Results of radiotherapy and surgery for glottic carcinoma

Cancer TreatmentReviews (1987) 14, 131-141

R e s u l t s of radiotherapy and surgery for glottic carcinoma L. J. A. S t a l p e r s , A. L. M. V e r b e e k * a n d W. A.

J.

van Daal

Departments of Radiotherapy and * Epidemiology, St Radboud Academic Hospital, Catholic University, No'megen , The Netherlands

Introduction Cancer of the larynx accounts for 2% of malignancies diagnosed in the United States. It is a predominantly male disease: the estimated incidence for 1983 was 9100 in men and 1800 in women, with an estimated death rate of 3100 in men and 600 in women (5, 50). About 60% of the patients are older than 50 with a median age of 60 (52). Smoking is strongly associated with laryngeal cancer with increased risks up to 25 times found for war-veterans smoking more than 40 cigarettes daily compared with non-smokers (5, 27). Laryngeal cancer originates in the glottic (55%), supraglottic (40%) and subglottic regions (5%). Patients with glottic carcinomas are curable both by radiotherapy and by surgery. The good prognosis can be attributed to: (1) (2) of the (3)

Early detection of the tumour because of early symptoms, especially hoarseness. Late metastatic tumour spread because of the sparse lymphatic and vascular supply vocal cords. Relatively easy technical approach of the tumour by surgery or radiotherapy.

Although the survival rates are favourable, the disease itself, as well as its treatment, can severely affect glottic anatomy and functioning, resulting in impaired voice qualities ranging from simple hoarseness to total loss of speech. Surgery, even so-called conservation surgery, gives more voice-debilitating results than radiotherapy (7, 20, 33). Currently, radiotherapy is accepted as the first mode of treatment for glottic carcinoma confined to the vocal cord (T~NoM0). Most therapeutic centres favour radiotherapy in the case of tumour extension to either the supraglottic or subglottic regions without fixation of the vocal cords (T2NoM0) (7, 8, 10, 11, 15, 23, 34, 37-39, 43, 49, 58 ). Others advocate surgery as first treatment, especially if conservation surgery is possible or if the mobility of the vocal cords is impaired (3, 4, 29, 32, 35, 44). Radiotherapy may also be the primary mode of treatment for patients with more extensive tumours (T~ and T4) , especially since the understanding of radiotherapeutic failures has improved and irradiation techniques have been optimized (9, 14, 16, 18, 19, 43, 45, 56). In a 1970 literature review on the role of radiotherapy for cancer of the larynx Vermund Address correspondence to: L. J. A. Stalpers, MD, Department of Radiotherapy, St Radboud Academic Hospital, NijmegenUniversity, Geert Grooteplein Zuid 32, 6500 HB Nijmegen, The Netherlands. 0305 7372/871020131 + I l $03.00/0

© 1987 Academic Press Limited 131

132

L.J.A. STALPERS E T AL.

stated: 'It is only by constant comparison and review of the various modes of treatment that we can hope to achieve better results.' Especially when treatment modalities are controversial, treatment results, as presented in scientific papers, have to be carefully reviewed and compared. The aim of this study was to see whether, by reviewing the literature, we could find factors and arguments that would favour radiotherapy or surgery for glottic cancer. This is essential in cases of more extensive tumours, for which the optimal choice of treatment is still controversial.

Data and methods The laryngologic and oncologic literature of the period 1973-1986 has been reviewed for factors and arguments which play a decisive role in the choice between primary radiotherapy and primary surgery, as well as for treatment results ofglottic carcinoma. Only articles using the T N M system for tumour classification were studied (1, 25). Because the degree of mobility in T 2 carcinomas is assumed to have prognostic significance, a distinction was made between T2a and Tzb. This literature study only deals with treatment results oftumours that had not metastasized to regional lymph nodes or distant organs at the time of primary diagnosis. We described treatment results in terms of 5-year survival rates, 5-year disease-free survival rates, recurrence rates and salvage rates. The 5-year period was chosen because it is used in most articles and because the few authors describing longer periods of investigation state that their survival results do not essentially differ from 5-year results (22, 43, 51, 53). Shorter periods (e.g. 3 years) were not evaluated for survival and diseasefree survival because data were scarce. In all, 26 articles were reviewed describing 5-year survival and 5-year disease-free survival; for the study of recurrence and salvage after recurrence 28 articles were evaluated. According to the U I C C T N M general rules, survival results can be presented in two ways (24): (1) The crude survival rate, calculated by the direct method, is the number of persons known to be alive at the end of the period considered, divided by the total number who were alive at the beginning of this period:

Scrude

alive alive + dead + lost

The alternative, or life table, method of computing survival rates uses all the information accumulated over the whole period of observation and provides a description of the survival pattern (2, 6, 28). In describing 5-year survival, an actuarial method gives a weighted correction for patients who left the study alive at the end of the study-period and had no 5-year follow-up. For these patients the term withdrawal is used. (2) The corrected or adjusted survival rate. There are different methods of correcting the crude rate for death from intercurrent diseases and for those patients lost to follow-up. In an actuarial method these types of corrections can be made by regarding those patients as withdrawals. This methodic analogy of correction may lead to the erroneous assumption that an actuarial method always gives a correction for death from intercurrent diseases and for patients lost to follow up. This explains why many authors seem to compare an

GLOTTIC CARCINOMA

133

'actuarial' method with a 'crude' method, which in fact they are comparing a 'corrected actuarial' method with an 'uncorrected actuarial' method in the sense described above. In this study 'corrected' rates are rates from studies where correction was made for death from intercurrent disease and for patients lost to follow-up. I f it was not clear from the study whether any or what correction was made, a 'crude' rate was assumed. Salvage rates and disease-free survival rates are given in ranges and means. These means are proportionally weighted for the n u m b e r of patients in every study:

Y~ (hi × p,) mean

i --

~ ni i

ni = n u m b e r of eligible patients in study i. Pi = survival rate in study i. In describing recurrence rates and salvage rates, cumulative means are given: i

cumulative mean = - i

ri = n u m b e r of recurred (or salvaged) patients in study i. n~ = n u m b e r o f patients at risk in study i. Salvage was defined as curation after recurrence, generally by surgery. Using this definition two kinds of salvage-rates are described in literature. T h e first salvage rate is the rate of successful salvages a m o n g all patients that had t u m o u r recurrence. T h e second is the rate of successful salvages a m o n g all patients that had undergone a salvage procedure. T h e second rate disregards patients that had tumour recurrence but, for whatever reason, did not undergo a salvage procedure. I f possible salvage rates of both types will be presented.

Results

Radiotherapeutic schedules and techniques differ within time and within the varying treatment centres. Table 1 summarizes irradiation dose, overall treatment time, dosefractionating schedules, techniques and some indicative survival-figures as described by the different authors. Articles in which no technical specification for radiotherapy were mentioned are not given in Table 1 (32, 37, 47).

Survival and disease-free survival Five-year survival results for non-metastasized glottic carcinoma are summarizerd in Table 2. For T~NoM0 tumours crude and corrected data are quite different. A similar difference between crude and corrected figures can be found in the review of T2NoM 0 carcinomas, although surgical results are scarce, as are survival results for Ta and T4 tumours. T h e broad ranges in survival for T 4 tumours can be ascribed to the small populations, both for radiotherapy and for surgery. Table 3 summarizes data on 5-year disease-free survival. Unlike radiotherapeutic results, only few surgical results have been published.

35 37, 55

50-70 6,%70 > 50 65-70

T2

40-70

47 76 4-7

,%8

6-7 4-10.5

6-7

--

5.5 7 8

6-7

--

2.25 or 2.5 Gy 2,0 Gy 1.8-2.0 Gy 2.0 Gy

5/week; 2.0 Gy

5/week; 2,0 Gy

5/week; 2-0 Gy 12-44 fit

5/week; 2.0 Gy Co;

5/week; 2.0 Gy 5/week; 1.4--2.0 Gy

5/week; 2.0 Gy

5/week; 5/week; 5/week; 5/week;

--

-; 1.73-2.50 Gy -4--S/week;2.0 Gy 24~26 fx 5/week; 20 fx 5[week; 2.5 Gy -16 fit

Fractionation (no/week; dose) T3

T4

--

--

--

98%

--

48%

76%

89% 98% --

--

2 MeV, Co, 6 MeV; opposed wedged fields CO, 4-5 MeV; anten~-lateral wedged fields; T I - 2 : 4 x 4-6 x 6 T3: booster, split, 6 x 6-8 x 8 Orthovolt, Co, 6 MeV, 22 MeV; parallel opposed fields: 5 x 6 Co; parallel opposed fields

76% 72%

62%

8"2% 85% 81%

92%

--

--

74% 64%

--

88%

94-% 85% 57% - -

92%

87%

90% 80% 95% 80%

95%

parallel opposed fields 6 x 8

250 kV Orthovoh

Co; parallel oppoe~ + wedged fields CO; 2 weeks sprit after 2 weeks

--

47% 33%

36% - -

T4

--

--

--

66% /NY..D.)

91%

(N.E,D.)

87% 72% (N.E.D.)

46%

'1"3

96% 75%

T2

MeV, Co; 1 anterior electron or 2 opposed Co fields 2 MeV, Co; single or opposed lateral or wedged fields

75% 59%

74%

TI

Corrccted

only 3-year survival results indeterminate results

T2

82% 6s% 34% 75%

TI

crude

5-year survival

-; parallel opposed fields 5 × 5 to 6 x 6 or anterior oblique wedged fields Co; parallel opposed fields 6 x 6

Co; > T I cervical nodes = 50 Gy Co; lateral fields + wedge Co; individual dose by response 4 MeV; lateral wedged fields 4 x 4 or 4 x 5 Co; compre~ion technique 5 x 5 or 6 x 6 Co;4×4or5x5 Co; aa'.gled down +wedge~ + call Co; 4 MeV; lateral angled wedged fields 4 MeV; antero-lateral wedged or parallel opposed fields

T ~ h n i q u e + fidd size (emxem)

fx ~ fraction(s); Co = Cobalt gamma; MeV = megavoh photons; Orthovolt = low energy photons; N.E.D. = no evidence of disease,

TI-2

Van den Bogaert (1980)

55 70 T3 20+36 or 40 TI before 1966: 3(~65 since 1966: 6~65 TI-4 6~70 TI-4 49-93

TI-2

TI 2 T3 T1-2 Tl-4

6-6,5

5 5.5--6.5 4--5 -3

55 50-70 55

60-65

5-7

50-70

ca 55

6-7 5-7 4-6.5

Time (weeks)

66-70 56-60 60-75

TI-4

Class.

Dose (Gy)

TI-4 TI-2 T1--4 TI~ Tt-2 TI T3~ TI TI-4

Sung (1979)

Nass (1976) Notter (1984)

Minja (1984)

Lippi (1984) Miller (1975); Wang (1974) Mills (1979)

39

Kim (1978)

Brandenburg (1977) Dickem (1983) Ennuyer (1975) Goflinet (1973) Harwood (1979) Harwood (1979) Harwood (1980, 1981) Hintz (1983) Hunter (1980); Stewart (1975) Kaplan (1983, 1984)

3I

29, 30

11 12, 15 13 16, 18 22 23, 49

8

4 7

Keference + Author (year of publication)

Table I. Radiotherapy for non-metastasized glottlc carcinoma

h.

t~

G¢)

.>

.t-,

46-78% mean = 68%

54% and 82% mean = 72%

40% and 58% mean = 51%

36q57% mean = 48%

25-75% mean = 45%

T2

T2a

T2b

T3

T4

640/0

57% and 74% mean = 68%

75-82% mean = 78%

80-96% mean = 91%

80-91% mean = 84%

87-98% mean = 94%

Corrected

@ 3-year survival (no 5-year survival described). N.P. = not published.

73-86% mean = 79%

T1

Crude

Radiotherapy

50% and 67% mean = 54%

79%@

N.P.

N.P.

59% and 72% mean = 66%

76-81% mean = 80%

Crude

Surgery

N.P.

59%

80%

89%

88%

89% and 91% mean = 89%

Corrected

11 (21), 15 (154), 23 (32), 29 (31),43 (100) 8 (18), 35 (58), 47 (54) 29 (24) 43 (58), 53 (33) 15 (95), 29 (25), 43 (58) 29 (9) 43 (42), 53 (28) 15 (54), 29 (6), 43 (42) 29 (15) 8 (26), 11 (33), 39 (15), 49 (67) 16 (112), 49 (67) 4 (48) 11 (14) 4 (4)@, 8 (4), 49 (3) 18 (56) 8 (9), 26 (32) RT SU SU RT RT SU RT RT SU RT RT SU SU RT RT SU

corr.: crude: corr.: crude: corr.: corr.: crude: corr.: corr.: crude: corr.: crude. corr.: crude: corr.: crude:

R T corr.: SU crude: SU corr.: R T crude:

References (patients at risk) 8 (71), 12 (333), 35 (63), 39 (49), 41 (38), 43 (95), 47 (52), 49 (168), 55 (183) 11 (78), 12 (333), 13 (151), 22 (91), 23 (175), 31 (129), 39 (49), 41 (38), 43 (168), 49 (168), 55 (183) 8 (16), 35 (217), 47 (17) 8 (16), 42 (182) 8 (26), 23 (32), 35 (22), 41 (21), 43 (100), 49 (37), 53 (61)

R T crude:

Table 2. 5-year survival of n o n - m e t a s t a s i z e d glottic carcinoma (literature review 1973-1985)

>

©

C~

O

37-72% mean = 63%

N.P.

N.P. 26% and 38% mean = 30%

25% ands 33% mean = 27%

T2

T2a

T2b T3

T4

N.P. = not published.

72% and 73% mean = 72%

T1

Crude

56%

77-80% mean = 78% 51-68% 51%

67-75% mean = 70%

7693% mean = 84%

Corrected

Radiotherapy

50% and 67% m e a n = 54%

N.P. 79%

N.P.

59% and 81% mean = 64%

95%

Crude

N.P.

N.P. N.P.

N.P.

65%

N.P.

Corrected

Surgery

crude: corr.: crude: crude:

RT RT RT SU RT RT SU

corr.: crude: corr.: crude: crude: corr.: crude:

R T corr.: SU crude: R T corr.:

RT RT SU RT

16 (112) 8 (26) 8 (4), 49 (3) 18 (56) 8 (9), 26 (32)

8 (26), 37 (45)

15 (52), 29 (6), 43 (42)

15 (154), 39 (29), 43 (100), 51 (22) 8 (16), 47 (63) 15 (93), 29 (25), 43 (58)

8 (71),41 (38) 22 (91), 23 (175), 30 (149), 31 (129), 40 (174), 51 (119) 30 (15) 8 (26), 23 (32), 37 (90), 39 (13), 41 (21), 49 (37)

References (patients at risk)

Table 3. 5-year no-evidence of d i s e a s e (N.E.D.) after r a d i o t h e r a p y or s u r g e r y for n o n - m e t a s t a s i z e d glottic c a r c i n o m a

t~

GLOTTIC CARCINOMA

137

Recurrence rate and salvage ( Tables 4 and 5) Table 4 summarizes ranges and mean values for local and/0r distant metastatic tumour recurrence. Few rates other than crude recurrence rates have been published. Correction for time under observation was mentioned in very few cases; actuarial correction for intercurrent diseases has never been described. Hence, no differentiation between crude or corrected rates could be made. This may explain the broad range of recurrence rates. A cumulative mean rate of all articles reviewed has been calculated. For all stages recurrence after radiotherapy proved higher than after surgery. As 5-year corrected survival for TI and Y 2 t u m o u r s is almost equal for either treatment, the discrepancy between recurrence rates and survival rates must to some extent be counterbalanced by better salvage results for radiotherapeutic failures than for surgical failures. This can be seen in Table 5. Salvage rates of the first type are lower than those of the second type. The discrepancy can run up from 3% for recurrences of T~ tumours to 21% for T3 tumours.

Discussion Comparing treatment results of competing therapeutic modalities is necessary but diffficult. The great variety ofstatisticai methods that have been used in describing 5-year survival of primary treated glottic carcinoma makes comparison of radiotherapy and surgery extremely difficult. By making a division between crude and corrected survival rates, we could partly overcome such problems. As shown above, corrected rates are considerably more favourable than crude ones, which is not surprising since the disease manifests itself in older age when death from cardiovascular and other diseases is substantial. Survival rates show almost equal results for primary radiotherapy ofT1 and T2 tumours and primary surgery. The scarce date for T~ and T, tumours suggest the same. Then, in T2, T, and T 4 t u m o u r s opting for radiotherapy in preference to surgery may depend on the value that a patient attaches to the quality of voice (20, 36, 48). Corrected and/or actuarial data for recurrence are seldom mentioned in the literature nor have such data for salvage ever been described. This methodological shortcoming may partly be excused considering the small patient populations at risk. T h a t also explains the broad range of recurrence rates and salvage rates (the latter are not summarized in Table 5). Therefore cumulative mean rates of recurrence rate and salvage rate may be more representative. As could be expected, recurrence rates increase with increasing tumour size, both after primary radiotherapy and, though to a lesser degree, after primary surgery. In general, recurrences after radiotherapy are more localized than after surgical failure. This may explain why salvage results are better after radiotherapy than after surgery. Differences of up to 23% may occur depending on whether salvage is described as successful salvage among all recurred cases (first type of salvage) or as successful salvage among all operated recurrences (second type of salvage). This difference can be ascribed to the number of patients with recurrent tumour who were not eligible for salvage. Reasons for non-eligibility can be numerous, but tend to increase with increased size of the original tumour, for both radiotherapeutic and surgical recurrences. Radiotherapeutic treatment schedules and techniques, when mentioned, showed relatively few differences between the different treatment centres, as can be read in Table 1.

16-60%

8-67%

27-50%

35-83%

66-75%

T2

T2a

T2b

T3

T4

N.P. = not published.

5-46%

T1

Range

%

N.P.

108[260 = 42%

19/61 = 31%

17/82 = 20%

105/353 = 29%

335/2438 = 14

Cumulative mean

Radiotherapy

31-50%

0% and 31%

N.P.

N.P.

11-31%

0-18%

Range

11%

N.P.

15/56 = 27%

3/24 = 13%

1/9 =

50/234 = 21%

59/515 = 11%

Cumulative mean

Surgery References (patients at risk) RT: 4 (26), 7 (90), 8 (67), 11 (78), 12 (333), 13 (151), 22 (91), 23 (176), 31 (129), 32 (121), 35 (63), 39 (49), 40 (174), 43 (95), 49 (168), 51 (119), 55 (183) SU: 4 (34), 8 (16), 30 (15), 32 (15), 35 (238), 42 (182), 42 (182), 43 (3), 55 (12) RT: 4 (5), 7 (49), 8 (27), 11 (21), 23 (32), 29 (31), 31 (17), 35 (22), 39 (22), 49 (37), 55 (90) SU: 3 (58), 4 (9), 8 (18), 29 (24), 35 (62), 47 (63) RT: 29 (25), 39 (12), 55 (45) SU: 29 (9) RT: 29 (6), 39 (10), 55 (45) SU: 29 (24) RT: 4 (12),8 (26), 11 (47), 37 (45), 39 (18),49 (67) SU: 4 (48), 8 (8) RT: 4 (4), 8 (4), 49 (3) SU: 4 (13), 8 (9), 26 (32)

Table 4. Recurrence rates for primary treated non-metastasized glottic carcinoma (not corrected)

;>

GLOTTIC CARCINOMA

139

T a b l e 5. C u m u l a t i v e m e a n r a t e s for s a l v a g e of r e c u r r e n c e after p r i m a r y r a d i o t h e r a p y or s u r g e r y of n o n - m e t a s t a s i z e d glottic c a r c i n o m a

Radiotherapy salvage rate 1st type

Surgery salvage rate

2nd type

1st type

2nd type

T1

211/292=72%

222/295 = 75%

39]60=65%

7/10=70%

T2

45•88 = 51%

781107= 73%

17/62 = 27%

11/23 = 47%

T3

40[108= 37%

38[66= 58%

5/19 = 26%

N.P.

T4

8%

N.P.

0%

0%

References RT: 4, 7, 8, 11, 12, 13, 21, 22, 23, 31, 32, 35, 37, 39, 40, 43, 46, 49, 51, 55 SU: 4, 32, 35, 42, 43, 55 RT: 4, 7, 8, 11, 23, 29, 31, 35, 37, 39, 43, 49 SU: 3, 4, 8, 29, 35, 46, 47 RT: 4, 8, 11, 37, 39, 49 SU: 4, 8 RT: 18 SU: 4, 8, 26

Salvage rate 1st type = successfullysalvaged/all recurred cases. Salvage rate 2nd type = successfullysalvaged/operated for recurrence. N.P. = not published. M o r e i m p o r t a n t l y , within each centre, t r e a t m e n t techniques m a y well have u n d e r g o n e a g r e a t evolution. H o w e v e r a b r e a k d o w n of t r e a t m e n t results for these technical changes is seldom mentioned. Therefore, a b r e a k d o w n of t r e a t m e n t results of r a d i o t h e r a p y in terms of different techniques could not be made. In s u m m a r y it can be said t h a t the g r e a t diversity and incomplete description of statistical means and methods by which treatment results of glottic carcinoma are presented in the l i t e r a t u r e m a k e evaluation a n d comparison of surgical a n d r a d i o t h e r a p e u t i c treatments a difficult venture. These methodological shortcomings can p a r t l y be overcome if an a u t h o r (1) Describes a c t u a r i a l results, both crude a n d corrected for i n t e r c u r r e n t disease a n d those lost to follow-up, a n d mentions the m e t h o d a p p l i e d (e.g. K a p l a n - M e i e r , B e r k s o n Gage, C u t l e r - E d e r e r ) (2, 6, 28). (2) Describes survival, disease-free survival (after p r i m a r y t r e a t m e n t ) , recurrences, eligibility for salvage (and reasons for non-eligibility) a n d success of salvage (if possible, of both types described above). Results based on a literature review for the period 1975-1985 show equal survival for T~ and T2 glottic c a r c i n o m a , both after r a d i o t h e r a p y a n d after surgery. Scarce results for more e x t e n d e d p r i m a r y tumours suggest the same. In the final choice between p r i m a r y r a d i o t h e r a p y a n d p r i m a r y surgery for glottic c a r c i n o m a , one should also consider the quality of life. Q u a l i t y of life can be expressed in terms of conservation of n o r m a l swallowing, n o r m a l b r e a t h i n g and a c c e p t a n c e of complications especially concerning the quality of speech. Decision analytic methods can be used to evaluate if a n d how a definite choice m a y change if" t r e a t m e n t results v a r y a n d if voice q u a l i t y were taken into account (48).

Acknowledgement

T h e authors wish to thank Professor J. Pliskin from the Ben G u r i o n University, Israel, for his critical comments.

140

L . J . A. STALPERS E T AL.

References 1. American Joint Committee (AJC) for Cancer Staging and End Results Reporting (1978) Clinical staging systems for carcinomas of the larynx. Chicago: American Joint Committee (AJC) for Cancer Staging and End Results Reporting. 2. Berkson, J. & Gage, R. P. (1950) Calculation of survival rates for cancer. Proc. StaffMeet. Mayo Clinic 25: 27(~286. 3. Biller, H. F., Ogura, J. H. & Pratt, L. L. (1971) Hemilaryngectomy for T2 glottic cancers. Arch. Otol. 93: 23~243. 4. Brandenburg, J. H. & Rutter, S. W. (1977) Residual carcinoma of the larynx. Laryngoscope 87: 224-236. 5. Cann, C. E. & Fried, M. P. (1984) Determinants and prognosis of laryngeal cancer. Otolaryngol. Clin. North. Am. 17: 139-150. 6. Cutler, S.J. & Ederer, F. (1958) Maximum utilization of the life table method in analyzing survival..]. Chron. Dis. 8: 699-712. 7. Dickens, W. J. & Cassisi, N. J. (1983) Treatment of early vocal cord carcinoma: a comparison of apples and apples. Laryngoscope 93: 216-219. 8. Ennuyer, A. & Bataini, P. (1975) Laryngeal carcinomas. Laryngoscope 85: 1467-1476. 9. Fletcher, G. H., Lindberg, R. D., Hamberger, A. & Horiot, J. C. (1975) Reasons for irradiation failure in squamous cell carcinoma of the larynx. Laorngoscope 85: 987-1003. 10. Fletcher, G. H. (edit) (1980) Squamous carcinoma of the glottic area. In: Textbook of radiotherapy. Philadelphia: Lea and Febiger. 11. Goffinet, D. R., Ehringham, J. R., Glatstein, E. & Bagshaw, M. A. (1973) Carcinoma of the larynx, results of radiation in 213 patients. Am. J. Roentg. Rad. Ther. Nucl. Med. 117: 553-564. 12. Harwood, A. R., Hawkins, N. V., Rider, W. D. & Bryce, D. P. (1979) Radiotherapy of early glottic cancer I. Int. J. Rad. Onc. Biol. Phys. 5" 473476. 13. Harwood, A. R. & Tierie, A. (1979) Radiotherapy of early glottic cancer--II . Int. J. Rad. Onc. Biol. Phys. 5: 477482. 14. Harwood, A. R., Hawkins, N. V., Beale, F. A., Rider, W. D. & Bryce, D. P. (1979) Management of advanced glottic cancer: a 10-year review of the Toronto experience. Int. J. Rad. Onc. Biol. Phys. 5: 899904. 15. Harwood, A. R. & DeBoer, G. (1980) Prognostic factors in "F2 glottic cancer. Cancer 45:991 995. 16. Harwood, A. R., Beale, F. A., Cummings, B.J., Hawkins, N. V., Keane, T . J . & Rider, W. D. (1980) T3 glottic cancer: an analysis of dose-time-volume factors. Int. J. Rad. Onc. Biol. Phys. 6: 6754i80. 17. Harwood, A. R., Beale, F. A., Cummings, B.J., Keane, T. J. & Rider, W. D. (1981) 'F2 glottic cancer: an analysis of dose-time-volume factors. Int. J. Rad. Onc. Biol. Phys. 7:1501 1505. 18. Harwood, A. R., Beale, F. A., Cummings, B.J., Keane, T.J., Payne, D. & Rider, W. D. (1981) TaNoM0 glottic cancer: an analysis of dose-time-volume factors. Int. J. Rad. Onc. Biol. Phys. 7: 1507-1512. 19. Harwood, A. R. (1982) Cancer of the larynx. J. Otolaryngol. 11 (suppl.): 3-21. 20. Harwood, A. R. & Rawlinson, E. (1983) The quality of life of patients following treatment for laryngeal cancer. Int. J. Rad. Onc. Biol. Phys. 9:335 338. 21. Hawkins, N. V. (1975) The treatment ofglottic carcinoma: an analysis of 800 cases. Laryngoscope 85: 14851493. 22. Hintz, B. L., Kagan, A. R., Wollen, M., Miles, J., Flores, L., Nussbaum, H., Rao, A. R., Chan, P. Y. M. & Ryoo, M. C. (1983) Local control of'F~ vocal cord cancer with radiation therapy: the importance of tumor characteristics vs. treatment parameters. Head Neck Surgery 5: 204-210. 23. Hunter, R. D. & Palmer, M. K. (1980) An analysis of the fate of patients treated radically for glottic carcinoma of the larynx. Clin. radiol. 31: 449452. 24. International Union Against Cancer (UICC) (1974) UICC-TNM General Rules. Geneva: International Union Against Cancer (UICC). 25. International Union Against Cancer (UICC) (1978) UICC-TNM Classification of malignant tumours. Geneva: International Union Against Cancer (UICC). 26. Jesse, R. H. (1975) The evaluation of treatment of patients with extensive squamous cancer of the vocal cords. Laryngoscope 85: 1424-1429. 27. Kahn, H. A. (1966) The Dorn study of smoking and mortality among US veterans: report on eight and one-half years of observation. Washington: NCI Monograph 19, US DHEW, PHS. 28. Kaplan, E. L. & Meier, P. (1958) Non parametric estimation from incomplete observations. Am. Stat. Assoc. J. 53: 457481.

GLOTTIC CARCINOMA

141

29. Kaplan, M. J., Johns, M. E., McLean, W. C., Fitz-Hugh, G. S., Clark, D. A., Boyd, J. C. & Cantrell, R. W. (1983) Stage II glottic carcinoma: prognostic factors and management. Laryngoscope 93: 725-728. 30. Kaplan, M . J . & Johns, M. E. (1984) Glottic carcinoma the roles of surgery and irradiation. Cancer 53: 2641-2648. 31. Kim, J. C., Elkin, D. & Hendrickson, F. R. (1978) Carcinoma of the vocal cord: results of treatment and time-dose relationships. Cancer 42:1114-1119. 32. Kirchner, J. A. & Owen, J. R. (1977) Five hundred cancers of the larynx and pyriform sinus results of treatment by radiation and surgery. Laryngoscope 87: 1288-1303. 33. Lederman, M. & Dalley, V. M. (1965) The treatment ofglottic cancer the importance of radiotherapy to the patient. J. Laryngol. Otol. 79:767 70. 34. Leroux-Robert, J. (1975) A statistical study of 620 laryngeal carcinomas of the glottic region personally operated upon more than five years ago. Laryngoscope 85:1440-1452. 35. Lippi, L., Del Maso, M., Cellai, E. & Olmi, P. (1984) Early glottic cancer: surgery or radiation therapy? Tumori 70:193 201. 36. McNeill, B.J., Weichselbaum, R. & Pauker, S. G. (1981) Speech and survival tradeoffs between quality and quantity of life in laryngeal cancer. N. Eng. J. Med. 305: 982-987. 37. Miller, D. (1975) Management ofglottic carcinoma. Laryngoscope 85:1435 1439. 38. Million, R. R. & Cassisi, N.J. (1984) Larynx. In: Million, R. R., Cassisi, N.J., eds. Management ofheadand neck cancer a multidisciplinary approach. Philadelphia: J. B. Lippincott Company. 39. Mills, E. E. D. (1979) Early glottic carcinoma factors affecting radiation failure, results of treatment and sequelae. Int. J. Rad. One. Biol. Phys. 5:811-817. 40. Minja, B. M., Van Den Brock, P., Huygen, P. L. M. & Kazem, I. (1984) Primary radiation therapy for TI glottic cancer. Factors influencing local control. Clin. Otolaryngol. 9:93 98. 41. Nass, J. M., Brady, L. W., Glassburn,J. R., Prasasvinichai, S. & Schatanoff, D. (1976) Radiation therapy ofglottic carcinoma. Int. J. Rad. Onc. Biol. Phys. 1: 867-872. 42. Neel, H. B., Devine, K. D. & DeSanto, L. W. (1980) Laryngofissure and cordectomy for early cordal carcinoma: outcome in 182 patients. Otolaryngol. Head Neck Surg. 88: 79- 84. 43. Notter, G., Sandbcrg, N., Turesson, I. & Heikel, P. (1984) Zur Strahlenbehandlung des Stimmbandcarcinoms. Bericht uber 287 Patienten. H.N.O. 32:237 244. 44. Ogura, J. H., Sessions, D. G. & Spector, G.J. (1975) Analysis of surgical therapy for epidermoid carcinoma of the laryngeal glottis. Laryngoscope 85:1522 1530. 45. Peters, L.J. & Fletcher, G. H. (1983) Causes of t~ailure of radiotherapy in head and neck cancer. Radioth. Oncol. 1:53 63. 46. Poncet, P. (1975) Total laryngectomy for salvage in cancers of the glottic region. Laryngoscope85:1430 1434. 47. Skolnik, E. M., Yee, K. F., Wheatley, M. A. & Martin, L. O. (1975) Carcinoma of the laryngeal glottis therapy and results. Laryngoscope 85:1453 1465. 48. Stalpers, L . J . A . , Verbeek, A. L. M. & van Daal, W. A . J . (1987) Radiotherapy or surgery for "l'2NoM0 glottic carcinoma? A decision analytic approach. (Submitted for publication.) 49. Stewart, J. G., Brown, J. R., Palmer, M. K. & Cooper, A. (1975) The management ofglottic carcinoma by irradiation with surgery in reserve. Laryngoscope 85:1477 1485. 50. Silverberg, E. (1983) Cancer Statistics 1983. Cancer J. Clin. 33: %25. 51. Sung, D. I., Chang, C. H., Harisiadis, L. & Rosenstein, L. M. (1979) Primary radiotherapy for carcinoma in situ and carly invasive carcinoma of the glottic larynx. Int. J. Rad. Onc. Biol. Phys. 5: 467472. 52. Till, J. E., Bruce, W. R., Elwan, A., 'Fill, M. J., Niederer, J., Reid, J., Hawkins, N. V. & Rider, W. D. (1975) A preliminary analysis ofend-resuhs for cancer of the larynx. Laryngoscope 85: 259-275. 53. Van den Bogacrt, W., Ostyn, F. & Van der Schucren, E. (1983) The significance of extension and impaired mobility in cancer of the vocal cord. Int. J. Rad. Onc. Biol. Phys. 9: 181-184. 54. Vcrmund, H. (1970) The role of radiotherapy in cancer of the larynx as related to the TNM system of staging a review. Cancer 25:485 504. 55. Wang, C. C. (1974) Treatment nf glottic carcinoma by megavoltage radiation therapy and results. Am..]. Radiol. 120:157 163. 56. Wey, W. (1979) Suspicion of persistent or recurrent carcinoma of the larynx after radiotherapy. O.R.L. 41: 301 311. 57. Woodhouse, R.J., Quivey, j . M., Fu, K. K., Sien, P. S., Dedo, H. H. & Phillips, T. C. (1981) Treatment of carcinoma of the vocal cord, a review of 20 years experience. Laryngoscope 91:1155-1162. 58. Zagars, G. & Novante, J. D. (1983) Head and Neck Tumors. In: Rubin, P., ed. Clinical oncologyfor medical students and physicians a multidisciplinary approach . 6th ed. Rochester: American Cancer Society Inc. t