Squamous Cell

Carcinoma of the Soft Palate Willard E. Fee, Jr, MD; Sonja L. Schoeppel; Ronald Rubenstein, MD; Don R. Goffinet, MD; Richard L. Goode, MD; Roger Boles, MD; Mark Tuschman, MA

\s=b\We performed a retrospective study of 106 patients with carcinoma of the soft palate who were treated at two university

hospitals. Computer analysis using

a new

interactive data base program called MING was made to determine Berkson\x=req-\ Gage survival and Gehan tests of statistical significance. Statistically significant associations with an increased survival included the following: smaller lesions, a clinically negative neck examination, well- and moderately well-differentiated histopathologic features, radiation therapy dose of \m=le\ 6,300 rads, absence of a simultaneous primary, and surgical salvage. No statistically significant differences were seen with age, sex, stage, or the number of days during which patients were treated with radiation therapy. There appears to be a need for a prospective, multi-institutional, randomized therapy study to solidify treatment policy. Consideration should be given to combine surgery-radiation vs radiation therapy alone.

(Arch Otolaryngol 105:710-718, 1979) Accepted for publication Oct 26, 1978. From the Divisions of Otolaryngology (Drs Fee and Goode) and Radiation Therapy (Dr Goffinet

and Mr Tuschman), and the Department of Human Biology (Ms Schoeppel), Stanford University Medical Center, Stanford, Calif; and the Division of Otolaryngology, University of California, San Francisco (Drs Rubenstein and

Boles).

Read before the joint meeting of the American for Head and Neck Surgery and the Society of Head and Neck Surgeons, Toronto, May 29, 1978. Reprint requests to Division of Otolaryngology, Stanford University Medical Center, Stanford, CA 94305 (Dr Fee).

Society

As part of the Head and Neck Committee of the Northern Cali¬ fornia Oncology Group (NCOG), Stan¬ ford University (SU) and the Univer¬ sity of California at San Francisco (UCSF) undertook a retrospective analysis of the outcome of all patients with squamous cell carcinoma of the soft palate seen at both centers between 1956 and 1977. The paucity of soft palate cancer in one institution necessitates analysis of patient popu¬ lations during a prolonged time span to formulate treatment recommenda¬ tions. Optimal, systematic treatment policies remain obscure due to inabili¬ ty of a single researcher to assemble enough cases for a randomized pro¬

spective study.

A new interactive computer pro¬ gram capable of evaluating small group medical data with respect to a large number of factors, 80 in this study, has made it possible to analyze the year by year survival of all

patients.

One hundred six cases were submit¬ ted to a detailed review and retrospec¬ tive restaging according to the Amer¬ ican Joint Committee 1977 guide¬ lines.1 Initial tests of total group survival and age, sex, and stage composition are compared with other published data. MATERIALS AND METHODS The charts of all

patients with squamous

Downloaded From: http://archotol.jamanetwork.com/ by a Oakland University User on 06/15/2015

palate were requested from the Departments of Medi¬ cal Records, Radiation Therapy, and Pathology at SU and UCSF medical centers. If only one of the resources had been used, results would not only have been based on a reduced sample, but may have cell carcinoma of the soft

been biased toward one mode of treatment. The only cases escaping detection were those due to improper coding, and it is probable that the number of cases missed was very few or none. One hundred twelve patients with soft palate neoplasms were available. Review of each chart's tumor description revealed six cases where the tumor included the soft palate, but obvious¬ ly originated on the tonsil or retromolar trigone. These cases were excluded from the study, leaving the total number of évaluable cases at 106. All treatment, complications, and followup data were obtained from the patients' records, correspondence with patients' pri¬ vate physicians, direct contact with the patients, and/or assistance from the Cali¬ fornia Tumor Registry. Despite these efforts, two cases were unavailable for '

follow-up. Patients

were

retrospectively restaged using the

at the time of first treatment

American Joint Committee for Cancer End Result Reporting 1977 TNM (tumor, node, metastasis) Guidelines (Table 1). Histologie variation was deter¬ mined by the degree of differentiation into poorly, moderately, moderately well-, and well-differentiated carcinoma. Complica¬ tions occurred to some degree in virtually all patients treated with a specific modali¬ ty. Only those complications present three or more months after completion of radia-

Staging and

therapy were considered significant. Surgical complications were scored from the immediate postoperative period and tion

thereafter.

Computer analysis was performed on¬ line, interactively, using a digital equip¬ ment computer system (PDP 11/45), running under the UNIX operating sys¬ tem. A special purpose data base manage¬

—Primary Tumor T,—Tumor 2 cm

greater than 2 cm but not greater than 4 cm in greatest

T.—Tumor

=

ment program, MING, was used for stor¬ age, retrieval, and analysis of the data. The interactive nature of the MING program makes it ideal for investigation of a large number of medical factors associated with numerous variables. The method of Berkson-Gage- was used to determine all sur¬ vival curves, and the endpoint for actuarial survival calculation was death due to any cause. The disease-free curve was lowered by first recurrence after disappearance of the tumor from treatment. If the tumor never was eradicated, the disease-free interval was zero. The method of Gehan1 was used to determine statistical signifi¬ cance. Illustration of the Berkson-Gage calculation is given in Table 2.

diameter

T—Tumor greater than 4 cm in greatest diameter T—Massive tumor greater than

4 cm

in diameter with invasion of bone, soft tissues of neck, or root (deep musculature) of

—

tongue N—Regional Lymph Nodes N„—No clinically positive node N,—Single clinically positive homolateral node less than 3 diameter

cm

lateral node 3 to 6 diameter

cm

12

18 33

Length

.,,—Multiple clinically positive homolateral nodes, none larger than 6

cm

in diameter

lateral nodes,

8 9 11 12 18 33 41 54 80 98

Censored,

Group

Yes/No

1 1 1 1 2 2 2 2 2 1

Yes No No No No No No No No No

Step 2.-Score the outcome of all possible

comparison

of survival between the two groups. The scoring system gives: +1 if group 2 has a better survival than group 1; -1 if group 1 has a better survival than group 2; 0 if censoring makes it impossible to say which patient will survive longer. Scoring is facilitated by using a table as shown in the following example.

41 54 80 98

homoin

or

SD(V)

V

N„—Contralateral clinically positive node(s) only

=

M—Distant Metastasis M„—No distant metastasis M,—Clinical and/or radiographie evi¬ dence of metastasis other than to cervical lymph nodes

Groupings l-T„ N,„ M„ ll-T.., N„, M„ lll-T,, N,„ M„; T,

or T.. or T„ N,, M(1 Stage IV—T,, N„ or N,, M„; any , N. or N,, M„; any T, any , M,

-'American Joint Committee for Cancer stag¬

ing.'

1 Months

Croup 9 +1 +1 +1 +1 +1

of the

8 0 0 0 0 0

98

this

sum

scores

V/SD(V)

-

10/8.16

=

1.22

=

RESULTS The study group composition is summarized in Table 3. Distribution of patients by age shows a heavy concentration in the sixth decade. There are approximately twice as many male patients as female pa¬ tients in the group. The and stage distribution is shown in Table 4. It is noteworthy that no patients had contralateral clinically positive nodes. Because of lack of adequate descriptions and/or diagrams, four patients could not be retrospectively restaged with regard to their primary tumor and seven patients could not be restaged with regard to their necks. Treatment Modalities

Step example, V +10. Step 4.-SD(V) {[inn d-]/[(m + n) (m + - )]}'-' 3.—The

=

Step 6.-The two-tailed value is found by consulting a cumulative normal distri¬ table.- In this example, bution of 0.11, for V* 1.22.

side of the neck should be staged separately; that is, N,„— right N,,, left N,)

12 +1 +1 +1 +1 +1

=

{[(5)(5)240]/[(10)(9)l}'*=8.16

ameter

11 +1 +1 +1 +1 +1

5.— V is the

sum of the d values for - is the sum of the squares of the d values for both samples (240).

Step

N:t„—Bilateral clinically positive nodes (in this situation each

54 41 33 18 80

d

sample 2 (10).

contralateral

node(s). N,,,—Clinically positive homolateral node(s), one over 6 cm in di¬

Stage Stage Stage Stage

R.

0 0 0 0 8-8 17-6 2 6-4 5-2 3 0 4 4 5 3+2 2+4 6 7 1+6 8 0+8

8 9 11

lateral node 3 to 6 cm in diam¬ eter or multiple clinically posi¬ tive homolateral nodes, none larger than 6 cm in diameter

,,,—Single clinically positive

R,

Length

N,—Single clinically positive homo-

The Gehan Test

Survival

Survival

in

N,—Massive homolateral node(s), bi¬

The Gehan test is a simple significance test for comparison of two populations containing censored observations. It re¬ sults in a two-tailed value to describe the statistical probabilities of difference be¬ tween the groups. A step-by-step method of calculation performed on two random groups of five patients is shown as follows. Step l.-Set up a table with columns for patient number, group, survival length, and censoring status. Order the data by increasing survival lengths as follows:

m

sample

less in greatest

or

diameter

is sample size of group 1 and is size of group 2. The d- value is determined by adding to the table from step 1. The three new columns to be added are R„ R,, and d. R, is the number of patients whose survival lengths are defi¬ nitely shorter than that case. Column R. is the opposite of R„ the number of all patients whose survival lengths are defi¬ nitely longer than that row's case. Column d is simply R, R... Summation of each dresults in