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Validity of sentinel node biopsy in early
oral and oropharyngeal carcinoma
C.G.U. Riese, J.-A. Karstadt, A. Schramm, S. Güleryüz, G. Dressel, K.J.
Lorenz, B. Klemenz, A. Sailer, S. Seitz, F. Wilde
Introduction
• Approximately 20-30% of patients with clinically N0 squamous cell
carcinoma in the head and neck region have subclinical (occult)
metastases in cervical lymph nodes (Acc. to Robbins et al., 2002)
•This means that elective neck dissection may be overtreatment for
approximately 70-80% of patients
•Magnetic resonance tomography (MRT), computed tomography (CT), and
positron emission tomography (PET) are used for staging head and neck
tumor. However, their accuracy is not sufficient.
•5-year survival rate of patients with metastases in cervical lymph nodes is
dependent on the stage/ involvement of neck nodes.
(Acc. To Spengler K: Langzeitresultate der Behandlung von Tumorerkrankungen im
Bereich von Mundhohle und Oropharynx, 2009)
Introduction
• Neck dissection brings along with it a large
number of functional impairments which are
linked to higher morbidity
•The concept of sentinel lymph node
identification and biopsy is based on the fact
that metastasis from a primary tumor occurs by
predictable orderly spread to the first-echelon
nodes before reaching nodes in the remainder
of the lymphatic basin.
•Overall survival rate in sentinel node negative
patients was found to be 93% at 3 years
whereas it was 67% in sentinel node positive
cases.
(Acc. to Oral & Maxillofacial Surgery Clinics of
North America, 2007)
Purpose of this study
•To evaluate whether SNB can be a suitable method to avoid
invasive elective neck dissections in patients with early
stage oral and oropharyngeal cancer and clinically non-
metastatic lymph nodes (cN0).
•To evaluate the feasibility of identifying and removing
lymph nodes in the draining area of the tumor, which may
have been left in place with conventional neck dissection
concepts.
Subjects & Methods
•Study design- Retrospective study
•Place of study-General Armed Forces Hospital, Ulm,
Germany
•The study was performed in accordance with the
Declaration of Helsinki. Ethics approval was obtained from
Ulm University in 2012.
•Inclusion criteria- All patients had a histopathologically
diagnosed SCC of head and neck region and had neither
regional metastases in cervical lymph nodes (cN0) nor
distant metastases (cM0) that could be detected by clinical
or radiological methods (CT, MRT, PET).
Subjects & Methods
•Study population- Non-randomised cohort of 36 SCC patients with
clinically and radiographically N0 necknode metastasis
•A total of 16 carcinomas were localized in the mouth floor, 10 patients
had tongue cancer, 4 had a tumor on the alveolar crest of the lower jaw,
2 carcinomas were found in the buccal mucosa, 2 in the mandibular
retromolar region, and only 1 was localized in the retro-pharyngeal
region.
•The inclusion criteria of this study was met by 24 men (66.6%) and 12
women (33.3%) with an average age of 62.8 years (range 29-81 years).
•All patients underwent preoperative SPECT before neck dissection and
excision of primary tumor
Study methodology
Preoperative lymphoscintigraphy for sentinel node (SLN) detection
24hrs before the surgery. 40MBq technetium-99m nanocolloid was used
as tracer for peritumoral injections.
Sentinel nodes were located using a gamma probe and their positions
were marked on the skin
Tumor resection and lymph node preparation:
1. The decision whether unilateral or a bilateral selective neck
dissection was performed was determined by the localization of the
tumor and the drainage of the medicinal radiochemistry during
sentinel node detection.
2. Excised SLN were subjected to HP examination and IHC for detection
of metastases. All other excised lymph nodes during neck dissection
were pathologically examined.
Results
•SLN could be detected by the gamma probe before surgery in 35 of 36
patients (97.2%).
•Occult metastases were detected in 12 of 36 patients (33.3%). The average
size of metastasised lymph nodes was 15.2 mm.
•Out of the 15 metastases , 14 were found in the excised SLN. Except of one,
all the metastases were found in a SLN.
•SLN in level V was detected in 4 cases (11.1%)
•No incidence of skip metastases seen.
•No incidence occult metastases were detected in the resected tissue in any
of the patients with negative SLN as well.
•The authors achieved a predictive value of 100% for true negative cervical
lymph node status when SLN were free of metastases.
Results
•In 1 patient, an affected lymph node was detected at the transition
between levels IV and V. All other occult metastases were located at
levels I to III. SLN at level V were also detected and successfully resected
in 3 other patients.
Discussion
•Occult metastases was found in only 33.3% of all cases selected in this
study.
• This shows that around 70% of patients are possibly undergoing
unnecessary neck dissections and may end up receiving overtreatment.
• Stoeckli et al. stated that SNB is a precise staging method for patients
with clinically N0 cervical lymph nodes.
•Using lymphoscintigraphy and a gamma probe, authors succeeded in
identifying SLN in all but one patient. This means that we achieved a
sentinel detection rate of 97.2%. This corresponds to average detection
rates described in the literature, i.e., 97%
(Pitman et al., 1998; Civantos et al., 2010).
Discussion
•In tumors with SLN containing micrometastases (<2mm), the chance of
non-SLNs harbouring disease is 4% whereas the presence of
macrometastases in an SLN is accompanied by non-SLN deposits in 26%
cases.
(Acc. To Hermanek et.al.,1999)
•It is very difficult to identify micrometastases using modern imaging
techniques (e.g.: PET/CT). SLN biopsy is useful in identifying these
micrometastatic nodes.
•Another advantage of SLN biopsy is that it also helps to identify the
small tumor affected lymph nodes which may not have been included in
conventional neck dissections.
•The study shows that SNB have a specificity of 100% and sensitivity of
94%.
Disadvantages of SNB
A fundamental problem of SNB is the fact that once a positive SLN has
been detected, the patient should undergo neck dissection/ a second
surgical procedure.
This problem can be overcome if we use a frozen section or a real time
PCR intraoperatively after the excision of the sentinel node.
SNB is a technique sensitive and expensive procedure.
Skip metastases may go undetected in SNB technique. Thus we may
miss neck metastases in carcinoma of the tongue.
Limitations of this study
The greatest disadvantage of this study is its retrospective study
design.
Nonrandomised study
Small sample size
Lots of variables as the study population includes carcinoma of the
whole head and neck region.
Conclusion
Study results show that the SNB method is a precise method for
mapping and detecting individual lymphatic drainage patterns and
staging of early-stage oropharyngeal squamous cell carcinomas.
SNB has the potential to reduce the overtreatment of clinically N0
patients where neck dissection can be avoided.
Prospective studies are needed to determine whether SNB without
elective neck dissection for clinically and radiologically unremarkable
cervical lymph nodes can become a reliable course of treatment for
carcinomas of the head and neck region.
Intraoperative examination of excised SLN using highly sensitive qRT-
PCR instead of conventional frozen section analysis could be a way to
ensure timely action when lymph nodes are affected.
Validity of sentinel node biopsy in early oral and oropharyngeal carcinoma

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Validity of sentinel node biopsy in early oral and oropharyngeal carcinoma

  • 1.
  • 2. Validity of sentinel node biopsy in early oral and oropharyngeal carcinoma C.G.U. Riese, J.-A. Karstadt, A. Schramm, S. Güleryüz, G. Dressel, K.J. Lorenz, B. Klemenz, A. Sailer, S. Seitz, F. Wilde
  • 3. Introduction • Approximately 20-30% of patients with clinically N0 squamous cell carcinoma in the head and neck region have subclinical (occult) metastases in cervical lymph nodes (Acc. to Robbins et al., 2002) •This means that elective neck dissection may be overtreatment for approximately 70-80% of patients •Magnetic resonance tomography (MRT), computed tomography (CT), and positron emission tomography (PET) are used for staging head and neck tumor. However, their accuracy is not sufficient. •5-year survival rate of patients with metastases in cervical lymph nodes is dependent on the stage/ involvement of neck nodes. (Acc. To Spengler K: Langzeitresultate der Behandlung von Tumorerkrankungen im Bereich von Mundhohle und Oropharynx, 2009)
  • 4. Introduction • Neck dissection brings along with it a large number of functional impairments which are linked to higher morbidity •The concept of sentinel lymph node identification and biopsy is based on the fact that metastasis from a primary tumor occurs by predictable orderly spread to the first-echelon nodes before reaching nodes in the remainder of the lymphatic basin. •Overall survival rate in sentinel node negative patients was found to be 93% at 3 years whereas it was 67% in sentinel node positive cases. (Acc. to Oral & Maxillofacial Surgery Clinics of North America, 2007)
  • 5. Purpose of this study •To evaluate whether SNB can be a suitable method to avoid invasive elective neck dissections in patients with early stage oral and oropharyngeal cancer and clinically non- metastatic lymph nodes (cN0). •To evaluate the feasibility of identifying and removing lymph nodes in the draining area of the tumor, which may have been left in place with conventional neck dissection concepts.
  • 6. Subjects & Methods •Study design- Retrospective study •Place of study-General Armed Forces Hospital, Ulm, Germany •The study was performed in accordance with the Declaration of Helsinki. Ethics approval was obtained from Ulm University in 2012. •Inclusion criteria- All patients had a histopathologically diagnosed SCC of head and neck region and had neither regional metastases in cervical lymph nodes (cN0) nor distant metastases (cM0) that could be detected by clinical or radiological methods (CT, MRT, PET).
  • 7. Subjects & Methods •Study population- Non-randomised cohort of 36 SCC patients with clinically and radiographically N0 necknode metastasis •A total of 16 carcinomas were localized in the mouth floor, 10 patients had tongue cancer, 4 had a tumor on the alveolar crest of the lower jaw, 2 carcinomas were found in the buccal mucosa, 2 in the mandibular retromolar region, and only 1 was localized in the retro-pharyngeal region. •The inclusion criteria of this study was met by 24 men (66.6%) and 12 women (33.3%) with an average age of 62.8 years (range 29-81 years). •All patients underwent preoperative SPECT before neck dissection and excision of primary tumor
  • 8. Study methodology Preoperative lymphoscintigraphy for sentinel node (SLN) detection 24hrs before the surgery. 40MBq technetium-99m nanocolloid was used as tracer for peritumoral injections. Sentinel nodes were located using a gamma probe and their positions were marked on the skin Tumor resection and lymph node preparation: 1. The decision whether unilateral or a bilateral selective neck dissection was performed was determined by the localization of the tumor and the drainage of the medicinal radiochemistry during sentinel node detection. 2. Excised SLN were subjected to HP examination and IHC for detection of metastases. All other excised lymph nodes during neck dissection were pathologically examined.
  • 9. Results •SLN could be detected by the gamma probe before surgery in 35 of 36 patients (97.2%). •Occult metastases were detected in 12 of 36 patients (33.3%). The average size of metastasised lymph nodes was 15.2 mm. •Out of the 15 metastases , 14 were found in the excised SLN. Except of one, all the metastases were found in a SLN. •SLN in level V was detected in 4 cases (11.1%) •No incidence of skip metastases seen. •No incidence occult metastases were detected in the resected tissue in any of the patients with negative SLN as well. •The authors achieved a predictive value of 100% for true negative cervical lymph node status when SLN were free of metastases.
  • 11. •In 1 patient, an affected lymph node was detected at the transition between levels IV and V. All other occult metastases were located at levels I to III. SLN at level V were also detected and successfully resected in 3 other patients.
  • 12. Discussion •Occult metastases was found in only 33.3% of all cases selected in this study. • This shows that around 70% of patients are possibly undergoing unnecessary neck dissections and may end up receiving overtreatment. • Stoeckli et al. stated that SNB is a precise staging method for patients with clinically N0 cervical lymph nodes. •Using lymphoscintigraphy and a gamma probe, authors succeeded in identifying SLN in all but one patient. This means that we achieved a sentinel detection rate of 97.2%. This corresponds to average detection rates described in the literature, i.e., 97% (Pitman et al., 1998; Civantos et al., 2010).
  • 13. Discussion •In tumors with SLN containing micrometastases (<2mm), the chance of non-SLNs harbouring disease is 4% whereas the presence of macrometastases in an SLN is accompanied by non-SLN deposits in 26% cases. (Acc. To Hermanek et.al.,1999) •It is very difficult to identify micrometastases using modern imaging techniques (e.g.: PET/CT). SLN biopsy is useful in identifying these micrometastatic nodes. •Another advantage of SLN biopsy is that it also helps to identify the small tumor affected lymph nodes which may not have been included in conventional neck dissections. •The study shows that SNB have a specificity of 100% and sensitivity of 94%.
  • 14. Disadvantages of SNB A fundamental problem of SNB is the fact that once a positive SLN has been detected, the patient should undergo neck dissection/ a second surgical procedure. This problem can be overcome if we use a frozen section or a real time PCR intraoperatively after the excision of the sentinel node. SNB is a technique sensitive and expensive procedure. Skip metastases may go undetected in SNB technique. Thus we may miss neck metastases in carcinoma of the tongue.
  • 15. Limitations of this study The greatest disadvantage of this study is its retrospective study design. Nonrandomised study Small sample size Lots of variables as the study population includes carcinoma of the whole head and neck region.
  • 16. Conclusion Study results show that the SNB method is a precise method for mapping and detecting individual lymphatic drainage patterns and staging of early-stage oropharyngeal squamous cell carcinomas. SNB has the potential to reduce the overtreatment of clinically N0 patients where neck dissection can be avoided. Prospective studies are needed to determine whether SNB without elective neck dissection for clinically and radiologically unremarkable cervical lymph nodes can become a reliable course of treatment for carcinomas of the head and neck region. Intraoperative examination of excised SLN using highly sensitive qRT- PCR instead of conventional frozen section analysis could be a way to ensure timely action when lymph nodes are affected.

Editor's Notes

  1. We generally treat most of head & neck carcinoma patients with WLE and elective neck dissection. But a large number of patients visit us with primary tumors, but with no clinically / radiographically detectable neck node metastases. Researchers are always in search of more accurate diagnostic staging techniques since cervical node status plays a pivotal role in Rx planning of H&N SCC.
  2. Thus SN status can act as a major factor for staging & treatment planning in SCC of head & neck region
  3. The only metastasis that was not found in as a SLN radiolabeled lymph node was found during histopathological analysis of the tumor preparation. It was excised together with the tumor
  4. Authors found both ipsilateral and contralateral lymph drainage patterns in 18 patients (50%). In 47.2% cases (n ¼ 17), only ipsilateral sentinel lymph nodes were detected. In 1 of the 36 patients (2.8%), we found only contralateral lymph drainage.