Making the Case for Sentinel Node Biopsy in Early Cancers of the Oral Cavity


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If no imaging tests are accurate enough to predict the presence of metastatic disease in the neck, sentinel node biopsy should be considered as an alternative to elective neck dissection.
— Sandeep Samant, MD

“The majority of patients with oral cavity cancers will undergo an unnecessary operation,” ­Sandeep Samant, MD, stated at a session on managing N0 neck cancer at the 2016 Lurie Cancer Center Multidisciplinary Head & Neck Symposium in Chicago.1 That operation is elective neck dissection, and it is unnecessary in most patients, he said, because metastatic disease occurs in only 20% to 30% of these patients. “So how do you avoid overtreating 70% of these patients?” The solution he proposed is sentinel lymph node biopsy for patients with early-stage disease (T1, N2).

Dr. Samant is Chief, Head and Neck Surgery, Northwestern Medicine, and he served as symposium chair. The symposium was sponsored by the Robert H. Lurie Comprehensive Cancer Center of Northwestern University and attended by more than 235 physicians and other health-care professionals.

No Good Predictive Factors

“There is now level 1 evidence that elective treatment offers a survival advantage,”2 Dr. Samant noted. The issue now becomes: “How do you choose a patient to offer this treatment? If you have a patient with a superficial lesion, do you still offer elective treatment?”

Dr. Samant noted that a lesion thickness of 4 mm is used by some physicians as the cutoff, beyond which they will offer a neck dissection. However, he said, neither thickness nor other factors, such as “depth, pattern of invasion, differentiation, lymphatic invasion, lymphocytic infiltration, or a variety of different biomarkers that have been looked at necessarily predict the presence or absence of metastatic disease in the head or neck with sufficient accuracy to act in lieu of a neck dissection.”

He cited a study that looked at all of these factors and found that “only the grade of differentiation, lymphatic invasion, and mode of invasion—factors that tended to covary—were associated with the presence of metastatic disease.3 But, in fact, neither tumor depth nor tumor thickness was associated with the presence of metastatic disease in the lymph nodes,” he said. “Calculating the association with presence or absence of metastatic disease at different levels of depth,” he added, showed tumor depth “essentially is an unreliable test,” with about the same predictive ability as a “flip of the coin.”

Other studies have looked at positron-emission tomography (PET) scans, and in Europe, “ultrasound-guided fine-needle aspiration is quite popular,” Dr. Samant said. “The problem is this: The majority of the metastatic disease in the lymph nodes is microscopic, so that it is just not something that will be picked up by a PET scan or necessarily by an ultrasound-guided needle biopsy. If no imaging tests are accurate enough to predict the presence of metastatic disease in the neck,” he continued, “sentinel node biopsy should be considered as an alternative to elective neck dissection.”

Smaller Scar, Better Outcomes

Sentinel node biopsy has been used in melanoma or breast cancer reliably, Dr. Samant noted, and that experience can be applied to head and neck cancer. “The concept of a sentinel node biopsy is that metastatic spread is orderly, such that if you were to assess the most proximal lymph node in the pattern of spread, which is the sentinel lymph node, and that lymph node turns out to be negative in pathology, then that is a reliable indicator that there is no metastatic disease in the rest of the nonsentinel lymph nodes in the neck,” Dr. Samant said.

“The sentinel lymph node biopsy offers the advantage of leaving a small scar,” he said. Other advantages are that the procedure causes significantly less soft-tissue fibrosis, requires reduced skin anesthesia, and is associated with reduced long-term pain and negligible shoulder morbidity. “It is not only that the scar is smaller, but the scope of the section is smaller as well, which results in better ultimate outcomes,”4 Dr. Samant said.

Important to Plan Incision

A scan is obtained before the start of the sentinel node biopsy procedure. “Once the patient goes to the operating room, it is important to plan the incision in the line of a future neck dissection, should that become necessary,” Dr. ­Samant noted. Using blue dye “helps identify the lymph nodes faster,” he added. “You can often see the lymphatic drainage intraoperatively, and that—when you keep doing this over and over again—gives you an added layer of appreciation for the pattern of lymphatic drainage in different varieties of head and neck cancer.”

Sentinel node biopsy is not simple, and there is a learning curve, not only on the part of the surgeon, but on the part of the team.
— Sandeep Samant, MD

Lymph nodes are serially sectioned, and the pathology results are available in 3 or 4 days. “If the patient has metastatic disease in those lymph nodes, then we bring the patient back for a complete neck dissection,” he said.

“In our group of 34 patients, 6 of whom had floor-of-mouth cancer, we were able to successfully perform a sentinel node biopsy in 32 patients (94%). In the two patients who did not have an identifiable sentinel lymph node, we performed an elective neck dissection. For all floor-of-mouth cancers, we could identify a sentinel node for pathologic analysis,” Dr. Samant stated.

“Of 29 patients who had negative sentinel node biopsies, 2 went on to develop metastatic disease, but fortunately, both of them responded to salvage therapy,” resulting in an ultimate regional control rate of 94% at 2 years, Dr. Samant reported. Neither of the two patients who had unsalvageable neck failure had negative sentinel node biopsy results.

Meta-analyses Show High Sensitivity

A meta-analysis of series in the literature on sentinel node biopsy showed that the sensitivity for occult metastases with sentinel node biopsy was greater than 90%,5 Dr. Samant said. What that means, he explained, is “if you had a population of 100 patients, of whom 30% actually did harbor metastatic disease, the sentinel node biopsy procedure would pick up 27 of them. It would miss 3 of those 30 patients.”

To compare sentinel node biopsy and elective neck dissection, Dr. Samant and colleagues performed a meta-analysis of 10 elective neck dissection studies and 8 sentinel node biopsy studies among patients with T1/T2, N0 oral cavity cancers who were previously untreated and whose sole staging procedure was either elective neck dissection or sentinel node biopsy. Using regional (neck node) failure as the endpoint, the sensitivity was superior for sentinel node biopsy, Dr. Samant reported. Sensitivity was 0.64 (95% confidence interval [CI] = 0.54–0.75) among the 444 patients in the 10 elective neck dissection studies vs 0.85 (95% CI = 0.74–0.97). “Additionally, there was an advantage to survival [with sentinel node biopsy],” he said, “although it was not statistically significant.”

Tailored, Scientific Approach

“It could be that individualized sampling—detecting the lymphatic drainage in each patient—is actually better than basing the sampling on historical patterns. Also, the sentinel node biopsy procedures are typically performed by more experienced surgeons. That may play a role.” In addition, he said, “you are more likely to catch aberrant drainage with elective neck dissection.”

That’s because the sentinel node biopsy procedure involves injecting dye around the tumor and testing which lymph node the dye goes to first. “That will be the sentinel node, and that is the correct drainage pattern for that individual,” Dr. Samant explained in an interview with The ASCO Post.

“We know from experience that there is tremendous variation in drainage patterns,” he continued. “When we do an elective neck dissection, we just choose lymph node levels I through III. But what if the draining node is on the other side? What if it is in level IV, and you have only taken out levels I through III? The sentinel node biopsy procedure is more scientific—a more tailored approach to sampling and staging the lymph nodes in the neck—than an elective neck dissection.”

Adoption of the Procedure

“As a result of this meta-analysis,” Dr. Samant said, “for the past 2 or 3 years, sentinel node biopsy procedure has been included in the National Comprehensive Cancer Network® (NCCN) Guidelines® for cancer of the oral cavity (version 2.2014). An overwhelming majority of panel members voted for inclusion of the sentinel node biopsy option for the oral cancers in the guidelines,” Dr. Samant reported. “It will be interesting to see how the adoption of the procedure progresses over the next 4 to 5 years.”

One of the reasons sentinel node biopsy for oral cancers has not “caught on” yet, Dr. Samant acknowledged, is that surgeons worry that it can miss 10% to 15% of occult metastatic disease. Other reasons include a slightly lower rate of identifying primary floor-of-mouth cancers and the fact that a second anesthetic is required if you find a positive sentinel node and the patient needs to come back for a complete neck dissection.

The “role of tradition in surgery” also contributes to the slow adoption of sentinel node biopsy. “Head and neck surgeons are used to doing elective neck dissections and are comfortable with doing selective neck dissections. Many don’t want to change,” Dr. Samant told The ASCO Post. “I don’t think that sentinel node biopsy is even offered as an option to a lot of patients, even at academic centers, because it has not become routine in the head and neck circles.”

Learning Curve

“Sentinel node biopsy is not simple, and there is a learning curve, not only on the part of the surgeon, but on the part of the team,” Dr. Samant continued. “The nuclear medicine doctor and pathologists have to become familiar with the mucosal cancers. Unlike breast cancer or melanoma—settings where the nuclear medicine doctors are comfortable injecting the lesion in the skin—nuclear medicine radiologists are not comfortable doing the injection in the oral cavity cancers. The head and neck surgeon generally has to come in and do the injection for oral cancers.”

Most major centers already have experience doing sentinel node biopsies for breast cancer and melanoma, Dr. Samant said. “The head and neck is an anatomically crowded area, and there was worry in the beginning that the sentinel node procedure might not be as accurate as it is for melanoma in the limb or trunk, where the nodes are quite far removed from the primary tumor. Indeed, early on, when the sentinel node procedure was done in melanoma of the head and neck by surgical oncologists, not head and neck surgeons, it was not as accurate as sentinel node biopsy for melanoma elsewhere.”

Since head and neck surgeons adopted the sentinel node biopsy procedure, however, and now have a good deal of experience doing the procedure, “the accuracy of the sentinel node biopsy procedure is the same as it is for melanoma and breast cancer,” Dr. Samant said.

“With experience, you have to be able to standardize the technique,” he told the symposium participants, “and make sure you don’t miss any positive nodes. If you do that, your patients will be happier and have a smaller scar.” ■

Disclosure: Dr. Samant reported no potential conflicts of interest.

References

1. Samant S: Management of N0 neck. 2016 Multidisciplinary Head & Neck Symposium. Presented December 3, 2016.

2. D’Cruz, AK, Vaish R, Kapre N, et al: Elective vs therapeutic neck dissection in node-negative oral cancer. N Engl J Med 373:521-529, 2015.

3. Goerkem M, Braun J, Stoeckli SJ: Evaluation of clinical and histomorphological parameters as potential predictors of occult metastases in sentinel lymph nodes of early squamous cell carcinoma of the oral cavity. Ann Surg Oncol 17:527-535, 2010.

4. Murer K, Huber GF, Haile SR, et al: Comparison of morbidity between sentinel node biopsy and elective neck dissection for treatment of the N0 neck in patients with oral squamous cell carcinoma. Head Neck 33:1260-1264, 2011.

5. Govers TM, Hannink G, Merkx MA, et al: Sentinel node biopsy for squamous cell carcinoma of the oral cavity and oropharynx: A diagnostic meta-analysis. Oral Oncol 49:726-732, 2013.


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