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Michigan Oncology Journal Summer 2001
Neck Metastasis from Squamous Cell Carcinoma of the Upper Aerodigestive Tract
Douglas B. Chepeha, M.D., M.S.P.H, F.R.C.S.(C)
As with most carcinomas, metastasis from squamous cell carcinoma (SCCa) of the upper aerodigestive tract is a poor prognostic indicator. To improve the outlook of our patients, major strides will have to be made to control metastatic disease. Over the past two decades there have been major improvements in detection, resulting in more timely and effective treatment of cancer. Unfortunately, these improvements, for the most part, uncovered an under-appreciated prevalence of metastases, and there was little net benefit in survival. With the assistance of grants from the Faculty Group Practice and the Clinical Research Center at the University of Michigan, a prospective cohort of patients who are at high risk for metastasis is being accrued and followed. The objective of this research effort is to improve diagnosis, tailor treatment and advance the understanding of the biology of metastasis.
Lymphatic Mapping -
In an effort to improve diagnosis, a lymphatic mapping protocol has been open for two years. Lymphatic mapping has been used extensively and has shown efficacy in melanoma and breast cancer. An excellent description was provided by Dr. A Yahanda in the summer 2000 Michigan Oncology Journal. Johns Hopkins reported the first case series in North America involving lymphatic mapping in the upper aerodigestive tract and concluded that the technique was unreliable (2). Our initial experience with our first 11 patients has been good. The sentinel node has been accurately predicted in all but one case.
Accrual to this efficacy trial has been slow due to a referral pattern where more advanced disease is sent into the U-M Head and Neck Oncology Clinic. The goal is to place 75 patients on this study, and we are anxious to improve enrollment. Any inquiries or referrals for this protocol can be made by contacting Cancer AnswerLine™ 800-865-1125.
Selective vs. Modified Radical Neck
As previously mentioned, a metastatic lymph node is representative of an adverse tumor-host relationship, and indicates that there is a propensity for the spread of disease (3). Cogent approaches have been developed for the management of metastatic neck disease. These approaches have traditionally been radical, as surgeons attempted to improve survival. Procedures such as the modified radical neck dissection (MRND) combined with selective post-operative radiation therapy have been successful in controlling disease in the neck (4). Unfortunately, these radical procedures leave overall survival relatively unchanged. In view of the morbidity of radical neck procedures, surgeons have attempted less radical, more selective procedures (5-7). The sequelae of neck dissection can be chronic pain and limitation of shoulder movement due to a weak trapezius muscle. These physical impairments can cause disabilities that affect a variety of work-related and leisure-related activities. Through cross-sectional and prospective cohort studies, we are attempting to evaluate the functional, quality of life (QOL), and oncologic implications of performing the selective node dissection (SND) versus the traditional MRND in patients who have SCCa of the upper aerodigestive tract with node-positive disease less than 3 cm.
Constant's Shoulder Function Test, a validated cross-disease instrument, was used to assess the functional implications of the SND versus the MRND (8). In a cross-sectional study, multivariable linear regression showed that the type of neck dissection, weight and radiation were the most important predictors of shoulder function. The selective neck dissection resulted in significantly better shoulder function than the MRND. In fact, it was less morbid to receive both a SND and post-operative radiation therapy than a MRND alone. In an ongoing longi-tudinal study with both pre-operative and one-year-post-operative shoulder assessments, the SND group showed almost no loss of shoulder function on average, whereas the MRND showed a 13% (p=0.002) loss in shoulder function.
Even if a significant difference in shoulder function is present, the question still remains: does this physical impairment cause any change in the patient's QOL? A new instrument, the neck dissection impairment index (NDII), was validated and tested on a cross section of patients who were at least one year from the completion of treatment (9). Multivariable linear regression showed that weight, age, type of neck dissection and radiation were the most important predictors of QOL. Again, patients who received a SND had a better overall QOL than patients who received MRND. Also, the more robust and, interestingly, the older a patient was the better the overall QOL after neck dissection. Radiation, when given post-operatively, reduced the patient's QOL.
Even if it can be established that SND is beneficial to a patient's shoulder function and QOL, the more limited procedure must be as oncologically sound as a MRND. A large cohort is under accrual and is being followed to better answer this question. Preliminary data from a cohort of 52 patients who were identified retrospectively and then followed prospectively until March of 2000 is encouraging. All patients received a SND and had at least one node pathologically positive. No node was greater than 3 cm, and minimum follow-up was two years. The proportion of patients disease-free in the neck with the primary site controlled is 0.94.
Molecular Epidemiology -
The molecular epidemiology phase of the study will be initiated in the summer of 2001 through a collaborative effort with University of Michigan pathologists Thomas Giordano, M.D., and Augusto Paulino, M.D.; the laboratory of Samir Hanash, M.D., at the University of Michigan; and the laboratory of Douglas Trask, M.D., at the University of Iowa. Our cohort is now large enough to make comparisons between groups of patients with and without neck metastasis, and to begin to develop molecular models of metastasis.
2.Koch WM, Choti MA, Civelek AC, Eisele DW, Saunders JR. Gamma probe directed biopsy of the sentinel node in oral squamous cell carcinoma. Archives of Otolaryngology - Head and Neck Surgery. 1998;124(4):455-9.
3.Pitman KT, Johnson JT, Myers EN. Effectiveness of the selective neck dissection for the management of the clinically negative neck. Archives of Otolaryngology - Head and Neck Surgery. 1997;123(10):917-22.
4.Leemans CR, Tiwari R, van der Waal I, Karim AB, Nauta JJ, Snow GB. The efficacy of comprehensive neck dissection with or without postoperative radiotherapy in nodal metastases of squamous cell carcinoma of the upper respiratory and digestive tracts. Laryngoscope. 1990;100(11):1194-8.
9.Chepeha DB, Taylor RT, Chepeha JC, Teknos TN, Bradford CR, Sharma PK, et al. Functional assessment using Constant's Shoulder Scale after modified radical and selective neck dissection. Otolaryngology - Head and Neck Surgery. 2000;123(2):98.