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A favorable subset of AJCC stage IV squamous cell carcinoma of the head and neck
Copyn&t
036&3016/84 103.00 t .oO 0 I984 Pergamon Press Ltd.
??Original Contribution
A FAVORABLE SUBSET OF AJCC STAGE IV SQUAMOUS CARCINOMA OF THE HEAD AND NECK
CELL
WILLIAM M. MENDENHALL, M.D.,* JAMES T. PARSONS, M.D.,* RODNEY R. MILLION, M.D., FACR,* NICHOLAS J. CASSISI, D.D.S., M.D.,? JOHN W. DEVINE, M.D.* AND BRUCE D. GREENE, M.D.* University of Florida, College of Medicine, Gainesville, FL 32610
AJCC (American Joint Committee and an unfavorablesubset IVB. Squamous
on Cancer) Stage
IV is
subdivided
cell carcinoma of the base of the tongue, tonsil, supraglottic
INTRODUCI’ION
IVA,
larynx, and pyriform sinus; Staging.
tember 1977 (base of tongue), February 1981 (tonsil), May 1981 (supraglottic larynx) or December 1980 (pyriform sinus). There is a minimum two-year follow-up. Patients were excluded from analysis of control above the clavicles if they died less than two years after treatment and were continuously disease-free above the clavicles. Patients were excluded from five-year determinate disease-free survival analysis if they had less than five year follow-up or if they died of intercurrent disease less than five years from treatment. Patients were treated with continuous- or split-course techniques: the details of treatment technique have been outlined elsewhere. 2*4-8
Patients with “advanced” local-regional carcinoma of the head and neck may have a broad spectrum of lesions that vary substantially with regard to the probability of controlling disease above the clavicles and curing the cancer. Obviously, a patient with a 2 cm lesion of the base of the tongue and with two 1 cm @lateral neck nodes has a better prognosis than a patient with a massive (T4) base of the tongue primary lesion and bilateral fixed nodes, yet both patients have AJCC Stage IV lesions.’ It is our contention that AJCC Stage IV
may be subdivided into a subset of lesions that have a relatively favorable prognosis, IVA, and another subset of lesions that have a poor prognosis, IVB (Fig. 1). Those patients with favorable lesions, Stage IVA, have relatively early primary cancers (T 1-T3) with manageable neck disease (N2, N3A), whereas patients with IVB lesions have advanced primary and/or neck disease. METHODS
into a relatively favorable subset,
RESULTS Table 1 shows the initial control rate above the clavicles as a function of modified AJCC stage. It is apparent that for all four sites, the control rate is better for IVA lesions than for IVB lesions. This analysis includes patients treated with a split-course technique, which has been shown to produce results that are inferior to those produced by continuous-course irradiation.’ In addition, the initial control rates do not take into account those patients whose disease recurs above the clavicles and who are salvaged by a surgical procedure.
AND MATERIALS
This is a retrospective analysis of 373 patients with squamous cell carcinoma of the base of the tongue (89), tonsil (145), supraglottic larynx (8 I), and pyriform sinus (58) treated with curative intent with radical irradiation with or without immediate neck dissection(s). Resection of the primary lesion was reserved for irradiation failure. Patients were treated between October 1964 and Sep * Division of Radiation Therapy. t Division of Otolaryngology. Dr. Mendenhall is the recipient of an American Cancer Society Junior Faculty Clinical Fellowship. Dr. Million is the American Cancer Society Ashbel C. Williams Memorial Professor of Clinical Oncology.
Reprint requests to: William M. Mendenhall, M.D., Division of Radiation Therapy, Box J-385, J. Hillis Miller Health Center, Gainesville, FL 32610. Accepted for publication 17 May 1984.
1841
Radiation Oncology 0 Biology0 Physics
1842
NI
NO
October 1984, Volume 10, Number 10 N2A
N2El
N3A
N3B
1
STAGE I
TI
I I I
STAGE 7PA
STAGE l?ZB
T4
Fig. 1. Modified AJCC stage classification.
Table 2 shows the 5 years determinate disease-free survival by modified AJCC stage. In all sites except tonsil there is a substantial difference in survival between Stage IVA and Stage IVB. DISCUSSION The data presented support the argument that AJCC Stage IV may be divided into a favorable subset, IVA, and an unfavorable subset, IVB, based on local-regional
control and disease-free survival. These subsets are not homogeneous so that Stage IVB, as we have defined it, could contain a few favorable lesions such as a 3 cm primary lesion of the base of the tongue with bilateral mobile 2 cm jugulodigastric nodes. The definition of these subsets may vary depending on the primary site and the initial mode of treatment so that additional data for other primary sites, and for patients treated with surgery alone or combined irradiation and surgery,
Table 1. Radiation therapy f neck dissection(s): Initial control above clavicles* (minimum
2 year follow-up)
Site
Exclusions I II III IVA IVB
Tonsil
Base of tongue
Stage
15 5/5 3/3 8/12 7/17 6/37
(100%) (100%) (67%) (41%) (16%) i
p = 0.041t
12/14 15/23 22/33 9/25 5124
Supraglottic larynx
26 (86%) (65%) (67%) (36%) (21%) 1 ’ = 0.295t
9/10 8/11 6/10 7/10 7124
16 (90%) (73%) (60%) (70%) p = 0.03t (29%) 1
Pyriform sinus 10 314 2/3 7/13 IO/l3 3/15
(75%) (67%) (54%) (77%) (20%)
p = o.oost
* Does not include those salvaged by an operation.
t Using Exact Test Procedures3 Table 2. Radiation therapy + neck dissection(s): Determinate
disease-free survival at 5 years*
Stage
Base of tongue
Tonsil
Supraglottic larynx
Pytiform sinus
Evaluable patients I II III IVA IVB
56
84
42
33
2/2 2/2 617 7/15 4/30
(100%) (100%) (86%) (47%) 1 (13%)
p = 0.017t
9/9 1 l/l2 16/26 3/21 3/16
(100%) (92%) (62%) (14%) 1 (19%)
p = 0.32t
* Includes patients salvaged by surgery and/or radiation therapy. t Using Exact Test Procedures3
6/6 5/5 215 417 l/l9
(100%) (100%) (40%) (57%) (5%)
p = O.O’t
314 (75%) 2/2 (100%) 318 (38%) 4/8 (50%) l/l 1 (9%)
p = 0.066t
Subset of AJCC Stage IV 0 W. M.
needed in order to confirm more accurately the distinction between IVA and IVB. It would appear to be useful to define these subsets of AJCC Stage IV
are
MENDENHALL et
al.
I843
lesions when reporting end results and when selecting patients for research protocols based on “dismal” results with conventional therapy.
REFERENCES 1. American Joint Commiuee on Cancer: Manual for Staging of Cancer (2nd edition). Philadelphia, J.B. Lippincott. 1983, pp. 31-42. 2. Kaplan, R., Million, R.R., Cassisi, N.J.: Carcinoma of the tonsil: Results of radical irradiation with surgery reserved for radiation failure. Laryngoscope 87: 600-607. 1977. 3. Mendenhall. W., Ott, L., Larson, R.F.: Statistics: A Tool for the Social Sciences. North Scituate, MA, Duxbury Press. 1974, p. 336. 4. Million, R.R., Cassisi, N.J.: Radical irradiation for carcinoma of the pyriform sinus. Laryngoscope 91: 439-450, 1981.
5. Million, R.R., Cassisi, N.J. (Eds.): Manpgemenl
of Head
and Neck Cancer: A Muhidisciplinar~* Approach. Philadelphia, J.B. Lippincott, 1984. 6. Million, R.R., Cassisi, N.J., Wittes, R.E.: Cancer in the head and neck. In Cancer: Principles and Practice of Oncology, DeVita, V.T., Hellman, S., Rosenberg, $.A. (Eds.). Philadelphia, J.B. Lippincott. 1982, pp. 301-395. Parsons, J.T., Bova, F.J., Million, R.R.: A reevaluation of 7’ split-course technique for squamous cell carcinoma of the head and neck. Int. J. Radiat. Oncol. Biol. Phys. 6: 16451652, 1980.
8. Parsons, J.T., Million, R.R., Cassisi, N.J.: Carcinoma of the base of the tongue: Results of radical irradiation with surgery reserved for irradiation failure. Laryngoscope 92: 689-696,
1982.
036&3016/84 103.00 t .oO 0 I984 Pergamon Press Ltd.
??Original Contribution
A FAVORABLE SUBSET OF AJCC STAGE IV SQUAMOUS CARCINOMA OF THE HEAD AND NECK
CELL
WILLIAM M. MENDENHALL, M.D.,* JAMES T. PARSONS, M.D.,* RODNEY R. MILLION, M.D., FACR,* NICHOLAS J. CASSISI, D.D.S., M.D.,? JOHN W. DEVINE, M.D.* AND BRUCE D. GREENE, M.D.* University of Florida, College of Medicine, Gainesville, FL 32610
AJCC (American Joint Committee and an unfavorablesubset IVB. Squamous
on Cancer) Stage
IV is
subdivided
cell carcinoma of the base of the tongue, tonsil, supraglottic
INTRODUCI’ION
IVA,
larynx, and pyriform sinus; Staging.
tember 1977 (base of tongue), February 1981 (tonsil), May 1981 (supraglottic larynx) or December 1980 (pyriform sinus). There is a minimum two-year follow-up. Patients were excluded from analysis of control above the clavicles if they died less than two years after treatment and were continuously disease-free above the clavicles. Patients were excluded from five-year determinate disease-free survival analysis if they had less than five year follow-up or if they died of intercurrent disease less than five years from treatment. Patients were treated with continuous- or split-course techniques: the details of treatment technique have been outlined elsewhere. 2*4-8
Patients with “advanced” local-regional carcinoma of the head and neck may have a broad spectrum of lesions that vary substantially with regard to the probability of controlling disease above the clavicles and curing the cancer. Obviously, a patient with a 2 cm lesion of the base of the tongue and with two 1 cm @lateral neck nodes has a better prognosis than a patient with a massive (T4) base of the tongue primary lesion and bilateral fixed nodes, yet both patients have AJCC Stage IV lesions.’ It is our contention that AJCC Stage IV
may be subdivided into a subset of lesions that have a relatively favorable prognosis, IVA, and another subset of lesions that have a poor prognosis, IVB (Fig. 1). Those patients with favorable lesions, Stage IVA, have relatively early primary cancers (T 1-T3) with manageable neck disease (N2, N3A), whereas patients with IVB lesions have advanced primary and/or neck disease. METHODS
into a relatively favorable subset,
RESULTS Table 1 shows the initial control rate above the clavicles as a function of modified AJCC stage. It is apparent that for all four sites, the control rate is better for IVA lesions than for IVB lesions. This analysis includes patients treated with a split-course technique, which has been shown to produce results that are inferior to those produced by continuous-course irradiation.’ In addition, the initial control rates do not take into account those patients whose disease recurs above the clavicles and who are salvaged by a surgical procedure.
AND MATERIALS
This is a retrospective analysis of 373 patients with squamous cell carcinoma of the base of the tongue (89), tonsil (145), supraglottic larynx (8 I), and pyriform sinus (58) treated with curative intent with radical irradiation with or without immediate neck dissection(s). Resection of the primary lesion was reserved for irradiation failure. Patients were treated between October 1964 and Sep * Division of Radiation Therapy. t Division of Otolaryngology. Dr. Mendenhall is the recipient of an American Cancer Society Junior Faculty Clinical Fellowship. Dr. Million is the American Cancer Society Ashbel C. Williams Memorial Professor of Clinical Oncology.
Reprint requests to: William M. Mendenhall, M.D., Division of Radiation Therapy, Box J-385, J. Hillis Miller Health Center, Gainesville, FL 32610. Accepted for publication 17 May 1984.
1841
Radiation Oncology 0 Biology0 Physics
1842
NI
NO
October 1984, Volume 10, Number 10 N2A
N2El
N3A
N3B
1
STAGE I
TI
I I I
STAGE 7PA
STAGE l?ZB
T4
Fig. 1. Modified AJCC stage classification.
Table 2 shows the 5 years determinate disease-free survival by modified AJCC stage. In all sites except tonsil there is a substantial difference in survival between Stage IVA and Stage IVB. DISCUSSION The data presented support the argument that AJCC Stage IV may be divided into a favorable subset, IVA, and an unfavorable subset, IVB, based on local-regional
control and disease-free survival. These subsets are not homogeneous so that Stage IVB, as we have defined it, could contain a few favorable lesions such as a 3 cm primary lesion of the base of the tongue with bilateral mobile 2 cm jugulodigastric nodes. The definition of these subsets may vary depending on the primary site and the initial mode of treatment so that additional data for other primary sites, and for patients treated with surgery alone or combined irradiation and surgery,
Table 1. Radiation therapy f neck dissection(s): Initial control above clavicles* (minimum
2 year follow-up)
Site
Exclusions I II III IVA IVB
Tonsil
Base of tongue
Stage
15 5/5 3/3 8/12 7/17 6/37
(100%) (100%) (67%) (41%) (16%) i
p = 0.041t
12/14 15/23 22/33 9/25 5124
Supraglottic larynx
26 (86%) (65%) (67%) (36%) (21%) 1 ’ = 0.295t
9/10 8/11 6/10 7/10 7124
16 (90%) (73%) (60%) (70%) p = 0.03t (29%) 1
Pyriform sinus 10 314 2/3 7/13 IO/l3 3/15
(75%) (67%) (54%) (77%) (20%)
p = o.oost
* Does not include those salvaged by an operation.
t Using Exact Test Procedures3 Table 2. Radiation therapy + neck dissection(s): Determinate
disease-free survival at 5 years*
Stage
Base of tongue
Tonsil
Supraglottic larynx
Pytiform sinus
Evaluable patients I II III IVA IVB
56
84
42
33
2/2 2/2 617 7/15 4/30
(100%) (100%) (86%) (47%) 1 (13%)
p = 0.017t
9/9 1 l/l2 16/26 3/21 3/16
(100%) (92%) (62%) (14%) 1 (19%)
p = 0.32t
* Includes patients salvaged by surgery and/or radiation therapy. t Using Exact Test Procedures3
6/6 5/5 215 417 l/l9
(100%) (100%) (40%) (57%) (5%)
p = O.O’t
314 (75%) 2/2 (100%) 318 (38%) 4/8 (50%) l/l 1 (9%)
p = 0.066t
Subset of AJCC Stage IV 0 W. M.
needed in order to confirm more accurately the distinction between IVA and IVB. It would appear to be useful to define these subsets of AJCC Stage IV
are
MENDENHALL et
al.
I843
lesions when reporting end results and when selecting patients for research protocols based on “dismal” results with conventional therapy.
REFERENCES 1. American Joint Commiuee on Cancer: Manual for Staging of Cancer (2nd edition). Philadelphia, J.B. Lippincott. 1983, pp. 31-42. 2. Kaplan, R., Million, R.R., Cassisi, N.J.: Carcinoma of the tonsil: Results of radical irradiation with surgery reserved for radiation failure. Laryngoscope 87: 600-607. 1977. 3. Mendenhall. W., Ott, L., Larson, R.F.: Statistics: A Tool for the Social Sciences. North Scituate, MA, Duxbury Press. 1974, p. 336. 4. Million, R.R., Cassisi, N.J.: Radical irradiation for carcinoma of the pyriform sinus. Laryngoscope 91: 439-450, 1981.
5. Million, R.R., Cassisi, N.J. (Eds.): Manpgemenl
of Head
and Neck Cancer: A Muhidisciplinar~* Approach. Philadelphia, J.B. Lippincott, 1984. 6. Million, R.R., Cassisi, N.J., Wittes, R.E.: Cancer in the head and neck. In Cancer: Principles and Practice of Oncology, DeVita, V.T., Hellman, S., Rosenberg, $.A. (Eds.). Philadelphia, J.B. Lippincott. 1982, pp. 301-395. Parsons, J.T., Bova, F.J., Million, R.R.: A reevaluation of 7’ split-course technique for squamous cell carcinoma of the head and neck. Int. J. Radiat. Oncol. Biol. Phys. 6: 16451652, 1980.
8. Parsons, J.T., Million, R.R., Cassisi, N.J.: Carcinoma of the base of the tongue: Results of radical irradiation with surgery reserved for irradiation failure. Laryngoscope 92: 689-696,
1982.