Carcinoma of the nasopharynx an optimization of radiotherapeutic management for tumor control and spinal cord injury

Inr J. Rodration Oncology Biol. Phys., Vol. 5. pp. 1741-1748 CTPergamon Press Ltd. 1979 PrInted I” the u S.A.

l Original Contribution CARCINOMA OF THE NASOPHARYNX AN OPTIMIZATION RADIOTHERAPEUTIC MANAGEMENT FOR TUMOR CONTROL AND SPINAL CORD INJURYJROGER P. TOKARS, B.Sc.$ The Pritzker

and MELVIN L. GRIEM,

OF

M.D.

School of Medicine, Department of Radiology and the Franklin McLean Institute (operated University of Chicago for the U.S. Energy Research and Development Administration) The University of Chicago, Chicago, ILL 60637, U.S.A.

by the

A series of 131 patients with carcinoma of the nasopharynx were seen at the University of Chicago between 1949 and 1977. Within this series a subset of 96 patients received initial radiation treatment with curative intent at our institution, and comprises the basis of this report. Treatment doses to both the primary tumor site and the cervical spinal cord were converted to nominal standard doses (NSD). The patients were categorized into NSD intervals from 1200 to greater than 2100 ret with corresponding incidence of complication: radiation induced cervical cord myelitis and recurrence at the primary site. Paired dose-response curves are presented that show tumor ablation and cervical myelitis as a complication of treatment versus NSD.The 5 % and 10 % incidence levels of radiation induced cervical myelitis are 1450 and 1750 ret, respectively. The therapeutic operating characteristic (TOC) curve of probability of tumor ablation versus the probability of cervical myelitis is developed and shown. A 10 % complication rate resulted from tumor control rates of 53 % and 33 % for Tl, T2 and T3, T4 primary lesions, respectively. An additional 5 % increase in cervical myelitis resulted from a 15 % gain in tumor ablation within all levels of primary tumor extension. Because of the higher tolerance of the cervical spinal cord and the poor prognosis for those patients who developed a recurrence at the primary site, the more aggressive treatment approach to all stages of nasopharyngeal carcinoma is proposed. Nasopharynx,

cervical myelitis, optimization,

dose-response curve, therapeutic operating curve.

INTRODUCTION

all five-year survival rates range from 21% to 68% when high-dose megavoltage radiation is used.4,6’3.‘7’9 In patients with more extensive local lesions, the survival is generally poor. Resulting sequelae of radiation therapy include xerostomia, serous otitis, dental caries, radiation fibrosis, and, more infrequently, bone necrosis. In most

instances these complications will resolve with time, or can be corrected by appropriate medical management. When complications are more permanent, they must be recognized as undesirable and unavoidable consequences of treatment. Other, more serious complications include radiation induced injury to the brain, crania1 nerves, spinal cord, and head-and-neck endocrine glands residing within the margins of the treatment ports. Cervical myelitis is the most frequent and devastating of these severe complications to the patient’s quality of life. The onset of the myelopathy usually occurs within two years of radiation treatment and commonly manifests as sensory abnormalities, motor paresis, and loss of sphincter control. The average survival rate is about five months, at which time the patient often succumbs to bronchopneumonia or an ascending urinary tract infection.12.13 PalmerI compiled a survey of the literature on documented reports of thoracic and cervical radiation my-

TThis work was done in the University of Chicago Cancer Research Center supported by grant #CA 14599. *Senior medical student at the Pritzker School of Medicine, recipient of an American Cancer Society Fellowship. Reprint Requests to: M.L. Griem, M.D., Department of Radiology, University of Chicago, 950 E. 59th Street, Chicago,

ILL 60637, U.S.A. Acknowledgement-Ms. Jean Vander Horst, dosimetrist, Section of Medical Physics, and Ms. Florence F. Lowenstein, Tumor Registry and Follow-up of Neoplastic Diseases, University of Chicago, assisted in this project. Accepted for publication 16 July 1979.

Radiation therapy is the primary treatment modality for carcinoma of the nasopharynx. Because of its highly malignant qualities and characteristic cryptic anatomic location, the malignancy is usually not discovered until either advanced local spread or metastasis to the cervical localymph nodes have occurred. The primary anatomic tion and the lateral retropharyngeal nodes comprising the usual first stage of lymphatic drain make surgical excision impossible. The ultimate prognosis of nasopharyngeal carcinoma depends on the radio-responsiveness of both the tumor tissue and the surrounding vital structures. Current over-

1741

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1742

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elopathy. Only single case reports are presented in most studies. Thus, little can be said concerning the development of cervical myelopathy as a treatment complication. Therefore, with the increased availability of megavoltage irradiation and the increased necessity of higher treatment levels to control the more advanced nasopharyngeal tumor lesions, it is essential to establish the radiation tolerance of the cervical spinal cord. In this report, we present our experience with nasopharyngeal carcinoma, with regard to the method of primary treatment and, correspondingly, the incidence of recurrence and radiation induced cervical myelitis as related to time, dose and fractionation. With these parameters in mind, the dose-response relationships corresponding to tumor ablation and treatment complication versus nominal standard dose (NSD)’ are presented. The resulting radiotherapeutic operating curve is demonstrated, and several interesting observations and their implications are considered and applied to current radiation treatment modalities. Particular regard is paid to expected radiotherapeutic response and the optimization of radiotheraPY. METHODS

AND MATERIALS

A total of 131 patients with carcinoma of the nasopharynx were treated from 1949 to 1977 at the Section of Radiation Oncology, University of Chicago. With the assistance of our Tumor Registry, their radiotherapy records were obtained for subsequent review. Thirty-five patients were excluded from the study for the following reasons: initial treatment was administered at another institution; treatment for palliation was the primary intention; surgery for excision of the primary lesion was the initial treatment; and death occurred during treatment. The remaining 96 patients comprise the basis of this report. Of the 96 patients, 66 were males and 30 were females; their ages ranged from 10 to 86 years. The mean age was 52 and the median was 57 years. The most frequent histological type was squamous cell (40 patients), followed by undifferentiated cell (19 patients), transitional cell (14 patients) and lymphoepithelioma (13 patients). Three reticulum cell sarcomas, 2 cylindromas, and 2 plasmacytomas comprised the majority of cell types in the remaining tumor group. Because of the markedly differing radiosensitivities and tumor growth characteristics, the patients in the plasmacytoma and reticulum cell sarcoma group were excluded from further analysis. The extent of the primary lesion was determined by indirect laryngoscopy and direct digital examination. Radiographic examinations included views of the sinuses and base of the skull. The neck was carefully palpated in each patient to determine the presence of lymph node metastases. The patients were then staged according to the criteria of the Tumor, Node, Metastasis (T. N. M.) classification of malignant tumors.’ Because of the efforts of our Tumor Registry, the follow-up of these

October

1979, Volume 5, Number

10

patients was excellent. All patients with recurrence received a repeat biopsy and histological conformation of disease, as well as a complete re-staging work-up. Every patient received high dose megovoltage irradiation by either a cobalt teletherapy unit or a 2-MeV Van de Graaff generator. The tumor dose was calculated using the central axis percent depth dose. Laterallyopposed ports were used in all cases to allow a symmetric dose distribution to the entire nasopharynx and base of the brain. In all patients the spinal cord location was reviewed on the corrresponding beam films and was found to be within the 100% isodose distribution. The infinite back scattering factor was considered in the isodose distribution calculations. Compensators, or wedges, were not used during treatment. The primary lesion received approximately 200-250 rad per fraction using a 5 fraction per week treatment schedule totaling 4000 to 7500 rad. The alternate side port was used on each successive treatment day. After 5000 rad had been delivered, the fields were reduced to encompass primarily the nasopharynx and exclude the cervical spinal cord. In the earlier years of the study, the port size contained the primary lesions and the first station nodes, as well as any regional cervical adenopathy. The remaining neck fields were treated in a limited fashion, if at all. More recently, full neck prophylactic therapy was instituted; 54 patients had treatment fields consisting of 2 lateral opposing ports encompassing the primary lesion and both sides of the neck. In 7 patients, entire prophylactic neck irradiation consisted of 3 ports: 2 lateral opposed ports, encompassing the entire nasopharynx, base of the skull, retropharyngeal lymph nodes, and primary lymphatic draining areas; and 1 anterior port, encompassing the low neck fields. In several other patients, the primary lesion was treated in the same manner; however, the neck nodes were treated through opposed anteroposterior tangential ports. In patients with no cervical involvement, the neck in its entirety received an average dose of 5000 rad at a rate of 1000 rad per week. A total of 6000-7000 rad over a period of 7 weeks was delivered to patients with cervical adenopathy. In the latter, the posterior cervical areas received megavoltage irradiation to a dose of 5000 rad followed with an additional 1000-2000 rad utilizing 9 MeV electrons generated by our linear accelerator. This arrangement spared the spinal cord of excessive irradiation, while allowing a therapeutic exposure to the posterior cervical lymph nodes. The eyes were shielded and remained outside the margins of the ports for all patients. RESULTS Table I shows the follow-up and survival of the series according to the T. M. N. staging classification.’ Of the entire series, 7 patients had distant metastases and were not included in this table. All 7 patients had survival rates of less than 5 years. The majority of patients, fell into the T3 and T4 classification, with more extensive ,primary lesions. As the extent of the primary lesion increased, the

Carcinoma

of the Nasopharynx

0 R. P. TOKARS

1743

Table 1. Nasopharyngeal Carcinoma: Comparison of Survival Rates Distributed By Stage With No Distant Metastases

(University of Chicago 1949-1977)

Died of Intercurrent Disease No.(%) No.(%) No.(%) No.(%)

Tl

T2

T3

T4

Total

No.(%)

No.(%)

Died with N-p* Ca.

NED** No.(%)

No.(%)

Cumulative Survival 3 yr. 5 yr. No.(%)

14

12

G3,

&,

$1)

(0")

(8

(:4)

A

&

(i33)

(i30)

$2)

$3)

CA,

(A,

G,

(A,

G2,

&

(5471

t:71

(3901 (2871 (2871 (P31

k

0571

(4,

GO,

G2,

(:O,

$1

(f,,

(1,)

(P3)

(621

(Y3,

$1

(0")

059,

(:1,

(S,

(ii)

$1

(h,

(54)

30

30

86

A* .a-^ . r . . _- ntu: no tviaence

* .I ., , - n-p: nasopnarynx

3- and 5-year survival rates lative 3- and 5year survival 42% and 24%, respectively. The entire patient series ries of local tumor extent:

_ _.

ot uisease

generally decreased. Cumurates for the entire series was was divided into two categopatients who belonged to Tl

and T2, and those who belonged to the T3 and T4 stage. This division was based on the widely differing percentage of patients with no evidence of disease (NED) in each group. The Tl, T2 and the T3, T4 groups had cumulative NED rates of 53% and 5%, respectively.

Table 2 Nasopharyngeal Classified

Carcinoma:

By Primary

Tumor

(University

Tumor Extension

1 yr. 0 No. (A)

Recurrence Site

Rates At The Primary Site

Extension

of Chicago

1949-1977)

Biopsied Recurrence Within 3 yrs. 2 yrs. No. 1%) No. (%I

5 yrs. No, (%I

Tl

l/14 (7)

2114 (14)

2/14 (14)

9::;

T2

2113 (15)

3/10 (30)

4/B (50)

6/7 (86)

T3

lo/32 (31)

13122 (59)

14/21 (67)

15/16 (94)

T4

14/30 (47)

16/26 (62)

27/89 (30)

34/72 (47)

Total

22/23 (96)

38167 (57)

46/58 (79)

Radiation Oncology 0 Biology 0 Physics

1144

October

1979, Volume 5, Number

10

Table 3 Nasopharyngeal

Carcinoma: Average NSD* and Probability of Recurrence At The Primary

Site In Relation To Six 5-year Intervals For Tumor Extent Tl,

T2,

T3,T4.

(University of Chicago 1950-1977)

No. of Patients

Probability of Recurrence

Average Dose

Average NSD

Recurrences

(Rad)

(Ret)

1950-1954

11

8

72

5631

1573

1955-1959

18

10

56

5620

1650

1960-1964

15

9

60

5955

1785

1965-1969

24

15

63

6520

1850

1970-1974

16

6

38

6692

1960

5

2

40

6701

1970

Years

1975-1977 A

* NSD: Nominal Standard

Dose

Table 2 presents the percentage of recurrences at the primary site occurring within 1, 2, 3 and 5 years after treatment for increasing degrees of primary tumor extension. The incidence and rapidity of recurrence was much higher for patients who presented initially with more advanced lesions. The most common location of recurrence was the primary site. The recurrent lesion frequently presented as extension into the base of the skull and less commonly, into the paranasal sinuses and orpharynx. Only 2 of a total of 18 attempts of radiation salvage for local recurrence were successful: at this writing, one has been free of disease for a period of 13 years; the other expired 2 years after the salvage attempt from a recurrence at the primary site. The probability of recurrence, average dose in rad, and the NSD* for patients in stages Tl through T4 divided into 5-year intervals from 1950 to 1977 is summarized in Table 3 and displayed graphicaliy in Figure 1. During the first 15 years of this period, the total radiation treatment doses steadily increased from approximately 1570 to 1785 ret with corresponding average recurrence rates of 72% to 60%. A more aggressive treatment approach was undertaken after the poor outcome of such management was realized. Average treatment doses were increased to 1970 ret average NSD during the remaining 10 year period.

clinician

With

this

approach

that the recurrences

it became

apparent

also decreased

to the

to a level of

*Total Dose = NSD x To” x No*“ Time Dose Fractionation factors (TDF) were used to calculate the NSD when rest periods occurred within any treatment

about 40%, as illustrated in Figure 1, and that more severe treatment complications developed. The most frequent and probably most severe was servical radiation myelopathy which occurred in 2 patients. A total of 4 patients in the entire series developed radiation induced cervical myelitis; they were included within the average NSD range of 1600 to 1900 ret.

z 2000. 0 3

.

? 1900.-E ii ti 1000E

1700-

n

- 100% -90%

;;

- 00%

g

-70%

gf

-60% -50 %

2 ki a

40%

'i;

- 30% z s 0 & 2

.e .= 20 % ;

1600-

- IO % ; 1500' 1950

1955

1960

1965

1970

1975

1960

T~meof Treatment

Fig. 1. Relationship of average Nominal Standard dose (NSD) and probability of recurrence versus time of treatment of nasopharyngeal carcinoma for tumor extent Tl, T2, T3, and T4.

schedule. T is the overall number of treatments.’

treatment

time in days. N is the

CarcinomaoftheNasopharynxOR.

1745

P.TOKARS

Table 4 Nasopharyngeal

Carcinoma: Probability of Recurrence and Ablation At the Primary Site

In Relation To NSD For Tumor Extent Tl, T2, T3, T4. (University of Chicago 1950-1977)

T3,T4

Tl,T2 NSD (Ret)

I

Prob. of Ablation

75

25

25

4

80

20

14

20

14

70

30

36

57

11

7

64

36

44

40

60

7

4

57

43

50

1

25

75

4

2

50

50

63

0

0

100

3

2

66

34

50

No. of Recurrences

0

0

__

1600-1699

2

2

1700-1799

8

1800-1899

No. of Patients

vo. of Recurrences

-_

12

9

100

0

5

4

50

50

7

3

43

1900-1999

5

2

2000-2099

4

>2100

1

Prob. of Recurrence

Prob. of Ablation

The probability of ablation, Pablation,which in effect, is the lack of recurrence is defined by Pablation = 1 Table 4 shows a progression of 7 NSD intervals P ~~~“~E”LX~ ranging from 1200 to over 2100 ret with corresponding probabilities of recurrence and ablation. The entire series was divided into 2 categories of primary tumor extent: Tl, T2, and T3, T4. The corresponding graphical representation of NSD versus the probability of ablation appears in Figure 2. The small sample size comprising the Tl, T2 group in intervals 1200 to 1699 ret probably

TI,T2

/

T3,T4

1200

1400

1600

1800

2000

of probability of tumor ablation versus of the nasopharynx for tumor extent Tl, T2, T3, and T4.

Prob. of Recurrence

accounts for the wide variation in response shown. The expected sigmoid response of control versus NSD for a dose ranging from 1700 to 2000 ret is shown to possess a somewhat depressed slope through its midportion. The data necessary to define the upper end of the curve is insufficient to generate the typical sigmoid appearance. An increasing ablation response in both groups of primary tumor extent correlates with a more aggressive treatment approach, while in contrast the more localized lesion has a relatively greater ablative response. The Tl, T2 and T3, T4 groups reach control rates of 7.5% and 50%, respectively, with doses averaging 2050 ret. Table 5 summarizes the incidence of cervical myelitis corresponding to 7 NSD intervals ranging from 1200 to

Table 5. Nasopharyngeal carcinoma: incidence of radiation cerival myelopathy (University of Chicago 1950-1977) Dose range (Ret)

No. of patients

1200-1299 1300-1399 1400-1499 150&1599 1600-1699 1700~1799 1800-1899

1 5 5 9 8 15 IO

1000-1300 1300-1500 1500-1800 1800

9 55 41 2

2200

Nominal Standard Dose (NSD) (Ret )

Fig. 2. Relationship NSD for carcinoma

I

Average Prob. of Ablation

No. of Patients

(1600

II

Incidence of cervical myelopathy No. (%) 0 (0) 0 (0) 0 (0) 0 (0) l(12.5) I (6.7) 2 (20) Wara et aI.19 1 (I 1.1) l(l.8) 1 (2.4) 0 (0)

*NIA: No information available.

NSD NIA* NIA NIA NIA 1688 1780 1891, 1861 1230 1477 1531 NIA

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1899 ret to the cervical spinal cord. In all cases the patients survived at least 18 months following radiation treatment. Because of the relatively small incidence of cervical myelopathy in our study, we included the incidence of radiation induced cervical myelopathy reported by Wara et al. in 1975.19 There data are shown in Table 5. All 4 patients in our series had a confirmatory diagnosis of cervical myelopathy based on a complete neurological evaluation by our neurosurgical service. Common presenting symptoms were, tingling of the distal extremities, paresthesias, and partial motor paralysis. One of the 4 patients had received initial treatment at another institution and was followed at our ENT clinic when the symptoms indicating cervical myelopathy developed. This patient was included in our study because of the completeness of his radiotherapy records and because the method of treatment was similar to that used in our department. Figure 3 illustrates the probability of treatment complication: cervical myelopathy occurring in Wara et aL’sI study and our own as a function of NSD. The curve shown is the non-linear least squares approximation. This approximation most likely corresponds to the initial segment of the expected sigmoid response curve, since the probability of complication ranges from 0% to 11%. At 1850 ret, or approximately 63 13 rad, the incidence of cervical myelitis is 1 1%. Figure 4 illustrates the radiotherapeutic operating characteristic for both tumor extension groups Tl, T2 and T3, T4 generated by expressing the probability of ablation as a function of treatment complication. This method of data expression is commonly utilized in optimizing the cost-benefit analysis of an investigative workup in diagnostic radiology. Mendelsohn” suggested this approach in 1969 as a method of summarizing the advan-

F

. University

of Chicago

0 Wara et al ‘s 4 Non-linear Approximotlon

October

1979, Volume 5, Number

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70%

.-5 +

TI, T2

60 %

0 z

a:

50%

.-5 c % a

i T3, T4 40%

;; ;

30%

rc 0

.t”

Z :: : a

20%

10% i,,

,

10% 20% 30% Probability of Complication (Cervical Myelopathy)

40%

Fig. 4. Radiotherapeutic operating characteristic curve of probability of tumor ablation versus probability of complication (cervical myelopathy).

tages of various modes of radiation therapy and of optimizing radiotherapeutic management. As depicted on Figure 4, the probability of ablation is highly responsive to small incremental increases in probability of cervical myelopathy. A higher complication rate is required to achieve relatively equal tumor control in the more advanced primary lesions compared to the localized primary lesions. A tumor ablation of 40% affords a complication rate of cervical myelopathy of 7% for Tl, T2, and -14% for T3, T4 lesions. The therapeutic operating characteristic (TOC) curve would be expected to approach a shoulder and subsequently level-off, but the data necessary to determine this point of inflection is not available in our study or in the literature. DISCUSSION

1200

1400 Nomlnal

1600 Standord (Ret

1800 Dose

2000

(NSD)

1

Fig. 3. Relationship of the probability of complication as cervical myelopathy versus NSD to the spinal cord. Wara et alI9

Current radiotherapeutic management of carcinoma of the nasopharynx entails a variety of time, dose, and fractionation schemes. As in any radiologic approach to a malignancy, the radiotherapist employs a treatment scheme which he/she believes will offer the greatest

Carcinoma

of the Nasopharynx

benefit to the patient in terms of survival time and quality of life. Since the cervical spinal cord is immediately posterior to the nasopharynx, it lends itself to unavoidable radiation exposure, and thus undergoes some degree of radiation change. Several models have been proposed which estimate the tissue response to radiation insult. summarizes the treatment The Strandqvist modelI scheme and tissue response in terms of total dose and duration of a course of treatment. The term “tumor cure probability” and the tumor control dose for various time, dose, and fractionation studies of laboratory animals was introduced by Suit and Howard.16 In 1969, Mendelsohn” suggested a method of optimization of the radiotherapeutic approach to a malignancy. By utilizing the typical sigmoid response of dose versus effect for both tumor ablation and treatment complication, he generated a therapeutic operating characteristic (TOC) curve upon which an independent cost analysis concerning the possible outcomes of treatment was superimposed. Our experience with the treatment of nasopharyngeal carcinoma lends itself as a good model of tumor control and recurrence probability in terms of time, dose, and fractionation. The nominal standard dose (NSD) concept proposed by Ellis’ allows a common denominator for schemes utilizing a variety of time, dose, and fractionations, although it is not clear yet whether it can be applied to human tumors correctly. In our study a 5% complication rate of cervical myelitis is a result of NSD of 1450 ret, a dose of 4500 rad using a 200 rad/fraction treatment schedule. With this low dosage level an average recurrence rate of 83% would result. In most studies8,‘7.‘8 as in our own, the salvage attempts generally carry a poor prognosis. This raises the question of whether to accept a fatal outcome as a complication of radiation treatment or as a recurrence of the primary malignancy. Perhaps, the radiotherapist is more likely to accept the latter as a consequence of the pressures of society. From the TOC curve, huge gains of tumor ablation are obtained with relatively small incremental increases in treatment complication. Thus, with the fear of inducing cervical myelitis and operating with a minimal risk of complication, gross benefit to the patient in terms of tumor ablation can be overlooked. In our study it was hoped that the shoulder of the TOC curve could be demonstrated; however the data was not available in our study, or in literature, since it is unlikely one would expose a group of patients to high treatment risks in order to generate data to complete the upper portion of this curve. When the therapeutic approach to a malignancy is optimized, the operating level should be located at or near the shoulder of the operating curve. This maxmizes the probability of destroying the primary malignancy, while *Equivalent Dose defined by: Total Dose = BD x No.377x T0.o58

0 R. P. TOKARS

1747

minimizing the probability of treatment complications. Our study indicates the endpoints of the illustrated radiotherapeutic operating curve to be closest to the shoulder, and thus offer the optimal treatment choice. In view of the higher tolerance of the cervical spinal cord, the more aggressive treatment approach is suggested. The use of high doses during primary treatment (in the range of 7500 rad in a 6 to 8 week period or an NSD of 2230 ret for Tl and T2 lesions) can achieve tumor control rates of 78% with an estimated complication rate of 18%. Tumor control rates of 6500 to 7000 rad in 6 to 7 weeks obtained in Hoppe, et al.‘s study at Stanford University Medical Center* correlate well with our study. These high doses applied to the T3 and T4 lesions would create the same complication rate, but with a lower tumor control of 50%. This control rate also means that there is a probability of 50% that the patient will eventually develop a recurrence at the primary site; since radiation salvage offers a poor prognosis, these patients are destined to an eventural fatal outcome. With these grave alternatives in mind, is an even more aggressive treatment approach justified? Most reports of radiation induced spinal cord myelopathy have been described in terms of thoracic cord involveIn comparison to our results, it appears the ment. 9.‘2~‘4~‘8 thoracic cord has a lower radiation tolerance level. As indicated in Wara et al.‘s study,” the incidence of thoracic myelopathy at 1800 ret (ED)* approaches lOO%, compared to 12% obtained from our study with the cervical cord. These sharply differing radiosensitivities may be regional and a function of the cord’s vascular supply and oxygenation. This concept was discussed by van den Brenk in 19685 when the incidence of cervical cord myelopathy was studied under hyperbaric oxygen conditions. The differences in cord tolerances may also account in part for the 20% variation of the Standqvist timedose plot for spinal cord tolerance obtained by Boden in 1948,’ compared to that generated by Pallis, et al. in 1961.” Boden studied 10 patients with myelopathy of the cervical cord, whereas Pallis et al. studied 5 patients with thoracic cord myelitis. It would seem that tolerance levels vary drastically at different levels of the spinal cord. A variety of techniques were used in our study to prevent excessive irradiation exposure to the cervical spinal cord during both primary tumor and prophylactic neck treatment. More recently we have reduced the nasopharyngeal and neck fields, to exclude the spinal cord after a dose of 5000 rad, and boosted the excluded regions with 9 MeV electrons; this method is highly recommended. A reduction of lateral opposed nasopharyngeal fields, however, may inadvertently exclude viable residual tumor tissue and result in inadequate tumor control.

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October 1979, Volume 5, Number 10

REFERENCES 1. American Joint Committee for Cancer Staging and EndResults Reporting, American Joint Committee, Chicago, Illinois, 1978; pp. 38. 2. Ballantyne, A.J.: Late sequella of radiation therapy in cancer of the head and neck with particular reference to the nasopharynx. Am. J. Surg. 130: 433-436, 1975. 3. Boden, G.: Radiation myelitis of the cervical spinal cord. Br. J. Radiol.

21: 464-469,

4. Bohorquez,

cancer

1948.

J.: Factors that modify of the nasopharynx. Amer.

the radio-response J.

Roentgenol.

of 126:

863-876, 1976. 5. Brenk, H.A.S. van den,

Richter, W., and Hurley, R.H.: Radiosensitivity of the human oxygenated cervical spinal cord based on an analysis of 357 cases receiving 4 MeV X-rays in hyperbaric oxygen. Br. J. Radiol. 41: 205-214,

1968. 6. Chaing, T.-C., and Griem, M.L.: Nasopharyngeal Surg. Clin. N. Amer. 53: 121-l 33, 1973. 7. Ellis, F.: Dose, time, and fractionation: A clinical sis. Clin. Radiol. 20: 1-7, 1969.

cancer. hypothe-

8. Hoppe, R.T., Goffinet, D.R., and Bagshaw, M.A.: Carcinoma of the nasopharynx: Eighteen years’ experience with megavoltage radiation therapy. Cancer 37: 2605-2612, 1976. 9. Locksmith, J.P., and Powers, W.E.: Permanent radiation myelopathy. Amer. J. Roentgenol. 102: 9 16-926, 1968. 10. Mendelsohn, M.L.: The biology of dose-limiting tissues. Conference on Time and Dose Relationships in Radiation Biology as Applied to Radiotherapy. NCI-A.E.C. Confer-

ence, Carmel, Calif., Sept. 1969, pp. 154-159, Karger, Base] and University Park Press, Baltimore. II. Pallis, C.A., Louis, S., and Morgan, R.L.: Radiation myelopathy. Brain 84: 460-479, 196 I. 12. Palmer, J.J.: Radiation myelopathy. Brain 95: 109-122, 1972. 13. Perez, C.A., Ackerman,

L.V., Mill, W.B., Ogura, J.H., and Powers, W.E.: Cancer of the nasopharynx: Factors influencing prognosis. Cancer 24: l-1 7, 1969. 14. Reinhold, H.S., Kaalen, J.G.A.H., and Unger-Gils, K.: Radiation myelopathy of the thoracic spinal cord. Int. J. Radiat.

Oncol. Biol. Phys. 1: 651-657,

1976.

15. Strandqvist, M.: Studien tlber die kumulative Wirkung der Riintgenstrahlen bei Frakionierung. Acta Radiol.. Stockh. (suppl.) 55: ll300, 1944. 16. Suit, H.D., and Howard, T.C.: Normal tissue damage and tumor cure probability for irradiation given under different conditions of tissue oxygenation in hybrid mice. Radiology 89: 720-730, 1969. 17. Urdaneta, N., Fischer,

J.J., Vera, R., and Gutierrez, E.: Cancer of the nasopharynx: review of 43 cases treated with supervoltage radiation therapy. Cancer 37: 1707-l 7 12, 1976. 18. Wang, C.C., and Schulz, M.D.: Management of locally recurrent carcinoma of the nasopharynx. Radiology 86: 900-903, 1966. 19. Wara, W.M., Phillips,

T.L., Sheline, G.E., and Schwade, J.G.: Radiation tolerance of the spinal cord. Cancer 35: 155881562, 1975.