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Carcinoma of the nasopharynx
Carcinoma of the Nasopharynx Review of 146 Patients with Emphasis on Radiation Dose and Time Factors
Howard C. Moench, MD,* San Francisco, Theodore L. Phillips, MD, San Francisco,
California California
Cancer of the nasopharynx is one of the most malignant diseases of the upper respiratory and digestive tract. Because of its “blind” location, the primary tumor is usually not discovered until there is either advanced local spread or metastases to the cervical lymph nodes. In recent studies the question of radiation dosage and tumor control in neighboring sites has been explored [1,2]. This report reviews our experience with the disease from 1940 to 1968, with emphasis on the relation of radiation dose and time factors to control of the primary disease. Clinical Material During this twenty-eight year period, 146 patients with a malignant nasopharyngeal tumor of squamous cell origin received primary treatment in the Section of Radiation Oncology, University of California Medical Center, San Francisco. These patients, some of whom were reported on by Vaeth [3] in 1960, constitute the basic material for this report. An additional eighteen patients seen in this period were omitted from the study because of the lack of histologic documentation, primary treatment not totally performed by us, or treatment not offered because of the extent of the tumor and/or the patient’s condition. Except for the period of infancy, all age groups were represented; the median age was fifty-three, and the youngest patient was a child of ten. Thirty-one per cent of the patients (46/146) were Chinese, a reflection of both
From the Section of Radiation Oncology, Department of Radiology, University of California School of Medicine, San Francisco, California. This investigation was supported by NI H Training Grant Ca 05177-06. Presented at the First Joint Meeting of the American Radium Society, James Ewing Society, and the Society of Head and Neck Surgeons on the occasion of the Eighteenth Annual Meeting of the Society of Head and Neck Surgeons, Boca Raton, Florida, May 14-19, 1972 *Present address and address for reprints: Division of Radiation Therapy, Shands Teaching Hospital, University of Florida, Gainesville, Florida 32601.
Volume 124, Pctober
1972
the large Chinese population in San Francisco and the susceptibility of this race to epidermoid tumors of the nasopharyngeal mucosa. We have used the following modification of the TNM classification presented by Perez et al [4]: Tr-tumor limited to soft tissue of nasopharynx Tz-tumor extension into nasal cavity, palate, or oropharynx Ts-nerve involvement, destruction of bone, or tumor extension below the oropharynx Td-more than one characteristic of Ts lesion No-no clinically palpable nodes Nl-single mobile node of 3 cm or less Ns-multiple ipsilateral nodes or single mobile node larger than 3 cm Ns-fixed unilateral node of multiple bilateral nodes It should be noted that this classification groups as T1 all lesions confined to the soft tissue nasopharynx, no matter how extensive. Since this tumor often spreads submucosally, we doubt the value of subdividing lesions on the basis of the number of walls involved, especially in a retrospective study. The majority of epidermoid tumors arising from the nasopharynx are poorly differentiated. They can be classified, however, by their predominant histologic character transitional tumors, lymphoepithelioma as follows: (transitional cell with lymphocyte infiltration), and poorly differentiated or anaplastic carcinoma. A small number of’ our patients (12/146) had carcinomas with some degree of keratinization; the remainder of the tumors were undifferentiated. Opinions differ concerning the clinical behavior and response to treatment of the lymphoepithelioma group [5,6]. This designation was given by our pathologist to 25 per cent of these patients (36/146). Three years after treat-
515
Moench and Phillips
100
8 INTERCURRENT
F
PERCENT SURVIVING
Figure 1. Clinical course and site of failure. * = no ewdence disease; t = patienis with both local recurrence and distant metastases are listed as local recurrence.
oi
A’ 20 METASTASES 2
A
6
8
IO
12
14
YEARS
ment by radiation, 36 per cent (13/36) of patients in the lymphoepithelioma group and 38 per cent (37/110) of the remaining 110 patients who had tumor of anaplastic, transitional, or keratinizing forms exhibited no evidence of disease. In our material we have been unable to detect differences in behavior or in response to treatment in these histologic subgroups. We, therefore, have combined the transitional, lymphoepithelioma, anaplastic and differentiated forms of squamous carcinoma of the nasopharynx. This grouping conforms to that proposed by Yeh [5].
Methods Since this study covers a considerable period of time, there are some inevitable differences in technics used. A relatively small number of patients were treated with orthovoltage, usually with an intraoral cone or an intracavitary cobalt or radium source to boost the dose [7J (Four of the eight patients with T1 lesions treated in this fashion were long-term controls.) The majority were treated using supervoltage ‘equipment (2 mev generator or cobalt 60 teletherapy apparatus). During the earlier years of the study the primary site was usually treated with small, laterally opposed radiation fields; the neck was treated in limited fashion if at all. Later the policy evolved of treating the primary lesion with wide margins and of treating the neck in its entirety whether clinically involved or not. During this period (1957 to 1966) two somewhat different fractionation and dose philosophies were in use and the analysis of their end results provided one of the incentives for this study. One method employed a rather prolonged fractionation scheme, delivering 700 to 800 rads tumor dose per week for a total dosage of 5,000 to 6,000 rads. This dose was delivered through constant lateral faciocervical fields. The second method employed a more aggressive treatment schedule of 906 rads a week for a total tumor dose of 6,000 to 6,500 rads. In these patients the primary site and upper part of the neck were treated through opposed lateral
fields, with sparing of the spinal cord after 5,000 rads, and the lower part of the neck was treated through an anterior field. The clinically positive neck usually received 6,000 to 6,500 rads at depth and the neck with no palpable adenopathy usually received 5,000 rads.
516
16
18
20
Figure 2. Absolute survival curve (Berkson-Gage method).
Results
Figure 1 presents an overview of the clinical course of these patients. Significantly, the primary location was the most common site of treatment failure, with subsequent invasion of the base of the skull. Much less common was uncontrolled spread anteriorly into the pterygoid fossa or paranasal sinuses or inferiorly down the walls of the oropharynx. The most common sites of metastases were the lung, viscera, and skeleton. The epidural space of the spinal canal was involved in three instances. In five patients second primary tumors developed consisting of carcinomas of the lung, bladder, thyroid, and oral cavity and a reticulum cell sarcoma of the retroperitoneal space. A survival curve (Berkson-Gage method) of this group of patients through twenty years is shown in Figure 2. Approximately 37 per cent of the total group were alive five years after treatment. Determinate (excluding intercurrent death) five and three year survival rates with no evidence of disease are shown in Table I. The clinical stages (I through IV) are our own and were selected to best correlate with prognosis. The results were generally good when the tumor was limited to the soft tissue of the nasopharynx (Tl) or extended only minimally to soft tissue outside this space (Ts) and when lymph node metastases were absent or of limited extent (stages I and II). Surprisingly, the survival of patients with N1 and Ns disease was not materially worse than that of patients who clinically lacked nodal involvement. Only when lymph node metastases were bilateral or fixed (Ns) was there a marked decrease in survival. In patients with nerve involvement or radiographic evidence of bone destruction (Ts and Tq lesions), long-term survival was not common. Only two patients with radiographic evidence of bone destruction survived disease-free more than three years. One of these had destruction of the middle cranial fossa and survived disease-free for seven years to die of a new primary lesion. The other pre-
The American Journal of Surgery
Carcinoma
I
TABLE
Tumor
Five and
Three Year Survival by Staging
Survival
of Nasopharynx
(See text for staging classification.)
(yr)
NI
N2
9114
9117
6126
12116
lo/la
10130
111
'I2
O/6
N3
STAGE
III
27%(10/37)
T3
3
l/l
l/2
o/7
5
O/5
017
l/11
O/5
O/6
l/11
O/l
0
011
I sented with proptosis and extensive destruction of the posterior bony orbit and base of the skull and at the time of this writing is clinically free of disease four years after treatment. Treatment to the Neck. Seventy-two per cent of these patients (104/146) presented with palpable, clinically positive cervical lymph node enlargement. All received definitive treatment to the neck with irradiation, with only fourteen failures in this group of 104 patients. Treatment failure occurred mainly in patients with advanced involvement (two with NI, four with Nz, and eight with Ns lesions). Two of the failures were clearly related to inadequate dosage (4,500 rads or less) and three were at field margins. Radical neck dissection was performed in eight patients in whom radiation treatment failed. Three of these patients survived free of disease for two and a half, three, and five years before dying of intercurrent disease. Forty-two patients had no palpable evidence of lymph node involvement. Twelve of these patients with clinically negative cervical nodes were not treated and disease subsequently developed in six. The remaining thirty patients with clinically negative cervical nodes received prophylactic treatment to the entire neck and all have remained free of disease in this area. Complications. Xerostomia is an inevitable consequence of treatment. This condition improves in the months after treatment although some patients continue to complain of dryness of the mouth and poor taste for years. Some of the patients in the earlier phase of the study were treated with large daily doses in a relatively short over-all time. As could be expected, this dosage produced subcutaneous fibrosis with some resultant impairment of motion at the temporomandibular joint. There was no occurrence of radiation myelitis. Volume 124, October 1972
012
Radiation Dose and Tumor Control As mentioned previously, failure in this series has occurred most commonly at the primary site. Figure 3 plots the control of the primary tumor as a function of dose and number of treatments in patients with TI disease whose treatment was solely by external irradiation. The great majority of patients were treated using supervoltage equipment; a small number (confined to the very low dose range) received their treatment with orthovoltage equipment. Most patients treated with the latter modality had a subsequent intraoral or intracavitary boost and are excluded from this graph. These data do not lend themselves to a simple regression line although there is an impression of decreased local control with lower dose. Some of the patients with local control at three years had subsequent failure at the primary site. To further delineate these factors, data for the same patients are shown in Figure 4 in which local control is plotted against post treatment interval and tumor dose in nominal standard dose (NSD) equivalent.* The horizontal bars represent tumor control rate over the corresponding dose ranges. Currently, we usually plan on a tumor dose of 6,500 rads in seven and a half weeks (NSD -1,750). Comments Nasopharyngeal carcinomas are characteristically undifferentiated and radiosensitive. The patient’s prognosis depends mainly on the extent of the primary tumor: when the tumor is limited to soft tissue, the prognosis is reasonably good, but when bone or nerve involvement is present, the chance of cure is *NDS [8] is an expression of radiation dose, number of treatments, and over-all treatment time in a single comparative value. The formula is NSD = dose in rads/N-24 X T-11 where N equals the number of treatments and T is the over-all time.
517
Moench
and Phillips
.
LOCAL
CONTROL
0 LOCAL
25 0’“’
”
DOSE IN RADS
o* 5000
.
.
l
l:
0
20F YEARS
0%
101 .
a 6
1,
A
Figure
3. Scattergram
.
. 15
0
OF
TREATMENTS
of
local fumor
control in T1 patients.
.
l
. 0
.”
NUMBER
FAILURE
2
.
.
.
l .
0*-
0. ..
9
1000
lo200
a0
. .
l.’ 0
.. lv** P.
0
0 001
1400
60
l
l
0.0
100
0 00
1600
40
. I
1800
CONTROL
20
0 0
% LOCAL
I
2000
NSD Figure 4. Graph of probability of local tumor control patients versus NSD.
markedly diminished. Cervical lymph metastases, usually present on initial evaluation, are radiocurable, often responding more readily than the primary lesion. The presence of cervical involvement in these patients does not have ‘the same dire prognostic significance that it has in patients with carcinoma in other sites in the head and neck. Because of the effectiveness of irradiation in controlling lymphatic metastases in the neck and the fact that the first relay of this spread in nasopharyngeal carcinoma may be in the high retropharyngeal nodes, radical neck dissection is not indicated as the initial measure; however, it may be effective as a salvage procedure after irradiation. The necessity and effectiveness of irradiation of the clinically negative neck in this disease are indicated by the fact that cervical metastases subsequently developed in half of our patients not treated in this fashion whereas all of those treated prophylactically remained free of disease in the neck. We have had the opportunity to compare primary tumor control in the nasopharynx over a wide dose and irradiation range. Although a better control rate with higher dosage is evident, the slope of this increase is shallow, rising from about 60 to 80 per cent over a wide dose span. (Figure 4.) In other words, the probability of tumor control was only moderately increased with higher dises. A closer correlation between tumor control and dose has been demonstrated by Shukovsky [1] in a similar study of supraglottic laryngeal cancer. The cure rate in cancer at that site increased sharply, rising from about 15 to 90 per cent with a dose increase of several hundred NSD units. The relatively shallow correlation between radiation dose and probability of tumor control demonstrated in this study may be related to biologic factors in-
518
herent in nasopharyngeal cancer such as the usually undifferentiated nature of these tumors. Summary
1. Survival of patients with carcinoma of the nasopharynx correlates with the local extent of disease; the prognosis, in the absence of bone or nerve involvement, is relatively good with irradiation. 2. Early to moderate nodal involvement (N1 and N2 disease) was usually controllable with irradiation and did not gravely affect prognosis. Even with bilateral or fixed adenopathy (Ns disease), the situation was not hopeless. 3. Primary tumor control increased with higher dosage, but the slope of this increase was shallow. References 1. Shukovsky LJ: Dose, time, volume relationships in squamous cell carcinoma of the supraglottic larynx. Amer J Roentgenol108: 27,197O. 2. Stewart JG, Jackson AW: Cited by Easson EC: A clinical approach to neutron therapy. In Current Topics in Radiation Research, vol 3. (Ebert M and Howard A, ed). Amsterdam, North-Holland Publishing Co, 1967, p 175. 3. Vaeth JM: Nasopharyngeal malignant tumors: 82 consecutive patients treated in a period of twenty-two years. Radiology 24: 364, 1960. 4. Perez CA, Ackerman LV, Mill WB. Ogura JH, Powers WE: Cancer of the nasopharynx. Factors influencing prognosis. Cancer 24: 1, 1969. 5. Yeh S: A histologic classification of carcinomas of the nasopharynx with a critical review as to the existence of lymphoepitheliomas. Cancer 15: 895, 1962. 6. Chen KY, Fletcher GH: Malignant tumors of the nasopharynx. Radiology99: 165, 1971. 7. Vaeth JM. Buschke F: Nasopharyngeal cancer. Five year results of treatment with intracavitary cobalt 60. Calif Med 94: 163, 1961. 8. Ellis F: The relationships of biological effect to close-timefractionation factors in radiotherapy. In Current Topics in Radiation Research. (Ebert M and Howard A, ed). Amsterdam, North-Holland Publishing Co, 1968. p 357.
The American Journal of Surgery
Howard C. Moench, MD,* San Francisco, Theodore L. Phillips, MD, San Francisco,
California California
Cancer of the nasopharynx is one of the most malignant diseases of the upper respiratory and digestive tract. Because of its “blind” location, the primary tumor is usually not discovered until there is either advanced local spread or metastases to the cervical lymph nodes. In recent studies the question of radiation dosage and tumor control in neighboring sites has been explored [1,2]. This report reviews our experience with the disease from 1940 to 1968, with emphasis on the relation of radiation dose and time factors to control of the primary disease. Clinical Material During this twenty-eight year period, 146 patients with a malignant nasopharyngeal tumor of squamous cell origin received primary treatment in the Section of Radiation Oncology, University of California Medical Center, San Francisco. These patients, some of whom were reported on by Vaeth [3] in 1960, constitute the basic material for this report. An additional eighteen patients seen in this period were omitted from the study because of the lack of histologic documentation, primary treatment not totally performed by us, or treatment not offered because of the extent of the tumor and/or the patient’s condition. Except for the period of infancy, all age groups were represented; the median age was fifty-three, and the youngest patient was a child of ten. Thirty-one per cent of the patients (46/146) were Chinese, a reflection of both
From the Section of Radiation Oncology, Department of Radiology, University of California School of Medicine, San Francisco, California. This investigation was supported by NI H Training Grant Ca 05177-06. Presented at the First Joint Meeting of the American Radium Society, James Ewing Society, and the Society of Head and Neck Surgeons on the occasion of the Eighteenth Annual Meeting of the Society of Head and Neck Surgeons, Boca Raton, Florida, May 14-19, 1972 *Present address and address for reprints: Division of Radiation Therapy, Shands Teaching Hospital, University of Florida, Gainesville, Florida 32601.
Volume 124, Pctober
1972
the large Chinese population in San Francisco and the susceptibility of this race to epidermoid tumors of the nasopharyngeal mucosa. We have used the following modification of the TNM classification presented by Perez et al [4]: Tr-tumor limited to soft tissue of nasopharynx Tz-tumor extension into nasal cavity, palate, or oropharynx Ts-nerve involvement, destruction of bone, or tumor extension below the oropharynx Td-more than one characteristic of Ts lesion No-no clinically palpable nodes Nl-single mobile node of 3 cm or less Ns-multiple ipsilateral nodes or single mobile node larger than 3 cm Ns-fixed unilateral node of multiple bilateral nodes It should be noted that this classification groups as T1 all lesions confined to the soft tissue nasopharynx, no matter how extensive. Since this tumor often spreads submucosally, we doubt the value of subdividing lesions on the basis of the number of walls involved, especially in a retrospective study. The majority of epidermoid tumors arising from the nasopharynx are poorly differentiated. They can be classified, however, by their predominant histologic character transitional tumors, lymphoepithelioma as follows: (transitional cell with lymphocyte infiltration), and poorly differentiated or anaplastic carcinoma. A small number of’ our patients (12/146) had carcinomas with some degree of keratinization; the remainder of the tumors were undifferentiated. Opinions differ concerning the clinical behavior and response to treatment of the lymphoepithelioma group [5,6]. This designation was given by our pathologist to 25 per cent of these patients (36/146). Three years after treat-
515
Moench and Phillips
100
8 INTERCURRENT
F
PERCENT SURVIVING
Figure 1. Clinical course and site of failure. * = no ewdence disease; t = patienis with both local recurrence and distant metastases are listed as local recurrence.
oi
A’ 20 METASTASES 2
A
6
8
IO
12
14
YEARS
ment by radiation, 36 per cent (13/36) of patients in the lymphoepithelioma group and 38 per cent (37/110) of the remaining 110 patients who had tumor of anaplastic, transitional, or keratinizing forms exhibited no evidence of disease. In our material we have been unable to detect differences in behavior or in response to treatment in these histologic subgroups. We, therefore, have combined the transitional, lymphoepithelioma, anaplastic and differentiated forms of squamous carcinoma of the nasopharynx. This grouping conforms to that proposed by Yeh [5].
Methods Since this study covers a considerable period of time, there are some inevitable differences in technics used. A relatively small number of patients were treated with orthovoltage, usually with an intraoral cone or an intracavitary cobalt or radium source to boost the dose [7J (Four of the eight patients with T1 lesions treated in this fashion were long-term controls.) The majority were treated using supervoltage ‘equipment (2 mev generator or cobalt 60 teletherapy apparatus). During the earlier years of the study the primary site was usually treated with small, laterally opposed radiation fields; the neck was treated in limited fashion if at all. Later the policy evolved of treating the primary lesion with wide margins and of treating the neck in its entirety whether clinically involved or not. During this period (1957 to 1966) two somewhat different fractionation and dose philosophies were in use and the analysis of their end results provided one of the incentives for this study. One method employed a rather prolonged fractionation scheme, delivering 700 to 800 rads tumor dose per week for a total dosage of 5,000 to 6,000 rads. This dose was delivered through constant lateral faciocervical fields. The second method employed a more aggressive treatment schedule of 906 rads a week for a total tumor dose of 6,000 to 6,500 rads. In these patients the primary site and upper part of the neck were treated through opposed lateral
fields, with sparing of the spinal cord after 5,000 rads, and the lower part of the neck was treated through an anterior field. The clinically positive neck usually received 6,000 to 6,500 rads at depth and the neck with no palpable adenopathy usually received 5,000 rads.
516
16
18
20
Figure 2. Absolute survival curve (Berkson-Gage method).
Results
Figure 1 presents an overview of the clinical course of these patients. Significantly, the primary location was the most common site of treatment failure, with subsequent invasion of the base of the skull. Much less common was uncontrolled spread anteriorly into the pterygoid fossa or paranasal sinuses or inferiorly down the walls of the oropharynx. The most common sites of metastases were the lung, viscera, and skeleton. The epidural space of the spinal canal was involved in three instances. In five patients second primary tumors developed consisting of carcinomas of the lung, bladder, thyroid, and oral cavity and a reticulum cell sarcoma of the retroperitoneal space. A survival curve (Berkson-Gage method) of this group of patients through twenty years is shown in Figure 2. Approximately 37 per cent of the total group were alive five years after treatment. Determinate (excluding intercurrent death) five and three year survival rates with no evidence of disease are shown in Table I. The clinical stages (I through IV) are our own and were selected to best correlate with prognosis. The results were generally good when the tumor was limited to the soft tissue of the nasopharynx (Tl) or extended only minimally to soft tissue outside this space (Ts) and when lymph node metastases were absent or of limited extent (stages I and II). Surprisingly, the survival of patients with N1 and Ns disease was not materially worse than that of patients who clinically lacked nodal involvement. Only when lymph node metastases were bilateral or fixed (Ns) was there a marked decrease in survival. In patients with nerve involvement or radiographic evidence of bone destruction (Ts and Tq lesions), long-term survival was not common. Only two patients with radiographic evidence of bone destruction survived disease-free more than three years. One of these had destruction of the middle cranial fossa and survived disease-free for seven years to die of a new primary lesion. The other pre-
The American Journal of Surgery
Carcinoma
I
TABLE
Tumor
Five and
Three Year Survival by Staging
Survival
of Nasopharynx
(See text for staging classification.)
(yr)
NI
N2
9114
9117
6126
12116
lo/la
10130
111
'I2
O/6
N3
STAGE
III
27%(10/37)
T3
3
l/l
l/2
o/7
5
O/5
017
l/11
O/5
O/6
l/11
O/l
0
011
I sented with proptosis and extensive destruction of the posterior bony orbit and base of the skull and at the time of this writing is clinically free of disease four years after treatment. Treatment to the Neck. Seventy-two per cent of these patients (104/146) presented with palpable, clinically positive cervical lymph node enlargement. All received definitive treatment to the neck with irradiation, with only fourteen failures in this group of 104 patients. Treatment failure occurred mainly in patients with advanced involvement (two with NI, four with Nz, and eight with Ns lesions). Two of the failures were clearly related to inadequate dosage (4,500 rads or less) and three were at field margins. Radical neck dissection was performed in eight patients in whom radiation treatment failed. Three of these patients survived free of disease for two and a half, three, and five years before dying of intercurrent disease. Forty-two patients had no palpable evidence of lymph node involvement. Twelve of these patients with clinically negative cervical nodes were not treated and disease subsequently developed in six. The remaining thirty patients with clinically negative cervical nodes received prophylactic treatment to the entire neck and all have remained free of disease in this area. Complications. Xerostomia is an inevitable consequence of treatment. This condition improves in the months after treatment although some patients continue to complain of dryness of the mouth and poor taste for years. Some of the patients in the earlier phase of the study were treated with large daily doses in a relatively short over-all time. As could be expected, this dosage produced subcutaneous fibrosis with some resultant impairment of motion at the temporomandibular joint. There was no occurrence of radiation myelitis. Volume 124, October 1972
012
Radiation Dose and Tumor Control As mentioned previously, failure in this series has occurred most commonly at the primary site. Figure 3 plots the control of the primary tumor as a function of dose and number of treatments in patients with TI disease whose treatment was solely by external irradiation. The great majority of patients were treated using supervoltage equipment; a small number (confined to the very low dose range) received their treatment with orthovoltage equipment. Most patients treated with the latter modality had a subsequent intraoral or intracavitary boost and are excluded from this graph. These data do not lend themselves to a simple regression line although there is an impression of decreased local control with lower dose. Some of the patients with local control at three years had subsequent failure at the primary site. To further delineate these factors, data for the same patients are shown in Figure 4 in which local control is plotted against post treatment interval and tumor dose in nominal standard dose (NSD) equivalent.* The horizontal bars represent tumor control rate over the corresponding dose ranges. Currently, we usually plan on a tumor dose of 6,500 rads in seven and a half weeks (NSD -1,750). Comments Nasopharyngeal carcinomas are characteristically undifferentiated and radiosensitive. The patient’s prognosis depends mainly on the extent of the primary tumor: when the tumor is limited to soft tissue, the prognosis is reasonably good, but when bone or nerve involvement is present, the chance of cure is *NDS [8] is an expression of radiation dose, number of treatments, and over-all treatment time in a single comparative value. The formula is NSD = dose in rads/N-24 X T-11 where N equals the number of treatments and T is the over-all time.
517
Moench
and Phillips
.
LOCAL
CONTROL
0 LOCAL
25 0’“’
”
DOSE IN RADS
o* 5000
.
.
l
l:
0
20F YEARS
0%
101 .
a 6
1,
A
Figure
3. Scattergram
.
. 15
0
OF
TREATMENTS
of
local fumor
control in T1 patients.
.
l
. 0
.”
NUMBER
FAILURE
2
.
.
.
l .
0*-
0. ..
9
1000
lo200
a0
. .
l.’ 0
.. lv** P.
0
0 001
1400
60
l
l
0.0
100
0 00
1600
40
. I
1800
CONTROL
20
0 0
% LOCAL
I
2000
NSD Figure 4. Graph of probability of local tumor control patients versus NSD.
markedly diminished. Cervical lymph metastases, usually present on initial evaluation, are radiocurable, often responding more readily than the primary lesion. The presence of cervical involvement in these patients does not have ‘the same dire prognostic significance that it has in patients with carcinoma in other sites in the head and neck. Because of the effectiveness of irradiation in controlling lymphatic metastases in the neck and the fact that the first relay of this spread in nasopharyngeal carcinoma may be in the high retropharyngeal nodes, radical neck dissection is not indicated as the initial measure; however, it may be effective as a salvage procedure after irradiation. The necessity and effectiveness of irradiation of the clinically negative neck in this disease are indicated by the fact that cervical metastases subsequently developed in half of our patients not treated in this fashion whereas all of those treated prophylactically remained free of disease in the neck. We have had the opportunity to compare primary tumor control in the nasopharynx over a wide dose and irradiation range. Although a better control rate with higher dosage is evident, the slope of this increase is shallow, rising from about 60 to 80 per cent over a wide dose span. (Figure 4.) In other words, the probability of tumor control was only moderately increased with higher dises. A closer correlation between tumor control and dose has been demonstrated by Shukovsky [1] in a similar study of supraglottic laryngeal cancer. The cure rate in cancer at that site increased sharply, rising from about 15 to 90 per cent with a dose increase of several hundred NSD units. The relatively shallow correlation between radiation dose and probability of tumor control demonstrated in this study may be related to biologic factors in-
518
herent in nasopharyngeal cancer such as the usually undifferentiated nature of these tumors. Summary
1. Survival of patients with carcinoma of the nasopharynx correlates with the local extent of disease; the prognosis, in the absence of bone or nerve involvement, is relatively good with irradiation. 2. Early to moderate nodal involvement (N1 and N2 disease) was usually controllable with irradiation and did not gravely affect prognosis. Even with bilateral or fixed adenopathy (Ns disease), the situation was not hopeless. 3. Primary tumor control increased with higher dosage, but the slope of this increase was shallow. References 1. Shukovsky LJ: Dose, time, volume relationships in squamous cell carcinoma of the supraglottic larynx. Amer J Roentgenol108: 27,197O. 2. Stewart JG, Jackson AW: Cited by Easson EC: A clinical approach to neutron therapy. In Current Topics in Radiation Research, vol 3. (Ebert M and Howard A, ed). Amsterdam, North-Holland Publishing Co, 1967, p 175. 3. Vaeth JM: Nasopharyngeal malignant tumors: 82 consecutive patients treated in a period of twenty-two years. Radiology 24: 364, 1960. 4. Perez CA, Ackerman LV, Mill WB. Ogura JH, Powers WE: Cancer of the nasopharynx. Factors influencing prognosis. Cancer 24: 1, 1969. 5. Yeh S: A histologic classification of carcinomas of the nasopharynx with a critical review as to the existence of lymphoepitheliomas. Cancer 15: 895, 1962. 6. Chen KY, Fletcher GH: Malignant tumors of the nasopharynx. Radiology99: 165, 1971. 7. Vaeth JM. Buschke F: Nasopharyngeal cancer. Five year results of treatment with intracavitary cobalt 60. Calif Med 94: 163, 1961. 8. Ellis F: The relationships of biological effect to close-timefractionation factors in radiotherapy. In Current Topics in Radiation Research. (Ebert M and Howard A, ed). Amsterdam, North-Holland Publishing Co, 1968. p 357.
The American Journal of Surgery