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FDA approves imaging agent to detect spread of head and neck cancers
The FDA today expanded its approval of the radioactive diagnostic imaging agent technetium 99m tilmanocept, endorsing its use as a component of sentinel lymph node biopsy in patients with squamous cell carcinoma of the head and neck.
The results can help clinicians determine whether certain patients — specifically those whose sentinel nodes are negative for cancer — have the option of undergoing more limited lymph node surgery, according to FDA.
Technetium 99m tilmanocept (Lymphoseek, Navidea Biopharmaceuticals) — approved last year to guide lymphatic mapping in patients with melanoma and breast cancer — helps with the localization of lymph nodes that drain a primary tumor site.
Clinicians inject the agent into a tumor area.
“Using a handheld radiation detector, [they] find the sentinel lymph nodes that have taken up Lymphoseek’s radioactivity,” Libero Marzella, MD, PhD, director of the division of medical imaging products in the FDA’s Center for Drug Evaluation and Research, said in a press release.
The FDA based its approval on the results of a phase 3 trial that evaluated the effectiveness of technetium 99m tilmanocept in 85 patients with squamous cell carcinoma of the skin, lip and oral cavity.
After administration of technetium 99m tilmanocept, surgeons performed dissection of nodes identified as suspicious by the agent, as well as those identified based on tumor location and other factors.
Results of pathologic evaluation showed 39 patients had positive lymph nodes, and technetium 99m tilmanocept accurately identified 38 of those cases. Researchers calculated an overall 2.56 false-negative rate (P=.0205).
Technetium 99m tilmanocept prompted the removal of an average of four lymph nodes per patient, compared with an average of 38 per patient removed based on multiple-level nodal dissection. This suggests the agent could considerably reduce morbidity among patients with head and neck cancers who undergo sentinel lymph node biopsy, Navidea Biopharmaceuticals officials said in a press release.
The most frequently reported side effects reported in the clinical trial were irritation or pain at the injection site, according to FDA.
Perspective
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Refinements in surgical techniques have allowed us to select patients who are appropriate candidates for less extensive, and typically less morbid, surgical procedures with improved functional outcomes. These are exemplified by larynx-preserving surgical procedures, transoral robotic surgery, etc. One of the continued challenges is how to address the neck in patients with no radiographic or clinical evidence of disease.
Neck lymph node dissections have historically provided valuable information to clinicians regarding the patient’s pathologic stage and high-risk features for recurrence, and they play an important role in regional control of disease in patients treated with surgery. However, there is a population of patients who are ultimately found to have no evidence of metastases to the neck, and they are exposed to the added cost and morbidity of this procedure.
This technology holds promise for being able to identify patients who may be spared a neck dissection. Yet, there are a few issues that merit consideration.
First, one cannot overlook regional control as a very important oncologic outcome in these patients undergoing curative intent therapy. I would be curious to know what the oncologic outcomes of patients undergoing sentinel lymph node biopsy compare to those receiving elective lymph node dissection (END) alone. Perhaps a prospective comparison of END and sentinel lymph node biopsy may make sense, with endpoints of interest being oncologic outcomes, cost-effectiveness and patient-reported quality-of-life measures.
Second, as in any curative-intent therapeutic approach, appropriate patient selection is key.
There have been published reports of the accuracy of sentinel lymph node dissection in early-stage oral cavity tumors (T1 and T2 disease). I am curious to see what the results are for patients with T3 to T4a disease (included in this study), and whether this technology ought to be used in these patients who routinely undergo elective lymph node dissection due to high risk of nodal involvement.
Perspective
Back to TopThe approval of Lymphoseek for head and neck cancers will make sentinel lymph node biopsy more available for patients with cancers of the upper aerodigestive tract. The sentinel lymph node biopsy technique for head and neck cancers is most useful for select patients with lower risk of nodal spread, when physicians are trying to avoid postoperative therapy (like radiation) and minimize the extent of neck node removal. One difficulty that is somewhat unique to head and neck cancers is that the site of the cancer that needs to be injected can be hard to reach for patients whose tumors are in locations other than the mouth.
Perspective
Back to TopTc-99-based sentinel lymph node mapping is a routine part of staging melanomas but remain investigational for early oral cancer. The technique has been studied most intensively in European centers, where it was found to be safe and accurate in detecting micrometastatic disease in oral cancer. Lymphoscintigraphy with sentinel lymph node biopsy potentially could replace elective cervical lymphadenectomy in approximately 70% of patients with early oral cancer. The FDA approval may enhance the adoption of the technology for head and neck cancers. However, adoption may be hampered by limited experience with the technique by some surgeons. Specialized centers that also treat melanoma are most likely to be early adopters.