rochester; University of Nebraska) have used the treatment protocol used in Heimbach (2006). This introduces uncertainty as to whether similar results reported in Heimbach (2006) can be achieved in other transplant centers. Please see attached recently published article in Gastroenterology (Murad et al 2012) which reports on outcomes at 12 US centers utilizing neoadjuvant chemoradiotherapy followed by liver transplantation, demonstrating similar excellent outcomes across all centers.

3. No quality of life outcomes were reported in the evidence we reviewed. We feel quality of life measures are very important. These data were analyzed and presented at ILTS (International Liver Transplantation Society Meeting) in 2011, and have been submitted for publication to the Journal of Hepatology. This manuscript is currently under peer review. The outcomes show similar or higher quality of life scores using validated measures (such as SF-36 and EUROQOL) for patients treated in the protocol compared to those who were transplanted for other indications.

4. Lack of Medicare age patients treated in the combined neoadjuvant chemoradiotherapy protocol for cholangiocarcinoma: this is largely because most patients of Medicare age have Medicare insurance coverage and thus have been denied access to this therapy. Therefore, they are not as well-represented in the data. However, please note in our most recent series published in Hepatology in 2012 reporting on outcomes for 199 patients, the age range for the population treated is 22-69, and there was not an increased risk for drop out or recurrence based on age. Cholangiocarcinoma greatly impacts Medicare-age patients and certainly they could benefit from access to this therapy.

I strongly agree this therapy should be limited to carefully selected patients. However I do hope approval could be granted to patients who meet the inclusion criteria at centers with existing protocols which are approved by the OPTN, and that this approval could be granted in a timely, standardized fashion rather than via an arduous appeal process that will result in effectively rending the patients ineligible for a therapy that is anticipated to provide a 5 year survival benefit of approximately 70% for patients with no other treatment options. I would be happy to provide any additional information that you may require.

Sincerely,

Julie Heimbach, MD
Liver Transplantation
Mayo Clinic
Rochester, MN 55905
(507)266-6640

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Members of the American Association for the Study of Liver Diseases are appreciative of the step forward that the CMS has given by modifying the liver transplantation NCD (see 260.1 of the Medicare NCD Manual)to remove the non-coverage for extrahepatic unresectable cholangiocarcinoma. However, we are still concerned about leaving this decision at the discretion of Medicare Administrative Contractors acting within their respective jurisdictions. Cholangiocdarcinoma affects up to 4,000 patients annually. In the era before neoadjuvant therapy, outcomes for liver transplantation for cholangiocarcinoma were universally poor with 5-year survival of only 30%. As a result,liver transplant was not considered a valid option for cholangiocarcinoma. However, there have been considerable advances in the treatment of this malignancy with the use of neoadjuvant therapy and this warrants a re-examination of the efficacy of liver transplant for cholangiocarcinoma and its coverage by CMS.

Since the early 1990s, several centers, including the Mayo Clinic and the University of Nebraska have pioneered the use of neoadjuvant therapy to improve outcomes for cholangiocarcinoma in liver transplant. Using pre-transplant chemosensitization and radiotherapy in patients with localized but unresectable cholangiocarcinoma, the Mayo Clinic groups have achieved 5-year survival rates of 73% (JK Heimbach et al, Transplantation 2006). However, this success is not limited to a single center. Murad et al recently published the success of neoadjuvant therapy and liver transplant for cholangiocarcinoma at 12 large-volume transplant centers from 1993 to 2012 (Efficacy of Neoadjuvant Chemoradiation, followed by Liver Transplantation, for Perihilar Cholangiocarcinoma at 12 US Centers. Gastroenterology 2012; epub ahead of print). The study included 287 eligible patients (age range 17-70) with unresectable perihilar (extrahepatic) cholangiocarcinoma who had completed neoadjuvant therapy before liver transplantation and who were followed for a median of 2.5 years. The unadjusted 5-year disease-free survival rate was 65%, a rate that is not only similar to results from earlier single-center series but is also similar to outcomes of liver transplantation for other malignant and non-malignant indications (Scientific Registry of Transplant Recipients, 2009. (Accessed at http://optn.transplant.hrsa.gov/ar2009/909a_li.htm).

Furthermore, in patients who fell within UNOS/OPTN criteria for standard MELD exception (N=166), that is, tumor mass < 3 cm and no evidence of metastic disease, absence of a direct tumor biopsy and no history of cancer in preceding 5 years, survival was 85% at 1 year and 72% at 5 years. These rates of survival are consistent with overall 5-year survival for all indications of 70.2%. (MS Roberts et al., Liver Transplantation 2004). Thus, in carefully selected patients, liver transplantation is a successful therapy for cholangiocarcinoma with success rates that parallel those of other indications for transplantation.

Therefore, AASLD urges CMS to establish standard coverage for liver transplantation in carefully selected patients with extrahepatic cholangiocarcinoma. Should you have any questions about this letter, please contact Sherrie Cathcart at scathcart@aasld.org or 703-299-9766.

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I represent [PHI Redacted] in DAB Board Docket No. A-11-98 [PHI Redacted]. I understand that our statement is part of the record in this NCD reconsideration.

In response to the concern expressed in the cholangiocarcinoma portion of the proposed decision memo, regarding uncertainty as to whether the Mayo Clinic and University of Nebraska results can be acheived elsewhere, I would like to note that on April 2, 2012, a multi-center study “Efficacy of Neoadjuvant Chemoradiation followed by Liver Transplantation for Perihilar Cholangiocarcinoma at 12 US Centers” was accepted for publication in Gastroenterology. The accepted manuscript was published in Gastroenterology’s on line journal on April 16, 2012, see http://www.gastrojournal.org/article/S0016-5085(12)00511-2/abstract. I will forward a copy of this manuscript to the appropriate person.

The proposed decision should become final, in order to allow contractors to cover treatment for these rare malignancies of the liver as effective protocols are developed, and approved by UNOS/OPTN, without the need to revisit a national coverage determination every ten years.

On behalf of [PHI Redacted], I would like to thank you for the opportunity to participate in this process.

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April 23, 2012

To Whom It May Concern:

I am writing on behalf of PSC Partners Seeking a Cure, a 501(c)3 foundation dedicated to providing education, awareness, and research for primary sclerosing cholangitis (PSC), a progressive bile duct disease that has no treatment other than liver transplantation. We have members in every state of the nation and throughout the world. We are the first point of access for newly diagnosed PSC patients who desperately seek support. We at PSC Partners Seeking a Cure are appealing to you to revise NCD 260.1 to include cholangiocarcinoma (CCA) in PSC as an indication for liver transplantation.

There are 29,000 PSC patients in the U.S., and CCA will affect approximately 7 % of the PSC population during the first eleven years after diagnosis, the chances increasing by 0.6 percent with each passing year (http://www.ncbi.nlm.nih.gov/pubmed/15056096). With liver transplantation,PSC patients with CCA nowhave an80% chance of 5-year survival ( http://www.hpbdint.com/upload/PDF/200764103438124875.pdf).

Within our population, cholangiocarcinoma is a very real and frightening diagnosis. We need your support to ensure that patients faced with this horrifying diagnosis get the treatment they so urgently need. For these reasons, we request that NCD 260.1 be changed to provide coverage for cholangiocarcinoma patients who would benefit from a potentially curative liver transplantation.

The Mayo Clinic has established a protocol for treating CCA, but without your help, this life-saving protocol may not be accessible to those who so desperately need it in our PSC population. To know that a potential treatment exists but is out of reach for this deserving population is impossible to comprehend. We seek your support to give us the treatment we need for survival. With the approval from insurance companies, lives can be saved, and our desperate population can be on equal footing with those who are given a place on the transplant list.

We can provide you with charts and statistics on post-transplant survival. But what we would like to impress on you is that the PSC population affected by cholangiocarcinoma is made of people with families, jobs and financial worries, grandparents, young people dreaming of a bright future, and parents desperately fighting for the lives of their children. A change to NCD 260.1 would give our people a chance. It could turn CCA into a mere footnote in their lives. Without your help, all our doors are closed shut upon us.

We appeal to you to look at our excellent survival statistics. We plead with you to remember that there are lives waiting for your verdict. A change to NCD 260.1 authorizing coverage of liver transplants for those with CCA is more than needed. Life is already difficult for PSC patients with CCA. Please give us an equal chance.

Thank you for accepting to consider our request to revise NCD 260.1 and allow so many of us the dream of receiving coverage and the chance to fight for our lives.

Respectfully yours,

Ricky Safer

President, PSC Partners Seeking a Cure

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