[Please note – providers should be sure to follow individual payers’ requirements for preparing
and submitting appeals. Although this template letter is intended to support an appeal, providers
may need to comply with additional requirements to appeal an adverse coverage decision.
Providers are responsible for customizing the letter to reflect the unique background and
diagnosis of a particular patient, as well as the special requirements of the particular payer
involved. The provider is responsible for ensuring the medical necessity of the procedure.]
[insert physician or practice letterhead]
[insert date]
[insert Claims Center / Department]
[insert Payer organization name]
[insert street address]
[insert City, State, Zip Code]
Attn: [Appeals Department]
RE: [insert patient name]
Date of Birth: [insert patient’s DOB]
Policy ID/Group Number: [insert policy ID/Group number]
Plan Number: [insert plan number]
Policy Holder: [insert policy holder’s name]
Date of Service: [insert date of service]
Claim Number: [insert claim number]
To whom it may concern:
I am a(n) [insert specialty]writing to appeal denial of a claim for treatment on behalf of my patient, [insert
patient name] with Lymphoseek® (technetium Tc 99m tilmanocept) injection, which is indicated for use,
with or without scintigraphic imaging, for lymphatic mapping using a hand held gamma counter to locate
lymph nodes draining a primary tumor site in patients with solid tumors for which this procedure is a
component of intraoperative management, and guiding sentinel lymph node biopsy using a hand held
gamma counter in patients with clinically node negative breast cancer, melanoma, and squamous cell
carcinoma of the oral cavity. The procedure was billed under CPT® code [insert code used here] and
Lymphoseek® was billed under HCPCS code [A9520 [Technetium Tc 99 tilmanocept, diagnostic, up to 0.5
millicuries]]. I believe that Lymphoseek® was medically necessary for this patient and should be covered.
Intraoperative Lymphatic Mapping (ILM) is a procedure to assist the [breast surgeon/oncologist] in the
diagnostic evaluation of the patient’s cancer. Identification of first draining lymph nodes is a strong
predictor of lymph node status. 1,2 [In breast cancer, ILM and sentinel node biopsy is recommended for
patients with early stage breast cancer (i.e., T1 or T2 tumors </=50 mm in greatest diameter), and in
select cases of ductal carcinoma in situ.3,4 In melanoma, ILM and sentinel lymph node biopsy is
recommended for patients with intermediate-thickness melanoma and or patients with thick melanomas
for staging purposes.5]
Current Procedural Terminology (CPT®) is copyright 2014 American Medical Association. All rights
reserved. CPT is a registered trademark of the American Medical Association. The American Medical
Association assumes no liability for data contained or not contained herein.
The safety and efficacy of Lymphoseek® in lymphatic mapping for the localization of lymph nodes
draining a primary tumor site were evaluated in two pivotal Phase 3 open-label, multicenter, single-arm,
within-subject, active-comparator trials of patients with either melanoma or breast cancer.6, 7, 8 In these
Phase 3 clinical trials, Lymphoseek® on average, was present in 97% (range 94%-100%) of resected and
histopathology confirmed lymph nodes.6 Lymphoseek® localized an average of 2 lymph nodes per
patient.6
In Study One, of 179 patients who received Lymphoseek®, 94 (53%) had known or suspected breast
cancer and 85 (48%) had known or suspected melanoma. The median age was 59 years (range 20 to 90
years) and most (72%) were women.6
In Study Two, of 153 patients who received Lymphoseek®, 77 (50%) had known or suspected breast
cancer and 76 (50%) had known or suspected melanoma. The median age was 61 years (range 26 to 88
years) and most (68%) were women.6
In 2014, the FDA reviewed a third Phase 3 study evaluating the use of Lymphoseek® in SLN biopsy in 83
patients with squamous cell carcinoma (T1-T4a, no nodal or metastatic disease) of the oral cavity (n=79,
including 20 patients with floor of mouth tumors), skin (n=5), and lip (n=1). Diagnostic efficacy was
determined by the patient level false negative rate (FNR) of sentinel lymph node detection by
Lymphoseek® as confirmed by pathologic assessment of lymph nodes removed during a required
elective neck dissection. 97.6% of patients had at least one SLN identified.9 Pathology-positive lymph
nodes were found in 39 patients, all of whom had squamous cell carcinoma of the oral cavity. Only 2.6%
of patients with pathology positive lymph nodes were not identified by Lymphoseek (per patient FNR =
2.6%). Lymphoseek® also demonstrated a high negative predictive value—98% of patients identified as
pathology-negative by Lymphoseek® were confirmed as true negative by END. 9, 10
In clinical trials, no serious adverse reactions were reported during clinical trials with Lymphoseek®. A
total of 553 subjects with either breast cancer, melanoma, or squamous cell carcinoma of the oral cavity,
skin and lip have received Lymphoseek in open-label, single-arm clinical trials. No patients experienced
serious adverse reactions related to Lymphoseek. The most common adverse reactions in clinical trials (n
= 553 patients) were:
 Injection site irritation (4 patients; 0.7%)
 Injection site pain: 0.2%; n = 1 of 542
 Other adverse reactions were uncommon, and of mild severity and short duration
A full discussion of Lymphoseek risks is provided below.
Diagnostic efficacy was determined by the number of histology-confirmed lymph nodes detected by
Lymphoseek®. Lymphoseek® (50 mcg; 0.5 mCi) was injected into patients at least 15 minutes prior to the
scheduled surgery, and blue dye was injected shortly prior to initiation of the surgery. Intraoperative
lymphatic mapping was performed using a hand-held gamma detection probe followed by excision of
lymph nodes identified by Lymphoseek®, blue dye, or the surgeon’s visual and palpation examination. The
resected lymph nodes were sent for histopathology evaluation.6
In short, it was demonstrated in clinical trials that Lymphoseek-guided SLN biopsy accurately determines
if the cancer has spread through the lymphatic system.6 SLN biopsy procedures may allow for the option
of more limited lymph node surgery in patients with sentinel nodes negative for cancer.4,6
Current Procedural Terminology (CPT®) is copyright 2014 American Medical Association. All rights
reserved. CPT is a registered trademark of the American Medical Association. The American Medical
Association assumes no liability for data contained or not contained herein.
For additional information regarding Lymphoseek, please visit www.lymphoseek.com or call Navidea at
1-800-476-5270. If you have additional questions regarding this specific procedure or patient, please
contact (insert physician contact information here).
[Mr./Ms./Mrs.] [insert patient’s last name] is a [insert age] year old [female/male] who has [breast
cancer/malignant melanoma] (ICD-9-CM [insert ICD-9 codes]). [Mr./Ms./Mrs.] [insert patient’s last
name] presented to me on [insert date] with [details such as physical exam results and clinical
impressions]. [If other localization products were used or considered prior to Lymphoseek®, would add:
Other therapies [tried/considered] as part of the localization of [Mr./Mrs./Ms.] [insert patient’s last
name]’s lymph nodes included [describe other products]. However, [provide rationale for using
Lymphoseek® as compared to comparator products, or why it was used following a comparator product.]
I treated [Mr./Ms./Mrs.] [insert patient’s last name] with Lymphoseek® (technetium Tc 99m tilmanocept)
injection on [insert date] to assist in the localization of lymph nodes draining a primary tumor site in
patients with breast cancer or melanoma. The Lymphoseek® dose required for this patient was [insert
dose] µg tilmanocept and a technetium Tc 99m dose of [insert dose].
This patient’s response to Lymphoseek® was [describe results]. Based on this outcome, I [plan to
treat/treated] [Mr./Mrs./Ms.] [insert patient’s last name] with [indicate how the results of the test impact
patient management – i.e., the planned course of treatment and duration]. Follow-up is expected to
involve [include expected additional evaluations and treatments].
Lymphoseek® was medically necessary in the localization of lymph nodes draining the primary tumor site
of [Mr./Mrs./Ms.] [insert patient’s last name]’s [breast cancer/malignant melanoma/squamous cell
carcinoma of the oral cavity/solid tumor]. Thank you for your consideration of this matter. If you have
any questions or require additional information, please contact me at [insert physician’s contact
information].
Respectfully submitted,
[Physician Signature]
[Physician’s full name]
[Address]
[Telephone number]
Current Procedural Terminology (CPT®) is copyright 2014 American Medical Association. All rights
reserved. CPT is a registered trademark of the American Medical Association. The American Medical
Association assumes no liability for data contained or not contained herein.
Indication:
Lymphoseek (technetium Tc 99m tilmanocept) injection is indicated with or without scintigraphic imaging for:


Lymphatic mapping using a handheld gamma counter to locate lymph nodes draining a primary tumor site
in patients with solid tumors for which this procedure is a component of intraoperative management.
Guiding sentinel lymph node biopsy using a handheld gamma counter in patients with clinically node
negative squamous cell carcinoma of the oral cavity, breast cancer or melanoma
Important Safety Information:
In clinical trials with Lymphoseek, no serious hypersensitivity reactions were reported, however Lymphoseek may
pose a risk of such reactions due to its chemical similarity to dextran. Serious hypersensitivity reactions have been
associated with dextran and modified forms of dextran (such as iron dextran drugs).
Prior to the administration of Lymphoseek, patients should be asked about previous hypersensitivity reactions to
drugs, in particular dextran and modified forms of dextran. Resuscitation equipment and trained personnel should
be available at the time of Lymphoseek administration, and patients observed for signs or symptoms of
hypersensitivity following injection.
Any radiation-emitting product may increase the risk for cancer. Adhere to dose recommendations and ensure safe
handling to minimize the risk for excessive radiation exposure to patients or health care workers.
In clinical trials, no patients experienced serious adverse reactions and the most common adverse reactions were
injection site irritation and/or pain (<1%).
References
1.
Schulze T, Mucke J, Markwardt J, Schlag PM, Bembenek A. Long-term morbidity of patients with early breast
cancer after sentinel lymph node biopsy compared to axillary lymph node dissection. J Surg Oncol.
2006;93(2):109-119.
2. Veronesi U, Galimberti V, Zurrida S, et al. Sentinel lymph node biopsy is an indicator for axillary dissection in
early breast cancer. Eur J Cancer. 2001;37(4):454-458.
3. Lyman GH, Giuliano AE, Sommerfeld MR, et al. American Society of Clinical Oncology Guideline
Recommendations for Sentinel Lymph Node Biopsy in Early-Stage Breast Cancer. J Clin Oncol.
2005;23(30):7703-7720.
4. NCCN Clinical Practice Guideline: Breast Cancer. Available at:
http://www.nccn.org/professionals/physician_gls/pdf/breast.pdf Accessed November 6, 2014.
5. Wong SL, Balch CM, Hurley P, et al. Sentinel Node Biopsy for Melanoma: American Society of Clinical Oncology
and Society of Surgical Oncology Joint Clinical Practice Guideline. Ann Surg Oncol, epub July 6, 2012.
6. LYMPHOSEEK® Injection Package Insert. Dublin, OH: Navidea Biopharmaceuticals, Inc., Dublin OH;
7. October 2014.
8. Sondak VK, King DW, Zager J, et al Combined analysis of Phase III trials evaluating [99mTc]Tilmanocept and
vital blue dye for identification of sentinel lymph nodes in clinically node-negative cutaneous melanoma. Ann
Surg Oncol 2013;20:680-8.
9. Wallace AM, Han LK, Povoski SP, et al. Comparative evaluation of [99mTc]Tilmanocept for sentinel node
mapping in breast cancer patients: results of two phase 3 trials. Ann Surg Oncol; 2013;20:2590-9.
10. Data on file, Navidea Biopharmaceuticals, Inc. Dublin, OH. Sept 2014
11. Lai SW. Receptor-targeted 99mTc-tilmanocept for sentinel lymph node biopsy (SLNB) in HNSCC: predictive
utility vs. elective neck dissection. Presented at 6th European Congress on Head and Neck Oncology. Liverpool,
UK. April 24-26, 2014. Abstract.
12. FDA news release. FDA approved Lymphoseek to help determine the extent of head and neck cancer in the body.
Available at: http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm401085.htm. Accessed
September 17, 2014
Current Procedural Terminology (CPT®) is copyright 2014 American Medical Association. All rights
reserved. CPT is a registered trademark of the American Medical Association. The American Medical
Association assumes no liability for data contained or not contained herein.